ObjectiveTo characterize the systemically absorbed components of Zhengqi prescription （ZQP） and investigate its therapeutic effects and mechanisms against cancer-related fatigue （CRF） through an integrated approach of network pharmacology and animal experiments. MethodsThe systemically absorbed components of ZQP were identified by ultra-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS）. Network pharmacology was employed to predict the potential targets and signaling pathways involved in the anti-CRF effects of ZQP. A mouse model of paclitaxel-induced CRF， mimicking breast cancer-related fatigue， was established. Mice were administered different doses of ZQP extract. The therapeutic efficacy was evaluated based on fatigue-related indicators， behavioral test results， and energy metabolism parameters. Western blot analysis was conducted to validate the regulation of core signaling pathways. ResultsA total of 48 systemically absorbed components were identified. Network pharmacology analysis revealed 124 intersecting targets （including Akt1） and implicated signaling pathways such as phosphatidylinositol 3-kinase/protein kinase （PI3K/Akt）. Pharmacodynamic studies with the established CRF model demonstrated that ZQP alleviated fatigue symptoms. Specifically， ZQP-treated mice exhibited increased exhaustive swimming time （P<0.05）， prolonged struggling time in the tail suspension test， and enhanced movement duration and distance in the open field test （P<0.05， P<0.01）. Furthermore， ZQP treatment decreased serum lactate and blood urea nitrogen levels （P<0.05， P<0.01）， increased liver and muscle glycogen content （P<0.05， P<0.01）， and upregulated the expression of phosphorylated （p）-Akt and p-PI3K in the gastrocnemius muscle （P<0.05， P<0.01）. ConclusionZQP exerts significant therapeutic effects on paclitaxel-induced breast cancer-related fatigue by regulating the PI3K/Akt signaling pathway. Furthermore， this study provides a preliminary foundation for subsequent quality control of the formula and further investigation into its mechanism against CRF.

Objective To compare differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects.Methods Kunming mice were randomly divided into eight groups,with 12 mice in each group consisting of equal numbers of males and females.These groups included a normal group,a model group,a positive group,a Angelica sinensis(AS)group,an Angelica sinensis water-soluble(AW)group,an Ethanol extract of Angelicae sinensis(AE)group,and an Angelica sinensis essential oil(AO)group.Except for the normal group,all other groups were established as blood deficiency constipation mouse models through subcutaneous injection of N-acetylphenylhydrazine combined with oral administration of loperamide hydrochloride.On the 7th day of modeling,each group received oral administration of the respective test substance once daily for three consecutive days.General condition and body weight changes of the mice were observed,peripheral blood cells were counted,stool morphology and fecal output were recorded,fecal moisture content and colonic tissue moisture content were determined,small intestine propulsion rate was assessed by a charcoal meal method,and serum levels of β-endorphin(β-EP),cholecystokinin octapeptide(CCK-8),substance P(SP),and vasoactive intestinal peptide(VIP)were determined by ELISA.Differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects were analyzed.Results Compared with the normal group,model group mice showed significantly reduced white blood cell(WBC),red blood cell(RBC),hemoglobin(HGB),hematocrit(HCT),and platelet(PLT)counts,and body weight(P＜0.05 or P＜0.01).Additionally,fecal moisture content,colon moisture content,and small intestine propulsion rate were decreased(P＜0.05 or P＜0.01)and serum CCK-8 and SP levels were also lower(P＜0.01),while serum β-EP