Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells. Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress. Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week⁻¹) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase. Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05). Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

ObjectiveTo analyze the epidemiological characteristics and trends of hand-foot-mouth disease (HFMD) in Hangzhou, so as to provide an evidence for developing effective prevention and control measures and evaluating the control effects. MethodsThe incidence data of HFMD in Hangzhou were collected from the Infectious Disease Reporting Information Management System of China Information System for Disease Control and Prevention. Descriptive epidemiology was applied to analyze the temporal, spatial and demographic distribution characteristics and etiology monitoring results of HFMD cases in Hangzhou from 2010 to 2023. Joinpoint regression model was used to analyze the trends of incidence rate of HFMD. Furthermore, circular distribution method was utilized to calculate the incidence peak of HFMD. ResultsFrom 2010 to 2023, the average annual reported incidence rate of HFMD in Hangzhou was 138.85/100 000, the proportion of severe cases was 0.04%, the mortality rate was 0.01/100 000, and the case fatality rate was 5.30/100 000. Both the total incidence rate and the incidence rate by sex showed an increasing trend. The annual reported incidence rate in males (158.72/100 000) was higher than that in females (117.61/100 000). The reported incidence rate showed a significant seasonal characteristic, with summer being the peak of epidemic. The results of surveillance samples suggested that the prevalence of HFMD in Hangzhou is characterized by the co-existence of multiple pathogens, with EV-A71 and CV-A16 being the dominant pathogens in the previous years and CV-A6 being the dominant pathogen since 2018. The proportion of EV-A71 in severe cases (77.19%) was higher than that in ordinary cases (15.37%), in addition, its proportion in ordinary cases, severe cases, and fatal cases all showed a decreasing trend. ConclusionThe incidence rate of HFMD in Hangzhou is still high, so it’s still necessary to continue to strengthen the prevention and control measures for key populations. In recent years, CV-A6 has been the main prevalent pathogen in Hangzhou. Further efforts in pathogen detection and analysis should be enhanced in the future.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Aim Based on the apoptotic pathway mediated by receptor interacting protein kinase(RIP)1-RIP3-mixed spectrum kinase domain like protein(MLKL), to explore the effects of naringenin on ovarian granulosa cell apoptosis in rats with polycystic ovary syndrome(PCOS). Methods SD rats were randomly assigned into normal control group, model group, naringenin group, RIP1 inhibitor(Nec-1)group, RIP1-RIP3-MLKL necrosis signal activator(Z-VAD-fmk)group, naringenin+Z-VAD-fmk group, 15 rats per group. ELISA method was performed to measure the levels of IL-1β and TNF-α in ovarian tissue. HE method was performed to observe the shape of the ovary. Granular cells were isolated from ovarian tissue, and flow cytometry was performed to measure apoptosis rate and necrosis rate. Immunohistochemistry was performed to measure the positive expression of p-RIP1 in ovarian tissue. Western blot was employed to detect the expression of RIP1-RIP3-MLKL pathway. Results RIP1 specific inhibitor Nec-1 and naringenin could block the phosphorylation and activation of RIP1, inhibit the RIP1-RIP3-MLKL signaling pathway, reduce the inflammation level in PCOS rats, and alleviate the necrosis and apoptosis of ovarian granulosa cells(P<0.05). Z-VAD-fmk could promote the activation of RIP1-RIP3-MLKL pathway, aggravate the apoptosis of ovarian granulosa cells, and partially weaken the anti-apoptosis effect of naringenin(P<0.05). Conclusions Naringenin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by blocking the activation of the necrotic apoptotic pathway mediated by RIP1-RIP3-MLKL.

Acute hepatic porphyria （AHP） is a rare disease with abnormal heme metabolism， and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods， this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage， including RNAi therapy， enzyme replacement therapy， genetic supplementation of DNA or mRNA， drug molecular chaperones， and glycine transporter inhibitors for reducing heme synthesis. Moreover， this article also reviews the treatment of AHP-related comorbidities and complications， such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China， and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP， and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.

