Zhonghua wei zhong bing ji jiu yi xue最新文献

Objective: To investigate whether 6-shogaol (6-SH) alleviates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal autophagy and calcium overload by promoting the expression of microRNA-26a-5p (miR-26a-5p) and inhibiting death-associated protein kinase 1 (DAPK1), and to explore its potential mechanisms.

Methods: Primary cultured logarithmic growth phase mouse hippocampal neurons HT22 cells were taken and cell counting kit-8 (CCK-8) was used to detect cell viability, searching for the optimal concentration of Na₂S₂O₄. HT22 cells were divided into blank control group (NC group), OGD/R group (sugar-free culture medium + 10 mmol/L Na₂S₂O₄ treatment for 1.5 hours followed by normal culture medium for 4 hours), 6-SH intervention group (cultured with 10 μmol/L 6-SH for 4 hours after OGD), negative control inhibitor pretreatment group (transfected with negative control inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours), and miR-26a-5p inhibitor pretreatment group (transfected with miR-26a-5p inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours). Cell viability of each group was detected by CCK-8 method; cell ultrastructure was observed under transmission electron microscopy; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of DAPK1 and miR-26a-5p; molecular docking were used to verify the interaction between 6-SH and miR-26a-5p; dual-luciferase assay was used to verify the targeting relationship between DAPK1 and miR-26a-5p; flow cytometry was used to determine the levels of intracellular Ca²⁺; Western blotting was used to detect the protein expressions of phosphorylated-glutamate receptor 2B (p-NMDAR2B) Ser1303, DAPK1, autophagy related protein Beclin1, light chain 3 (LC3), and p-DAPK1 Ser308; immunofluorescence was used to detect the expression of LC3 and Beclin1.

Results: The results of the CCK-8 assay showed that the cell viability of the 6-SH intervention group was significantly increased compared to the OGD/R group, while the cell viability of the miR-26a-5p inhibitor pretreatment group was significantly decreased compared to the 6-SH intervention group. Transmission electron microscopy revealed that the number of autophagosomes in the 6-SH intervention group was significantly reduced compared to the OGD/R group, while the number of autophagosomes in the miR-26a-5p inhibitor pretreatment group was significantly increased compared to the 6-SH intervention group. RT-qPCR results showed that compared with the OGD/R group, the expression of miR-26a-5p was significantly upregulated and the expression of DAPK1 mRNA was significantly downregulated in the 6-SH intervention group; compared with the 6-SH intervention group, the expression of miR-26a-5p was significantly downregulated and the expre

Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.

Objective: To observe the clinical characteristics and prognosis of patients with acute respiratory distress syndrome (ARDS) in sepsis combined with acute gastrointestinal injury (AGI) of different grades, and to further explore the risk factors associated with the poor prognosis of patients.

Methods: The clinical data of patients with septic ARDS admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from March to October 2023 were collected. According to the 2012 European Association of Critical Care Medicine AGI definition and grading criteria, the patients were categorized into AGI grade 0- IV groups. The clinical characteristics and 28-day clinical outcomes of the patients were observed; the risk factors related to the prognosis of patients with septic ARDS combined with AGI were analyzed by using univariate and multivariate Logistic regression; and the receiver operator characteristic curve (ROC curve) and calibration curves were plotted to evaluate the predictive value of each risk factor on the prognosis of patients with septic ARDS combined with AGI.

Results: A total of 92 patients with septic ARDS were enrolled, including 7 patients in the AGI 0 group, 20 patients in the AGI I group, 38 patients in the AGI II group, 23 patients in the AGI III group, and 4 patients in the AGI IV group. The incidence of AGI was 92.39%. With the increase of AGI grade, the ARDS grade increased, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), intra-abdominal pressure (IAP), white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), lymphocyte percentage (LYM%), and 28-day mortality all showed a significant increasing trend, while the oxygenation index (PaO₂/FiO₂) showed a significant decreasing trend (all P < 0.05). Pearson correlation analysis showed that APACHE II score, SOFA score, and ARDS classification were positively correlated with patients' AGI grade (Pearson correlation index was 0.386, 0.473, and 0.372, respectively, all P < 0.001), and PaO₂/FiO₂ was negatively correlated with patients' AGI grade (Pearson correlation index was -0.425, P < 0.001). Among the patients with septic ARDS combined with AGI, there were 68 survivors and 17 deaths at 28 days. The differences in APACHE II score, SOFA score, ARDS grade, AGI grade, PaO₂/FiO₂, IAP, AGI 7-day worst value, length of ICU stay, and total length of hospital stay between the survival and death groups were statistically significant. Univariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.350, 95% confidence interval (95%CI) was 1.071-1.702, P = 0.011], PaO₂/FiO₂ (OR = 0.964, 95%CI was 0.933-0.996, P = 0.027) and AGI 7-day worst value (OR = 2.103, 95%CI was 1.194-3.702, P = 0.010) were the risk factors for 28-day mortality

Objective: To explore the protective effect of methylene blue (MB) on myocardial injury in sepsis and its possible signaling pathway.

