Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

BACKGROUND:Polycystic ovary syndrome is a common reproductive endocrine disease leading to infertility in women of reproductive age.Currently,there is no effective treatment.Human umbilical cord mesenchymal stem cells may help to repair ovarian function,but few studies have reported their role in the treatment of polycystic ovary syndrome.OBJECTIVE:To explore the effect and mechanism of human umbilical cord mesenchymal stem cells in the treatment of polycystic ovary syndrome.METHODS:3-week-old female ICR mice were divided into three groups(n=15).Normal control group was not treated.Model group was given letrozole for 21 days to induce polycystic ovary syndrome.Treatment group was given letrozole via intragastric administration for 21 consecutive days,and human umbilical cord mesenchymal stem cell suspension was injected through the tail vein.The body weight of mice was monitored before treatment,7 and 14 days after treatment.The estrous cycle of mice was detected by continuous vaginal smears for 10 consecutive days after treatment.Fourteen days after treatment,peripheral blood sex hormone levels of mice were detected by ELISA.Hematoxylin-eosin staining was used to observe ovarian morphological changes.Immunofluorescence and immunohistochemistry were used to detect the expression of Rab27A protein in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the estrous cycle of mice in the model group was disturbed;body weight was significantly increased;follicle stimulating hormone was decreased;luteinizing hormone and testesterone were both increased;more follicles were found in the ovaries,and the relative expression level of Rab27A protein was decreased.(2)Compared with the model group,the treatment group had diminished body weight,increased follicle stimulating hormone,decreased luteinizing hormone and testesterone,decreased follicles with polycystic dilatation,and increased Rab27A protein relative expression level.(3)These findings suggest that human umbilical cord mesenchymal stem cells improve serum sex hormone levels and ovarian function in polycystic ovary syndrome mice by upregulating the expression of Rab27A.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Objective:To investigate the effect of IL-37 on oxidized low-density lipoprotein(ox-LDL)-induced calcification in human aortic vascular smooth muscle cells(HA-SMCs)and the influence of toll-like receptor(TLR)/nuclear transcription factor(NF-κB)pathway and osteogenic transcription factors,to demonstrate the mechanism of IL-37 in calcification.Methods:The calcifica-tion model of HA-SMCs was treated with ox-LDL,and the model group was pretreated with 100 ng/ml IL-37 or 100 μmol/L PDTC.CCK8 was used to detect cell proliferation activity;flow cytometry was used to detect apoptosis.Alizarin red staining was used to detect calcified nodules.The mRNA levels of smooth muscle actin(SMA),bone morphogenetic protein(BMP2)and IL-37 were detected by qPCR;mRNA and protein expression levels of TLR,NF-κB,p-NF-κB,RUNX-associated transcription factor(RUNX2),alkaline phosphatase(ALP),SMA and smooth muscle 22α(SM22α)were detected by qPCR and Western blot.Results:Compared with the control group,ox-LDL treatment enhanced cellular proliferation activity and was concentration-dependent(P<0.05),and apoptosis rate was increased,while the model group produced significant orange-red calcified nodules,up-regulated mRNA and protein expres-sion of inflammatory factors such as TLR and NF-κB,up-regulated mRNA expression of IL-37,RUNX2,BMP2,ALP,while SMA and SM22α mRNA expressions were decreased,and the protein expressions of p-NF-κB and RUNX2 were increased significantly;compared with the modeling group,the IL-37 pretreatment group showed lower viability and decreased apoptosis rate(P<0.05),sig-nificantly reduced calcified nodules,and the mRNA and protein expression of inflammatory factors such as TLR and NF-κB,and mRNA of RUNX2,BMP2,ALP expressions were downregulated,mRNA expression of SMA and SM22α were elevated,and protein expressions of p-NF-κB and RUNX2 were significantly decreased,showing the same trend as the inhibitor PDTC group in cytokines.Conclusion:IL-37 inhibits calcification of HA-SMCs,which may be related to the inhibition of NF-κB pathway and osteogenic pheno-type transformation.

