Objective To investigate the effects of astragaloside Ⅳ on cardiac hypertrophy in chronic heart failure(CHF)rats,and the regulation of phosphoinositol-3-kinase/protein kinase B/glycogen synthase kinase 3 β(PI3K/Akt/GSK3β)signaling pathway.Methods CHF rat model was established by anterior descending coronary artery ligation,and randomly divided into model group,control group and experimental-L,-M,-H groups,with 8 rats in each group.Another 8 rats were hooked up without ligature as blank group.The experimental-L,-M,-H groups were given 20,40 and 80 mg·mL-1 astragaloside solution according to the dose of 5 mL·kg-1.The control group was given 1.50 mg·kg-1 lisinopril solution at a dose of 5 mL·kg-1.Both blank group and model group were given equal volume of 0.9％NaCl.Six groups of rats were given the drug once a day for 8 weeks by intragastric administration.The cardiac function of rats was measured by echocardiography,the cross-sectional area of cardiomyocytes was observed by wheat embryo lectin staining,and the expression levels of PI3K,Akt and GSK3β were detected by Western blot.Results The left ventricular ejection fraction of experimental-H,control,model and blank groups were(66.27±5.18)％,(67.75±4.98)％,(46.67±3.68)％and(81.65±6.46)％;left ventricular end-diastolic diameter was(0.53±0.05),(0.55±0.05),(0.45±0.02)and(0.57±0.05)mm;the cross-sectional areas of cardiomyocytes were(1.97±0.13),(1.61±0.18),(3.56±0.59)and(1.00±0.04)mm;the relative expression levels of phosphorylated PI3K protein were 0.45±0.04,0.71±0.07,0.11±0.02 and 0.85±0.06;the relative expression levels of phosphorylated Akt protein were 0.43±0.05,0.75±0.06,0.10±0.03 and 0.82±0.06;the relative expression levels of phosphorylated GSK3 β protein were 0.47±0.04,0.85±0.05,0.12±0.04 and 0.89±0.08,respectively.The above indexes of experimental-H group and control group were significantly different from those of model group(all P＜0.05).Conclusion Astragaloside Ⅳ can improve cardiac dysfunction and inhibit myocardial hypertrophy in CHF rats,which may be related to the regulation of PI3 K/Akt/GSK3 β signaling pathway.

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.

Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.

Objective To explore the impact of Suzi Jiangqi decoction(SJD)on the inflammatory state of patients with chronic obstructive pulmonary disease(COPD)through the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 70 patients with stable COPD,treated from April 2023 to April 2024 at the Department of Traditional Chinese Medicine and Department of Respiratory outpatient clinic of Affiliated Jinhua Hospital,School of Medicine Zhejiang University were selected and randomly divided into observation group and control group,with 35 cases in each group.The control group received tiotropium bromide powder inhalation combined with budesonide/formoterol powder inhalation treatment,while the observation group was given SJD in addition to treatment of control group.After 12 weeks of treatment,the therapeutic effects were evaluated by assessing lung function,airway mucus hypersecretion,levels of interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α,CT quantitative parameters of the lung,as well as the expression levels of IL-17,p38MAPK,nuclear factor kappa-B(NF-κB)and C-X-C motif chemokine ligand 8(CXCL8)mRNA in sputum.Results Following treatment,there was a significant improvement in lung function indicators such as first second expiratory volume/forced vital capacity％,cough score,sputum difficulty score,sputum quality score,and sputum volume score for patients in both groups,with more pronounced improvements observed in observation group(P＜0.05).The levels of serum cytokines IL-17,IL-6 and TNF-αdecreased in both groups after treatment,with observation group showing a more significant reduction(P＜0.05).Additionally,the percentage ratio of low attenuation area to lung area(LAA％),emphysema index of lung CT in observation group significantly decreased after treatment(P＜0.05).Similarly,the expression levels of IL-17,p38MAPK,NF-κB and CXCL8 mRNA in sputum were also significantly reduced after treatment in observation group(P＜0.05).Conclusion SJD may improve lung function and inflammatory status in COPD patients by regulating the MAPK signaling pathway mediated by IL-17,demonstrating a positive therapeutic effect on the treatment of COPD.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden

Rhythm control is crucial part of comprehensive management of atrial fibrillation (AF). Rhythm control can reduce the burden of AF effectively, reduce symptoms, and improve the prognosis in early AF. Antiarrhythmic drugs (AADs) are the first-line treatment for rhythm-control strategies. This consensus focuses on the principle of rhythm control in AF, the characteristics of AADs, and the medication recommendations for patients in different populations suffering from AF. Hence, this consensus aims to support clinical decision-making for AF therapy.
Humans ; Anti-Arrhythmia Agents/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Consensus ; China

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

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Purpose: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). Methods: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients’ initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)–free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. Results: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). Conclusion For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.