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1.
Angew Chem Int Ed Engl ; : e202407037, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767062

RESUMEN

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket-independent STING-activating agonists (piSTINGs), which act through multivalency-driven oligomerization to activate STING. Additionally, a piSTING-adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING-based vaccine combination with aPD-1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists.

2.
Adv Mater ; 36(16): e2308155, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38295870

RESUMEN

Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity. Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Vacunación , Ingeniería Celular , Células Mieloides , Células Dendríticas
3.
J Med Chem ; 66(18): 13266-13279, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37676021

RESUMEN

Protein or peptide cancer vaccines usually include immune potentiators, so-called adjuvants. However, it remains challenging to identify structurally simple, chemically accessible synthetic molecules that are effective and safe as vaccine adjuvant. Here, we present cholicamideß (6), a self-assembling small-molecule vaccine adjuvant with an improved toxicity profile and proven efficacy in vivo. We demonstrate that cholicamideß (6), which is less cytotoxic than its parent compound, forms virus-like particles to potently activate dendritic cells with the concomitant secretion of cytokines. When combined with a peptide antigen, cholicamideß (6) potentiated the antigen presentation on dendritic cells to induce antigen-specific T cells. As a therapeutic cancer vaccine adjuvant in mice, a mixture of cholicamideß (6) and a peptide antigen protected mice from the challenges of malignant cancer cells without overt toxicity. Cholicamideß (6) may offer a translational opportunity as an unprecedented class of small-molecule cancer vaccine adjuvants.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Animales , Ratones , Vacunas contra el Cáncer/uso terapéutico , Adyuvantes de Vacunas , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/química , Linfocitos T , Adyuvantes Farmacéuticos , Vacunas de Subunidad , Péptidos , Células Dendríticas
4.
Zhongguo Zhen Jiu ; 43(8): 937-43, 2023 Aug 12.
Artículo en Chino | MEDLINE | ID: mdl-37577892

RESUMEN

OBJECTIVE: To observe the effects of acupuncture at "Kongzui" (LU 6) and "Yuji" (LU 10) on the latent period of inducing asthma, pulmonary function and the expression of endothelin-1 (ET-1) and metallothionein-2 (MT-2) in asthma rats, and to explore the possible mechanism of acupuncture in alleviating airway smooth muscle spasm and improving the acute attack of asthma. METHODS: A total of 40 male SD rats of SPF-grade were randomly divided into a normal group, a model group, a medication group and an acupuncture group, 10 rats in each group. Except for the normal group, ovalbumin sensitization method was used to establish the asthma model in the other 3 groups. Salbutamol nebulization was adopted in the medication group, while acupuncture was applied at bilateral "Kongzui" (LU 6) and "Yuji" (LU 10) in the acupuncture group. The intervention was given once a day for 14 days in the two groups. The latent period of inducing asthma and pulmonary function were observed, the levels of ET-1 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA method, the morphology of the airway was observed by Masson staining, the ultrastructure of the airway smooth muscle was observed by transmission electron microscopy, the mRNA and protein expression of ET-1 and MT-2 in lung tissue was detected by real-time PCR and Western blot methods. RESULTS: Compared with the normal group, in the model group, the latent period of inducing asthma was shortened (P<0.01); the airway resistance (RL) was increased while the dynamic compliance (Cdyn) was decreased (P<0.01, P<0.05); the levels of ET-1 and TNF-α in serum and BALF were increased (P<0.01); collagen fibers and collagen depositions were found around the bronchi, airway smooth muscle was thickened, the cell damage was severe and mitochondria were swollen; the mRNA and protein expression of ET-1 was increased while the mRNA and protein expression of MT-2 was decreased (P<0.01). Compared with the model group, in the acupuncture group, the latent period of inducing asthma was prolonged (P<0.05), the RL was decreased while the Cdyn was increased (P<0.01, P<0.05). Compared with the model group, in the medication group and the acupuncture group, the levels of ET-1 and TNF-α in serum and BALF were decreased (P<0.01, P<0.05); collagen fibers and collagen depositions around the bronchi were reduced, the thickened airway smooth muscle was lightened, the cell damage was improved; the mRNA and protein expression of ET-1 was decreased while the mRNA and protein expression of MT-2 was increased (P<0.01). Compared with the medication group, the mRNA expression of MT-2 was increased in the acupuncture group (P<0.05). CONCLUSION: Acupuncture at "Kongzui" (LU 6) and "Yuji" (LU 10) can improve the pulmonary function and alleviate the airway smooth muscle spasm in rats with asthma. Its mechanism may be related to the down-regulation of ET-1 expression and up-regulation of MT-2 expression.


