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.

Network pharmacology has gained widespread application in drug discovery, particularly in traditional Chinese medicine (TCM) research, which is characterized by its "multi-component, multi-target, and multi-pathway" nature. Through the integration of network biology, TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms, establishing a novel research paradigm for TCM modernization. The rapid advancement of machine learning, particularly revolutionary deep learning methods, has substantially enhanced artificial intelligence (AI) technology, offering significant potential to advance TCM network pharmacology research. This paper describes the methodology of TCM network pharmacology, encompassing ingredient identification, network construction, network analysis, and experimental validation. Furthermore, it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods. Finally, it addresses challenges and future directions regarding cell-cell communication (CCC)-based network construction, analysis, and validation, providing valuable insights for TCM network pharmacology.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Network Pharmacology/methods* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Drug Discovery

Objective:To analyze the practical experiences and challenges faced by nurses in community-based elderly care institutions in the management of insulin therapy for elderly patients with diabetes.Methods:This qualitative study employed purpose sampling to recruit nurses from two community-based elderly care institutions in Beijing from June to October 2023. Semi-structured interviews were conducted focusing on their experiences and challenges in insulin use for elderly patients with type 2 diabetes. All interviews were audio-recorded and transcribed into text. Framework analysis was used to analyze the interview data.Results:A total of 15 nurses participated in the interviews, all of whom were female with work experience ranging from 4 to 12 years. The analysis revealed three main themes and 2-3 subthemes under each theme. Theme 1 patients′ experiences with insulin injection: concerns about adverse reactions such as hypoglycemia, obesity, and injection pain; attention to insulin dosage, blood glucose levels, dietary management, and weight control. Theme 2 nurses′ practices and challenges in insulin management: communication and emotional support; trust-building between nurses and elderly patients; impact of insufficient human resources. Theme 3 nurses′ experiences with diabetes knowledge education and training: motivation for training; adaptation of training content, format and frequency to local conditions; implementation and significance of health education.Conclusions:The management of elderly people with diabetes in community-based elderly care institutions presents significant challenges. It is essential to provide personalized insulin management support, emotional support, and psychological counseling for elderly diabetic patients. Additionally, nurses require access to relevant diabetes knowledge education and training to enhance their ability of effective care.

Objective:To investigate the clinical efficacy of liquid nitrogen cryopreservation and reimplantation versus allograft reconstruction in patients underwent resection of primary malignant bone tumors of the long bones of the extremities.Methods:A retrospective analysis was conducted on 144 patients who underwent resection of primary malignant bone tumors of the long bones of the extremities followed by either liquid nitrogen cryopreservation and reimplantation or massive allografts reconstruction at the Beijing Jishuitan Hospital affiliated with Capital Medical University from January 2012 to July 2023. The study included 82 males and 62 females, with an average age of 23.8±12.3 years (range, 6-64 years). Patients were divided into two groups based on the reconstruction method: the cryopreservation and reimplantation group (72 cases) and the allograft group (72 cases). The following outcomes were recorded during follow-up: local tumor recurrence, bone union, union time, graft survival, and reasons for graft removal. Graft-related complications were recorded using the modified Henderson classification system of the International Limb Salvage Association. Limb function was assessed at the last follow-up using the Musculoskeletal Tumor Society score (MSTS-93).Results:All patients completed surgery and were followed up for a mean of 60.2±32.1 months (range, 12-149 months). At the last follow-up, 24 patients were dead from the tumor, 16 patients survived with the tumor (2 cases of local recurrence and 14 cases of distant metastasis), and 104 patients survived without the tumor. The bone union rate and union time in cryopreservation and reimplantation group were 90% (65/72) and 9.6±4.8 months, respectively, which was significantly superior to those in allograft group [68% (49/72) and 15.9±6.7 months, P<0.05]. The 5-year overall graft survival rate was 86.8% [95% CI (80.1%, 95.7%)] in cryopreservation and reimplantation group, higher than 73.2% [95% CI(68.4%, 84.5%)] in allograft group significantly (χ 2=7.122, P=0.017). The rates of graft removal due to non-union and infection in the cryopreservation and reimplantation group were 0% (0/72) and 1.4% (1/72), respectively, which were significantly lower than those in the allograft group [5.6% (4/72) and 9.7% (7/72), P<0.05]. Overall, 48.6% (70/144) of patients experienced at least one graft-related complication, with a complication rate of 33.3% in cryopreservation and reimplantation group, lower than the 61.1% in allograft group significantly (χ 2=11.146, P<0.001). The complications with the highest incidence rate were nonunion (20.8%, 30/144), followed by structural failure (17.4%, 25/144), tumor progression (10.4%, 15/144), infection (10.4%, 15/144), and soft tissue failure (5.6%, 8/144). The incidence rates of the atrophic non-union and the structural failure of grafts were 9.7% (7/72) and 1.4% (1/72) respectively in the cryopreservation and reimplantation group, which were significantly lower compared to the allograft group [29.2% (21/72) and 13.9% (10/72), P<0.05]. At the last follow-up, the MSTS-93 score was 89.7%±8.3% in the cryopreservation and reimplantation group, and 87.6%±7.5% in the allograft group, with no statistically significant difference ( t=0.326, P=0.542). Conclusion:Compared with allograft reconstruction, autologous inactivated bone grafting demonstrated superior bone union efficiency and fewer complications, it may be considered for reconstruction in cases whose tumor bone is not severely osteolytic or pathologically fractured.

