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Objective To compare the effect of serratus anterior plane block(SAPB)and thoracic para-vertebral block(TPVB)on acute and chronic pain and plasma tumor necrosis factor-α(TNF-α)level after breast cancer modified radical operation.Methods A total of 99 patients with elective breast cancer modified radical operation,aged 35-70 years,American Society of Anesthesiologists physical status(ASA):grade Ⅰ-11,Body Mass Index(BMI):18-25 kg/m2,were randomly divided into three groups:the simple patient-con-trolled intravenous analgesia(PCIA)group(C group),PCIA combined with TPVB group(TC group)and PCI A combined witj SAPB group(SC group).TPVB and SAPB were performed before induction in the TC group and the SC group,and the relevant situation of regional blocking operation was recorded.The Visual Analogue Scales(VAS)scores in rest and activity at 2,4,8,12,24,48 h after operation,effective pressing times of analgesic pump and remedial analgesia situation after operation were recorded.The TNF-α levels be-fore anesthesia and at postoperative 12,48 h,in postoperative 3,6 months were measured by enzyme linked immunosorbent assay(ELISA).Results Compared with the TC group,the block operation time in the SC group was shorter(P＜0.05).Compared with the C group,the VAS scores in the state of rest and activity at postoperative 2,4,8,12,24 h in the TC group and SC group were significantly decreased(P＜0.05),and the dosage of remifentanil during operation,incidence rates of postoperative nausea and vomiting,effective press-ing times of analgesic pump and rate of remedial analgesia were all decreased(P＜0.05).There was no statis-tical difference in the incidence rate of post-mastectomy pain syndrome(PMPS)among the three groups(P＞0.05).Compared with the C group,the levels of plasma TNF-α in the TC group and SC group were decreased at postoperative 12,48 h,in postoperative 3,6 months,moreover the VAS score in the patients with PMPS was lower(P＜0.05).Compared with the patients without PMPS occurrence,the levels of plasma TNF-α in postoperative 3,6 months in the patients with PMPS were significantly up-regulated(P＜0.05).Conclusion By blocking the afference of pain signals caused by peripheral injury and reducing plasma TNF-α level,SAPB or TPVB may relieve the acute and chronic pain degree in the patients with breast cancer modified radi-cal operation.
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Objective To investigate the changes and clinical significance of serum tumor necrosis fac-tor-α(TNF-α),adiponectin(ADP)and their ratio in patients with depression.Methods A total of 40 patients with depression admitted to Shandong Daizhuang Hospital from January to December 2020 were selected as the observation group,and 26 healthy volunteers were selected as the control group.The observation group was treated with oral antidepressants for four weeks,and the severity of depressive symptoms was assessed by Hamilton depression scale(HAMD).The levels of serum TNF-α and ADP in the observation group before and after treatment and the control group were detected by ELISA,and the change of TNF-α/ADP was ana-lyzed.Results HAMD scores of the observation group were 25.5(21.0,30.0)before treatment and 2.0(1.0,4.0)after treatment,the difference was statistically significant(P<0.05).The levels of TNF-α and TNF-α/ADP in the observation group before treatment were higher than those in the control group,which af-ter treatment were also higher than those before treatment(P<0.05).The level of ADP in the observation group after treatment was lower than that before treatment and in the control group,the differences were sta-tistically significant(P<0.05).Conclusion The level of TNF-α/ADP in patients with depression is more ob-vious than TNF-α.
