Snakebite is a common clinical emergency with the characteristics of acute onset,rapid changes in condition,and high disability and mortality rates.In addition to the common systemic and local tissue damage,snake envenomation can cause significant complications,including immediate and delayed effects.These complications are the main causes of disability and even death caused by snakebites,which seriously affect the long-term prognosis and quality of life.This article summarizes the symptoms,diagnosis,and treatment of snakebite complications from the aspects of blood,nervous,motor,endocrine,and reproductive systems and other aspects to provide references for effective and precise treatment of snakebite in clinical practice.

Snake bites are characterized by acute onset,rapid changes in condition,and high disability and mortality rates.The effects of snake venom on the human body are divided into systemic and local toxic effects.The popu-larity of antivenom has greatly reduced the mortality of snake bites,but local tissue damage and permanent dysfunction are still problems to be solved urgently.Studies have found that snake venom metalloproteinases,hyaluronidases,phospholi-pases and other venoms participate in a variety of local pathological effects by interfering with the degradation and remodel-ing of extracellular matrix(ECM).This article reviews the mechanism of ECM in the development of local tissue damage caused by snake bites,in order to find effective therapeutic targets and provide reference and ideas for the clinical research and prevention of local tissue damage caused by snake bites.

Objective:To investigate the relationship between the activation level of Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and the change of cognitive functions in patients with acute ischemic stroke.Methods:A total of 88 patients with acute ischemic stroke in Department of Neurology from October 2018 to July 2020 were selected as case group and 100 healthy physical examinees were selected as control group.Peripheral blood of the case group and the control group was collected, and peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation.Then the NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and interleukin-1β (IL-1β) expression were detected by Western blot.The cognitive function of patients with acute ischemic stroke was detected by Montreal Cognitive Assessment (MoCA). The differences in expression levels of NLRP3, ASC, Caspase-1 and IL-1β were compared between the case group and the control group.Pearson correlation analysis was used to analyze the correlation between expression levels of NLRP3, ASC, Caspase-1, IL-1β and MoCA score.Logistic multivariate regression was used to analyze the relationship between expression levels of NLRP3, ASC, caspase-1, IL-1β and the cognitive dysfunction.Results:(1)Western blot results showed that NLRP3, ASC, Caspase-1 and IL-1β expressions in PBMCs cells in the case group were higher than those in the control group (all P<0.05). (2)The expression level of NLRP3 in stroke patients with hypertension, hyperlipidemia, National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 points was significantly higher than that in patients without hypertension, hyperlipidemia and NIHSS score<8 points ( P<0.05); (3)The incidence of cognitive dysfunction in the case group was 34.09% (30/88). The MoCA scores of the cognitive dysfunction group and the non-cognitive dysfunction group were 20 (24, 28) and 27 (26, 28) points respectively, and the difference between the groups was statistically significant ( P<0.05); (4)Pearson correlation analysis showed that NLRP3, ASC, caspase-1 and IL-1β expression in PBMCs cells were negatively correlated with MoCA scores ( r=-0.426, -0.396, -0.417, -0.320 respectively, all P<0.05). (5)Logistic regression analysis showed that hyperlipidemia, NIHSS scores, frontotemporal lobe infarction, and NLRP3 expression were the influencing factors for the occurrence of cognitive dysfunction (all P<0.05). Conclusion:Patients with acute ischemic stroke have high activated NLRP3 inflammasome, and its activation degree is closely related to the condition and the occurrence of cognitive dysfunction after stroke.Targeted inhibition or regulation of NLRP3 inflammasome activation may become a new idea of neuroprotection for acute ischemic stroke.