Asunto(s)
Terapia por Acupuntura , Asma , Ratas , Masculino , Animales , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Sprague-Dawley , Pulmón , Asma/genética , Asma/terapia , Asma/metabolismo , Espasmo , ARN Mensajero/metabolismo
5.
Chem Commun (Camb) ; 58(87): 12228-12231, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36254577

RESUMEN

The effective co-delivery of antigens and immune potentiators (adjuvants) and the high degree of antigen presentation have been two major challenges in the development of subunit vaccines. Here, we address these issues by conjugating peptide antigens with cholicamide, a self-assembling small molecule adjuvant. Co-assemblies of the conjugates and cholicamide achieved high levels of both cytokine induction and MHC class II peptide presentation.


Asunto(s)
Adyuvantes Inmunológicos , Antígenos , Adyuvantes Inmunológicos/farmacología , Péptidos
6.
Nano Res ; 15(5): 4191-4200, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35126879

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here, we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein. The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs, which might be capable of protecting the host from infection without systemic toxicity. In addition, the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2. Furthermore, inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection. This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff. Electronic Supplementary Material: Supplementary material (the immune activation of CS-mediated nanovacccine on BMDCs, cell viability, immune responses in lungs and BALF, serum chemistry and H&E histopathological analysis.) is available in the online version of this article at 10.1007/s12274-021-4012-9.

7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-865680

RESUMEN

Objective:To investigate the risk factors for delayed gastric emptying (DGE) following pancreaticoduodenectomy (PD).Methods:Clinical data of 385 patients who underwent PD in Changhai Hospital of Navy Medical University from January 2017 to November 2017 were retrospectively analyzed, including 235 men and 150 women. According to the definition of DGE by the International Study Group of Pancreatic Surgery (ISGPS), patients were divided into-clinically irrelevant DGE (non CR-DGE) group and clinically relevant DGE(CR-DGE) group. Univariate analysis and multivariate logistic analysis were used to identify the risk factors of CR-DGE after PD.Results:Of the 385 patients, 78 cases (20.3%) developed DGE. There were 35 cases of CR-DGE (9.1%). In the multivariate analysis, BMI( OR=1.117, 95% CI1.006-1.240, P=0.038), preoperative serum albumin( OR=0.902, 95% CI 0.832-0.977, P=0.012), the main pancreatic duct diameter (MPD)≤3 mm( OR=2.397, 95% CI 1.016-5.653, P=0.046), soft texture of pancreas( OR=2.834, 95% CI 1.093-7.350, P=0.032), clinically relevant postoperative pancreatic fistula (CR-POPF)( OR=4.498, 95% CI 1.768-11.441, P=0.002) were independent risk factors for CR-DGE after PD. Conclusions:High BMI, low preoperative serum albumin, MPD ≤3 mm, soft texture of pancreas and CR-POPF after surgery were independent risk factors for CR-DGE, and early clinical interventions should be performed.

