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.

OBJECTIVE: To evaluate the early efficacy of local application of tranexamic acid on the osteotomy surface during hallux valgus surgery in reducing postoperative occult blood loss and thus postoperative swelling. METHODS: The data of 40 cases with hallux valgus osteotomy admitted to the Department of Foot and Ankle Surgery of Jishuitan Hospital from July 11, 2022 to October 8, 2022, including 5 males and 35 females were retrospectively analyzed. According to the inclusion and exclusion criteria, 32 cases were finally divided into 16 cases in the observation group (application of tranexamic acid) and 16 cases in the control group (no application of tranexamic acid). The observation group was paired with the control group one by one in accordance with the operation style, and the change in the anterior and posterior diameter of the first metatarsal head, the change in the circumferential diameter of the foot, the length of the first metatarsal midline and the length of the plumbline of the foot measured by postoperative CT were compared between the two groups before and after surgery, in order to evaluate the degree of swelling around the incision after the surgery. The first metatarsal midline and plumb line were measured by reference to the two auxiliary lines that intersect the soft tissue border in the sesamoid bone position to measure the rotation angle of the first metatarsal. A total of three clinicians completed the measurements of these two line segments and interobserver comparisons were performed. RESULTS: By interobserver comparison, the consistency of the length of the midline of the first metatarsal and the plumbline measured by CT was high and could be considered a reliable measurement. After the paired t-test, there was no statistical difference in the amount of changes in the anteroposterior diameter of the first metatarsal before and after surgery between the observation and control groups (P>0.05), and the amount of changes in the circumferential diameter of the foot before and after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05); the length of the midline of the first metatarsal and the plumbline of the foot measured by CT after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05). CONCLUSION Local application of tranexamic acid on the osteotomy surface during hallux valgus osteotomy can relieve postoperative swelling to some extent, which may be related to the fact that tranexamic acid reduces occult blood loss in the postoperative period.
Humans ; Hallux Valgus/surgery* ; Tranexamic Acid/administration & dosage* ; Female ; Male ; Osteotomy/adverse effects* ; Retrospective Studies ; Edema/etiology* ; Adult ; Middle Aged ; Postoperative Complications/prevention & control* ; Antifibrinolytic Agents/administration & dosage*

OBJECTIVE: To standardize the operative procedure for tissue-engineered cartilage repair, by demonstrating surgical technique of arthroscopic implantation of decalcified cortex-cancellous bone scaffolds, and summarizing the surgical experience of the sports medicine department team at Peking University Third Hospital. METHODS: This article elaborates on surgical techniques and skills, focusing on the unabridged implantation technology and surgical procedure of decalcified cortex-cancellous bone scaffolds under arthroscopy: First, the patient was placed in the supine position. After anesthesia had been established, the surgeon established an arthroscope and explored the damaged area under the scope. After confirming the size and location of the injury site, the surgeon cleaned the damaged cartilage, and also trimmed the edges of the cartilage to ensure that the cut surface was smooth and stable. the surgeon performed the micro-fracture surgery in the area of cartilage injury, and then measured the size of the injured area under the scope. Next, the surgeon manually trimmed the tissue-engineered scaffold based on the measurements taken under the arthroscope, and then directly implanted the scaffold using a sleeve. A honeycomb-shaped fixator was used to implant absorbable nails to fix the scaffold. After the scaffold was installed, the knee was repeatedly flexed and extended for 10-20 times to ensure stability and range of motion. Finally, the arthroscope was withdrawn and the wound was closed. RESULTS: Decalcified cortex-cancellous bone scaffolds possessed unparalleled advantages over synthetic materials in terms of morphology and biomechanics. The cancellous bone part of the scaffold provided a three-dimensional, porous space for cell growth, while the cortical bone part offered the necessary mechanical strength. The surgery was performed entirely under arthroscopy to minimize invasiveness to the patient. Absorbable pins were used for fixation to ensure the stability of the scaffold. This technique could effectively improve the prognosis of the patients with cartilage injuries and standardized the surgical procedures for arthroscopic tissue-engineered scaffold operations in the patients with cartilage damage. CONCLUSION With the standard arthroscopic tissue-engineered scaffold repair technique, it is possible to successfully repair damaged cartilage, alleviate symptoms in the short term, and provide a more ideal long-term prognosis. The author and their team explain the surgical procedures for tissue-engineered scaffolds under arthroscopy, with the aim of guiding future clinical practice.
Tissue Engineering/methods* ; Humans ; Tissue Scaffolds ; Arthroscopy/methods* ; Cartilage, Articular/surgery*

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.

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 explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

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 evaluate knee biomechanics of patients about 12 months after anterior cruciate ligament(ACL)reconstruction during cutting and determine the abnormal biomechanical characteristics.Methods:Sixteen males about 12 months after ACL reconstruction were recruited for this study.Three-dimensional kinematic and kinetic data were collected during cutting movement.Knee joint angles and moments were calculated.Paired t-tests were used to compare the differences in knee biomechanics be-tween the surgical leg and nonsurgical leg.Results:The peak posterior ground reaction force(surgical leg:0.380±0.071;nonsurgical leg:0.427±0.069,P=0.003)and vertical ground reaction force(surgical leg:1.996±0.202,nonsurgical leg:2.110±0.182,P=0.001)were significantly smaller in the surgical leg than in the nonsurgical leg.When compared with the uninjured leg,the surgical leg demonstrated a smaller knee flexion angle(surgical leg:38.3°±7.4°;nonsurgical leg:42.8°±7.9°,P＜0.001)and larger external rotation angle(surgical leg:10.3°±2.4°;nonsurgical leg:7.7°±2.1°,P=0.008).The surgical leg also demonstrated a smaller peak knee extension moment(surgical leg:0.092±0.031;nonsurgical leg:0.133±0.024,P＜0.001)and peak knee external rotation moment(surgical leg:0.005±0.004;nonsurgical leg:0.008±0.004,P=0.015)when com-pared with the nonsurgical leg.Conclusion:The individuals with ACL reconstruction mainly showed asymmetrical movements in the sagittal and horizontal planes.The surgical leg demonstrated a smaller peak knee flexion angle,knee extension moment,and knee external rotation moment,with greater knee external rotation angle.