A case of an elderly patient with severe aortic insufficiency who carried high risks for surgical valve replacement. After a detailed preoperative evaluation, the patient successfully received transapical transcatheter aortic valve replacement. Postoperatively, complete left bundle branch block developed, resulting in impaired left ventricular function. Despite guideline-directed medical therapy for heart failure, cardiac function showed no significant recovery. At 4.5 months post-surgery, left bundle branch pacing was performed, leading to a marked improvement in cardiac function.
Aged ; Humans ; Male ; Aortic Valve Insufficiency/surgery* ; Bundle-Branch Block/etiology* ; Cardiac Pacing, Artificial ; Postoperative Complications/therapy* ; Transcatheter Aortic Valve Replacement/adverse effects*

OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

OBJECTIVE: To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD). METHODS: Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y (SRY) gene and azoospermia factor (AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). RESULTS: Case 1 had a karyotype of 45,X[22]/46,XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+), AZFb+c (-). Case 2 had a karyotype of 45,X[12]/46,X,del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46,XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+) and AZFa+b+c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46,XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+) and AZFa+b+c (+), and WES revealed a c.1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+PP1+PM2_Supporting). CONCLUSION The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.
Humans ; Male ; Female ; Chromosomes, Human, Y/genetics* ; Disorders of Sex Development/genetics* ; Sex-Determining Region Y Protein/genetics* ; Karyotyping ; In Situ Hybridization, Fluorescence ; Exome Sequencing ; Adult ; Child

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.

OBJECTIVETo observe the differences in the clinical therapeutic effects on insomnia of spleen and stomach disharmony pattern in comparison of the combination of acupoint catgut-embedding therapy and auricular point pressure with the simple application of auricular point pressure.

METHODSOne hundred and eighty patients of insomnia of spleen and stomach disharmony pattern were randomized into an observation group (93 cases) and a control group (87 cases). In the observation group, the combination of acupoint catgut-embedding therapy and auricular point pressure was adopted. The acupoint catgut-embedding therapy was applied at Zhongwan (CV 12), Anmian (Extra), Xinshu (BL 15), Pishu (BL 20), Weishu (BL 21), Zusanli (ST 36), Yinlingquan (SP 9) and Sanyinjiao (SP 6), once every two weeks. The auricular point pressure was applied to Shenmen (TF), Pizhixia (AT), Xin (CO), Pi (CO), Wei (CO) on both sides alternatively, twice a week. The duration of treatment was 2 months for the two groups. In the control group, the auricular point pressure was simply used with the same points, manipulation and treatment duration as the observation group. After treatment, the clinical therapeutic effects were observed in the patients of the two groups. The Pittsburgh sleep quality index (PSQI) score was compared before and after treatment in the two groups. The recurrence was followed up in 3 months after the end of treatment.

RESULTSIt was observed that 2 cases were dropped out in the observation group, 4 cases in the control group. The dropped out cases were considered to be ineffective. After treatment, the total effective rate was 92.5% (86/93) in the observation group and was 80.5% (70/87) in the control group. The result in the observation group was better than that in the control group (<0.05). After treatment, PSQI scores were all reduced apparently in the two groups as compared with those before treatment (both<0.05). The score after treatment and the different value before and after treatment in the observation group were lower than those in the control group (both<0.05). In 3-month follow-up after treatment, the recurrence rate was 3.2% (3/93) in the observation group, which was lower than 13.8% (12/87) in the control group (<0.05).

CONCLUSIONIn the treatment of insomnia of spleen and stomach disharmony pattern, the acupoint catgut-embedding therapy combined with auricular point pressure are superior to the simple application of auricular point pressure in the clinical therapeutic effects, improving sleep quality and reducing the recurrence rate.

