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OBJECTIVE: Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC. METHODS: The "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored. RESULTS: GDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression. CONCLUSION: GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

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Objective To explore the role and molecular mechanism of Lnc-BM in the occurrence and development of gastric cancer (GC). Methods GC tissues and paired adjacent normal tissues of 36 GC patients were collected, and the expression of Lnc-BM was detected by RT-qPCR. Colony formation and CCK-8 assays were used to investigate the proliferation of GC cells. The migration and invasion properties of GC cells were investigated via Transwell assay. RNA pull-down assay was applied to confirm the interaction between FASTK and Lnc-BM. Western blot assay was used to detect FASTK protein level in Lnc-BM overexpressing or knockdown cells. Mitochondrial respiratory capacity and the related proteins expression levels were detected by Seahorse and Western blot assays, respectively. Lnc-BM stably overexpressing GC cells were constructed and then injected subcutaneously into nude mice. The tumor growth was observed. Results Lnc-BM was highly expressed in GC tissues compared with their paired adjacent normal tissues. Lnc-BM overexpression significantly promoted GC cells proliferation migration and invasion, while Lnc-BM knockdown inhibited GC cells proliferation, migration and invasion (P < 0.05). RNA pull-down experiment demonstrated that Lnc-BM can directly bind to FASTK. Western blot results indicated that overexpression of Lnc-BM increased the protein levels of FASTK, while knockdown of Lnc-BM inhibited the expression of FASTK (P < 0.05). Compared to the control group, overexpression of Lnc-BM increased the levels of mitochondria associated proteins, such as MT-ND6 and TOM20 (P < 0.05). Seahorse results indicated that overexpression of Lnc-BM enhanced mitochondrial respiratory capacity (P < 0.05). Knocking down FASTK in Lnc-BM stably overexpressing cells can reverse the increase in mitochondrial respiratory capacity caused by Lnc-BM overexpression (P < 0.05). In vivo, the results of subcutaneously implanted tumor model in nude mouse showed that Lnc-BM overexpression promoted the tumor growth (P < 0.05). Conclusion Lnc-BM promotes GC progression by regulating mitochondrial respiratory function through the FASTK/MT-ND6 axis.

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The Rh blood grouping system is a critical standardized test in transfusion medicine,espe-cially for the cases related to haemolytic transfusion reactions and neonatal haemolytic disease caused by clinical RhD blood group incompatibility.In the present case report,we presented two cases with the un-common RHD gene variation RHD*DEL37.The blood samples of the two subjects were mistakenly iden-tified as RhD-negative through conventional serological testing.Firstly,both blood samples were tested negative for the RhD antigen using traditional tube test and gel microcolumn methods.The phenotyping of RhCE were identified as ccEe and ccee for each sample,respectively.Secondly,genetic analysis was performed using polymerase chain reaction-sequence specific prime(PCR-SSP)which revealed that nei-ther sample belonging to the several common RHD gene variants which was found in Asia.Moreover,they turned out to be positive for the RHD haplotype,which indicated that exons 1-10 on one of the RHD al-leles were entirely absent.In addition,a T＞C mutation was observed at bases 1154-31 in intron 8 of the other allele,which was located at the intron 8 breakpoint.This result was obtained after further Sanger sequencing of exons 1-10 of the RHD gene.The mutant allele was designated as RHD*DEL37 by the International Society of Blood Transfusion(ISBT)and was identified as D-elute(Del)by phenotype ana-lysis.Both samples were genotyped as RHD*DEL37 and showed positive results.In summary,the true genotype of the two blood samples,of which the screening results only using serological testing method was negative,were RHD*DEL37/RHD-(RHD*01N.01).Notably,this kind of genotype was reported for the first time in Chinese population.Moreover,the two individuals did not have ties of consanguinity,indicating that some of the Chinese individuals could be carriers of the genetic mutation.Therefore,it might be necessary to further confirm the frequency of this mutation in the Chinese population and the possibility of homozygosity for this mutation.This report identifies infrequent RHD gene mutation samples by coupling molecular biology and serological methods to prevent misclassification of blood groups.Com-bining serological and molecular biology test results to determine blood group is critical in protecting pa-tients during clinical transfusion procedures.

