BACKGROUND:The pathogenesis of moyamoya disease is unclear,and there is a lack of early diagnostic methods and effective medical treatments.OBJECTIVE:To identify biomarkers of moyamoya disease through machine learning,and analyze the therapeutic mechanism of Bu Huang Si Wu Tang in moyamoya disease.METHODS:Moyamoya disease gene dataset from gene expression omnibus database was retrieved.R language was used to screen differentially expressed genes and perform enrichment analysis on differentially expressed genes.Moyamoya disease biomarkers were screened using least absolute shrinkage and selection operator and support vector machine-recursive feature elimination machine learning algorithms.A diagnostic model was constructed by establishing a column chart,and its clinical utility and diagnostic value were evaluated and further validated through detecting clinical serum markers of patients with moyamoya disease.In vitro experiments were performed to observe the effect of Bu Huang Si Wu Tang on umbilical vein endothelial cells under oxygen glucose deprivation,and the main components of Bu Huang Si Wu Tang were selected for molecular docking and molecular dynamics simulation with the screened targets to explore its potential mechanism.RESULTS AND CONCLUSION:This study identified 76 differentially expressed genes,mainly enriched in immune and metabolic related pathways.Two potential biomarkers,complement factor D(CFD)and DKFZp434L192,were obtained through machine learning.The calibration curve,decision curve analysis,and clinical impact curve showed that the column chart had good predictive ability.qRT-PCR analysis showed that CFD and DKFZp434L192 expression levels were significantly upregulated in patients with moyamoya disease(P<0.001).In vitro experiments showed that Bu Huang Si Wu Tang significantly enhanced the activity and migration ability(P<0.01)of umbilical vein endothelial cells under oxygen glucose deprivation.Molecular docking results showed that all four active ingredients of Bu Huang Si Wu Tang could bind to the target site,and the dynamic simulation results further verified its binding stability.To conclude,CFD and DKFZp434L192 exhibit good diagnostic efficacy for moyamoya disease and can serve as potential diagnostic biomarkers and therapeutic targets for moyamoya disease.Bu Huang Si Wu Tang has a certain protective effect on vascular endothelial cells under ischemic conditions,which may be related to CFD.

Objective:To observe the effects of electroacupuncture at "Shenting", "Benshen" and "Baihui" acupoints on the mechanical pain threshold and JAK/PI3K/TRPV1 pathway in the trigeminal ganglion of rats with trigeminal neuralgia model; To explore the related mechanism.Methods:Totally 36 male SD rats were divided into sham-operation group, model group and electroacupuncture group using random number table method, with 12 rats in each group. Except for the sham-operation group, rats in the model group and electroacupuncture group were modeled by infraorbital nerve chronic constriction injury. In the electroacupuncture group, electroacupuncture was performed at "Shenting", "Benshen" and "Baihui" 14 days after surgery, 20 min every day, once every other day, and every 3 times for 1 course of treatment with an interval of 2 d between each course of treatment. A total of 2 courses of treatment were performed. VonFrey fiber wire was used to measure the mechanical pain threshold of rat whisker pads. HE staining was used to observe the morphology and structure of trigeminal ganglion of rats in each group. Immunohistochemistry and Western blot method were used to observe the protein expressions of JAK, PI3K and TRPV1 in trigeminal ganglion of rats, and the serum level of IL-6 was detected in the serum of rats by ELISA.Results:Compared with the model group, the pain threshold of the electroacupuncture group increased significantly ( P<0.05), and the infiltration of inflammatory cells and demyelination in the trigeminal nerve ganglion decreased, and the positive expressions of JAK, PI3K, and TRPV1 in the trigeminal ganglion decreased ( P<0.05 or P<0.01), the protein expressions of JAK2, PI3K, and TRPV1 decreased ( P<0.05 or P<0.01), and the serum IL-6 level decreased ( P<0.01). Conclusions:Electroacupuncture at "Shenting", "Benshen" and "Baihui" may play an analgesic role by regulating IL-6 levels and inhibiting the activation of JAK/PI3K/TRPV1 signaling pathway.

The therapeutic efficacy and possible mechanism of action of superficial needling therapy for knee osteoarthritis(KOA)are reviewed by analyzing relevant medical literature.Superficial needling therapy exerts certain efficacy in treating KOA,and the clinical efficacy could be further improved by combining it with conventional acupuncture,as well as Chinese medicine and other acupuncture methods alone.The therapy of stimulation of meridian qi and invigoration of yang qiare in line with the pathogenesis of KOA.Superficial needling therapy exerts certain effect on KOA by enhancing acupuncture stimulation,enlarging the treatment area,and releasing muscle and fascia.

