Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Phytotherapy ; Rheumatic Diseases ; diagnosis ; drug therapy

China ; Cognition ; Digestive System Surgical Procedures ; Enhanced Recovery After Surgery ; Humans ; Length of Stay

OBJECTIVETo explore the effect of hypoxia on the peripheral blood T lymphocyte subsets and co-stimulatory molecules in rats so as to provide the basis for studying the intervention measure.

METHODSBefore hypoxia and during hypoxia at 8 000 m for 8 h, 3 d, 6 d and 10 d the change of peripheral blood T lymphocyte subsets and co-stimulatory molecules in rats were detected by flowcytometer with three-color immunofluorescence label.

RESULTSRats were exposed to hypoxia at 8 000 m for 8 hours, and CD3+, CD8+, CD8+ CD28- lymphocyte percentages were significantly decreased (P < 0.01) compared with that before hypoxia. After 3 days of hypoxia, besides aforesaid change, CD4+ CD28+ lymphocyte percentage also prominently decreased (P < 0.01) and CD4+ CD28- prominently increased (P < 0.01). After 6 and 10 days of hypoxia, CD3+, CD4+ lymphocyte percentages were further decreased, while CD8+ CD28+ lymphocyte percentage significantly increased (P < 0.01).

CONCLUSIONAfter exposed to hypoxia at 8 000 m for 8 hours and 3 days, activation of CD8+ and CD4+ T lymphocyte was prominently decreased, while with the prolong of exposed time activation of CD8+ T lymphocyte was significantly increased.

Altitude ; Altitude Sickness ; physiopathology ; Animals ; CD4-Positive T-Lymphocytes ; physiology ; CD8-Positive T-Lymphocytes ; physiology ; Hypoxia ; immunology ; physiopathology ; Lymphocyte Activation ; physiology ; Male ; Rats ; Rats, Wistar ; T-Lymphocytes ; physiology

OBJECTIVETo explore the characteristic of hypoxia-induced immune injury, its mechanisms and the intervention measure.

METHODSThe change of immune organ index, T lymphocyte subsets of peripheral blood and immune organ in mice during hypoxia were detected. Lymphocyte apoptosis of immune organ, pathology of lung and kidney in mice were observed. Then by way of prophylaxis we studied the effect of Chinese Traditional Medicine on hypoxia-induced immune injury in mice.

RESULTS(1) Exposure to hypoxia at 8 000 m simulated altitude for 8 h resulted in marked decrease in CD4+ CD8+ thymocytes and marked increase in CD4+ CD8-, CD4- CD8+ thymocytes (P < 0.01). After 3 days of hypoxia, the mice had a much lower percentage of CD4+ T-cell (P < 0.05). The ratio of CD4+/CD8+ decreased significantly and aforesaid changes of thymocyte were further enlarged. Also mice had a pronounced increase in rates of late apoptosis or necrosis of spleen lymphocyte and thymocyte (P < 0.05). After 6 days of hypoxia, index of spleen was significantly increased (P < 0.05), index of thymus was significantly decreased (P < 0.05) and CD3+, CD4+, CD8+ lymphocyte percentage of spleen were significantly decreased (P < 0.01). Also late apoptosis or necrosis lymphocytes of spleen and thymus were further increased (P < 0.01), viable cell rates of spleen lymphocyte and thymocytes were markedly decreased (P < 0.01), early apoptosis rates of spleen lymphocyte were markedly increased (P < 0.01). There was no significant change in the percentage of CD8+ lymphocyte in peripheral blood during the whole hypoxia period. (2) New Compound Codonopsis Pilosula (NCCP), Xiang Qi Polysaccharide (XQP) and NCCP + XQP could significantly increase the number of peripheral blood CD3+, CD4+ and spleen CD4+, but had no significant influence on the number of spleen CD8+. XQP and XQP+ NCCP could significantly decrease the number of CD4+ CD8+ (P < 0.01), increase that of CD4+ CD8- (P < 0.01), and had no significant influence on CD4- CD8+ in thymus. However, NCCP didn't influence the component of thymocytes.

