BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

AIM:To investigate the molecular mechanisms of KG-1 cell proliferation by profiling its responses to various protein kinase inhibitors.METHODS:CCK-8 assay,real time quantitative PCR(qRT-PCR)and Western-blot were used to detect the effect of various protein kinase inhibitors on KG-1 cell proliferation,the expression levels of mRNA and phosphorylation level of signaling pro-teins in the FGFR1 downstream pathways.RE-SULTS:NVP-BGJ398 and PD173074 effectively in-hibited the proliferation of KG-1 cells,indicative of a crucial role of FGFR downstream signaling.After treatment with FGFR inhibitors,the levels of p-FG-FR1OP2-FGFR1 and p-STAT5 decreased significantly(P<0.001),p-AKT decreased slightly(P<0.05),with-out affecting the p-ERK level(P>0.05).CONCLU-SION:FGFR1OP2-FGFR1 mainly acts on the down-stream STAT5 signaling pathway to promote cell proliferation.Comprehensive protein kinase inhibi-tion analysis is a reliable and direct approach to identify functional drivers of cancer cell prolifera-tion.

Objective To analyze the epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan during 2016-2020, and to provide a basis for formulating effective prevention and control strategies and measures. Methods Using the National Tuberculosis Information Management System, a descriptive statistical analysis was performed on the medical records of elderly (≥60 years old) pulmonary tuberculosis patients registered in Wuhan from 2016 to 2020. Results A total of 9 427 elderly pulmonary tuberculosis patients were registered in Wuhan during 2016-2020, accounting for 32.07% of the total number of registrations in the whole population. The reported incidence rate of tuberculosis in the elderly was significantly higher than that in the total population, and the reported incidence rates in both the elderly and the general population showed declining trends (whole population χ²_trend=216.97, P<0.05, elderly population χ²_trend=153.57, P<0.05). The time distribution showed that more cases occurred from April to November (70.90%). The top three districts with the largest number of registered cases were far urban areas, namely Huangpi District (13.81%), Xinzhou District (11.55%), and Jiangxia District (9.82%). The ratio of male to female with pulmonary tuberculosis in elderly patients was 2.85:1. Among the elderly pulmonary tuberculosis, the most registered cases were in the age group of 60 ~ years old, followed by 65 ~ years old. The proportion of smear-positive in elderly patients with pulmonary tuberculosis retreatment was 16.83%. Conclusion From 2016 to 2020, the epidemic situation of elderly pulmonary tuberculosis showed a downward trend in Wuhan. However, the elderly population with tuberculosis registrations still accounted for a relatively high proportion of the total population. According to the epidemiological characteristics of pulmonary tuberculosis among the elderly, the city should carry out tuberculosis prevention and control work in a timely, appropriate and focused manner.

The paper introduces professor ZHUANG Li-xing's clinical experience in treatment of dyskinesia of Parkinson's disease with acupuncture at triple-acupoint prescription. In pathogenesis, dyskinesia of Parkinson's disease refers to yang deficiency and disturbing wind. In treatment, acupuncture focuses on warming yang, promoting the circulation of the governor vessel, regulating the spirit and stopping trembling; and Baihui (GV 20), Suliao (GV 25) and Dingchanxue (Extra) are selected to be "trembling relief needling". In combination with Jin's three needling, named "three-trembling needling" "three-governor-vessel needling" and "three-spasm needling", the triple-acupoint prescription is composed. To ensure the favorable therapeutic effect, this prescription is modified according to the symptoms and the specific techniques of acupuncture are combined such as conducting qi, harmonizing yin and yang, and manipulating gently for reinforcing and reducing.
Humans ; Acupuncture Points ; Parkinson Disease/therapy* ; Acupuncture Therapy/methods* ; Acupuncture ; Dyskinesias

