The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

Objective To evaluate the clinical efficacy of traditional Chinese medicine turbid phlegm obstructing lung decoction on patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and its influence on laboratory indexes.Methods A total of 191 patients with AECOPD who were hospitalized in the First People's Hospital of Changde from January 2021 to December 2022 were selected.Patients were divided into observation group(96 cases)and control group(95 cases)according to their treatment intention.The control group received conventional treatment of western medicine,and the observation group received oral administration of traditional Chinese medicine turbid phlegm obstructing lung decoction for one week.TCM symptom scores,COPD assessment test(CAT),lung function,laboratory indicators and efficacy were compared between two groups.Results The total effective rate of observation group was significantly higher than that of control group(χ2=4.573,P=0.030).After treatment,TCM symptom score,CAT score,hypersensitive C-reaction protein(hsCRP)and interleukin-6(IL-6)of patients in both groups were significantly lower than before treatment,percentage of forced vital capacity to predicted value(FVC%)and percentage of forced expiratory volume in one second to predicted value(FEV1%)were significantly higher than before treatment(P<0.05),arterial partial pressure of carbon dioxide(PaCO2)of observation group was lower than before treatment,and arterial partial pressure of oxygen(PaO2)was higher than before treatment(P<0.05).The TCM symptom score,CAT score,hsCRP and IL-6 of observation group were significantly lower than those of control group,while FVC%,FEV1%and PaO2 were significantly higher than those of control group(P<0.05).Conclusion On the basis of western medicine treatment,traditional Chinese medicine turbid phlegm obstructing lung decoction can more effectively improve clinical symptoms of AECOPD patients,relieve the inflammation in the body,contribute to the recovery of lung function and improve the quality of life of patients.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Humans ; Clinical Relevance ; Leukemia, Myeloid, Acute ; Transcription Factors ; Neoplasm Proteins ; Antigens, CD ; GPI-Linked Proteins

Abstract: Objective　To analyze the epidemiological characteristics and related factors of norovirus in Guangxi from 2015 to 2020, and to provide scientific recommendations for norovirus prevention and control. Methods The foodborne diseases surveillance data were collected from 11 sentinel hospitals through the National Foodborne Disease Monitoring and Reporting System from 2015 to 2020. R software with version 4.0.3 was used for descriptive and statistical analysis, including epidemic curve, chi-square test, and trend chi-square and so on. Logistic regression was used to analyze norovirus-related factors, OR values and 95% confidence intervals were calculated respectively with the statistical test level of P<0.05. Results There were 1 008 norovirus cases detected, with a detection rate of 12.75% (1 008/7 903). Children with age less than 5 years (OR=1.43, 95%CI: 1.13-1.82) and patients at age 20-45 (OR=1.45, 95%CI: 1.13-1.87) were high risk population. The detection rate was higher in autumn (OR=1.29, 95%CI: 1.08-1.53) but lower in summer (OR=0.67, 95%CI: 0.55-0.80). In addition, the tourist area (Guilin City) presented a higher detection rate than other areas (OR=1.41, 95%CI: 1.10-1.80). Aquatic products (OR=1.40, 95%CI: 1.03-1.91), meat and dairy products (OR=1.31, 95%CI: 1.06-1.61) were high-risk foods for norovirus infection. The prevention and control policies of COVID-19 can reduce the possibility of norovirus by 61% (OR=0.39, 95%CI: 0.31-0.49) showed a declining trend (Trend χ2=85.33, P<0.001). In addition, prolonged visit time can lead to 19%-23% decrease in the detection rate of norovirus (OR24-48 hours=0.81, 95%CI: 0.70-0.95; OR>48 hours=0.77, 95%CI: 0.63-0.93). Conclusions　The epidemic of norovirus presented seasonal and regional distribution in Guangxi with a declining detection rate trend in diarrhea patients during recent 6 years. Young children were high-risk population in infection norovirus. The intake of seafood can increase the risk of norovirus infection. The prevention and control policies of COVID-19 can sharply decrease the possibility of infection norovirus. The monitoring of key foods such as seafood should be strengthened, and the early screening of suspected cases should be taken. The norovirus monitoring should be improved to ensure the health of the population.