Objective:To explore the differences in the CVD risk and lipid profiles in psoriatic arthritis (PsA) patients with different disease activity and investigate lipid management status in Chinese patients with PsA.Methods:Patients were enrolled from PKUPsA-PC cohort in Peking University First Hospital from January 2016 to January 2024. Data were collected at their first visit, including disease activity score, lipid profiles and treatment. Two modified CVD risk prediction models (modified China-PAR and modified FRS-CVD) were applied to predict the CVD risk over 10 years. All enrolled patients were subsequently stratified into low, intermediate and high-risk groups. The status of lipid target achievement was assessed based on lipid management recommendations proposed by prediction models. In addition, DAPSA was used to stratify PsA patients into remission, low, moderate and high-disease activity groups, and the differences in CVD risk and lipid profiles among PsA patients with different disease activity status were explored. The t test was used for comparison between 2 groups for measures that conformed to normal distribution; the Mann-Whitney U test was used for comparison between 2 groups for measures that were skewed; and the chi-square test was used for comparison between 2 groups for categorical data.Results:Three hundred and seven PsA patients were included in this study. They were aged 47 (36, 57) years with 121 (39.4%) female, disease duration of skin lesions of 14 (7, 23) years and disease duration of PsA for 3 (1, 8) years. There were 148 (48.2%) patients with dyslipidemia, and 38 (25.7%) of them were receiving lipid lowering drugs. By the modified China-PAR model, there were 174 (56.7%), 76 (24.8%) and 57 (18.5%) in the low-, moderate- and high-risk groups. By the modified FRS-CVD model, there were 173 (56.4%), 58 (18.9%) and 76 (24.7%) patients in the corresponding groups. According to the recommendations for lipid management based on FRS-CVD model, 80 (26.1%) patients did not achieve the target of lipid profile, including 9/174 (5.2%) in the modified model low-risk group, 20/76 (26.3%) in the intermediate-risk group, and 51/57 (89.5%) in the high-risk group, but there were only 12 (15.0%) patients receiving statin therapy. Compared with the remission and low disease activity groups, patients in the moderate-to-high disease activity group were older [50 (37, 60) years vs. 43 (35, 55) years, Z=-2.42, P=0.016]; had a higher proportion of hypertension (30.3% vs. 15.0%, χ2=9.60, P=0.002); and had lower HDL-C levels [1.1 (0.9, 1.3) mmol/L vs. 1.2 (1.0, 1.4) mmol/L, Z=-3.18, P=0.001]. Under the modified China-PAR and modified FRS-CVD risk prediction models, a higher proportion of patients with high disease activity in PsA were stratified at high 10-year CVD risk compared with the remission and low disease activity groups (29.5% vs. 19.6%, χ2=3.81, P=0.005) and (23.5% vs. 12.4%, χ2=6.00, P=0.014). Conclusion:Nearly half of the PsA patients are at medium-high risk to CVD. CVD risk is significantly higher in patients with moderate to high disease activity than in patients with remission and low disease activity. HDL-c levels are lower in patients with high disease activity. Nevertheless a quarter of patients did not achieve the target of lipid profile, and few patients are receiving statin. More attention should be paid to CVD risk evaluation and lipid management as a part of treat-to-target strategy to improve the prognosis.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