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The purpose of minimally invasive thyroid surgery is to perform refined surgery through an intelligent operating system, achieving minimal physical and psychological trauma for patients, thereby improving their quality of life. At present, the commonly used minimally invasive surgical methods are laparoscopic surgery and robotic surgery, both by creating tunnels from a distance to the thyroid gland, requiring high technical requirements for surgical instruments and robotic surgeons. Regardless of the type of minimally invasive surgery, in the early stages of implementation, doctors have a process of exposure, understanding, proficient mastery, and innovative expansion of the system, instruments, operating methods, and surgical thinking. In this process, it is inevitable to encounter some erroneous operations, which are the main causes of medical safety adverse events, including complications, and bring a failed medical experience to patients. At the same time, mistakes can also cause psychological burden for robotic surgeons and have an impact on the development of new technologies. The occurrence of errors also depends on the open surgical experience and clinical adaptability of robotic surgeons, and experienced robotic surgeons can significantly reduce errors. With the innovation of medical technology and the urgent demand of patients for efficacy and beauty, errors should not be a factor hindering the development of minimally invasive thyroid surgery. This article will analyze the erroneous operations of robot surgeons, formulates countermeasures, and provides reference for the safe implementation of robot surgery, thereby promoting the development of intelligent precision minimally invasive surgery, and further benefiting patients with minimally invasive needs.

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The progress and clinical application of troponin detection technology have continuously improved the diagnosis rate of acute myocardial infarction(AMI),which effectively shortens the time of necrotic myocardial reperfusion.Earlier studies have found that high-sensitivity troponin(hs-cTn)is elevated to varying degrees in patients with chronic kidney disease(CKD).Therefore,when patients with CKD have AMI,the application of hs-cTn is limited to a certain extent,and with the lack of chest pain symptoms and the non-specificity of electrocardiogram performance in patients with CKD,it is particularly difficult to make a quick and accurate diagnosis of such patients.Based on this,this article will summarize the application of hs-cTn in AMI,the clinical characteristics of patients with CKD combined with AMI,how to improve the diagnostic accuracy of patients with CKD combined with AMI,and the value of hs-cTn in risk stratification and prognosis assessment of such patients to provide clinical medical staff with reference for early intervention or revascularization of patients.

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Objective To investigate the effect of circFOXK2 on the proliferation,migration and invasion of lung cancer cells and its possible mechanism.Methods The cancer tissues and adjacent tissues of 45 patients with lung cancer were collect-ed,and the expression of circFOXK2 and miR-409-3p in the tissues were detected by qRT-PCR.Lung cancer cell A549 and H1299 was cultured in vitro,and the dual-luciferase reporter assay was used to verify the regulatory relationship between circ-FOXK2 and miR-409-3p.The CCK-8,clone formation and Transwell assays were used to detect cell proliferation,migration and invasion.Western blot was used to detect the protein expression of E-cadherin and N-cadherin in cells.Results The expression of circFOXK2 was significantly higher(P＜0.05),but the expression of miR-409-3p was significantly lower(P＜0.05)in lung cancer tissues.circFOXK2 could target miR-409-3p and negatively regulate its expression in lung cancer cells.The proliferation,migration and invasion were reduced in circFOXK2(all P＜0.05),N-cadherin level was decreased(P＜0.05),but E-cadherin level was increased(P＜0.05)in circFOXK2 knockdown or miR-409-3p overexpressed A549 and H1299 cells.The inhibitory effects of circFOXK2 knockdown on the proliferation,migration and invasion of lung cancer cells could be reversed by miR-409-3p inhibitor.Conclusion The circFOXK2 was upregulated in lung cancer,which promoted the proliferation,migration and inva-sion of lung cancer cells by targeting miR-409-3p.