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Objective To investigate the relationship between serum tumor necrosis factor α stimulated gene 6(TSG-6)and collagen ⅩⅥ(col-16)levels and severity of the illness and clinical outcome in patients with active ulcerative colitis(UC).Methods A total of 79 patients with active UC admitted to the department of gastroenterology in the hospital from January 2020 to January 2023 were selected as the active UC group,56 patients with UC in remission who were similar in gender and age to the active UC group were selected as the remission UC group,and 60 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.Patients with active UC were divided into mild group(n=25),moderate group(n=34)and severe group(n=20)according to the modified Mayo score.Patients with active UC were divided into good prognosis group(n=58)and poor prognosis group(n=21)according to colonoscopy results after 2 months of treatment.Serum TSG-6 and col-16 levels in each group were detected by enzyme-linked immunosorbent assay,Spearman rank correlation analysis was used to analyze the relation-ship between serum TSG-6 and col-16 levels and severity of the illness,and the influence of serum TSG-6 and col-16 levels on clinical outcome was analyzed by multivariate Logistic regression.Receiver operating charac-teristic(ROC)curve was used to evaluate the predictive value of serum TSG-6 and col-16 for poor prognosis in patients with active UC.Results The serum TSG-6 and col-16 levels in active UC group and remission UC group were higher than those in control group,and the serum TSG-6 and col-16 levels in active UC group were higher than those in remission UC group,the difference was statistically significant(P＜0.05).Serum TSG-6 and col-16 levels in severe group and moderate group were higher than those in mild group,and serum TSG-6 and col-16 levels in severe group were higher than those in moderate group,with statistical significance(P＜0.05).By Spearman rank correlation analysis,serum TSG-6 and col-16 in active UC patients were positively correlated with modified Mayo scores(rs=0.695、0.627,P＜0.05).Multivariate Logistic regression analysis showed that compared with＜159.32 ng/mL,patients with serum TSG-6 interquartile interval of 289.15-413.55 ng/mL and＞413.55 ng/mL had a higher risk of poor prognosis.ROC curve analysis results showed that the area under the curve of TG-6 and col-16 in predicting poor prognosis was 0.776 and 0.764,respective-ly.The predictive value of serum TG-6 and col-16 combined detection was better than that of single index(Z=3.392,4.218,P＜0.05).Conclusion The serum TSG-6 and col-16 levels in active UC patients are ab-normally elevated,which is closely related to severity of the illness and clinical outcome.The levels of serum TSG-6 and col-16 can be used as potential biochemical indicators to judge the disease and predict the clinical outcome.
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Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.
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Objective:To design a specialized ultrasound therapeutic device for rabbit urethral scars and to verify its applicability and effectiveness.Methods:New Zealand male rabbits were used as the experimental objects, and the ultrasound therapeutic instrument was customized according to the structure and size of the rabbit penises. The ultrasound therapeutic instrument included the ultrasound pulse emission and control system, the final-stage amplifier, and the ultrasound probe. Firstly, the ultrasound probe was designed according to the size and structure of rabbit penises, and the parameters of the ultrasound probe were determined by COMSOL finite element simulation and actual testing of the sound field distribution. Secondly, the driving circuit of the ultrasound probe was designed according to the parameters of the elements. Then the ultrasound pulse emission and control system based on the field-programmable gate array (FPGA) and the serial screen were designed. Subsequently, the ultrasound therapeutic instrument was subjected to a performance test and a safety test. The ultrasound therapeutic instrument was constructed to include the ultrasound amplifier and the ultrasound probe. Finally, a rabbit urethra reconstruction model was constructed, and eight white rabbits were randomly divided into a model group and an experimental group. The rabbits in the experimental group received the ultrasound therapeutic instrument for treatment of the urethra immediately, with an ultrasound frequency of 2 MHz, a pulse interval of 10 ms, and an output sound intensity of 0.73 W/cm 2. The treatment was performed twice a week (on Tuesday and Thursday), with 10 min of irradiation each time, lasting for four weeks. The rabbits in the model group did not receive any treatment. The area percentage of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tumor necrosis factor-α (TNF-α) staining-positive areas in rabbit urethral tissues were quantitatively analyzed, and the urethral circumference was calculated using Image J software. Results:Due to the addition of sound-absorbing materials, the sound pressure distribution in the treatment chamber was more uniform, and the average value of the standing wave ratio was 1.11, indicating that the structural design met the design requirements. In the overall performance test, the natural focal position of the three ultrasonic transducers was 10 mm, and the consistency of the sound field distribution meet the experimental requirements. The relationship between the peak sound pressure of each transducer and the power supply voltage was close to linear. The output sound intensity ranged from 0.35 to 0.74 W/cm 2, which met the experimental requirements. With the ultrasound output, the temperature of the test point increased slowly, and this experiment could increase the temperature of the tissue by up to 3.3 ℃, which would not lead to thermal damage to the tissue. Animal experiment results showed that the immunopositive area fraction of TGF-β1 in the urethral tissues of rabbits in the experimental group [(4.21 ± 1.32)%] was smaller than that of the model group [(8.53 ± 3.43)%] ( t = ?4.24, P < 0.001). The immunopositive area fraction of TNF-α in the urethral tissues of rabbits in the experimental group [(5.14 ± 2.72)%] was smaller than that of the model group [(7.23 ± 1.57)%] ( t = ?3.37, P < 0.05). The MMP-2 level in the urethral tissue of rabbits in the experimental group [(10.65 ± 2.24)%] was higher than that of the model group[(6.98 ± 2.74)%] ( t = 2.19, P < 0.05). The urethral circumference [(12 209 ± 2 743) μm] was higher than that of the model group [(10 127 ± 2 237) μm] ( t = 15.46, P < 0.05). Conclusions:An ultrasound therapeutic instrument dedicated to rabbit urethral scars has been successfully designed and can be used for the study of ultrasound treatment of rabbit urethral scars.
