ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

Objective To explore the predictive value of combined detection of serum CXC chemokine lig-and 12(CXCL12),caspase-cleaved cytokeratin 18(CCCK-18)and matrix metalloproteinase-9(MMP-9)for short-term poor prognosis in patients with acute hemorrhagic stroke.Methods A total of 138 patients with a-cute hemorrhagic stroke admitted to a hospital from October 2021 to March 2023 were selected as the study objects.Serum CXCL12,CCCK-18 and MMP-9 levels were detected after admission and before treatment.Pa-tients were followed up for 6 months after treatment and were divided into good prognosis group and poor prognosis group according to the modified Rankin scale score.Clinical data and serum CXCL12,CCCK-18 and MMP-9 levels of the two groups were compared to analyze the factors affecting the short-term poor prognosis of patients with acute hemorrhagic stroke.Receiver operating characteristic(ROC)curve was drawn to evalu-ate the predictive value of single and combined detection of serum CXCL12,CCCK-18 and MMP-9 in patients with acute hemorrhagic stroke.Results Among 138 patients,there were 52 cases in the poor prognosis group and 86 cases in the good prognosis group,and the poor prognosis rate was 37.68%.Serum CXCL12,CCCK-18 and MMP-9 levels,age,blood loss at admission,National Institutes of Health Stroke Scale(NIHSS)score at admission,systolic blood pressure and diastolic blood pressure at admission in the poor prognosis group were higher than those in the good prognosis group.The score of Glasgow Coma Scale(GCS)at admission was lower than that of good prognosis group,and the difference was statistically significant(P<0.05).Multivari-ate Logistic regression analysis showed that high level of serum CXCL12,high level of CCCK-18,high level of MMP-9,older age,large amount of blood loss upon admission,high NIHSS score and high systolic blood pres-sure were all risk factors for short-term poor prognosis of acute hemorrhagic stroke(P<0.05).High GCS score on admission was a protective factor(P<0.05).ROC curve analysis showed that the area under the combined prediction curve of serum CXCL12,CCCK-18 and MMP-9 was higher than that of the single and pairwise combined prediction of each index(P<0.05).Conclusion The combined detection of serum CX-CL12,CCCK-18 and MMP-9 has a good value in predicting the short-term poor prognosis of patients with a-cute hemorrhagic stroke.

Objective To systematically evaluate qualitative studies on the experience of inhalation therapy for patients with chronic obstructive pulmonary disease(COPD),in order to provide a basis for healthcare professionals to optimize the care strategies.Methods A systematic search was conducted for qualitative studies on the experience of inhalation therapy for patients with COPD included in domestic and international databases,with a timeframe from the establishment of the database to September 2024.Literature quality was evaluated using the Australian JBI Centre for Evidence-Based Health Care Literature Quality Assessment Criteria for Qualitative Research,and the results were integrated by a pooled integration approach.Results A total of 12 articles were included,and 84 original findings were extracted and summarized into 10 new categories to form 4 integrated results,including low level of drug literacy,differences in perceived efficacy,multiple medication burdens,and multi-dimensional support for inhalation therapy.Conclusion COPD patients have multiple experiences during inhalation therapy.Medical staff should strengthen drug education,enhance patients'cognition and medication skills,foster a positive treatment attitude,and integrate multiple resources to improve patients'inhalation therapy experience.

Objective To investigate the risk factors of perioperative aspiration to the pregnant women with gestational diabetes mellitus(GDM)and caesarean section,hence to develop a nomogram model for prediction of perioperative aspiration in the pregnant women with caesarean section.Methods A convenience sampling method was used to select a total of 960 pregnant women who had GDM and received caesarean section in our hospital from January 2019 to July 2023.The data obtained from the pregnant women were used as the training set.Further 320 pregnant women who had GDM and received caesarean section in our hospital between August 2023 and December 2024 were assigned as the validation set.Logistic regression was used to analyse the risk factors of perioperative regurgitation and aspiration.A nomogram model of perioperative regurgitation and aspiration for the pregnant women with GDM was established using the R software.The Bootstrap method was adopted to conduct repeated sampling for 1,000 times for model validation.The receiver operating characteristic(ROC)curve and the calibration curve were used to evaluate the reliability and prediction of the model.Results The included predictive variables in the model were:the strict preoperative fasting and water deprivation,general anaesthesia,emergency caesarean section,BMI≥28kg/m2,administration of inhaled anaesthetics,operation time over 1 hour,and administration of prenatal antibiotics.The calibration curves of both the training set and the validation set were found comprehensively consistent with the ideal curve.The areas under the ROC curves of the training set and the validation set were 0.855(95%CI:0.781-0.929)and 0.843(95%CI:0.771-0.915),respectively.Conclusion The predictive variables for perioperative regurgitation and aspiration in the pregnant women with GDM include obesity,strict preoperative fasting and water deprivation,general anaesthesia,emergency caesarean section,administration of inhaled anaesthetics,over 1 hour of operation time and administration of prenatal antibiotics.The nomogram model established in this study has a high accuracy and a high clinical value.

