Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

ObjectiveTo analyze the detected results of CD4⁺T lymphocytes and viral load in newly identified human immunodeficiency virus (HIV) infected patients in Huangpu District of Shanghai in 2023, to explore the correlation between them, so as to provide a scientific basis for the development of targeted prevention and control measures and antiviral treatment programs. MethodsThe data of CD4 cell count, viral load and demographic characteristics of the newly infected patients living with HIV in Huangpu District, Shanghai in 2023 were collected and analyzed by using descriptive epidemiological method. ResultsThe mean CD4 cell count of the 67 newly identified HIV infected patients in Huangpu District was (301.22±235.19) cells·µL^-1, with a mean viral load of (5.15±1.28) ×10⁵ copies·mL^-1.There were statistically significant differences in CD4 cell count and viral load among different age groups (P<0.05), but there were no statistically significant differences by gender and marital status (both P>0.05). The CD4 cell count and CD4/CD8 ratio both were negatively correlated with the lg value of viral load (r=-0.290, -0.378; P=0.027, 0.002). ConclusionThe CD4 cell counts of the newly identified HIV infected patients in Huangpu District in 2023 were generally low, the proportion of patients with high viral load was high, but the risk for elderly infected with HIV was high. The elderly have gradually become the key population for AIDS prevention and control in Huangpu District. It is recommended to expand HIV screening in the elderly to reduce the risk of HIV transmission and increase the rate of early detection and treatment.

OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanisms of Geranium wilfordii Maxim(GWM)in the treatment of liver injury.Mice were randomly divided into a control group(CON group),a model group(CCl4 group),a high-dose drug group(GWM-H group),and a low-dose group(GWM-L group).The liv-er injury model in mice was induced by CCl4,and liver tissue pathological morphology was ob-served,along with the measurement of the relative gene expression levels of liver inflammatory factors.Active ingredients of traditional Chinese medicine and target information of Chinese medi-cine and diseases were obtained through databases such as TCMSP,PubChem,Swiss Target Pre-diction,Super-PRED,Gene Cards,and DisGeNET.Intersecting the targets of liver injury,necropto-sis,and drugs yielded potential drug targets.String database was used for protein-protein interac-tion(PPI)analysis of the potential targets.Furthermore,Cytoscape was utilized to construct a net-work diagram of"drug-disease-active ingredient-intersection target,"Wei Sheng Xin was used for GO and KEGG pathway analysis.Molecular docking was performed using MOE software,and the results of molecular docking were experimentally validated to detect the expression of key targets in the RIPK1/RIPK3/MLKL signaling pathway.Animal experiments showed that compared to the CON group,the CCl4 group of mice exhibited a significant increase in liver organ index(P＜0.05),markedly elevated serum AST activity(P＜0.05),and a highly significant increase in ALT activity(P＜0.01).Pathological examination revealed chaotic liver lobules,severe hepatocyte steatosis,ex-tensive hepatocyte necrosis,and inflammatory cell infiltration in the livers of mice in the CCl4 group.In comparison to the CCl4 group,the GWM-H group showed a significant decrease in liver organ index(P＜0.05),while the GWM-L group displayed a downward trend.The GWM-H group exhibited a significant reduction in serum AST activity(P＜0.05),the GWM-L group showed a decreasing trend in serum AST activity,the GWM-H group demonstrated a highly significant de-crease in serum ALT activity(P＜0.01),and the GWM-L group displayed a significant decrease in serum ALT activity(P＜0.05).Histopathological examination revealed that the drug treatment groups could improve CCl4-induced liver injury,with the GWM-H group showing better efficacy than the GWM-L group.RT-qPCR results of liver tissues showed that compared to the CON group,the CCl4 group exhibited a highly significant increase in the relative expression of IL-1βand PGE2 mRNA(P＜0.01),while the mRNA relative expression of COX2 showed an increasing trend.In contrast,compared to the CCl4 group,the GWM-H group showed a remarkably significant decrease in the relative expression of IL-1βmRNA(P＜0.01),a significant decrease in PGE2 mR-NA expression(P＜0.05),and a decreasing trend in COX2 mRNA expression.Through network pharmacology,56 potential targets related to GWM in ameliorating necroptosis-induced liver injury were identified.Key targets,based on degree value,include TNF,Bcl2,HSP90AA1,and Caspase8,while the key components are quercetin,luteolin,kaempferol,and ellagic acid.Functional enrich-ment analysis yielded 2 173 entries for GO and 146 biological pathways for KEGG.Molecular doc-king results indicated a strong binding capacity between the main components of GWM and key targets.RT-qPCR experimental results showed that compared to the CON group,the CCl4 group exhibited a extremely significantly increase in the mRNA relative expression of TNF-α,TNFR1,MLKL(P＜0.01),significantly increase in the mRNA relative expression of FAS,RIPK1,RIPK3 mRNA(P＜0.05),and a significant decrease in Caspase 8 mRNA expression(P＜0.05).The addi-tion of GWM successfully reversed this trend;compared to the CCl4 group,the GWM-H group showed a highly significant decrease in the mRNA relative expression of TNF-α,TNFR1,FAS and MLKL mRNA(P＜0.01),significant decrease in RIPK1,RIPK3 mRNA expression(P＜0.05),and an increasing trend in CASPASE8 mRNA expression.GWM exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the RIPK1/RIPK3/MLKL pathway reduces hepatocyte necroptosis,potentially serving as one of the essential mechanisms for its protective effects.