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×10⁹/L, among which 15 cases (68.18%) were >10×10⁹/L, and the median count of platelet (PLT) was 24(4-55)×10⁹/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.
Middle Aged ; Humans ; Male ; Female ; Aged ; Leukemia, Myelomonocytic, Acute ; Retrospective Studies ; Leukemia, Myeloid, Acute/diagnosis* ; Prognosis ; Mutation ; Receptors, Colony-Stimulating Factor/genetics*

ObjectiveTo investigate the analgesic effect and its mechanism of （-）-gallocatechin gallate （EGCG） on high-frequency stimulation （HFS）-induced chronic primary pain in female mice. MethodsThe model of chronic primary pain in female mice were established by HFS of sciatic nerve in left hind limb at 10 V （100 Hz， 0.5 ms， 4 trains of 1-s duration at 10-s intervals）. The mice were randomly divided into sham operation group， vehicle （saline） + HFS group， different concentrations of EGCG + HFS groups （4~5 mice in each group）. 10 μL EGCG （10， 20， 50， 200 μmol/L） or vehicle was injected intrathecally 1 h before surgery. The therapeutic effect of EGCG was evaluated by paw withdrawal threshold （PWT） and analgesic efficiency. Immunofluorescence of lumbar spinal cord was used to evaluate the possible mechanisms. ResultsCompared with vehicle HFS group， intrathecal administration of EGCG alleviated HFS-induced mechanical allodynia in a dose-dependent manner， and the maximum analgesic efficiency was 84.95%. EGCG also blocked the increases in c-Fos （a marker for neuronal excitability） positive neurons and the expressions of calcitonin gene-related peptide （CGRP⁺） terminals， Iba1 （a marker for microglia） and GFAP （a marker for astrocytes） in the ipsilateral spinal dorsal horn. ConclusionIntrathecal injection of EGCG exerts an analgesic effect against HFS-induced chronic primary pain， mediated by inhibiting the increases in presynaptic CGRP⁺ terminals， postsynaptic neuronal excitability and glial activation in the spinal dorsal horn.

ObjectiveTo evaluate the value of four-chamber view （4CV） and three-vessel trachea view （3VTV） combined with HD-flow in screening for fetal cardiovascular mailformations （CVMs） in unselected population during early pregnancy （11~13⁺⁶ weeks）. MethodsFrom May 2018 to December 2019， 1145 fetuses were ultrasonic scanned routinely at 11~13⁺⁶ weeks at our hospital. The 4CV and 3VTV of fetal hearts were assessed by Power Doppler with flow direction （high definition flow， HD-flow），and the sonographic findings and follow-up outcomes were documented. Suspected CVMs were confirmed by the postpartum echocardiography or autopsy results. The sensitivities， specificities， PPVs and NPVs of diagnostic tests were compared among the two views and combined views. ResultsThere were 948 fetuses included in this study， with 19 cases of CVMs. The sonographic findings of 12 cases （12/19） with 22 CVMs were consistent entirely with the follow-up outcomes， including 7 cases of complex CVMs. In 1 case （1/19） with complex CVM， the diagnosis was not entirely consistent to the autopsy result. The 6 cases （6/19） of abnormal atrioventricular septum were not detected in early pregnancy. In the 19 cases of CVMs， abnormalities were found by displaying 4CV in 8 cases， by displaying 3VTV in 11 cases， and by displaying 4CV combined with 3VTV in 13 cases. The sensitivity of 4CV， 3VTV， 4CV+3VTV was 31.5%， 57.9%， 68.4%， with significant difference between 4CV and 4CV+3VTV（P=0.016） .The specificity and PPVs were all 100% （P>0.05）. The NPVs of them were 98.6%， 99.1% and 99.4%， with no statistical difference （P>0.05）. ConclusionsDisplaying the 4CV combined with 3VTV of fetal heart in the first-trimester ultrasound examination resulted in higher detect ratio of fetal cardiovascular malformations rather than scanning only with the 4CV， especially for those serious CVMs with poor prognosis， which is important for clinical management appropriately.