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.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Objective To evaluate the value of high-resolution computed tomography(HRCT)signs combined with artificial intelligence(AI)quantitative indexes in differentiating mycoplasma pneumoniae pneumonia(MPP)from bacterial pneumonia(BP)in adults.Methods A total of 100 patients with adult MPP and 100 with adult BP were selected.Univariate and multivariate logistic regression analyses were used to identify independent factors that contribute to the differentiation of these two types of pneumonia.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were employed to evaluate the discrimination ability of the two types of pneumonia.Results A comparison of gender and age between the two groups revealed statistically significant differences(P＜0.05).A comparison of bronchial wall thickening,bud sign,and solid shadows between the two groups yielded statistically significant differences(P＜0.05),while small nodules did not(P＞0.05).AI-based quantification revealed significant differences in distribution of inflammatory foci,consolidation/total lesion ratio,ground-glass opacity(GGO)/total lesion ratio,consolidation density,and GGO density(P＜0.05).Univariate and multivariate logistic regression analyses revealed that left upper lobe(％),left lower lobe(％),right upper lobe(％),right middle lobe(％),and right lower lobe(％)were independent factors that contributed to the identification of the two types of pneumonia.The AUC for HRCT signs alone,AI quantitative indexes alone,and HRCT signs combined with AI quantitative indexes in differentiating the two types of pneumonia were 0.715[95％confidence interval(CI)0.643-0.787],0.822(95％CI 0.764-0.881),and 0.853(95％CI 0.801-0.905),respectively.The utilization of HRCT signs combined with AI quantitative indexes had been demonstrated to possess a substantial capacity to accurately identify two types of pneumonia.Conclusion HRCT signs combined with AI quantitative indexes can improve the accuracy of differentiating MPP from BP in adults.

Objective To evaluate the value of high-resolution computed tomography(HRCT)signs combined with artificial intelligence(AI)quantitative indexes in differentiating mycoplasma pneumoniae pneumonia(MPP)from bacterial pneumonia(BP)in adults.Methods A total of 100 patients with adult MPP and 100 with adult BP were selected.Univariate and multivariate logistic regression analyses were used to identify independent factors that contribute to the differentiation of these two types of pneumonia.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were employed to evaluate the discrimination ability of the two types of pneumonia.Results A comparison of gender and age between the two groups revealed statistically significant differences(P＜0.05).A comparison of bronchial wall thickening,bud sign,and solid shadows between the two groups yielded statistically significant differences(P＜0.05),while small nodules did not(P＞0.05).AI-based quantification revealed significant differences in distribution of inflammatory foci,consolidation/total lesion ratio,ground-glass opacity(GGO)/total lesion ratio,consolidation density,and GGO density(P＜0.05).Univariate and multivariate logistic regression analyses revealed that left upper lobe(％),left lower lobe(％),right upper lobe(％),right middle lobe(％),and right lower lobe(％)were independent factors that contributed to the identification of the two types of pneumonia.The AUC for HRCT signs alone,AI quantitative indexes alone,and HRCT signs combined with AI quantitative indexes in differentiating the two types of pneumonia were 0.715[95％confidence interval(CI)0.643-0.787],0.822(95％CI 0.764-0.881),and 0.853(95％CI 0.801-0.905),respectively.The utilization of HRCT signs combined with AI quantitative indexes had been demonstrated to possess a substantial capacity to accurately identify two types of pneumonia.Conclusion HRCT signs combined with AI quantitative indexes can improve the accuracy of differentiating MPP from BP in adults.

