OBJECTIVE:Chronic ankle instability is mainly characterized by symptoms such as muscle weakness,intermittent pain,and repeated sprains,which seriously affect exercise and daily life.Loss of proprioception,prolongation of fibular reaction time,and weakening of valgus force may be the main symptoms of chronic ankle instability,so exercise intervention can effectively improve the symptoms related to ankle instability.Meta-analysis was used to quantitatively evaluate the effect of balance training on the rehabilitation intervention of chronic ankle instability,providing a reliable theoretical basis and practical basis for chronic ankle instability patients to scientifically formulate exercise prescriptions. METHODS:The randomized controlled trial of balance training on symptom rehabilitation and dynamic equilibrium of patients with chronic ankle instability was retrieved on CNKI,VIP,Web of Science,and PubMed.The literature was published from the inception to November 23,2022.Two reviewers were included to evaluate the quality of the included literature based on the physical therapy evidence scale.The primary outcome measure is the Self Functional Rating Scale,and the secondary outcome measure is the Star Shift Balance Test,both of which are continuous variables.Forest mapping,meta-regression,subgroup analysis,sensitivity analysis,and publication bias evaluation were performed on the included literature using RevMan 5.3 and Stata-SE 15 software. RESULTS:(1)A total of 18 articles of randomized controlled trials were screened and 641 patients with chronic ankle instability were included in the study.Overall,the methodological quality of the literature was relatively high.(2)Meta-analysis results showed that balance training improved the functional rehabilitation effect of chronic ankle instability patients(SMD=0.82,95%CI:0.41-1.23,P<0.000 1).Meta-regression exhibited that intervention time might be the main reason for heterogeneity(P=0.008).(3)The subgroup analysis results revealed that 6 weeks of intervention(SMD=0.98,95%CI:0.31-1.65,P=0.03),more than 3 interventions per week(SMD=0.87,95%CI:0.30-1.44,P=0.003),and each intervention time less than 20 minutes(SMD=0.89,95%CI:0.61-1.66,P<0.000 1)were the best rehabilitation plans to improve the functional rehabilitation effect of chronic ankle instability patients.(4)Meta-analysis results also showed that balance training improved the stretching degree of the anterior side(SMD=0.56,95%CI:0.31-0.80,P<0.05),posterior inner side(SMD=0.88,95%CI:0.45-1.32,P<0.05),and posterior outer side(SMD=0.84,95%CI:0.22-1.46,P<0.05)of the star shift balance test. CONCLUSION:Current clinical evidence shows that balance training can improve ankle instability symptoms and elevate dynamic equilibrium ability in chronic ankle instability patients.It is recommended to intervene more than 3 times a week,with each intervention lasting less than 20 minutes,to achieve better rehabilitation effects.

Objective:To investigate the quality of life in patients with early-stage extra-nodal NK/T cell lymphoma of nasal type (ENKTL) arising from the upper aerodigestive tract, who had remained progression-free survival (PFS) for over 3 months after definitive intensity-modulated radiation therapy (IMRT), and to analyze the factors related to main adverse symptoms.Methods:276 patients who received IMRT from March, 2012 to June, 2021 were included. There were 201 males and 75 females with a median age of 41.5 years (range: 13-81 years) upon diagnosis. Consistent target delineation schemes and similar dose gradients were adopted for IMRT, with a median prescribed dose of 54.6 Gy/26F. Cross-sectional investigation was performed with a modified EORTC QLQ-H&N35 questionnaire, the incidence and severity of adverse symptoms, severity of disease and their influencing factors at each time-point during their survival were statistically analyzed.Results:The median age of patients at the investigation was 46.2 years, and the median PFS after IMRT was 47.2 months (range: 3.1-115.7 months). The most common adverse symptoms included nasal symptoms (incidence rate 63.8%), dry mouth (50%), tooth diseases (47.1%), smell and taste alteration, and sexual apathy, etc. Most symptoms were mild (the average standardized score was 5.50, the full score of 100 indicating the most severe), and could be relieved remarkably over survival time, but some symptoms, such as tooth diseases and sexual apathy, were more obvious and recurred for several years. Age and anti-PD-1 immune therapy influenced the symptom scores, and tooth diseases were closely correlated with dry mouth. Conclusion:The quality of life in patients with early-stage ENKTL after definitive IMRT is high, and the most significant symptoms include nasal symptoms, tooth diseases, and sexual apathy, etc. , which need to be mitigated with more studies.

