By April 19, 2021, the ongoing coronavirus disease 2019 (COVID-2019), which is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has infected more than one hundred and fourty million individuals across more than 200 countries or territories and killed more than three million twenty-six thousand individuals worldwide. There are currently no specific drugs available for patients with COVID-19 infection, but a number of potential drug targets have been identified with the further understanding of the virological characteristics and pathogenesis of SARS-CoV-2. Some candidate drugs have shown good antiviral activity against SARS-CoV-2 in preclinical or clinical trials. This paper summarizes the current status of potential therapeutic drugs for COVID-19 in order to provide references for future COVID-19 therapy.

High-altitude pulmonary edema (HAPE) is a plateau-specific disease caused by low-pressure hypoxia in the plateau, which seriously threatens the quality of life and operational ability and, in severe cases, life in healthy people who have sharply advanced to the plateau. Although the treatment of the disease has been significantly improved, there are still some existing issues in the treatment. For instance, how to balance diuretic use, the effective blood volume supplementation, the timing of hyperbaric oxygen chamber application, and mechanical ventilation parameter settings in pulmonary edema, etc. This review reflects on the typology, pathogenesis, clinical manifestations, prevention and treatment considerations in plateau pulmonary edema.

Objective To explore the diagnostic value of thrombomodulin (TM) for sepsis-induced coagulopathy. Methods A prospective study was conducted on 172 hospitalized patients with sepsis from intensive care units (ICU) of the 908th Hospital of Chinese PLA Logistical Support Force between May 2018 and October 2019. All the subjects were divided into sepsis-induced coagulopathy (SIC) group (n=68) and sepsis alone (SA) group (n=104) according to the diagnostic criteria of International Society on Thrombosis and Haemostasis. Baseline characteristics [gender, age, acute physiology and chronic health evaluationⅡ (APACHE Ⅱ), sequential organ failure assessment (SOFA), mean arterial pressure (MAP), lactate (Lac), comorbidity, ICU mortality and length of stay in ICU], coagulation tests [prothrombin time (PT), international normalized ratio (INR), platelet count (PLT)] and molecular markers of coagulation [tissue plasminogen activator-inhibitor complex (t-PAIC), TM, thrombin-antithrombin complex (TAT), plasmin-α₂-plasmin inhibitor complex (PIC)] were compared. Multivariate logistic regression analysis was used to identify risk factors for SIC. The effectiveness of TM in diagnosing SIC was analyzed by ROC curve analysis. Kaplan- Meier analysis was used to analyze the cumulative survival rate. Results Compared with TM [10.5(7.8-14.9) TU/ml], TAT[8.6(4.8-18.0) ng/ml] and t-PAIC [11.6(7.1-22.2) ng/ml] in SA group, TM [15.0(10.5-25.9) TU/ml], TAT [15.1(5.7-34.6) ng/ml]and t-PAIC [22.1(11.0-39.1) ng/ml] in SIC group were significantly increased (P<0.05). Multivariate logistic regression analysis showed that TM and Lac were the independent risk factors for SIC. The area under the curve of TM for diagnosing SIC was 0.685 and its diagnostic threshold was 11.5 TU/ml. Its diagnostic sensitivity, specificity, positive predictive value and negative predictive value were 72.1%, 61.5%, 55.2% and 77.1%, respectively. Kaplan-Meier analysis revealed that the death risk of patients with sepsis in TM >11.5 TU/ml group was 3.61 times higher than TM ≤11.5 TU/ml group. The mortalities of patients who met or didn't meet the ISTH-SIC diagnosis criteria were respectively 47.1%(32/68) and 21.2%(22/104). The mortality of patients with SOFA≥2 and TM>11.5 TU/ml was 47.2%(42/89), while the other patients was 14.5%(12/83). Conclusions Elevated serum TM level could be found in patients with SIC. SOFA combined with TM has a better diagnostic efficacy for SIC.

