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.

BACKGROUND:Precision therapy based on multifunctional nanomaterials is a novel therapeutic model for malignancies that can integrate multiple imaging and therapeutic models into one nanoscale platform to achieve visual combination treatment. OBJECTIVE:To prepare novel nanoparticles loaded with Cu2(OH)PO4 nanoparticles(CuNPs)and nuciferine(NF)(h-PCuNF),and to explore their ability to mediate combined photothermal therapy/photodynamic therapy/chemodynamic therapy/chemotherapy for malignancy. METHODS:The h-PCuNF nanoparticles were synthesized through a double-emulsion procedure,through which the CuNPs and NF were loaded into the shell of hollow poly(lactic-co-glycolic)acid nanocarriers.The morphology,structure,particle size,and zeta potential of the h-PCuNF nanoparticles were characterized.In deionized water,the magnetic resonance imaging and photothermal conversion performances of the h-PCuNF nanoparticles,as well as their capability to implement reactive oxygen species production by mediating photocatalysis and Fenton-like reactions,were evaluated.In liver malignant tumor cell line HepG2 cells,the effectiveness of the photothermal therapy/photodynamic therapy/chemodynamic therapy/chemotherapy combination therapy mediated by the nanoparticles was detected by employing fluorescence imaging and MTT assay. RESULTS AND CONCLUSION:(1)The h-PCuNF nanoparticles possessed a hollow spherical structure in which the CuNPs(drug loading rate and encapsulation rate were 26.3%and 63.2%,respectively)and NF(drug loading rate and encapsulation rate were 11.0%and 52.6%,respectively)were loaded into the shell.The average particle size of the h-PCuNF nanoparticles was(309.2±10.0)nm,while the zeta potential was determined to be(-12.5±0.9)mV.In physiological environments,the nanoparticles possess favorable suspension stability.(2)In deionized water,the h-PCuNF nanoparticles could markedly enhance T1-weighted magnetic resonance imaging images.The h-PCuNF nanoparticles showed remarkable photothermal conversion and photocatalytic reactive oxygen species generation capabilities under near infrared laser irradiation.In addition,the h-PCuNF nanoparticles could consume glutathione and mediate Fenton-like reactions to produce·OH.(3)The h-PCuNF nanoparticles could be taken up by HepG2 tumor cells and were mainly distributed in the cytoplasm.The synergistic therapeutic effect was demonstrated after the nanoparticles were activated by near infrared laser irradiation,because CuNPs mediated photothermal therapy/photodynamic therapy/chemodynamic therapy and NF mediated chemotherapy could synergistically eliminate the tumor cells.

Objective: To explore the distribution of traditional Chinese medicine (TCM) syndromes in patients with interstitial lung disease (ILD) and its influencing factors. Methods: This cross-sectional study included 385 patients with ILD admitted to the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) from January 2018 to June 2022. Data on sex, age, body mass index, smoking history, respiratory rate, hospitalization time, treatment cost, whether velcro rales can be heard, comorbidities with rheumatic immune diseases, TCM four examination information, and clinical examination results, including CT imaging, D-dimer level, and lung function-related indicators, were collected. The distribution pattern of TCM syndromes in patients with ILD and the association between TCM syndromes and clinical indicators were analyzed using the cluster analysis and binary Logistic regression analysis. Results: Among the 385 patients with ILD, sticky phlegm (59.74%) and shortness of breath (56.10%) were common symptoms, while greasy tongue coating (55.32%), red tongue (52.73%), and slippery and rapid pulse (25.71%) were common tongue and pulse manifestations. The patients were divided into five syndromes using cluster analysis: syndrome of phlegm-heat stagnation in the lung (36.62%), syndrome of turbid phlegm obstructing lung (29.35%), syndrome of deficiency of both qi and yin (12.99%), syndrome of qi deficiency of lung and kidney (11.95%), and syndrome of phlegm and blood stasis obstructing lung (9.09%). The D-dimer level was lower in patients with syndrome of phlegm-heat stagnation in the lung, syndrome of turbid phlegm obstructing lung, syndrome of deficiency of both qi and yin, and syndrome of qi deficiency of lung and kidney than in those with syndrome of phlegm and blood stasis obstructing lung (P<0.05). The percentage of predicted forced vital capacity (FVC%pred) of patients with syndrome of phlegm-heat stagnation in the lung, syndrome of turbid phlegm obstructing lung, syndrome of deficiency of both qi and yin, and syndrome of phlegm and blood stasis obstructing lung was higher than in those with syndrome of qi deficiency of lung and kidney (P<0.05). Among patients aged 60 and above, those with syndrome of phlegm-heat stagnation in the lung, syndrome of phlegm and blood stasis obstructing lung, and syndrome of deficiency of both qi and yin containing dual pathogenic syndrome elements were more likely to experience moderate to severe pulmonary diffusion impairment than those with syndrome of turbid phlegm obstructing lung and syndrome of qi deficiency of lung and kidney containing single pathogenic syndrome elements (P<0.05). The Logistic regression showed that the FVC%pred was an influential factor for syndrome of qi deficiency of lung and kidney, and the area under the receiver operating characteristic (ROC) curve (AUC) between FVC%pred and the formation of syndrome of qi deficiency of lung and kidney was 0.676 (95%CI: 0.598-0.755), P=0.002. The sensitivity was 0.431, the specificity was 0.966, and the best threshold on the ROC curve of 0.397 was 79.1%. The D-dimer level was an influential factor in the formation of syndrome of phlegm and blood stasis obstructing lung. The AUC between D-dimer level and the formation of syndrome of phlegm and blood stasis obstructing lung was 0.729 (95%CI: 0.655-0.802), P<0.001. The sensitivity was 0.914, the specificity was 0.523, and the best threshold on the ROC curve of 0.437 was 0.675 mg/L. Conclusion syndrome of phlegm-heat stagnation in the lung and syndrome of turbid phlegm obstructing lung are common among patients with ILD. Complex pathological syndromes are more likely to exacerbate pulmonary diffusion dysfunction. The FVC%pred can assist in differentiating syndrome of qi deficiency of lung and kidney, whereas the D-dimer level can assist in differentiating syndrome of phlegm and blood stasis obstructing lung.