Objective:To analysis of the efficacy and safety of entecavir monotherapy and entecavir combined with probiotic therapy in the treatment of hepatitis B cirrhosis.Methods:A total of 88 patients with hepatitis B cirrhosis diagnosed and treated in Binzhou Central Hospital from May 2020 to May 2022 were prospectively selected as the study objects, and divided into the control group (44 cases) and the observation group (44 cases) according to random number table method. The control group was given entecavir monotherapy, and the observation group was given entecavir combined with probiotics. The levels of intestinal flora, blood ammonia (BUN), liver function index and liver fibrosis were compared between the two groups before and after treatment, and the clinical efficacy after 3 months of treatment and the occurrence of adverse reactions during treatment were compared between the two groups.Results:After treatment, the ratio of harmful/beneficial bacteria, serum BUN, total bilirubin (TBIL), alanine aminotransferase (ALT), azelaic aminotransferase (AST), glutamyltransferase (GGT), pre-collagen type Ⅲ(PCⅢ), collagen type Ⅳ (Ⅳ-C), laminin (LN), and hyaluronidase (HA) in the observation group were lower than those in the control group: (10.52 ± 1.35)% vs. (11.38 ± 2.19)%, (70.26 ± 6.94) μmol/L vs. (76.34 ± 10.59) μmol/L, (32.76 ± 4.27) μmol/L vs. (36.82 ± 6.41) μmol/L, (51.82 ± 6.37) U/L vs. (56.34 ± 5.74) U/L, (37.83 ± 5.61) U/L vs. (42.75 ± 12.89) U/L, (42.67 ± 11.84) U/L vs. (48.16 ± 13.49) U/L, (118.76 ± 23.65) μg/L vs. (129.24 ± 21.16) μg/L, (74.34 ± 17.58) μg/L vs.(82.39 ± 20.05) μg/L, (127.65 ± 12.23) mg/L vs. (138.97 ± 11.76) mg/L, (107.78 ± 23.47) mg/L vs. (119.65 ± 22.35) mg/L, there were statistical differences ( P<0.05). During the 3-month treatment period, the total effective rate in the observation group was higher than that in the control group and the total incidence of adverse reactions was lower than that in the control group: 88.64%(39/44) vs. 70.45%(31/44), 4.55%(2/44) vs. 18.18%(8/44), there were statistical differences ( χ2 = 4.47, 4.06, P<0.05). Conclusions:In the treatment of hepatitis B cirrhosis patients, entecavir combined with probiotics can effectively regulate gastrointestinal function, reduce BUN level, and then more conductive to liver function recovery, reduce the process of liver fibrosis, improve efficacy, and reduce the occurrence of adverse reactions.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

Objective:To analysis of the efficacy and safety of entecavir monotherapy and entecavir combined with probiotic therapy in the treatment of hepatitis B cirrhosis.Methods:A total of 88 patients with hepatitis B cirrhosis diagnosed and treated in Binzhou Central Hospital from May 2020 to May 2022 were prospectively selected as the study objects, and divided into the control group (44 cases) and the observation group (44 cases) according to random number table method. The control group was given entecavir monotherapy, and the observation group was given entecavir combined with probiotics. The levels of intestinal flora, blood ammonia (BUN), liver function index and liver fibrosis were compared between the two groups before and after treatment, and the clinical efficacy after 3 months of treatment and the occurrence of adverse reactions during treatment were compared between the two groups.Results:After treatment, the ratio of harmful/beneficial bacteria, serum BUN, total bilirubin (TBIL), alanine aminotransferase (ALT), azelaic aminotransferase (AST), glutamyltransferase (GGT), pre-collagen type Ⅲ(PCⅢ), collagen type Ⅳ (Ⅳ-C), laminin (LN), and hyaluronidase (HA) in the observation group were lower than those in the control group: (10.52 ± 1.35)% vs. (11.38 ± 2.19)%, (70.26 ± 6.94) μmol/L vs. (76.34 ± 10.59) μmol/L, (32.76 ± 4.27) μmol/L vs. (36.82 ± 6.41) μmol/L, (51.82 ± 6.37) U/L vs. (56.34 ± 5.74) U/L, (37.83 ± 5.61) U/L vs. (42.75 ± 12.89) U/L, (42.67 ± 11.84) U/L vs. (48.16 ± 13.49) U/L, (118.76 ± 23.65) μg/L vs. (129.24 ± 21.16) μg/L, (74.34 ± 17.58) μg/L vs.(82.39 ± 20.05) μg/L, (127.65 ± 12.23) mg/L vs. (138.97 ± 11.76) mg/L, (107.78 ± 23.47) mg/L vs. (119.65 ± 22.35) mg/L, there were statistical differences ( P<0.05). During the 3-month treatment period, the total effective rate in the observation group was higher than that in the control group and the total incidence of adverse reactions was lower than that in the control group: 88.64%(39/44) vs. 70.45%(31/44), 4.55%(2/44) vs. 18.18%(8/44), there were statistical differences ( χ2 = 4.47, 4.06, P<0.05). Conclusions:In the treatment of hepatitis B cirrhosis patients, entecavir combined with probiotics can effectively regulate gastrointestinal function, reduce BUN level, and then more conductive to liver function recovery, reduce the process of liver fibrosis, improve efficacy, and reduce the occurrence of adverse reactions.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