Objective To investigate the supernatant of umbilical cord-derived mesenchymal stem cells (UCMSCs) on tumor necrosis factor-α(TNF-α) and apoptosis protein caspase-3 in diabetic rats model with skin ulcer. Methods 45 Sprague-Dawley rats were randomly divided into control group (acute wounds group), phosphate buffered saline (PBS) group and UCMSCs supernatant group. The diabetic rat model was constructed by injecting with alloxan by tail vein and feeding with high-fat diet. Diabetic skin ulcer (DSU) rat model was constructed by scratching a wound and infusing suspension of Staphylococcus aureus. In the control group, the diabetic rats (n=15) were scratched to form a wound and treated by tail vein injection of 100μl PBS. In the PBS group, DSU rats (n=15) were treated by tail vein injection of 100μl PBS, and then 100μl PBS was dropped at the ulcer site. In the UCMSCs supernatant group, freeze-dried powder of UCMSCs supernatant was dissolved in 200μl PBS, 100μl of which was injected into the tail vein of DSU rats (n=15), and other 100μl was dropped at the ulcer site. After 5 days of the treatments, the levels of serum TNF-αwere detected by radioimmunoassay method, and the expression of TNF-αand caspase-3 in the ulcer tissues of rats was detected by polymerase chain reaction and Western Blot. Results The levels of TNF-αin the PBS group [(35.9±3.7)μg/L] were significantly higher than that of the control group [(11.4±4.9)μg/L] and the UCMSCs group [(14.7±6.6)μg/L] (all P<0.05). The levels of mRNA and protein expression of TNF-αand caspase-3 in the UCMSCs group were significantly lower than those of the PBS group (all P<0.05), and have no significant differences with respect to those of the control group (all P>0.05). Conclusions UCMSCs supernatant treatments can effectively down-regulate the expression of TNF-αand caspase-3 in ulcer tissue of DSU rats, and play an anti-inflammatory and anti-apoptotic effect.

Non-invasive brain stimulation techniques,including transcranial direct current stimula-tion (TDCS) and transcranial magnetic stimulation (TMS),are safe and non-invasive techniques,which can change the local excitability of the brain. The application of these techniques in the field of psychology,espe-cially decision making,has developed rapidly. These techniques provide the researchers a new perspective to study how people make decisions and to explore the neural mechanisms behind decision-making behaviors. This paper reviews the studies of non-invasive brain stimulation techniques in the field of different decision-making behaviors (risky choice,intertemporal choice and social decision-making) and the problems existing in the current studies,and puts forward some possible solutions.

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

Objective:To investigate the association of plasma EBV-DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators.Methods:Clinical data of 173 newly-diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I-II and 47 cases of stage Ⅲ-IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra-upper aerodigestive tract (extra-UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV-DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10 4 copies/ml, n=73) and high load group (≥10 4 copies/ml, n=64). Serum cytokines including IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α were detected. Correlation analysis was performed by Cochran-Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan-Meier survival analysis. Results:The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV-DNA copy levels. In addition, serum levels of IFN-γ, IL-6 and IL-10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN-γ, IL-6, and IL-10 levels were also positively correlated with plasma EBV-DNA copy number. The occurrence of B symptoms was associated with high-risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre-treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV-DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression-free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion:This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV-DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.

