Bone morphogenetic proteins are a large subclass of the transforming growth factor β family,and Their signaling pathways are mainly classified into two kinds based on whether they depend on Smad protein to mediate or not.BMP signaling pathways are involved in regulating cell proliferation and differentiation,as well as the formation and development of multiple tissues and organs.Recent studies have shown that BMP signaling path-ways mainly promote the differentiation and growth of neurons and astrocytes,and are closely related to the my-elination of oligodendrocytes.In addition,BMP signaling pathways also play an important role in the occurrence of central nervous system diseases,such as spinal cord injuries,multiple sclerosis,neural tube defects,and Parkin-son's disease.This article reviews the BMP signaling pathways'composition,transduction mechanism and their role in the central nervous system and related diseases,in order to provide more potential ideas for basic research and clinical treatment of central nervous system diseases.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

Bone morphogenetic proteins are a large subclass of the transforming growth factor β family,and Their signaling pathways are mainly classified into two kinds based on whether they depend on Smad protein to mediate or not.BMP signaling pathways are involved in regulating cell proliferation and differentiation,as well as the formation and development of multiple tissues and organs.Recent studies have shown that BMP signaling path-ways mainly promote the differentiation and growth of neurons and astrocytes,and are closely related to the my-elination of oligodendrocytes.In addition,BMP signaling pathways also play an important role in the occurrence of central nervous system diseases,such as spinal cord injuries,multiple sclerosis,neural tube defects,and Parkin-son's disease.This article reviews the BMP signaling pathways'composition,transduction mechanism and their role in the central nervous system and related diseases,in order to provide more potential ideas for basic research and clinical treatment of central nervous system diseases.

Objective:To explore the risk factors of deaths caused by influenza-associated encephalopathy (IAE) in children.Methods:A case control study was conducted.The clinical data (including baseline fata, organ function indices, inflammatory factors, imaging data, treatment, and outcomes) of IAE children hospitalized in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from January 2020 to December 2023 were retrospectively analyzed.The children were divided into a survival group and a death group.The Logistic regression and receiver operating characteristic (ROC) curve were used to analyze the risk factors of death in IAE children.Results:A total of 46 cases were included, with an onset age of 74.8(46.0, 92.5) months.The main cause of IAE was influenza A virus infection, which was detected in 45 cases(97.8%), and 32 cases (69.6%) of them had H3N2.One child (2.2%) was infected by influenza B virus.Eight children died, showing a mortality of 17.4%.There was significant difference in Glasgow Coma Scale between the survival and death groups when they were admitted into the PICU [10 (9, 11) points vs.3 (3, 5) points] ( Z=-4.510, P<0.05).All patients in the death group had multiple organ dysfunction syndrome, respiratory failure and circulatory system failure.Serum procalcitonin (PCT)[15.7 (3.3, 37.4) μg/L], interleukin-6 (IL-6)[1 039.1 (319.3, 2 884.3) ng/L], and cerebrospinal fluid protein(CSFP)[13 050.0 (5 865.0, 21 100.0) mg/L] in the death group compared with those in the survival group [0.2 (0.1, 0.8) μg/L, 15.5 (7.9, 44.8) ng/L, 227.0 (190.0, 332.0) mg/L]were highly increased ( Z=-3.364, -4.088, -3.757, all P<0.001).Logistic regression analysis showed that PCT ( OR=0.660, P<0.05), IL-6 ( OR=1.014, P<0.05) and CSFP ( OR=1.001, P<0.05) were risk factors of death in IAE.The areas under the ROC curve for these three factors were 0.88 (95% CI: 0.77-0.97), 0.96 (95% CI: 0.86-1.00) and 0.93 (95% CI: 0.76-1.00), respectively.When a cutoff value of 2.50 μg/L, 269.67 ng/L and 5 240.00 mg/L was taken, PCT achieved a sensitivity of 0.875 and a specificity of 0.816, IL-6 achieved a sensitivity of 0.875 and specificity of 0.974, and CSFP achieved a sensitivity of 0.875 and specificity of 0.974, respectively. Conclusions:High levels of serum PCT, IL-6 and CSFP at PICU admission are risk factors of poor prognosis in children with IAE.