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Objective To investigate the effect and mechanism of pomalidomide(POM)on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease(COPD).Methods Thirty-six SD rats were randomly divided into control group,model group and POM group,with 12 in each group,half male and half female.The COPD model was established by smoke exposure combined with Klebsiella pneumoniae infection in model group and POM group.The rats in POM group were treated with POM(0.5 mg/kg,once a day for 1 week).The lung function,lung tissue pathology,the proportion of inflammatory cells in bronchoalveolar lavage fluid(BALF)and the levels of serum inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-13 were observed and detected in each group.AB-PAS staining and immunohistochemistry were used to analyze the proliferation of goblet cells and the secretion of mucin(MUC)5AC and MUC5B in airway epithelium of rats.The expression levels of TNF-α receptor 1(TNFR1),IκB kinase(IKK),phosphorylated IKK(p-IKK)and P65 protein in lung tissue were detected by Western blotting.Results Compared with control group,model group showed significant decreased of tidal volume(TV),minute ventilation(MV),forced expiratory vital capacity(FVC),0.1s forced expiratory volume(FEV0.1)and 0.3 s forced expiratory volume(FEV0.3)(P<0.05),increased of the mean linear intercept(MLI)of the alveoli(P<0.01),decreased of the mean alveolar number(MAN)(P<0.01),increased of the proportion of neutrophils and lymphocytes in BALF sediment(P<0.05),and decreased of the proportion of macrophages in BALF sediment(P<0.01);increased of the levels of serum inflammatory factors TNF-α,IL-1β,IL-13 and IL-6(P<0.05),the proportion of goblet cells in airway epithelium(P<0.01),the secretion of MUC5AC and MUC5B in lung tissue(P<0.01),the content of TNFR1 and the ratio of p-IKK/IKK(P<0.01),the content of P65 in nucleus(P<0.01);and decreased of the content of P65 in cytoplasm(P<0.05).Compared with model group,after one week of POM treatment,POM group showed significant improved of the TV,MV,FVC,FEV0.1,FEV0.3,MLI and MAN of rats(P<0.05);decreased of the proportion of neutrophils and lymphocytes in BALF(P<0.05);increased of the proportion of macrophages(P<0.01);decreased of the levels of serum TNF-α,IL-1β,IL-6 and IL-13(P<0.05),the proportion of goblet cells in airway(P<0.01),the secretion of MUC5AC and MUC5B(P<0.01),and the expression of TNFR1,P-IKK and P65(nucleus)(P<0.05);and increased of the level of P65(cytoplasm)(P<0.01).Conclusions POM can improve airway inflammation and mucus hypersecretion in COPD rats,which may be achieved by inhibiting TNF-α/NF-κB signaling pathway.
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BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.
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BACKGROUND:Tumor necrosis factor-α is a broadly acting inflammatory cytokine that plays an important role in the immune inflammatory response of the body.The current study concluded that tumor necrosis factor-α has significant biological effects on a variety of bone tissue cells. OBJECTIVE:To summarize the expression and action pathways of tumor necrosis factor-α in osteoblastic and osteoclastic cells to further elucidate the regulatory role of tumor necrosis factor-α on bone tissue cells. METHODS:PubMed and CNKI were searched until March 2023,and the Chinese search terms included"tumor necrosis factor α,osteoblast,osteoclast,osteoclast,osteoprogenitor";the English search terms included"TNF-α,osteoblast,osteoclast,osteocyte,osteoprogenitor cell".The corresponding criteria were established according to the research needs,and the final literature was screened.Finally,77 articles were included for review. RESULTS AND CONCLUSION:(1)Tumor necrosis factor-α is participating in regulating the recruitment,appreciation,and differentiation of osteoprogenitor cells,but leads to osteoprogenitor cell stripping and death under specific environments.It also participates in bone resorption directly or indirectly through secreted enzymes.(2)Tumor necrosis factor-α can increase the level of inflammatory factors in the environment by activating relevant signaling pathways in osteoclast lineage cells or directly induce the generation of osteoclasts in specific environments.(3)Tumor necrosis factor-α can inhibit osteogenic differentiation by activating nuclear factor-κB signaling pathway,inhibiting the expression of transcription factors such as RUNX2 and Osterix,and inducing apoptosis and necrotizing apoptosis in osteoblasts.(4)Tumor necrosis factor-α inhibits osteogenesis and promotes osteoclastogenesis by activating the nuclear factor-κB signaling pathway in osteocytes and inducing cytokines such as RANKL,SOST,and DKK1,while enhancing apoptosis of the osteocytes,as well as bone resorption around the apoptotic bone tissue.(5)Taken together,the effect of tumor necrosis factor-α in bone tissue is mainly to inhibit osteogenesis and promote osteoclastosis.The biological effect of tumor necrosis factor-α in bone tissue cells is usually dependent on the activation of tumor necrosis factor receptor and nuclear factor-κB signaling pathways.(6)The interaction of tumor necrosis factor-α with other tissue cell types surrounding bone tissue and its role in bone immune regulation still deserve attention in future studies.