8.
Chinese Journal of Surgery ; (12): 534-539, 2019.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-810711

RESUMEN

Objective@#To investigate the prognostic factors of hyperamylasemia following pancreaticoduodenectomy (PD) .@*Methods@#Clinical data of 359 patients were collected prospectively who underwent PD by the same group at Changhai Hospital of Navy Medical University from January 2017 to June 2018.There were 212 males and 147 females.The median age was 63 years old (range: 23 to 82 years old) .According to whether the patient′s serum amylase was greater than 120 U/L at 0 or 1 day after surgery,the patients were divided into hyperamylasemia group and non-hyperamylasemia group. Univariate analysis and multivariate analysis were used to find out the prognostic factors of hyperamylasemia after PD.@*Results@#Of the 359 patients, 238 cases (66.3%) developed hyperamylasemia.The incidence rate of clinically related pancreatic fistula (15.1% vs.2.5%, P<0.01) , grade B/C post pancreatectomy hemorrhage (8.8% vs. 2.5%, P<0.01) , and surgical site infection (9.2% vs. 3.3%, P=0.04) was significantly higher in the hyperamylasemia group.The severity of complications (CD grade≥Ⅲ: 11.3% vs.4.1%, P=0.023) and postoperative hospital stay (11 days vs. 9 days, P=0.001) were higher in the hyperamylasemia group.In the multivariate analysis, the main pancreatic duct diameter (MPD) ≤3 mm (OR=4.469, 95% CI: 2.563-7.793, P<0.01) , pathological type of disease (pancreatic cancer or pancreatitis) (OR=0.230, 95% CI: 0.122-0.436, P<0.01) and soft texture of pancreas (OR=3.297, 95%CI: 1.930-5.635, P<0.01) were independent prognostic factors for hyperamylasemia.@*Conclusions@#Post-PD hyperamylasemia increased the incidence and severity of postoperative complications after PD.MPD≤3 mm, soft texture of pancreas and pathological type of disease were independent prognostic factors of hyperamylasemia.

9.
Chinese Journal of Surgery ; (12): 840-847, 2019.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-800964

RESUMEN

Objective@#To examine the prognostic value of four important driver gene mutations in patients with radical resection of pancreatic cancer.@*Methods@#The clinical data and follow-up data of pancreatic cancer patients undergoing radical pancreatectomy and targeted sequencing from January 2016 to March 2018 at Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital were retrospectively analyzed.There were 159 males and 88 females,aged of (60.8±8.7)years(range:33-83 years) and preoperative CA19-9 of (492.4±496.6)kU/L(range: 2-1 200 kU/L). One hundred and fifty nine cases of tumors were located in the head and 88 cases in the body and tail of the pancreas. After univariate analysis of clinical pathological factors (including gender, age, preoperative CA19-9, tumor location, tumor differentiation, pathological T and N stage, Micr. perineural invasion, Micr. lympho-vascular invasion, resection margin), the variable whose P<0.1 was included in COX regression model with four important driver gene mutations to find which mutation was related to prognosis independently. The number of gene mutations and KRAS subgroups were analyzed by Kaplan-Meier curve.@*Results@#Among 247 patients,the number of KRAS,TP53, SMAD4 and CDKN2A mutations was 212 cases(85.8%), 160 cases(64.8%), 66 cases(26.7%) and 44 cases(17.8%),respectively.KRAS mutation was correlated with the tumor differentiation and pathological T stage (χ2=24.570/6.690, P=0.000/0.035), TP53 mutation was correlated with the tumor differentiation and the resected margin(χ2=5.500/4.620, P=0.019/0.032), and CDKN2A mutation was correlated with gender(χ2=16.574, P=0.000).COX regression model analysis showed that only KRAS mutation was an independent risk factor for disease free survival and overall survival(HR=1.776, 95%CI: 1.079-2.923, P=0.024; HR=1.923, 95%CI: 1.016-3.639, P=0.045); KRASG12D mutation was associated with shorter OS(P=0.007).@*Conclusion@#KRAS and its subgroup KRASG12D mutation can be used as a prognostic index for patients with radical resection of pancreatic cancer.

