BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions. Mitochondria are vital organelles that function in diverse metabolic processes in the body, including redox reactions, lipid metabolism, and cell death. Mitophagy, a specific form of autophagy for damaged mitochondria, plays a critical role in the pathophysiology of liver diseases. In this review, we explain in detail the roles of the Nrf2 signaling pathway and mitophagy, and the relationship between them, in various hepatic diseases (nonalcoholic fatty liver disease, viral hepatitis, alcoholic liver disease, drug-induced liver injury, autoimmune hepatitis, hepatic ischemia‒reperfusion injury, and liver cancer). We also offer some potential insights and treatments relevant to clinical applications.
Humans ; NF-E2-Related Factor 2/metabolism* ; Mitophagy/physiology* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; Liver Diseases/etiology* ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Non-alcoholic Fatty Liver Disease ; Liver Neoplasms

Objective:To explore the genetic basis of eighteen patients with tetrahydrobiopterin deficiency (BH4D) from Gansu Province.Methods:Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing.Results:All of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c. 259C>T (34.38%) and c. 286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 259C>T was classified as a pathogenic variant, whilst the c. 286G>A, c. 166G>A, c. 200C>T, c. 272A>G, c. 402A>C, c. 421G>T, c. 84-291A>G and c. 317C>T were classified as likely pathogenic variants. A novel c. 289_290insCTT variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3+ PP4). The two variants (c.478C>T and c. 665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:Genetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.

Objective To analyze the effect of luteinizing hormone (LH) change amplitude in follicular phase on ovarian response and pregnancy outcome after fresh embryo transfer cycle in infertility patients with normal ovarian function during controlled ovarian hyperstimulation (COH) with antagonist protocol. Methods A total of 277 infertility patients who underwent in vitro fertilization and embryo transfer (IVF-ET) in the Center for Reproductive Medicine of this hospital from January 2019 to December 2021 were se-lected.Patients were divided into the high LH group (n=91),medium LH group (n=93) and low LH group (n=93) according to the tertiles of changes between LH level on the fourth day of COH and basal LH level before COH administration.The basic clinical features,use of exogenous gonadotropin (Gn) during COH, hormone levels at different periods,indexes of ovarian response,laboratory outcomes and pregnancy outcomes during fresh embryo transfer cycle were compared among all groups.Results There was no significant differ-ence in age,infertility duration,infertility types,basal follicle stimulating hormone (FSH),estradiol and tes-tosterone levels among the three groups (P>0.05).The duration of use of Gn in the high LH group was the shortest,the total amount and initiation dose of Gn was the smallest,and the estradiol level,ovarian sensitivity index (OSI),numbers of oocytes,metaphase Ⅱ(MII) oocytes,diprokaryotic fertilization,embryo formation and high-quality embryos were the highest after exogenous Gn stimulation,and the differences were statisti-cally significant compared with the other two groups (P<0.016).There was no significant difference in the clinical pregnancy rate,biochemical pregnancy rate and early miscarriage rate during fresh embryo transfer cy-cle among the three groups (P>0.05).Conclusion The infertility patients with normal ovarian function who have a large decrease in LH level during COH with antagonist protocol can obtain better embryo quantity and quality,but there was no effect on the pregnancy outcome during fresh embryo transfer cycle.

Objective To investigate the unmet needs for assistive technology for people with physical disabilities in Chengdu,and analyze the related factors. Methods From November,2023 to March,2024,the persons with physical disabilities in Chengdu were selected from Sichuan Individuation service platform,and investigated using World Health Organization rapid Assistive Tech-nology Assessment. Results A total of 558 questionnaires were set up,and 527 effective questionnaires retured.26.8%of them reported un-met needs for aids,with the highest need for mobility aids(66.0%).Lack of support(54.9%),high price(26.3%)and lack of knowledge about aids(20.3%)were the main reasons for not obtaining the aids they needed.Loss of spouse(OR=3.615),serious mobility impairment(OR＞2.926)and serious self-care impairment(OR＞2.781)were the risks of unmet needs for aids. Conclusion It is important to popularize policies and products of aids,pay attention to personal adaptation for people with different barriers,and strengthen the service system,to meet the needs of people with disabilities.

