OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

Oxidative stress(OS)and dopaminergic neuron(DN)dysfunction are implicated in the pathogenesis and progression of various neurological disorders.As the primary active component of the traditional Chinese herb Scutellaria baicalensis,baicalin has garnered significant attention due to its potent antioxidant and anti-inflammatory properties.Baicalin exhibits a particular affinity for the dopamine(DA)system,maintaining cerebral DA levels by regulating oxidative stress(OS)-related pathways,suggesting that the DA system serves as the"intracerebral target system"through which it exerts its neuroprotective effects.Nuclear factor erythroid 2-related factor 2(Nrf2),a central transcription factor regulating redox homeostasis,plays a pivotal role in the anti-OS process mediated by baicalin.This systematic review covers the pharmacological effects of baicalin,providing an in-depth mechanistic analysis of the interaction between OS and DN,with a focus on the latest research progress in baicalin-mediated treatment of OS through the Nrf2 signaling pathway in neurological diseases to provide theoretical references for the pharmacological and molecular mechanisms of baicalin's anti-OS modulation of the DA system for the treatment of neurological diseases.

Objective To investigate the expression levels of serum tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β(14-3-3β)and clara's cell secretory protein 16(CC16)in patients with chronic obstructive pulmonary disease(COPD)complicated by respiratory failure,and their relationship with prognosis.Methods A total of 232 patients with COPD complicated with respiratory failure admitted to Yantian Hospital of Southern University of Science and Technology from April 2020 to October 2023 were enrolled in the COPD complicated with respiratory failure group.According to the severity of the disease,they were divided into mild group(n=67),moderate group(n=73)and severe group(n=92).According to the 28-day prognosis,they were divided into death group(n=73)and survival group(n=159).In addition,80 patients with simple COPD(COPD group)and 80 healthy subjects(control group)were selected at the same time.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of serum 14-3-3β and CC16.Multivariate Logistic regression analysis was used to analyze the factors of death in patients with COPD complicated with respiratory failure.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum 14-3-3β and CC16 expression on the death of patients with COPD complicated with respiratory failure.Results The expression of serum 14-3-3β in COPD complicated with respiratory failure group was higher than that in COPD group and control group(U=3.894,11.417),the expression of CC16 was lower than that in COPD group and control group(t=5.845,14.306),and the differences were statistically significant(all P<0.05),respectively.The expression of serum 14-3-3β in severe group was higher than that in moderate group and mild group(U=5.179,8.234),the expression of CC16 was lower than that of moderate group and mild group(t=4.090,9.281),and the differences were statistically significant(all P<0.05),respectively.The 28-day mortality rate of 232 COPD patients with respiratory failure was 31.47%(73/232).The expression of serum 14-3-3β in the death group was higher than that in the survival group,and the expression of CC16 was lower than that in the survival group,the differences were statistically significant(U/t=6.790,8.265,all P<0.05).The age of the death group was older than that of the survival group,the degree of airflow limitation and the number of acute exacerbations within 1 year were higher than those of the survival group,and the differences were statistically significant(t/χ2/U=3.895,7.202,3.360,all P<0.05).Age,severe airflow limitation,extremely severe airflow limitation,and the number of acute exacerbations within 1 year,elevated 14-3-3β were independent risk factors for death in patients with COPD complicated with respiratory failure(Wald χ2=3.914～22.668,all P<0.05),and elevated CC16 was an independent protective factor(Wald χ2=23.675,P<0.05).The area under the curve(AUC)of serum 14-3-3β combined and CC16 expression in predicting the death of patients with COPD complicated with respiratory failure which was greater than that of serum 14-3-3β and CC16 expression alone,the differences were statistically significant(Z=3.995,3.813,all P<0.01).Conclusion The increase of serum 14-3-3β expression and the decrease of CC16 expression in patients with COPD complicated by respiratory failure are closely related to the aggravation of the disease and poor prognosis.The combination of serum 14-3-3β and CC16 expression is of high value in predicting the death of patients with COPD complicated with respiratory failure.