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BACKGROUND:Lycium barbarum polysaccharide has many biological activities and has been found to have potential effects on promoting wound healing. OBJECTIVE:To investigate the mechanism of lycium barbarum polysaccharide in tumor necrosis factor-α-mediated keratinocyte apoptosis and its effect on the healing of burn wounds. METHODS:(1)In vitro experiment:Keratinocytes were divided into four groups:cells were cultured in the α-MEM medium(complete medium)containing 15%fetal bovine serum and 1%glutamine in normal group,cultured in the complete medium containing lycium barbarum polysaccharide in positive control group,cultured in the complete medium containing tumor necrosis factor-α in model group,and cultured in the complete medium containing lycium barbarum polysaccharide and tumor necrosis factor-α in experimental group.After 24 hours of culture,cell proliferation was detected using cell counting kit-8 assay;Cleaved caspase-8,TNF R1,FADD,and LC3 were detected using western blot.Then an autophagy inhibitor group(the complete medium containing 3-methyladenine)and an autophagy inhibitor+lycium barbarum polysaccharide group(the complete medium containing lycium barbarum polysaccharide,tumor necrosis factor-α,and 3-methyladenine)were set up.After 24 hours of culture,keratinocyte apoptosis was detected by flow cytometry.(2)In vivo experiment:Six Sprague-Dawley rats were randomly divided into a control group and an experimental group,with three rats in each group.Four deep Ⅱ degree burn wounds with a diameter of 2 cm were made on the back of each rat.At 24 hours after modeling,mice in the control and experimental groups were coated with normal saline and lycium barbarum polysaccharide solution,respectively,once a day.Wound healing was observed regularly after treatment.Samples were taken 28 days after treatment and the pathologic pattern of the wound was observed. RESULTS AND CONCLUSION:(1)In vitro experiment:Addition of lycium barbarum polysaccharide alone did not affect cell proliferation and apoptosis and the expression of apoptotic and autophagic proteins in keratinocytes.After the addition of tumor necrosis factor α,the proliferation of keratinocytes was inhibited,the apoptotic rate increased,and the expression of apoptotic and autophagic proteins was elevated,while lycium barbarum polysaccharide could antagonize the above effects of tumor necrosis factor-α.Lycium barbarum polysaccharide combined with autophagy inhibitors further reduced the apoptotic rate of keratinocytes.(2)In vivo experiment:The wound healing rate of rats in the experimental group was higher than that of the control group at 12,16,20,24,and 28 days after treatment(P＜0.05,P＜0.01).Hematoxylin-eosin staining results at 28 days after treatment showed an intact and well-defined epidermis of the wound in the experimental group compared with the control group.To conclude,lycium barbarum polysaccharide protects the integrity of skin epidermal tissue and promotes wound healing by inhibiting autophagy and apoptosis of keratinocytes.
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BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.
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BACKGROUND:Unicompartmental knee arthroplasty has been paid more and more attention because of its advantages of fewer traumas,less blood loss,less complications,faster recovery,excellent knee function and high prosthetic survival rate.Most of the relevant reports focused on its clinical effect,but the changes in the levels of relevant inflammatory cytokines in patients after unicompartmental knee arthroplasty were rarely reported. OBJECTIVE:To investigate the effect of unicompartmental knee arthroplasty in patients with medial compartment osteoarthritis of the knee and the changes of interleukin-1,interleukin-6,and tumor necrosis factor-α levels. METHODS:A total of 30 patients with medial compartment osteoarthritis of the knee who received unicompartmental knee arthroplasty from September 2021 to March 2023 and met the inclusion criteria were selected as the study subjects.Medial angle of proximal tibia,femoral and tibial angle,pain visual analog scale score,hospital for special surgery score,knee joint range of motion,synovial fluid interleukin-1,interleukin-6,and tumor necrosis factor-α levels before and after surgery were compared and statistically analyzed. RESULTS AND CONCLUSION:(1)All 30 patients had grade I wound healing.All patients were followed up for more than 6 months after surgery.There were no complications such as prosthesis loosening and dislocation of prosthesis liner in all patients.(2)The medial proximal tibia angle and the femoral and tibial angles measured after operation were significantly improved(P<0.05).(3)The visual analog scale score,hospital for special surgery score and range of motion measured at 1,3,and 6 months after operation were better than those before operation(P<0.05),and showed a gradual improvement(P<0.05).(4)The levels of interleukin-1,interleukin-6,and tumor necrosis factor-α in synovial fluid at 3 and 6 months after operation were decreased gradually compared with those before operation(P<0.05)and showed a gradual downward trend at each time point after operation.(5)It is indicated that unicompartmental knee arthroplasty can effectively treat medial compartment osteoarthritis of the knee,significantly relieve pain,restore knee joint function,improve knee varus deformity and lower limb strength line,and reduce the levels of inflammatory cytokines interleukin-1,interleukin-6,and tumor necrosis factor-α in joints to a certain extent.
