Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

Objective: To analyze the epidemiological characteristics of influenza in Huzhou City, Zhejiang Province from 2014 to 2023, so as to provide a reference for the improvement of influenza prevention and control measures. Methods: The data of influenza cases in Huzhou City from 2014 to 2023 were collected from the China Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the population and regional distribution characteristics of influenza. Annual percent change (APC) and average annual percent change (AAPC) were used to analyze the trend of influenza incidence in Huzhou City from 2014 to 2023. Results: A total of 83 277 influenza cases were reported in Huzhou City from 2014 to 2023, with an average annual reported incidence of 268.68/105. From 2014 to 2023, the reported incidence of influenza in Huzhou City showed an upward trend (AAPC=68.748%, P<0.05), with a slow upward trend from 2014 to 2021 (APC=31.055%, P<0.05) and a sharp upward trend from 2021 to 2023 (APC=308.782%, P<0.05). The average annual reported incidence of influenza was 270.72/105 in males and 266.54/105 in females, and the difference was not statistically significant (P>0.05). The average annual reported incidence of influenza in children aged 5-<15 years was 1 502.77/100 000. The reported incidences of influenza in Deqing county, Changxing county, and Anji county were 551.44/100 000, 370.47/100 000, and 175.31/100 000, respectively. From 2014 to 2023, the trends of reported influenza incidence in males, females, residents aged 5-<15 years, and 15-<25 years were consistent with the whole population. The reported influenza incidence in each district (county) from 2021 to 2023 was consistent with Huzhou City from 2021 to 2023. Conclusions The reported incidence of influenza in Huzhou City showed an overall upward trend from 2014 to 2023, especially from 2021 to 2023. There was no significant gender difference. The majority of the cases were aged 5-<15 years, and the high incidence areas were Deqing County.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Cadmium is a non-essential,non-degradable heavy metal element,the accumulation of cadmium can cause kidney damage.The purpose of this study was to reveal the ferroptosis mecha-nism induced by cadmium exposure in porcine kidney PK-15 cells.First of all,cell viability of gradi-ent concentration of cadmium chloride(CdCl2)on PK-15 cells was detected by CCK-8 method to screen suitable work concentration of CdCl2.Secondly,PK-15 cells were treated with 10 μmol/L CdCl2 for 3,6 and 12 h.The contents of lactate dehydrogenase(LDH)malondialdehyde(MDA)were detected by colorimetry,the expression of ferroptosis related protein were detected by West-ern blot,and the content of ferrous ion(Fe2+)was detected by fluorescence probe.Finally,PK-15 cells were pretreated with 10 μmol/L HO-1 inhibitor zinc protoporphyrin(ZnPP)for 6 h,and then treated with 10 μmol/L CdCl2 for 12 h.The morphology of PK-15 cells was observed by phase contrast microscope and the expression of ferroptosis related proteins was detected by West-ern blot.The results showed that CdCl2 treatment caused a significant decrease in cell viability.The levels of LDH,MDA and Fe2+,the protein levels of Nrf2,HO-1 and ALOX5,and the expression level of FTH1 protein were significantly decreased in CdCl2 treatment cells(P＜0.01).ZnPP could significantly improve the ferroptosis of PK-15 cells induced by CdCl2 treatment.Compared with CdCl2 treatment cells,the cell morphology was significantly improved,the protein levels of Nrf2,HO-1 and ALOX5 protein were significantly decreased,and the protein levels of FTH1 protein were significantly increased in ZnPP pretreatment group(P＜0.01).The results showed that cad-mium induced iron overload and lipid peroxidation,which result in ferroptosis in PK-15 cells through Nrf2/HO-1 pathway.

