Background Co-exposure to noise and microwave radiation occurs frequently. The central nervous system has been identified as a sensitive target organ for both noise and microwave exposure individually, and the underlying mechanisms remain poorly understood. The specific biological effects resulting from co-exposure to these two factors have yet to be fully elucidated. Objective To clarify the effects of co-exposure to noise and microwave on neurobehavior and hippocampal tissue structure, and to explore the underlying mechanism through the assessment of serum cytokines. Methods C57BL/6N mice were selected and randomly assigned to a blank control group, a noise group, a microwave group, and a combined noise & microwave exposure group. To establish the exposure models, the noise group was subjected to broadband noise at 100 dB for 2 h, while the microwave group received radiation at a central frequency of 9.375 GHz with an average power density of 12 mW·cm⁻² and a specific absorption rate of 2.58 W·kg⁻¹ for 15 min. Open field and tail suspension tests assessed anxiety-like emotional behaviour; novel object recognition and Y-maze tests evaluated cognitive function. Histological changes in hippocampal tissue were examined using haematoxylin and eosin (HE) staining, and Nissl staining under light microscopy. Serum cytokine levels were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Results After 3 d of exposure, the noise, microwave, and combined exposure groups showed significant reductions in exploration frequency, duration, and distance within the central zone of the open field test compared to the control group (P < 0.01); the combined exposure group exhibited increased ratios of peripheral-to-central exploration time and distance (P < 0.05). After 7 d of exposure, compared with the control group, the noise group maintained a decrease in central zone exploration time (P < 0.01), while the combined exposure group showed persistent decline across all central zone metrics (P < 0.05) and elevated peripheral-to-central ratios (P < 0.05); compared to the microwave group, the combined exposure group showed significant less time in the central zone (P < 0.05) and higher peripheral-to-central ratios (P < 0.05). Regarding behaviour and cognition, compared with the control group, the combined exposure group showed increased immobility time in the tail suspension test after 3 d of exposure (P < 0.01). At this interval, all exposure groups demonstrated reduced frequency and duration of novel object recognition (P < 0.05), with the combined exposure group showing a marked decrease in novel arm exploration time (P < 0.01). After 7 d of exposure, compared with the control group, the noise group showed reduced novel object recognition frequency (P < 0.05), and both the noise and microwave groups exhibited decreased novel arm exploration time (P < 0.05). Pathological alterations including an increased number of hyperchromatic nuclei and depleted Nissl bodies were observed in the CA3 and DG regions across all exposure groups with the most severe lesions observed in the combined exposure group. Serum levels of central nervous system-specific protein β (S-100β), glial fibrillary acidic protein (GFAP), and corticosterone (CORT) were significantly elevated in all exposure groups compared with the control group (P < 0.05). Aquaporin-4 (AQP4) levels increased in the combined exposure group (P < 0.05), while CXC chemokine ligand 10 (CXCL10) levels rose in both the noise and combined groups compared with the control group (P < 0.05). Specifically, S-100β and CXCL10 levels in the combined exposure group were higher than those in the microwave group (P < 0.05); moreover, levels of S-100β, GFAP, CORT, AQP4, and CXCL10 in the combined exposure group were significantly higher than those in the noise group (P < 0.05). Conclusion Combined exposure to noise and microwave radiation induces pathological changes in the hippocampus of mice, increases levels of serum stress hormones and neuro-specific biomarkers. These impairments are more severe than those observed following single-factor exposure. The underlaying mechanism may be related to systemic stress response, neuronal damage, astrocyte activation, and changes in blood-brain barrier permeability, leading to emotional behavioral abnormalities and cognitive decline.

