Objective To explore the effects of schisandrin B (Sch B) on myocardial remodeling and electrocardiogram changes of atrial fibrillation rats. Methods A total of 60 SD rats were randomly divided into normal group, model group, positive control group, low-dose group and high-dose group (12 rats each). Except normal group, rats in other groups were injected with Ach-CaCl₂ mixed solution through tail vein to establish atrial fibrillation model. From the 4th day of modeling, 1 h before Ach-CaCl₂ mixture injection through tail vein injection, rats in positive control group, low-dose and high-dose Sch B group were given intragastric administration of amiodarone 50 mg/kg, Sch 40 mg/kg and Sch 80 mg/kg, respectively, once a day for consecutive 7 days. ECG of each group was recorded during the last caudal vein injection of Ach-CaCl₂ mixture. Echocardiography was used to measure left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular end-diastolic diameter (LVEDD)and left ventricular end-systolic diameter (LVESD). The relative expression levels of collagen Ⅰ (Col Ⅰ) and collagen Ⅲ (Col Ⅲ)mRNA were detected by qRT-PCR, the pathological changes of atrial tissue were observed by HE staining, the myocardial fibrosis was detected by Masson staining, and the relative expression levels of p-Akt, p-mTOR and p-S6K were detected by Western blotting. Results The results of echocardiography showed that LVEF and LVFS were higher, while LVEDD and LVESD were shorter in positive control group, low-dose and high-dose Sch B groups than in model group; Compared with the low-dose Sch B group, the LVEF and LVFS increased significantly, and the LVEDD and LVESD shortened significantly in high-dose Sch B group (P<0.05). The results of qRT-PCR showed that the relative expression levels of Col Ⅰ and Col Ⅲ mRNA were lower in positive control group, low-dose and high-dose Sch B group than in model group; Compared with the low-dose Sch B group, the relative expression levels of Col Ⅰ and Col Ⅲ mRNA were decreased in high-dose Sch B group (P<0.05). The results of HE staining showed that the cardiomyocytes in normal group were in order and dense, and the morphology of the cells was normal with no edema in the interstitium. While those in model group were out of order, intercellular space widened and intercellular interstitium was with edema. The injury of myocardial cells in positive control group, low-dose and high-dose Sch B group was significantly improved. Masson staining showed that the percentage of collagen area in atrial tissue of rats decreased in positive control group, low-dose and high-dose Sch B groups than that in model group; Compared with the low-dose Sch B group, the percentage of collagen area in atrial tissue of rats decreased in high-dose Sch B group (P<0.05). Western blotting results showed that the relative protein expression levels of p-Akt, p-mTOR and p-S6K were lower in positive control group, low-dose and high-dose Sch B groups than those in model group;Compared with the low-dose Sch B group, the relative expression levels of p-Akt, p-mTOR and p-S6K proteins were decreased in high-dose Sch B group (P<0.05). Conclusion Sch B can mitigate rats' atrial fibrillation, improve myocardial injury and cardiac dysfunction, possibly by inhibiting the Akt/mTOR/S6K signaling pathway.

Objective To observe the effects of free sound field blast shock waves on damage effect and neuro behavior in rats, so as to provide the experimental basis for evaluating the biological damage effect of ammunition and proposing the related protective and treatment measures. Methods Ninety SD rats were randomly divided into trinitrotoluene (TNT) explosion group(n=40), thermobaric (TB) explosion group (n=40) and control group (n=10) according to ammunition type and laying distance(18, 20, 25, 30 m). TNT and TB ammunition were detonated in the free field and the shock wave parameters at different distances from the explosion source were measured by pressure transducers. The degree index of injury of rats was evaluated by grass anatomy, histopathology and adjusted severity of injury index (ASII) scoring system. Behavioral changes of the rats were evaluated with Open field test and Morris water maze test. Results The peak pressure and impulse of explosion shock wave decreased continuously with increasing distance from the explosion center in TNT explosion group and TB explosion group. The rats in TNT explosion group died at 18 m (3/10) and 20 m (1/10), while all rats in TB explosion group survived. The dead rats showed a combined lung blast injury. HE staining showed widened alveolar septa and infiltration of red blood cells and inflammatory cells, and no obvious pathological changes were found in brain tissue 24 hours after explosion. Significant correlation existed between ASII score and shock wave peak pressure in TNT explosion groups (r=0.81, P<0.05) and TB explosion groups (r=0.70, P<0.05). The parameters of total move time and total move distance of rats in different positions were shorter in TNT explosion group than in control group, but without statistical significance (P>0.05). Compared with the control group, the move time and distance of rat in 20 m central region were shorter in TNT explosion group (P<0.05). Compared with the control group, the escape latency of rats in TNT explosion group 18 m and TB explosion group 20 m was shortened, the platform crossing time increased, and the residence time in target quadrant prolonged (P<0.05). Conclusions The injury degree of free-field blast shock wave in rats is related to the distance to explosion center with a shock wave peak pressure and impulse dependence. The blast shock wave can affect the behavior and spatial memory ability of rats.

