Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

Objective:To analyze the protective effect of neurotracheal catheter monitoring on recurrent laryngeal nerve in patients with bilateral cervical lymph node dissection of thyroid cancer.Methods:The clinical data of 92 patients undergoing bilateral cervical lymph node dissection for thyroid cancer at the First People's Hospital of Shangqiu from Jul 2019 to Aug 2022 were retrospectively analyzed. Patients were divided into control group (routine exposure, 52 cases) and study group (intraoperative neurotrachatic catheter monitoring, 40 cases) The general data, perioperative indicators, parathyroid function, vocal cord function, voice disorder index, quality of life and postoperative complications were compared between the two groups.Results:The intraoperative blood loss in the study group [(12.3±3.3) ml] was less than that in the control group [(16.9±4.0) ml]. The exposure time [(8.7±2.6) min], operation time [(4.0±0.8) h] and postoperative hospitalization time [(3.2±0.9) d] were shorter than those of control group [(14.4±3.6) min, (4.5±1.2) h, (5.7±1.3) d] ( t=5.770, 8.391, 2.387, 10.853, all P<0.05);Amplitude perturbation (4.85%± 0.58%), fundamental frequency perturbation (0.28%±0.17%), standardized noise energy [(-20.3±4.4) dB], VHI-10 score [(1.6±0.5) score], Quality of life scale for cancer patients 1 month after surgery the TG-V4 score [(43.7±4.8) points] was lower than that of control group [(3.05%±0.54%), (0.42%±0.16%), (-14.6±3.3) dB, (3.3±0.4) points, (50.4±5.6) points]. The harmonic noise ratio [(24.9±4.1) dB] was higher than that of the control group [(20.3±4.4) dB] ( t=10.446, 4.049, 7.036, 19.076, 6.116, 5.144, all P<0.001);The incidence of postoperative complications in the study group (8%) was lower than that in the control group (23%) ( χ2=4.020, P=0.045). Conclusion:Neurotracheal catheter monitoring during bilateral cervical lymph node dissection for thyroid cancer can improve vocal cord function, reduce recurrent laryngeal nerve injury, reduce voice disturbance and improve quality of life.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

OBJECTIVE To investigate the clinical efficacy and safety of rituximab （RTX） followed by belimumab （BLM） in patients with severe systemic lupus erythematosus（SSLE）. METHODS Nine SSLE patients， who were treated with RTX followed by BLM for more than 6 months in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Zhengzhou University from October 2020 to June 2021， were enrolled. Baseline clinical data of patients， laboratory examination results and basic treatment status at weeks 0， 4， 12， and 24 of medication were collected retrospectively. The patients’ systemic lupus erythematosus disease activity index （SLEDAI） score， glucocorticoid dosage and serological indicators （complement C3， complement C4， serum albumin， and 24-hour urine protein quantification） level were analyzed. At the same time， the occurrence of adverse drug reaction was collected. RESULTS All 9 patients completed more than 24 weeks of RTX followed by BLM therapy. All patients suffered from renal impairment， of which 7 （77.8%） had renal pathology support， 3（33.3%） had blood system damage and 2 （22.2%） had nervous system damage. During treatment， with the prolongation of treatment time， the SLEDAI score， 24- hour urinary protein quantification， and glucocorticoid dosage of patients showed a significant downward trend， and ultimately decreased to the normal index level （P＜0.05）； serum albumin， complement C3 and complement C4 all showed a significant upward trend， eventually rose to the normal index level （P＜0.05）. During treatment and follow-up， 1 patient developed herpes zoster， 1 patient developed upper respiratory tract virus infection， and 1 patient developed urinary system bacterial infection. All patients recovered after symptomatic treatment. CONCLUSIONS In sequential use of RTX followed by BLM for SSLE， early administration of RTX can quickly stabilizethe condition， significantly alleviate clinical symptoms， and gradually normalize specific serological indicators； subsequent administration of BLM can reduce the type and dosage of basic treatment drugs； there is no increase in the incidence of adverse drug reactions.

Objective:To investigate the differences between the expression levels of ribosomal protein L32 (RPL32) in human breast cancer tissue and normal breast tissue and the effects on the proliferation of breast cancer cells.Methods:Paraffin samples of breast cancer tissues and adjacent tissues (more than 3 cm from the tumor margin) were collected from 56 breast cancer patients in the Department of Thyroid and Breast Surgery of the First People's Hospital of Shangqiu City from July 2020 to May 2022. The expression of RPL32 in 56 breast cancer patients and their corresponding paracancer tissues was detected by immunohistochemistry. MCF7 cells were divided into experimental group (ribosomal protein L32, RPL32) and control group (negative control, NC). MCF7 cells in experimental group were transfected with RPL32-siRNA vector, while MCF7 cells in control group were transfected with scramble siRNA vector. RPL32 mRNA content in each group was detected by RT-PCR. The expressions of RPL32 and P53 in the experimental group and control group were detected by western blot. The proliferative ability of cells in each group was detected by CCK8 assay. The clonogenesis ability of each group of cells was detected by clone formation experiment.Results:The positive rate of RPL32 in breast cancer patients was 8.93% (5/56), and the expression rate of RPL32 in paracancer tissues was 78.57% (44/56). The expression rate of RPL32 in breast cancer patients was significantly higher than that in paracancer tissues, with statistical significance ( P=0.007). After transfection with siRNA vector, the mRNA content of RPL32 in MCF7 cells of experimental group and control group decreased, and the protein expression level of RPL32 was 1.09±0.21 and 0.40±0.11, respectively. The expression levels of P53 protein were 1.24±0.32 and 0.37±0.09, respectively. The absorbance of CCK8 at 120 h was 1.11±0.24 and 2.19±0.28, respectively, and the proliferation ability of MCF7 cells in the experimental group was significantly decreased ( P=0.043). The results of clone formation experiment showed that the cell clone formation rate of the experimental group and the control group was (21.11±3.46) % and (58.75±4.29) %, respectively, and the cell clone formation of the experimental group was decreased ( P=0.026) . Conclusions:The expression of RPL32 is significantly increased in breast cancer, which may be related to the malignant degree of breast cancer. Inhibition of RPL32 expression in breast cancer cells affects its proliferation ability.