BACKGROUND:Polycystic ovary syndrome is a common reproductive endocrine disease leading to infertility in women of reproductive age.Currently,there is no effective treatment.Human umbilical cord mesenchymal stem cells may help to repair ovarian function,but few studies have reported their role in the treatment of polycystic ovary syndrome.OBJECTIVE:To explore the effect and mechanism of human umbilical cord mesenchymal stem cells in the treatment of polycystic ovary syndrome.METHODS:3-week-old female ICR mice were divided into three groups(n=15).Normal control group was not treated.Model group was given letrozole for 21 days to induce polycystic ovary syndrome.Treatment group was given letrozole via intragastric administration for 21 consecutive days,and human umbilical cord mesenchymal stem cell suspension was injected through the tail vein.The body weight of mice was monitored before treatment,7 and 14 days after treatment.The estrous cycle of mice was detected by continuous vaginal smears for 10 consecutive days after treatment.Fourteen days after treatment,peripheral blood sex hormone levels of mice were detected by ELISA.Hematoxylin-eosin staining was used to observe ovarian morphological changes.Immunofluorescence and immunohistochemistry were used to detect the expression of Rab27A protein in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the estrous cycle of mice in the model group was disturbed;body weight was significantly increased;follicle stimulating hormone was decreased;luteinizing hormone and testesterone were both increased;more follicles were found in the ovaries,and the relative expression level of Rab27A protein was decreased.(2)Compared with the model group,the treatment group had diminished body weight,increased follicle stimulating hormone,decreased luteinizing hormone and testesterone,decreased follicles with polycystic dilatation,and increased Rab27A protein relative expression level.(3)These findings suggest that human umbilical cord mesenchymal stem cells improve serum sex hormone levels and ovarian function in polycystic ovary syndrome mice by upregulating the expression of Rab27A.

Objective:To investigate the effect of IL-37 on oxidized low-density lipoprotein(ox-LDL)-induced calcification in human aortic vascular smooth muscle cells(HA-SMCs)and the influence of toll-like receptor(TLR)/nuclear transcription factor(NF-κB)pathway and osteogenic transcription factors,to demonstrate the mechanism of IL-37 in calcification.Methods:The calcifica-tion model of HA-SMCs was treated with ox-LDL,and the model group was pretreated with 100 ng/ml IL-37 or 100 μmol/L PDTC.CCK8 was used to detect cell proliferation activity;flow cytometry was used to detect apoptosis.Alizarin red staining was used to detect calcified nodules.The mRNA levels of smooth muscle actin(SMA),bone morphogenetic protein(BMP2)and IL-37 were detected by qPCR;mRNA and protein expression levels of TLR,NF-κB,p-NF-κB,RUNX-associated transcription factor(RUNX2),alkaline phosphatase(ALP),SMA and smooth muscle 22α(SM22α)were detected by qPCR and Western blot.Results:Compared with the control group,ox-LDL treatment enhanced cellular proliferation activity and was concentration-dependent(P<0.05),and apoptosis rate was increased,while the model group produced significant orange-red calcified nodules,up-regulated mRNA and protein expres-sion of inflammatory factors such as TLR and NF-κB,up-regulated mRNA expression of IL-37,RUNX2,BMP2,ALP,while SMA and SM22α mRNA expressions were decreased,and the protein expressions of p-NF-κB and RUNX2 were increased significantly;compared with the modeling group,the IL-37 pretreatment group showed lower viability and decreased apoptosis rate(P<0.05),sig-nificantly reduced calcified nodules,and the mRNA and protein expression of inflammatory factors such as TLR and NF-κB,and mRNA of RUNX2,BMP2,ALP expressions were downregulated,mRNA expression of SMA and SM22α were elevated,and protein expressions of p-NF-κB and RUNX2 were significantly decreased,showing the same trend as the inhibitor PDTC group in cytokines.Conclusion:IL-37 inhibits calcification of HA-SMCs,which may be related to the inhibition of NF-κB pathway and osteogenic pheno-type transformation.

[Objective] To analyze factors influencing the postoperative progression-free survival (PFS) in patients with renal cell carcinoma (RCC), construct a nomogram model for predicting PFS, and compare it with other predictive models. [Methods] A retrospective analysis was conducted on the general and clinical data of 263 RCC patients who underwent surgery at the Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, during Apr.2014 and Nov.2021.Patients were divided into the progression group (n=34) and non-progression group (n=229). The data of the two groups were analyzed to identify prognostic variables associated with PFS, and a nomogram model was constructed.The performance of this model was compared with that of the University of California, Los Angeles Integrated Staging System (UISS) score, tumor staging, tumor size, tumor pathological grade, and tumor necrosis scoring system (SSIGN score), and Leibovich score by plotting receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Calibration curve of the nomogram was used to validate the model's performance, and K-fold cross-validation was employed to assess its external validity. [Results] Multivariate Cox regression analysis revealed that age (HR=2.255, 95%CI: 1.032-4.926), T stage (HR=5.766, 95%CI: 2.351-14.142), pathological grade (HR=3.100, 95%CI: 1.445-6.651), and pathological necrosis (HR=2.656, 95%CI: 1.253-5.629) were independent risk factors of PFS (P<0.05). The nomogram model based on these four independent variables had AUCs (95%CI) of 0.750 (0.630-0.870), 0.803 (0.705-0.902), and 0.847 (0.757-0.937) for 1, 3, and 5 years, respectively, which were higher than those of UISS score, SSIGN score, and Leibovich score.The calibration curve of the nomogram showed good consistency between predicted and actual probabilities.In K-fold cross-validation, the average AUCs of the nomogram at 1, 3, and 5 years were 0.761, 0.808, and 0.842, indicating good external validity of the nomogram. [Conclusion] The nomogram based on age, T stage, pathological grade and pathological necrosis can accurately predict the risk of postoperative PFS in RCC patients at 1, 3, and 5 years, which can aid clinicians in the early identification of high-risk progression.