Objective To evaluate the protective effect of Rhubarb on vascular endothelial cell function in the sepsis patients. Methods We carried out a prospective, single-center, randomized controlled study based on 41 patients with sepsis who admitted to the Intensive Care Unit of the 908th Hospital of PLA. The patients were randomly divided into Rhubarb treatment group (n=20) and control group (n=21). Blood samples were collected before, 24 h and 72 h after the medication. Conventional coagulation tests [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, thrombin time (TT), fibrin degradation products (FDP), D-dimer, antithrombin (AT-Ⅲ), platelet count, platelet distribution width] and coagulation molecular markers including thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin- antithrombin complex(TAT), plasmin-α₂ antiplasmin complex (PIC) were detected and statistically analyzed. Results The fibrinogen level [(3.5±1.0) g/L] at the 72 h after administration in Rhubarb treatment group was significantly higher than that in control group [(2.7±0.8) g/L] and Rhubarb treatment group before administration [(2.7±0.9) g/L] (P<0.05). Compared with the serum TM [19.0(15.5,22.6) TU/ml] and t-PAIC [15.4(9.7, 20.9) ng/ml] levels before treatment in control group, the TM [27.3(20.8, 31.2) TU/ml] and t-PAIC [22.2 (15.5, 38.6) ng/ml] at the 72 h after administration in control group significantly increased (P<0.05). Compared with TM [27.3(20.8, 31.2) TU/ml] and t-PAIC [22.2(15.5, 38.6) ng/ml] of control group, the TM [13.2(10.9, 18.0) TU/ml] and t-PAIC [9.2(7.3, 23.1) ng/ml] at the 72 h after administration in Rhubarb treatment group were significantly decreased (P<0.05).Compared with the serum TM [19.7(17.1, 23.4) TU/ml] levels before treatment and the TM [18.6(15.3, 21.1) TU/ml] at the 24 h after administration in Rhubarb treatment group, the TM at the 72 h after administration were significantly decreased (P<0.05).Kaplan-Meier analysis revealed that there was no statistically significant difference in 14-day survival rate between the two groups(P>0.05). Conclusion Chinese Rhubarb can down-regulate TM and t-PAIC levels and improve vascular endothelial cell function in patients with sepsis.

Nuclear transcription factor TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein commonly expressed and highly conserved in evolution. In physiological state, TDP-43, when localized mainly in nucleus and cytoplasm (no more than 30%), may play a physiological role, such as participating in mRNA transcription, splicing, translation, transport and maintaining the stability of mRNA, while its mislocalization in mitochondria might play a corresponding pathological role. Recent researches found that, in addition to produce a marked effect in neurodegenerative diseases, TDP-43 also plays an important role in the pathological process of tumors, male infertility, osteoarthritis (OA) and other diseases. Therefore, the gene expression, subcellular organelle translocation, function and the relationship with diseases of TDP-43 have attracted more and more attention. The research progress of pathological effects of TDP-43 has been reviewed in present paper, so as to provide more help for diagnosis and treatment of related diseases.

Objective To observe the effects and possible mechanism of exposure to high altitude environment on liver function in rats. Methods Forty-eight healthy male SD rats were randomly divided into plain group, plateau 1-month group, plateau 2-month group and plateau 4-month group (12 each). Rats in plain group were fed at an altitude of about 500 m for 1 month, and in the plateau groups were fed in a simulated chamber of high altitude (5000 m) for 1 month, 2 months and 4 months, respectively. Serum and liver tissue were collected at the end of the model. The contents of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were measured with automatic biochemical analyzer. The pathological morphology of liver tissue was observed by HE staining. The levels of reduced glutathione (GSH) and superoxide dismutase(SOD) in liver tissue were measured by ELISA. The ultra structural changes of hepatocytes were observed by transmission electron microscope. The relative expressions of autophagy associated proteins LC3-Ⅱ and Beclin-1 were determined by Western blotting. Results Compared with the plain group, the serum levels of ALT, AST and TBIL significantly increased in the plateau 2-month group (P<0.05); compared with the plateau 2-month group, the serum levels of ALT, AST and TBIL significantly decreased in the plateau 4-month group (P<0.05). HE staining showed that the lobule structure of liver tissue in each group was clear without obvious inflammatory infiltration, cell edema or necrosis. The results of transmission electron microscope showed that the number of autophagy corpuscles in hepatocytes of rats was significantly higher in plateau 1-month group and plateau 2-month group than in plain group, and was significantly lower in plateau 4-month group than in plateau 2-month group. Western blotting and ELISA results showed that the relative expression levels of LC3-Ⅱ and Beclin-1 protein increased significantly, while the GSH and SOD levels decreased significantly in plateau 1-month group and plateau 2-month group than in the plain group (P<0.05); the relative expression levels of LC3-Ⅱ and Beclin-1 protein significantly decreased, and the levels of GSH and SOD significantly increased in plateau 4-month group than in plateau 2-month group (P<0.05), but no significant differences compared with those in plain group(P>0.05). Conclusion In the process of adapting to hypobaric and hypoxic environment, abnormal changes of liver function indexes of rats occurred, the mechanism may be related to the changes of oxidative stress level and autophagy of hepatocytes.

