Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

OBJECTIVES: To evaluate the one-year outcomes of valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) using SAPIEN 3 valve for treating mitral bioprosthetic valve failure. METHODS: A retrospective analysis was conducted on 26 patients with mitral bioprosthetic valve failure who underwent ViV-TMVR at West China Hospital, Sichuan University, between November 2022 and July 2024. The age of patients was 71.5 (64.5, 74.5) years, and 69.2% were female. Bioprosthetic valve failure occurred at (9.7±3.7) years after initial surgical implantation, with the most common failure mode being mixed stenosis and regurgitation (53.8%). The SAPIEN 3 valve was implanted via either a transseptal or transapical approach. Echocardiography was performed preoperatively, immediately post-procedure, and at 1 month, 6 months, and 1 year post-procedure. Outcomes included all-cause mortality, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score, and postoperative complications. RESULTS: The procedure was performed via the transseptal approach in 21 patients (80.8%) and the transapical approach in 5 patients (19.2%). All procedures were technically successful. No paravalvular leakage was observed immediately post-procedure, and mitral valve hemodynamics improved significantly. At the 1-year follow-up, 2 patients had died. Two patients (8.3% of survivors) were of NYHA functional class Ⅲ, and KCCQ-12 score improved to (88.4±14.6) points (both P<0.01). Echocardio-graphy at 1 year postoperatively showed significant reductions in peak mitral valve velocity [to (2.29±0.32) m/s] and mean transvalvular pressure gradient [to (9.5±3.5) mmHg, 1 mmHg=0.133 kPa] compared to baseline (both P<0.05). No moderate or severe mitral regurgitation or paravalvular leakage was observed. The proportion of patients with moderate-to-severe pulmonary hypertension decreased from 65.4% preoperatively to 13.0% at 1 year (P<0.05). CONCLUSIONS ViV-TMVR with the SAPIEN 3 valve for mitral biopro-sthetic valve failure is associated with high procedural success, significantly improved valve hemodynamics of the mitral value, alleviation of pulmonary hypertension, enhanced quality of life, and a low rate of complications at 1 year after the operation.
Humans ; Female ; Male ; Retrospective Studies ; Aged ; Bioprosthesis ; Heart Valve Prosthesis ; Mitral Valve/surgery* ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Prosthesis Failure ; Treatment Outcome ; Mitral Valve Insufficiency/surgery*

OBJECTIVES: To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD). METHODS: Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting. RESULTS: HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors. CONCLUSIONS NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.
Non-alcoholic Fatty Liver Disease/metabolism* ; Animals ; Hepatocytes/metabolism* ; Lipid Metabolism ; Mice ; Humans ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; AMP-Activated Protein Kinases/metabolism* ; Carnitine O-Palmitoyltransferase/metabolism* ; Diet, High-Fat ; Male ; Mice, Inbred C57BL ; Signal Transduction