Objective To investigate the significance of using procalcitonin (PCT) combined with acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores to estimate the prognosis of elderly patients with sepsis. Methods One hundred and fourteen elderly patients with sepsis admitted into the Department of Intensive Care Unit (ICU) of 13th Division Xinjiang Production and Construction Corps Red Star Hospital from January 2011 to December 2017 were enrolled, general information of all patients [sex, age, body mass index (BMI), smoking, drinking alcohol, site of infection, underlying disease or complication, education level and marital status], vital signs (pulse, respiration frequency, pH value, body temperature, oxygenation index, diastolic blood pressure, systolic blood pressure), blood and biochemical indicators [blood sugar, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)], D-dimer, PCT, C-reactive protein (CRP), APACHE Ⅱ, chronic health score (CHS) were recorded and survival situation of all patients after entering the study for 28 days. Univariate and multivariate analyses were used to analyze the prognostic factors of elderly patients with sepsis, and the receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic efficacy of the factors in sepsis. Results Within 28 days from admission to hospital, 64 patients (44.44%) died, 80 patients (55.56%) survived, and there were no significant differences in the sex, age, BMI, infected site, underlying disease or complication, education level, marital status, smoking, drinking alcohol, pulse, respiration frequency, pH, body temperature, oxygenation index, blood pressure, blood glucose, HDL, LDL and infection type in the comparisons between the survival and death groups (all P > 0.05). Compared with the survival group, the D-dimer, PCT, CRP, APACHE Ⅱ, mechanical ventilation ratio were higher in the death group [D-dimer (mg/L):3.6±1.1 vs. 3.2±1.2, PCT (mg/L): 15.4±3.5 vs. 4.1±1.4, CRP (ng/L): 637.0±8.9 vs. 596.0±9.6, APACHEⅡ:31.4±5.5 vs. 16.4±4.5, proportion of mechanical ventilation: 87.5% (56/64) vs. 56.2% (45/80), all P < 0.05];multivariate analyses showed that PCT, APACHEⅡ and proportion of mechanical ventilation were independent risk factors of the prognosis of sepsis [PCT: odds ratio (OR) = 4.126, 95% confidence interval (95%CI) = 2.045-6.115, P = 0.000; APACHEⅡ: OR = 2.935, 95%CI = 1.237-4.118, P = 0.001; mechanical ventilation: OR = 2.012, 95%CI =1.068-3.048, P = 0.034, all P < 0.05]. The PCT, APACHE Ⅱ and PCT combined with APACHEⅡ all can be used to diagnose the prognosis of senile sepsis, and the diagnostic value of PCT combined with APACHEⅡ was the largest [area under the ROC curve (AUC) = 0.946, 95%CI = 0.894-0.971, sensitivity = 86.7%, specificity = 90.8%, P = 0.000]. Conclusion PCT combined with APACHE Ⅱscore can be used to estimate the prognosis of elderly patients with sepsis.

Objective To investigate the optimal injury time point of cardiac arrest (CA) induced electrically, and establish a reproducible prolonged CA and cardiopulmonary resuscitation (CPR) model in pigs. Methods Forty healthy domestic male pigs were randomly divided into four groups, which were ventricular fibrillation (VF) 8, 10, 11, and 12 minutes groups, each group for 10 animals. In these groups, VF was induced by alternating current delivered to right ventricular endocardium and untreated for 8, 10, 11, and 12 minutes, respectively, followed by 6 minutes of CPR procedure. The resuscitation and survival outcomes were recorded. Hemodynamic parameters and arterial blood gases of animals after successful resuscitation were measured and recorded for 6 hours. Those successful resuscitation animals were regularly evaluated for the neurological deficit score (NDS) and survival outcomes every 24 hours till 96 hours after resuscitation. Results The shortest duration of CPR (minute: 6.9±1.3) and the highest successful ratio of the first defibrillation (7/10) were observed in group VF 8 minutes, and the ratio of successful resuscitation was 100%. The best coronary perfusion pressure (CPP) during the CPR, less neurological impairment, longer survival time, more stable hemodynamics, and shorter time for arterial pH and lactate level restoring to the original state after CPR were also observed in group VF 8 minutes, and no severe damage was found in those animals. The longest duration of CPR (minute:10.3±2.9) and the lowest successful ratio of the first defibrillation (1/10) were observed in group VF 12 minutes, and only 4 animals achieved restoration of spontaneous circulation (ROSC), and no animal survived to CPR 96 hours. The worst CPP during CPR and the highest NDS after resuscitation were also found in VF 12 minutes animals compared to those animals in the other groups. The injuries caused by ischemia and hypoxia in groups VF 10 minutes and VF 11 minutes were in between those of the groups VF 8 minutes and VF 12 minutes, and the duration of CPR were (7.0±2.1) minutes and (8.2±2.6) minutes. There were 9 and 7 animals achieved ROSC in groups VF 10 minutes and VF 11 minutes correspondingly, and 6 and 4 animals survived to 96 hours respectively. Obviously unstable hemodynamics was observed during the period of CPR 2 hours in the two groups. At CPR 1 hour, the heart rates (HR, beats/min) in groups VF 10 minutes and VF 11 minutes increased to 172 (155, 201) and 168 (136, 196) respectively, and the mean arterial pressures (MAP, mmHg, 1 mmHg = 0.133 kPa) declined to 97 (92, 100) and 81 (77, 100), the cardiac output (CO, L/min) decreased to 5.0 (4.0, 5.8), 3.7 (3.0, 5.4) correspondingly. Distinct injuries were found in the two groups [CPR 24-96 hours NDS in groups VF 10 minutes and VF 11 minutes: 180 (110, 255)-20 (0, 400) and 275 (223, 350)-240 (110, 400)], and the arterial pH of the two group decreased to 7.26±0.09 and 7.23±0.09 respectively, and the level of lactate (mmol/L) increased to 9.17±1.48 and 12.80±2.71 correspondingly at CPR 0.5 hour. Significantly lower pH was observed in group VF 11 minutes compared to group VF 8 minutes at CPR 0.5 hour (7.23±0.09 vs. 7.33±0.04, P < 0.05). The highest level of lactate (mmol/L) was also found at the same time point in group VF 11 minutes, which recovered to normal slowly, and was still significantly higher than groups VF 8, 10, 12 minutes (7.58±3.99 vs. 2.55±1.53, 2.13±2.00, 3.40±2.30, all P < 0.05) at CPR 4 hours. Conclusions The longer duration of CA was, the more severe damage would be, the longer CPR time would be required, and the harder of the animals to achieve ROSC. In this prolonged CA and CPR porcine model, 10-11 minutes for untreated VF, was an optimal time point with appropriate successful rate of resuscitation, survival outcomes, and post-resuscitation injuries. Therefore, we recommended 10-11 minutes might be the rational length of no-flow time in this model.