Objective To analyze the antihypertensive compliance rate,drug use and complication distribution among very old hypertensive inpatients under the antihypertensive standard of 150/90 mm Hg in our country(1 mm Hg=0.133 kPa).Methods A total of 409 hospitalized patients aged ≥80 years and diagnosed with hypertension in all departments of Air Force Medical Center of PLA were enrolled,and according to their clinical outcomes,they were divided into intensive antihypertensive group(106 cases,SBP＜130 mm Hg),standard antihypertensive group(155 ca-ses,SBP 130-149 mm Hg)and non-standard blood pressure group(148 cases,SBP ≥150 mm Hg).The status of blood pressure control was analyze in each group.Results When 150/90 mm Hg was used as the blood pressure standard,25.9％were in the intensive blood pressure group,37.9％were in the standard blood pressure group,36.2％were in the non-standard blood pressure group.The proportion of patients aged＞90 years was significantly lower in the non-standard blood pressure group than the intensive antihypertensive group and the standard anti-hypertensive group(4.1％vs 7.5％and 12.3％,P＜0.05).The ratio of single-drug therapy was significantly higher in the standard antihypertensive group than the intensive antihypertensive group(46.5％vs 32.1％,P＜0.05),and that of dual combination therapy was obviously higher in the intensive antihypertensive group than the standard antihypertensive group(35.8％vs 22.6％,P＜0.05).The proportions of heart damage and cerebrovascular damage were significantly higher(43.4％vs 21.9％,26.4％vs 14.8％),and the proportion of complicated retinopathy was notably lower(11.3％vs 23.9％)in the intensive antihypertensive group than the standard antihypertens-ive group(P＜0.05).Conclusion For very old hypertensive patients in our country,it is more sci-entific and practical to use 150/90 mm Hg as the starting standard for blood pressure reduction.Intensified blood pressure reduction increases cardiovascular and cerebrovascular damages in them instead.

Objective:To explore the application value of quantitative flow ratio (QFR) in the hemodynamic evaluation of myocardial bridge and to preliminarily evaluate the correlation and related influencing factors between deformation quantitative flow ratio (D-QFR) and QFR.Methods:This is a cross-sectional study. Patients with CAG-confirmed simple myocardial bridge of the middle anterior descending coronary artery from June 2012 to June 2022 at the Air Force Medical Center were retrospectively included in this study. Systolic stenosis of mural coronary arteries (MCA) and myocardial bridge length were measured using quantitative coronary angiography. The patients were divided into mild stenosis group (<50% systolic stenosis) and moderate-to-severe stenosis group (≥50% systolic stenosis) according to the Nobel grading criteria. At different time periods (systolic and diastolic), the QFR values were measured at 3 locations (1 to 2 cm before the MCA entrance, the middle segment of the MCA, and 1 to 2 cm after the MCA exit), denoted as QFRa, QFRb, and QFRc, respectively, and the D-QFR values, incorporating vessel deformation information, were recorded. The MCA distal QFR≤0.8 in either stage was defined as an abnormal QFR value. QFR values were compared between the two groups at different locations and within each group. Factors associated with abnormal QFR values were analysed using multifactorial logistic regression. Spearman rank correlation analysis was used to examine the correlation between D-QFR values and systolic and diastolic QFR values.Multiple linear regression was used to analyse the factors associated with D-QFR.Results:A total of 83 patients were enrolled, including 58 males, aged (57.1±13.1) years. There were 48 cases in the mild stenosis group and 35 cases in the moderate-to-severe stenosis group, and the differences in systolic and diastolic QFRb and QFRc values between the two groups were statistically significant (all P<0.05). Within-group comparisons showed the values of QFRb and QFRc in the systolic phase were lower than those in the diastolic phase; QFRb and QFRc were both lower than QFRa during the same period (all P<0.05). Multifactorial logistic regression analysis showed that MCA systolic stenosis ( OR=1.225, 95% CI 1.093-1.372, P<0.001) was an influential factor for abnormal QFR. D-QFR values were positively correlated with both systolic and diastolic QFR values (correlation coefficients were 0.849 and 0.675, respectively, both P<0.01). Multiple linear regression analysis showed that D-QFR values were negatively correlated with age ( β=-0.208, P=0.029), systolic stenosis ( β=-0.500, P<0.001), and myocardial bridge length ( β=-0.211, P=0.036). Conclusions:The QFR values in middle and distal of myocardial bridge decrease. The systolic stenosis rate of myocardial bridge is an important factor affecting QFR value. D-QFR is positively correlated with both systolic and diastolic QFR values. Age, myocardial bridge systolic stenosis rate and length are factors influencing the D-QFR values.