Objective:To investigate the changes of ocular surface microbiota in obese patients before and after dietary intervention.Methods:From November 1, 2020 to May 1, 2021, 35 obese patients in the obesity management center of the Department of Endocrinology and Metabolic Diseases of Henan Provincial People′s Hospital were selected for a 4-week low-calorie dietary intervention of 1 600-1 800 kcal/day. The body weight, body mass index(BMI), body composition(body fat, body fat percentage, visceral fat grade, total body water, and skeletal muscle) were observed before and after dietary intervention. The characteristics of ocular surface flora in obese patients before and after intervention were analyzed by 16S rRNA sequencing.Results:The body weight, BMI, body fat, percentage of body fat, visceral fat grade and total body water decreased significantly after 4 weeks( P<0.05), while there was no significant difference in skeletal muscle( P>0.05). There was no significant difference of ocular surface flora α and β in diversity( P>0.05). Opportunistic pathogens Pseudomonas and Cutibacterium decreased significantly, while Faecalibacterium, Lachnospiraceae NK4A136 group, Oscillospiraceae UCG 002, and Blautia, which producing short chain fatty acids, increased significantly( P<0.05). Functional prediction analysis showed that the metabolic pathways such as degradation related pathways and insulin signaling pathways of volatile organic compounds(VOCs) were significantly enriched. Conclusion:After dietary intervention, opportunistic pathogenic bacteria decreased and short chain fatty acid producing bacteria increased in obese patients. The altered ocular surface flora may be related to the degradation of VOCs and the improvement of insulin sensitivity.

To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%), P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.

BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*

Background::Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods::A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool. Results::In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-α inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P < 0.001); higher risk of URTI for TNF-α inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P= 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-α inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P= 0.006). Conclusions::This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Objective To evaluate the factors related to contralateral hip fracture in the elderly patients with hip fracture by meta analysis.Methods Pubmed,Cochrane,CBMdisc,CNKI Chinese Journal Full Text Database and Wan Fang Database were searched for publications at home and abroad from January 2005 to April 2018 on factors related to contralateral hip fracture after hip fractures in the elderly.The publication quality was strictly evaluated before the data were extracted concerning gender and age(＞ 65years) of the patients,concomitant osteoporosis (Singh sign ≥ 4),primary fracture type,concomitant Parkinson disease,concomitant stroke,concomitant senile dementia,concomitant cataract,concomitant rheumatoid arthritis,concomitant diabetes,type of internal fixation for primary fracture and therapeutic compliance.Revman5.0 was used to perform the statistical analysis and the OR value and 95％ CI were calculated fore each index.Results A total of 17 studies were included involving 1,504 patients with contralateral hip fracture among 13,717 elderly patients with hip fracture.The factors related to the refracture of the contralateral hip were the age of the patients (OR ＝-3.55,95％ CI:-5.60 ～-1.50,P ＜ 0.001),osteoporosis (OR=2.38,95％CI:1.36～4.17,P=0.002),Parkinson disease (OR=4.54,95％CI:2.74～7.53,P ＜0.001),stroke (OR=0.33,95％ C I:0.18～0.59,P ＜ 0.001),senile dementia (OR=0.43,95％CI:0.29～0.62,P ＜0.001),cataract (OR=0.37,95％CI:0.22～0.63,P ＜0.001),rheumatoid arthritis (OR =0.32,95％ CI:0.21 ～ 0.50,P ＜ 0.001),diabetes (OR =0.65,95％ CI:0.47～0.91,P=0.01),type of internal fixation for primary fracture (OR=0.51,95％ CI:0.30 ～ 0.85,P =0.01),and therapeutic compliance (OR =0.36,95％ CI:0.21 ～ 0.64,P ＜ 0.001).However,the refracture of the contralateral hip was not related to gender (OR =1.07,95％ CI:0.45 ～2.56,P=0.88),smoking (OR=0.86,95％CI:0.40～1.86,P=0.70),fracture type (OR=0.97,95％ CI:0.60～1.57,P=0.90),or hypertension (OR=0.70,95％ C I:0.41～1.21,P=0.20).Conclusions In elderly patients with hip fracture,the risks for contralateral hip fracture may be advanced age,concomitant osteoporosis,Parkinson disease,stroke,senile dementia,cataract,rheumatoid arthritis and diabetes,type of internal fixation for primary fracture,and poor therapeutic compliance.However,no sufficient evidence has suggested that gender,smoking,type of hip fracture or concomitant hypertension might be associated with the contralateral hip fracture.