ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P < 0. 05). And after silencing of miR-23 b-5 p expression, the expression of PINkl mRNA also significantly decreased (P < 0. 05 ). Dual-Luciferase Reporter Assay showed that Rno-miR-23b-5p could significantly down- regulate the luciferase activity of Rno-PINKl-WT (P < 0. 05 ), but could not down-regulate the luciferase activity of mutant Rno-PINKl -mut ( P > 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.

Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions, etc. Internal causes include age, sex, disease, etc. This paper analyzes and systematically combs how independent variables and covariates directly or indirectly affect the three time-related factors by affecting the body's physiology and internal environment, thus changing the complex process of Fa. Understanding this theoretical framework can better optimize the independent variables to reduce the impact of covariates on Fa. In addition, this paper also introduces the latest progress of prediction and evaluation of Fa, including the progress of complex dissolution device and the status of software prediction.

Comprehensive improvement in course teaching quality is an important link in deepening the reform of undergraduate education and teaching. Since 2018, West China Medical School, Sichuan University, has implemented the collective lesson preparation system of "two meetings, seven decisions, and three preparation sessions" for undergraduate clinical courses, thereby effectively implementing subject cooperation, organizational guidance, and resource integration among clinical teachers and determining the key elements of the course through "teaching, learning, and exam preparations" before class. In the process of course operation, the concept of quality control based on plan-do-check-act cycle is deeply integrated with the collective lesson preparation system, and active implementation of the whole-process quality control loop of planning (plan), organization and implementation (do), inspection of results (check), and treatment and improvement (action) has effectively improved the teaching quality of undergraduate clinical courses.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To investigate the chemical constituents of Vitex negundo var.heterophylla.Methods:The chemical constituents were separated and purified by silica gel,opening ODS column chromatography,Sephadex LH-20,and semi-preparative HPLC.Their structures were elucidated on the basis of physico-chemical properties and spectroscopic data.Results:Five compounds were isolated from the 95%ethanol extract of the leaves and seeds of Vitex negundo var.heterophylla.They were identified as 5,4'-dihydroxy-3,6,7-trimethoxyflavone,5,4'-dihydroxy-3,6,7,8-tetramethoxyflavone,p-hydroxybenzaldehyde,p-hydroxybenzoic acid,and p-hydroxybenzoic acid methyl ester.Conclusion:The study of the chemical constituents of Vitex negundo var.heterophylla enriches the chemical composition of Vitex negundo var.heterophylla and the material basis for its potential pharmacological effects.

Objective To investigate the relationship between serum homocysteine(Hcy)and mental symptoms in elderly patients with Parkinson disease(PD)and its predictive value.Methods A total of 112 elderly patients with PD mental disorder(PD group)who were treated and treated in Taizhou Second People's Hospital from June 2020 to June 2023 were selected as the study objects,and 55 elderly PD patients without mental disorder(without mental disorder PD group)and 56 healthy physical examination subjects(control group)were selected as the study objects.The serum Hcy changes of the three groups were compared.Results The scores of Hcy,Hamilton anxiety rating scale(HAMA)and Hamilton depression rating scale(HAMD)in PD group were higher than those in without mental disorders PD group and control group,while the scores of mini mental state examinationscale(MMSE)and Montreal cognitive assessment scale(MoCA)were lower than those in without mental disorders PD group and control group(P<0.05).Kendall's tau-b correlation analysis showed that serum Hcy was positively correlated with Hoehn-Yahr grade,MMSE grade,MoCA grade,HAMA grade and HAMD grade(P<0.05).Receiver operating characteristic curve analysis showed that the area under the curve values of Hcy in predicting major cognitive dysfunction,anxiety and depression in elderly PD patients with mental disorders were 0.848,0.864 and 0.846.Conclusion Serum Hcy showed an abnormal increase trend in elderly patients with PD mental disorder,and its level would increase with the deterioration of patients'mental symptoms.