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BACKGROUND:Intervertebral disc degeneration is the basis of spinal degenerative diseases;however,there is no effective treatment. OBJECTIVE:To investigate whether sinomenine can inhibit interleukin-1β-induced apoptosis in nucleus pulposus cells and its molecular mechanism. METHODS:Rat nucleus pulposus cells were cultured in vitro by trypsin combined with type II collagenase digestion,and the cell growth curve was plotted.An appropriate sinomenine concentration was determined using the cell counting kit-8 kit.Nucleus pulposus cells were divided into control group,sinomenine group,interleukin-1β group,sinomenine+interleukin-1β group,zinc protoporphyrin group,zinc protoporphyrin+sinomenine group,zinc protoporphyrin+interleukin-1β group,and sinomenine+zinc protoporphyrin+interleukin-1β group.Proliferative activity,reactive oxygen species content,apoptosis rate,and heme oxygenase-1 expression in nucleus pulposus cells were detected. RESULTS AND CONCLUSION:The rat nucleus pulposus cells cultured in vitro were polygonal,triangular,and short wedge-shaped,and the cell growth showed an"S"curve.The cells grew slowly in the first 3 days of culture,rapidly in 4-6 days,and slowly again in 7-8 days.The cells then entered the"platform stage"where the number of cells no longer increased.The proliferative activity of myeloid cells showed no significant changes when the concentration of sinomenine was≤80 μmol/L(P>0.05).Interleukin-1β significantly reduced the proliferative activity of nucleus pulposus cells,increased the content of reactive oxygen species and led to apoptosis(P<0.01).Sinomenine intervention not only promoted heme oxygenase-1 expression(P<0.05)but also inhibited interleukin-1β-induced decrease in proliferative activity and increase in reactive oxygen species content and apoptosis rate in nucleus pulposus cells(P<0.05).These effects could be reversed by zinc protoporphyrin(P<0.01).

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Objective To establish a stable and reliable method for the determination of ethylene oxide residue,and to analyze ethylene oxide residue in multi components made of different materials involved in some medical devices,so as to provide references for sample selection and ethylene oxide residue detection of multi-component medical device kits.Methods A method for the determination of ethylene oxide residue of multi-component medical devices was developed using headspace-gas chromatography and DB-WAX column under the conditions of headspace extraction with equilibration at 80℃ for 20 min,and the weighing mass,linearity,limit of detection,limit of quantification,precision and recovery of the method were determined.Trials of the method were carried out on the items undergoing ethylene oxide sterilization,including disposable perineal care kit,disposable gynecological examination kit,disposable suture dressing kit,disposable debridement kit and the components contacting human body in the disposable dialysis kit,and the abilities of different materials of the components were analyzed in absorbing,retaining and releasing ethylene oxide.Results The method showed high linearity(r=0.999 8)in the range of ethylene oxide mass concentration from 0.4 to 16.0 μg/mL with a weighing mass of 1.00 g,which had the limit of detection being 0.11 μg/mL,the limit of quantification being 0.37 μg/mL and the relative standard deviations(RSDs)for the precision from 0.35％to 1.52％.The average recoveries of different spiked amounts of ethylene oxide in the three blank matrices ranged from 92.68％to 101.42％with the relative standard deviations(RSDs)from 2.46％to 7.59％,which all satisfied the detection requirements.The components made of rubber and acrylonitrile-butadiene-styrene copolymer(ABS)in multi-component medical device kits had the highest ethylene oxide residues,followed by the components made of wood,degreased cotton,polypropylene and polystyrene.Conclusion The method proposed gains advantages in easy operation and high specificity,quantification and reproducibility,which can be used for the determination of ethylene oxide residue in the multi-component medical device kit undergoing ethylene oxide sterilization.References are provided for sample selection of multi-component medical devices.[Chinese Medical Equipment Journal,2024,45(1):56-61]