ObjectiveTo investigate the effects of Asari Radix et Rhizoma-Zingiberis Rhizoma herb pair （XGHP） on lung and liver lipid metabolism in rats with chronic obstructive pulmonary disease （COPD）. MethodForty SD male rats were divided into a normal group （10 rats） and a model group （30 rats）. The method of cigarette smoke + tracheal injection of lipopolysaccharide（LPS） + cold stimulation was used to replicate COPD model with the syndrome of cold phlegm obstruction in lung. A COPD group， a XGHP group （5.4 g·kg^-1·d^-1）， and an aminophylline group （0.5 g·kg^-1·d^-1） were established after successfully inducing the model， with 10 rats in each group. After treatment， the serum triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels of rats in each group were measured. Gas chromatography-mass spectrometer （GC-MS） was used to detect the differential metabolites in the lung and liver tissues of rats in each group， and the relevant targets of the differential metabolites were predicted by network pharmacology. Molecular docking was used to verify the binding ability of key components in XGHP to the relevant targets in network pharmacology. The mRNA and protein expression levels of peroxisome proliferator-activated receptor α （PPARα） and fatty acid binding protein 4 （FABP4） in lung and liver tissues of rats in each group were detected by real-time polymerase chain reaction （PCR） and Western blot. ResultXGHP significantly increased the levels of TG， TC， and LDL-C in serum （P<0.05）， and decreased the level of HDL-C （P<0.05） in rats with COPD. GC-MS results showed that there were 8 lung differential metabolites and 17 liver differential metabolites in the COPD group and XGHP group. Network pharmacology predicted 59 common targets for the two differential metabolites， mainly enriched in the PPAR signaling pathway. Molecular docking results showed that the main components in XGHP were well combined with both PPARα and FABP4. Real-time PCR showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 mRNA （P<0.05）， and Western blot showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 proteins （P<0.05） in lung and liver tissues of rats with COPD. ConclusionXGHP effectively improves the blood lipid levels of rats with COPD， which may be related to the increase of the expression levels of PPARα and FABP4 mRNA and proteins in the PPAR signaling pathway， thus regulating lung and liver lipid metabolism.

Background::As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.Methods::Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.Results::Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera ( Enterobacter and Enterococcus) are unaffected by rifaximin therapy. Conclusions::IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.Registration::Chinese Clinical Trial Registry, ChiCTR1800017911.

Objective:To explore the characteristics of the sleep structures of patients with both chronic insomnia and obstructive sleep apnea (OSA) in plateau area.Methods:Polysomography Alice 5 was applied to 23 patients with primary chronic insomnia [insomnia group, age (48.2±9.9) years], 22 patients with both chronic insomnia and OSA [comorbidity group, age (46.8±8.9) years], who both came from Qinghai Red Cross Hospital between January, 2014 to June, 2015 and 20 subjects with normal sleep [healthy group, age (46.2±7.1) years] in plateau area (mainly in Xining, altitude 2 250 meters or above) to compare and explore their sleep structures by the whole night sleep monitoring in the sleep monitoring room. The sleep structures were compared according to the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events.Results:Compared to healthy group, insomnia group and comorbidity group both had significantly lower sleep efficiency [(62.4%±16.7%), (59.8%±16.0%) vs (80.9%±8.8%)], non-rapid eye movement (NREM) phase 2 sleep ratio [(37.9%±12.2%), (36.2%±12.5%) vs (49.7%±6.2%)] and rapid eye movement (REM) sleep ratio [(7.7%±4.0%), (6.5%±4.0%) vs (12.5%±4.6%)] (all P<0.05); comorbidity group had a significantly higher oxygen desaturation index than insomnia group and healthy group [(30.8±29.2) vs (7.9±7.5), (5.9±2.7) times/h] ( P<0.05); insomnia group′s sleep latency of NREM3 stage was significantly longer than comorbidity group and healthy group [(148.9±113.6) vs (89.3±51.8), (59.1±40.3) min] (both P<0.05). Conclusion:Patients with both chronic insomnia and OSA and patients with chronic insomnia only in plateau area have different sleep structures, and both of their sleep quality are lower than the people with normal sleep; patients with both chronic insomnia and OSA could enter deep sleep more quickly after sleep onset.