Background and purpose:Members of the serine protease inhibitor(SERPIN)family can influence tumorigenesis,progression,and prognosis by modulating processes such as apoptosis,invasion,metastasis,and angiogenesis in tumor cells.However,their role in pancreatic cancer remains unclear.This study aimed to investigate the impact of high expression of serine protease inhibitor A3(SERPINA3)on the proliferation,apoptosis,migration,and chemoresistance of pancreatic cancer cells and its mechanism.Methods:This study analyzed the SERPINA3 expression levels in the normal pancreatic ductal epithelial cell line hTERT-HPNE and pancreatic cancer cell lines SW1990,Capan-1,PANC-1,and ASPC-1 by real-time reverse transcription quantitative polymerase chain reaction(qRT-PCR).We established gemcitabine-resistant pancreatic cancer cell lines PANC-1/R and ASPC-1/R,and used qRT-PCR assay and cell counting kit-8(CCK-8)to determine the SERPINA3 expression levels in the constructed resistant cell lines and their parental sensitive cell lines,as well as the differences in their chemosensitivity to gemcitabine.We constructed the SERPINA3-knockdown cell line si-SERPINA with siRNA,and the negative control group si-SERPINA#NC with siRNA negative control.We used MDA assay,CCK-8 assay,EdU cell proliferation assay,transwell migration assay,matrigel invasion assay,scratch assay,and apoptotic assay to respectively detect the lipid oxidation levels,proliferation,migration,invasion,wound-healing ability,and the influence on apoptosis of the gemcitabine-resistant pancreatic cancer cells in the si-SERPINA group and the si-SERPINA#NC group.Results:Compared with normal pancreatic ductal epithelial cells hTERT-HPNE,the expression level of SERPINA3 in various pancreatic cancer cell lines was significantly increased(P＜0.05).mRNA and protein expression levels of SERPINA3 in PANC-1/R and ASPC-1/R were significantly increased compared with those in parent cells(P＜0.001).When SERPINA3 was knocked down in PANC-1/R and ASPC-1/R cells,the survival rate of the cells under different concentrations of gemcitabine chemotherapy decreased,and MDA detected that the lipid oxidation level was increased(P＜0.001).In addition,the proliferation rate of PANC-1/R and ASPC-1/R cell lines with SERPINA3 knockout,the number of migrating/invading cells and the healing rate of scratch test were significantly decreased(P＜0.01),and flow cytometry demonstrated that the number of apoptotic cells was increased(P＜0.05).These results suggest that SERPINA3 knockdown can inhibit the proliferation,migration,invasion and wound healing ability of gemcitabine-resistant pancreatic cancer cells,and promote the apoptosis of these resistant cells.Conclusion:SERPINA3 overexpression was found in various pancreatic cancer cells.SERPINA3 overexpression promoted malignant progression and chemotherapy resistance of pancreatic cancer,and interference with SERPINA3 expression promoted ferroptosis and enhanced chemotherapy sensitivity of gemcitabine-resistant pancreatic cancer cells.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective:To establish a quantitative diagnostic standard for Crohn's disease with dampness syndrome based on clinical data using a disease syndrome combination model and conduct bidirectional validation.Methods:256 patients with Crohn's disease from the Department of Spleen and Stomach Diseases at Guangdong Provincial Hospital of Chinese Medicine, the Department of Gastroenterology at the Sixth Affiliated Hospital of Sun Yat-sen University, and the Outpatient Department of Guangdong Provincial Hospital of Chinese Medicine from October 2021 to January 2022 were selected as the observation objects. They were divided into an operation group of 205 patients and a verification group of 51 patients in an 8:2 ratio using a random number table method. The frequency advantage method, χ2 test, and binary logistic regression analysis were used to screen for relevant standard factors. The conditional probability method was used to assign scores to relevant items, and the maximum likelihood method was used to determine the quantitative diagnostic threshold. A quantitative diagnostic standard for Crohn's disease with dampness syndrome based on disease syndrome combination was established, and it was retrospectively analyzed and prospectively verified. Results:On the basis of the 20 candidate quantitative diagnostic criteria items for Crohn's disease dampness syndrome, binary logistic regression analysis was performed to calculate the OR values between each item. The quantitative diagnostic criteria for Crohn's disease with dampness syndrome included tongue coating greasiness (7 points), body heaviness (13 points), waist and knee soreness (8 points), head weight (9 points), bland mouth (6 points), anal heaviness (8 points), uncomfortable bowel movements (8 points), and sticky stools (7 points), with a quantitative diagnostic threshold of 11. Conclusion:The scoring of relevant items in the quantitative diagnostic criteria for Crohn's disease with dampness syndrome is reasonable and has good diagnostic value, which can provide reference for further quantitative research on Crohn's disease syndromes.