Objective To study the effect of Streptococcus pneumoniae pneumonia (S.pp) on the lung structure and function of mice. Methods Fifty neonatal BALB/c mice (1-week-old) were randomly divided into S.pp group and control group (25 each).Mice in S.pp group were infected intranasally with 2×10⁷ cfu of S. pneumoniae (D39) in 5 μl to establish the S.pp model, same dosage of PBS were used synchronously to treat the mice in control group. Three and five weeks after treatment, lung tissues and bronchoalveolar lavage fluid (BALF) of the two groups were collected, HE staining was performed to detect the pathological changes of lung tissue and alveolar structure; the collagen fiber deposition around alveoli was identified by Masson staining; the levels of IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) in BALF were examined by ELISA. Five weeks after the infection, lung resistance was evaluated by EMKA pulmonary system. Results HE staining showed that, compared with control group, the radial alveolar count (RAC) decreased significantly in infancy and adult S.pp group (8.00±1.10 vs. 3.53±0.35, P=0.018; 13.73±2.49 vs.4.02±0.21, P=0.018), the mean linear intercept (MLI) increased obviously (88.99±5.55 vs. 127.10±9.54, P=0.006; 74.45±4.84 vs. 131.30±17.86, P=0.020), and the alveolar septum thickness increased markedly [(2.38±0.18) μm vs. (3.28±0.13) μm,P=0.002; (3.41±0.60) μm vs. (5.78±0.75) μm, P=0.023]. Compared with control group, the mean alveolar diameter (MAD)increased significantly in infancy S.pp group [(167.00±8.85) μm vs. (193.40±5.14) μm, P=0.042], but no significant difference existed between control group and adult S.pp group. The infiltration of inflammatory cells around alveoli increased obviously in infancy and adult S.pp group compared with that in control group (1.68±0.24 vs. 0.72±0.12, P=0.002; 1.88±0.30 vs.0.67±0.23, P=0.006). Compared with control group, the concentrations of IL-25, IL-33 and TSLP in BALF of adult S.pp group increased significantly [(36.16±2.80) pg/ml vs. (45.16±1.74) pg/ml, P=0.024; (52.06±1.70) pg/ml vs. (61.42±1.50) pg/ml,P=0.004; (13.32±0.74) pg/ml vs. (16.71±0.54) pg/ml, P=0.007]; Collagen fiber deposition around alveoli increased markedly[(0.01±0.01) mm² vs. (0.44±0.01) mm², P<0.001], and the airway resistance increased significantly when the concentration of inhaled aerosolized methacholine reached to 12.5–50.0 mg/ml in adult S.pp group mice (P<0.001). Conclusion Streptococcus pneumoniae pneumonia may induce the decrease of mean alveolar count, the increase of MLI, the alveolar septum thickness and airway resistance in BALB/c mice, thus lead to abnormal lung tissue structure and function.

Trauma-induced hypercoagulopathy is a hypercoagulable phenotype of trauma-induced coagulopathy (TIC) characterized by vascular endothelial injury, excessive release of procoagulants, hyperfibrinogenemia, platelet hyperactivity, anticoagulant pathways impairment and fibrinolysis shutdown. Recent studies have found that the incidence, mortality and disability rate of trauma-induced hypercoagulopathy increased significantly with the severity of trauma. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and China Medical Education Association Professional Committee of Thrombosis, Hemostasis and Critical Care Medicine jointly formulated Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy published in Military Medical Research in April, 2021. In present paper, the main contents of the consensus were interpreted from the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.

Objective To investigate the alterations of hepatokines fatty acid binding protein 1 (FABP1) in patients with dyslipidemia and their correlation with dyslipidemia. Methods The clinical data of 122 patients hospitalized in the Department of Cardiovascular Medicine of General Hospital of Western Theater Command during March to October 2020 were analyzed retrospectively. According to the blood lipids level and the criteria of inclusion and exclusion, 72 patients with abnormal blood lipids level (abnormal blood lipid group) and 50 patients with normal blood lipids level (normal blood lipid group) were identified. General information of all subjects was collected, including gender, age, height, weight, smoking and drinking habits, etc. Blood lipid, blood glucose, angiopoietin like protein (ANGPTL)3, ANGPTL4, ANGPTL6, FABP1 were detected. Propensity score matching (PSM) method was used to balance the confounding factors in the baseline data for comparing the alterations of hepatokines between the two groups. Binary logistic regression was used to analyze the risk factors of dyslipidemia, and multiple linear regression was used to analyze the correlation between FABP1 and blood lipid components. Results After balancing confounding factors by PSM method, no statistically significant difference existed in age, gender, tobacco and alcohol addiction, BMI and blood glucose between the two groups (P>0.05). The level of HDL-C was significantly lower, and the levels of TC, LDL-C and TG were significantly higher in abnormal blood lipid group than in normal blood lipid group (P<0.05). FABP1 level was significantly higher in abnormal blood lipid group than that in normal blood lipid group (P<0.05), while no statistical difference existed between the two groups in the serum levels of ANGPTL3, ANGPTL4 and ANGPTL6 (P>0.05). Binary logistic regression analysis showed that FABP1 was an independent risk factor for dyslipidemia (OR=1.011, P<0.05). Multiple linear regression analysis showed that a significant positive correlation existed between TG and FABP1 (β=0.291, P<0.05), and a significant negative correlation existed between TC+LDL-C and FABP1, as well as blood glucose and FABP1 (β=–0.443 and β=–0.268, P<0.05). Conclusion FABP1 is closely related to dyslipidemia, especially to the abnormal metabolism of triglyceride.