Objective:To analyze the current situation and influencing factors of work-related musculoskeletal disorders (WMSDs) among scientific researchers in a computer workstation of a high-tech aerospace enterprise, and to provide data support for the improvement of occupational health management policies in this type of enterprise.Methods:From March to April 2023, using convenient sampling method, 1398 scientific researchers using computer workstations in an aerospace high-tech enterprise in Beijing were selected as the research subjects. The incidence of WMSDs in various parts of the body was investigated by using the Musculoskeletal Disorders Questionnaire, and the influencing factors of WMSDs in neck, lower back, shoulder and upper back were analyzed by logistic regression.Results:The total incidence of WMSDs was 55.4% (774/1398) in the scientific researchers who used computer workstations. The top 4 body parts in WMSDs incidence were neck (24.3%, 340/1398), lower back (20.4%, 285/1398), shoulder (18.7%, 262/1398), upper back (12.7%, 177/1398). The results of multivariate logistic regression analysis showed that feeling slightly tired and tired after work, setting a rest/break time of 10 to 15 min before the next continuous job, and operating computer for 2 to 4 hours and >4 hours were the influencing factors for the occurrence of neck WMSDs ( OR=3.08, 1.90, 0.60, 2.00, 1.49, P<0.05). Female, 5-<10 years of working experience, feeling slightly tired, tired and very tired after work, operating computer for 6-<8 hours and 8-10 hours a day were all the influencing factors for the occurrence of WMSDs in the lower back ( OR=1.82, 0.64, 2.95, 1.80, 1.61, 1.82, 1.73, P<0.05). Female, feeling slightly tired and tired after work were the influencing factors of shoulder WMSDs occurrence ( OR=2.42, 2.09, 2.00, P<0.05). Female, 5-<10 years, 10-15 years of working age, 1-3 times of physical exercise/quarter, feeling slightly tired, tired and very tired after work were the influencing factors for the occurrence of upper back WMSDs ( OR=2.76, 2.19, 2.78, 0.48, 4.20, 2.66, 2.19, P<0.05) . Conclusion:The incidence of WMSDs among scientific researchers in computer workstations of aerospace high-tech enterprises is high, which is closely related to individual characteristics and workstation usage characteristics. Measures should be taken to prevent and improve the WMSDs status of scientific researchers.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To analyze the current situation and influencing factors of work-related musculoskeletal disorders (WMSDs) among scientific researchers in a computer workstation of a high-tech aerospace enterprise, and to provide data support for the improvement of occupational health management policies in this type of enterprise.Methods:From March to April 2023, using convenient sampling method, 1398 scientific researchers using computer workstations in an aerospace high-tech enterprise in Beijing were selected as the research subjects. The incidence of WMSDs in various parts of the body was investigated by using the Musculoskeletal Disorders Questionnaire, and the influencing factors of WMSDs in neck, lower back, shoulder and upper back were analyzed by logistic regression.Results:The total incidence of WMSDs was 55.4% (774/1398) in the scientific researchers who used computer workstations. The top 4 body parts in WMSDs incidence were neck (24.3%, 340/1398), lower back (20.4%, 285/1398), shoulder (18.7%, 262/1398), upper back (12.7%, 177/1398). The results of multivariate logistic regression analysis showed that feeling slightly tired and tired after work, setting a rest/break time of 10 to 15 min before the next continuous job, and operating computer for 2 to 4 hours and >4 hours were the influencing factors for the occurrence of neck WMSDs ( OR=3.08, 1.90, 0.60, 2.00, 1.49, P<0.05). Female, 5-<10 years of working experience, feeling slightly tired, tired and very tired after work, operating computer for 6-<8 hours and 8-10 hours a day were all the influencing factors for the occurrence of WMSDs in the lower back ( OR=1.82, 0.64, 2.95, 1.80, 1.61, 1.82, 1.73, P<0.05). Female, feeling slightly tired and tired after work were the influencing factors of shoulder WMSDs occurrence ( OR=2.42, 2.09, 2.00, P<0.05). Female, 5-<10 years, 10-15 years of working age, 1-3 times of physical exercise/quarter, feeling slightly tired, tired and very tired after work were the influencing factors for the occurrence of upper back WMSDs ( OR=2.76, 2.19, 2.78, 0.48, 4.20, 2.66, 2.19, P<0.05) . Conclusion:The incidence of WMSDs among scientific researchers in computer workstations of aerospace high-tech enterprises is high, which is closely related to individual characteristics and workstation usage characteristics. Measures should be taken to prevent and improve the WMSDs status of scientific researchers.