Objective To explore the relationship between serum miRNA-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma.Methods A total of 118 patients with renal clear cell carcinoma admitted to the Qinghai University Hospital from February 2019 to April 2021 were selected as the study subjects,and another 118 healthy patients in the same period as the control group.Real time fluorescence quantitative polymerase chain reaction(PCR)was used to detect the expression of miR-21 and miR-27b in the serum of all subjects.The relative expression levels of serum miR-21 and miR-27b between the patients with renal clear cell carcinoma and healthy control patients were compared.The expression and correlation of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma of different pathological stages and Fuhrman grading were analyzed.The relationship between the expression of serum miR-21 and miR-27b and the survival and prognosis of the patients was explored as well.Results The expression levels of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma were higher than those in the healthy control group(P＜0.05).The serum miR-21 expression level in stage Ⅲ patients was higher than in stageⅠ(P＜0.05),while the serum miR-21 expression level in the stage Ⅳ patients was higher than that in stagesⅠ,Ⅱ,and Ⅲ(P＜0.05).The expression level of miR-27b in the serum of patients gradually increased across the four stages,with a significant difference(P＜0.05).The pathological staging was positively correlated with the expression of miR-21 and miR-27b(P＜0.001).The expression levels of miR-21 and miR-27b in serum of patients gradually increased across grades Ⅰ,Ⅱ and Ⅲ by Fuhrman grading,with significant difference(P＜0.05).Fuhrman grading was positively correlated with the serum miR-21 and miR-27b expression(P＜0.001).There was a statistically significant difference in the survival curve between the miR-21 high expression group and the low expression group(P＜0.05).There was a statistically significant difference in the survival curve between the high expression group and the low expression group of miR-27b(P＜0.05).Conclusion The expression levels of serum miR-21 and miR-27b in patients with renal clear cell carcinoma is indicative of the progression and prognosis of the patient's condition.

Objective To investigate the medication and blood glucose control of type 2 diabetes patients under chronic diseases management in Xi'an chain pharmacies,and provides reference for improving the management policy of diabetes at grassroots level.Methods A number of chain pharmacies in the sixth district of Xi'an were selected by random sampling method,and on-site interviews were conducted by questionnaire survey to patients with type 2 diabetes under the management of chronic diseases.The basic information of patients,medication status(medication plan,drug adherence,etc.),diabetes-related conditions(blood glucose status,family history,course and complications,etc.)were collected.Multivariate logistic regression was used to analyze the relevant factors of blood glucose control in patients.Results A total of 403 patients were surveyed,the largest number of patients use oral hypoglycemic drugs alone(53.4％),followed by insulin medication(including insulin only and insulin in combination with oral hypoglycemic drugs)(35.7％),and the differences between disease course and glycemic control among patients with different drug regimens were statistically significant(P＜0.05).Only 43.7％of patients had good medication compliance.In addition,the patient's fast plasma glucose compliance rate was only 39.2％.The results of multivariate logistic regression analysis showed that good medication compliance(OR=1.744,95％CI 1.104 to 2.754,P=0.017)were independent influencing factors for achieving glycemic control.Conclusion The medication compliance of type 2 diabetes patients with poor blood glucose control in chronic disease management of chain pharmacies in Xi'an needs to be strengthened.Pharmacies should emphasize and give full play to the professional and service advantages of pharmacists to realize the functional role of pharmacies and strengthen diabetes management.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

【Objective】 To measure and analyze foot development indicators of children under 3 years old, in order to provide basis for the correct clinical assessment of children foot development. 【Methods】 A total of 5 894 children under 3 years old who took physical examination in the Child Health Care Department of Xi′an People′s Hospital from August 2022 to March 2023 were randomly selected. Foot length, foot width, the ratio of foot width to length and arch index were measured by image processing system, and were compared among different age groups and sex groups. 【Results】 1) Foot length, foot width and arch index of children under 3 years old increased significantly with age, while the ratio of foot width to length decreased significantly with age(F=1 345.23, 396.21,184.65, 287.03, P<0.05). 2) There was no statistical significance in foot length, foot width and arch index between left and right foot of children under 3 years old(P>0.05). 3) Foot length and foot width of boys were greater than those of girls in all age groups, and the difference was statistically significant(tfoot length:3.45 - 10.19, tfoot width: 3.77 - 9.21, P<0.05). There was no significant difference in arch index between boys and girls in all age groups(P>0.05). 【Conclusion】 Foot shape of children under 3 years old changes with age, there are differences in foot length and width between boys and girls.