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Objective:To exploring the effect of selenium on tumor necrosis factor-α (TNF-α) induced inflammatory injury of AC16 cardiomyocytes.Methods:AC16 cardiomyocytes cultured in vitro were divided into control group, selenium pretreatment group (100 μg/L sodium selenite pretreatment for 4 h), 50 μg/L TNF-α group, selenium pretreatment + 50 μg/L TNF-α group, 100 μg/L TNF-α group, and selenium pretreatment + 100 μg/L TNF-α group. After 24 h of culture, the cell culture medium or cells were collected for detection. Griess method was used to detect nitric oxide (NO) level in cell culture medium. Hoechst 33342 nuclear staining was detected by fluorescence inverted microscope and karyopyknosis ratio was analyzed. The mRNA expression levels of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2 associated X protein (Bax) and inducible nitric oxide synthase (iNOS) were detected by real-time fluorescence quantitative PCR. The protein expression levels of nuclear factor-kappa B (NF-κB) p65 and inhibitory κB-α (IκB-α) were detected by Western blotting. Results:The levels of NO in the control group, selenium pretreatment group, 50 μg/L TNF-α group, selenium pretreatment + 50 μg/L TNF-α group, 100 μg/L TNF-α group and selenium pretreatment + 100 μg/L TNF-α group were (10.58 ± 2.32), (9.07 ± 0.73), (15.53 ± 3.97), (12.05 ± 1.11), (30.65 ± 4.16) and (19.02 ± 3.72) μmol/L, respectively. Selenium and TNF-α had main effects on NO level ( F = 37.71, 99.07, P < 0.001) and interaction effect ( F = 11.80, P < 0.001). Selenium and TNF-α had main effects on karyopyknosis ratio and Bcl-2 and Bax mRNA expression levels ( F = 56.37, 462.81, 18.04, 32.85, 18.38, 170.77, P < 0.05). Selenium and TNF-α had an interactive effect on both karyopyknosis ratio and Bax mRNA expression level ( F = 21.48, 19.96, P < 0.001). Selenium and TNF-α had main effects on iNOS mRNA expression level ( F = 129.98, 1 051.76, P < 0.001) and interaction effect ( F = 53.28, P < 0.001). Selenium and TNF-α had main effects on the protein expression levels of NF-κB p65 and IκB-α ( F = 73.65, 145.49, 710.20, 105.66, P < 0.001) and interaction effects ( F = 26.73, 197.59, P < 0.001). Conclusion:Selenium may inhibits iNOS expression through NF-κB signal system and protects cardiomyocytes from TNF-α induced inflammatory injury.
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As a new treatment option after conventional corticosteroids and immunomodulatory drugs, biologics have been widely used in the clinical management of non-infectious uveitis in many countries due to their approved efficacy and safety. Anti-tumor necrosis factor-alpha monoclonal antibody is the most commonly used one. However, the guidance on its standardized application is lacking. The Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association compiled the Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody. This evidence-based consensus is made according to the principle of consensus building and combines the clinical experience of the experts. Twelve recommendations are formatted on the application of Adalimumab and Infliximab. The interpretation of this consensus point will help improve the normative and effective application of anti-tumor necrosis factor-alpha monoclonal antibody in ophthalmologists, rheumatologists and immunologists.
