Tumor is the result of long-term and unlimited proliferation of cells. Tumor cells adjust various metabolic fluxes to meet increased bioenergy and biosynthetic requirements. Serine is one of the eight non-essential amino acids in the human body. It plays an important role in a variety of physiological activities and can provide one carbon unit, glycine, etc. for cell proliferation. Serine hydroxymethyltransferase (SHMT) is a key enzyme that catalyzes the conversion of glycine and serine. It is highly expressed in a variety of tumors and is a potential target for anti-tumor drugs. This article focuses on the potential of SHMT as a new target for cancer treatment and the preliminary application of its inhibitors in preclinical studies of tumors, providing reference for the development of new targeted drugs for tumors.

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg^-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L^-1), a specific TLR4 blocker, against S1 (10 µmol·L^-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL^-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

OBJECTIVE To construct a predictive model for timely medication retrieval of outpatients， accurately identify high-risk patients with delayed medication retrieval， and provide data support for the development of differentiated registration strategies and resource optimization allocation in smart pharmacies. METHODS Based on 680 568 valid outpatient prescription records from January to March 2025 at the First Affiliated Hospital of Xi’an Jiaotong University， a dual-clustering analysis was conducted using K-means algorithm and Gaussian mixture model （GMM）. An adaptive threshold for medication retrieval time difference was determined by combining contour coefficients， and “timely medication retrieval” and “delayed medication retrieval” were divided to construct binary objective variables； six types of features were screened through a multi-method fusion strategy； the performance of 6 kinds of base learners and 4 kinds of ensemble learning models were evaluated from three dimensions： discrimination， overall performance， and calibration， and explanatory analysis of the models were conducted. RESULTS The results of the dual-clustering analysis showed that the silhouette coefficient of GMM was better than K-means （0.702 4 vs. 0.698 8）， and the final adaptive threshold was determined to be 49.82 min. Among the prescriptions included， 74.99% were for timely medication retrieval and 25.01% were for delayed medication retrieval. Among the 10 candidate models， the Stacking model performed the best， with an area under the test set curve of 0.954 4， F1 score of 0.942 4， accuracy of 0.911 5， Brier score of 0.066， and good discrimination and calibration. The explanatory analysis results of the model showed that its predictions were driven by multiple factors such as patient historical behavior， and diagnostic related characteristics. CONCLUSION This study constructed a timely medication retrieval prediction model for outpatients based on a two-stage adaptive threshold ensemble learning algorithm， which has high accuracy and stability， and can achieve dynamic judgment of patient medication retrieval behavior.

Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.

Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.

Background::High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response. Methods::We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes.Results::High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m 2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 years, with anti-Mullerian hormone >1.395 ng/mL, and the first time for IVF. Conclusions::High BMI was related to poor IVF/ICSI outcomes in women with a normal ovarian response, and CLBR declined with increasing BMI, partly due to suppressed endometrial receptivity. A high BMI had the most negative effect on young women with anticipated positive prognoses.

Objective:To evaluate the prevalence of euthyroid sick syndrome(ESS)in sepsis patients and to explore its influencing factors.Methods:In the study,365 patients diagnosed with sepsis in the emergency critical care department of Shanghai First People's Hospital from January 2017 to January 2023 were retrospectively enrolled.The patients were divided into ESS and non-ESS groups based on whether the patients were complicated with ESS.Baseline variables and relevant clinical data of the enrolled pa-tients were collected.The prevalence of ESS in sepsis patients and its influencing factors were evaluated by multivariate Logistic regression analysis,and the 30-day survival rates were compared between the two groups.The optimal cutoff value for free triiodothyronine(FT3)was explored to predict death in the pa-tients with sepsis.Results:There were 103 sepsis patients with ESS,accounting for 28.2％of the total cases.The severity of sepsis in ESS group was significantly higher than that in non-ESS group(P＜0.05).The acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score and sequential organ failure assessment(SOFA)score of ESS group were significantly higher than those of non-ESS group(P＜0.05).C-reactive protein(CRP),procalcitonin(PCT),serum amyloid A(SAA)and interleu-kin-6(IL-6)in ESS group were higher than those in non-ESS group.total cholesterol(TC)and high-den-sity liptein cholesterol(HDL-C)in ESS group were lower than those in non-ESS group,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that PCT,IL-6,CRP,SAA and activated partial thromboplatin time(APTT)were independent risk factors for ESS in the sepsis patients(OR values were 1.105,1.006,1.005,1.009 and 1.033,respectively;95％CI were 1.044-1.170,1.001-1.012,1.001-1.009,1.005-1.014,1.004-1.062,respec-tively,P＜0.05).The 30-day survival rate in ESS group was significantly lower than that in non-ESS group,the Long-rank chi-square test value was 16.611,and the difference was statistically significant(P＜0.05).The receiver operation characteristic area under the curve(AUCROC)of FT3 predicted death in the patients with sepsis was 0.924(95％CI 0.894-0.954).The serum FT3 cutoff point was 3.705 pmol/L,the specificity was 0.868,and the sensitivity was 0.950.Conclusion:In this study,the inci-dence of ESS in sepsis patients was determined to be 28.2％with poor prognosis.The results showed that PCT,IL-6,CRP,SAA and APTT were independent risk factors for ESS in sepsis patients,while HDL-C was a protective factor(P＜0.05).FT3 is a novel potential biomarker for predicting death in patients with sepsis.

