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 and regulatory mechanisms of carboxyamidotriazole orotate(CTO)on the metabolism and inflammatory mediators of glioma-associated microglia(GAM).Methods Tumor volume was regularly monitored by in vivo imaging,and histological examination was performed to detect the extent of tumor in-filtration;non-targeted metabolomics analysis was used to detect the level of tricarboxylic acid cycle metabolites in cells;seahorse cell energy measurement method was used to detect the oxygen consumption rate(OCR)and extra-cellular acidification rate(ECAR)of cells;immunofluorescence was used to detect the degree of hypoxia in cells;quantitative PCR was used to detect the mRNA level of pro-cancer mediators M1/M2 in cells;Western blot was used to detect the protein level of hypoxia-inducible factor-1α(HIF-1α)and programmed death receptor-ligand 1(PD-L1).Results CTO inhibited the tumor progression in mice,and down-regulated the oxidative phosphorylation level and improved cell hypoxia in vitro(P＜0.01).It also downregulated the expression of pro-oncogenic mediators iNos,Arg-1,Il-10,and Irf4 in GAM(P＜0.01).When combined with lactate dehydrogenase inhibitor stiripentol(STP),CTO-induced enhancement of glycolysis and upregulation of PD-L1 expression in GAM was attenuated(P＜0.01),and the expressions of Arg-1 and Il-10 was further downregulated(P＜0.000 1).Conclusions CTO down-regulates the expression of several oncogenic genes in GAM and inhibits tumor progression in mice.Combined use of lactate dehydrogenase inhibitors can weaken the adverse effect of CTO and reduce the transcriptional level of GAM oncogenic mediators.

Objective:To evaluate the efficacy of glottic closure in preventing postoperative aspiration in elderly patients undergoing supraglottic horizontal partial laryngectomy.Methods:A retrospective case series analysis was conducted on the clinical data of 12 elderly patients who underwent supraglottic horizontal partial laryngectomy with concurrent glottic closure at the Sixth Medical Center of Chinese PLA General Hospital from January 1, 2002, to December 31, 2024. Among them, there were 8 males and 4 females, aged from 68 to 80 years, with an average age of 74 years. There were 11 cases of supraglottic laryngeal cancer and 1 case of tongue base cancer. The TNM staging was T2N0M0 in 8 cases, T3N0M0 in 2 cases, T3N1M0 in 1 case, and T3N2M0 in 1 case. All patients existed comorbid cardiovascular dysfunction of varying severity. Pulmonary function tests were impaired in 8 cases. Comorbidities included hypertension ( n=5), prior coronary stent placement ( n=3), and thrombocytopenia ( n=1). Swallowing function was assessed using the EAT-10 (Eating Assessment Tool-10) one month postoperatively. All patients were followed up regularly. Results:The mean EAT-10 score at one month postoperatively was 2.42±1.71. Eleven patients successfully resumed oral feeding without obvious aspiration. Voice quality was intelligible when the tracheostomy tube was blocked. In the early stage, in 1 case, due to the suture technique problem of the glottis closure, the suture site of the glottis completely split open after the operation. The patient′s breathing was normal when the tube was blocked, and the tracheostomy tube was removed. As arytenoid edema resolved, the patient developed varying degrees of dysphagia with recurrent aspiration. This patient was hospitalized twice due to aspiration pneumonia, at 5 months and 19 months, postoperatively. The remaining 11 patients exhibited no signs of significant aspiration during follow-up. The 3-year and 5-year postoperative survival rates were 7/8 and 5/7, respectively.Conclusion:For elderly patients with supraglottic laryngeal cancer or tongue base cancer, and those who are at high risk for persistent postoperative aspiration after fully evaluated systematically, glottis closure during supraglottic horizontal partial laryngectomy is an effective strategy to prevent aspiration and to facilitate safe oral intake.