Objective To investigate the effect of platelet lysate on mitochondrial function of astrocytes after spinal cord injury.Methods Astrocytoma cells SVGp12 were incubated with different concentrations of H2O2 (100 μmol/L,400 μmol/L,1000 μmol/L,2000 μmol/L),and the OD value was determined by CCK-8 assay. The H2O2 concentration with a cell inhibition rate of about 50％ was selected for follow-up experiments. The cells were incubated with different concentrations of platelet lysate (the volume ratios of platelet lysate to culture medium were 1∶10,1∶40,1∶80,1∶160 and 1∶320) for 24 hours,and the OD value was determined,thereby selecting the optimal concentration of platelet lysate based on the cell survival rate. SVGp12 cells were divided into the normal group (cultured normally without special treat-ment),the model group (incubated with 1000 μmol/L of H2O2 for 3 hours),and the treatment group (incubated with 1000 μmol/L of H2O2 for 3 hours and then treated with platelet lysate at a volume ratio of 1∶80). The mitochondrial function was evaluated by mitochondrial activity staining,mitochondrial membrane potential detection,and mitochondrial permeability transition pore detection. Results After incubating cells with 1000 μmol/L of H2O2 for 3 hours,the cell inhibition rate was 48％,and the OD value decreased significantly (P<0.01),confirming the successful establishment of a model of astrocytes with spinal cord injury. After treated with different concentrations of platelet lysate,the OD values and cell survival rate of the cells were higher than those in the model group (P<0.05). The concentration of platelet lysate (volume ratio of 1∶80) with cell viability of 20％ was selected for follow-up experiments. Platelet lysate could improve the morphology of injured astrocytes. The mitochondrial activity of the treatment group was significantly higher than that of the model group,and the mitochondrial activity of the model group was significantly lower than that of the normal group,with statistically significant differences (P<0.05). The mitochondrial membrane potential in the model group was lower than that in the normal group,and the mitochondrial membrane potential in the treatment group was higher than that in the model group,with statistically significant differences (P<0.01). The mitochondrial permeability in the model group was greater than that in the normal group,and the mitochondrial permeability in the treatment group was smaller than that in the model group,with statistically significant differences (P<0.01).Conclusion Platelet lysate can improve the survival rate of astrocytes after spinal cord injury,enhance the mitochondrial activity of cells,and improve the mitochondrial membrane potential and mitochondrial permeability transition pore opening.

Objective Based on the local anatomic relationship between right sternocleidomastoid and right internal jugular vein,the application value of modified anatomic positioning method in right internal jugular vein puncture during critical cesarean section was discussed.Methods A total of 360 critical patients who underwent elective operation in obstetrics department of our hospital were selected,all of whom received right internal jugular vein puncture. According to different puncture approaches,they were divided into the observation group (punctured by modified anatomic positioning method) and the control group (punctured by traditional middle approach method),with 180 cases in each group. The differences in the success rate of one-time puncture,the overall success rate of puncture and the failure rate of guide wire implantation were compared between the two groups. The incidence of complications such as misplacement into the artery,artery hematoma,hemopneumothorax,arrhythmia and brachial plexus injury were compared in the two groups. Results The success rate of one-time puncture and overall success rate of puncture in the observation group were significantly higher than those in the control group,and the differences were statistically significant (P<0.05). The failure rate of guide wire implantation in the observation group was lower than that in the control group,and the difference was statistically significant (P<0.05). The incidences of misplacement into the artery and artery hematoma in the observation group were significantly lower than those in the control group,and the differences were statistically significant (P<0.05). No complications such as hemopneumothorax,arrhythmia or brachial plexus injury occurred in the two groups. Conclusion Compared with the traditional middle approach method puncture,the modified anatomic positioning method puncture has the advantages of higher puncture success rate,fewer complications and higher safety.

