The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Dalbergia ; Myocardial Ischemia ; Metabolomics ; Heart ; Heart Injuries ; Creatine Kinase, MB Form

Objective:To investigate the clinical features and risk factors of multiple organ dysfunction syndrome (MODS) caused by wasp sting.Methods:A retrospective cohort study was conducted to collect the general data of wasp sting patients who had a clear history of wasp sting disease and clinical manifestations from June 2016 to December 2020 and were first diagnosed as wasp sting in hospital. Patients with hematological diseases, malignant tumors, severe liver and kidney dysfunction, cardiac insufficiency, and patients who had received hormone therapy before admission were excluded. Patients who were unable to obtain effective laboratory results due to hemolysis or other reasons within 48 h of admission were also excluded. The white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), hemoglobin count (HB), myoglobin (Mb/MYO), activated partial thromboplastin time (APTT), albumin (ALB), K, Na, and Cl of the blood samples collected within 48 h after admission were recorded. Patients were divided into the MODS group and non-MODS group according to whether MODS occurred during hospitalization. Uni- and multivariate analysis were used to analyze the factors affecting the occurrence of MODS in wasp sting patients during hospitalization, and the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive effect of myoglobin level on the occurrence of MODS in wasp sting patients during hospitalization.Results:Mb, WBC, NEU, APTT and serum potassium in the MODS group [3890.00 (1416.90-4057.00) ng/mL, (21.99 ± 8.18) × 10 9/L, (19.61 ± 7.33)× 10 9/L, (93.75 ± 45.77) s, and (4.99 ± 0.95) mmol/L] were significantly higher than those in the non-MODS group [73.50 (34.30-264.20) ng/mL, (13.40 ± 4.14)× 10 9/L, (11.18±4.73)× 10 9/L, (37.00 ± 17.16) s, and (4.05 ± 0.56) mmol/L] (all P < 0.05); blood chlorine and ALB [(101.50 (98.25-105.00) mmol/L and (35.36 ± 6.44) g/L)] were significantly lower than those in the non-MODS group [(105.00 (103.00-107.00) mmol/L and (40.71 ± 5.48) g/L)] (all P < 0.05). Multivariate logistic regression analysis showed that NEU ( OR = 0.729, 95% CI: 0.542~0.981), Mb ( OR = 0.999, 95% CI: 0.998~1.000), and APTT ( OR = 0.951, 95% CI: 0.921~0.982) were independent risk factors for MODS in wasp sting patients. ROC curve analysis showed that NEU, Mb and APTT could be used to evaluate the occurrence of MODS in wasp sting patients. Among them, Mb had the highest predictive value (AUC = 0.950, 95 % CI: 0.891~0.982). The optimal cutoff value of Mb for predicting the occurrence of MODS in wasp sting patients was 515.30 ng/mL, and the corresponding sensitivity and specificity were 90.62% and 87.23%, respectively. Conclusion:Mb is an independent risk factor for MODS in wasp sting patients, which can be used as a good predictor of MODS in wasp sting patients.

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
Animals ; Berberine/therapeutic use* ; Fatty Liver ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Necrosis

Objective:To evaluate the efficacy and safety of Chinese medicinal formulae in the treatment of antimicrobial-resistant pneumonia. Method:Following article retrieval from eight databases and data extraction by two reviewers， the methodological quality of the included trials was assessed and the outcome indicators were subjected to Meta-analysis using RevMan 5.3. Result:A total of 24 randomized controlled trials （RCTs） were included， involving 1 818 cases. Meta-analysis showed that Chinese medicinal formulae combined with western routine intervention was superior to the western routine intervention in improving the overall response rate （ORR） ［relative risk （RR）=1.27， 95% confidence interval （CI） （1.21， 1.34）， P<0.000 01］， the bacterial clearance rate ［RR=1.49，95% CI （1.33， 1.66）， P<0.000 01］， and the clinical pulmonary infection score （CPIS） ［mean difference （MD）=-1.64， 95% CI （-1.87， -1.41）， P<0.000 01］. There was no significant difference in the incidence of adverse reactions ［RR=0.72， 95% CI （0.48， 1.07）， P=0.1］. The comparison with the western routine intervention also revealed that Chinese medicinal formulae better improved the ORR and CPIS. Conclusion:According to the current research results， the Chinese medicinal formulae alone or combined with western routine intervention yielded more favorable clinical outcomes than western routine intervention in the treatment of antimicrobial-resistant pneumonia， without increasing the incidence of adverse events. Due to limited quality and quantity of the included RCTs， more high-quality trials are required to verify the above conclusions.