ObjectiveTo investigate the correlation among the botanical characteristics， biological characteristics， chemical composition， and medicinal properties and efficacy of traditional Chinese medicines （TCM） from latex-containing plants， so as to strengthen the theory of "identifying symptoms for qualities" and provide a reference for the development and utilization of the latex-containing plant resources. MethodStatistics on the meridians for properties and tastes， efficacy， medicinal parts， family and genus， and chemical components of TCM from latex-containing plants were carried out. A total of 53 TCM from latex-containing plants included in the 2020 edition of the Chinese Pharmacopoeia were screened by mining the Chinese Botanical Journal， Chinese Materia Medica， Dictionary of Traditional Chinese Medicines， and related literature. In addition， their meridians for properties and tastes， medicinal parts， chemical components， and TCM classifications were summarized and statistically analyzed by using Excel 2013 and ChiPlot 2023.3.31 software. ResultIt was found that latex-containing plants were mainly distributed in one kingdom， one phylum， two classes， and 20 families， and most of the TCM from latex-containing plants belonged to Dicotyledonaceae under Angiosperms. In terms of properties and tastes， plain>cold>warm>cool>hot and bitter>pungent>sweet>sour>salty. In terms of meridians， liver>lung>kidney>spleen=large intestine=stomach>heart>bladder=gallbladder=small intestines. In terms of medicinal parts， roots （root， rhizomes， tuberous root， and root bark）>resin>seed>whole herb （whole herb and above-ground part）>stem （stem and branch）>fruit>leaf>flower=skin. In terms of research on chemical components， they were mostly glycosides. In terms of TCM classification， they were mostly medicines for activating blood circulation and removing blood stasis. ConclusionThe TCM from latex-containing plants is mainly plain， with a uniform warm and cold distribution. The tastes are mainly bitter and pungent， and the major meridians are the liver and lung. The roots and resins are mainly used as medicines. The components mostly contain glycosides， alkaloids， and volatile oils， and most of them are medicines for activating blood circulation and removing blood stasis， as well as for removing heat and toxins. There is a certain degree of correlation among the growth habits， medicinal parts， chemical components， and the properties， tastes， and efficacy of the TCM from latex-containing plants. It may provide a reference for resource development and utilization of TCM from latex-containing plants.

ObjectiveThe relevant laws among the biological characteristics， medicinal parts， growth environment， and medicinal properties and efficacy of traditional Chinese medicines （TCM） from fungi were excavated， so as to strengthen the theory of distinguishing symptoms for quality and provide a reference for the development and utilization of TCM from fungi. MethodThe medicinal parts， meridians for properties and tastes， heterotrophic mode， and efficacy of commonly used TCM from fungi were summarized. By consulting the Compendium of Materia Medica， Shennong Materia Medica， Flora of China， and literature， the TCM from fungi indexed in the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias were checked. ResultA total of 28 common TCM from fungi were selected. Different TCMs from fungi have different meridians for properties and tastes， medicinal parts， habits， and growth environments. The relevant information was counted. Among the four properties， plain>cold>warm. Among the five tastes， sweet>bitter>light>pungent=salty. In terms of medicinal parts， fruiting body>sclerotia>complex>spermia=outer skin=other. In terms of meridians， lung>liver=heart>spleen=kidney>stomach. In terms of habits， parasitism>saprophysis>symbiosis=facultative parasitism=facultative saprophysis. ConclusionTCM from fungi are mainly parasitic and saprophytic， and the plain property and sweet taste the most. The meridians are mostly lung， heart， and liver. Nourishment and diuresis are the main efficacy. There is a certain correlation between the color， habit， medicinal parts， and growth environment of TCM from fungi and their properties， tastes， and efficacy， providing comprehensive literature reference and theoretical basis for their in-depth research， clinical use， and resource development.