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Objective To investigate the effect of trunk control on the biomechanical characteristics of lower limb movements during Asian squats(AS)and Western squats(WS)in young adults to provide empirical support for the application and promotion of deep squat training.Methods Twenty-four healthy young male collegiate students performed AS and WS with and without bar control,and their lower limb kinematic and kinetic characteristics were collected using an infrared light-point motion capture system and a three-dimensional(3D)dynamometer.The 3D angles of the lower limbs were obtained using Cortex-642.6.2 software,based on the calculation of Euler angles,and the 3D moments were obtained by applying the inverse dynamics method.The effects of trunk control and deep squatting posture on the lower limb kinematic characteristics were examined using a two-factor analysis of variance with a 2×2 repeated design.Results There was no significant interaction between trunk control and the deep squatting posture for either kinematic or kinetic parameters(P>0.05).The WS group had a large knee flexion angle,peak patellofemoral contact force,and ratio of peak hip and knee extension moments,and small ankle dorsiflexion and hip flexion angles(P<0.05).The deep squat with a bar had a large ankle dorsiflexion angle,peak patellofemoral contact force,and hip flexion angle as well as a small knee flexion angle and ratio of peak hip and knee extension moments(P<0.05).Conclusions WS is helpful for training hip extension muscle groups,whereas AS is helpful for training knee extension muscle strength.The peak patellofemoral joint contact force of the WS is significantly greater than that of the AS;therefore,it is recommended that patients with patellofemoral joint pain use the AS.A squat with a bar can compensate for the body's balance;thus,people with limited ankle dorsiflexion range of motion or anterior tibial muscle weakness may consider trunk control training,such as a deep squat with a bar.This may help improve lower limb stability during squats.

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Objective To analyze the antihypertensive compliance rate,drug use and complication distribution among very old hypertensive inpatients under the antihypertensive standard of 150/90 mm Hg in our country(1 mm Hg=0.133 kPa).Methods A total of 409 hospitalized patients aged ≥80 years and diagnosed with hypertension in all departments of Air Force Medical Center of PLA were enrolled,and according to their clinical outcomes,they were divided into intensive antihypertensive group(106 cases,SBP＜130 mm Hg),standard antihypertensive group(155 ca-ses,SBP 130-149 mm Hg)and non-standard blood pressure group(148 cases,SBP ≥150 mm Hg).The status of blood pressure control was analyze in each group.Results When 150/90 mm Hg was used as the blood pressure standard,25.9％were in the intensive blood pressure group,37.9％were in the standard blood pressure group,36.2％were in the non-standard blood pressure group.The proportion of patients aged＞90 years was significantly lower in the non-standard blood pressure group than the intensive antihypertensive group and the standard anti-hypertensive group(4.1％vs 7.5％and 12.3％,P＜0.05).The ratio of single-drug therapy was significantly higher in the standard antihypertensive group than the intensive antihypertensive group(46.5％vs 32.1％,P＜0.05),and that of dual combination therapy was obviously higher in the intensive antihypertensive group than the standard antihypertensive group(35.8％vs 22.6％,P＜0.05).The proportions of heart damage and cerebrovascular damage were significantly higher(43.4％vs 21.9％,26.4％vs 14.8％),and the proportion of complicated retinopathy was notably lower(11.3％vs 23.9％)in the intensive antihypertensive group than the standard antihypertens-ive group(P＜0.05).Conclusion For very old hypertensive patients in our country,it is more sci-entific and practical to use 150/90 mm Hg as the starting standard for blood pressure reduction.Intensified blood pressure reduction increases cardiovascular and cerebrovascular damages in them instead.