10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-699187

RESUMEN

Objective To investigate the clinical efficacy of pancreaticoduodenectomy using artery first approach and prior portal vein (PV)-superior mesenteric vein (SMV) shunting for complicated pancreatic head tumors.Methods The retrospective cohort study was conducted.The clinicopathological data of 91 patients with pancreatic head cancer who were admitted to the Changhai Hospital of Navy Medical University from February 2011 to December 2016 were collected.Among 91 patients undergoing pancreaticoduodenectomy combined with vascular resection and reconstruction,27 using artery first approach and PV-SMV shunting and reconstruction were allocated into the PD-PVR group,23 using conventional approach were allocated into the PD-CVR group,and 41 receiving pancreaticoduodenectomy with vascular resection were allocated into the PD-SVR group.Observation indicators:(1) comparison of intra-and post-operative situations among groups;(2) comparison of postoperative pathological results among groups;(3) comparison of postoperative survival among groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2017.Comparisons among groups of count data were done by the chi-square test or Fisher exact probability.Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA,and pairwise comparison was done using the LSD method.Measurement data with skewed distribution were described as M(Q),comparison among groups was analyzed using the Kurskal-Wallis rank sum test,and pairwise comparison was done using the paired comparison with adjusted P value.Ordinal data were compared using the nonparametric test.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Comparison of intra-and post-operative situations among groups:operation time,time of hepatic inflow occlusion,volume of intraoperative blood loss,cases with intraoperative blood transfusion,length of PV or SMV removal,cases with vascular grafts,grading 1,2,3,4 and 5 of Clavien-Dindo classification of postoperative complications and duration of hospital stay were respectively (274±36)minutes,(22±7)minutes,1 661 mL (110 mL,3 800 mL),20,(5.6±1.4)cm,6,11,1,1,1,1,(20±7)days in the PD-PVR group and (281±41)minutes,(27±5)minutes,1 888 mL (176 mL,4 162 mL),18,(5.4±1.5) cm,3,1,8,2,0,0,(21±7)days in the PD-CVR group and (201± 36)minutes,(16±6)minutes,1052 mL (74 mL,3 926 mL),17,(3.2±2.0) cm,5,15,2,3,1,1,(13± 6)days in the PD-SVR group,with statistically significant differences among groups (F=37.060,34.530,x2=13.771,14.015,F=32.260,x2 =39.309,F =19.880,P<0.05).Patients with postoperative complications were improved by symptomatic and supporting treatment.(2) Comparison of postoperative pathological results among groups:mnaximum tumour dimension was respectively (3.6± 1.3) cm,(4.0± 1.3) cm and (2.6± 1.3) cm in the PD-PVR,PD-CVR and PD-SVR groups,with a statistically significant difference among groups (F =7.845,P<0.05).Cases with high-differentiated,moderate-differentiated and low-differentiated tumors of tumor differentiation,staging Ⅱ A and Ⅱ B of tumor staging,nerve invasion,positive lymph node,positive resection margins in neck of pancreas,bile duct and SMV were respectively 0,13,14,17,10,17,21,0,0,0 in the PD-PVR group and 1,12,10,10,13,15,19,1,0,0 in the PD-CVR group and 1,29,11,17,24,30,29,2,1,1 in the PD-SVR group,with no statistically significant difference among groups (x2 =4.122,3.306,0.902,1.214,P>0.05).(3) Comparisons of postoperative survival among groups:of 91 patients,52 were followed up for 3.0-69.3 months,with a median time of 18.0 months and follow-up rate of 57.1% (52/91),including 16 in the PD-PVR group and 14 in the PD-CVR group and 22 in the PD-SVR group.The median survival time,1-,2-and 3-year overall survival rates in 52 patients were respectively 16.6 months,63.5%,35.7% and 26.8%.The survival time in the PD-PVR,PD-CVR and PD-SVR groups were respectively 12.3 months (3.9-69.3 months),15.0 months (3.0-63.3 months) and 20.0 months (6.0-65.2 months),with a statistically significant difference in survival among groups (x2=6.201,P<0.05),and between PD-PVR and PD-SVR groups (x2 =4.412,P<0.05).There was no statistically significant difference in survival between PD-PVR and PD-CVR groups (x2 =0.001,P>0.05).Conclusion Pancreaticoduodenectomy using artery first approach and PV-SMV shunting and reconstruction for complicated pancreatic head tumors can reduce the time of hepatic inflow occlusion,it also contributes to the risk control of surgery for complicated pancreatic tumors,increases surgical safety and improves patients' prognosis.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-708353

