Latest ArticlesObjective To explore whether dexmedetomidine (DEX) can alleviate exertional heatstroke (EHS)-induced rhabdomyolysis (RM) in rats by activating adrenergic α2 receptors, and to explore its potential mechanism based on the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) pathway. Methods Thirty-six male Sprague-Dawley (SD) rats, after a 7-day acclimatization training, were randomly divided into six groups: control group (CN group), EHS group, low-dose DEX group (EHS+low DEX group), high-dose DEX group (EHS+high DEX group), DEX combined with yohimbine (YOH) group (EHS+high DEX+YOH group), and YOH group (EHS+YOH), with six rats in each group. Before modeling, EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg, while the other four groups were injected intraperitoneally with an equal dose of physiological saline (0.9% NS). During modeling, except for CN group, the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model. After successful modeling, EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg, EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg, and CN group, EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline. After 6 h of observation, all rats were anesthetized, and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and myoglobin (MB) in rats; biochemical assay kit was used to measure the level of creatine kinase (CK) in rat serum; HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues; transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle; 2′,7′-dichlorofluorescent yellow diacetate (DCFH-DA) fluorescent probe was used to detect the level of reactive oxygen species (ROS); and Western blotting was performed to detect the expression levels of NOD-like receptors 3 (NLRP3), aspartic protease-1 (caspase-1) and adrenergic α2A receptor (ADRA2A). Results Compared with CN group, the levels of serum IL-6, IL-1β, TNF-α, CK and MB in EHS group rats were significantly elevated (P<0.01). HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure, hemorrhage, edema, and infiltration of inflammatory cells. Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size, cytoplasmic vacuolization, and mitochondria with obvious swelling, degranulation, and disappearance of double cristae. Compared with CN group, the expression levels of ROS, NLRP3, and caspase-1 in gastrocnemius of rats in EHS group significantly increased (P<0.01); Compared with EHS group, the levels of TNF-α, IL-6, IL-1β, CK, MB and the expression levels of ROS, NLRP3, caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX. After YOH pretreatment, compared with the EHS+high DEX group, the serum levels of TNF-α, IL-6, IL-1β, CK, MB and ROS, NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated. The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group (P<0.01), and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group (P<0.05). Conclusions DEX can alleviate EHS-induced RM by activating ADRA2A, potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.
Objective To investigate how flavokawain B (FKB) affects the proliferation and migration of triple-negative breast cancer (TNBC) cells by downregulating the androgen receptor (AR). Methods The expression of AR in breast cancer and normal tissues was analyzed using the GEPIA2 database. Expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and AR was detected in six breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, Hs-578T, and MDB-MA-231) by Western blotting. The effect of FKB (0, 10, 20, 30, 40, 50, 60 μmoL/L) treatment of 24, 48, and 72 h on the proliferative activity of SUM159PT breast cancer cells was assessed using the CCK-8 assay under normal or androgen deprivation conditions. The mRNA and protein of AR expression was measured by qRT-PCR and Western blotting after 30 μmoL/L FKB treatment of SUM159PT cells for 0, 4 and 8 h. SUM159PT cells were set as control group (treatment with 0.1% DMSO), dihydrotestosterone (DHT) group (treatment with 10 nmol/L DHT), FKB group (treatment with 15 μmol/L FKB), DHT+FKB group (treatment with 10 nmol/L DHT and 15 μmol/L FKB), AR antagonist enzalutamide (ENZA) group (treatment with 40 μmol/L ENZA), and DHT+ENZA group (treatment with 10 nmol/L DHT and 40 μmol/L ENZA) under androgen deprivation conditions. Cell proliferation, migration, and colony formation abilities in the above groups were determined using the CCK-8 method, Transwell assay, and clone formation test. Western blotting was also used to detect the expression levels of EMT-related proteins (N-cadherin, Occludin, Vimentin) and AR protein. Results AR mRNA expression level was significantly higher in breast cancer tissue than in normal breast tissue (P<0.05). AR was expressed at comparable levels in five different breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, and Hs-578T) in addition to MDB-MA-231. FKB can downregulate AR mRNA and protein levels (P<0.05). Western blotting results showed that DHT could upregulate AR protein levels in SUM159PT cells, but FKB could prevent the DHT-induced upregulation of AR protein levels (P<0.05). FKB and ENZA decreased SUM159PT cell proliferation and migration and DHT-mediated cell proliferation and migration (P<0.05). FKB and ENZA can reduce N-cadherin and Vimentin protein levels and counteract DHT-induced increases in N-cadherin and Vimentin protein levels (P<0.05). In addition, FKB may increase Occludin expression and counteract the DHT-induced decrease in Occludin protein expression (P<0.05). Conclusion Flavokawain B could inhibit the proliferation, migration, and clonogenic ability of TNBC cells by regulating AR expression.