Objective To construct a decision aid scheme for surgical methods of thyroid cancer patients and explore its application effect.Methods A retrospective analysis was conducted on 692 patients with thyroid cancer who were treated in the department of breast and thyroid surgery in the First Affiliated Hospital of Army Medical University from January 1 to December 31,2022,patients who underwent surgery from January 1 to June 30,2022 were selected as the control group(n=346),while patients who underwent surgery from July 1 to December 31,2022 were selected as the observation group(n=346).Patients in the control group chose surgical methods after conventional education,while patients in the observation group chose the surgical methods through the decision aid scheme.The decision conflict and decision-making at admission and 1 day before surgery of patients in the two groups were assessed.The psychological state at admission,1 day before surgery,and 1 month after surgery of patients in the two groups were evaluated.The decision satisfaction of patients in the two groups were assessed 1,3,and 6 months after surgery.Results There was no significant difference in the decision conflict score,decision making score or anxiety and depression scores at admission of patients between the two groups(P>0.05).One day before surgery,the decision conflict score of patients in the observation group was significantly lower than that in the control group(t=21.099,P<0.001),and the decision-making score was significantly higher than that in the control group(t=8.806,P<0.001).The anxiety and depression scores of patients in the two groups decreased over time,among which the anxiety and depression scores 1 day before surgery and 1 month after surgery of patients in the observation group were lower than those in the control group(P<0.05).The decision satisfaction scores 1,3 and 6 months after surgery of patients in the observation group were higher than those in the control group(P<0.05).Conclusion The implementation of decision aid scheme can effectively reduce decision conflicts of patients with thyroid cancer regarding the choice of surgical methods,relieve negative emotions,and enhance decision satisfaction.

