Objective To study the clinical characteristics and bacterial antimicrobial susceptibility testing results of patients with clinically isolated Ralstonia pickettii(R.pickettii),and provide basis for the rational use of antimi-crobial agents.Methods Inpatients with R.pickettii infection who were treated at the Tianjin First Central Hospi-tal from January 2014 to December 2023 were analyzed retrospectively.Clinical characteristics and antimicrobial sus-ceptibility testing results were analyzed.Results A total of 80 strains of Ralstonia spp.were isolated over 10-year period,including 42(52.5％)non-repetitive strains of R.pickettii.Among 42 R.pickettii strains,64.3％were isolated from male patients.The strains isolated from sputum,catheter,blood,throat swabs,and drainage fluid specimens accounted for 38.1％,28.6％,19.0％,4.8％,and 2.4％,respectively.The clinical distribution of R.pickettii was highest in the intensive care unit(ICU),with a proportion of 52.4％.The number of infected patients first increased and then decreased with the years,followed by a slight fluctuation.There was no statistically signifi-cant difference in the number of infected patients in each department over the years(P＞0.05).R.pickettii had higher susceptibility rates to doxycycline,levofloxacin,ciprofloxacin,and minocycline,susceptibility rates were 78.3％-90.9％,but was completely resistant to compound sulfamethoxazole and cefazolin(100％),it also had higher resistance rates to aztreonam,colistin,cefotetan,tobramycin,amikacin,ceftazidime,and gentamicin(80.0％-97.4％).There was no statistically significant difference in the resistance rates to 21 antimicrobial agents among different years(all P＞0.05).Conclusion R.pickettii is mainly from ICU,and the majority of the infected population are adult males.Most strains are isolated from sputum and catheter.R.pickettii presents multidrug re-sistance.Attention should be paid to the changes in the resistance rates of antimicrobial agents,strengthen the dy-namic monitoring of bacterial resistance and guide the rational selection of antimicrobial agents in clinic,implement early and effective treatment to improve the prognosis of the patients.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg^-1•d^-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg^-1•d^-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.
Animals ; Rats ; Rats, Sprague-Dawley ; Propionates ; Serotonin ; Depression/therapy* ; Electroacupuncture ; Fatty Acids, Volatile ; Stroke/complications* ; Acetic Acid ; Butyric Acid ; Water

OBJECTIVE: To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology. METHODS: The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn. RESULTS: Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters. CONCLUSION Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.
Humans ; Moxibustion ; Acupuncture Points ; Acupuncture Therapy ; Stroke/therapy* ; Data Mining ; Epilepsy

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser2P),and Ser5-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser5P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rifl.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interact-ing with RNA Pol Ⅱ Ser2P and Ser5P.

Animals ; Schistosoma japonicum ; Colitis, Ulcerative

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8⁺T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.
B7-H1 Antigen/metabolism* ; Humans ; Ki-67 Antigen ; Prognosis ; Recurrence ; Triple Negative Breast Neoplasms/surgery*