Uric acid, the end product of purine metabolism in human body, can lead to uric acid metabolism abnormality when its production and excretion are out of balance. This abnormality has emerged as one of the important risk factors for metabolic diseases, including diabetes, obesity, hypertension and metabolic syndrome. Recent studies have found that abnormal uric acid metabolism increases the risk of occurrence and development of type 2 diabetes mellitus (T2DM) and its complications, suggesting that uric acid metabolism could be a novel approach for intervening in T2DM. This review summarizes the research progress on how uric acid metabolism abnormality influences the occurrence, development and pathogenesis of T2DM, the beneficial effects of uric acid-lowering therapy, and the selection of hypoglycemic drugs on T2DM, which provide evidence for the early prevention and treatment of T2DM and its complications.
Chronic kidney disease (CKD) commonly used dietary assessments including 24-hour dietary recall (24 h DR)/3-day dietary recall (3DDR), food frequency questionnaire (FFQ), dietary records, and estimation of dietary protein intake based on nitrogen balance. Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method, it is crucial to develop an FFQ suitable for Chinese CKD patients. This review summarizes the advantages and disadvantages of dietary assessment methods for CKD, the current research status, and the content and steps involved in establishing an FFQ, with the aim of providing reference for the modification of FFQ for Chinese CKD patients.
Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a rare and highly malignant hematologic disease with a poor prognosis. It can be divided into two categories: primary HLH and secondary HLH. HLH is characterized by a large number of abnormal immune cells that continuously activate and regulate out of control, leading to systemic inflammatory factor storm and multiple organ failure. Clinical manifestations mainly include persistent malignant hyperthermia, pancytopenia, hepatosplenomegaly, and hemophagocytosis in tissues and organs. The pathogenesis of adult HLH is complex, with rapid onset and rapid disease progression, and the fatality rate remains high. The main causes of death in HLH patients are multiple organ failure, abnormal coagulation and septic shock. Due to the specificity of HLH and the lack of effective understanding of the severity and prognosis in clinical practice, some HLH patients are misdiagnosed or overlooked, missing the best opportunity for diagnosis and treatment. Therefore, this review systematically explores and discusses the latest diagnostic and treatment progress of adult HLH, aiming to provide reference for clinical diagnosis, treatment and prognosis assessment of HLH.
Incompressible massive hemorrhage at the junction of trunk and limbs is the major cause of the potential preventable death in modern military conflicts, natural disasters and sudden trauma accidents. Because of the failure of direct compression hemostasis, aortic occlusion can reduce the amount of bleeding and provide a short time for injury recovery and accurate control of bleeding. As an effective assistant hemostasis method, resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown initial potential in military and civilian hospitals and even pre-hospital trauma emergency treatment. With the continuous development of catheter guide technology, it is expected to achieve the emergency hemostasis treatment of war wound and massive hemorrhage. Basic and pre-clinical studies have been carried out in Europe and America, and the technology has been applied to the treatment of some patients with massive bleeding, but rarely reported in China. This paper reviews the history, scope, limitations and improvement of application and military application of REBOA in the treatment of traumatic hemorrhage, so as to promote the recognition of REBOA.
Linezolid, a fully synthetic oxazolidinone antibiotic, is mainly used to treat severe infections caused by Gram-positive drug-resistant bacteria. In recent years, with the rise in drug-resistant bacteria, the clinical utilization rate of linezolid and the incidence of linezolid-related adverse reactions in the hematological system and metabolic system have increased. The main adverse reactions include thrombocytopenia, anemia and lactic acidosis. Studies have shown that the causes of adverse reactions in linezolid-induced hematological system and metabolic system are diverse, and the mechanisms are not fully elucidated. In this review, the pharmacokinetic characteristics, mechanism of adverse reactions, risk factors, as well as preventive measures and individualized drug administration strategies of linezolid in vivo were discussed based on literature reports at home and abroad, aiming to provide references for clinical prevention and treatment of linezolid-related adverse reactions of hematological system and metabolic system.
Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel. Methods A total of 180 patients (360 eyes) with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi, Tibet (average altitude of 3100 meters) were selected as the research subjects. Patients were divided into four block groups based on the course of the disease: <1 month, 1-3 months, 3-6 months, and ≥6 months, and each block group was randomly assigned to control group, traditional group and modified group by random number table method, with 60 cases in each group. Control group received routine treatment (artificial tear drops and atomization fumigation); on the basis of routine treatment, traditional group underwent traditional meibomian gland massage, and modified group underwent modified meibomian gland massage. After 3 months of treatment, the scores of symptoms and signs, total effective rate, duration of treatment and incidence of adverse events were compared among the 3 groups. Results In the intra-group comparison before and after treatment, except for control group's symptom scores difference which was not statistically significant (P>0.05), all other scores decreased significantly (P<0.05). In the inter-group comparison after treatment, the scores of both traditional group and modified group were significantly better than those of control group (P<0.05), but no significant difference was observed in symptom and sign scores between traditional and modified groups (P>0.05). Compared with control group, the total effective rates of traditional group and modified group both significantly increased (P<0.01), but there was no significant difference in total effective rate between traditional and modified groups (P>0.05). The treatment time in modified group was significantly longer than that in control group (P<0.05), but significantly shorter than that in traditional group (P<0.05). The incidence of adverse events was significantly lower in modified group than that in traditional group (P<0.001). Conclusion In high-altitude areas, modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective, non-invasiveness and easy to perform, and suitable for promoting and application in military field training.