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Objective:To establish a reliable,stable and clinically realistic model of blunt contusion injury to the rat skele-tal muscle. Method:A model of the rat gastrocnemius muscle blunt contusion injury was established by using a weight of 170g,a height of 70cm and a spring with a diameter of 0.5cm at the bottom to buffer the polymeric strik-ing part and guide the fall to hit for 5 consecutive times.The gait changes of rats were evaluated by CatWalk analysis system at 0h,12h,24h,3 days,7 days and 14 days after modeling;local histopathological changes were observed by HE staining and local ultrastructural changes were observed by transmission electron micros-copy.Enzyme-linked immunosorbent assay(ELISA)was used to detect the changes of tumor necrosis factor-α(TNF-α)in local tissues. Result:Compared with the blank group,the mean speed and maximum speed change rate of the model group were significantly decreased,and the difference was statistically significant(P＜0.001);compared with the normal foot group,the maximum contact area,footprint area and standing phase duration of the limb of the injured limb group were significantly decreased,and the difference was statistically significant(P＜0.05).A large infiltration of inflammatory cells and massive lysis necrosis of muscle fibers were observed on HE stain-ing after 3 days.By 14 days,although scar tissue was still present,tissue repair with HE staining was almost indistinguishable from that of the blank group.Vacuolation was observed in part of the sarcoplasmic reticulum at 0h after the blow,and lysis of muscle fibers and part of the sarcoplasmic reticulum at 3 days with in-creased inflammatory response which basically returned to normal by 14 days.The TNF-α level began to rise gradually and reached a peak from 0h to 12h after injury,and remained higher level from 12h to 72h,and the difference was statistically significant compared with the blank group(P＜0.05),and basically returned to the normal level by 14 days. Conclusion:The model can cause moderate damage of skeletal muscle in rats,with a 14-day natural recovery time at least.It can provide as one of the methods for for the establishment of the rat skeletal muscle blunt contusion model.
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Objective To investigate the application of anesthesia management plan based on the concept of enhanced recovery after surgery(ERAS)in thoracoscopic surgery.Methods From December 2021 to December 2022,100 patients underwent thoracoscopic surgery were randomly divided into control group and observation group with 50 patients in each.The control group received routine anesthesia management,and the observation group received anesthesia management based on ERAS concept.The two groups were compared in terms of clinical indicators,the degree of incision pain on day 1,3,5 and 7 after surgery,the levels of inflammatory factors on day 1 and 3 after surgery.The incidence rates of pulmonary complications,nausea and vomiting,and respiratory depression in the two groups were calculated.Results Awakening and extubation time and hospital stay of observation group were shorter than those of control group,the treatment costs of observation group was less than that of control group,the visual analogue scale(VAS)of observation group at each time point after surgery were lower than those of control group,the levels of C-reactive protein(CRP)and tumor necrosis factor-α(TNF-α)of observation group on day 1 and 3 after surgery were lower than those of control group,the differences were statistically significant(P<0.05).The total incidence of pulmonary complications of observation group was lower than that of control group(6.00%vs 22.22%),the difference was statistically significant(P<0.05).The incidence rates of respiratory depression and nausea and vomiting in the observation group were 0.00%and 2.00%,respectively,while the incidence rates of respiratory depression and nausea and vomiting in the control group were 4.00%and 6.00%,respectively.There was no statistically significant difference in the total incidence rates of other complications between the two groups of patients(P>0.05).Conclusion Applying the anesthesia management plan based on ERAS concept in thoracoscopic surgery can promote postoperative recovery,reduce pain and pulmonary complications,and save treatment costs.It is worthy of clinical application.
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Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.
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Objective To investigate the risk factors of lower extremity deep venous thrombosis(DVT)after internal fixation in patients with type C pelvic fracture,and to establish a relevent nomogram model.Methods Atotal of 217 patients with type C pelvic fractures who were admitted to the Orthopedic Center of the hospital from January 2018 to January 2022 were included in the study.All patients underwent internal fixation.According to whether DVT of the lower extremities was formed after operation,they were divided into the DVT group and the non-DVT group(N-DVT).The general clinical data and preoperative in-flammatory factor expression levels of the two groups was compared.Multivariate analysis was used to obtain independent predictors of DVT formation after internal fixation in patients with type C pelvic fractures.The correlation between preoperative inflammatory factors and DVT formation after internal fixation in patients with type C pelvic fractures was analyzed.The relevant nomograph model was constructed,and the Bootstrap method and calibration curve were used to verify the nomograph model internally.The ROC curve and deci-sion curve for predicting DVT formation after internal fixation in patients with type C pelvic fracture were drawn,and the predictive efficiency and net rate of return of independent prediction and combined prediction were an-alyzed.Results Multivariate analysis showed that age,diabetes,preoperative tumor necrosis factor-α(TNF-α),traction and braking,and bed rest time were independent predictors of DVT formation after internal fixa-tion in patients with type C pelvic fractures(P＜0.05).A nomograph model was constructed based on inde-pendent predictors to predict the formation of DVT after internal fixation in patients with type C pelvic frac-ture,and the C index of the distinguishing evaluation index of the nomogram model was 0.834(95％CI:0.812-0.924),the results of goodness of fit(H-L)test showed that the predicted value of DVT formation probability after internal fixation in patients with type C pelvic fracture was in good agreement with the actual observed value(P＞0.05).ROC curve analysis and decision curve analysis showed that age,diabetes,TNF-α,traction and braking,bed rest time and combined prediction model had good predictive performance and net yield in predicting DVT formation after internal fixation in patients with type C pelvic fracture.Conclusion Age,diabetes,TNF-α,traction braking and bed rest time are independent predictors of DVT formation after internal fixation in pa-tients with type C pelvic fracture.The nomogram model based on the above independent predictors has a high value in predicting DVT formation after internal fixation in patients with type C pelvic fracture.
