BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear. OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

ObjectiveTo develop a classification model based on complete blood count （CBC） parameters combined with clinical factors to predict severe respiratory infections caused by Human adenovirus （HAdV） in pediatric patients. MethodsFrom September 2023 to September 2024， the CBC parameters and related clinical data from pediatric patients diagnosed with HAdV infection were collected. Principal component analysis and random forest models were used to identify potential predictors of severe cases. ResultsA total of 668 pediatric patients were included， with 564 cases assigned to the training cohort and 104 cases to the validation cohort. Severe cases were defined as pneumonia and/or fever lasting ≥5 days （pneumonia or prolonged fever， PorPF）. Principal component analysis and feature importance analysis （Mean Decrease Gini value） identified the monocytosis ratio （PMono）， red blood cell count （RBC）， and platelet count （PLT） as the most critical CBC parameters. Logistic regression analysis revealed that oxygen therapy （OR = 4.367， 95% CI： 1.568–12.161） and increased work of breathing （OR = 3.904， 95% CI： 2.146–7.101） were relative risk factors for PorPF. Meanwhile， higher PMono （OR = 0.696， 95% CI： 0.640–0.757）， RBC （OR = 0.201， 95% CI： 0.124–0.325）， and PLT （OR = 0.990， 95% CI： 0.987–0.994） were protective factors. When PMono was used as a predictive marker for PorPF， the area under the receiver operating characteristic curve （AUC） was 0.648 and 0.705， respectively. A random forest model incorporating four risk factors ［PMono， RBC， PLT， and hematocrit （HCT）］ was constructed to classify PorPF and general cases， achieving AUCs of 0.688 and 0.768， respectively. ConclusionsPMono， RBC， and PLT may serve as characteristic CBC indicators for predicting pneumonia or prolonged fever in children with HAdV infection. A risk factor model built using PMono， RBC， PLT， and HCT offers a relatively simple and accurate approach to predicting severe cases in pediatric HAdV infections.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

Objective To explore the correlation between speech fluency and diadochokinetic rate in children aged 7～11 years with cochlear implant.Methods Speech samples were collected from 62 children aged 7～11 years with cochlear implant using language retelling task and diadochokinetic rate test task.Their speech rate,articulation rate,syllable duration and pause duration were analyzed.The data were input into ICF converter to obtain the im-pairment limit of each parameter and analyze the speech fluency and diadochokinetic rate characteristics.Partial cor-relation analysis was performed for speech rate,articulation rate,syllable duration and pause duration by two tasks.Results ① For children with cochlear implant,the mean ICF impairment limit of diadochokinetic rate was 1.3± 0.1,the mean ICF impairment limit of fluency in retelling was 1.0±0.3,with various degree of impairment in both tasks.② There was a moderate or low correlation between speech rate,articulation rate,syllable duration in retell-ing task and those in diadochokinetic rate task(0.3＜|r |≤0.8).There was a low correlation between pause dura-tion in retelling task and speech rate and pause duration in diadochokinetic rate task(0.3＜|r |≤0.5).Conclusion The speech fluency and diadochokinetic rate of children aged 7～11 years with cochlear implant is underdeveloped,and the poor articulation movement ability limits their development of speech fluency.

Objective To observe the value of radiomics combined with CT features for distinguishing mycoplasma pneumonia(MP)and non-MP in children.Methods Data of 153 children with pneumonia were retrospectively analyzed.The children were divided into MP group(n=101)and non-MP group(n=52)according to mycoplasma RNA detection,and also were divided into training set(n=107,including 71 MP and 36 non-MP)and validation set(n=46,including 30 MP and 16 non-MP)at the ratio of 7∶3.CT findings were compared between groups.Six best CT features were selected in training set using F test algorithm,and a CT model was constructed using logistic regression(LR)method.The best radiomics features were extracted and screened in training set,and machine learning(ML)models were constructed using LR,support vector machine(SVM),random forest(RF),linear discriminant analysis(LDA)and stochastic gradient descent(SGD)classifiers,respectively.Based on the best CT features and radiomics features,CT-ML models were constructed using the above classifiers.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated,the efficacy of each model for distinguishing MP and non-MP was evaluated.Results Lesions involved the upper,middle and lower lobe of right lung,thickened bronchial wall,tree bud sign and edge retract sign were the best CT features.AUC of CTLR was 0.710,of MLLR,MLSVM,MLRF,MLLDA and MLSGD in validation set was 0.715,0.663,0.623,0.706 and 0.494,respectively,and MLLR was the optimal radiomics model.AUC of CT-MLLR,CT-MLSVM,CT-MLRF,CT-MLLDA and CT-MLSGD in validation set was 0.813,0.823,0.649,0.796 and 0.665,respectively,and CT-MLSVM was the optimal CT-ML model.In training set,AUC of CT-MLSVM(0.840)was higher than that of CTLR and MLLR model(AUC=0.713,0.740,both P＜0.05).In validation set,no significant difference of AUC was found among CTLR,MLLR and CT-MLSVM(AUC=0.710,0.715 and 0.823,all P＞0.05).Conclusion Radiomics combined with CT features could effectively distinguish MP and non-MP in children.