Aim To explore the material basis and un-derlying mechanism of Qingre Huoxue Formula(QRHXF)in the treatment of non-small cell lung cancer(NSCLC)by applying network pharmacology,molecular docking technology and bioinformatics com-bined with animal experiments.Methods TCMSP,ECTM,and BATMAN databases were used to obtain active components and corresponding targets of QRHXF;GEO and DisGeNENT databases were con-ducted to acquire NSCLC-associated differential expres-sion genes.By intersecting them,the common targets were obtained.It was chosen to construct a herb-com-ponent-disease network and protein-protein interaction(PPI)network.Furthermore,DAVID database was used to perform gene ontology(GO)function and Kyo-to encyclopedia of genes and genomes(KEGG)path-way enrichment analyses.The molecular docking was presented by adopting Autodock Vina program to verify key targets.RNA-seq datawere downloaded from TC-GA database to obtain differential gene expression.Ka-planMeier(KM)analysis was performed to analyze the relationship between gene expression and overall sur-vival.Mouse subcutaneous tumor model of LLC was established.The effects of QRHXF on body weight,tumor volume and weight were monitored for pharmaco-dynamic analysis.Tumor tissues slides were stained with hematoxylin and eosin(HE)for histopathological examination.Immunohistochemistry(IHC)staining was employed for detecting Ki67 and EP300.Western blot was performed to measure the protein expression of TP53,CDK1 and NTRK1.Results The results of net-work pharmacology showed that a total of seven com-mon targets were screened from NSCLC and QRHXF,and the effect of QRHXF on anti-NSCLC may occur via multiple signaling pathways,including cell cycle.The results of molecular docking indicated that the main ac-tive components of QRHXF had low binding energy and stable docking conformation with the molecular target for treating NSCLC.According to bioinformatic analy-sis,there were significant differences in BRCA1,CDK1 and NTRK1 mRNA expression between tumor tissues and normal tissues,which were also prognostic factors for overall survival.Animal experimental research showed QRHXF inhibited subcutaneous tumor growth(P＜0.01)and improved the quality of life in mice with NSCLC.After QRHXF intervention,the density of tumor cells was significantly reduced,and necrotic are-as were increased.The expressions of Ki67 and EP300 were significantly decreased.Compared with the model group,Western blot showed up-regulation of TP53 and NTRKA(P＜0.05),whereas CDK1 were down-regu-lated(P＜0.05).Conclusion QRHXF exerted anti-NSCLC effects by regulating NTRK1,EP300,TP53,CDK1 and inducing cell cycle,cell cycle arrest and in-hibiting tumor growth,metastasis and angiogenesis.

Objective:To evaluate the preventive effects of transcutaneous electrical acupoint stimulation (TEAS) on chronic pain after lumbar spine surgery.Methods:This was a secondary analysis conducted on the studies assessing the effect of TEAS on gastrointestinal function in patients undergoing lumbar spinal surgery. Fifty lumbar spinal stenosis patients of either sex, aged 50-75 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status cassification Ⅰ or Ⅱ, with expected operation time≥3 h, undergoing lumbar spinal surgery under general anesthesia, were enrolled and assigned into 2 groups ( n=25 each) using a random number table method: control group (C group) and TEAS group. In group C, stimulating electrodes were placed at the non-acupoint parts of the limbs, but no electrical stimulation was applied. In group TEAS, the bilateral Neiguan (PC6), Hegu (L14), Zusanli (ST36), Shangjuxu (ST37) and Xiajuxu (ST39) were stimulated with disperse-dense waves at a frequency of 2/100 Hz. The intensity of stimulation was the maximum current that patients could tolerate. The intervention was performed once a day for 30 min per session at 30 min prior to anesthesia induction and on postoperative days 1-7. Telephone follow-ups were conducted at 3, 6 and 12 months after surgery to record the occurrence of postoperative moderate-to-severe lower back pain and leg pain (Numerical Rating Scale score ≥4), and the Oswestry Disability Index (ODI) value and four-item neuropathic pain questionnaire scores. The pain-related medical visits and usage of nonsteroidal anti-inflammatory drugs were also recorded after surgery. Results:Three patients in each group were lost to follow-up. Compared with group C, the incidence of chronic low back pain was significantly decreased at 6-12 months after surgery, the ODI value and four-item neuropathic pain questionnaire scores were decreased at 12 months after surgery ( P<0.05), ODI value difference reached the minimal clinically important difference, the proportion of patients requiring medical visits due to postoperative pain and usage rate of nonsteroidal anti-inflammatory drugs were decreased at 6-12 months after surgery ( P<0.05), and no significant change in the incidence of chronic moderate-to-severe leg pain was found at each time period after surgery in group TEAS( P>0.05). Conclusions:TEAS can prevent the occurrence of chronic lower back pain and improve functional impairment in patients undergoing lumbar spine surgery.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.