This article reports the diagnosis and treatment of two cases of complex ureteral obstruction (UO) in transplanted kidneys managed at Tangdu Hospital of Air Force Medical University of PLA in 2023. UO is a challenging complication following kidney transplantation, with surgical repair being the primary treatment approach. Both patients underwent robot-assisted laparoscopic (RAL) anastomosis of the transplanted kidney collecting system with the autologous ureter. The procedures were successfully performed, and both recipients were discharged without complications. During a six-month postoperative follow-up, the morphology and function of the transplanted kidneys remained stable, with no recurrence of hydronephrosis, fever, pain, urinary frequency, or urgency. This case report provides new insights into the diagnosis and surgical management of complex UO in kidney transplant recipients.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Background and purpose:Members of the serine protease inhibitor(SERPIN)family can influence tumorigenesis,progression,and prognosis by modulating processes such as apoptosis,invasion,metastasis,and angiogenesis in tumor cells.However,their role in pancreatic cancer remains unclear.This study aimed to investigate the impact of high expression of serine protease inhibitor A3(SERPINA3)on the proliferation,apoptosis,migration,and chemoresistance of pancreatic cancer cells and its mechanism.Methods:This study analyzed the SERPINA3 expression levels in the normal pancreatic ductal epithelial cell line hTERT-HPNE and pancreatic cancer cell lines SW1990,Capan-1,PANC-1,and ASPC-1 by real-time reverse transcription quantitative polymerase chain reaction(qRT-PCR).We established gemcitabine-resistant pancreatic cancer cell lines PANC-1/R and ASPC-1/R,and used qRT-PCR assay and cell counting kit-8(CCK-8)to determine the SERPINA3 expression levels in the constructed resistant cell lines and their parental sensitive cell lines,as well as the differences in their chemosensitivity to gemcitabine.We constructed the SERPINA3-knockdown cell line si-SERPINA with siRNA,and the negative control group si-SERPINA#NC with siRNA negative control.We used MDA assay,CCK-8 assay,EdU cell proliferation assay,transwell migration assay,matrigel invasion assay,scratch assay,and apoptotic assay to respectively detect the lipid oxidation levels,proliferation,migration,invasion,wound-healing ability,and the influence on apoptosis of the gemcitabine-resistant pancreatic cancer cells in the si-SERPINA group and the si-SERPINA#NC group.Results:Compared with normal pancreatic ductal epithelial cells hTERT-HPNE,the expression level of SERPINA3 in various pancreatic cancer cell lines was significantly increased(P＜0.05).mRNA and protein expression levels of SERPINA3 in PANC-1/R and ASPC-1/R were significantly increased compared with those in parent cells(P＜0.001).When SERPINA3 was knocked down in PANC-1/R and ASPC-1/R cells,the survival rate of the cells under different concentrations of gemcitabine chemotherapy decreased,and MDA detected that the lipid oxidation level was increased(P＜0.001).In addition,the proliferation rate of PANC-1/R and ASPC-1/R cell lines with SERPINA3 knockout,the number of migrating/invading cells and the healing rate of scratch test were significantly decreased(P＜0.01),and flow cytometry demonstrated that the number of apoptotic cells was increased(P＜0.05).These results suggest that SERPINA3 knockdown can inhibit the proliferation,migration,invasion and wound healing ability of gemcitabine-resistant pancreatic cancer cells,and promote the apoptosis of these resistant cells.Conclusion:SERPINA3 overexpression was found in various pancreatic cancer cells.SERPINA3 overexpression promoted malignant progression and chemotherapy resistance of pancreatic cancer,and interference with SERPINA3 expression promoted ferroptosis and enhanced chemotherapy sensitivity of gemcitabine-resistant pancreatic cancer cells.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