BACKGROUND:Percutaneous kyphoplasty through a unilateral puncture approach is considered more effective than a bilateral puncture approach for the treatment of osteoporotic vertebral compression fractures.However,due to the unique anatomical shape and location of the L5 vertebral body,the traditional unilateral puncture approach has limited applicability in treating L5 osteoporotic vertebral compression fractures.To address this issue,we propose the use of the"O"point puncture approach.OBJECTIVE:To compare the effectiveness of percutaneous kyphoplasty via basal transversal process-posterior superior pedicle-lateral articular process intersection("O"point)with conventional approach percutaneous kyphoplasty in treating the L5 osteoporotic vertebral compression fractures.METHODS:A retrospective analysis was conducted on 54 patients with L5 osteoporotic vertebral compression fractures treated with traditional percutaneous kyphoplasty or percutaneous kyphoplasty via the"O"point approach between January 2020 and December 2022 at Affiliated Hospital of Southwest Medical University.According to the surgical method,the patients were divided into the"O"point approach group(group A,n=29)and the traditional approach group(group B,n=25).The position of the"O"point and iliac spine and puncture angle were measured by orthography before operation in group A.Cobb angle,anterior vertebral margin,middle height,and bone cement distribution were compared between the two groups prior to and 2 days after surgery,and during final follow-up.Pain relief and daily living ability were assessed using the visual analog scale and Oswestry disability index prior to and 2 days after surgery,and during final follow-up.Complications related to the surgery were recorded.RESULTS AND CONCLUSION:(1)Operative time and intraoperative fluoroscopy times were significantly shorter in group A than in group B(P＜0.05).However,no significant differences were observed in intraoperative blood loss or bone cement injection amounts between the two groups.(2)Both groups demonstrated significantly lower visual analog scale scores and Oswestry disability index on day 2 after surgery and at the last follow-up in comparison to before surgery.However,group A experienced a more noticeable decrease than group B(P＜0.05).(3)On both sides,the"O"point was located on average 1.23 cm below the highest point of the iliac spine line.The mean transverse distance between the"O"point and the iliac spine was 2.89 cm.(4)During the final follow-up,the Cobb angle of both groups exhibited significant improvements compared to their respective preoperative values(P＜0.05).However,there was no significant difference between the two groups(P＞0.05).(5)After operation,the distribution of bone cement was good in group A,accounting for 97％(28/29),and good in group B,accounting for 88％(22/25).Group A was significantly better than group B(P＜0.05).(6)The efficacy of percutaneous kyphoplasty utilizing the"O"point puncture technique on osteoporotic vertebral compression fractures of the L5 vertebra was superior to that of the traditional percutaneous kyphoplasty approach.However,the bone cement distribution achieved with percutaneous kyphoplasty via"O"point puncture was more satisfactory,and the puncture approach was able to circumvent the influence of a high iliac spine on the L5 vertebra.

Objective:To summarize and analyze the clinical characteristics and treatment outcomes of patients with recurrent pericarditis.Methods:This observational study consecutively recruited patients with recurrent pericarditis who were hospitalized at Peking University People′s Hospital between January 2017 and February 2024. Clinical characteristics and treatment outcomes were collected and summarized during follow-up.Results:A total of 8 recurrent pericarditis patients including 3 males were included, with an age of 34.0 (22.0, 39.5) years. In terms of clinical features, all patients presented with acute-onset severe chest pain, accompanied by fever in 7 and an audible pericardial friction rub in 2 patients. Electrocardiogram showed no diffuse ST-segment elevation or PR-segment depression in any patient. Echocardiography revealed pericardial effusion in all cases, with extensive fibrinous exudate and transient pericardial thickening observed in 6 patients. CT identified concurrent pleural and/or peritoneal effusions in 6 patients. All patients exhibited marked elevations in C-reactive protein, erythrocyte sedimentation rate and D-dimer levels. Whole-exome sequencing identified MEFV gene mutations associated with familial Mediterranean fever in 3 cases. Two patients developed cardiac tamponade requiring pericardiocentesis, which revealed hemorrhagic effusion. In the aspect of treatment outcomes, the time from recurrence to first confirmed diagnosis of recurrent pericarditis of this cohort was 14.5 (13.3, 19.5) d. Upon diagnosis, all patients promptly received standard anti-inflammatory therapy with ibuprofen and colchicine, achieving rapid relief. However, during a follow-up of 12.0 (6.0, 25.3) months, 3 patients experienced recurrence, and 2 developed transient constrictive pericarditis.Conclusion:Patients with recurrent pericarditis typically exhibit characteristic clinical presentations, laboratory abnormalities, imaging findings and potential genetic associations. Although standard anti-inflammatory therapy demonstrates favorable short-term efficacy, long-term management remains challenging due to the risks of recurrence and progression to constrictive pericarditis.