Objective To analyze the procurement data of lipid-lowering drugs in hospitals at different levels in Jiangsu Province from October 2019 to September 2023,to evaluate the impact of the volume-based procurement(VBP)policy,and to provide references for clinical rational drug use and healthcare policy optimization.Methods Based on procurement data from the Jiangsu Provincial Health Information Center,statistical analyses of procurement expenditures,defined daily doses(DDDs),and defined daily cost(DDC)were conducted.Mixed-effects models were applied to assess changes in procurement expenditures,DDDs,and DDC before and after VBP implementation.Results From 2019 to 2023,statins dominated the market in Jiangsu Province,with rosuvastatin recording the highest DDDs(748 million).Statins,traditional Chinese medicines,and cholesterol absorption inhibitors ranked highest in procurement expenditures.Tertiary hospitals accounted for the largest share of usage(47.6%)and expenditures(55.8%),while secondary hospitals had the lowest DDC(1.22 yuan)and tertiary hospitals the highest(1.89 yuan).Post-VBP,procurement expenditures and DDC decreased by 53.9%and 35.4%,respectively.Primary hospitals showed the largest expenditure reduction(61.6%),and secondary hospitals exhibited the greatest DDC decline(53.9%).DDDs increased significantly in primary care settings(e.g.,pitavastatin surged by 239.79%in secondary hospitals),while tertiary hospitals saw reduced usage of some drugs(e.g.,amlodipine/atorvastatin decreased by 7.34%).Mixed-effects models confirmed that VBP significantly reduced expenditures(OR=-1.07,P<0.01)and DDC(OR=-2.70,P<0.01)while indirectly lowering prices of non-VBP drugs.After covariate adjustment,expenditure reductions for rosuvastatin and atorvastatin narrowed,ezetimibe expenditures increased(OR=0.13,P<0.01),and pitavastatin usage declined(OR=-0.10,P<0.01).Changes in amlodipine/atorvastatin and ezetimibe lacked statistical significance due to short VBP implementation periods.Tertiary hospitals demonstrated the strictest policy adherence,with the largest expenditure and DDC reductions(P<0.01).Subgroup analysis revealed that the policy did not significantly affect clinical demand(DDDs)in hospitals at different levels,though it was considered to have triggered adjustments in medication structure.Conclusion Jiangsu's lipid-lowering drug structure aligns with guidelines(statin-based,moderate-intensity preference).VBP effectively reduced costs,with tertiary hospitals prioritizing originator-to-generic substitution and primary hospitals reflecting cost-control and demand variations.Confounding factors influenced policy evaluation.The study recommends continuous monitoring and policy optimization to enhance procurement efficiency,ensure rational clinical use,and sustain cost savings,providing insights for further healthcare reform.

Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.

Objective To establish dynamic nomogram models for postoperative recurrence and survival risk of patients with AFP-negative hepatocellular carcinoma(ANHC)based on multimodal clinical data,to identify ANHC-specific prognostic biomarker combinations by integrating tumor biological characteristics and treatment response parameters through machine learning,and to provide an individualized risk assessment tool for overcoming the limitations of traditional serum biomarkers.Methods A retrospective analysis was performed for 421 ANHC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from April 2012 to December 2018,and they were randomly divided into training group with 210 patients and validation group with 211 patients.The univariate and multivariate Cox proportional-hazards regression models were used to identify independent prognostic factors and establish a nomogram model,and the receiver operating characteristic(ROC)curve,the calibration curve,and the decision curve analysis were used to assess the performance of the model.Related indicators were measured,including prealbumin(PA),white blood cell count(WBC),tumor size,and microvascular invasion.The chi-square test or the Fisher's exact test was used for comparison of categorical variables between two groups,and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous variables between two groups.Results The multivariate analysis showed that multiple tumors(hazard ratio[HR]=3.30,P<0.001),WBC(HR=1.05,P=0.005),blood glucose(HR=1.15,P=0.026),CA19-9(HR=1.17,P=0.005),and tumor size(HR=1.17,P<0.001)were independent risk factors for disease-free survival(DFS),while PA(HR=0.99,P=0.022)was a protective factor.Incomplete tumor capsule(HR=0.60,P=0.009),age(HR=1.02,P=0.035),prothrombin time(PT)(HR=1.27,P=0.023),CA19-9(HR=1.01,P<0.001),and tumor size(HR=1.15,P<0.001)were independent risk factors for overall survival(OS).The DFS nomogram achieved an AUC of 0.74(95%confidence interval[CI]:0.64-0.84)in the training group and 0.67(95%CI:0.57-0.77)in the validation group,while the OS nomogram had an AUC of 0.76(95%CI:0.64-0.88)and 0.73(95%CI:0.60-0.87),respectively.The calibration curve and the decision curve analysis showed that the models had good predictive accuracy and clinical practicability.Conclusion Preoperative indicators,including tumor number,PA,WBC,and tumor size,can effectively predict postoperative recurrence in ANHC patients,while tumor capsule integrity,age,and PT are significantly associated with OS.The nomogram models established have good performance and can provide a basis for individualized prognostic assessment.