Objective To investigate the expression levels of serum tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β(14-3-3β)and clara's cell secretory protein 16(CC16)in patients with chronic obstructive pulmonary disease(COPD)complicated by respiratory failure,and their relationship with prognosis.Methods A total of 232 patients with COPD complicated with respiratory failure admitted to Yantian Hospital of Southern University of Science and Technology from April 2020 to October 2023 were enrolled in the COPD complicated with respiratory failure group.According to the severity of the disease,they were divided into mild group(n=67),moderate group(n=73)and severe group(n=92).According to the 28-day prognosis,they were divided into death group(n=73)and survival group(n=159).In addition,80 patients with simple COPD(COPD group)and 80 healthy subjects(control group)were selected at the same time.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of serum 14-3-3β and CC16.Multivariate Logistic regression analysis was used to analyze the factors of death in patients with COPD complicated with respiratory failure.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum 14-3-3β and CC16 expression on the death of patients with COPD complicated with respiratory failure.Results The expression of serum 14-3-3β in COPD complicated with respiratory failure group was higher than that in COPD group and control group(U=3.894,11.417),the expression of CC16 was lower than that in COPD group and control group(t=5.845,14.306),and the differences were statistically significant(all P<0.05),respectively.The expression of serum 14-3-3β in severe group was higher than that in moderate group and mild group(U=5.179,8.234),the expression of CC16 was lower than that of moderate group and mild group(t=4.090,9.281),and the differences were statistically significant(all P<0.05),respectively.The 28-day mortality rate of 232 COPD patients with respiratory failure was 31.47%(73/232).The expression of serum 14-3-3β in the death group was higher than that in the survival group,and the expression of CC16 was lower than that in the survival group,the differences were statistically significant(U/t=6.790,8.265,all P<0.05).The age of the death group was older than that of the survival group,the degree of airflow limitation and the number of acute exacerbations within 1 year were higher than those of the survival group,and the differences were statistically significant(t/χ2/U=3.895,7.202,3.360,all P<0.05).Age,severe airflow limitation,extremely severe airflow limitation,and the number of acute exacerbations within 1 year,elevated 14-3-3β were independent risk factors for death in patients with COPD complicated with respiratory failure(Wald χ2=3.914～22.668,all P<0.05),and elevated CC16 was an independent protective factor(Wald χ2=23.675,P<0.05).The area under the curve(AUC)of serum 14-3-3β combined and CC16 expression in predicting the death of patients with COPD complicated with respiratory failure which was greater than that of serum 14-3-3β and CC16 expression alone,the differences were statistically significant(Z=3.995,3.813,all P<0.01).Conclusion The increase of serum 14-3-3β expression and the decrease of CC16 expression in patients with COPD complicated by respiratory failure are closely related to the aggravation of the disease and poor prognosis.The combination of serum 14-3-3β and CC16 expression is of high value in predicting the death of patients with COPD complicated with respiratory failure.

Oxidative stress(OS)and dopaminergic neuron(DN)dysfunction are implicated in the pathogenesis and progression of various neurological disorders.As the primary active component of the traditional Chinese herb Scutellaria baicalensis,baicalin has garnered significant attention due to its potent antioxidant and anti-inflammatory properties.Baicalin exhibits a particular affinity for the dopamine(DA)system,maintaining cerebral DA levels by regulating oxidative stress(OS)-related pathways,suggesting that the DA system serves as the"intracerebral target system"through which it exerts its neuroprotective effects.Nuclear factor erythroid 2-related factor 2(Nrf2),a central transcription factor regulating redox homeostasis,plays a pivotal role in the anti-OS process mediated by baicalin.This systematic review covers the pharmacological effects of baicalin,providing an in-depth mechanistic analysis of the interaction between OS and DN,with a focus on the latest research progress in baicalin-mediated treatment of OS through the Nrf2 signaling pathway in neurological diseases to provide theoretical references for the pharmacological and molecular mechanisms of baicalin's anti-OS modulation of the DA system for the treatment of neurological diseases.