Objective To analyze the acupoint selection rule of acupuncture and moxibustion in the treatment of gastrointestinal dysfunction associated with sepsis,thereby providing a reference for clinical treatment.Methods A systematic search was conducted in several databases,including China national knowledge infrastructure(CNKI),China Science Periodical Database,Chinese Science and Technology Journal Database,Chinese Biomedical literature database(CBM),Wanfang Data,and VIP Database,from the inception of the databases until September 30,2023.The collected literature was organized in an Excel database and subjected to descriptive analysis.Association rule analysis and cluster analysis were performed using SPSS 26.0 and SPSS Modeler 18.0 software.Results Finally,35 acupuncture and moxibustion prescriptions in 35 articles were selected for frequency statistics.The results showed 33 acupoints were used to treat gastrointestinal dysfunction in sepsis,with an overall frequency of use of 176 acupoints.The top 10 acupoints used by acupuncture and moxibustion for the treatment of gastrointestinal dysfunction in sepsis from high to low were Zusanli,Tianshu,Shangjuxu,Zhongwan,Neiguan,Xiajuxu,Guanyuan,Qihai,Shangwan,Xiawan.The top 3 were Zusanli(16.5%),Tianshu(13.6%),Shangjuxu(11.9%).The most commonly used meridians were the Foot Yangming Stomach Meridian(52.8%),Ren Meridian(23.9%),and Foot Taiyin Spleen Meridian(8.0%).The main sites for acupoint selection were the lower limbs(44.9%)and abdomen(41.5%).The most commonly used acupoints were combined acupoints below specific acupoints(35.2%),followed by recruited acupoints(27.8%).The results of high-frequency acupoint correlation analysis showed that the acupoints with the highest comprehensive support were Zusanli,Tianshu,Zhongwan,and Shangjuxu.Cluster analysis identified 5 effective clusters(Quchi acupoint-Sanyinjiao acupoint-Neiting acupoint-Daheng acupoint-Jiaji acupoint-Yinlingquan acupoint-Shangwan acupoint-Xiawan acupoint,Guanyuan acupoint-Qihai acupoint-Neiguan acupoint-Xiajuxu acupoint,Tianshu acupoint-Shangjuxu acupoint,Zhongwan acupoint,Zusanli acupoint)and 4 commonly used acupoint combinations(Guanyuan acupoint-Qihai acupoint-Neiguan acupoint-Xiajuxu acupoint,Tianshu acupoint-Shangjuxu acupoint,Zhongwan acupoint,Zusanli acupoint).Conclusions Acupuncture treatment for gastrointestinal dysfunction in sepsis is mainly based on the treatment of"spleen and stomach",with local acupoint selection and acupoint selection along the meridian as the main approach.It emphasizes the application of specific acupoints,especially the Xiahe and Mu acupoints.

Objective:To summarize evidence for physical activity management in cancer patients based on the Joanna Briggs Institute (JBI) approach for evidence synthesis in health care, providing a scientific basis for the clinical standardization of physical activity management in cancer patients.Methods:Literature was searched according to the "6S" pyramid model of evidence, using BMJ Best Practice, UpToDate, JBI Evidence-Based Practice Database, Cochrane Library, global guideline websites, professional cancer association websites, and relevant Chinese and English databases for all evidence regarding physical activity in cancer patients. The search covered the period from February 13, 2018, to February 13, 2023. Guided by the JBI approach for evidence synthesis, two researchers independently evaluated the quality of the literature and extracted relevant evidence in accordance with clinical scenarios.Results:Thirty articles were included, comprising two guidelines, three expert consensuses, one evidence summary, 21 systematic reviews, and three randomized controlled trials. A total of 29 best evidence points were summarized in six aspects: benefits of physical activity, physically active people, pre-activity assessment, implementation of physical activity programs, safety monitoring of physical activity, and ongoing support strategies.Conclusions:This study supplements and updates 15 pieces of evidence based on existing evidence, ultimately forming a best evidence summary for the management of physical activity in cancer patients, providing evidence-based support for clinical management. Most evidence comes from international studies. It is recommended that Chinese researchers consider the activity ability and willingness of cancer patients when applying these findings in future research, and consider the specific clinical context, or conduct foundational research to further validate the evidence, to comprehensively improve the quality of life of cancer patients.