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Objective:This study was conducted to investigate the independent risk factors for predicting the occurrence of acute Stanford type A aortic dissection(TAAD), and to construct a nomogram model for predicting the occurrence of TAAD.Methods:The clinical data of patients meeting the diagnostic criteria for TAAD admitted to Tianjin Chest Hospital from June 2016 to December 2021 and healthy people examined by the physical examination center of Tianjin Chest Hospital during the same period were retrospectively collected, and the independent risk factors for TAAD were predicted by propensity matching analysis. Univariate and multivariate Logistic regression were used to analyze the variables with statistical differences, and a nomogram model was constructed to predict the occurrence of TAAD disease according to the screened risk factors. Results:A total of 148 patients in the TAAD group and 5 690 patients in the control group were collected. After bias matching analysis, 148 pairs were successfully matched. Multivariate Logistic regression analysis was performed on the matching results. The results showed that hypertension(HBP), diabetes mellitus(T2DM), Lp(a), very low density lipoprotein(VLDL) and apolipoprotein A1/B(ApoA1/B) were independent risk factors for the development of TAAD. HBP, Lp(a) and ApoA1/B were pathogenic factors( OR 7.267, 1.010 and 2.199, P<0.05, respectively), while T2DM and VLDL were protective factors( OR 0.173 and 0.139, P<0.05). Based on the independent risk factors obtained by multi-factor Logistic regression analysis, a nomogram model of TAAD incidence was constructed. The area under ROC curve( AUC) for predicting the onset of TAAD was 81.6%(95% CI: 0.766-0.863), and the internal calibration curve was close to the standard curve. Conclusion:This model has a good degree of differentiation and calibration, which is helpful for clinicians to guide healthy people to prevent the occurrence of TAAD and provide a theoretical basis for the prevention of TAAD.

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ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B1（AFB1） in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups： Control （n=6）， AFB1 （n=7）， and linalool （n=7） groups. Linalool solution （200 mg·kg-1） was administered preventatively for 14 days， while the control and AFB1 groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool， AFB1 solution （1 mg·kg-1， dissolved in saline） was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin（HE） staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase（ALT）， aspartate transaminase（AST）， γ-glutamyl transferase（GGT）， lactate dehydrogenase（LDH）， alkaline phosphatase（ALP）， total bilirubin（TBil）， direct bilirubin（DBil）， indirect bilirubin（IBil）， malondialdehyde（MDA）， superoxidedismutase（SOD）， catalase（CAT） ， glutathione（GSH）， Fe3+， and Fe2+ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2（Nrf2） and heme oxygenase-1（HO-1）. Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB1 group， the liver structure in the linalool group tended to be normal， with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT， AST， GGT， LDH， ALP， TBil， DBil， and IBil （P<0.01）， Fe3+ and Fe2+ content， and oxidative stress marker MDA （P<0.01）. The levels of antioxidants SOD， CAT， and GSH significantly increased （P<0.01）. Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol-1（1 cal≈4.186 J）， respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression （P<0.05） and a decrease in HO-1 protein expression （P<0.01） in the linalool group. ConclusionLinalool may protect against AFB1-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels.

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ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

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Objective To observe the clinical efficacy of Shen Shuai Ⅱ Granules combined with integrated Western medicine therapy in patients with primary chronic kidney disease(CKD)in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis,and its effects on expression of serum autophagy related proteins.Methods Totally 88 patients were randomly divided into treatment group and control group,with 44 cases in each group.Both groups were given an integrated Western medicine therapy.On this basis,the treatment group was given Shen Shuai Ⅱ Granules,while the control group was given Shen Shuai Ⅱ placebo,1 bag at a time,twice a day,orally.The treatment for both groups lasted for 24 weeks.The clinical efficacy of the two groups was observed.The TCM symptom scores,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),blood phosphorus(P3-),parathyroid hormone(PTH),and 24-hour urinary protein quantification(24 UPro)before and after treatment were compared in the two groups.The serum levels of autophagy related protein Beclin-1,Atg7,and LC3-Ⅱ were detected by ELISA before and after treatment in the two groups.Safety indexes of both groups were monitored.Results During the treatment,4 cases fell off in the treatment group and 4 cases in the control group.The total effective rate in the treatment group was 55％(22/40),while that in the control group was 30％(12/40).The therapeutic effect in the treatment group was better than that in the control group(P<0.01).Compared with before treatment,the TCM symptom scores in the treatment group decreased after treatment(P<0.01),the levels of Scr,BUN,UA,P3-,PTH,and 24 UPro decreased(P<0.05,P<0.01),while eGFR increased(P<0.01).The levels of Scr in the control group increased(P<0.05),while eGFR decreased(P<0.01).After treatment,the treatment group had lower various TCM symptom scores,Scr,BUN,UA,P3-,PTH,and 24 UPro levels than the control group(P<0.01,P<0.05),and higher eGFR than the control group(P<0.01).Compared with before treatment,the serum levels of Beclin-1,Atg7,and LC3-Ⅱ increased in the treatment group after treatment(P<0.01,P<0.05),while the serum level of Beclin-1 decreased in the control group after treatment(P<0.01).After treatment,the improvement of the above indicators in the treatment group were better than those in the control group(P<0.01,P<0.05).Correlation analysis showed that Beclin-1,Atg7,and LC3-Ⅱ were negatively correlated with Scr and BUN(P<0.05),and positively correlated with eGFR(P<0.05).There was no obvious adverse reaction in both groups.Conclusion The combination of Shen Shuai Ⅱ Granules and integrated Western medicine therapy for the treatment of primary CKD in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis has confirmed efficacy,which can effectively alleviate clinical symptoms,improve renal function,and delay the progression of CKD.The mechanism may be related to improving the level of autophagy in renal.