Objective: To investigate the association between medium to long term PM 2.5 exposure around school areas and overweight/obesity among primary and secondary school students in Guangxi, providing data support and theoretical foundations for scientifically addressing overweight and obesity in primary and secondary school students. Methods: From September to November 2023, a stratified cluster random sampling method was employed to select 251 183 students aged 7-18 years (grade 1 to grade 12) from 14 prefecture level cities (111 districts and counties) in Guangxi. PM 2.5 mass concentration data were obtained from the Tracking Air Pollution in China (TAP) dataset. Preliminary comparative analysis was conducted using the Mann-Whitney U test, while binary Logistic regression models were applied to quantify the relationship between PM 2.5 exposure and overweight/obesity. Restricted cubic spline analysis was further utilized to examine the nonlinear association between PM 2.5 concentration and overweight/obesity risk. Results: The detection rate of overweight/obesity among Guangxi students in 2023 was 19.5%. The median PM 2.5 concentration in the year prior to the study was higher in the overweight/obesity group (23.22 μg/m 3) compared to the non overweight/obesity group (22.63 μg/m 3) ( Z=-15.66, P <0.01), and consistent trends were observed across gender (male/female) and educational stage (primary/junior/senior high school) subgroups (all P <0.01). Binary Logistic regression revealed that for every 10 μg/m 3 increase in the annual average PM 2.5 concentration, the risk of overweight/obesity increased by 12% ( OR=1.12, 95%CI=1.09- 1.15 , P <0.01). Restricted cubic spline analysis indicated a nonlinear relationship between monthly PM 2.5 levels and overweight/obesity risk ( P trend <0.01). Below 22.68 μg/m 3, PM 2.5 exposure showed no significant association with obesity risk; above the threshold, the risk increased with rising PM 2.5 levels. Conclusion Medium to long term PM 2.5 exposure around school environments is significantly associated with overweight/obesity among primary and secondary school students.

Objective: To analyze the association between altitudes and nutritional status of children and adolescents, and to explore the moderating effects of dietary behaviors and physical activity, so as to provide a scientific basis for developing lifestyle interventions tailored to local conditions. Methods: From September to November 2023, physical examinations and questionnaire surveys were conducted among children and adolescents aged 7-17 in two autonomous regions, Inner Mongolia and Xizang, with a final sample of 156 511 participants by the stratified cluster random sampling method. Height and weight were measured to calculate body mass index (BMI). Sociodemographic characteristics, dietary behaviors, and physical activity were collected via questionnaires, while the altitude of each participant s school was obtained using Amap. Logistic regression was performed to examine the relationship between altitudes and nutritional status. Interaction terms and stratified analyses were applied to assess the moderating effects of dietary behaviors and physical activity. Restricted cubic spline (RCS) were used for visualization. Results: In 2023, the prevalence of wasting and overweight/obesity among children and adolescents in Xizang were 9.7% and 9.0%, respectively, compared to 2.9% and 22.0% in Inner Mongolia. Logistic regression analysis results showed that for every 1 km increase in altitude, the risk of wasting increased, while the risk of overweight/obesity decreased ( OR =1.43, 0.19, both P <0.05). The results of the stratified analysis showed that compared to those living at altitudes <1 km, children and adolescents with healthy diets showed no significant association between altitudes (1-<2 and 2-<3 km) and wasting ( OR =1.22, 0.75, both P >0.05), whereas significant associations were observed at 3-<4 and ≥4 km altitudes ( OR =2.25, 2.89, both P <0.05). In contrast, unhealthy dietary groups showed statistically significant associations across altitudes ( OR =1.18-4.04, all P <0.05), consistent with RCS results. No moderating effects were observed for physical activity on the altitude wasting association or for dietary behaviors and physical activity combined on the altitude overweight/obesity association ( P interaction =0.63, 0.10, 0.53). Conclusion Healthy dietary behaviors play a critical role in improving the nutritional status of children and adolescents and reducing regional disparities, providing a scientific foundation for public health policy formulation and implementation.

Objective To investigate the epidemiological characteristics and effectiveness of emergency responses to epidemic foci in Guangzhou City in 2024, so as to optimization of the dengue fever control strategy in Guangzhou City. Methods All data pertaining to dengue fever cases in Guangzhou City in 2024 were collected from the National Notifiable Infectious Disease Surveillance Information Reporting System. The temporal, spatial and population distributions of dengue fever cases and sources of infections were descriptively analyzed, and the effectiveness of emergency responses to epidemic foci of dengue fever was evaluated through standard space index (SSI), the interval from disease onset to case reporting and the percentage of isolation in hospital. Results A total of 3 656 dengue fever cases were reported in Guangzhou City in 2024, including 3 102 local cases and 554 imported cases. Of all cases, 67.86% (2 481 cases) occurred at ages of 20 to 59 years, and the three most common occupations included housework/unemployment (793 cases, 21.69%), business servants (744 cases, 20.35%) and retirees (669 cases, 18.30%). The peak of dengue fever epidemics was concentrated during the period from the 39th to the 45th weeks in 2024, when a total of 2 317 local cases were reported, accounting for 74.69% of all local cases in 2024. Dengue fever cases were reported across all 11 districts in Guangzhou City in 2024, with local cases concentrated in Baiyun District (754 cases, 24.31%), Liwan District (398 cases, 12.83%), Panyu District (365 cases, 11.77%), Haizhu District (332 cases, 10.70%) and Tianhe District (328 cases, 10.57%). Imported dengue fever cases were predominantly domestically imported (492 cases, 88.81%), with the majority imported from Foshan City (377 cases), and overseas imported cases were predominantly imported from southeastern Asian countries. The mean proportion of case isolation in hospital was 9.16% (284/3 102), and the mean interval from disease onset to case reporting was (3.99 ± 2.70) days, while the percentages of mosquito density meeting the required standard were 61.68% (462/ 749) and 66.32% (126/190) on the 4th and 7th day of emergency responses to epidemic foci, respectively. Conclusions The prevention and control cycle of dengue fever in Guangzhou in 2024 took longer than in previous years, with a larger scale of the epidemic. Although some progress has been made in epidemic management, there are still problems such as unsustainable mosquito vector control and low hospitalization isolation rates for cases. Further optimization of control measures in mosquito vector control, case monitoring and management is required to improve the effectiveness of dengue fever control measures.