Objective To analyze the peripheral 1-de-amino-8-D-arginine vasopressin (hereinafter referred as DDAVP)irritant test as the best cut-off point for the differential diagnosis of Cushing's disease and ectopic adreno-cortico-tropic-hormone(ACTH) syndrome (hereinafter referred as EAS), so as to explore the value of peripheral DDAVP irritant test in differential diagnosis of ACTH-dependent Cushing's syndrome. Methods The clinical data of 102 cases with ACTH-dependent Cushing's syndrome, diagnosed in the Endocrinology Department of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2019, were retrospectively analyzed, including 93 cases with Cushing's disease (Cushing's disease group) and 9 cases with EAS (EAS group). Based on the ROC curve, the blood ACTH level after stimulation was used as the detection variable, and the diagnosis result of Cushing's disease was used as the status variable to search the best cut-off point for the diagnosis of Cushing's disease. The sensitivity and specificity were analyzed of the peripheral DDAVP irritant test in the differential diagnosis of EAS and Cushing's disease at different cut-off points. Results Compared with Cushing's disease group, the course of disease was shorter and the basic blood cortisol and ACTH values were higher in EAS group with statistical significance (P<0.05). On the ROC curve, taking the increase by 33.6% of ACTH after stimulation as the cut-off point, the sensitivity and specificity for Cushing's disease and EAS were 98.9% and 55.6%, respectively, which were the best cut-off point. With the increase of blood ACTH value after stimulation, the sensitivity for diagnosing Cushing's disease decreased. If the increase by 20.0% of blood cortisol value after stimulation as the cut-off point simultaneously, then, the sensitivity for diagnosing Cushing's disease decreased and the specificity not increased. Thus, the blood ACTH was more specific than the blood cortisol. If taking the increase by 33.6% of the blood ACTH after peripheral DDAVP stimulation test, as well as the greater than or equal to 50.0% of the blood cortisol suppression ratio (or urinary free cortisol suppression ratio) in classical high-dose dexamethasone suppression test (HDDST) were taken as cut-off points, the sensitivity and specificity for identifying ACTH dependent Cushing's syndrome were 73.3% and 87.5%, respectively. Conclusion When taking the increase by 33.6% of blood ACTH after peripheral DDAVP stimulation as the cut-off point, the sensitivity was the highest in diagnosing Cushing's disease, so this method can be used as a screening test for and improve the detection rate of Cushing's disease.