and VIP levels increased(P＜0.05).Compared with the model group,AS and AW groups had higher WBC,RBC,HGB,HCT,and PLT counts,defecation volume,fecal moisture content,and colon moisture content(P＜0.05 or P＜0.01).The AE group showed increased WBC,RBC,HGB,HCT,and PLT counts,and colon moisture content(P＜0.05 or P＜0.01),but defecation volume and fecal moisture content were not significantly altered.The AO group exhibited increased fecal moisture content,colon moisture content,and defecation volume(P＜0.05 or P＜0.01),but no significant changes in WBC,RBC,HGB,HCT,and PLT counts.The AE group showed no significant changes in defecation volume,fecal moisture content,and colon moisture content.The AS and AO groups had increased small intestine propulsion rates(P＜0.01),while there was no significant difference in small intestine propulsion rate between the AW and AE groups.The AS group had elevated serum CCK-8 and SP levels(P＜0.01)and decreased serum β-EP and VIP levels(P＜0.01).The AO group had increased serum CCK-8 and SP levels(P＜0.05),but no significant change in serum β-EP and VIP levels.The AW group had decreased serum VIP levels(P＜0.05),but no statistically significant difference in serum CCK-8 and SP levels.Compared with the AS group,the AW group had higher WBC,RBC,HGB,HCT,and PLT counts,while the AO and AE groups had lower levels of these parameters(P＜0.05).Both AW and AO groups had increased fecal moisture content(P＜0.05),and both AW and AE groups had increased colon moisture content(P＜0.05).AO,AE,and AW groups had elevated serum CCK-8 and SP levels and decreased serum β-EP and VIP levels(P＜0.05).In summary,the groups were ordered as follows:AE＞AO＞AS＞AW in terms of blood replenishment,AO＞AS＞AW＞AE in terms of promoting bowel movements,and AO＞AS＞AE＞AW in terms of intestinal motility.Conclusions Angelica sinensis and its components have varying degrees of blood replenishing and bowel-promoting activities.The AE component has strong blood replenishing activity,while the AO component has strong bowel-promoting and defecation-stimulating activity.These findings provide a reference for the development of traditional Chinese medicines based on Angelica sinensis components.

Objective To construct a machine learning prediction model for diabetic kidney disease(DKD)in type 2 diabetes mellitus(T2DM)patients in the plain-sand and loess hilly areas of Gansu Province,and analyze the interpretability of the model.Methods A multi-stage stratified random sampling method was used to collect the data of T2DM patients in the two areas.After key feature screening,eight ML prediction models were constructed for the risk of DKD in the two areas.The receiver operating characteristic(ROC)curve,accuracy and F1 index were used to evaluate the model,and Shapley additive explanation(SHAP)algorithm was used for model interpretation.Results A total of 1599 patients with T2DM were enrolled in this study.After feature screening,ten variables were selected for model construction in the plain-sand areas.Among the eight models,the gradient boosting decision tree(GBDT)model had the highest prediction efficiency.The area under the curve(AUC)of the test dataset was 0.972,the accuracy was 0.949,and the F1 index was 0.884.In the loess hilly region,12 variables were included in the model,and the best model was the random forest(RF).The AUC of the test set was 0.966,the accuracy was 0.951,and the F1 index was 0.861.SHAP analysis showed that in addition to serum creatinine,age,LDL-C,HbA1c,DM duration,serum uric acid and urinary microalbumin were also closely related to the high risk of DKD.Conclusions The GBDT and RF models have good predictive efficiency for the occurrence of DKD in the two areas,which can be used for the screening of DKD high-risk populations and the in-depth exploration of potential risk factors in the two areas.

