ObjectiveTo investigate the potential mechanism of Danggui Buxuetang （DBT） in the treatment of vascular dementia （VAD）. MethodsSixty male SD rats were randomly assigned to the sham-operated group， model group， DBT low-， medium-， and high-dose groups， and the donepezil group. Except for the sham-operated group， rats in all other groups underwent bilateral common carotid artery ligation. After successful modeling， DBT was administered at doses of 9.2， 18.4， 36.8 g·kg^-1 for the low-， medium-， and high-dose groups， respectively， while the donepezil group received 3 mg·kg^-1 donepezil solution by gavage once daily. After 4 consecutive weeks of drug treatment， rats underwent the Morris water maze test， novel object recognition test， Nissl staining to observe hippocampal neurons， and immunofluorescence staining to detect the expression of neuronal nuclear protein （NeuN） in the hippocampus. Western blot was used to assess the expression of PTEN-induced kinase 1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Transmission electron microscopy was used to observe hippocampal neuronal ultrastructure. Real-time PCR was used to detect the expression of NADPH oxidase subunits p22^phox and p47^phox in hippocampal tissues. The levels of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， and total antioxidant capacity were measured to evaluate oxidative stress levels. ResultsIn the Morris water maze test， escape latency changed significantly over time in all groups except the model group. Compared with the sham-operated group， the model group showed significantly prolonged escape latency （P<0.01）. Compared with the model group， rats in the DBT groups and the donepezil group exhibited significantly shorter escape latency （P<0.05， P<0.01）. The number of crossings over the original platform was significantly reduced in the model group compared with the sham-operated group （P<0.01）， whereas rats in the DBT and donepezil groups showed significantly increased platform crossings compared with the model group （P<0.05， P<0.01）. Compared with the sham-operated group， exploration time of new objects was significantly reduced in the model group （P<0.01）. Compared with the model group， exploration time of new objects increased significantly in the medium- and high-dose DBT groups and the donepezil group （P<0.05， P<0.01）， while no significant change was observed in the low-dose DBT group. Compared with the high-dose DBT group， rats in the donepezil group had significantly prolonged escape latency and reduced platform crossings and new-object exploration time （P<0.05）. Nissl staining showed decreased density of healthy neurons in the CA1 and CA3 regions of the hippocampus in the model group， with loss of Nissl bodies and nuclear atrophy or disappearance. In the high-dose DBT group， neuronal density in CA1 and CA3 increased， with neurons arranged closely and displaying normal morphology. Immunofluorescence showed that compared with the sham-operated group， the hippocampal NeuN⁺ cell count in the VAD model group was significantly decreased（P<0.01）， compared with the VAD model group， the hippocampal NeuN⁺ cell count in the high-dose DBT group was significantly increased（P<0.01）. Compared with the sham-operated group， the expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins was significantly increased（P<0.01）， while the expression of Bcl-2 was significantly decreased in the VAD model group（P<0.01）. Compared with the VAD model group， the high-dose DBT group showed significantly decreased expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins（P<0.01）and significantly upregulated Bcl-2 expression（P<0.01）. The medium-dose DBT group exhibited significantly reduced expression of Parkin， LC3Ⅱ， and Bax proteins（P<0.05，P<0.01） and significantly increased Bcl-2 expression（P<0.01）， while no statistically significant differences were observed in the low-dose DBT group. Transmission electron microscopy showed mitochondrial pyknosis， thickened cristae， increased electron density， and the presence of mitochondrial autophagy in the model group. In contrast， hippocampal neurons in the high-dose DBT group contained abundant mitochondria with intact morphology， clear cristae， and uniform matrix. Compared with the sham-operated group， total antioxidant capacity， SOD activity， and GSH levels were significantly decreased， while MDA levels were significantly increased in the model group （P<0.01）. Compared with the model group， total antioxidant capacity and antioxidant levels （SOD， GSH） increased significantly， and MDA decreased significantly in the medium- and high-dose DBT groups （P<0.01）， while no significant changes were observed in the low-dose DBT group. Compared with the sham-operated group， mRNA expression of p22^phox and p47^phox was significantly increased in the model group （P<0.01）. Compared with the model group， expression of p22^phox and p47^phox was significantly decreased in the DBT groups （P<0.05， P<0.01）. ConclusionDBT may exert neuroprotective effects by regulating PINK1/Parkin-mediated mitochondrial autophagy， thereby improving learning and memory abilities and treating VAD.