Objective To investigate the changes of airway resistance before and after Bronchial Diulation Test in patients with senile asthma and the effect of age on the degree of airway resistance. Methods A total of 29 (> 60 years)senile asthma patients and 21 younger(< 60 y)patients were enrolled in the study. The status of their pulmonary function was determined by MEFV(Maximum expiratory flow?volume curve)and an IOS(impulse oscillometry) system before and after Bronchial Diulation Test,The spirometric indexes such as forced vital capacity,total respiratory impedance,respiratory resistance and respiratory system reactance were collected and analyzed. Results Significant decreases of indexs were found after Bronchial Diulation Test compared with those before Bronchial Diulation Test in the study group(P<0.05,respectively). No significant difference in improvement of indexs was found between the group of patients with senile asthma(age > 60 years)and the group of healthy control(age < 60 years ). Each index of the airway resistance has a very good correlation with FEV1%,with the highest degree of relation is X5%. Conclusion The airway resistance of senile asthmatic patients was significantly improved after diuslation test and these indexes IOS would be valuable in evaluating the changes of airway resistance of senile asthma.

Objective To explore the reasonable construction of the bilingual teaching training mode for medical professional teachers so as to improve the effectiveness of the bilingual teacher training,promote the development of faculties and the quality of bilingual teaching in colleges and universities.Methods First,need analysis was done on 45 medical teachers who had taught medical scienc.e in English or intended to do it in Third Military Medical University and four basic modules were formed lectures in class,one on one instruction,self training,simulation teaching.Lectures in class are related to how to improve students' ability of language,make PPT and design teaching plans.One on one instruction focuses on pronunciation,lecture notes writing in English,trial teaching and teaching attitude;self training includes human-computer interaction in listening and speaking,independent preparation for lessons and video learning;simulation teaching is composed of trial lecture in class,teacher-student comments and demo lessons.Then 3 students participating the training was investigated and the analytic hierarchy process (AHP) was applied to calculate the weights of every indices.Results Primary index weights are:0.490 for one-on-one tutoring;0.240 for simulated teaching;0.180 for having English lessons;0.082 for independent learning.Weights of secondary indices are as the following.Trial teaching,the lecture notes writing in English and the training for English pronunciation and teachers' classroom language which are subordinate to the primary index of one-on-one tutoring are 0.180 0,0.150 0 and 0.096 0 respectively;teachers' comments and peer feed-back and demo class under the primary indices of simulated teaching are 0.120 0 and 0.091 0.Conclusion In order to improve the teaching ability in English,it is necessary to strengthen the one-onone tutoring for medical professional teachers,highlight English teachers' comments and peer assessment and excavate the effect of demo classes in the training program.