This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Objective:To investigate the molecular pathogenic mechanism of venous thrombosis caused by heterozygous missense mutations in two protein C (PROC) genes through laboratory phenotype analysis, genetic mutation analysis, and in vitro expression experiments.Methods:Two probands presented with venous thromboembolism at the First Affiliated Hospital of Wenzhou Medical University. Clinical data and blood samples were collected from the probands and their family members to evaluate the plasma protein C (PC) activity (PC∶A), PC antigen (PC∶Ag) levels, and other relevant coagulation parameters. The anticoagulant capacity was assessed using the thrombin generation test (TGT). The mutation sites of the PROC gene were identified using direct DNA sequencing. Bioinformatics software was used to analyze the conservation and pathogenicity of the mutated gene. PyMOL software was used for the analysis of the protein three-dimensional models and interactions between mutated amino acids. Wild-type and two mutant expression vectors were constructed and HEK293T cells were transiently transfected. Total cellular RNA was extracted from positively transfected cells to investigate the transcriptional levels of the mutant PROC gene. Enzyme-linked immunosorbent assay, Western blot, and cellular immunofluorescence assays were used to investigate the translation levels of the mutant PROC protein.Results:Probands 1 and 2 exhibited PC∶A levels of 35% and 40% and PC∶Ag levels of 44% and 39%, with increasing D-dimer levels to 4.42 mg/L and 0.83 mg/L, respectively. Meanwhile, other coagulation parameters revealed no significant abnormalities. TGT demonstrated impaired anticoagulant function in both proband witnesses and their familial PC carriers. Sequencing analysis revealed heterozygous missense mutations c. 833T>C (p. Leu278Pro) in proband 1 and c. 1330T>C (p. Trp444Arg) in proband 2 within exon 9 of the PROC gene. Conservation analysis revealed that Leu278 and Trp444 were highly conserved across homologous species. Pathogenicity analysis indicated that both p. Leu278Pro and p. Trp444Arg mutations are deleterious. Protein modeling analysis demonstrated that both mutations induce structural alterations in the protein. In vitro expression experiments revealed that compared with the wild-type, both p. Leu278Pro and p. Trp444Arg mutations showed no significant differences in the mRNA expression level of the PC protein. However, both mutations caused significantly lower PC∶Ag content and protein expression levels in the cell culture supernatant compared with the wild-type, whereas higher levels were observed in the cell culture lysate. This indicates the association of both mutations with the secretion function of the PC protein.Conclusion:The heterozygous missense mutations p. Leu278Pro and p. Trp444Arg in exon 9 of the PROC gene in both probands are associated with decreased PC levels.