Objective:To summarize and analyze the diagnostic and therapeutic characteristics of asymptomatic primary hyperparathyroidism (aPHPT).Methods:A retrospective analysis was conducted on the clinical data of 103 patients with aPHPT admitted to the Chinese PLA General Hospital from January 2012 to September 2023. The clinical characteristics, treatment modes, and prognoses of the patients were analyzed. GraphPad Prism 8.0 software was used for statistical analysis.Results:Among the 103 cases, there were 37 males and 66 females, aged from 25 to 78 years, with an average age of (53.81±11.34) years. Ninety-eight cases (95.15%) visited due to abnormal findings during physical examination and 5 cases (4.85%) due to hypertension, diabetes or other diseases. All patients underwent minimally invasive parathyroidectomy with small incision, with 96 cases (93.20%) pathologically diagnosed as adenomas and 7 cases as hyperplasia (6.80%). Postoperative mean serum calcium, parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels were respectively significantly lower than preoperative levels, while postoperative serum phosphorus level was significantly higher than preoperative level ( P<0.05). The mean lesion volume was (3.32±6.72)cm 3 (range 0.05-49.50 cm 3). Patients with different lesion volumes had significant differences in preoperative serum calcium, PTH and ALP levels. Lesion volume was positively correlated to preoperative serum calcium(ρ=0.36, P<0.01), PTH(ρ=0.50, P<0.01) and ALP(ρ=0.39, P<0.01). Among 103 patients, 94 cases were followed up (91.26%), 9 cases were lost (8.74%), and the mean follow-up period was (60.15±29.23) months. The followed-up patients were alive and had no recurrence of lesions or complications, and their blood calcium levels were normal. Conclusion:aPHPT can be preliminarily diagnosed through blood biochemistry and imaging examination, and minimally invasive surgery can offer good prognosis without serious complications.

The methodological framework for interventional clinical research of Chinese medicine （CM） under the research mode of syndrome dominating disease provides a set of technical principles and methods to design， evaluate， and implement of this kind. It consists of three main parts including general principles， research points and key design elements， with a total of 25 items. This methodological framework proposes implementing requirements and recommendations in a variety of aspects， including basic norms to be followed in relevant studies， perspectives for selecting research topics， as well as the technological details on study population （P）， intervention （I） and comparison（C）， outcome measurement （O）， time frame （T） of treatment and follow-up， sample orientation （prospective versus retrospective）， study design （S） format and type. To provide practical guidance for future studies， this article clearly explains each items of the methodological framework through some supportive cases.

Objective: To understand the nutritional literacy level and associated factors of primary and secondary school students in Beijing, so as to provide a scientific basis for improving student nutrition. Methods: From October 2022 to May 2023, a multi stage cluster random sampling method was employed to select a total of 14 568 primary, junior and senior high school students from 16 districts (ecluding the Economic Technological Development area) in Beijing. Through a survey questionnaire on nutritional literacy and dietary hehavior of school age children, basic information as well as data on nutritional literacy levels across four dimensions:nutrition related knowledge concepts, food selection, food preparation, and food intake dimensions were obtained. The Wilcoxon rank sum test, Kruskal-Wallis test, Spearman correlation analysis, Chi square test and binary Logistic regression were used for the analysis. Results: The median total score of nutritional literacy among primary and secondary school students in Beijing was 68.8. Approximately 26.0% of primary and secondary school students achieved nutritional literacy standards. The median scores and rates of meeting the standards for nutrition related knowledge concepts, food selection, food preparation and food intake dimensions were 23.0, 42.1%; 17.0, 27.4%; 6.5, 33.5%; 23.0, 33.3%, respectively. There were positive correlations between all pairs of the four dimensions ( r=0.33-0.49, P <0.05). The results of multiple Logistic regression analysis showed that primary school students, junior high school students, female students, suburban students, caregivers with a college education level and a bachelor s degree or above were the positive arrelation factors that promoted the achievement of nutritional literacy standards ( OR =2.21, 1.39, 1.18, 1.27, 1.42, 1.66, P <0.05). Conclusion The literacy level of primary and secondary school students in Beijing needs to be significantly improved. School stage, gender, region and caregiver s education level are associated factors.