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Objective:To investigate the value of the virtual monoenergetic image (VMI) obtained by a new dual-layer detector spectral CT combined with metal artifact reduction algorithms(O-MAR) in reduction of different types of artifacts caused by 125I seeds implantation and in improvement of the post-operative CT image quality. Methods:This was a cross-sectional study. Thirty-five patients who underwent dual-layer detector spectral CT scanning of the chest and abdomen after 125I seeds implantation were retrospectively included at the First Affiliated Hospital of Zhengzhou University from March to September 2022. The spectral data were collected and reconstructed into conventional CT image (CI), VMI image (50-150 keV, 20 keV/level), CI+O-MAR image, and VMI+O-MAR image (50-150 keV, 20 keV/level). The artifacts′ removal effects and image quality improvement in each group were evaluated. Two slices with the strongest artifacts were selected for analysis for each patient, resulting in a total of 70 slices. Objective indicators including artifact index (AI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of soft tissue regions affected by artifacts were measured and calculated. Subjective indicators including the overcorrected artifacts and new artifacts, the different forms of artifacts, the diagnosis of artifacts, and the image quality were assessed. One-way analysis of variance was used for comparisons among multiple groups. Paired t test was used to compare the quantitative indicators between the combined O-MAR group and the non-O-MAR group. Kappa statistics was used to evaluate the consistency between observers. Results:In high/low-density artifacts (ROI H/L), the AI values in all groups showed decrease with increasing VMI keV. In artifact-affected tissue (ROI T), SNR of the CI/VMI (70-150 keV)+O-MAR group were significantly higher than those of the CI/VMI group ( P<0.05), CNR of the CI/VMI(50-150 keV)+O-MAR group were significantly higher than those of the CI/VMI group ( P<0.05). Both overcorrection and new artifacts mainly presented in VMI 50 keV and VMI 70 keV groups; Compared with VMI (50-70 keV) group, significantly less numbers of overcorrection and new artifacts were found in VMI (50-70 keV)+O-MAR group ( P<0.05); regarding the comparison of artifact types, with the VMI keV increasing, the number of a-type banded artifacts gradually decreased on images with high-density artifacts, reaching a minimum of 3 in the VMI 150 keV+O-MAR group; while the number of e-type artifacts with little or no artifacts increased, with the highest number of 23 in the VMI 150 keV+O-MAR group. The total number of high-density artifacts in each type decreased with increasing VMI keV. As VMI keV increased, the diagnostic and image quality scores of high-density artifacts in each group were significantly higher than those of low-density artifacts in the VMI+O-MAR group ( P<0.05). Conclusions:VMI combined with O-MAR can significantly improve the objective and subjective image quality of follow-up CT imaging after 125I seed implantation, enhancing lesion visibility and diagnostic confidence. Additionally, VMI+O-MAR showed more pronounced correction effect on high-density artifacts.

