BACKGROUND:Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown. OBJECTIVE:To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique. METHODS:The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.The βvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages. RESULTS AND CONCLUSION:A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with age:age-unspecified bone mineral density[β=0.038,95%confidence interval(CI):1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI:1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI:1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI:0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI:0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI:0.96-1.04,P=0.716).Similar results were obtained from the MR-Egger regression and weighted median estimator analyses.These findings indicate that type 2 diabetes mellitus may be one of the protective factors of bone mineral density,and there is a correlation with age.

Objective:To compare the curative effects between modified double-reverse traction technique and traditional open reduction in the treatment of tibial plateau fractures.Methods:A retrospective study was conducted to analyze the data of 70 patients with Schatzker type Ⅳ-Ⅴ tibial plateau fracture who had undergone surgical treatment at The Third Department of Orthopaedics, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine from January 2017 to December 2022. The patients were divided into an observation group treated with modified double-reverse traction and a control group treated with traditional open reduction. In the observation group of 37 cases, there were 20 males and 17 females with an age of (44.6±13.5) years, and 9 cases of type Ⅳ and 28 cases of type V by the Schatzker classification; in the control group of 33 cases, there were 18 males and 15 females with an age of (45.9±13.7) years, and 10 cases of type Ⅳ and 23 cases of type Ⅴ by the Schatzker classification. The 2 groups were compared in terms of operation time, length of main incision, intraoperative blood loss, Rasmussen imaging score before discharge, and knee function score of American Hospital for Special Surgery (HSS), Visual Analogue Scale (VAS), fracture healing and complications at 6 months postoperatively.Results:There was no significant difference in the preoperative general data between the 2 groups, showing group comparability ( P>0.05). All patients were followed up for (14.3±1.4) months. The observation group was significantly better than the control group in operation time [(113.9±11.4) min versus (151.82±10.37) min], length of main incision [4 (4, 5) cm versus 6 (6, 7) cm], intraoperative blood loss [30 (20, 35) mL versus 55 (50, 65) mL], VAS [0 (0, 0) point versus 0 (0, 1) points] and HSS score [(89.8±3.1) points versus (86.0±3.5) points] ( P<0.05). There were no significant differences between the 2 groups in Rasmussen imaging score before discharge, or fracture healing rate or complication rate at 6 months postoperatively ( P>0.05). Conclusion:In the treatment of Schatzker type Ⅳ-Ⅴ tibial plateau fractures, modified double-reverse traction technique is worthy of clinical application and promotion, because it is advantageous over traditional open reduction in terms of shorter operation time, smaller surgical incision, less intraoperative blood loss, less postoperative pain and better knee function.

Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2％response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.

Objective:To investigate the expression of long non-coding RNA (Lnc RNA) RP5-919F19 in gastric cancer tissues and its correlation with gastric cancer invasion and metastasis.Methods:Non-tumor gastric mucosa (more than 3cm away from the cancer tissue) and gastric adenocarcinoma tissues were collected from Jan. 2020 to Jan. 2022 in our hospital. TRIzol kit was used to extract total RNA from cells and tissues, and reverse transcription kit was used to reverse transcribed RNA into cDNA. Quantitative real-time PCR kit was used for quantitative analysis. SGC-7901 and AGS human gastric cancer cells were used to construct RP5-919F19 knockdown and overexpression models. CCK-8 assay was used to confirm cell proliferation, and Transwell invasion assay was used to confirm the invasion ability of gastric cancer cells.Results:The expression of RP5-919F19 was detected in 79 cases of gastric cancer tissues and adjacent normal tissues, and it was found that the relative expression of RP5-919F19 in gastric cancer tissues was 1.51±0.05 significantly higher than that of 0.82±0.04 in adjacent normal tissues ( P<0.05) . The levels of RP5-919F19 in patients with different pathological conditions were compared and analyzed. The results showed that there were statistically significant differences in RP5-919F19 expression in patients with different TNM stages, distant metastasis, lymph node metastasis and different depth of invasion ( P<0.05) . There was no significant difference in RP5-919F19 expression among patients with different tumor sizes, ages and genders ( P>0.05) . AGS gastric cancer cells were transfected with RP5-919F19 overexpression plasmid and control plasmid, and the efficiency of RP5-919F19 was detected. The results showed that the expression level of RP5-919F19 in the overexpression group was 1.83±0.14 higher than that of 0.82±0.05 in the control group ( P<0.05) . SGC-7901 gastric cancer cells were transfected with RP5-919F19 knockout vector and control vector, and the efficiency of RP5-919F19 was detected. The results showed that the expression level of RP5-919F19 in the knockout group was 0.42±0.07 lower than that of 0.89±0.08 in the control group ( P<0.05) . CCK-8 was used to detect the proliferation ability of gastric cancer cells. The results showed that the proliferation ability of AGS cells in RP5-919F19 overexpression group was significantly increased compared with that of the control group at 24 and 48h after culture ( P<0.05) . However, the proliferation ability of SGC-7901 cells in RP5-919F19 knockdown group was lower than that in the control group at 24 h and 48 h ( P<0.05) . Transwell invasion assay showed that the invasion and migration abilities of AGS cells in RP5-919F19 overexpression group were higher than those in the control group ( P<0.05) , and the invasion and migration abilities of SGC-7901 cells in RP5-919F19 knockout group were lower than those in the control group ( P<0.05) . Western blot showed that compared with control cells, the expression of MMP-2 and MMP-9COPS7A proteins in down-regulated Lnc RNA RP5-919F19 SGC-7901 cells was decreased. Conclusion:The expression of LncRNA RP5-919F19 is abnormally increased in gastric cancer tissues, and the increased expression of RP5-919F19 can promote the proliferation and metastasis of gastric cancer cells.