Objective To investigate the predictive value of bone metabolism parameters on cardiac autonomic nervous system function in patients with type 2 diabetes mellitus(T2DM).Methods A total of 328 patients with T2DM hospitalized in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2022 to October 2023.According to the serum 25(OH)D level,all the participants were divided into<10 ng/ml group(n=80),10～20 ng/ml group(n=173),and 20～30 ng/ml group(n=75).Biochemical indicators,bone metabolic parameters,left ventricular mass(LVM)and left ventricular mass index(LVMI)were compared.Time domain indicators ofheart rate variability(HRV)in 24 h holter electrocardiogram,including the global standard deviation of normal sinus RR interval(SDNN),sinus RR interval mean standard deviation(SDANN),and normal continuous sinus RR interval difference root mean square(RMSSD).Meanwhile,adjacent RR interval difference>50 ms as a percentage of the total inter-period(PNN50),HRV triangle index,standard deviation of the difference between the length of the entire adjacent NN interperiod(SDSD),and 24 h holter electrocardiogram HRV time-domain relevant indicators were compared among the three groups.The influence of bone metabolism parameters on cardiac autonomic nervous function and their correlation were analyzed,and the optimal cutting point of cardiac autonomic nervous function was predicted by receiver operating characteristic(ROC)curve.Results SBP,heart rate(HR),FPG,PWV,PTH and β-CTX in groups of 10 ng/ml,10～20 ng/ml and 20～30 ng/ml decreased in turn(P<0.05),while HDL-C,ABI,25(OH)D,Ca2+and PNN50 decreased.Correlation analysis between Spearman and Pearson showed that 25(OH)D was positively correlated with SDNN,HRV triangle index,PNN50 and rMSSD(P<0.01).Logistic regression analysis showed that 25(OH)D,Ca2+and HR were the influencing factors of cardiac autonomic nervous dysfunction in patients with T2DM.The ROC curve analysis showed that the areas under the ROC curve of 25(OH)D,Ca2+and HR were 0.791,0.607 and 0.629,respectively,with sensitivity of 73.4%,53.2%and 38.7%,and specificity of 74.0%,93.6%and 81.4%,respectively.Conclusions 25(OH)D is the influencing factor of cardiac autonomic nervous dysfunction in patients with T2DM,and patients with high degree of deficiency are more prone to cardiac autonomic nervous dysfunction.

Ischemic stroke is a devastating neuro-logical disease worldwide,with high global burden.The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke.After the ictus of brain ischemic attack,cy-tosolic double-stranded DNA(dsDNA)released by necrotic neuronal cells is a potential damage-asso-ciated molecular pattern(DAMP)to activate cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.cGAS-STING sig-naling pathway has emerged as a key player in mi-croglial activation,sterile neuroinflammation,and cell death following ischemic stroke.Targeting this pathway holds promise for developing novel thera-peutics that effectively mitigate neuroinflamma-tion,prevent cell death,and enhance patient out-comes.In this review,we first outline the principal elements of the cGAS-STING signaling cascade,then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke.Then,we outline selec-tive small-molecules modulators that function as cGAS-STING inhibitors and summarize their mecha-nisms to treat Ischemic stroke.Finally,we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.