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Follicle-stimulating hormone (FSH), luteinizing hormone (LH), miR-23a, apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase (JNK), autophagy and apoptosis play crucial roles in follicular development. However, their role in yak granulosa cells (GCs) remains unknown. Therefore, we examined the effect of miR-23a, ASK1, FSH, and LH on apoptosis, autophagy, and the release and reception of some steroid hormones in these cells. Our results showed that miR-23a overexpression significantly increased the abundance of Beclin1, the LC3II/I ratio, and the number of Ad-mRFP-GFP-LC3-labeled autophagosomes, and decreased p62 abundance. Additionally, Bax abundance and the number of terminal deoxynucleotidyl transferase deoxynucleotide triphosphate nick end labeling-positive cells were reduced, while Bcl2 expression was increased. Overexpression of miR-23a also significantly increased the abundance of estradiol receptor α (ER-α) and ß (ER-ß) and the concentrations of estradiol (E2), progesterone (P4) in yak GCs. Here, treating yak GCs with miR-23a decreased ASK1 expression, which regulates ASK1/JNK-mediated apoptosis, autophagy, E2 and P4 levels, and ER-α/ß abundance. In contrast, treatment of yak GCs with FSH (10 µg/mL) and LH (100 µg/mL) increased miR-23a abundance, regulating the subsequent effect on ASK1/JNK-mediated apoptosis, autophagy, ER-α/ß abundance, and E2 and P4 concentrations. In conclusion, miR-23a enhances autophagy in yak GCs, attenuates apoptosis, and increases ER-α/ß abundance and E2 and P4 concentrations by downregulating ASK1. Additionally, FSH and LH can regulate these effects of miR-23a by altering its expression. These results provide important insights that can inform the development of strategies to reduce abnormal follicular atresia and improve the reproductive rate of yaks.

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Importance: Emerging data suggest that the incidence of early-onset cancers, defined as cancers diagnosed in people younger than 50 years, is increasing, but updated data are limited. Objective: To characterize the patterns in the incidence of early-onset cancers in the US from 2010 to 2019 and provide granular data on the cancers with the fastest-growing incidence rates. Design, Setting, and Participants: This population-based cohort study analyzed data from 17 National Cancer Institute Surveillance, Epidemiology, and End Results registries from January 1, 2010, to December 31, 2019. Age-standardized incidence rates per 100 000 people were extracted for early-onset cancers, with rates age adjusted to the US standard population. A total of 562 145 patients with early-onset cancer between 2010 and 2019 were identified and included. Data were analyzed from October 16, 2022, to May 23, 2023. Main Outcomes and Measures: Primary outcomes were incidence rates and descriptive epidemiological data for people younger than 50 years with cancer. The annual percentage change (APC) of the age-standardized incidence rate was estimated using the Joinpoint regression program. Results: Among 562 145 patients (324 138 [57.7%] aged 40-49 years; 351 120 [62.5%] female) with early-onset cancer, 4565 (0.8%) were American Indian or Alaska Native, 54 876 (9.8%) were Asian or Pacific Islander, 61 048 (10.9%) were Black, 118 099 (21.0%) were Hispanic, 314 610 (56.0%) were White, and 8947 (1.6%) were of unknown race and/or ethnicity. From 2010 to 2019, the age-standardized incidence rate of early-onset cancers increased overall (APC, 0.28%; 95% CI, 0.09%-0.47%; P = .01) and in female individuals (APC, 0.67%; 95% CI, 0.39%-0.94%; P = .001) but decreased in male individuals (APC, -0.37%; 95% CI, -0.51% to -0.22%; P < .001). In contrast, the age-standardized incidence rate of cancers in individuals aged 50 years and older decreased over the study period (APC, -0.87%; 95% CI, -1.06% to -0.67%; P < .001). In 2019, the highest number of incident cases of early-onset cancer were in the breast (n = 12 649). From 2010 to 2019, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancer groups (APC, 2.16%; 95% CI, 1.66%-2.67%; P < .001). Among gastrointestinal cancers, those with the fastest-growing incidence rates were in the appendix (APC, 15.61%; 95% CI, 9.21%-22.38%; P < .001), intrahepatic bile duct (APC, 8.12%; 95% CI, 4.94%-11.39%; P < .001), and pancreas (APC, 2.53%; 95% CI, 1.69%-3.38%; P < .001). Conclusions and Relevance: In this cohort study, the incidence rates of early-onset cancer increased from 2010 to 2019. Although breast cancer had the highest number of incident cases, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancers. These data may be useful for the development of surveillance strategies and funding priorities.