Objective:To explore the in vitro anticancer effect of bleomycin (Ble) combined with cisplatin (DDP) on human gastric cancer cells.Methods:CCK-8 experiment was conducted to detect the effect of Ble and DDP alone or in combination on the proliferation of gastric cancer cells; Flow cytometry was used to detect changes in cell apoptosis and changes in reactive oxygen species. Cell scratch test was employed to detect cell migration; Western blot experiment was conducted to detect protein expression.Results:The results of CCK-8 showed that 20 μM DDP could inhibit the proliferation of six types of gastric cancer cells by 40%, while the effect of 20 μM Ble was only about 20%. When used in combination, the inhibitory rate on six types of gastric cancer could reach over 60%, with the strongest inhibitory effect on AGS cells. When 10 μM Ble and 10 μM DDP were combined, the proportion of AGS apoptotic cells reached 75.68%, higher than that of the two drugs treated with 20%, respectively 20 μM processing effect. When 10 μM Ble and 10 μM DDP were used in combination, the number of migrating and invading cells was significantly reduced, and the inhibition rate reached 50%. Compared with single use, the difference was statistically significant ( P<0.05). Flow cytometry results showed that the combination of Ble and DDP promoted cancer cell apoptosis by up-regulating the level of reactive oxygen species in cells; Western blot results showed that the expression of p-JAK2 and p-STAT3 decreased after Ble and DDP were combined, indicating that the JAK2/STAT3 signal pathway was inhibited. Conclusions:The combination of Ble and DDP can inhibit the proliferation and migration of gastric cancer cells, promote the apoptosis of gastric cancer cells, and play a synergistic anti-cancer effect. Its mechanism may be related to the up-regulation of ROS levels in cells, thereby inhibiting the activation of the JAK2/STAT3 pathway.

Objective:To study the effects of water fluoride and tea fluoride on the occurrence of dental fluorosis in children, and to provide a basis for scientific prevention and control of the disease.Methods:From April to September 2020, Baolongshan Town with qualified water fluoride but no habit of drinking brick tea, Xingyao Town with qualified water fluoride and habit of drinking brick tea, Baokang Town with exceeded water fluoride but no habit of drinking brick tea, and Wuliyasitai Town with exceeded water fluoride and habit of drinking brick tea were selected as survey sites in Inner Mongolia Autonomous Region based on historical monitoring data. In all Gacha (villages) of 4 towns, a survey was carried out on residents' drinking water, brick tea drinking habits and children's dental fluorosis detection, and the water fluoride, tea fluoride exceeding standard rates, daily per capita intake of brick tea fluoride and the detection rate of children's dental fluorosis were calculated. At the same time, multivariate logistic regression was used to analyze the influencing factors affecting the occurrence of dental fluorosis in children.Results:In 2020, a total of 165 water samples were collected in 4 towns of Inner Mongolia Autonomous Region, and the total water fluoride exceeding standard rate was 38.18% (63/165). A total of 320 tea samples were collected, the tea fluoride exceeding standard rates in Xingyao Town and Wuliyasitai Town were 96.38% (213/221) and 89.90% (89/99), respectively; the daily per capita intake of brick tea fluoride was 5.67 and 7.35 mg, respectively. A total of 1 652 children were examined for dental fluorosis, and 639 cases were detected, the detection rate was 38.68%. The detection rates of dental fluorosis in boys and girls were 37.18% (322/866) and 40.33% (317/786), respectively, with no significant difference between sexes (χ 2 = 1.72, P = 0.104); the detection rates of dental fluorosis in children aged 8 - 12 years were 