RESUMEN

Objective To study the effect of robot-assisted distal pancreatectomy.Methods 63 patients who were originally scheduled for robot-assisted distal pancreatectomy were vetrospectively analyzed from July 2013 to June 2017 in Changhai Hospital.Results The operations were successfully carried out in 61 patients.One patient was converted to open surgery because of extensive adhesions,and another patient underwent local excision of a pancreatic tumor.17 patients underwent robot-assisted spleen-preserving distal pancreatectomy,and 44 patients robot-assisted distal splenopancreatectomy.The mean operative time was 164.1 minutes.The intraoperative blood loss was 153.7 ml.Only 1 patient received 400 ml.of blood transfusion.The rate of postoperative pancreatic fistula was 45.9%.The rates of biochemical fistula and level B fistula were 37.7% and 8.2%,respectively.No level C fistula was observed.Conclusion Robot-assisted distal pancreatectomywas an efficacious and safe technique with its unique advantages in spleen-preserving operations.

12.
Chinese Journal of Surgery ; (12): 909-915, 2017.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-809641

RESUMEN

Objective@#To compare the clinical therapeutic effects of arterial first approach pancreaticoduodenectomy(AFA-PD) with standard approach pancreaticoduodenectomy(SPD) in the treatment of borderline resectable pancreatic cancer (BRPC).@*Methods@#A retrospective analysis of the clinical data of 113 cases of pancreatic cancer patients from January 2014 to August 2015 at Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital, the Second Military Medical University, including 43 cases in AFA-PD group and 70 cases in SPD group.Every patient had gone high-resolusion computed tomography before the surgery, when BRPC was definitely diagnosed by both experienced radiologist and pancreatic surgeon.There were 24 males and 19 females in the AFA-PD group, with average age of (61.6±10.2)years.And in the SPD group, there were 47 males and 23 females, with average age of (62.7±9.4)years.@*Results@#The operation time was (210.7±31.5)minutes in AFA-PD group, (187.9±27.4)minutes in SPD group, and peroperative bleeding volume was (1 007.1±566.3)ml in AFA-PD group, (700.0±390.0)ml in the other group.Those two indicators of AFA-PD group, compared with SPD group, were relatively higher, the difference was statistically significant(all P<0.01). And with regard to postoperative diarrhea(9.3% vs.5.7%), postoperative 1, 3 days of white blood cells(postoperative 1 day: (13.3±1.1)×109/L vs.(12.4±2.4)×109/L; postoperative 3 days: (12.7±1.6)×109/L vs.(11.7±2.5)×109/L), postoperative 1, 3, 5 days of peritoneal drainage fluid volume(postoperative 1 day: (184±42)ml vs.(156±54)ml; postoperative 3 days: (155±48)ml vs.(133±35)ml; postoperative 5 days: (66±20)ml vs.(47±31)ml), the differences between the two groups were statistically significant (all P<0.05). One patient in the SPD group was treated with unplanned secondary surgery for postoperative intraperitoneal hemorrhage, and the patient was cured and discharged.There was no death in the two groups within 30 days after surgical operation and no patient with positive gastric margin, duodenal margin, or anterior margin.The resection rate of superiormesenteric artery(SMA) margin R0 in AFA-PD group was higher than that in SPD group (P=0.019). The two groups were followed up for 14 to 30 months.As for AFA-PD group, the average survival time, progression free survival time and median survival time was respectively (20.4±1.2)months, (21.5±1.4)months and 20 months.There were 3 cases(7.0%) with local recurrence and 8 cases(18.6%) with liver metastasis or distant metastasis.In the SPD group, the average survival time, progression free survival time and median survival time was (17.1±1.1)months, (16.4±1.3)months and 16 months, respectively.There were 13 cases(18.6%) with local recurrence and 25 cases(35.7%) with liver metastasis or distant metastasis.As a result, the AFA-PD group had longer survival time(P=0.001)and progression free survival time(P=0.002). However, the lower local recurrence and distant metastasis rate in AFA-PD group did not reach statistical standard (P>0.05).@*Conclusion@#The arterial first approach pancreaticoduodenectomy is safe and effective in the treatment of borderline resectable pancreatic cancer, which can improve the resection rate of SMA margin R0, and prolong patient survival time.