Objective To explore the prognostic value of serum glutathione reductase(GR),superoxide dismutase(SOD),cystatin C(Cys-C),homocysteine(Hcy)and lipoprotein a[Lp(a)]levels in patients with cerebral ischemic stroke(CIS),and to provide a reference for improving the prognosis of CIS patients.Methods 126 patients with CIS admitted to the 980th Hospital of Joint Logistics Support Force from June 2022 to April 2023 were selected as the observation group,another 126 healthy individuals were selected as the control group at a ratio of 1:1.The expression levels of GR,SOD,Cys-C,Hcy and Lp(a)in the two groups were detected and compared after admission and during physical examination.The degree of neurological deficit in patients with CIS was classified into mild(NIHSS:2～4 points,n=35),moderate(NIHSS:5～15 points,n=47),moderate-severe(NIHSS:16～20 points,n=26)and severe(NIHSS:21～42 points,n=18)according to the National Institutes of Health Stroke Scale(NIHSS).The expression of serum GR,SOD,Cys-C,Hcy and Lp(a)in patients with different degrees of neurological deficit was compared,and the correlation between each indicator and the degree of neurological deficit was analyzed.The observation group received intravenous thrombolytic therapy after admission and was re-examined one day after thrombolysis.After treatment,follow-up visits were conducted for 28 days.According to the patient's condition(modified Rankin scale),patients were divided into good prognosis(n=94)and poor prognosis groups(n=32).The levels of each indicator in patients with different prognoses were compared,and the predictive value of GR,SOD,Cys-C,Hcy and Lp(a)expression for poor prognosis and early warning were analyzed.Results The expression levels of serum GR(48.54±3.07U/L)and SOD(157.17±25.47U/ml)in the observation group were lower than those in the control group(61.68±3.15U/L,203.63±18.31U/ml),while the expression levels of Cys-C(1.24±0.28mg/L),Hcy(15.21±1.62μmol/L)and Lp(a)(386.53±52.16mg/L)were higher than those in the control group(0.82±0.23mg/L,9.58±0.60μmol/L,257.83±45.34mg/L),with statistically significant differences(t=13.011～36.582,all P<0.05).As the disease progressed,the expression levels of GR and SOD gradually decreased,while the expression levels of Cys-C,Hcy and Lp(a)gradually increased,with statistically significant differences(F=14.685～197.041,all P<0.05).Spearman analysis,GR and SOD were negatively correlated with the degree of neurological deficit in patients with CIS(r=-0.814,-0.753,all P<0.05),while Cys-C,Hcy and Lp(a)were positively correlated with the degree of neurological deficit in patients with CIS(r=0.647,0.782,0.724,all P<0.05).The expression of GR and SOD in patients with good prognosis at admission and 1 day after thrombolysis was higher than that in patients with poor prognosis(t=9.109,6.338;2.934,4.358,all P<0.05),while the expression of Cys-C,Hcy and Lp(a)was lower than that in patients with poor prognosis(t=5.246,5.118,8.561;4.636,5.298,7.461,all P<0.05).The AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at admission was 0.898(0.832～0.945),and the AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis was 0.931(0.871～0.968).The RR(95%CI)values caused by the expression of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis were 2.868(1.594～5.161),3.194(1.807～5.645),0.155(0.082～0.291),0.150(0.071～0.319)and 0.227(0.119～0.435).Conclusion Abnormal changes in the levels of GR,SOD,Cys-C,Hcy and Lp(a)are closely related to the degree of neurological deficit and prognosis in patients with CIS.Early combined detection of GR,SOD,Cys-C,Hcy and Lp(a)levels has high predictive value and early warning for evaluating the poor prognosis of patients with CIS.

Objective:This study aims to explore the job preferences of county-level Centers for Disease Control and Prevention(CDC)personnel and to provide a basis for the development of effective incentive mechanisms.Methods:This study used a combination of stratified sampling and latent class sampling to investigate 1 809 respondents from 56 county-level CDCs in Shandong Province,Hubei Province,and Guizhou Province.Data were analysed using a mixed logit model and a latent class model,and willingness to pay was calculated.Results:The results of the mixed logit model showed that,all attributes and their levels had a significant influence(P<0.05),with establishment being the most important motivating factor(β=2.249).In the latent class model,respondents were divided into three categories.The main differences between the three classes were the choice of exit options and differences in preferences for job attributes.Conclusion:County-level CDC personnel preferred jobs with higher incomes,very good benefit levels,establishment,low workload,better recognition and respect from the public,more opportunities for career advancement,and abundant training opportunities.It is recommended that the total number of establishment should be rationally controlled and dynamically adjusted to balance the differences between working conditions within and outside the establishment;that a comprehensive approach should be adopted to improve both hygiene and motivation factors;and that different incentives should be adopted for different categories of CDC staff. Those who are willing to make a change should be provided with more opportunities for training and career advancement.

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.

Objective:To assess the feasibility and efficacy of transperineal laser ablation(TPLA)with single laser fiber in treating benign prostatic obstruction(BPO).Methods:From April 2021 to March 2024,a total of 13 BPO patients were selected from Beijing Friendship Hospital.TPLA was performed using a single laser fiber,which was guided by transrectal biplane ultrasound.The single laser fiber was used to undergo TPLA under the guidance of trans-rectal dual-plane ultrasound.The intraoperative time,ablation time,energy consumption,indwelling time of catheter,and complications were observed.The postoperative 6 months was chosen as the cut-off point of follow-up,and the pre and postoperative changes of international prostate symptom score(IPSS),quality of life index(QoL),prostate volume(PV),residual urine volume(RUV)and the maximum urine flow rate(Qmax)were compared.Results:All 13 patients successfully underwent TPLA with single laser fiber.The average operation time was(55.1±18.3)min,and the average ablation time was(16.3±1.7)min,and average energy consumption was(3951.6±459.7)J,and the median value of indwelling time of catheter was 7(7,10)days.The number of postoperative complication was 2 cases,and both them belonged to Clavien-Dindo grade II complication.At the postoperative 6th month,the IPSS,QoL,PV,Qmax and RUV of all patients were improved,all of which were better than preoperative these indicators,and the differences were significant(t=12.102,-3.228,-3.181,-2.581,-2.936,P<0.05).Conclusion:The application of single laser fiber in conducting TPLA operation is feasibility at technical aspect,and it can achieve the therapeutic goals of improving patients'symptoms and enhancing their quality of life.Although its operational time is slightly longer than that of using multiple fibers simultaneously,it can effectively reduce the cost of expenditure for consumables.