Porcine kidney cell line(PK-15)with HO-1 gene knockout was constructed by CRISPR/Cas9 system to provide experimental materials for exploring the role and molecular mechanism of HO-1 in cadmium-induced ferroptosis in PK-15 cells.Three sgRNA targeting HO-1 gene were de-signed,synthesized and ligated to lentiviral vector Lenti CRISPRv2.The constructed lentiviral plas-mid was transfected into human embryonic cells(HEK293FT)to obtain recombinant lentivirus,which was used to infect PK-15 cells.The monoclonal cell line with HO-1 knockout was obtained by puromycin screening and limited dilution method.The knockout effect was analyzed by sequencing and Western blot detection.The HO-1 gene knockout cells were treated with 10 μmol/L cadmium chloride(CdCl2).The cell viability was detected by CCK-8 method,the cell morpholo-gy was observed by phase contrast microscope,and the content of ferrous ion(Fe2+)was detected by fluorescence probe.The results showed that sgRNA2 possessed the highest editing efficiency.The base insertion or deletion of HO-1 gene and the frameshift of the target gene occurred in all five knockout cells.Western blot results showed that no expression of HO-1 protein was detected,indicating that the PK-15 cell line with HO-1 gene knockout was successfully constructed.After CdCl2 treatment,compared with the control cells,the cell viability was significantly increased and the Fe2+content was significantly decreased in PK-15 cells with HO-1 gene deletion,indicating that HO-1 gene knockout could significantly alleviate the abnormal iron metabolism caused by cadmium treatment.In conclusion,this study successfully constructed a PK-15 cell line knocking out HO-1 gene by using CRISPR/Cas9 gene editing technique,and confirmed that HO-1 plays an important role in iron metabolism abnormality in PK-15 cells induced by cadmium treatment,which lays a foundation for further study on the regulatory mechanism of HO-1 in ferroptosis in PK-15 cells induced by cadmium exposure.

Objective:To analyze the disease burden of chronic kidney disease (CKD) in the Belt and Road countries and its change trend.Methods:It was a cross-sectional epidemiological study based on surveillance data. Data on age-standardized prevalence rate (ASPR) and age-standardized mortality rate (ASMR) of CKD were derived from the 2019 Global Burden of Disease Study. The annual percentage change (APC) was calculated to evaluate the ASPR trend of CKD from 1990 to 2019.Results:In 2019, the number of CKD cases and deaths in the Belt and Road countries was 426 million and 798 000, respectively, accounting for 61.1% and 55.9% of CKD cases and deaths worldwide. The ASPR and ASMR of CKD in China were 8.1% and 11.2 per 100 000 population, slightly lower than the global average. Countries in North America and Oceania had a higher burden of CKD, and European countries had a lower burden. In the etiology, hypertension and diabetes-related CKD morbidity and mortality accounted for 23.7% and 68.8% of total CKD morbidity and mortality, respectively. From 1990 to 2019, the ASPR of CKD increased in 150 countries (98.0%) and the fastest increase was observed in Morocco ( APC=1.52%). The hotspots with high ASPR of CKD were located in Belt and Road countries from Asia, South/North America and Oceania, and the hotspots with high ASMR were distributed in countries from Africa, South/North America and Oceania. The sociodemographic index and life expectancy were positively correlated with the ASPR of CKD ( r=0.409, P<0.001; r=0.361, P<0.001) , and negatively correlated with the ASMR of CKD ( r=-0.317, P<0.001; r=-0.391, P<0.001). Conclusions:Belt and Road countries have substantial disease burdens of CKD, and the prevalence rate of CKD is rising fast. Health cooperation among member states should be strengthened to jointly address the challenges posed by chronic diseases such as CKD.

Rheumatoid arthritis(RA)is a chronic and progressive autoimmune disease.Current clinical treatments for RA often exhibit inadequate drug responses and severe adverse effects,underscoring the necessity for alternative therapies.Baicalin,a flavonoid derived from Scutellaria baicalensis roots,possesses anti-inflammatory,antioxidant,and immunomodulatory properties.Research suggests that baicalin can inhibit the release of inflamma-tory mediators,thereby reducing inflammation.Moreover,it demonstrates antioxidant effects by decreasing reactive oxygen species production and mitigating synovial damage induced by oxidative stress.Baicalin may impede the activation of inflammatory cytokines through pathways such as NF-κB,MAPKs,and JAK-STAT signaling cascades while inducing apoptosis,regulating immune cell activity,and balancing immune mediators to impact synovitis progression.Clinically,both monotherapy with baicalin or its combination with other formulations have exhibited efficacy and safety profiles.The advancement in targeted drug delivery systems has improved its bioavailability further suggesting promising clinical applications.This review provides an overview of research progress on baicalin's mechanisms in inhibiting RA synovitis along with its clinical applications.