CONCLUSIONAfter hypoxia at 8 000 m simulated altitude decrease of lymphocyte of periphery in mice may be related with increase of apoptosis and necrosis of lymphocyte, and with increase of distribution of lymphocyte to lung in early period of exposure. NCCP and XQP have hopeful prospect in intervention study of hypoxia-induced immune injury.

Altitude ; Animals ; Apoptosis ; drug effects ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Drugs, Chinese Herbal ; pharmacology ; Flow Cytometry ; Hypoxia ; immunology ; pathology ; prevention & control ; Lung ; cytology ; Lymphocyte Count ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C ; Spleen ; cytology ; T-Lymphocyte Subsets ; cytology ; drug effects ; Thymus Gland ; cytology

OBJECTIVETo study on the protective effects of new compound codonopsis tablets against acute mountain sickness (AMS).

METHODSForty-five male plain resident soldiers stayed at 1400 m altitude for 3 months were randomly divided into two groups, control (15 men) and treatment group (30 men). Single blind trial was used in this study. The subjects in the two groups took placebo and new compound codonopsis tablets respectively for 5 days before climbing to high mountain, and continued to take for another 10 days until the 3rd day after arriving at 5200 m altitude. On the 1st , 3rd, and 5th day after they arrived at 5200 m altitude, the score and the degree of AMS symptoms of soldiers were followed up and recorded according to State Military Standard GJB1098-91--"Principles of diagnosis and treatment of benign form of acute mountain sickness", heart rate (beats/min) and arterial oxygen saturation (%) were detenrmined. On the 6th day after they arrived at high altitude, forced vital capacity(FVC), forced expired volume in one second(FEV1.0), FEV1% (FEV1.0/FVC), FEF25%-75%, peak expiratory flow (PEF) and maximal voluntary ventilation (MVV) were detected, total frequency of hands cross movement and memory of order numbers test were measured.

RESULTSComparison with control, AMS symptoms of treatment group reduced on the 1st, 3rd, and 5th day after arriving at 5200 m high altitude (P < 0.01). The degree of AMS symptoms of treatment group was significantly different from that of control. The proportion of slight symptoms in treatment group was high, and that of relative serious symptoms in control was high. Compared with control, FVC, FEV1.0, FEF25%-75%, PEF and MVV of treatment group increased (P < 0.05, P < 0.01), and Ttis, Ctis of treatment group increased (P < 0.05, P < 0.01), Atime decreased markedly (P < 0.05), there was no statistically significant difference in Etis and Sum between the two groups.

CONCLUSIONNew compound codonopsis tablets could decrease the incidence of AMS, mitigate the symptoms of AMS, and improve breathing function and fingers movement function. New compound codonopsis tablets have an obvious effect on prevention and treatment of acute mountain sickness.

Acute Disease ; Adolescent ; Altitude Sickness ; prevention & control ; Codonopsis ; chemistry ; Drug Compounding ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Phytotherapy ; Tablets ; Young Adult

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; China ; Female ; Gastrointestinal Stromal Tumors/genetics* ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local ; Prognosis ; Proto-Oncogene Proteins c-kit/genetics* ; Pyrazoles ; Pyrroles ; Receptor, Platelet-Derived Growth Factor alpha/genetics* ; Retrospective Studies ; Triazines

UHPLC-QTOF-MS was applied to non-targeted metabolomics study of mice infected with K. pneumoniae ATCC^® BAA 2146 to discover potential biomarkers and metabolic pathways that are associated with sepsis. Fifty-eight metabolites were identified by principal components analysis (PCA) and partial least-squares discriminant analysis (OPLS-DA), which was combined with variable projection importance (VIP) and nonparametric test. Eighteen of the 58 metabolites were further found to be involved in 8 metabolic pathways, including nicotinate and nicotinamide metabolism, pyrimidine metabolism, vitamin B6 metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism and glycerophospholipid metabolism.