OBJECTIVE To investigate the analgesic effects and potential mechanisms of the partial agonist of the 5-hydroxytryptamine 1A(5-HT1A)receptor and the selective 5-HT reuptake inhibitor,viladazone(Vil),in various animal models of pain.METHODS ① Mouse acetic acid writhing test:KM mice were divided into the model group,model+morphine 10 mg·kg-1 group,and model+Vil 2,4,8 mg·kg-1 groups.Thirty minutes after ig administration of saline(model group)or corresponding drugs,each group was ip injected with a 2%acetic acid aqueous solution(0.01 mL·g-1),and the writhing frequency of the mice was observed and recorded from 5 to 20 min.② Mouse formalin pain test:KM mice were divided into the model group and model+Vil 2,4 and 8 mg·kg-1 groups.Thirty minutes after ig adminis-tration of saline(model group)or drugs,20 μL of 5%formalin solution was sc injected into the right plantar region of the mice.The licking time(the sum of the duration of licking and biting the paw)of the mice was observed and recorded during two periods:the acute phase(0-5 min after sc formalin injec-tion)and the delayed phase(15-35 min after sc formalin injection).③ Rat chronic constriction injury(CCI)of the sciatic nerve experiment:SD rats successfully examined with a paw withdrawal threshold(PWT)<5 g were randomly divided into a CCI model group and a CCI model+Vil 2,4 and 8 mg·kg-1 group.Solvent(model group)or corresponding drugs were ig administered,and the PWT of the modeled side was measured at 30,60,120 and 240 min after the first administration to evaluate the acute anal-gesic effect of Vil on mechanical pain.Then,Vil was continuously ig administered for 14 d,and the PWT was measured 1 h after Vil administration on the 7th and 14th d to evaluate the long-term analgesic effect of Vil.Immunofluorescence staining was employed to analyze the expression levels of inflamma-tion-related proteins,ionized calcium binding adapter molecule 1(IBA-1),tumor necrosis factor α(TNF-α),and interleukin 1β(IL-1β),in brain tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IBA-1,TNF-α and IL-1β in the dorsal root ganglion of the spinal cord in the CCI model.RESULTS ① In the mouse model of acetic acid writhing,single ig administration of morphine 10 mg·kg-1 and Vil at varied doses significantly reduced the number of writhings induced by acetic acid compared to the model group.② In the formalin-induced pain model,the average licking time of the model group was 50.5 s during the acute phase of inflammatory pain(0-5 min after intraplantar injec-tion of 5%formalin),and 347.9 s during the delayed phase of inflammatory pain(25-35 min after formalin injection).Compared to the model group,single ig administration of Vil 2-8 mg·kg-1 reduced chronic pain induced by formalin in mice,and each dose of Vil significantly decreased the licking time of mice,but had no notable impact on the licking duration exhibited by mice during acute phase.③ In the CCI model,the PWT values of CCI model rats significantly decreased compared with the control group.Pathological damage to varying extents was observed in brain slices,manifested as enlarged intercellular spaces and the appearance of vacuoles.The expression of IBA-1 in brain tissue significantly increased,while TNF-α and IL-1β hardly changed.The levels of IBA-1,TNF-α and IL-1β in the spinal dorsal root ganglion significantly increased.Compared with the CCI model,after single administration of Vil 2-8 mg·kg-1 for 60,120 and 240 min,Vil significantly reduced the PWT values.After two-week continuous administration,the PWT values in Vil 4 and 8 mg·kg-1 were significantly reduced,and Vil 2-8 mg·kg-1 could alleviate the neuropathic pain to some extent.Vil 8 mg·kg-1 significantly reduced the elevated levels of inflammatory factors compared to CCI rats.CONCLUSION The antidepressant Vil exhibits analgesic effects in mouse models of acetic acid writhing,formalin-induced inflammation,and neuropathic pain induced by CCI in rats,with a more pronounced effect on neuropathic pain.The mechanism of action may be related to the inhibition of inflammatory pathways of IBA-1.