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The basic helix-loop-helix (bHLH) transcription factors (TFs) gene family is an important gene family in plants, and participates in regulation of plant apical meristem growth, metabolic regulation and stress resistance. However, its characteristics and potential functions have not been studied in chestnut (Castanea mollissima), an important nut with high ecological and economic value. In the present study, 94 CmbHLHs were identified in chestnut genome, of which 88 were unevenly distributed on chromosomes, and other six were located on five unanchored scaffolds. Almost all CmbHLH proteins were predicted in the nucleus, and subcellular localization demonstrated the correctness of the above predictions. Based on the phylogenetic analysis, all of the CmbHLH genes were divided into 19 subgroups with distinct features. Abundant cis-acting regulatory elements related to endosperm expression, meristem expression, and responses to gibberellin (GA) and auxin were identified in the upstream sequences of CmbHLH genes. This indicates that these genes may have potential functions in the morphogenesis of chestnut. Comparative genome analysis showed that dispersed duplication was the main driving force for the expansion of the CmbHLH gene family inferred to have evolved through purifying selection. Transcriptome analysis and qRT-PCR experiments showed that the expression patterns of CmbHLHs were different in different chestnut tissues, and revealed some members may have potential functions in chestnut buds, nuts, fertile/abortive ovules development. The results from this study will be helpful to understand the characteristics and potential functions of the bHLH gene family in chestnut.

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Esophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment. It conducted a comprehensive analysis of DPY30 in patients with ESCA using The Cancer Genome Atlas (TCGA) database and clinical tissue microarray specimens of ESCA. Immunohistochemistry was performed to assess the expression levels of DPY30 in tissues. Receiver operating curve analysis, Kaplan-Meier survival analysis and Cox regression analysis were performed to identify the diagnostic and prognostic value of DPY30. Gene Set Enrichment Analysis, protein-protein interaction network and Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data were used to screen DPY30-associated genes and evaluate the immune score of the TCGA samples. The results demonstrated that the expression of mRNA and protein levels of DPY30 were significantly upregulated in tumor tissues compared with normal tissue samples. The expression of DPY30 was closely associated with the poor prognosis of patients with ESCA. The present study also found that DPY30 expression and the pathological characteristics of ESCA were significantly correlated. Additionally, the expression of DPY30 demonstrated a significant positive correlation with various immune cells infiltration. The results suggested that DPY30 might influence tumor immune infiltration. In conclusion, the findings suggested that DPY30 might be a potential prognostic biomarker and an immunotherapeutic target in ESCA.

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The purpose of this study is to investigate the effect of Reduning injection (RI) on influenza A virus (IAV) and its mechanism. We evaluated the cytotoxicity of RI in A549 and MDCK cells by cell counting kit-8 (CCK-8) assay. Western blot and cytopathic effect (CPE) assays were applied to test the effects of RI on viral protein, CPE and virus virulence to evaluate its inhibitory effect. The proteins level of heme oxygenase 1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), phosphorylation of P38 mitogen-activated protein kinases (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2) were detected by Western blot. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the RNA expression of interferon-α/β (IFN-α/β). The relative luciferase reporter assay was used to analyze the promoter activity and transcriptional regulation of Nrf2. The results indicated that RI inhibited IAV-induced MDCK cytopathies in a dose-dependent manner, decreased M2 protein of influenza virus and viral titer, indicating that it has definite effect on inhibiting IAV. RI promotes the phosphorylation of P38 MAPK and ERK1/2, activates the activity of Nrf2 nuclear transcription factor, increases the expression of Nrf2 protein in the nucleus, thus up-regulates the expression of HO-1 protein, and ultimately increases the IFN-α/β mRNA level. In summary, our results demonstrated that RI inhibits the replication of IAV by activating MAPK/Nrf2/HO-1 signaling pathway, revealing a new mechanism of RI against influenza virus, and providing theoretical basis for clinical treatment of influenza virus.