Objective:To apply mass spectrometry as well as bioinformatics techniques to analyze HBV peptides derived from Pol and X proteins presented by human immortalized B lymphocytes(BLCLs),and to screen for effective T-cell epitopes,which lays the foundation for the development of therapeutic vaccines.Methods:The group has constructed a genome-wide expression plasmid containing 1.2-fold HBVC2 isoforms and transfected it into BLCLs by electro-transfection,isolated and identified HBV peptides by LC-MS/MS,bioinformatically predicted peptide sequences in terms of sensitization,antigenicity,toxicity,HLA molecular affinity,and the ability of peptide HLA-class Ⅰ complex to bind to specific T cells,and retrieved reported sequences.Results:HBV peptides from lysates of five immortalized B cells(BLCLs-1 to BLCLs-5)carrying HBVC2 subtype-expressing recombinants were analyzed,and 141 peptides with sequence lengths of no less than 8 amino acid residues(≥8 aa)were successfully isolated and identified,of which 133 were derived from Pol,and 8 from X proteins.The 141 HBV peptides were analyzed for sensitization,antigenicity and toxicity,and 50 antigenic,non-toxic and sensitizing HBV peptides(47 from Pol and 3 from X protein)were screened for affinity analysis with HLA-class Ⅰ and Ⅱ molecules and for prediction of the binding ability of the peptide HLA-class Ⅰ complexes to specific T cells.Among these peptides,37 had affinity to the corresponding genotypes of HLA-class Ⅰ and Ⅱ molecules.Finally,we obtained 37 peptides with antigenic,nontoxic,and sensitizing properties with IC50<500 nmol/L to HLA-class Ⅰ and Ⅱ molecules,which have affinitied to the corresponding genotypes but have not been reported,and can be continued to be explored as potential epitopes.Finally,15 HBV peptide hotspot core regions were formed by intra-and inter-strain common,contained,overlapping or neighboring sequence analysis of 141 peptides,with 7 core region sequences with antigenic,nontoxic,and sensitizing properties restricted to the corresponding geno-types.Peptides with affinity IC50<500 nmol/L had an affinity core sequence overlap of no less than 8 amino acids,and can be priori-tized for candidate T cell epitopes for subsequent studies.Conclusion:Peptides derived from Pol and X proteins have been successfully isolated and identified,and potential T cell epitopes have been screened.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To investigate the clinical effect of reconstruction of the degloving injury of thumb and finger with free perforator flap of superficial peroneal artery.Methods:This is a retrospective study. From June 2020 to June 2023, 18 superficial peroneal artery perforator flaps from 14 calves were used to treat 15 degloved digital wounds of 14 patients in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. There were 13 single digital degloving wounds and 1 two-digital degloving wounds. Of which, 3 digits were reconstructed with 2 free perforator flaps of ipsilateral superficial peroneal artery and 12 with a single free perforator flap of superficial peroneal artery. The size of wounds was 4.0 cm×2.0 cm-10.0 cm×4.0 cm, and the flaps were 5.0 cm×3.0 cm-12.0 cm×4.0 cm in size. The donor sites in calves were sutured layer by layer with absorptive sutures. Postoperative follow-ups were conducted through regular outpatient visits, phone calls or WeChat. Survival of flaps, postoperative complications, therapeutic effect of the flaps and patient satisfaction were observed.Results:There was no vascular compromise or wound infection of the flaps. All patients were included in the 4 to 36 months of postoperative follow-up, with an average of 9.86 months. All flaps had good appearance, without obvious swelling. Colour and texture of the flaps was close to the surrounding skin. The flaps had no obvious pigmentation or ulcer and scar hyperplasia at recipient site. Sensation of the flaps recovered to S 2 to S 3. There was no obvious scar hyperplasia, pain or dysfunction at donor sites. According to the comprehensive evaluation scale of flap, the scores were found at 81 to 91, with an average score of 85 in the 14 patients, and of whom 2 were excellent and 12 were good. Patient satisfaction was evaluated according to the Michigan Hand Outcomes Questionnaire (MHQ) and 10 patients were very satisfied and 4 were satisfied. Conclusion:Free perforator flap of superficial peroneal artery is one of the ideal flaps in reconstruction of degloving injury of thumb and fingers. It features constant and multiple perforators, reliable blood supply, high survival rate, flexible in design, thin and a small damage to the donor site.

Objective:In the context of China's cardiovascular disease(CVD)high-risk population screening and intervention project,this study systematically evaluates the applicability of the EQ-5D-5L and SF-6Dv2 instruments among individuals at high risk of CVD.Methods:Convergent validity was assessed using Spearman's correlation coefficient.Measurement agreement was evaluated through intraclass correlation coefficients(ICC)and Bland-Altman plots.Factors influencing utility differences were explored using multiple linear regression analysis.Kruskal-Wallis test and t-test were used to examine discriminant validity.Sensitivity was compared by effect size(ES),relative efficiency(RE),and the area under the receiver operating characteristic curve(ROC-AUC).Floor and ceiling effects were also compared.Results:Among 5,415 individuals at high risk of CVD,the two instruments showed moderate overall correlation and acceptable convergent validity,but dimension-specific correlations were weak,and measurement consistency was low(ICC=0.367).Both instruments effectively distinguished different health states,yet the SF-6Dv2 demonstrated superior sensitivity and a milder ceiling effect.Conclusion:When measuring the health utility value of CVD patients,scale selection should be cautious,especially for high-risk groups,and SF-6Dv2 is more appropriate.

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN). METHODS: Related test results of 283 newborns and their mothers' blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil). RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the "direct antibody+indirect antibody+release+" group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants. CONCLUSION ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Erythroblastosis, Fetal/epidemiology* ; Female ; China/epidemiology* ; Blood Group Incompatibility ; Male ; Bilirubin/blood*