This article reports the diagnosis and treatment of two cases of complex ureteral obstruction (UO) in transplanted kidneys managed at Tangdu Hospital of Air Force Medical University of PLA in 2023. UO is a challenging complication following kidney transplantation, with surgical repair being the primary treatment approach. Both patients underwent robot-assisted laparoscopic (RAL) anastomosis of the transplanted kidney collecting system with the autologous ureter. The procedures were successfully performed, and both recipients were discharged without complications. During a six-month postoperative follow-up, the morphology and function of the transplanted kidneys remained stable, with no recurrence of hydronephrosis, fever, pain, urinary frequency, or urgency. This case report provides new insights into the diagnosis and surgical management of complex UO in kidney transplant recipients.

Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.

  Objective  To investigate the predictive value of albumin-bilirubin (ALBI) score combined with liver function index and carcinoembryonic antigen (CEA) for liver metastasis of colorectal cancer.  Methods  We retrospectively analyzed the clinical data of patients with colorectal cancer who underwent surgical treatment in the Second Hospital & Clinical Medical Hospital, Lanzhou University from January 2016 to July 2021 and were followed up for 24 months. According to the follow-up results, the enrolled patients were divided into liver metastasis group and non-liver metastasis group, and were randomly divided into modeling group and validation group by a ratio of 2∶1. The risk factors of liver metastasis in the patients with colorectal cancer were analyzed. Lasso-Logistic regression was used to construct the prediction model. Bootstrap method was used for internal verification. Receiver operating characteristic curve, calibration curve and clinical decision curve were used to evaluate the reliability of the prediction model. Finally, a nomogram was drawn to show the prediction results.  Results  A total of 195 patients who met the inclusion and exclusion criteria were enrolled, including 130 in the modeling group and 65 in the validation group. Through Lasso regression variable screening and Logistic regression analysis, the results showed that ALBI score(OR=8.062, 95% CI: 2.545-25.540), alanine transaminase (ALT) (OR=1.037, 95% CI: 1.004-1.071) and CEA (OR=1.025, 95% CI: 1.008-1.043) were independent predictors of liver metastasis in colorectal cancer. The area under curve (AUC) of the combined prediction of liver metastasis of colorectal cancer in the modeling group was 0.921, the sensitivity was 78%, the specificity was 95%, the C-index was 0.921, the H-L fitting curve χ²=0.851, P=0.654, and the slope of the calibration curve was close to 1, suggesting that the accuracy of the model was high, and the DCA curve showed that the model had good clinical application value. For the data of the modeling group, the Bootstrap method was used for internal verification of 1000 resamplings. The accuracy was 0.869, the kappa consistency was 0.709, and the AUC was 0.913. When ALBI score, ALT and CEA were used to diagnose liver metastasis of colorectal cancer alone, the AUC of CEA was the largest (0.897), and the combination of the three had the highest efficacy in the diagnosis of liver metastasis of colorectal cancer. In the validation group, the AUC, sensitivity, specificity, C-index of the combined prediction of liver metastasis of colorectal cancer were 0.918, 85.0%, 95.6%, 0.918, respectively, and H-L fitting curve χ²=0.586, P=0.746.  Conclusions  ALBI score, ALT and CEA have certain predictive value for liver metastasis of colorectal cancer. The combined diagnosis of liver metastasis of colorectal cancer has high efficacy, and the risk prediction model constructed has a good predictive effect.