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

Objective To predict the mechanism of Chaihu Shugan Powder against depression based on network pharmacology and molecular docking technology;To verify them through animal experiment of chronic unpredictable mild stress(CUMS)depression model rats.Methods TCMSP was used to screen the active components of Chaihu Shugan Powder and the related targets were obtained.Disease targets were retrieved by DisGeNET,GeneCards and GEO databases.The protein-protein interaction(PPI)network construction,GO and KEGG pathway enrichment analyses were conducted to determine the action pathway of Chaihu Shugan Powder against depression.Molecular docking of main active components and potential targets was performed.The depression model was established by CUMS combined with solitary rearing method,in which Chaihu Shugan Powder and PI3K specific inhibitor LY294002 were used to intervene depression model rats.Western blot and qPCR were respectively used to detect the action pathway related proteins and mRNAs.ELISA was used to detect the contents of monoamine neurotransmitters 5-HT and NE in hippocampal tissue,and their pathways of action were integrated and analyzed.Results Totally 118 active components of Chaihu Shugan Powder against depression and 74 potential targets were screened;KEGG pathway enrichment analysis indicated that action pathway of Chaihu Shugan Powder against depression were closely related to PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking showed that quercetin,kaempferol,β-sitosterol,isorhamnetin,naringenin had good binding activity with AKT1,PIK3CA,GSK3B,IL6,IL1B.The animal experiments showed that Chaihu Shugan Powder could improve the depression-like behavior of model rats,increase the phosphorylation levels of PI3K and Akt in hippocampal tissue,down-regulate the expression of GSK3β,and increase the contents of 5-HT and NE.LY294002 could reverse the effect of Chaihu Shugan Powder.The results of integration analysis showed that PI3K/Akt signaling pathway of Chaihu Shugan Powder was closely related to metabolism of 5-HT and NE.Conclusion Chaihu Shugan Powder can exert antidepressant effects by activating the PI3K/Akt signaling pathway,inhibiting the expression of GSK3β,and increasing the levels of monoamine neurotransmitters 5-HT and NE.

Objective:To evaluate the efficacy of oliceridine for postoperative analgesia in patients undergoing breast-conserving surgery for breast cancer.Methods:In this prospective, randomized, double-blind, single-center, positive-control clinical study, 123 patients with breast cancer, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification I or Ⅱ, with a body mass index of 18-28 kg/m 2, undergoing breast-conserving surgery under general anesthesia at the Affiliated Cancer Hospital of Zhengzhou University from May to August 2024, were divided into 2 groups using a random number table method: sufentanil group (group S, n=62) and oliceridine group (group O, n=61). During anesthesia induction, sufentanil 15 μg was intravenously injected in group S, and oliceridine 3 mg was intravenously injected in group O. At 2 min before skin incision, sufentanil 10 μg was intravenously injected in group S, and oliceridine 2 mg was intravenously injected in group O. Postoperative patient-controlled intravenous analgesia was performed, with group S receiving sufentanil 50 μg and group O receiving oliceridine 10 mg, each diluted with normal saline to 100 ml. The pain visual analog scale scores at rest and during activity were recorded at 6, 12, 24 and 48 h postoperatively. The time of the first pressing of the postoperative analgesic pump, effective pressing times of patient-controlled analgesia and requirement for rescue analgesia within 24 h after surgery were recorded. The Ramsay sedation scores were recorded at 5, 15 and 30 min after tracheal extubation. The postoperative recovery quality was measured using the 15-item quality of recovery questionnaire at 24 h before surgery and at 24 and 48 h after surgery. The adverse reactions were recorded within 48 h after surgery. Results:Compared with group S, no significant change was found in visual analog scale scores at rest and during activity at different time points, the time of the first pressing of the postoperative analgesic pump, effective pressing times of patient-controlled analgesia and requirement for rescue analgesia within 24 h after operation, or the Ramsay sedation scores at 5, 15 and 30 min after tracheal extubation ( P>0.05), and 15-item quality of recovery scores were significantly increased at 24 and 48 h after surgery, and the incidence of postoperative nausea and vomiting was decreased in group O ( P<0.05). Conclusions:Oliceridine produces postoperative analgesic effects comparable to sufentanil without affecting patient awakening and reduces postoperative nausea and vomiting, which is helpful for early postoperative recovery when used in the patients undergoing breast-conserving surgery for breast cancer.

Attention deficit disorder(ADHD)is a common neurodevelopmental disorder in childhood,which seriously affects the physical and mental health of children.Up to now,the etiology and pathogenesis of ADHD are not clear,which is also the focus of global research.Animal model is an important carrier for basic research of ADHD,but the use of ADHD animal model is still controversial.This paper introduces the main emerging ADHD animal models in the world in recent years and analyzes their advantages and disadvantages.The genetic model,environmental induction model and neurodevelopmental disorder model are introduced and summarized from three aspects:surface validity,construct validity and predictive validity.The purpose of this study is to find a suitable animal model for the basic research of ADHD and to provide reference for the basic research of ADHD in China.