BACKGROUND:The pathogenesis of moyamoya disease is unclear,and there is a lack of early diagnostic methods and effective medical treatments.OBJECTIVE:To identify biomarkers of moyamoya disease through machine learning,and analyze the therapeutic mechanism of Bu Huang Si Wu Tang in moyamoya disease.METHODS:Moyamoya disease gene dataset from gene expression omnibus database was retrieved.R language was used to screen differentially expressed genes and perform enrichment analysis on differentially expressed genes.Moyamoya disease biomarkers were screened using least absolute shrinkage and selection operator and support vector machine-recursive feature elimination machine learning algorithms.A diagnostic model was constructed by establishing a column chart,and its clinical utility and diagnostic value were evaluated and further validated through detecting clinical serum markers of patients with moyamoya disease.In vitro experiments were performed to observe the effect of Bu Huang Si Wu Tang on umbilical vein endothelial cells under oxygen glucose deprivation,and the main components of Bu Huang Si Wu Tang were selected for molecular docking and molecular dynamics simulation with the screened targets to explore its potential mechanism.RESULTS AND CONCLUSION:This study identified 76 differentially expressed genes,mainly enriched in immune and metabolic related pathways.Two potential biomarkers,complement factor D(CFD)and DKFZp434L192,were obtained through machine learning.The calibration curve,decision curve analysis,and clinical impact curve showed that the column chart had good predictive ability.qRT-PCR analysis showed that CFD and DKFZp434L192 expression levels were significantly upregulated in patients with moyamoya disease(P<0.001).In vitro experiments showed that Bu Huang Si Wu Tang significantly enhanced the activity and migration ability(P<0.01)of umbilical vein endothelial cells under oxygen glucose deprivation.Molecular docking results showed that all four active ingredients of Bu Huang Si Wu Tang could bind to the target site,and the dynamic simulation results further verified its binding stability.To conclude,CFD and DKFZp434L192 exhibit good diagnostic efficacy for moyamoya disease and can serve as potential diagnostic biomarkers and therapeutic targets for moyamoya disease.Bu Huang Si Wu Tang has a certain protective effect on vascular endothelial cells under ischemic conditions,which may be related to CFD.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Objectives:To evaluate the valvular and cardiac function,cardiac reverse remodeling at 6-month after transcatheter edge-to-edge repair(TEER)for patients with functional and degenerative mitral valve regurgitation,and summarize the experience of echocardiography application. Methods:The clinical data of 93 patients with moderate to severe mitral regurgitation(MR)treated with TEER and completed 6-month follow-up in Yunnan Fuwai Cardiovascular Hospital from July 2022 to February 2023 were retrospectively analyzed.Patients were divided into functional mitral regurgitation(FMR)and degenerative mitral regurgitation(DMR)groups according to MR etiology.The valve characteristic parameters,as well as valvular function,chamber volume and cardiac functional parameters before and at 6 months after operation were compared.The key points of echocardiography application were summarized. Results:Among all patients,71 were FMR and 22 were DMR.There were differences in valve structure between the two groups.Mitral TEER were successfully accomplished and all patients completed 6-month follow-up.The key points of echocardiography application included:valve structure analysis,atrial septal puncture location,device delivery process monitoring and image optimization during clamping process.The mitral regurgitation grade and NYHA grade were significantly improved in all patients at 6 months after TEER(P<0.05),and the mean mitral valve pressure gradient was higher than that before operation(P<0.05).Left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV)and left atrial volume index in FMR group were significantly decreased(P<0.05),while left ventricular and left atrial volume in DMR group remained unchanged(P>0.05).There were no significant changes in left ventricular ejection fraction and left ventricular global strain in both groups during the observation period(P>0.05).The changes of LVEDV and LVESV before and after operation were more significant in FMR group than those in DMR group(P<0.05). Conclusions:Mitral TEER can reduce the degree of regurgitation and improve cardiac function in the early postoperative period for moderate and severe MR patients with different etiologies.There are differences in preoperative valve structure and postoperative cardiac reverse remodeling between FMR and DMR patients.Echocardiography is an important imaging technique for the evaluation and monitoring process before,during and post mitral TEER.