Objective To observe and compare the clinical efficacy of fire needling versus electroacupuncture in treating knee osteoarthritis of kidney and marrow deficiency type.Methods One hundred and ten patients with knee osteoarthritis of kidney and marrow deficiency type were randomly allocated to two groups, a fire needling group of 56 cases and an electroacupuncture group of 54 cases. The fire needling group received filiform needle acupuncture and fire needle pricking and the electroacupuncture group, electroacupuncture. Treatment was given once every other day, for a total of four weeks as one course. The Visual Analogue Scale (VAS) score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups.Results The VAS score and the WOMAC subscores significantly decreased in both groups after treatment compared with those before treatment (P<0.01). There were no statistically significant post-treatment differences in the VAS score and the WOMAC subscores between the two groups (P>0.05). The VAS score and the WOMAC subscores decreased further in both groups at four weeks after treatment compared with those at the end of treatment (P<0.01). In the electroacupuncture group, there were statistically significant differences in the VAS score and the WOMAC pain and stiffness subscores between eight weeks and four weeks after treatment (P<0.01) and in the WOMAC pain, stiffness and joint function subscores between at eight weeks after treatment and at the end of treatment (P<0.01). In the fire needling group, there were statistically significant differences in the VAS score and the WOMAC pain, stiffness and joint function subscores between at eight weeks after treatment and at the end of treatment (P<0.01). At four weeks after treatment, the VAS score and the WOMAC pain, stiffness and joint function subscores were significantly lower in the fire needling group than in the electroacupuncture group (P<0.05,P<0.01). At eight weeks after treatment, the VAS score and the WOMAC pain and stiffness subscores were still significantly lower in the fire needling group than in the electroacupuncture group (P<0.01). The total efficacy rate was 94.6% in the fire needling group and 90.7% in the electroacupuncture group; there was no statistically significant difference between the two groups (P>0.05).Conclusions Both filiform needle acupuncture plus fire needle pricking and electroacupuncture can markedly relieve the pain and stiffness and improve joint function in knee osteoarthritis of kidney and marrow deficiency type. Both have an equivalent short-term therapeutic effect. Filiform needle acupuncture plus fire needle pricking has a better long-term therapeutic effect than electroacupuncture.

Objective To analyze the gonadal hormone and seminal plasma of patients with abnormal semen liquefaction and investigate the influence mechanism in order to provide guidance for the diagnosis and treatment. Methods 152 men of childbearing age were divided into two groups according to the liquefaction time (cut?off point: 60 minutes). Routine semen parameters,gonadal hormone and seminal plasma were tested and compared between the above groups. T?test was applied to compare individual gland function (pH value,neutralα?glycosidase,fructopyranose,seminal plasma zinc and citric acid) and gonadal hormone (FSH,LH,PRL,T and E2). Logistic regression analysis was adopted to probe the influencing factors for abnormal semen liquefaction. Results Seminal pH value (7.47 ± 0.13 vs. 7.32 ± 0.18),citric acid(51.12 ± 12.95 vs. 83.11 ± 33.46)and FSH (4.40 ± 1.03 vs. 4.85 ± 1.50)levels were significant different between the two groups (P < 0.05),but the other indexes showed no significant difference. Correlation regression analysis showed that semen liquefaction capacity has correlative relationship with seminal plasma fructose (OR=2.644),citric acid (OR=0.922),serum T (OR=1.029) and E2,while no correlative relationship with other indexes. Conclusions Correlation between two glands (seminal vesicle and prostate) and balance in the two hormones (T and E2) influence the liquefaction time. Specific causes should be distinguished before diagnosis.