Objective To investigate the effects of combined exercise training on exercise ability and inflammatory factors in elderly patients with chronic obstructive pulmonary disease(COPD)complicated with sarcopenia.Methods Sixty elderly patients with COPD complicated with sarcopenia who were treated in Hangzhou Third People's Hospital from July 2022 to May 2023 were selected as study objects,and were divided into control group and treatment group according to random number table method,with 30 cases in each group.The control group received routine treatment of COPD,while the treatment group received combined exercise training on the basis of routine treatment for 12 weeks.The appendicular skeletal muscle mass index(ASMI),grip strength,walking speed,6 min walking distance(6MWD),COPD assessment test(CAT),forced expiratory volume in one second(FEV1)/forced vital capacity(FVC)、serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were compared.The correlation between serum IL-6、TNF-α and ASMI,grip strength、walking speed were analyzed.Results After treatment,6MWD in both groups was significantly longer than before treatment,and CAT score was significantly lower than before treatment(P＜0.05).The ASMI,grip strength and walking speed of patients in treatment group were significantly higher than before treatment,and the serum IL-6 and TNF-α were significantly lower than before treatment(P＜0.05).The ASMI,grip strength and walking speed of treatment group were significantly higher than those of control group,6MWD was significantly longer than that of control group,CAT score,serum IL-6 and TNF-α were significantly lower than those of control group(P＜0.05).There was no significant difference in FEV1/FVC between two groups before and after treatment(P＞0.05).Pearson correlation analysis showed that serum IL-6、TNF-α were negatively correlated with ASMI、grip strength and walking speed.Conclusion Combined exercise training can improve muscle mass and strength,improve exercise ability and clinical symptoms,and inhibit inflammatory response in elderly patients with COPD complicated with sarcopenia.

Objective To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury.Methods From January 2016 to December 2020,the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed,includ-ing 35 males and 22 females,aged from 18 to 47 years old with an average of(32.9±7.9)years old.Knee function was evaluat-ed using the International Knee Documentation Committee(IKDC)and Lysholm scores both before the operation and at the fi-nal follow-up.Meniscus healing was evaluated according to the postoperative Barrett standard.Wound healing complications,such as vascular injury,nerve injury,and lower extremity venous thrombosis,were recorded.Results All 57 patients were fol-lowed up for 12 to 58 months with an average of(38.1±14.9)months.The incisions of the patients after the operation were all Grade A healing without infection,popliteal tendon injury,blood vessel injury,nerve injury and lower extremity venous throm-bosis.The IKDC score increased from(49.7±3.6)points preoperatively to(88.5±4.4)points in the final follow-up(P＜0.05).The Lysholm score increased from(48.8±4.9)points preoperatively to(91.9±3.9)points at the final follow-up(P＜0.05).At 3,6 months and 1 year after operation,according to Barrett's criteria,54 cases were clinically healed,the healing rate was 94.7％(54/57).Conclusion This study preliminarily confirmed that arthroscopic suture technique can result in clinical sta-bility through suture and fixation of the meniscus in the injured lateral popliteal tendon area.No adverse effects on knee joint function were found in the mid-term follow-up after the operation.

Objective To investigate the relationship between serum autotaxin,copeptin,lipopolysaccharide binding protein(LBP)and prognosis in patients with hepatitis B virus-related decompensated cirrhosis(HBV-DC)complicated with liver failure(LF).Methods 143 patients with HBV-DC complicated with LF who admitted to our hospital from February 2018 to August 2023 were selected as the research objects.Patients were followed up for 90 d,patients were divided into death group(55 cases)and survival group(88 cases)according to the prognosis,the levels of serum Autotaxin,Copeptin and LBP were compared between two groups.The clinical data of patients with HBV-DC complicated with liver failure were collected,the prognostic factors of HBV-DC complicated with LF patients were analyzed by univariate and multivariate Logistic regression models.The clinical value of serum Autotaxin,Copeptin and LBP alone or in combination in predicting the prognosis of patients with HBV-DC complicated with LF were analyzed by receiver operating characteristic(ROC)curve.Results 143 patients with HBV-DC complicated with LF 90 d follow-up,55 died,and 88 survived,with a mortality rate of 38.46％.Compared with survival group,the serum levels of Autotaxin,Copeptin and LBP in death group were significantly increased(P＜0.05).Compared with survival group,the proportion of hospitalization time ≥14 d,the proportion of ascites,the proportion of hepatic encephalopathy,alanine aminotransferase,total bilirubin and model for end-stage liver disease(MELD)score in death group were significantly increased(P＜0.05),and albumin was significantly decreased(P＜0.05),there was no significant difference in age,gender,diabetes mellitus,hypertension,serum creatinine,platelet count and fibrinogen(P＞0.05).Elevated total bilirubin,concurrent hepatic encephalopathy,elevated MELD score,and elevated serum Autotaxin,Copeptin,and LBP levels were risk factors for poor prognosis in patients with HBV-DC complicated with LF(P＜0.05).ROC curve results showed that,the area under the curve(AUC),sensitivity and specificity of combined detection of serum Autotaxin,LBP and Copeptin in predicting poor prognosis of patients with HBV-DC complicated with LF were 0.930,85.45％and 88.64％,respectively,which were significantly better than those of single index detection.Conclusion The high expression of serum Autotaxin,Copeptin and LBP are related to the risk of short-term death in patients with HBV-DC complicated with LF,and the combined detection has a high clinical predictive value for the occurrence of short-term death in patients with HBV-DC complicated with LF.