The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

The triterpenoid saponins of Centella asiatica, including asiaticoside, madecassoside, asiatic acid, and madecassic acid, are pivotal bioactive compounds of the plant. These constituents exhibit a spectrum of pharmacological activities, such as antioxidant, antitumor, and antidepressant effects, promotion of wound healing, and enhancement of microcirculation. Owing to these therapeutic properties, C. asiatica is widely employed in pharmaceutical and cosmetic industries. However, the escalating global demand for its extracts has led to potential supply shortages, prompting researchers to use multiple strategies such as multi-omics, molecular biology, and synthetic biology to conduct extensive studies. These studies encompass the elucidation of the biosynthetic pathways of triterpenoid saponins in C. asiatica, metabolic regulation, the hormonal induction of secondary metabolite synthesis, and the application of biotechnological strategies for natural product production to increase the yield of secondary metabolites in C. asiatica, or to produce active components via microbial chassis, thus satisfying market demands and promoting the sustainable exploitation of wild C. asiatica resources. This article first introduced the triterpenoid saponins of C. asiatica and their biological activities, then summarized the latest research advancements in their biosynthetic pathways, metabolic regulation, and heterologous biosynthesis, and provided an outlook on future development directions, with the aim of providing reference for comprehensive resource development and biotechnological synthesis of active components from C. asiatica.
Centella/genetics* ; Triterpenes/chemistry* ; Biosynthetic Pathways ; Humans ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.
Humans ; Amygdala/diagnostic imaging* ; Female ; Premenstrual Dysphoric Disorder/pathology* ; Premenstrual Syndrome/pathology* ; Emotions/physiology* ; Magnetic Resonance Imaging

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

Objective:To investigate the value of antioxidant-associated long non-coding RNAs(lncRNAs)risk score model in prognosis and the association with immune microenvironment of the gastric cancer patients.Methods:Gastric cancer transcriptome data and clinical information were downloaded from TCGA database.Antioxidant-associated lncRNAs were obtained by co-ex-pression analysis of lncRNAs and antioxidant genes.Risk score was constructed using univariate cox regression analysis and lasso regression analysis.Log-Rank test was used to compare the survival differences between two groups.Receiver operating characteristic curve(ROC)was used to assess the specificity and sensitivity of the prognostic risk score model.Nomogram was constructed com-bining risk score and clinical parameters.Immune cell infiltration was assessed by TIMER 2.0.Im-munotherapy sensitivity of each sample was analyzed at TIDE website.Results:A risk score in-cluding 12 IncRNAs was constructed by univariate cox regression analysis and lasso regression anal-ysis.The risk score was an independent factor influencing patient prognosis[HR=5.406(3.131～9.335),P＜0.001].Risk score was positively correlated with multiple suppressive immune cells infil-tration(M2 macrophage,tumor-associated fibroblast).Meanwhile,multiple aberrant expression of immune checkpoint genes and higher TIDE score were found in high-risk group,suggesting that high-risk groups may be more sensitive to immunotherapy.Conclusion:The antioxidant-associ-ated IncRNAs risk score is a good prognostic predictor and can act as a reference in individualized immunotherapy for gastric cancer patients.

Objective:To explore brain network properties and their relationship with cognitive function in children with spastic cerebral palsy (SCP) using diffusion tensor imaging (DTI) based graph theory analysis.Methods:The study was a cross-sectional study. Clinical and imaging data of 21 children with SCP (SCP group) and 32 healthy children (control group) who underwent cranial MRI at the Affiliated Hospital of Zunyi Medical University from August 2020 to April 2022 were analyzed retrospectively. 3D-T 1WI, DTI and Wechsler Intelligence Scale were assessed for all subjects. The Wechsler Intelligence Scale included the verbal comprehension index (VCI), the processing speed index (PSI), the work memory index (WMI), and the perceptual reasoning index (PRI), etc., and ultimately the full scale intelligence quotient (FSIQ) scores were obtained based on the indices of each subscale. Independent samples t-test was used to analyze the differences in the small world attributes [small-world index (σ), normalized shortest path length (λ), normalized clustering coefficients (γ)], global attributes [global efficiency (Eglob), local efficiency (Eloc), characteristic path length (Lp), clustering efficiency (Cp)] and node attributes [degree centrality(DC), nodal efficiency (Ne), betweeness centrality (Bc), nodal shortest path length (NLp), nodal clustering efficiency, nodal local efficiency] between two groups of children′s brain networks. Brain network indicators with statistically significant differences between the 2 groups were correlated with Wechsler Intelligence Scale scores using Spearman. Results:The FSIQ scores on the Wechsler Intelligence Scale and the VCI, WMI, PSI, and PRI were lower in the SCP group than in the control group, and the differences were all statistically significant (all P<0.05). Both groups of children′s brain networks had small world properties. Compared with the control group, Eglob decreased, Lp and λ increased in the SCP group (all P<0.05). Compared with the control group, DC and Ne in multiple brain regions decreased, NLp increased in the SCP group (all P<0.05, FDR corrected). Correlation analysis showed that DC in the right parsopercularis was positively correlated with FSIQ, VCI, WMI and PRI( r=0.53, 0.47, 0.47, 0.60, P=0.019, 0.045, 0.044, 0.020, respectively); NLp in the right parsopercularis was negatively correlated with PRI( r=-0.56, P=0.030); Ne in left paracentral, the right parsopercularis, right precentral, right postcentra were positively correlated with PRI( r=0.62, 0.56, 0.53, 0.54, P=0.015, 0.031, 0.044, 0.039, respectively); Ne in the right precentral was positively correlated with WMI ( r=0.48, P=0.039) in the SCP group. Conclusions:There are changes in the topological attributes of global and multiple regional brain networks in SCP. The changes in the attributes of nodes in the right parsopercularis, right precentral, right postcentral, and left paracentral could reflect cognitive dysfunction in children with SCP.

AIM To study the phenylethanoid glycosides from Verbenae Herba.METHODS The 80%ethanol extract from Verbenae Herba was isolated and purified by silica gel,Sephadex LH-20,TLC and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Nine compounds were isolated and identified as verbofficoside A(1),cistanoside D(2),epimeredinoside A(3),verbascoside(4),isoverbascoside(5),cistanoside C(6),cistanoside F(7),decaffeoylacteoside(8),jionoside C(9).CONCLUSION Compound 1 is a new compound.Compounds 3 and 6-9 are isolated from this plant for the first time.