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

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.

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.

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.

Objective To investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

Acute kidney injury(AKI)is a common perioperative complication,which is associated with an increased incidence rate of other postoperative complications and death risk of the patients.Remote ischemic preconditioning(RIPC)performs multiple transient ischemia/reperfusion cycles at remote sites far from the target organs to enhance the tolerance of target organs to oxidative stress.A large number of animal experiments have shown that RIPC can improve kidney function,alleviate AKI,and increase the survival rate of AKI patients.However,there is still controversy about the mechanism of RIPC in alleviating AKI in clinical studies.In this article,the research progress on the role and mechanism of RIPC in renal protection in recent years is reviewed,in order to provide a reference for further exploration of perioperative renal protection strategies and mechanisms.

Objective To investigate the correlation between serum nickel-like protein(Metrnl)level and glycolipid metabolism and inflammatory state in patients with T2DM complicated with abdominal obesity.Methods One hundred and twenty-four T2DM patients and 140 non-diabetic controls who were hospitalized in Gansu Provincial People's Hospital from May to September 2022 were selected and divided into T2DM combined abdominal obesity group(T2DM+AO,n=81),T2DM group(n=43),abdominal obesity group(AO,n=69)and normal control group(NC,n=71)according to whether they suffered from T2DM and abdominal obesity.ELISA method was used to determine the levels of serum Metrnl,IL-4 and IL-13.The correlation between serum Metrnl and the indicators of glucose and lipid metabolism,WC,BMI,VFA,FPG,HbA1c,TC,TG,LDL-C,HDL-C and the indicators of inflammatory state,IL-4 and IL-13 were analyzed.Results Compared with NC group,serum Metrnl levels in T2DM group,AO and T2DM+AO group were decreased(P＜0.05).Serum Metrnl was negatively correlated with WC,BMI,VFA,FPG,HbA1c,TG,IL-4,IL-13(P＜0.01),and positively correlated with HDL-C(P＜0.05).Age,WC,BMI and IL-4 were the influencing factors of Metrnl.WC,VFA,FPG and Metrnl were the influencing factors of T2DM combined with abdominal obesity.The ROC curve showed that serum Metrnl had a sensitivity of 82.5%and a specificity of 93.8%for the diagnosis of T2DM with abdominal obesity.Conclusions Serum Metrnl in T2DM patients with abdominal obesity is significantly reduced,and is closely related to glucose and lipid metabolism and inflammatory status.Serum Metrnl may be a novel biomarker factor for T2DM complicated with abdominal obesity.

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.