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Objective:To investigate the expression level of miR-21 in patients with septic acute respiratory distress syndrome, and analyze its correlation with inflammatory factors and its value in evaluating clinical prognosis.Methods:Patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Hebei North University from October 2020 to March 2022 were prospectively recruited. The patients were divided into an ARDS group and a non-ARDS group according to whether ARDS occurred within 3 days after admission. The ARDS group was divided into a low-risk group and a high-risk group according to the oxygenation index, and the ARDS group was divided into a survival group and a death group according to their 28-day survival status. In addition, 50 healthy volunteers who underwent physical examination during the same period were included in the control group. The expression levels of serum miR-21 and inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were compared in each group at admission. To analyze the relationship between miR-21 expression and inflammatory factors and explore the value of miR-21 in predicting the prognosis of sepsis patients with ARDS.Results:A total of 106 patients with sepsis were included. Compared with the healthy control group, the levels of serum miR-21, TNF-α and IL-6 in the ARDS group and non-ARDS group were significantly increased (all P<0.05). Compared with the low-risk group, the levels of serum miR-21, TNF-α and IL-6 in the high-risk group were significantly increased (all P<0.05). Compared with the survival group, the serum miR-21 expression level and TNF-α and IL-6 levels in the death group were significantly increased (all P<0.05). Pearson correlation analysis showed that the serum miR-21 expression level in the ARDS group was positively correlated with IL-6 and TNF-α levels ( r=0.842, 0.697, P<0.001). ROC curve analysis showed that the AUC of serum miR-21 in predicting death from sepsis complicated with ARDS was 0.876 (95% CI: 0.761-0.942), the best cut-off value was 2.25, and its sensitivity and specificity were 92.9% and 71.7%, respectively. Conclusions:The expression level of serum miR-21 is significantly increased in patients with sepsis ARDS, is positively correlated with the level of inflammatory factors, is closely correlated with the severity and prognosis of the disease, and has great value in evaluating the prognosis of patients with sepsis ARDS.
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Objective:To investigate the effect of tumor necrosis factor-α (TNF-α) on the differentiation of orbital fibroblasts (OF) in thyroid-associated ophthalmopathy (TAO) and its regulation mechanism.Methods:Six patients (six eyes) diagnosed with TAO were collected in Tianjin Medical University Eye Hospital from December 2019 to August 2020.Adipose connective tissue was collected during the orbital decompression surgery.OF was isolated and cultured using the tissue block method and vimentin was identified by immunofluorescence.Lipogenic differentiation of OF was induced and identified by oil red O staining.Complete culture medium containing 0, 0.1, 1.0 and 10.0 μg/L TNF-α was used to induce the dedifferentiation of orbital mature adipocytes.Primary culturing cells, 14-day differentiation cells and 20-day dedifferentiation cells were collected.The relative mRNA expression levels of peroxisomal proliferation-activated receptor (PPARγ), extracellular regulatory protein kinase1 (ERK1), ERK2 and fat-coated protein1 (perilipin1) were detected by real-time fluorescent quantitative PCR.The relative protein expression levels of PPARγ, P-ERK1/2 and perilipin1 were detected by Western blot.Results:Human TAO-derived OF were successfully cultured in vitro, spindle-shaped or polygonal, tightly arranged in a vortex pattern, and immunofluorescence staining for vimentin was positive.After OF adipogenic differentiation, lipid droplet structures could be seen in the cytoplasm of some cells, and the stained lipid droplet structures in the cytoplasm could be seen by oil red O staining, which confirmed that the cells obtained after differentiation were adipocytes.Dedifferentiation of adipocytes was induced by 0.1, 1.0, and 10.0 μg/L TNF-α.With the extension of induction time, the volume of lipid droplets in the cytoplasm and the number of cells containing lipid droplets decreased.Lipid