Objective:To assess the application effects of an energy-restricted diet combined with high-protein, high-dietary-fiber meal replacement powder and probiotics in overweight/obese adults.Methods:It was a randomized controlled trial. A consecutive sample of 150 overweight/obese adults who underwent physical examinations at the Health Care Center of the First Hospital of Hebei Medical University between November 2021 and March 2022. The participants were randomly assigned into the combined group, the high-protein group, and the common group (50 participants per group) using a random number table method. All three groups of subjects received weight loss health education, energy-restricted diet, and interventions with meal replacement powder and probiotics (or probiotic placebo). The combined group was given high-protein and high-dietary fiber meal replacement powder and probiotics. The high-protein group was given high-protein meal replacement powder and probiotic placebo. The common group was given ordinary meal replacement powder and probiotic placebo. The meal replacement powder was packaged in 35 g per bag, with main components of varying amounts of protein, fat, carbohydrates, vitamins, and trace elements. Both the probiotic powder and the probiotic placebo came in 2 g sachets. The primary components of probiotic powder were various Bifidobacterium, Lactobacillus and excipients, while the main component of probiotic placebo was excipients. The meal replacement powder and the probiotic powder or probiotic placebo were taken twice a day for a total of 12 weeks, one sachet of each time, followed by a 4-week follow-up. The body weight, body mass index, body fat mass, abdominal circumference and hip circumference were measured before the trial (week 0) and at the end of weeks 2, 4, 8, 12, and 16. The change rates of each indicator were calculated. Biochemical indicators, trace elements, and 25-hydroxyvitamin D levels were measured at the end of week 0, 4, 8, and 12. A product evaluation questionnaire was conducted at the end of week 12. A total of 19 cases dropped out due to various reasons. Finally, 46 cases in the combined group, 42 cases in the high-protein group, and 43 cases in the common group were included in the analysis. Paired-samples t test, Kruskal-Wallis H test, one-way analysis of variance, and Mann-Whitney U test were used to compare the differences in weight-loss and maintenance effects, safety and patient acceptance among the three intervention groups, and to analyze the application effect of the energy-restricted diet combined with high-protein and high-dietary fiber meal replacement powder plus probiotics in overweight/obese adults. Results:Among the 131 overweight/obese adults included in the analysis, there were 57 males and 74 females, with a mean age of (37.30±8.33) years. By the end of the week 12, the body mass index [26.87(25.77, 30.38) vs 29.61(27.96, 33.09) kg/m2; 27.10(24.70, 31.37) vs 29.40(27.20, 34.17) kg/m2; 27.98(26.43, 30.12) vs 29.88(28.22, 31.93) kg/m2] and body fat masses [22.15(17.70, 30.15) vs 30.75(25.63, 35.40) kg; 23.35(19.12, 28.70) vs 29.45(26.20, 37.05) kg; 26.80(24.10, 31.60) vs 30.00(26.00, 34.70) kg] in the combined group, the high-protein group and the common group were all lower than those at baseline (week 0) (all P<0.05). At the end of the week 12, the change rates of body fat mass and body mass index in the combined group were both higher than those in the high-protein group and the common group [(25.98%±9.58%) vs (23.88%±11.15%) and (9.35%±11.00%), 9.29%(7.23%, 11.58%) vs 7.96% (5.51%, 10.92%) and 5.77% (2.68%, 10.03%)] (all P<0.05). At the end of the week 12, the body fat mass in the combined group and the high-protein group were both lower than that in the common group [22.15(17.70, 30.15), 23.35(19.12, 28.70) vs 26.80(24.10, 31.60) kg] (both P<0.05). At the end of the week 12, the decreased values of uric acid and high-sensitivity C-reactive protein in the combined group were both higher than those in the high-protein group and the common group [17.15(13.02, 23.45) vs 1.50(0.22, 28.60) and 4.20(0.15, 19.95) μmol/L, 0.43(0.24, 0.60) vs 0.21(0.06, 0.43) and 0.28(-0.04, 0.88) mg/L](both P<0.05). No serious adverse events were observed during the intervention period and at the end of the intervention. In the product evaluation questionnaire, the combined group scored higher than the high-protein group and the common group on items such as usage frequency, taste, satiety, willingness to continue use, willingness to recommend to others, and willingness to purchase [4(3, 4) vs 3(3, 4) and 3(2, 4) points, 4(3, 4) vs 3(3, 4) and 3(2, 4) points, 4(3, 4) vs 3(3, 4) and 3(3, 3) points, 4(3, 4) vs 3(3, 4) and 3(3, 4) points, 4(3, 4) vs 3(3, 4) and 3(3, 3) points, 3(3, 4) vs 3(3, 4) and 3(2, 3) points] (all P<0.05). Conclusion:An energy-restricted diet combined with high-protein, high-dietary-fiber meal replacement powder and probiotics demonstrates superior weight-loss and weight-maintenance effects in overweight/obese adults, with high safety and great user acceptability.