Background and objective The therapeutic effect and side effect of neoadjuvant chemotherapy were still disputing issues when applied to resectable Ⅲa stage non-small cell lung cancer (NSCLC) patients. The retrospective analysis was aimed to investigate the short-term efficacy and postoperative complications in resectable Ⅲa NSCLC patients treated with neoadjuvant chemotherapy.Methods According to inclusion criteria and exclusion criteria, 370 patients with clinical diagnosis of ⅢaNSCLC were selected from our hospital between January 2011 and October 2013 were retrospectively analyzed. According to treatment method, group A (preoperative neoadjuvant chemotherapy+surgery group) contained 97 cases, and 273 patients were included in group B (direct surgery without neoadjuvant treatment group). The clinical data, surgi-cal approach, main postoperative complications and disease-free survival (DFS) among patients in two groups were recorded. Results The total down-staging in group A was 65.98% (64/97), the R0 resection in group A and group B were 96.91% (94/97) and 90.48% (247/273), respectively. The operation time, bleeding, postoperative hospitalization were no statistical difference (P>0.05), and the main postoperative complications of the patients in two groups were 76.29% (74/97) and 72.52% (198/273) (P>0.05). All patients followed-up for 2 months-36 months, the median follow-up time was 12.7 months, the total recurrence and metastasis rates were 63.92% (62/97) and 94.87% (259/273) (P<0.05) and the median DFS were 19.46 months and 11.34 months (P<0.001).Conclusion Neoadjuvant chemotherapy can benefit patients of Ⅲa stage NSCLC partly in down-staging T and N stage in tumor, enhance the R0 resection, but not significantly increased the postoperative complications of the patients, which can reduce the local recurrence and metastasis, enhance the DFS effectively.

Interferon stimulated gene 15 kDa protein (ISG15) is the first ubiquitin-like protein identified, which plays vital roles in a variety of fields including viral infection and immunological regulation. In this study, liquid chromatography-tandem mass spectrometry was used to analyze ISG15-modified proteins in A549 cells in response to infection by influenza virus, which was enriched by immunoprecipitation. A total of 22 cellular host proteins were identified in A549 cells infected by influenza virus, including ubiquitin-like ISG15 protein, cyclin-T1, heat shock protein 71 kDa, caldesmon, eukaryotic translation initiation factor, and so on. Besides, non-structural protein (NS1) from influenza virus was also identified. Among the 22 host proteins identified, 6 proteins were also identified in the control non-infected A549 cells, including annexin A1, fructose-bisphosphate aldolase A, ATP synthase subunit g, enolase, actin, and tubulin. Bioinformatics analysis revealed that the identified ISG15-modified host proteins induced by influenza virus infection could be classified into 9 protein classes: chaperone, oxidoreductase, enzyme modulator, transferase, nucleic acid binding, transcription factor, kinase, cytoskeletal protein, and structural protein. This study provided a specific and effective tool for analyzing ISG15-modified proteins in proteome level.

Abstract Formaldehyde has been widely employed to immobilize clinical tissue specimens, inactivate toxins and viruses in biomedical fields. Formaldehyde can react with active groups in bio-molecules such as proteins, resulting in protein cross-linking, inactivation, and immobilization. By using several standard peptides and tryptic peptides from matrix protein of influenza virus as experimental models, we studied the chemical modifications of peptides and proteins with formaldehyde by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and nano-electrospray quadruple time-of-flight tandem mass spectrometry. The reaction between formaldehyde and peptides was performed under the same conditions as those during inactivation of virus (4℃, 0. 025% Formalin (V/V), 37% formaldehyde solution (w/w), and 72 h). The results indicated that under above conditions, formaldehyde could react with amino group of N-terminus of standard peptide to generate a methylol adduct, which was further condensed into an imine to generate+12 Da product. Besides, formaldehyde could react with side chain of two amino acids such as arginine and lysine, yielding +12 Da product respectively. The analysis of the reaction between formaldehyde and tryptic peptides from matrix protein of influenza virus showed that +24 Da products could be detected in most peptides due to combinational contribution from N-terminus of peptide (+12 Da ) and side chain of C-terminal arginine or lysine (+12 Da) . Moreover, a +36 Da product was detected for a peptide with miss-cut site. The results indicated that low-concentration formaldehyde primarily reacted with amino group on N-termini of peptides and proteins, as well as the side chains of arginine and lysine residues. The present study suggested an effective mass spectrometry-based method for analyzing the reaction between low-concentration formaldehyde and peptides and proteins, thus provided strategies for interpretation for the mass spectra of reaction products.