droplets disappeared in the cytoplasm on the 20th day of dedifferentiation, and the cells became long spindle-shaped and tightly arranged, dedifferentiated into fibroblast-like cells.Real-time fluorescence quantitative PCR detection results showed that the relative expression levels of PPARγ, ERK1, ERK2 and perilipin1 mRNA in 14-day differentiation group were 4.26±0.09, 2.01±0.09, 3.23±0.10 and 8.69±0.33, respectively, which were significantly higher than 1.00±0.09, 1.05±0.19, 1.00±0.10 and 1.05±0.07 in primary group, and 1.06±0.03, 1.15±0.11 and 6.27±0.09 in 20-day dedifferentiation group (all at P<0.05). Western blot analysis showed that the expression levels of PPARγ, ERK1/2 and perilipin1 proteins in 14-day differentiation group were 1.07±0.03, 1.00±0.03 and 1.13±0.02, respectively, which were significantly higher than 0.37±0.02, 0.29±0.02 and 0.00±0.00 in primary group, and 0.20±0.02, 0.38±0.06 and 0.00±0.00 in 20-day dedifferentiation group (all at P<0.001). Conclusions:TNF-α has a dedifferentiation effect on TAO orbital adipocytes.The mechanism may be related to the downregulation of ERK1/2-PPARγ-perilipin1 signaling pathway.
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ObjectiveTo explore the mechanism of Zhuangyao Tongluo Formula（壮腰通络方，ZTF） in delaying intervertebral disc degeneration. MethodsM1 macrophages were induced from THP-1 cells using LPS， IFN-γ and PMA. The induced M1 macrophages were then co-cultured with nucleus pulposus cells in a transwell system. Fetal bovine serum was used as the control serum， and the effects of different concentrations （5%， 10%， 15%， 20%） of serum from rats treated with ZTF on the activity of M1 macrophages and nucleus pulposus cells were analyzed using MTT assay. Experiment 1 was established， including the nucleus pulposus cell control group， M1 macrophage control group， nucleus pulposus cell + ZTF group， nucleus pulposus cell + TNF control group， nucleus pulposus cell + TNF + ZTF group， co-culture group， and co-culture + ZTF group. The levels of IL-1β， and IL-18 in the culture supernatant were detected using ELISA. The mRNA expression of IL-1β and IL-18 in nucleus pulposus cells was detected using qPCR. Additionally， the expression of GSDMD protein in nucleus pulposus cells was detected using cell immunofluorescence. In experiment 2， co-culture groups were constructed using TNF-α overexpression （OE） or empty vector （EV） plasmids， including co-culture group， TNF-EV + co-culture group， TNF-EV co-culture group + ZTF， co-culture + ZTF group， TNF-OE co-culture group + ZTF， and TNF-OE + co-culture group. The mRNA and protein expression of TNF-α in M1 cells in each group were detected using qPCR and WB. ResultsThe ZTF with 10% serum was selected for subsequent experiments. The results of experiment 1 showed that compared to the control group of nucleus pulposus cells， there was no statistically significant difference in the levels of IL-1β， IL-18， mRNA， and GSDMD expression in the nucleus pulposus cells + ZTF group （P＞0.05）. However， the TNF-α + co-culture group showed a significant increase in IL-1β， IL-18 levels， mRNA， and GSDMD expression （P＜0.01）. When compared to the co-culture group， the ZTF+ co-culture group showed a significant decrease in IL-1β， IL-18 levels， mRNA， and GSDMD expression （P＜0.01）. The results of experiment 2 showed that there was no statistically significant difference in TNF-α mRNA and protein expression between the empty vector plasmids + co-culture group and the co-culture group （P＞0.05）. Compared to the empty vector + co-culture group， the expression of TNF-α mRNA and protein was significantly reduced in the empty vector co-culture + ZTF group （P＜0.01）. Compared to the co-culture group and the empty vector + co-culture group， the expression of TNF-α mRNA and protein was significantly reduced in the co-culture + ZTF group （P＜0.01）. Compared to the co-culture + ZTF group， the expression of TNF-α mRNA and protein significantly increased in the overexpression vector co-culture + ZTF group （P＜0.01）. Compared to the overexpression vector co-culture + ZTF group， the expression of TNF-α mRNA and protein significantly increased in the overexpression vector co-culture group （P＜0.01）. ConclusionZTF serum can inhibit the TNF-α-induced apoptosis of nucleus pulposus cells and delay lumbar disc degeneration by reducing the expression of TNF-α in M1 macrophages.