Objective To explore the effect of hsa-microRNA-203-3p (miR-203) targeted-regulating Cullin2 (CUL2) on the biological characteristics of human papillomavirus 16 (HPV16) positive cervical cancer cells. Methods A total of 10 patients underwent cervical cancer screening from September 2018 to September 2019 in the Department of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University. HPV genotyping was performed as single HPV16 positive, and pathological examination showed cervical squamous cell carcinoma (SCC). Ten corresponding paracancer normal tissue samples were collected as control group. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression of miR-203 in cervical squamous cell carcinoma and corresponding adjacent tissues, cervical cancer cell line (SiHa) and human immortal keratinocyte line (HaCaT) cells. GO and KEGG enrichment were applied to analyze the functions and pathways miR-203 involved. The regulatory relationship between miR-203 and CUL2 were verified via TargetScan website and dual luciferase reporter assay. The miR-203 mimics or inhibitor were transfected into SiHa cells to establish cell models of high and low expression of miR-203,and the expressions of CUL2 mRNA and protein were detected by qRT-PCR and Western blotting. The proliferation, migration and apoptosis of SiHa cells were assessed by CCK-8, scratch assay and Annexin V-APC/PI double staining, respectively. Results Results of qRT-PCR indicated that, compared with the corresponding adjacent tissues and HaCaT cells, the relative expression level of miR-203 decreased obviously in both cervical SCC tissues and SiHa cells (P<0.01). The results of GO and KEGG enrichment methods showed that miR-203 was widely involved in the ubiquitination process and the signaling pathways involved in the malignancies. TargetScan website and dual-luciferase reporter assay showed that the targeting regulatory relationship existed between miR-203 and CUL2 (P<0.01). qRT-PCR and Western blotting indicated that overexpression of miR-203 reduced the expressions of CUL2 mRNA and protein (P<0.05 or P<0.01); While low expression of miR-203 up-regulated the expressions of CUL2 mRNA and protein (P<0.01). CCK-8, scratch experiments and Annexin V-APC/PI double staining method confirmed that overexpression of miR-203 decreased proliferation rate and migration rate of SiHa cells (P<0.01), and elevated cell apoptosis rate (P<0.05). In contrast, low expression of miR-203 increased the proliferation rate and migration rate of SiHa cells (P<0.01), and reduced the apoptosis rate(P<0.01). Conclusion The miR-203 might suppress the biological characteristics of HPV16-positive cervical cancer cells SiHa by targeting CUL2, and it was expected to become a new candidate gene in diagnosis and treatment of cervical cancer.