13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-608542

RESUMEN

Objective To investigate the utility of plasma procalcitonin (PCT) as an early predictor for postoperative complications in patients who underwent elective pancreaticoduodenectomy (PD).Methods Clinical data of 87 patients who underwent elective PD in Changhai Hospital from March.1, 2016 to Dec.31, 2016 were collected.The general data, postoperative recovery, serum PCT level and white blood cell (WBC) count before, 1 d, 3 d and 5 d after PD were recorded.ROC curve was drawn and AUC was calculated to determine the cutoff value, sensitivity and specificity.Patients were divided into complication group (n=42) and noncomplication group (n=45) based on the occurrence of post-operative complications, and the comparisons between the two groups were performed.Results There were no significant differences on the age, gender, diabetes, obstructive jaundice, laboratory tests including PCT, operative time, blood loss volume during surgery and tumor type between the two groups, which were comparable.Complication group had longer hospitalization than noncomplication group (24 d vs 15 d,P0.05), but the plasma PCT level in patients with pancreatic fistula and peritoneal infection on 3 d and 5 d after PD was significantly higher than those in noncomplication group, and the difference was statistically significant (all P<0.05).The combination of plasma PCT and WBC on 3 d and 5 d after PD was superior to PCT or WBC alone in predicting pancreatic fistula (sensitivity 88.9%, 72.7%;specificity 68.5%, 78.2%) and abdominal infection (sensitivity 100%, 100%;specificity 45.9%, 44.4%).Conclusions Plasma PCT could predict the occurrence of abdominal infection and pancreatic fistula after PD.The combination of PCT and WBC might be more valuable in predicting abdominal infection and pancreatic fistula.

14.
Zhong Yao Cai ; 39(7): 1618-22, 2016 Jul.
Artículo en Chino | MEDLINE | ID: mdl-30204364

RESUMEN

Objective: To study Jianpi Qingre Huoxue decoction( JPQRHX) in preventing colon cancer by observing SW480 cells proliferation,apoptosis,cycle and the expression of P-ß-catenin, and to research its mechanism. Methods: SW480 cells were incubated with serum containing blank serum, different concentrations of JPQRHX decocition and PI3 K blocking agent LY294002 for 24 h,respectively. Cell proliferation was detected by MTT assay, cell cycle and apoptosis were detected by flow cytometry. The protein translocation of P-ß-catenin was assayed by immunofluorescent staining. Results: The inhibitory rate and apoptosis rate in JPQRHX decoction group were higher than control group( P < 0. 05),respectively. S phase cells were increased significantly, and G1 phase cells and LY294002 group cells were decreased significantly( P < 0. 05). The P-ß-catenin in JPQRHX decoction groups were mainly expressed in membrane, while the P-ß-catenin in the control group was characterized by deletion in membrane and increased in nucleus. Conclusion: JPQRHX decoction has the ability in curing colon cancer, and the mechanism is associated with altering the expression of P-ß-catenin in the cells nucleus, blocking SW480 cells cycle at G1 phase, inhibiting SW480 cells proliferation, and inducing SW480 cell apoptosis.


Asunto(s)
Medicamentos Herbarios Chinos , Apoptosis , Ciclo Celular , División Celular , Línea Celular Tumoral , Proliferación Celular , Cromonas , Neoplasias del Colon , Humanos , Morfolinas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , beta Catenina
15.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-494925