Background Exposure to ozone (O₃) is closely associated with an increased risk of mortality in the population, but this association exhibits regional heterogeneity, and relevant research in northern and central-western China is limited. Hohhot, as a typical city in the northern and western region, has seen a significant upward trend in O₃ concentrations (an increase of 17.9 μg·m⁻³ in 2020 compared to 2016). Studies targeting this region can fill the regional research gap. Objective To evaluate the health effects of ground-level O₃ exposure on resident mortality in Hohhot from 2018 to 2023. Methods Air quality, meteorological, and mortality data in Hohhot from 2018 to 2023 were collected. A time-series analysis based on Quasi-Poisson generalized additive model (GAM) was employed, controlling for meteorological factors, day-of-week effects, and holiday effects, to assess the impact of O₃ on non-accidental mortality, mortality from circulatory system diseases (CSD), and mortality from respiratory system diseases (RSD). Results From 2018 to 2023, the non-accidental, CSD, and RSD mortalities in Hohhot amounted to 89721, 47394, and 11378 cases, respectively. The daily maximum 8-hour average O₃ concentration (O₃-8 h) was 90.00 μg·m⁻³. According to the Class I limit (100 μg·m⁻³) of GB 3095—2012 Ambient Air Quality Standard, the annual average number of days exceeding the standard was 144 d. For single-day lag effects, O₃ had the strongest health impact on non-accidental mortality and CSD mortality on the current day (lag0), with effect sizes of 0.78% (95%CI: 0.33%, 1.24%) and 1.10% (95%CI: 0.50%, 1.71%), respectively. The strongest impact on RSD mortality occurred on the second day (lag2), with an effect size of 1.61% (95%CI: 0.61%, 2.62%). The subgroup analyses showed that for every 10 μg·m⁻³ increase in O₃-8 h concentration, the risk of non-accidental mortality in females increased by 0.70% (95%CI: 0.01%, 1.41%); for CSD mortality, the risk in males and individuals aged ≥65 years increased by 0.73% (95%CI: 0.01%, 1.47%) and 0.76% (95%CI: 0.13%, 1.39%), respectively. During the warm season, statistically significant risks were observed for non-accidental, CSD, and RSD mortalities, with increases of 1.07% (95%CI: 0.54%, 1.60%), 1.31% (95%CI: 0.59%, 2.04%), and 2.27% (95%CI: 1.07%, 3.49%), respectively. In the two-pollutant models incorporating sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), particulate matter with an aerodynamic diameter of 10 micrometers or less (PM₁₀), and fine particulate matter (PM_2.5), the effect estimates (excess risk) of O₃ remained stable and statistically significant (P<0.05), indicating model robustness. Conclusion Ground-level O₃ exposure in Hohhot increases mortalities due to non-accidental causes, CSD, and RSD, with more pronounced effects during the warm season. Females and individuals aged ≥65 years may be susceptible populations. Therefore, relevant authorities should prioritize the potential health risks of O₃ exposure, particularly to vulnerable groups, and promote targeted prevention and control strategies.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective To construct a machine learning prediction model for diabetic kidney disease(DKD)in type 2 diabetes mellitus(T2DM)patients in the plain-sand and loess hilly areas of Gansu Province,and analyze the interpretability of the model.Methods A multi-stage stratified random sampling method was used to collect the data of T2DM patients in the two areas.After key feature screening,eight ML prediction models were constructed for the risk of DKD in the two areas.The receiver operating characteristic(ROC)curve,accuracy and F1 index were used to evaluate the model,and Shapley additive explanation(SHAP)algorithm was used for model interpretation.Results A total of 1599 patients with T2DM were enrolled in this study.After feature screening,ten variables were selected for model construction in the plain-sand areas.Among the eight models,the gradient boosting decision tree(GBDT)model had the highest prediction efficiency.The area under the curve(AUC)of the test dataset was 0.972,the accuracy was 0.949,and the F1 index was 0.884.In the loess hilly region,12 variables were included in the model,and the best model was the random forest(RF).The AUC of the test set was 0.966,the accuracy was 0.951,and the F1 index was 0.861.SHAP analysis showed that in addition to serum creatinine,age,LDL-C,HbA1c,DM duration,serum uric acid and urinary microalbumin were also closely related to the high risk of DKD.Conclusions The GBDT and RF models have good predictive efficiency for the occurrence of DKD in the two areas,which can be used for the screening of DKD high-risk populations and the in-depth exploration of potential risk factors in the two areas.