Peritoneal dialysis (PD) is a crucial renal replacement therapy for end-stage renal disease (ESRD), offering significant advantages as high flexibility, hemodynamic stability, and high cost-effectiveness. However, prolonged exposure to intra-abdominal dialysate may predispose to the mechanical complication of abdominal external hernia. Abdominal external hernia may lead to various adverse clinical outcomes. In severe cases, it can progress to incarceration or even rupture, ultimately necessitating discontinuation of the therapy. The authors systematically review PD-associated abdominal external hernias, including their clinical landscape, risk factors, surgical treatment strategies and prognostic determinants. They also assess the effects of hernia repair on residual renal function, aiming to provide references for clinical decision-making.

Objective:To investigate whether the rs612529 C/T and rs11669663 G/A in VSTM1 gene are associated with leukocyte signaling inhibitory receptor-1(SIRL-1)expression and an increased risk for systemic lupus erythematosus(SLE)in a Han Chinese cohort.Methods:A total of 200 patients with SLE and 218 healthy controls(HC)were enrolled.Relevant laboratory characteris-tics of patients with SLE were also collected.Genotyping of rs612529 C/T and rs11669663 G/A were performed by Sanger sequencing technology.SIRL-1 expression was assessed in peripheral blood neutrophils and monocytes was detected by flow cytometry.Levels of autoantibodies associated with SLE were detected by ELISA.Results:In both SLE group and HC,the C allele of rs612529 was asso-ciated with a decreased expression level of SIRL-1 on monocytes,with a gradual increased in SIRL-1 protein level from the CC over the CT to the TT genotype.C allele of rs612529 was associated with higher serum anti-dsDNA antibody titers in patients with SLE(P<0.05).In the case of rs11669663 G/A,no significant association of genotypes with SLE susceptibility was detected.Conclusion:VSTM1 rs612529 C/T may contribute to SLE disease activity and regulate SIRL-1 expression on monocytes in the Han Chinese cohort.

Background and purpose:Single-week ultra-hypofractionated whole breast irradiation(WBI)after breast-conserving surgery could shorten the treatment duration while ensuring efficacy and safety,making it a viable option for WBI.However,ultra-hypofractionated WBI requires daily image-guided radiotherapy(IGRT),and its impact on setup errors remains unclear.This study aimed to identify factors associated with set-up errors in ultra-hypofractionated WBI guided with daily cone-beam computed tomography(CBCT)and calculate margin expanded from clinical target volume(CTV)to planning target volume(PTV).Methods:This study included patients enrolled in a prospective trial that explored the safety of single-week ultra-hypofractionated WBI(NCT04926766)in Shanghai Ruijin Hospital,which was approved by Shanghai Ruijin Hospital Ethics Committee(No.2020-352).All patients received CBCT1 after positioning.After correcting errors,patients received CBCT2.CBCT3 was conducted after radiotherapy was completed.The translational errors between CBCT1,CBCT2,and plan CT were initial and residual inter-fractional errors.The translational error between CBCT2 and CBCT3 was an intra-fractional error.The PTV margin was calculated according to the van Herk formula.Results:A total of 34 patients were enrolled in this study,and 510 CBCT images were collected.Daily CBCT significantly reduced set-up error in anterior-posterior(AP),superior-inferior(SI)and right-left(RL)directions(initial inter-fractional error vs residual inter-fractional error:AP,2.8 mm vs 0.4 mm;SI,1.6 mm vs 0.5 mm;RL,1.8 mm vs 0.3 mm,all P＜0.001).Higher CTV volume(＞402.5 cm3 vs≤402.5 cm3)was associated with larger residual inter-fractional error(0.5 mm vs 0.3 mm,P=0.023)and intra-fractional error(0.5 mm vs 0.2 mm,P=0.001)in AP direction.Higher CTV volume was also associated with larger residual inter-fractional error in the SI direction(0.6 mm vs 0.5 mm,P=0.037).Higher BMI(＞23.2 kg/m2 vs≤23.2 kg/m2)and larger weight(＞60.0 kg vs≤60.0 kg)were associated with larger intra-fractional error in AP direction:0.7 mm vs 0.2 mm(P＜0.001)and 0.5 mm vs 0.2 mm(P=0.033),respectively.Under guidance with daily CBCT,the recommended margins were 2.3 mm in AP direction,2.8 mm in SI direction,and 2.0 mm in RL direction.However,in patients with CTV volume＞402.5 cm3 and BMI＞23.2 kg/m2,a larger margin was recommended in SI direction:3.1 mm and 3.4 mm,respectively.Conclusion:The 3 mm margin was feasible under guidance with daily CBCT.The CTV to PTV margin should be larger in patients with higher BMI or CTV volume.