Objective To understand the effect of resveratrol (RSV) on vascular repair after the common carotid balloon injury in rats. Methods Forty SD rats were randomized into four groups (n=10): sham group, model group, solvent control group(DSMO group) and RSV group. After establishing the carotid artery balloon injury model, the rats in model group had no special treatment, while the rats in DMSO group and RSV group were given the same dose of DMSO or RSV respectively at the outside of the adventitia of carotid balloon injury segments. The rats in sham group received external carotid artery ligation. Fourteen days after the surgery, excessive anesthesia was applied to rats. The injured segments of the carotid arteries were collected, followed by HE staining to observe the degree of vascular intimal hyperplasia and stenosis. The expression of CD31 using immunohistochemical staining was detected to evaluate the degree of the re-endothelialization, and Western blotting was used to detect the expression levels of vascular endothelial growth factor (VEGF) in the arterial tissues. Results HE staining results showed that there was no significant difference in EEL circumference, EEL area and IEL area between groups (P>0.05); compared with sham group and DMSO group, the lumen area of RSV group decreased significantly (P<0.05). Compared with sham group, the degree of intimal hyperplasia increased in model group and RSV group (P<0.05); compared with model group, the degree of intimal hyperplasia decreased in DMSO group (P<0.05); compared with DMSO group, the degree of intimal hyperplasia increased in RSV group(P<0.05). Compared with sham group, the degree of stenosis in model group and RSV group were significantly higher (P<0.05); compared with model group, the degree of stenosis in DMSO group decreased significantly (P<0.05); compared with DMSO group, the degree of stenosis in RSV group was significantly higher (P<0.05). CD31 immunohistochemical staining results showed that the expression of CD31 in model group was significantly lower than that in sham group (P<0.05), and the expression of CD31 in RSV group was significantly higher than that in model group (P<0.05). Western blotting results showed that the expression of VEGF in model group significantly decreased than that in sham group (P<0.05); compared with model group and DMSO group, the expression of VEGF in RSV group significantly enhanced (P<0.05). Conclusion RSV can promote vascular repair and intimal hyperplasia, and enhance re-endothelialization after the common carotid balloon injury in rats, and the mechanism may be related to the proliferation and migration of adjacent resident endothelial cells and the recruitment of bone marrow endothelial cells or circulating endothelial cells.

Objective To investigate the effect and mechanism of Z-guggulsterone (Z-GS) on removing slough and promoting muscle growth in skin ulcer of diabetic rats by extracellular regulated protein kinase (ERK)/mitogen activated protein kinase (MAPK) pathway. Methods Ten of the 65 rats were selected as healthy group, and the rest were used to establish the diabetic skin ulcer model. Removing 11 rats died during modeling, 44 successful modeling rats were randomly divided into model group, Z-GS group, inhibitor+Z-GS group and positive control group (11 each). No intervention was given to the rats in healthy group, the model groups were treated with vaseline gauze to cover the wounds. Z-GS was used in Z-GS group, PD98059+Z-GS was used in inhibitor+Z-GS group, and compound sulfadiazine zinc gel was used in positive control group, the treatment lasted for 4 weeks. The changes of healing rate of skin ulcer within 4 weeks after intervention in the model groups were recorded. The changes of serum inflammatory factors were detected by ELISA. HE staining was used to observe the histological structure of skin ulcer. The microvessel density (MVD) in wound tissue was detected by immunohistochemistry. Western blotting was used to detect the expression levels of ERK/MAPK pathway related proteins in the model group, inhibitor+Z-GS group and Z-GS group. Results From model group to inhibitor+Z-GS group, Z-GS group and positive control group, the wound healing rate of rats in turn increased in a time-dependent manner (P<0.05), while the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α)decreased in turn (P<0.05). Compared with model group, the new skin structure was nearly complete, inflammatory cell infiltration was rare, capillary content was abundant and collagen fibers were thicker in positive control group; the epidermis was obviously thickened, and the wound coverage was thicker scab, inflammatory cell infiltration decreased, capillary content was abundant and collagen fibers were small in inhibitor+Z-GS group and Z-GS group; compared with that in positive control group, the new skin was less complete, the inflammatory cell infiltration relatively increased, and the capillary blood vessels and collagen fibers were not abundant in inhibitor+Z-GS group and Z-GS group. From model group, inhibitor+Z-GS group to Z-GS group, the expression levels of phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated MAPK (p-MAPK) protein in wound tissue of rats increased in turn (P<0.05). Conclusion Z-GS may play the role of removing slough and promoting muscle growth by activating ERK/MAPK pathway in diabetic rats with skin ulcer.

Atherosclerosis is the basis of a variety of cardiovascular and cerebrovascular diseases, which may further lead to myocardial infarction, cerebral infarction and other life-threatening diseases. At present, the main therapy for atherosclerosis is to control the levels of cholesterol and low density lipoprotein. High density lipoprotein (HDL) is one of the main protective factors of cardiovascular disease. In recent years, more and more studies have revealed the relationship among atherosclerosis, HDL and immune system. The inhibitory effect of HDL on immuno-inflammatory responses could be one of the targets for treatment of atherosclerosis. The mechanism of HDL involved in the regulation of immuno-inflammatory responses of atherosclerosis was summarized in present paper for providing a new idea on treatment of atherosclerosis