The discovery of penicillin has effectively controlled the infection caused by Gram-positive bacteria. Afterwards, the research and development of antibacterial drugs has entered the golden age, and made a great contribution to human health. However, in recent years, with the increasing use of antibiotics around the world, pathogenic bacteria drive gene mutation to obtain drug resistance to ensure its survival advantage, and promote the transfer of drug-resistant genes, resulting in a sharp increase of drug-resistant bacteria. In addition, the current development speed of new antibiotics is far slower than the growth and spread speed of drug-resistant bacteria, which makes the drug-resistant crisis more serious and becomes one of the biggest threats to the global community. Compared with the same type of bacterial infection, drug-resistant bacterial infection has the characteristics of complexity and refractoriness, which causes worse clinical outcome and higher risk of death in patients, and brings severe challenges to clinical work. If the trend of bacterial drug resistance is not controlled, the crisis of no drug available will come. Therefore, it is urgent to explore effective alternative means to fight against bacterial drug resistance and reduce the harm of drug-resistant bacterial infection. Traditional Chinese medicine（TCM） has unique advantages in the treatment of infectious diseases. Compared with modern antibacterial drugs, it has the characteristics of wide sources, rich active ingredients, and is not easy to produce drug resistance. It may be an important source for screening and developing new anti-infective drugs. Therefore, it is promising to develop and utilize TCM to solve the problem of drug-resistant bacteria infection. This paper will review relevant studies in recent years in terms of interfering with the biochemical metabolism of drug-resistant bacteria to directly inhibit or kill drug-resistant bacteria, improving bacterial drug resistance to indirectly inhibit bacteria and kill bacteria, and maintaining the balance of the body and regulating the treatment of drug-resistant bacteria infection as a whole, so as to provide references for guiding clinical medication and research and development of new traditional Chinese medicines.

Diabetes mellitus complicated with cerebral infarction is the commonest and most serious vascular complication of diabetes mellitus. With a high disability and mortality rate, it seriously threatens human health. Because the pathogenesis is still unclear, more and more scholars have focused on the research of diabetic cerebral infarction at home and abroad. Traditional Chinese medicine(TCM) compounds have a remarkable curative effect in the treatment of diabetic cerebral infarction. Its mechanisms of action mainly include anti-hypertension, reduction of blood sugar and lipid, promotion of vascular regeneration and vascular endothelial function, anticoagulation, anti-thrombosis, improvement of nerve function defect, reduction of infarct volume, improvement of hemorheological, inhibition of inflammation and platelet aggregation, and promotion of collateral circulation. Through literature search, this paper summarizes the research progress of the mechanisms of TCM compounds in treating diabetic cerebral infarction in recent five years at home and abroad, in order to provide reference for clinical treatment.

Objective: To explore the relationship between ABO blood group and acute non-ST-segment elevation myocardial infarction (NSTEMI) occurrence. Methods: Our research included 2 groups: NSTEMI group, 1039 relevant patients treated in Anzhen hospital from 2013-01 to 2014-12 were retrospectively enrolled; Control group, 1039 subjects with normal coronary artery which was confirmed by coronary angiography. The Baseline condition including age, previous disease history and ABO blood group was studied. Logistic regression model was used to conduct single and multivariate analysis. Results: In NSTEMI group and Control group, blood type A was 287/1039 (27.6％) vs 259 (24.9％), type B was 345 (33.3％) vs 356 (34.3％), type AB was 102 (9.8％) vs 114 (11.0％) and type O was 305 (29.4％) vs 310 (29.8％), ABO blood group distribution for A and non-A, B and non-B, AB and non-AB blood group, O and non-O had no statistic meaning between 2 groups, P>0.05. Logistic regression analysis indicated that with adjusted risk factors of MI such as age, gender, hypertension, diabetes, hyperlipemia, cerebrovascular disease and smoking, the patients with blood types A, B and AB had the similar risk for NSTEMI occurrence than type O patients; there was no relationship between ABO blood group and NSTEMI occurrence. Conclusion: ABO blood group had no relationship to NSTEMI occurrence.

Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.

Objective To study the effects and mechanism of Glyphosate induced cell cycle arrest and apoptosis in mouse spermatogenic cells(GC-2).Methods Morphology of the GC-2 cells was observed by optical microscope and Transmission Electron Microscopy.Flow cytometry were used to detect cell cycle arrest and apoptosis.Cell cycle arrcst and apoptosis related proteins were detected by Western blot.Results Glyphosate could inhibit cell proliferation and impair endoplasmic reticulum and mitochondria significantly,which was associated with G1 phase arrest and apoptosis in GC-2 cells.Glyphosate lead to cell cycle arrest and apoptosis by regulating the expressions of G1/S phase checkpoint regulatory factor proteins such as p21,CyclinD1,CyclinE and activating caspase3.Conclusion Glyphosate has adverse effects on male germ cells by inducing cell cycle arrest and apoptosis.