43.93% (105/239), 40.50% (147/363), 46.57% (163/350), 30.56% (88/288) and 33.01% (136/412), respectively, with statistical significant difference among ages (χ 2 = 26.07, P < 0.001); the detection rates of dental fluorosis in children in Baolongshan, Baokang, Xingyao and Wuliyasitai towns were 0.68% (2/293), 14.09% (31/220), 24.79% (89/359) and 66.28% (517/780), respectively, with statistical significant differences among regions (χ 2 = 213.05, P < 0.001). Multivariate logistic regression analysis showed that when the fluoride content in water was 1.2 - < 2.0, 2.0 - < 2.5, and ≥2.5 mg/L, the risk of dental fluorosis in children was 3.93, 6.60, and 9.02 times of water fluoride content < 1.2 mg/L; when the daily per capita intakes of brick tea fluoride was 3.6 - 7.0 and > 7.0 mg, the risk of dental fluorosis in children was 2.94 and 3.90 times of daily per capita intakes of brick tea fluoride ≤3.5 mg; the risk of dental fluorosis in children aged 10 years was 1.81 times of children aged 8 years; the risk of dental fluorosis in children in Xingyao, Baokang, and Wuliyasitai towns was 22.35, 40.93, and 151.58 times of Baolongshan Town, respectively. Conclusions:The prevalence of dental fluorosis in children still exists in Inner Mongolia Autonomous Region, and the detection rate of dental fluorosis is high. High water fluoride and high tea fluoride are the main risk factors for dental fluorosis in children.

Objective To investigate the association of ideal cardiovascular health metrics with the incidence rate of nonalcoholic fatty liver disease (NAFLD), and to provide a basis for the prevention and control of NAFLD. Methods A prospective cohort study was conducted for the data of 50 511 employees of Kailuan Group who participated in physical examination from July 2006 to June 2007, and the onset of NAFLD was observed during follow-up once every two years. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test used for comparison of continuous data with skewed distribution between multiple groups; the chi-square test was used for comparison of categorical data between groups. The subjects were divided into four groups according to the quartile of cardiovascular health score (CHS), and person-year incidence rate was used to calculate the incidence rate of NAFLD in each group. Restricted cubic spline (RCS) curve was used to calculate the dose-response relation between continuous variables and outcome events; the Cox proportional hazards model was used to analyze hazard ratio ( HR ) and 95% confidence interval ( CI ) in each group and investigate the effect of ideal cardiovascular health metrics on the incidence rate of NAFLD. Results During the mean follow-up time of 5.58 years, a total of 15 265 cases of NAFLD were observed, and the incidence rate of NAFLD was 77.88/1000 person-year in the Q1 group, 61.33/1000 person-year in the Q2 group, 46.37/1000 person-year in the Q3 group, and 33.69/1000 person-year in the Q4 group. RCS results showed a non-linear relationship between CHS continuous variable and the risk of NAFLD ( P < 0.05). The multivariate Cox proportional risk model analysis showed that compared with the Q1 group in terms of the risk of NAFLD, the Q2, Q3, and Q4 groups had an HR of 0.78 (95% CI 0.74~0.81), 0.57 (95% CI 0.54~0.59), and 0.38 (95% CI 0.36~0.41), respectively, and similar results were observed in subjects stratified by sex and age. The analysis of each component showed that ideal body mass index ( HR =0.37, 95% CI : 0.36~0.39), ideal blood glucose ( HR =0.80, 95% CI : 0.77~0.84), ideal blood pressure ( HR =0.72, 95% CI : 0.69~0.75), ideal cholesterol ( HR =0.86, 95% CI : 0.83~0.89), and ideal diet ( HR =0.94, 95% CI : 0.90~0.99) were protective factors against NAFLD. Conclusion Ideal cardiovascular health metrics are protective factors against NAFLD, and maintaining a healthy lifestyle may help to prevent the onset of NAFLD.