All four patients were female, with an average age of 28.8 days and an average weight of 3.64 kg. Only case 4 was born prematurely at 34 W+5 and was treated conservatively until 71 days to complete operation. All the others completed primary corrective surgery in the neonatal period, and all survived after operation. Two different surgical techniques were used to repair the aortic-pulmonary window and the aortic origin of the right pulmonary artery, including 1 case using the aortic internal baffle technique and another 3 cases underwent replantation of the right pulmonary artery (1 case was reconstructed in situ, and the other 2 cases were reconstructed by moving the right pulmonary artery in the anterior of aorta). Case 2 who received aortic internal baffle technique underwent two reoperation because of right pulmonary artery stenosis. While, right pulmonary artery of cases 3 and 4 developed well after being reconstructed the right pulmonary artery anterior translocation. After the diagnosis of Berry syndrome through cardiac color ultrasound and CT angiography, a primary surgical radical treatment should be performed as soon as possible at an experienced pediatric cardiac center. Although the surgery is high-risk and complex, it is safe and effective.

Objective To observe the clinical effects of the stereotaxic oblique-pulling manipulation under different mechanical parameters in the treatment of patients with lumbar disc herniation,and to explore the muscle-relaxing effects of the stereotaxic oblique-pulling manipulation and the traditional lumbar oblique-pulling manipula-tion in the treatment of lumbar disc herniation under the optimal mechanical parameters.Methods Using a three-factor,three-level orthogonal test method,27 LDH patients included in this study were randomly divided into 9 parameter groups,with 3 patients in each group,and were treated with different parameters of the stereotactic angled wrench method.3 factors were set up for the pressing force,the number of times,and the treatment interval,and each factor consisted of 3 levels,i.e.,pressing force:300～400 N,400～500 N,and 500～600 N;the number of times pressed 3 levels were set up:6 times,9 times,12 times;3 levels of treatment interval:1 day interval,2 days interval,3 days interval.After screening the optimal mechanical parameters through VAS,ODI and FDD evaluation indexes,94 patients were included and randomly divided into two groups;the treatment group was stereotaxic oblique-pulling manipulation under the configuration of optimal mechanical parameters,and the control group was the traditional lumbar oblique-pulling manipulation,and the changes of patients'VAS and ODI scores as well as the thickness of multifidus muscle and cross-sectional area before and after treatment were observed in the treatment of the two groups of patients.Through the comparison of lumbar multifidus muscle between healthy volunteers and patients with lumbar keyboard herniation,the characteristics of lumbar disc herniation multifidus muscle were clarified.The correlation between each observation index and parameter was analyzed by the statistical analysis software SPSS 26.0 to derive the optimal parameters for manipulative treatment.Results Orthogonal test analysis yielded that the order of influence on the efficacy was pressing force>treatment interval>pressing times,and the pressure interval with the best efficacy was:500～600 N,the number of times was 12 times,and the Treatment internal of 2 days.The degree of degeneration of lumbar multifidus muscle in patients with lumbar disc herniation was more obvious compared with that of healthy volunteers,and the difference was stati stically signifi-cant(P<0.05).Observed in both groups of patients with lumbar disc herniation after 6 weeks of treatment time,the VAS and ODI scores of both groups decreased significantly after treatment compared with those before treatment(P<0.05),with greater improvement in the treatment group.The results of the multifidus muscle showed that after treatment,the treatment group could significantly increase the resting thickness,contraction thickness,contraction rate and cross-sectional area of the multifidus muscle had significant changes(P<0.05),in which the contraction thickness,contraction rate before and after the treatment changes were more significant than the control group.Conclusions The stereotaxic oblique-pulling manipulation is effective in the treatment of lumbar disc herniation,in which the manipulation parameter pressure of 500～600 N,the number of presses 12 times,and the treatment interval of 2 days once for the treatment of lumbar disc herniation has better analgesia and improves the dysfunction effect.Compared with the traditional lumbar oblique-pulling manipulation,the stereotaxic oblique-pulling manipulation is better in improving the pain symptoms and dysfunction of patients with lumbar disc hernia-tion,as well as the resting thickness of the multifidus muscle,the contraction thickness,the contraction rate of change,and the cross-sectional area.