Objective To analyze the procurement data of lipid-lowering drugs in hospitals at different levels in Jiangsu Province from October 2019 to September 2023,to evaluate the impact of the volume-based procurement(VBP)policy,and to provide references for clinical rational drug use and healthcare policy optimization.Methods Based on procurement data from the Jiangsu Provincial Health Information Center,statistical analyses of procurement expenditures,defined daily doses(DDDs),and defined daily cost(DDC)were conducted.Mixed-effects models were applied to assess changes in procurement expenditures,DDDs,and DDC before and after VBP implementation.Results From 2019 to 2023,statins dominated the market in Jiangsu Province,with rosuvastatin recording the highest DDDs(748 million).Statins,traditional Chinese medicines,and cholesterol absorption inhibitors ranked highest in procurement expenditures.Tertiary hospitals accounted for the largest share of usage(47.6%)and expenditures(55.8%),while secondary hospitals had the lowest DDC(1.22 yuan)and tertiary hospitals the highest(1.89 yuan).Post-VBP,procurement expenditures and DDC decreased by 53.9%and 35.4%,respectively.Primary hospitals showed the largest expenditure reduction(61.6%),and secondary hospitals exhibited the greatest DDC decline(53.9%).DDDs increased significantly in primary care settings(e.g.,pitavastatin surged by 239.79%in secondary hospitals),while tertiary hospitals saw reduced usage of some drugs(e.g.,amlodipine/atorvastatin decreased by 7.34%).Mixed-effects models confirmed that VBP significantly reduced expenditures(OR=-1.07,P<0.01)and DDC(OR=-2.70,P<0.01)while indirectly lowering prices of non-VBP drugs.After covariate adjustment,expenditure reductions for rosuvastatin and atorvastatin narrowed,ezetimibe expenditures increased(OR=0.13,P<0.01),and pitavastatin usage declined(OR=-0.10,P<0.01).Changes in amlodipine/atorvastatin and ezetimibe lacked statistical significance due to short VBP implementation periods.Tertiary hospitals demonstrated the strictest policy adherence,with the largest expenditure and DDC reductions(P<0.01).Subgroup analysis revealed that the policy did not significantly affect clinical demand(DDDs)in hospitals at different levels,though it was considered to have triggered adjustments in medication structure.Conclusion Jiangsu's lipid-lowering drug structure aligns with guidelines(statin-based,moderate-intensity preference).VBP effectively reduced costs,with tertiary hospitals prioritizing originator-to-generic substitution and primary hospitals reflecting cost-control and demand variations.Confounding factors influenced policy evaluation.The study recommends continuous monitoring and policy optimization to enhance procurement efficiency,ensure rational clinical use,and sustain cost savings,providing insights for further healthcare reform.