In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

At present, the treatment of sepsis depends largely on non-specific methods, highlighting an urgent need for novel therapeutic strategies. Stem cells have garnered significant attention in the treatment of various diseases due to their unique biological properties. Stem cells enhance sepsis survival through mechanisms such as reducing bacterial burden, modulating inflammation, and ameliorating organ dysfunction. Recent studies have shown that stem cells can increase the survival rate of sepsis patients through multiple pathways such as reducing the bacterial load of the host, regulating inflammatory homeostasis, and improving multi-organ dysfunction. Their derivatives, exosomes, can also alleviate the imbalanced immune response in sepsis patients. Recent advances in stem cell-based therapies for sepsis were summarized in this paper.

Innovation entities bear primary responsibility for the management of scientific and technological ethics. Understanding the current construction status of the scientific and technological ethical governance capacity among Chinese innovation entities is conducive to grasping effectiveness and shortcomings of scientific and technological ethical governance of innovation entities， providing a scientific basis and practical guidance for innovation entities to fulfill their primary responsibilities better. Based on a questionnaire survey targeting 313 innovation entities， this paper investigated and analyzed the current status and existing challenges of scientific and technological ethical governance capacity among Chinese innovation entities from five aspects. It was found that China has made certain achievements in scientific and technological ethical governance， yet there were still issues such as incomplete construction of regulatory systems， low efficiency of ethical review， unestablished regular education and training systems， and imperfect dynamic monitoring systems for ethical risks. Among these issues， the scientific and technological ethical governance capacity of enterprises was identified as requiring urgent improvement. Additionally， strengthening multi-stakeholder collaboration remained a key challenge in building a collaborative and co-governance system for scientific and technological ethics. Based on these issues identified in the survey， countermeasures and suggestions were proposed from five perspectives， that is， enhancing the capacity in institutional construction， ethical review， value transmission， risk early warning， and collaborative governance of innovation entities on scientific and technological ethical governance. The aim was to provide references for accelerating the construction of the scientific and technological ethical governance system and improving the scientific and technological ethical governance capacity of innovation entities.

ObjectiveTo investigate the regulatory effects and underlying mechanisms of Liuhuang Zhike prescription （LHZK） on blood glucose in type 2 diabetic db/db mice based on the AMP-activated protein kinase/protein kinase B/glycogen synthase kinase-3β （AMPK/Akt/GSK-3β） signaling pathway. MethodsDb/db mice were used as the model animals， and db/m mice served as the blank control. Forty db/db mice were randomly divided into the model group， metformin group （0.14 g·kg^-1）， and low-， medium-， and high-dose （4.11， 8.21， 16.43 g·kg^-1） LHZK groups， with 8 mice in each group. The db/db mice in the metformin and LHZK groups were administered the corresponding drugs by gavage， while the blank control and model groups were given distilled water by gavage once daily for 8 consecutive weeks. Food intake， water consumption， body weight， and fasting blood glucose （FBG） were measured weekly. An automatic biochemical analyzer was used to determine glycated serum protein （GSP）， serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） staining was used to observe pathological morphological changes in the liver and pancreatic tissues. Oil red O staining was used to assess lipid accumulation in liver tissue. The anthrone colorimetric method was used to determine hepatic glycogen content. Real-time quantitative PCR （Real-time PCR） was used to detect the mRNA expression levels of insulin receptor substrate-1 （IRS-1）， Akt2， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6Pase） in liver tissue. Western blot was used to detect the protein expression of AMPKα， phosphorylated AMPKα （p-AMPKα）， GSK-3β， p-GSK-3β， glycogen synthase （GS）， and phosphorylated GS （p-GS） in liver tissue. ResultsCompared with the blank control group， the model group showed significantly increased food intake， water consumption， body weight， FBG， and GSP levels （P<0.01）. Pancreatic islets exhibited marked parenchymal cell hyperplasia and interstitial inflammatory cell infiltration. Liver tissue showed obvious steatosis， accompanied by a compensatory increase in hepatic glycogen content （P<0.01）. Hepatic G6Pase mRNA expression was increased， while IRS-1 and Akt2 mRNA expression levels were significantly decreased （P<0.01）. The p-AMPKα/AMPKα protein expression ratio showed a decreasing trend， whereas the p-GSK-3β/GSK-3β and p-GS/GS protein expression ratios were significantly increased （P<0.01）. Compared with the model group， food intake and water consumption showed decreasing trends in all treatment groups. Food intake was significantly reduced in the low- and high-dose LHZK groups and in the metformin group （P<0.05， P<0.01）， and water consumption was significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. No statistically significant differences in body weight were observed among the LHZK groups， whereas body weight in the metformin group was significantly increased （P<0.05， P<0.01）. FBG showed a decreasing trend in all treatment groups， with significant decreases in the low-dose LHZK group and the metformin group （P<0.05， P<0.01）. GSP levels were significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. Hepatic steatosis and pancreatic pathological injury were alleviated to varying degrees in all treatment groups. Hepatic glycogen content further increased in all treatment groups， with significant increases in the medium- and high-dose LHZK groups （P<0.05）. Real-time PCR results showed that all treatment groups downregulated the mRNA expression of G6Pase and PEPCK in the liver tissues of db/db mice， with significant downregulation of PEPCK mRNA in the low-dose LHZK and metformin groups （P<0.01）. Meanwhile， all treatment groups upregulated IRS-1 and Akt2 mRNA expression， with the most pronounced upregulation observed in the medium-dose LHZK group （P<0.01）. The p-AMPKα/AMPKα protein expression ratio was significantly increased in the low- and medium-dose LHZK groups （P<0.01）. The p-GSK-3β/GSK-3β protein expression ratio was significantly increased in all treatment groups （P<0.05， P<0.01）， whereas the p-GS/GS protein expression ratio was significantly decreased in all treatment groups （P<0.01）. ConclusionLHZK effectively reduces FBG and GSP levels in type 2 diabetic mice and improves hepatic steatosis and pancreatic islet pathological injury. Its hypoglycemic mechanism may be associated with regulation of the AMPK/Akt/GSK-3β signaling pathway and promotion of hepatic glycogen synthesis.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