Objective:To explore the influence of deviation of the bolt in femoral neck system (FNS) on the short-term outcomes in young and middle-aged patients with displaced femoral neck fracture.Methods:A retrospective analysis was conducted of the 114 young and middle-aged patients with displaced femoral neck fracture who had been treated with FNS at Department of Orthopaedics, Suzhou Municipal Hospital from December 2019 to January 2023. Based on the postoperative measurements of the deviation of the bolt tip to the central axis of the femoral head and neck (W), the patients were divided into a central group (W≤20%) and a deviation group (W>20%). In the central group of 63 cases, there were 27 males and 36 females with a mean age of (46.4±8.0) years. In the deviation group of 51 cases, there were 20 males and 31 females with a mean age of (45.1±9.8) years. The 2 groups were compared in terms of weight-bearing time, fracture healing time, tip-apex distance, degree of femoral neck shortening, Harris Hip Score and EuroQol five-dimensional questionnaire-5L (EQ-5D-5L) utility value at the last follow-up, as well as complications and revision surgeries.Results:There was no statistically significant difference in the preoperative general information, auxiliary reduction or quality of fracture reduction between the 2 groups, showing comparability between groups ( P>0.05). There was no significant difference in the partial weight-bearing time between the 2 groups ( P>0.05). In the central group, the full weight-bearing time [15.0 (14.0, 16.0) weeks] and fracture healing time [14.0 (12.0, 15.0) weeks] were significantly shorter than those in the deviation group [16.0 (15.0, 19.0) weeks; 15.0 (13.0, 17.0) weeks], the tip-apex distance [(21.4±3.4) mm] was significantly shorter than that in the deviation group [(23.5±2.7) mm], the Harris Hip Score [(90.6±6.1) points] and EQ-5D-5L utility value [0.9 (0.8, 0.9)] at the last follow-up were significantly higher than those in the deviation group [(87.7±6.2) points; 0.9 (0.8, 0.9)], and the incidences of moderate and severe femoral neck shortening [25.4% (16/63)], avascular necrosis of the femoral head [0 (0/63)] and revision surgery [0 (0/63)] were significantly lower than those in the deviation group [66.7% (34/51), 7.8% (4/51), 9.8% (5/51)] (all P< 0.05). Conclusion:A closer positioning of the FNS bolt to the central axis of the femoral head and neck favors satisfactory short-term outcomes and a lower revision surgery rate in young and middle-aged patients with displaced femoral neck fracture.

BACKGROUND:Total knee arthroplasty is one of the effective methods to treat end-stage knee osteoarthritis.However,some patients still experience chronic post-surgical pain.It is significant to find out the influencing factors of chronic post-surgical pain.Demographic factors,social psychological factors and perioperative pain were the focus of previous studies,but muscle factors closely related to the occurrence and development of knee osteoarthritis were rarely reported. OBJECTIVE:To evaluate the value of preoperative quantitative ultrasound analysis of quadriceps femoris in predicting chronic post-surgical pain after total knee arthroplasty. METHODS:A total of 250 patients with knee osteoarthritis who underwent the first unilateral total knee arthroplasty under elective general anesthesia from January to August 2022 in the Affiliated Hospital of Xuzhou Medical University were selected.All patients were treated with the same anesthesia and operative methods.Before the surgery,clinical data were recorded,and the thickness and echo intensity of quadriceps femoris on the operated side were measured by ultrasound imaging,which could quantify the degree of quadriceps femoris atrophy.Multivariate logistic regression was used to analyze the independent factors affecting the occurrence of chronic post-surgical pain,and receiver operating characteristic curves were used to evaluate its predictive value. RESULTS AND CONCLUSION:(1)250 subjects were involved in the result analysis,and 91 of them had chronic post-surgical pain,with an incidence of 36.4%.(2)There were significant differences between the chronic pain and non-chronic pain groups in preoperative pain score during movement,preoperative Western Ontario and McMaster University Osteoarthritis Index,preoperative anxiety and depression scale score,preoperative muscle thickness and echo intensity of quadriceps femoris,and postoperative acute pain score(P<0.05).(3)Multivariate logistic regression analysis showed that preoperative thickness of quadriceps femoris was an independent protective factor for chronic post-surgical pain and preoperative pain score during movement was an independent risk factor for chronic post-surgical pain.(4)Receiver operating characteristic curves showed that the area under the curve of the preoperative thickness of quadriceps femoris was 0.625(95%CI:0.555-0.695),and the critical value was 2.78 cm,sensitivity was 0.802,specificity was 0.415.(5)It is concluded that the preoperative thickness of quadriceps femoris is an independent protective factor for chronic post-surgical pain,but its predictive efficacy is low,and its clinical application needs to be further verified or modified.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.