Objective To analyze the clinical features, diagnosis and treatment and prognosis of acute megakaryocytic leukemia (AMKL), and then review the relative of AMKL. Methods Retrospectively study the clinical data of 14 AMKL patients admitted to Fujian Medical University Union Hospital and the First Affiliated Hospital of Gannan Medical University from January 2016 to May 2021, analyze and discuss the clinical features, diagnosis and differential diagnosis, treatment and prognosis of AMKL patients, and search domestic or foreign literature for the literature review at the same time. Results A total of 14 AMKL patients were included in present study, including 6 children [4 males and 2 females, with a median age of 2 years (13 months to 6 years)]; 8 adult patients [5 males and 3 females, with a median age of 57 (19-78) years]. The clinical manifestations of the patients were mainly non-specific symptoms of blood diseases. All patients underwent bone marrow biopsy, and a large number of primitive megakaryocytes were seen under the microscope. Except for 2 patients with incomplete flow immunophenotyping, cytogenetics and molecular biology tests, all the remaining 12 patients had megakaryocyte antigens (CD41, CD61, CD42b) expression, accompanied by genetic or molecular biology abnormalities. Except for 1 patient who survived after bone marrow transplantation and 1 patient who was lost to follow-up, the remaining 12 patients died, the median survival time was 5.5 (0–21) months. A total of 249 cases of AMKL patients in mainland of China (excluding Hong Kong, Macao and Taiwan) were reported from 2002 to 2022,of which 16 cases were transformed by other hematological tumor diseases: 6 cases were transformed by chronic myeloid leukemia(CML), 4 cases were transformed by myelodysplastic syndrome (MDS), 3 cases were transformed by myelofibrosis (MF), 2 cases were transformed by primary immune thrombocytopenia (ITP), and 1 was transformed by acute lymphoblastic leukemia (ALL).Among the 249 AMKL patients, 24 survived and 225 died. Most of the causes of death were disease progression, recurrence after chemotherapy or transplantation, severe infection, and fatal hemorrhage. Conclusions AMKL is rare and has an extremely poor prognosis with lack of specificity in clinical manifestations. It is helpful for diagnosis and differential diagnosis of AMKL by the results of bone marrow routine and pathology, flow cytometry, cytogenetics, molecular biology and electron microscopy. Clinical trials should be the first choice for the treatment of AMKL, correspondingly, close monitoring of measurable residual disease (MRD),and the remission induction chemotherapy combined with epigenetic drugs and targeted therapy may benefit patients. In addition,AMKL patients should undergo hematopoietic stem cell transplant as soon as possible after the first complete remission induced by standard chemotherapy, which will maximize the prognosis of patients.

It is a common phenomenon that the working ability of the people from moderate temperature areas generally decreases after entering high temperature areas, while heat acclimatization can improve the heat tolerance of human. This review summarized the molecular mechanism of the formation of heat acclimatization and the specific key markers produced after heat acclimatization from the perspectives of physiological function, biochemical metabolism and epigenetics. In addition, Genome-Wide Association Study (GWAS) strategy in exploring the main genetic differences among people with different heat adaptation was also discussed. Heat acclimatization changes the sensitivity of central and peripheral thermal effectors, reduces heart rate and increases stroke volume by regulating myocardial autonomic nerve tension to reduce endogenous heat production and accelerate exogenous heat dissipation. Heat acclimatization enhances the secretion of H₂O and sodium retention hormones such as aldosterone and arginine vasopressin and the enrichment of NaCl in diet, which expands the plasma volume to maintain cardiovascular stability. The transcriptional activity of heat shock protein (HSP) and the calcium release of mitochondrial respiratory chain increases after heat acclimatization, in which HSP70 is a potential key genetic marker to distinguish between those with good heat adaptation (hot zone soldiers, firefighters, athletes, etc.) and those with poor heat adaptation. Moderately high concentration of Na⁺, Cl^–, Ca²⁺ and low concentration of K⁺ in plasma can help to enhance heat tolerance and promote the formation of heat acclimatization, which can be used as potential markers for the study of heat acclimatization. Furthermore, heat acclimatization effect in the population has great heterogeneity. How heat acclimatization enhances human's heat tolerance and the balance between the plasticity of this heat tolerance and congenital genetic and acquired epigenetic modification need to be further explored.

Glioma is of the most common malignant tumors in the central nervous system. The prognosis of patients is poor, and its effective treatment has always been a major clinical challenge. In tumor cells, genetic instability often leads to a large number of mutations. The expression of nonsynonymous mutations can produce tumor-specific antigens, called neo-antigens, which have high immunogenicity. They could activate specific T cells to produce an immune response and become a new tumor immunotherapy target. Among the tumor vaccines targeting neo-antigens, the mRNA tumor vaccine has obvious advantages: easy access, low cost, high safety, and great stability. Therefore, a neo-antigen mRNA vaccine is likely to become an effective treatment for glioma. At present, some clinical trials have proved the safety and effectiveness of these vaccines. This article reviews the research progress of the neo-antigen tumor mRNA vaccine and its application in glioma therapy, and predict the direction of future research.

Surgery and resuscitation are the core capabilities of combat casualty care. Early treatment should be carried out within 3 hours, and divided into two phases, emergency treatment and surgical resuscitation, emphasizing the capability building of resuscitation and surgery. This paper interprets the capability requirements of the early casualty care level. According to the domestic and international progress in the care of civilian trauma and combat casualty, the relationship between "surgery" and "resuscitation" in the early treatment level of combat casualty, and the key technological progress are summarized, indicating that only the coordinated development of surgery and resuscitation ability and mutual support can provide safe, standardized and efficient treatment and reduce the death rate of the combat casualties.