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

OBJECTIVE To clarify the mecha-nism of Tou Tong Ning capsule(TTNC)and elu-cidate crosstalk between multi-components drug and trigeminal ganglia cells in migraine.METH-ODS We integrated single-cell RNA sequencing data and a quantitative evaluation algorithm of the disturbance of multi-target drugs on the dis-ease network to explore the specific pathology of TTNC for migraine.Cerebrovascular smooth muscle spasmolytic activity experiment was car-ried out to verify the results of bioinformatics analysis.RESULTS TTNC can effectively regu-late the functions of synaptic signaling,inflamma-tion and immune response,and cerebrovascular smooth muscle.For different cell subtypes of tri-geminal ganglia,TTNC can significantly disturb the robustness on neuronal cell networks and non-neural networks(fibroblast and vascular cells),indicating TTNC vasodilation activity of brain vessels and neural regulation activities of various neuro types.Contraction of cerebrovas-cular smooth muscle of mouse ex vivo confirmed the vasodilation activity of TTNC and active com-pounds(Emodin,Luteolin and Levistilide A).And literature mining confirmed the vasospasmolytic activity and neuroprotective effect activity of TTNC.CONCLUSIONS Integrating single-cell data and network disturbance tools provides a new strategy for the MoA of multi-components drug through cell subtyping.

【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the diagnosis of fetal chromosomal aneuploidies among women with advanced gestational age. METHODS: 14 047 pregnant women have voluntarily accepted the NIPT test. The results of NIPT and amniocytic karyotyping analysis were compared, and the outcome of pregnancy was followed up. RESULTS: NIPT has identified 104 cases with a high risk for trisomies 21, 18 and 13, and 44 cases with a high risk for sex chromosome abnormalities. After genetic consultation, 87 of 104 cases have accepted amniocyte chromosomal karyotyping. 63 cases of fetal chromosome abnormality were confirmed, including 46 cases of 21 trisomy, 11 cases of 18 trisomy and 6 cases of 13 trisomy. The positive predictive value was 83.64% (46/55), 61.11% (11/18), and 42.86% (6/14), the specificity was 99.93%, 99.95%, 99.94%, and the sensitivity was 100%. Among the 44 cases, 34 received amniocytic chromosomal karyotyping analysis, 11 cases were confirmed, the positive predictive value was only 32.35%. No aneuploidy was found in the low-risk cases. The negative predictive value was 100%. CONCLUSION As a prenatal screening method for women with advanced gestational age, NIPT has the highest positive predictive value for trisomy 21 and trisomy 18, but a lower positive predictive value for sex chromosome abnormalities. NIPT has a very low rate of missed diagnosis of trisomies 21, 18 and 13, which can significantly reduce the number of women undergoing invasive prenatal diagnosis.