Methods: A total of 32 female Wistar rats were randomly divided into sham operation group, sepsis model group, MB prevention group, and MB treatment group, with 8 rats in each group. The MB prevention group was injected with 15 mg/kg MB in the peritoneal cavity 6 hours before modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. The sepsis model was established by cecal ligation puncture (CLP); the sham operation group was only subjected to an exploratory incision without ligation or puncture of the caecum. The MB treatment group was injected with 15 mg/kg MB in the peritoneal cavity 0.5 hours after modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. Peripheral blood and myocardial tissue were collected from each group at 6 hours and 12 hours after modeling. Histological changes in the myocardial tissue were observed under the microscope; the levels of serum cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); and the expressions of inducible nitric oxide synthase (iNOS), light chain 3 (LC3), and p62 in the myocardial tissue were detected by Western blotting.

Results: Under light microscopy, no obvious abnormalities were found in the myocardium of the sham operation group; the myocardium of the sepsis model group showed obvious inflammatory changes; the myocardium of the MB prevention group showed mild inflammatory changes at 6 hours after modeling, severe inflammatory changes at 12 hours but less severe than the sepsis model group; the myocardium of the MB treatment group showed more obvious inflammatory changes at 6 hours after modeling but less severe than the MB prevention group at 12 hours after modeling, and the inflammatory changes at 12 hours after modeling were alleviated but more severe than the 6 hours after modeling in MB prevention group. Compared with the sham operation group, the levels of cTnI, CK-MB, TNF-α and IL-6 in the MB prevention group at 6 hours and 12 hours after modeling were not significantly changed; compared with the sepsis model group, the cTnI, CK-MB, TNF-α and IL-6 levels in the MB treatment group at 6 hours and 12 hours after modeling were significantly lower [cTnI (ng/L): 175.03±12.26, 411.24±21.20 vs. 677.79±43.95 at 6 hours of modeling, 159.52±6.44, 412.46±32.94 vs. 687.61±55.09 at 12 hours of modeling; CK-MB (ng/L): 8.38±0.49, 16.87±1.41 vs. 24.87±1.74 at 6 hours of modeling, 7.94±0.30, 16.66±2.03 vs. 25.02±7.29 at 12 hours of modeling; TNF-α (ng/L): 26.98±3.31, 46.95±3.74 vs. 112.60±6.64 at 6 hours of modeling, 31.31±5.83, 90.97±5.14 vs. 149.30±4.67 at 12 hours of modeling; IL-6 (ng/L): 40.86±4.48, 128.90±3.14 v

Objective: To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism.

Methods: Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue.

Results: After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and

Objective: To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism.

Methods: Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting.

Results: Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the contr

Resveratrol is a polyphenolic plant extract with many biological activities such as anti-inflammation and anti-oxidative stress. Vascular endothelial cell (VEC) is the main sites for maintaining normal vascular permeability and participating in vasomotor regulation and substance exchange. VEC injury plays a key role in various diseases or pathological processes such as cardiovascular disease, chronic inflammation and sepsis. Studies have shown that resveratrol protects VEC and reduces endothelial damage by regulating nitric oxide (NO) and its related enzymes, reducing oxidative stress and inhibiting apoptosis, thereby exerting beneficial effects.

Objective: To explore the optimal blood glucose-lowering strategies for patients with diabetic ketoacidosis (DKA) to enhance personalized treatment effects using machine learning techniques based on the United States Critical Care Medical Information Mart for Intensive Care- IV (MIMIC- IV).

Methods: Utilizing the MIMIC- IV database, the case data of 2 096 patients with DKA admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center from 2008 to 2019 were analyzed. Machine learning models were developed, and receiver operator characteristic curve (ROC curve) and precision-recall curve (PR curve) were plotted to evaluate the model's effectiveness in predicting four common adverse outcomes: hypoglycemia, hypokalemia, reductions in Glasgow coma scale (GCS), and extended hospital stays. The risk of adverse outcomes was analyzed in relation to the rate of blood glucose decrease. Univariate and multivariate Logistic regression analyses were conducted to examine the relationship between relevant factors and the risk of hypokalemia. Personalized risk interpretation methods and predictive technologies were applied to individualize the analysis of optimal glucose control ranges for patients.

Results: The machine learning models demonstrated excellent performance in predicting adverse outcomes in patients with DKA, with areas under the ROC curve (AUROC) and 95% confidence interval (95%CI) for predicting hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stays being 0.826 (0.803-0.849), 0.850 (0.828-0.870), 0.925 (0.903-0.946), and 0.901 (0.883-0.920), respectively. Analysis of the relationship between the rate of blood glucose reduction and the risk of four adverse outcomes showed that a maximum glucose reduction rate > 6.26 mmol×L^-1×h^-1 significantly increased the risk of hypoglycemia (P < 0.001); a rate > 2.72 mmol×L^-1×h^-1 significantly elevated the risk of hypokalemia (P < 0.001); a rate > 5.53 mmol×L^-1×h^-1 significantly reduced the risk of GCS score reduction (P < 0.001); and a rate > 8.03 mmol×L^-1×h^-1 significantly shortened the length of hospital stay (P < 0.001). Multivariate Logistic regression analysis indicated significant correlations between maximum bicarbonate levels, blood urea nitrogen levels, and total insulin doses with the risk of hypokalemia (all P < 0.01). In terms of establishing personalized optimal treatment thresholds, assuming optimal glucose reduction thresholds for hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stay were x₁, x₂, x₃, x₄, respectively, the recommended glucose reduction rates to minimize the risks of hypokalemia and hypoglycemia should be ≤min{x₁, x₂}, while those to reduce GCS score decline and extended hospital stay should be ≥ max{x