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective:To analyze the epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia and explore the related factors of these two health problems.Methods:In September 2022, a stratified random cluster sampling method was employed to select 188 635 children and adolescents aged 6-18 in Inner Mongolia for physical examinations and questionnaire surveys. Data on height, weight, as well as dietary behavior, physical activity, classroom environment, academic tasks, writing posture, and screen behavior were collected. The epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity were analyzed. Additionally, a multivariate logistic regression model was used to analyze the factors associated with wasting, spinal curvature abnormalities and multimorbidity.Results:A total of 188 635 children and adolescents aged 6-18 years participated in this study, including 95 393 boys (50.6%) with an average age of (11.53±3.32) years. The detection rate of wasting was 3.79%, with a higher detection rate in boys (4.18%) than in girls (3.38%) ( P<0.001). The detection rate of spinal curvature abnormalities was 3.64%, with a higher detection rate in girls (4.04%) than in boys (3.25%) ( P<0.001). The detection rate of multimorbidity between wasting and spinal curvature abnormalities was 0.17%, and there was no statistically significant difference between genders ( P>0.05). The detection rates of wasting, spinal curvature abnormalities, and multimorbidity all increased with age ( P t<0.001). The multivariate logistic regression analysis showed that, after adjusting for gender, age, urban/rural status, and school grade, compared to children and adolescents who exercised ≥1 hour of moderate-to-vigorous physical activity (MVPA) for at least 5 days per week and had daily screen time <2 hours, those who exercised <5 days per week ( OR=1.28, 95% CI: 1.19-1.37) and had daily screen time ≥2 hours ( OR=1.11, 95% CI: 1.03-1.19) had a higher risk of wasting. Compared to children and adolescents who had ≥5 physical education (PE) classes per week, adjusted desk and chair height,<1 hour of after-school study/writing time, and whose parents or teachers rarely or never reminded them about posture, those with <5 PE classes per week ( OR=1.11, 95% CI: 1.02-1.21), unadjusted desk and chair height ( OR=1.08, 95% CI: 1.01-1.15),≥1 hour of after-school study/writing time ( OR=1.15, 95% CI: 1.07-1.24), frequent reminders from parents ( OR=1.16, 95% CI: 1.09-1.23), and frequent reminders from teachers ( OR=1.10, 95% CI: 1.04-1.16) had a higher risk of spinal curvature abnormalities. Compared to children and adolescents who did not consume sugary drinks daily, exercised ≥1 hour of MVPA for at least 5 days per week, and whose teachers rarely or never reminded them about posture, those who consumed sugary drinks daily ( OR=1.61, 95% CI: 1.00-2.46), exercised <5 days per week ( OR=1.33, 95% CI: 1.01-1.79), and had teachers who frequently reminded them about posture ( OR=1.35, 95% CI: 1.05-1.75) had a higher risk of multimorbidity between wasting and spinal curvature abnormalities. Conclusion:The detection rates of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia are generally low, with an increasing trend observed with age. Both lifestyle and school environmental factors are associated with wasting, spinal curvature abnormalities and multimorbidity.

Objective:To analyze the causal relationship between type 2 diabetes and lumbar bone mineral density and spinal fractures and to further explore the impact of central obesity on the diabetic bone paradox.Methods:A Mendelian randomization (MR) study was implemented. Single nucleotide polymorphisms (SNPs) associated with type 2 diabetes were selected from the data of genome-wide association studies as instrumental variables, with lumbar bone density and spinal fractures as the outcome variables. The inverse variance weighting method, weighted median method, and MR-Egger regression were applied to identify a causal relationship between type 2 diabetes and osteoporosis at the genetic level. Additionally, to analyze the impact of central obesity in the diabetic bone paradox, the waist-to-hip ratio was introduced as a new exposure variable, with type 2 diabetes and lumbar bone density as outcome variables, and the MR method was applied again to uncover the influencing factors.Results:The screening criteria were based on the three main assumptions of MR. Finally, 62 SNPs for type 2 diabetes and 241 SNPs for waist-to-hip ratio were included in the MR analysis. Using inverse variance weighting as the primary analysis, the causal association effect analysis indicated a causal relationship between type 2 diabetes and increased lumbar bone density ( OR=1.047 6, P=0.007) and spinal fractures ( OR=1.000 9, P=0.014). A causal relationship between waist-to-hip ratio and type 2 diabetes ( OR=1.638 6, P<0.001) was identified, indicating that the waist-to-hip ratio was a risk factor for type 2 diabetes and may have a causal association with increased lumbar bone density ( OR=1.096 3, P=0.044). This suggests that the waist-to-hip ratio may indirectly affect the relationship between diabetes and osteoporosis. The MR-Egger intercept test showed no horizontal pleiotropy in this study. The leave-one-out analysis indicated that no single SNP had a significant impact on the overall results. Furthermore, the MR-pleiotropy residual sum and outlier (MR-PRESSO) test results did not detect any outlier SNPs. Conclusion:MR analysis identified a causal relationship between type 2 diabetes and increased lumbar bone density as well as a higher risk of spinal fractures, a paradox that may be related to central obesity.