Objective To compare differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects.Methods Kunming mice were randomly divided into eight groups,with 12 mice in each group consisting of equal numbers of males and females.These groups included a normal group,a model group,a positive group,a Angelica sinensis(AS)group,an Angelica sinensis water-soluble(AW)group,an Ethanol extract of Angelicae sinensis(AE)group,and an Angelica sinensis essential oil(AO)group.Except for the normal group,all other groups were established as blood deficiency constipation mouse models through subcutaneous injection of N-acetylphenylhydrazine combined with oral administration of loperamide hydrochloride.On the 7th day of modeling,each group received oral administration of the respective test substance once daily for three consecutive days.General condition and body weight changes of the mice were observed,peripheral blood cells were counted,stool morphology and fecal output were recorded,fecal moisture content and colonic tissue moisture content were determined,small intestine propulsion rate was assessed by a charcoal meal method,and serum levels of β-endorphin(β-EP),cholecystokinin octapeptide(CCK-8),substance P(SP),and vasoactive intestinal peptide(VIP)were determined by ELISA.Differences in the pharmacological activities of Angelica sinensis and its components on hematopoietic and laxative effects were analyzed.Results Compared with the normal group,model group mice showed significantly reduced white blood cell(WBC),red blood cell(RBC),hemoglobin(HGB),hematocrit(HCT),and platelet(PLT)counts,and body weight(P＜0.05 or P＜0.01).Additionally,fecal moisture content,colon moisture content,and small intestine propulsion rate were decreased(P＜0.05 or P＜0.01)and serum CCK-8 and SP levels were also lower(P＜0.01),while serum β-EP and VIP levels increased(P＜0.05).Compared with the model group,AS and AW groups had higher WBC,RBC,HGB,HCT,and PLT counts,defecation volume,fecal moisture content,and colon moisture content(P＜0.05 or P＜0.01).The AE group showed increased WBC,RBC,HGB,HCT,and PLT counts,and colon moisture content(P＜0.05 or P＜0.01),but defecation volume and fecal moisture content were not significantly altered.The AO group exhibited increased fecal moisture content,colon moisture content,and defecation volume(P＜0.05 or P＜0.01),but no significant changes in WBC,RBC,HGB,HCT,and PLT counts.The AE group showed no significant changes in defecation volume,fecal moisture content,and colon moisture content.The AS and AO groups had increased small intestine propulsion rates(P＜0.01),while there was no significant difference in small intestine propulsion rate between the AW and AE groups.The AS group had elevated serum CCK-8 and SP levels(P＜0.01)and decreased serum β-EP and VIP levels(P＜0.01).The AO group had increased serum CCK-8 and SP levels(P＜0.05),but no significant change in serum β-EP and VIP levels.The AW group had decreased serum VIP levels(P＜0.05),but no statistically significant difference in serum CCK-8 and SP levels.Compared with the AS group,the AW group had higher WBC,RBC,HGB,HCT,and PLT counts,while the AO and AE groups had lower levels of these parameters(P＜0.05).Both AW and AO groups had increased fecal moisture content(P＜0.05),and both AW and AE groups had increased colon moisture content(P＜0.05).AO,AE,and AW groups had elevated serum CCK-8 and SP levels and decreased serum β-EP and VIP levels(P＜0.05).In summary,the groups were ordered as follows:AE＞AO＞AS＞AW in terms of blood replenishment,AO＞AS＞AW＞AE in terms of promoting bowel movements,and AO＞AS＞AE＞AW in terms of intestinal motility.Conclusions Angelica sinensis and its components have varying degrees of blood replenishing and bowel-promoting activities.The AE component has strong blood replenishing activity,while the AO component has strong bowel-promoting and defecation-stimulating activity.These findings provide a reference for the development of traditional Chinese medicines based on Angelica sinensis components.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective: To propose updates and amendments for the nitroglycerin tablets quality in the Chinese pharmacopoeia 2020 due to the failure of effective separation of 4 known impurities and nonseparation of free nitrate ion and excipients.
Methods: Related substances were analyzed using gradient elution by HPLC, and free nitrate ion was determined on SAX column by different HPLC method.
Results: Using the improved method to test the related substances and free nitrate ion of nitroglycerin tablets,the content of the maximum individual impurity were not more than 0.5%, the total content was not more than 2.4% and the content of free nitrate ion was not more than 6.3%.
Conclusion: The improved method is accurate and feasible. It provided a reference for the updates and amendments of the quality standard of nitroglycerin tablets in the Chinese Pharmacopoeia 2020.