BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

BACKGROUND:Currently,numerous experiments delve into the intricate anatomy and biomechanical behavior of distinct segments of the supraspinatus muscle.However,the impact of shoulder joint stress resulting from damage to various regions of this muscle remains a scarcely explored domain.Understanding the repercussions of supraspinatus muscle injuries across different regions on the stress distribution and magnitude of articular cartilage and the glenoid is crucial for providing some theoretical support for clinical diagnosis and treatment. OBJECTIVE:To ascertain the maximum stress values by simulating different degrees of supraspinatus muscle rupture on the humeral cartilage surface,glenoid lip,and glenoid cartilage joint surface using three-dimensional finite element software. METHODS:Normal and healthy shoulder joint CT or MRI scans were processed through Mimics and Geomagic to extract molds.Subsequently,models were constructed via Solidworks.Varying degrees of supraspinatus muscle damage were simulated for each model to mimic fractures in different regions.Finally,Ansys,mechanical software,was employed for three-dimensional finite element biomechanical analysis,calculating stress values for the humeral cartilage surface,glenoid lip,and glenoid cartilage joint surface. RESULTS AND CONCLUSION:(1)With worsening degrees of supraspinatus muscle injury,the stress on the shoulder joint cartilage surface and glenoid lip escalated.(2)Among various regions,the anterior part of the supraspinatus muscle exhibited paramount significance.(3)While supraspinatus muscle fractures of differing degrees impacted the magnitude of cartilage stress on the glenoid labial surface,the stress distribution remained constant.(4)It is indicated that during the initial stages of horizontal abduction of the shoulder joint,the anterior region assumes a pivotal role,followed by the posterior deep region.Injury to the anterior part of the supraspinatus muscle leads to a significant surge in stress within the shoulder joint's soft tissue,potentially causing damage to the top of the glenoid lip and the anterior part of the glenoid cartilage.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective:To construct a core competency indicator system for oncology advanced practice nurses.Methods:This study is a cross-sectional study. A preliminary draft of the core competency indicator system for oncology advanced practice nurses was developed through literature review and expert group coordination from June to November 2022. The core competency indicator system for oncology advanced practice nurses was established using the Delphi method for expert consultation and the analytic hierarchy process.Results:A total of 54 experts from 11 hospitals and four medical schools in 10 provinces and municipalities directly under the central government across the country were included in two rounds of expert consultation. The effective response rates of the questionnaire were all 100%, with an expert authority coefficient of 0.90, Kendall coordination coefficients of 0.089 to 0.179 and 0.101 to 0.176 ( P<0.01). The final established core competency indicator system for oncology advanced practice nurses included seven primary indicators and 69 secondary indicators. Conclusions:The core competency indicator system for oncology advanced practice nurses is comprehensive and has the characteristics of specialized oncology nursing, and the construction process is scientific and reliable, laying the foundation for future training of oncology advanced practice nurses.

The purpose of this study was to understand the prevalence of Neoehrlichia mikurensis in rodents in Yunnan commensal rodent plague foci.Lianghe Country,Mangshi City,and Mile City in Yunnan Province were chosen as sampling sites,where rodents were captured with dead-traps.The N.mikurensis groEL gene in rodent spleen samples was detected with nested PCR,and the positive products were sequenced with Sanger bidirectional assays.The infection rate of N.mikurensis a-mong plague foci,habitats,species,and sexes was compared with Chi-square tests or Fisher's exact probability method.Of 656 rodent spleen samples,12 N.mikurensis positive samples were detected in R.tanezumi,R.sladeni,N.confucianus,and B.bowersi.The positivity rate was 1.83％.No significant difference in the N.mikurensis positivity rate was observed a-mong plague foci,habitats,species,and sexes(P＞0.05).Genetic evolution analysis of the groEL gene indicated that the se-quence similarity of nucleic acid sequences in 12 positive samples was 99.5％-100％,and the nucleic acid sequences of N.mikurensis were in the same branch,belonging to cluster Ⅳ.Thus,four species of rodents were found to have low frequency infection with N.mikurensis in Yunnan commensal rodent plague foci.