Objective To establish dynamic nomogram models for postoperative recurrence and survival risk of patients with AFP-negative hepatocellular carcinoma(ANHC)based on multimodal clinical data,to identify ANHC-specific prognostic biomarker combinations by integrating tumor biological characteristics and treatment response parameters through machine learning,and to provide an individualized risk assessment tool for overcoming the limitations of traditional serum biomarkers.Methods A retrospective analysis was performed for 421 ANHC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from April 2012 to December 2018,and they were randomly divided into training group with 210 patients and validation group with 211 patients.The univariate and multivariate Cox proportional-hazards regression models were used to identify independent prognostic factors and establish a nomogram model,and the receiver operating characteristic(ROC)curve,the calibration curve,and the decision curve analysis were used to assess the performance of the model.Related indicators were measured,including prealbumin(PA),white blood cell count(WBC),tumor size,and microvascular invasion.The chi-square test or the Fisher's exact test was used for comparison of categorical variables between two groups,and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous variables between two groups.Results The multivariate analysis showed that multiple tumors(hazard ratio[HR]=3.30,P<0.001),WBC(HR=1.05,P=0.005),blood glucose(HR=1.15,P=0.026),CA19-9(HR=1.17,P=0.005),and tumor size(HR=1.17,P<0.001)were independent risk factors for disease-free survival(DFS),while PA(HR=0.99,P=0.022)was a protective factor.Incomplete tumor capsule(HR=0.60,P=0.009),age(HR=1.02,P=0.035),prothrombin time(PT)(HR=1.27,P=0.023),CA19-9(HR=1.01,P<0.001),and tumor size(HR=1.15,P<0.001)were independent risk factors for overall survival(OS).The DFS nomogram achieved an AUC of 0.74(95%confidence interval[CI]:0.64-0.84)in the training group and 0.67(95%CI:0.57-0.77)in the validation group,while the OS nomogram had an AUC of 0.76(95%CI:0.64-0.88)and 0.73(95%CI:0.60-0.87),respectively.The calibration curve and the decision curve analysis showed that the models had good predictive accuracy and clinical practicability.Conclusion Preoperative indicators,including tumor number,PA,WBC,and tumor size,can effectively predict postoperative recurrence in ANHC patients,while tumor capsule integrity,age,and PT are significantly associated with OS.The nomogram models established have good performance and can provide a basis for individualized prognostic assessment.

Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

Background: Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy. Raw pieces of Rhei Radix et Rhizoma (RP) are known for their strong laxative effects, often accompanied by side effects, while steamed Rhei Radix et Rhizoma pieces (SP) possess a milder laxative effect and are widely used clinically. However, there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness, particularly from a bioavailability perspective. Objective: This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics, tissue distribution, and excretion assays. Methods: An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites. Pharmacokinetic, tissue distribution, and excretion assays were conducted in constipation rats following oral administration of RP and SP. Blood, tissue, urine, and fecal samples were collected and analyzed to compare the absorption, distribution, metabolism, and excretion profiles of anthraquinones, highlighting differences in bioavailability and safety between RP and SP. Results: Compared with the RP group, the SP group showed significantly reduced area under the plasma concentration-time curve, mean residence time, and half-life time values for rhein-8-O-β-D-glucopyranoside, rhein, emodin, aloe-emodin, and their glucuronide metabolites. The clearance values were significantly increased in the SP group. These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP. Additionally, these components were primarily distributed in the large intestine, where they exerted their laxative effects. Glucuronide metabolites were mainly excreted through urination, while prototype components were excreted in both urine and feces. Notably, the cumulative excretion of aloe-emodin, emodin, rhein, and their glucuronide metabolites was significantly higher in both urine and feces after SP administration, indicating that SP enhances the excretion of these components compared with RP. Conclusion: The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion, demonstrating that the steaming process significantly promotes the elimination of key components. This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma, offering a scientific basis for the improved safety and clinical use of SP. These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines. This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.