Objective To investigate the diagnostic value of CT radiomics features in pulmonary alveolar proteinosis (PAP). Methods The general data and clinical characteristics of 24 patients with PAP in the Chinese PLA General Hospital from November 2008 to August 2022 were retrospectively collected and analyzed. Another 53 patients with other diffuse lung diseases except for PAP during the same period served as control group. The differences in the 10 conventional CT signs (semantic features) and 107 radiomics features between the two groups were compared. All patients were randomly divided into the training group (n=53) and the validation group (n=24) at a ratio of 7:3. CT semantic feature model, radiomics model and combined model to diagnose PAP were constructed in training group, and the diagnostic efficacy of models was compared using the receiver operating characteristic (ROC) curve in validation group. Decision curve analysis (DCA) was used to assess the value of models for practical clinical application. Radscore was calculated for the model with the highest diagnostic efficacy. Results A total of 24 patients with pathologically confirmed PAP were enrolled, with a male to female ratio of 3:1 and an average age of (44.6±15.2) years. The main clinical symptoms of patients with PAP included shortness of breath, cough, sputum and chest tightness. Compared with control group, the incidence of pleural effusion in PAP group was significantly lower (P<0.05), while no significant differences were observed in other CT features (P>0.05). The areas under the curve (AUC) of the semantic feature model for diagnosing PAP in training and validation group were 0.590 and 0.594, respectively, and in validation group, the accuracy, sensitivity, and specificity for diagnosis of PAP were 0.188, 1.000, and 0.188, respectively. The AUCs of the radiomics model in training group and validation group were 0.845 and 0.867, respectively, and in validation group, the accuracy, sensitivity, and specificity were 0.641, 0.938, and 0.703, respectively. The AUCs of the combined model in training group and validation group were 0.850 and 0.883, respectively, and in validation group, the accuracy, sensitivity, and specificity were 0.688, 0.750, and 0.938, respectively. The AUCs of the radiomics model and the combined model were significantly greater than that of the semantic feature model, but there was no significant difference in the AUCs between the first two models. The decision curve analysis showed that both the radiomics model and the combined model had high application value for predicting PAP. Conclusion CT radiomics shows higher clinical value in the diagnosis of PAP compared with conventional CT features.
Objective To explore the clinicopathological characteristics, prognosis and influencing factors of different pathological subtypes of gastric signet ring cell carcinoma (GSRC). Methods A retrospective analysis was performed on the clinical data of 232 patients with GSRC collected from January 2016 to December 2018 in Lanzhou University Second Hospital. According to the WHO classification criteria for GSRC, the patients were divided into pure gastric signet-ring cell carcinoma (pGSRC, n=36) and mixed gastric signet-ring cell carcinoma (mGSRC, n=196). The follow-up as of September 30, 2022, the survival analysis was done using Kaplan-Meier method, the univariate and multivariate Cox regression were performed to analyze the risk factors affecting the prognosis of GSRC patients. Results The median survival time of pGSRC and mGSRC patients was 41.0(6.0-70.0) months and 24.0(2.0-74.0) months, respectively. Kaplan-Meier analysis showed that combination with diabetes, anemia, tumor diameter, nerve invasion, lymphovascular invasion, T stage, N stage, GSRC pathological subtype, CA125 and tumor diameter could affect the overall survival (OS) of patients with GSRC after radical gastrectomy (P<0.05), but Her-2, whether adjuvant chemotherapy or not and others elements had no significant effect on OS of GSRC patients after radical gastrectomy (P>0.05). Univariate Cox regression analysis showed that the combination with diabetes (P=0.031), anemia (P=0.028), tumor diameter >5 cm (P=0.009), nerve invasion (P=0.002), lymphovascular invasion (P=0.002), mGSRC pathological type (P=0.039), T2-T4 stage (P=0.001), N1-N4 stage (P=0.004), pTNM stage Ⅲ (P=0.044), the number of lymph node metastasis >30 (P=0.044) and CA125 positive (P=0.009) were related to the prognosis of patients with GSRC after radical gastrectomy. Multivariate Cox regression analysis showed that mGSRC pathological type (P=0.035), T2-T4 stage (P=0.003), CA125 positive (P=0.010) were independent risk factors for poor prognosis of patients with GSRC after radical gastrectomy. Conclusion Compared with pGSRC, patients with mGSRC at diagnosis have higher pTNM stages, more aggressive, and shorter median survival time. mGSRC pathological type, T2-T4 stage, and CA125 positive were all independent factors affecting the prognosis of patients with GSRC.