Objective To investigate the risk factors of perioperative aspiration to the pregnant women with gestational diabetes mellitus(GDM)and caesarean section,hence to develop a nomogram model for prediction of perioperative aspiration in the pregnant women with caesarean section.Methods A convenience sampling method was used to select a total of 960 pregnant women who had GDM and received caesarean section in our hospital from January 2019 to July 2023.The data obtained from the pregnant women were used as the training set.Further 320 pregnant women who had GDM and received caesarean section in our hospital between August 2023 and December 2024 were assigned as the validation set.Logistic regression was used to analyse the risk factors of perioperative regurgitation and aspiration.A nomogram model of perioperative regurgitation and aspiration for the pregnant women with GDM was established using the R software.The Bootstrap method was adopted to conduct repeated sampling for 1,000 times for model validation.The receiver operating characteristic(ROC)curve and the calibration curve were used to evaluate the reliability and prediction of the model.Results The included predictive variables in the model were:the strict preoperative fasting and water deprivation,general anaesthesia,emergency caesarean section,BMI≥28kg/m2,administration of inhaled anaesthetics,operation time over 1 hour,and administration of prenatal antibiotics.The calibration curves of both the training set and the validation set were found comprehensively consistent with the ideal curve.The areas under the ROC curves of the training set and the validation set were 0.855(95%CI:0.781-0.929)and 0.843(95%CI:0.771-0.915),respectively.Conclusion The predictive variables for perioperative regurgitation and aspiration in the pregnant women with GDM include obesity,strict preoperative fasting and water deprivation,general anaesthesia,emergency caesarean section,administration of inhaled anaesthetics,over 1 hour of operation time and administration of prenatal antibiotics.The nomogram model established in this study has a high accuracy and a high clinical value.

Objective To investigate the predictive value of bone metabolism parameters on cardiac autonomic nervous system function in patients with type 2 diabetes mellitus(T2DM).Methods A total of 328 patients with T2DM hospitalized in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2022 to October 2023.According to the serum 25(OH)D level,all the participants were divided into<10 ng/ml group(n=80),10～20 ng/ml group(n=173),and 20～30 ng/ml group(n=75).Biochemical indicators,bone metabolic parameters,left ventricular mass(LVM)and left ventricular mass index(LVMI)were compared.Time domain indicators ofheart rate variability(HRV)in 24 h holter electrocardiogram,including the global standard deviation of normal sinus RR interval(SDNN),sinus RR interval mean standard deviation(SDANN),and normal continuous sinus RR interval difference root mean square(RMSSD).Meanwhile,adjacent RR interval difference>50 ms as a percentage of the total inter-period(PNN50),HRV triangle index,standard deviation of the difference between the length of the entire adjacent NN interperiod(SDSD),and 24 h holter electrocardiogram HRV time-domain relevant indicators were compared among the three groups.The influence of bone metabolism parameters on cardiac autonomic nervous function and their correlation were analyzed,and the optimal cutting point of cardiac autonomic nervous function was predicted by receiver operating characteristic(ROC)curve.Results SBP,heart rate(HR),FPG,PWV,PTH and β-CTX in groups of 10 ng/ml,10～20 ng/ml and 20～30 ng/ml decreased in turn(P<0.05),while HDL-C,ABI,25(OH)D,Ca2+and PNN50 decreased.Correlation analysis between Spearman and Pearson showed that 25(OH)D was positively correlated with SDNN,HRV triangle index,PNN50 and rMSSD(P<0.01).Logistic regression analysis showed that 25(OH)D,Ca2+and HR were the influencing factors of cardiac autonomic nervous dysfunction in patients with T2DM.The ROC curve analysis showed that the areas under the ROC curve of 25(OH)D,Ca2+and HR were 0.791,0.607 and 0.629,respectively,with sensitivity of 73.4%,53.2%and 38.7%,and specificity of 74.0%,93.6%and 81.4%,respectively.Conclusions 25(OH)D is the influencing factor of cardiac autonomic nervous dysfunction in patients with T2DM,and patients with high degree of deficiency are more prone to cardiac autonomic nervous dysfunction.

Objective To systematically evaluate qualitative studies on the experience of inhalation therapy for patients with chronic obstructive pulmonary disease(COPD),in order to provide a basis for healthcare professionals to optimize the care strategies.Methods A systematic search was conducted for qualitative studies on the experience of inhalation therapy for patients with COPD included in domestic and international databases,with a timeframe from the establishment of the database to September 2024.Literature quality was evaluated using the Australian JBI Centre for Evidence-Based Health Care Literature Quality Assessment Criteria for Qualitative Research,and the results were integrated by a pooled integration approach.Results A total of 12 articles were included,and 84 original findings were extracted and summarized into 10 new categories to form 4 integrated results,including low level of drug literacy,differences in perceived efficacy,multiple medication burdens,and multi-dimensional support for inhalation therapy.Conclusion COPD patients have multiple experiences during inhalation therapy.Medical staff should strengthen drug education,enhance patients'cognition and medication skills,foster a positive treatment attitude,and integrate multiple resources to improve patients'inhalation therapy experience.