RESUMEN

Objective To investigate the application value of double-layer continuous suture in pancreatic jejunum anastomosis of pancreatoduodenectomy (PD).Methods A retrospective analysis of 114 consecutive patients (67 men and 47 women) who underwent PD from June 2012 to July 2013 were conducted. There were 79 patients who were treated by double-layer continuous suture technique and 35 patients by double-layer interrupted suture technique .The incidence of pancreatic fistula and other complications after PD with two different suture techniques were compared .Results The operation time of double-layer continuous suture group and double-layer interrupted suture group is respectively ( 284 ±5 ) and ( 288 ±7 ) mins, the intraoperative bleeding volume is respectively (236 ±29) and (282 ±49) ml, the differences between two groups were no statistical significance .The postoperative fasting time in two group was respectively (7.8 ± 0.5) and (9.7 ±0.5) days, the length of hospital stay time was respectively (14.0 ±1.0) and (17.2 ± 10.0) days, the incidence of postoperative pancreatic fistula ( POPF) was respectively 17.1%(6/35) and 39.2%(317/9 ), the differences between two groups were statistically significant (all P<0.05).Grade A POPF was found in 4 patients ( 11.4%) from the double-layer continuous suture group and in 5 patients (6.3%) from the double-layer interrupted suture group.Grade B POPF was identified only in 1 patients (2.9%) from the double-layer continuous suture group and in 23 patients (29.1%) from the double-layer interrupted suture group .The presence of Grade C POPF was only documented in 1 patient from the double-layer continuous suture group and in 3 patients from the interrupted suture group .Conclusions Continuous suture can be safely used in the duct-to-mucosa pancreatojejunostomy .The double-layer continuous suture can be more effective in reducing pancreatic fistula , improving the feeding time , and reducing the length of hospital stay, and it is worthy of clinical popularization and application .

16.
Artículo en Inglés | MEDLINE | ID: mdl-24744811

RESUMEN

Objective. Hypertension is one of the most common cardiovascular disorders with high mortality. Here we explored the antihypertension effects of Huanglian Jiedu Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive rats. Methods. A rat model of spontaneous hypertension was used. The gene change profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC) analysis using the Agilent Whole Rat Genome Oligo Microarray. Results. Hypertension induced 441 genes upregulated and 417 genes downregulated compared with the normal control group. Treatment of HJD resulted in 76 genes downregulated and 20 genes upregulated. GC data analysis showed that the majority of change genes were involved in immune system process, developmental process, and cell death. Conclusion. Hypertension altered expression of many genes that regulate various biological functions. HJD significantly reduced hypertension and altered the gene expression profiles of SHR rats. These changing genes were involved in many cellular functions such as regulating smooth muscle contraction, Ca(2+) homeostasis, and NO pathway. This study provides the potential novel insights into hypertension and antihypertension effects of HJD.

17.
Ann Hematol ; 93(7): 1177-83, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24599583

RESUMEN

Castleman's disease (CD) is a benign lymphoproliferative disorder characterized by dysfunctional lymphatic node hyperplasia. Lymphatic node hyperplasia is associated with elevated levels of inhibitor of differentiation 1 (ID1) in many human tumors. To assess the possible role of ID1 expression as a prognostic marker in multicentric CD (MCD), intra-lymph node ID1 expression was analyzed and related to clinical characteristics and outcomes in 48 patients. Furthermore, the correlation between ID1 and possible signaling molecules such as interleukin-6 (IL6), phosphorylated extracellular response kinase (p-ERK), and vascular endothelial growth factor C (VEGFC) was explored on six fresh MCD surgical specimens. Immunohistochemistry revealed that the patients with extensive ID1 expression had significantly poorer prognosis, compared to those with localized ID1. In addition, ID1 was positively associated with levels of IL6, p-ERK, and VEGFC. We conclude that ID1 may ultimately be a prognostic marker in MCD and that the IL6/ERK/VEGFC pathway is involved in the progress of this disease.


Asunto(s)
Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/metabolismo , Regulación de la Expresión Génica , Proteína 1 Inhibidora de la Diferenciación/biosíntesis , Anciano , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-447038

RESUMEN

Objective To study the prevention and treatment of chylous leakage after Whipple operation.Methods Clinical data of 381 patients underwent Whipple operation from Jan 2010 to march 2013 were retrospectively analyzed.Results Among 381 patients,23 patients had chylous leakage,the incidence was 6.04%.While in 89 patients,in which intraoperative precautionary physical ligation or mattress suturing of the lymphatic vessels were undertaken,no chyle leakage occurred ; Most of chyle leakage occurred in malignant tumor after radical resection(21 patients),most chylous leakage was found 5-8 days after surgery,with daily volume of 260-450 ml.All patients of chylous leakage were cured by conservative treatment.Conclusions Chylous leakage are common in PD.Intraoperative preventive measures such as lymphatic duct ligation or safe suturing can effectively prevent chyle leakage.Conservative therapy heals most chylous leakage after Whipple operation.