Objective To analyze the changing trend of disease burden attributable to renal insufficiency in cardiovascular disease (CVD) among the elderly in China from 1990 to 2019, and to forecast the disability-adjusted life years (DALY) in the next 10 years, so as to provide a reference basis for accurate prevention and control of CVD attributable to renal insufficiency in China. Methods Data were obtained from the Global Health Data Exchange (GHDx) database to describe the current status of CVD prevalence attributable to renal insufficiency. The joinpoint model was used to estimate the annual percentage change and average annual percentage change to assess the temporal trend of CVD attributable to renal insufficiency in China. An autoregressive moving average model was created by R4.0.2 software to predict the disease burden of CVD attributable to renal insufficiency in China. Results Compared with 1990, CVD mortality and DALY rates attributed to renal insufficiency increased in the male elderly population and decreased in women. Mortality and DALY rates attributed to ischemic heart disease, ischemic stroke, and peripheral arterial disease attributed to renal insufficiency showed an increasing trend, and mortality and DALY rates for cerebral hemorrhage decreased. There was an overall increasing trend in the attribution of CVD due to renal insufficiency. Conclusion The burden of diseases attributable to renal insufficiency in Chinese elderly with CVD is relatively high, and the impact on each disease is different, which requires the attention of relevant authorities.

The precise etiology of oral lichen planus(OLP)is still unclear,but the existing evidence suggests that drug intake,virus infection,fungal infection,psychological disorders,and immunodeficiency are closely associated with the pathogenesis of OLP.We report a case of OLP accompanied with candidiasis induced by long-term use of antimicrobials for recurrent aphthous ulcer(RAU)and update the literature,to discuss the possible association between OLP and misuse of antimicrobials,and to inform general dentists and pharmacists the importance for practice with optimal antimicrobial stewardship.In this case,a 42-year-old man presented to Xiangya Stomatological Hospital with white reticular patterns spreading in the oral cavity for almost 1 year.He was diagnosed with OLP via histopathological examination.He had a 5-year history of RAU which occurred every 1-2 months,and he was given antimicrobials ingested or injected whenever the ulcers came up.Satisfactory treatment results were obtained by stopping the abuse of antimicrobials and local antifungal therapy.Meanwhile,the exacerbation and alleviation of OLP was closely related to the administration of antimicrobials.Combined with literature review,antimicrobial might contribute to the development of OLP by inducing candidiasis,a common side-effect of misuse of antimicrobials.Considering the seriousness of antimicrobial resistance and opportunistic infection,dentists should prescribe antimicrobials judiciously according to guidelines and evidence-based indications.Appropriate prescribing of antimicrobials is a professional responsibility to all dentists.

Objective To analyze the disease burden of multidrug-resistant tuberculosis (MDR-TB) in China and regions with different income levels in the world from 1990 to 2019. Methods Using the Global Burden of Disease Study 2019 (GBD2019) results, the changes of the disease burden of MDR-TB in China and regions with different income levels in the world were described and analyzed using the Joinpoint Regression Program 4.8.0.1 software. Results From 1990 to 2019, the age standardized incidence, mortality and DALY rates in China and other areas with different income levels in the world basically showed a trend of first rising and then decreasing at the turning point of the late 20th century and early 21st century, except for low-income areas where the age standardized incidence rate showed an overall upward trend. In 2019, the incidence rate, mortality and DALY rate of MDR-TB in China were 9 times, 6.67 times and 6.89 times higher than those in high-income areas, respectively. The incidence rate in China was 6 times lower than that in low and middle-income areas, while the mortality and DALY rate in China were 26 times and 32.53 times lower than those in low-income areas, respectively. The age standardized incidence, mortality rate and DALY rate of MDR-TB in men were higher than those in women. Risk factors for the burden of MDR-TB disease included alcohol consumption, smoking, and high fasting blood glucose. Conclusion From 1990 to 2019, there are significant regional and gender differences in the disease burden of multidrug-resistant tuberculosis in China and regions with different income levels in the world. Multidrug-resistant tuberculosis is still a major challenge for tuberculosis control in the world. It is necessary to develop more effective control strategies and health care systems to deal with multidrug-resistant tuberculosis.