BACKGROUND:It has been found that mitochondrial function is abnormal in patients with chronic fatigue syndrome,and the administration of coenzymes can improve the symptoms.Warm acupuncture is one of the most important treatments for this disease,but its mechanism of action is unclear. OBJECTIVE:To investigate the effects of warm acupuncture on the phosphatase and tensin inducible kinase 1(PINK1)/Parkin pathway in the skeletal muscle of rats with chronic fatigue syndrome. METHODS:After 3 days of adaptive feeding,32 male Sprague-Dawley rats were randomly divided into normal control,model,warm acupuncture,and coenzyme Q groups with 8 rats in each group.The chronic fatigue syndrome model was established by multiple factors,including swimming exhaustion,chronic immobilization and fasting.After successful modeling,the normal group and the model group were treated with the same fixation and gavage procedures,and the warm acupuncture group was treated with acupuncture at Guanyuan,Zhongwan and Zusanli(bilateral)points,once a day.After the needling was inserted,the moxa pillar was put on the needle handle and ignited,three sessions once.The coenzyme Q group was given 1 mL/kg coenzyme by gavage,once a day for 14 days.The body mass,exhaustive swimming time and food utilization rate during the treatment were recorded.After the treatment,the bilateral gastrocnemius muscles of rats in each group were collected.The pathological morphology of the gastrocnemius muscle was observed by hematoxylin-eosin staining,the mitochondrial morphology and autophagosome of the gastrocnemius muscle were observed by transmission electron microscope.The expression level of microtubule-associated protein light chain 3(LC3)Ⅱ protein in the skeletal muscle was detected by immunohistochemistry.Western blot was used to detect the expression of PINK1,Parkin,LC3 Ⅰ,and LC3 Ⅱ in the skeletal muscle. RESULTS AND CONCLUSION:Compared with the normal group,the gastrocnemius muscle nuclei of the model group were pyknotic,condensed,the number of cells was increased,the cells were arranged disorderly,and the fibers in the gastrocnemius muscle were tightly arranged in the model group.Compared with the model group,the intercellular space became smaller,the nuclei were reduced,and the cell arrangement was orderly in the warm acupuncture group and coenzyme Q group.Compared with the normal group,the skeletal muscle mitochondria in the model group were swollen,fused,and vacuolated seriously,the membrane was partially broken,the matrix was more dissolved,the cristae was broken and disappeared,and autophagy appeared.Compared with the model group,the number of mitochondria increased,the arrangement was relatively neat,mitochondrial vacuolization and rupture of cristae in the gastrocnemius muscle were improved,the membrane structure was relatively intact,and autophagy occurred.Compared with the normal group,the expression of PINK1 protein in the skeletal muscle of the model group was significantly increased(P<0.05),while the expression of Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ protein was slightly upregulated(P>0.05).Compared with the model group,the protein expressions of PINK1,Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ were significantly upregulated in the warm acupuncture and coenzyme Q groups(P<0.05),and the up-regulation was more significant in the warm acupuncture group.To conclude,warm acupuncture can play a role in the treatment of chronic fatigue syndrome by activating the PINK1/Parkin pathway,upregulating LC3 Ⅱ expression,forming mitochondrial autophagosomes,promoting the degradation of damaged mitochondria,and improving mitochondrial quality.