19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-840839

RESUMEN

Objective: To compare post-orthotopic liver transplantation(OLT) survival rates between patients with recurrent HCC after partial hepatectomy and those with de novo OLT for HCC, and to screen for the risk factors associated with post-OLT mortality. Methods: From July 2003 to August 2005, 77 consecutive HCC patients underwent OLT, including 15 patients with recurrent HCC after partial hepatectomy for tumor resection (the rescue OLT group) and 62 patients with de novo OLT for HCC (the de novo OLT group); the post-operation survival rates were compared between the 2 groups. Thirty-three demographic, clinical, histological, laboratory and intra- and post-operative variables were analyzed. Cox proportional hazards regression model were used to screen for the factors associated with the survival rate. Results: The median age of the patients was 48.6 years and the median follow-up period was 20 months. Three patients(20.0%) in the rescue OLT group and 15 patients (24.2%) in the de novo OLT group died during follow-up(P=0.73). The 30 day-mortality of OLT was 6.7% for the rescue OLT group vs. 1.6% for the de novo OLT group(P=0.27). Cox proportional hazards model showed that the presence of pre-OLT hyperbilirubinemia, requirement of post-OLT transfusion, size of the largest tumor, tumor macroembolism and family history of HCC were significantly associated with a higher hazard for mortality. Conclusion: No significant difference is found in the survival rates between OLT as de novo therapy and OLT as a rescue therapy for patients with HCC. Pre-OLT hyperbilirubinemia, post-OLT requirement of transfusion, size of the largest tumor, tumor macroembolism, and family history of HCC are associated with a poor survival outcome.

20.
Zhong Xi Yi Jie He Xue Bao ; 6(8): 843-51, 2008 Aug.
Artículo en Chino | MEDLINE | ID: mdl-18664355

RESUMEN

OBJECTIVE: To reveal the characteristics of gene expression in adrenal gland of H22 tumor mice with typical syndromes and in different liver cancer stages. METHODS: By the quantitative four diagnosis and syndrome differentiation methods and GeneChip Mouse Exon 1.0 ST Array, we observed adrenal gland gene expression in H22 tumor mice with pathogenic factor-toxin predominance syndrome and qi deficiency syndrome in the earlier stage, yang-qi deficiency syndrome in the intermediate stage, and qi-yin-yang deficiency syndrome in the advanced stage. Genes highly expressed and remarkably different were analyzed in this study. RESULTS: A total of seventy-three up-regulated coincident genes and twenty-six down-regulated coincident genes in different stages were investigated in the study. Up-regulated coincident genes included Hp, C3, Anxa1, Procr, C2, Il4ra, Cd14, Ptprc, Cd52, C4b, Eno3, Xdh, Gpx3, and so on. Down-regulated coincident genes included nervous system function-related genes such as Plp1, Mbp, Aldh1a1, Cck, Atn1, genes associated with electrolyte metabolism such as Aldh1a1 and Slc22a17, genes related to signal transduction such as Cxcr4, Spag5 and Stmn3, etc, and genes related to transcriptional control and protein biosynthesis such as Hspa1a, Dnajb1, Thra, Hhex and so on. CONCLUSION: With the development of the tumorigenesis, the symptoms and signs and differentially expressed genes in adrenal gland of H22 tumor mice can be measured. Up-regulated and down-regulated coincident genes may be the features of H22 tumor mice different from those of normal mice.


Asunto(s)
Glándulas Suprarrenales/metabolismo , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Neoplasias Hepáticas Experimentales/genética , Medicina Tradicional China , Animales , Regulación Neoplásica de la Expresión Génica , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Distribución Aleatoria , Síndrome
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