Objective To assess the prevalence and severity of burnout in medical staffs,and investigate associated demographic,perceived social support and job burnout.Methods Totally 618 medical staffs form Sichuan province people's hospital were selected by the systematic sampling method,and were tested by general state questionnaire,job burnout questionnaire and perceived social support scale.Results ①The prevalence of job burnout was 75.6％,including mild job burnout (36.1％),moderate (32.2％),severe (7.3％).②The scores of emotional exhaustion in the female medical staffs(20.50±8.35) was higher than the male medical staffs (19.07±7.76,P＜0.05).Divorced medical staffs had higher scores(18.28±7.13) than that of single and married medical staffs (15.05±5.00) in low personal accomplishment (P＜ 0.01).The medical personnel of different ages were statistically significant difference in total job burnout scores,emotional exhaustion and depersonalisation (F=4.475,3.061,3.942,all P＜0.05).The medical personnel of different post,professional title and working years were statistically significant difference in total job burnout scores and emotional exhaustion (F=6.920,13.968; 3.506,3.391;3.190,3.300,all P＜ 0.05).The medical personnel of different educational attainment were statistically significant difference in total job burnout scores,emotional exhaustion and low personal accomplishment(F=6.218,2.837,2.850,all P＜0.05).)Correlation analysis found that emotional exhaustion,depersonalisation,low personal accomplishment and total job burnout respectively with family support,friend support,and other support and total social support was significantly negative correlation (r=-0.126～-0.403,P＜0.01).④Regression analysis showed that education,family and friends support were protective factors for total job burnout(OR=-0.248,95％ CI =0.625-0.975 ; OR=-0.084,95％ CI =0.862-0.980 ; OR=-0.091,95％ CI =0.860-0.968 ; all P＜0.05).Conclusion The prevalence of job burnout is high in medical staffs.The medical staffs of different sex,age,title,jobs,education,working years,marital status are showed the differences job burnout scores,which is closely related to the perceived social support.

Objective To compare the effect of kidney-tonifying blood-activating recipe (KBR) and Aescuven Forte Tablets ( AFT) in improving the sperm quality of varicocele-induced male sterility, thus to optimize the therapeutic therapy for varicocele-induced male sterility. Methods A total of 102 varicocele-induced male sterility with abnormal sperm parameters after conservative treatment were randomized into KBR group (N=53) and AFT group ( N=49) . KBR group was given KBR plus natural vitamin E and AFT group was given AFT plus natural vitamin E, and the treatment lasted for 8 continuous weeks. Before and after treatment, the quality of seminal fluid was analyzed, sperm quantization parameters such as total number of sperm (TNS) , total number of progressive motility sperm ( TNPS) , total number of normal form sperm ( TNNS) and total number of nor mal form and progressive motility sperm ( TNNPS) were observed, and the improvement rate of sperm quantization parameter was compared. Results (1) Before treatment, the differences of TNS, TNPS, TNNS and TNNPS were insignificant between the two groups ( P>0.05) . After treatment, TNNS was not improved in AFT group ( P>0.05) , but TNS, TNPS, TNNPS were much improved in both groups ( P<0.01 compared with those before treatment) . The improvement of KBR group was superior to that of AFT group ( P<0.05) . ( 2) The improvement rate for TNS, TNPS, TNNS, TNNPS was 90.57%, 79.25%, 67.92%, 77.36%in KBR group, and was 75.51%, 73.47%, 28.57%, 61.22% in AFT group respectively. The improvement rate for TNS and TNNS in KBR group was superior to that in AFT group ( P<0.05 or P<0.01) . Conclusion Varicocele-induced male sterility patients usually have the syndrome of kidney deficiency and blood stasis, so KBR, which has the function of tonifying kidney and activating blood, has synergistic action on the effect of AFT in improving sperm quality of varicocele-induced male sterility patients.

This study was aimed to analyze correlation between traditional Chinese medicine (TCM) syndromes and symptoms of acute exacerbation chronic obstructive pulmonary disease (AECOPD) based on complex network in order to provide a scientific basis for TCM syndrome amendments of diagnostic criteria, and explore relevant technologies to promote its application. By way of the current Clinical Research Information Sharing System, data and data pro-cessing were carried out (EHR 3000 between August 2011 and January 2013) into the database by ETL software. The MISCR (correlation between common symptoms and common syndromes) from both common symptoms and com-mon syndromes of AECOPD was analyzed with existing diagnosis standards of AECOPD. The comparative analysis on TCM syndromes such as heat phlegm obstructing the lung, lung and kidney qi deficiency, phlegm turbid obstructing the lung and their correspondent existing diagnosis standards of AECOPD showed that the common TCM syndromes in the clinic are the mixture of deficiency and excess syndromes. However, some individual symptom is contradicted to its correspondent syndrome. It was concluded that based on the Clinical Research Information Sharing System, the research on correlation analysis between syndromes and symptoms of AECOPD can provide strong evidence and methodology for the validation and revision of TCM diagnostic criteria.