Objective:To evaluate the effect of low-opioid anesthesia based on combination of esketamine and dexmedetomidine on the postoperative mood in patients undergoing thoracoscopic surgery.Methods:In this randomized controlled trial, 130 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients of either sex, aged 18-65 yr, with body mass index ≤30 kg/m 2, undergoing elective video-assisted thoracoscopic surgery, were divided into 2 groups using a random number table method: low-opioid anesthesia group and conventional opioid anesthesia group, with 65 patients in each group. The patients in two groups received either a low-opioid anesthesia based on combination of esketamine and dexmedetomidine or a sufentanil-based opioid anesthesia. Depression and anxiety were assessed using the Self-Rating Depression Scale and Self-Rating Anxiety Scale on day 1 before surgery and days 1, 3 and 7 after surgery. The intraoperative consumption of opioid, usage of vasoactive drugs, extubation time, duration of stay in the post-anesthesia care unit, Riker Sedation-Agitation Scale score after extubation, consumption of sufentanil within 24 h postoperatively, and pain score at 24 h postoperatively were recorded, and the occurrence of adverse reactions within 24 h postoperatively was also recorded. Results:Compared with conventional opioid anesthesia group, the postoperative Self-Rating Depression Scale score and incidence of depression were significantly decreased, the Self-Rating Anxiety Scale score and incidence of anxiety were decreased, the intraoperative consumption of opioid was reduced, the usage rate of metaraminol was decreased, the usage rate of nicardipine was increased, the duration of stay in the post-anesthesia care unit was shortened, the Riker Sedation-Agitation Scale score was decreased after tracheal extubation, the consumption of sufentanil was reduced after operation, the pain score was decreased, and the incidence of postoperative nausea and vomiting and dizziness was decreased in low-opioid anesthesia group ( P<0.05). Conclusions:The low-opioid anesthesia based on combination of esketamine and dexmedetomidine can relieve the postoperative depression and anxiety and improve the quality of postoperative recovery when used in patients undergoing thoracoscopic surgery.

OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.

Objective:To evaluate the effect of low-opioid anesthesia based on combination of esketamine and dexmedetomidine on the postoperative mood in patients undergoing thoracoscopic surgery.Methods:In this randomized controlled trial, 130 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients of either sex, aged 18-65 yr, with body mass index ≤30 kg/m 2, undergoing elective video-assisted thoracoscopic surgery, were divided into 2 groups using a random number table method: low-opioid anesthesia group and conventional opioid anesthesia group, with 65 patients in each group. The patients in two groups received either a low-opioid anesthesia based on combination of esketamine and dexmedetomidine or a sufentanil-based opioid anesthesia. Depression and anxiety were assessed using the Self-Rating Depression Scale and Self-Rating Anxiety Scale on day 1 before surgery and days 1, 3 and 7 after surgery. The intraoperative consumption of opioid, usage of vasoactive drugs, extubation time, duration of stay in the post-anesthesia care unit, Riker Sedation-Agitation Scale score after extubation, consumption of sufentanil within 24 h postoperatively, and pain score at 24 h postoperatively were recorded, and the occurrence of adverse reactions within 24 h postoperatively was also recorded. Results:Compared with conventional opioid anesthesia group, the postoperative Self-Rating Depression Scale score and incidence of depression were significantly decreased, the Self-Rating Anxiety Scale score and incidence of anxiety were decreased, the intraoperative consumption of opioid was reduced, the usage rate of metaraminol was decreased, the usage rate of nicardipine was increased, the duration of stay in the post-anesthesia care unit was shortened, the Riker Sedation-Agitation Scale score was decreased after tracheal extubation, the consumption of sufentanil was reduced after operation, the pain score was decreased, and the incidence of postoperative nausea and vomiting and dizziness was decreased in low-opioid anesthesia group ( P<0.05). Conclusions:The low-opioid anesthesia based on combination of esketamine and dexmedetomidine can relieve the postoperative depression and anxiety and improve the quality of postoperative recovery when used in patients undergoing thoracoscopic surgery.

OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.