Objective:To evaluate the relationship between prognostic nutritional index (PNI) and risk of functional dependence in patients receiving maintenance hemodialysis (MHD).Methods:It was a cross-sectional survey study. The clinical data of MHD patients in the Second Affiliated Hospital of Soochow University from June to December 2023 were collected. The Katz and Lawton-Brody questionnaires were used to assess the functional status. The patients were divided into normal functional status group and functional dependence group, and the differences of the clinical data between the two groups were compared. Serum albumin and lymphocytes were used to determine PNI, and the patients were divided into four subgroups: Q1 group (PNI≤44.3), Q2 group (44.349.8) according to the quartile of PNI. Logistic regression analysis method was used to analyze the relationship between PNI and risk of functional dependence in MHD patients, and subgroup analysis was conducted. The receiver-operating characteristic (ROC) curve was used to assess the efficacy of PNI, serum albumin, and lymphocytes in predicting the risk of functional dependence in MHD patients.Results:A total of 206 MHD patients were included in this study, with age of (58.35±0.98) years old, and 132 (64.1%) males. There were 58 (28.2%) patients with diabetes, 179 (86.9%) patients with hypertension, and 36 (17.5%) patients with cardiovascular diseases. There were 95 (46.1%) patients developing functional dependence. Compared with normal functional status group, functional dependence group had higher age ( t=-6.87, P<0.001), proportion of diabetes ( χ2=6.58, P=0.010), and pulse pressure ( t=-3.17, P=0.002), and lower diastolic pressure ( t=3.88, P<0.001), serum creatinine ( t=3.44, P=0.001), serum albumin ( t=4.09, P<0.001) and PNI ( t=3.92, P<0.001). The incidence of functional dependence in PNI Q1 group (69.2%, 36/52) was significantly higher than those in Q2 group (49.0%, 25/51), Q3 group (34.0%, 18/53) and Q4 group (32.0%, 16/50), and the differences among groups were statistically significant (all P<0.05). Logistic regression analysis showed that after adjusting for confounding factors: age, diabetes, pulse pressure, and serum creatinine, the risk of functional dependence of PNI Q1 group was 3.217 folds higher than that in Q4 group ( OR=3.217, 95% CI 1.229-8.422, P=0.017). The risk probability model of PNI predicting the occurrence of functional dependence in MHD patients: logit (odds)=5.854-0.128 3×PNI. The area under the ROC curve ( AUC) for PNI predicting the risk of functional dependence in MHD patients was 0.66 (95% CI 0.58-0.73, P<0.001), slightly higher than that of serum albumin ( AUC=0.64, 95% CI 0.54-0.73, P<0.001). The optimal cutoff value of PNI predicting the occurrence of functional dependence was 46.15, with sensitivity of 72.07% and specificity of 57.89%. Conclusion:Low PNI is associated with high risk of functional dependence in MHD patients.

Objective:To investigate the correlation between the clinical features and endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) in patients with cirrhosis.Methods:A total of 148 patients with cirrhosis and portal hypertension who underwent EUS-PPG measurement at the Third Xiangya Hospital of Central South University from March 15, 2022 to June 20, 2023 were selected. The clinical data of patients collected before EUS-PPG measurement were analyzed. Variations in the EUS-PPG across different clinical data subgroups were analyzed. Multivariate linear regression analysis was used to explore the independent factors influencing EUS-PPG.Results:The EUS-PPG was significantly elevated in patients exhibiting red signs (16.62±5.33 mmHg VS 13.44±5.34 mmHg, t=3.616, P<0.001), gastroesophageal varices (15.78±5.30 mmHg VS 9.70±4.77 mmHg, t=4.247, P<0.001), hepatic encephalopathy (20.83±7.52 mmHg VS 14.92±5.35 mmHg, t=2.606, P=0.010), thrombocytopenia (15.66±5.39 mmHg VS 13.29±5.83 mmHg, t=2.136, P=0.034), hypoproteinemia (16.13±5.86 mmHg VS 14.12±5.03 mmHg, t=2.230, P=0.027), and an increased international normalized ratio (16.25±6.00 mmHg VS 14.40±5.11 mmHg, t=2.022, P=0.045). Conversely, the EUS-PPG was significantly reduced in patients with a history of splenectomy and devascularization (13.17±5.88 mmHg VS 15.73±5.34 mmHg, t=-2.379, P=0.019). The EUS-PPG in patients with varying degrees of ascites (no VS slight VS moderate or severe: 13.40±5.48 mmHg VS 15.90±5.49 mmHg VS 16.69±5.17 mmHg, F=5.188, P=0.007) and different Child-Pugh classifications (A VS B VS C: 14.07±5.05 mmHg VS 15.69±5.74 mmHg VS 17.64±5.99 mmHg, F=3.066, P=0.049) increased gradually. Multivariable linear regression analysis showed that red signs ( β=2.44, t=2.732, P=0.007), gastroesophageal varices ( β=4.45, t=2.990, P=0.003), ascites ( β=1.75, t=2.368, P=0.019), and hepatic encephalopathy ( β=5.82, t=2.644, P=0.009) were independent factors for the elevated EUS-PPG. Conclusion:There is a significant correlation between EUS-PPG and the clinical features related to the severity of cirrhotic portal hypertension, which indicates the feasibility of EUS-PPG in evaluating cirrhotic portal hypertension.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.