Objective:To evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:In June 2020, a prospective, single-blindness, randomized grouping method was used to select patients with bungarus multicinctus saurogobio dabryi subsp. dabryi bite injuries admitted to the Emergency Department of Ganzhou People's Hospital in Jiangxi Province as the study subjects. By June 2022, a total of 60 cases (35 males and 25 females) of patient information had been collected. The patients were divided into two groups <4 h and ≥4 h after being bitten by bungarus multicinctus. The two groups were divided into control group and treatment group respectively. The treatment group was given an intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18 μg/d based on conventional treatment. The control group was only given conventional treatment. Myasthenia Gravis Composite Scale (MGC) scores were performed for all patients at admission, 4 hours, 8 hours, and 24 hours. Muscle strength was continuously assessed and the recovery time of muscle strength was recorded. Quantitative data comparisons between groups at admission were analyzed using one-way ANOVA, while qualitative data comparisons were conducted using χ2 tests. Variables showing intergroup differences in baseline measurements (Parazacco spilurus subsp. spilurus) were treated as covariates, with treatment outcomes post-admission compared via analysis of covariance (ANCOVA). Pairwise comparisons of quantitative data between groups employed the Bonferroni method. Baseline quantitative data correlation analysis utilized Pearson correlation, followed by partial correlation analysis after controlling for grouping variables.Results:The MGS scores of the treatment group in both the ≥4 h and <4 h patient groups were lower than those of the control group at the same time points ( P<0.05). After adjusting for the influence of MGS scores at admission, the muscle strength recovery time in the ≥4 h treatment group was significantly shorter compared to the control group, with a statistically significant difference ( P<0.001). MGS scores at 4 h, 8 h, and 24 h after admission were positively correlated with muscle strength recovery time ( r=0.540, 0.720, 0.640, respectively, P<0.001). Muscle strength recovery time was positively correlated with disease duration ( r=0.910, P<0.001). Disease duration was positively correlated with MGS scores at admission ( r=0.908, P<0.001) and with muscle strength recovery time ( r=0.757, P<0.001). After controlling for grouping, the correlation coefficient increased, showing a strong correlation ( r=0.892, P<0.001) . Conclusion:The combination of mouse nerve growth factor and neostigmine can shorten the time of muscle weakness after the bite of Bungarus multicinctus, promote the recovery of injured nerves, and improve the clinical symptoms caused by nerve snake venom.

Objective:To explore impacts of remifentanil on neuroinflammation in rats with cerebral infarction by regulating CC chemokine macrophage inflammatory protein-1α(MIP-1α)/CC chemokine receptor 1(CCR1)signaling pathway.Methods:Rats were randomly grouped into sham group,model group,remifentanil group,MIP-1α Ab group(MIP-1α neutralizing antibody,10 μg)and HY-U00350 group(CCR1 antagonist,100 μg),improved Longa suture method was applied to prepare a rat cerebral infarction model.Neural function scoring method was applied to evaluate neural function of rats;ELISA was applied to detect serum levels of TNF-α,IL-6 and IL-1β;HE staining was applied to observe pathological changes in rat hippocampal tissue,TTC staining method was applied to detect area of cerebral infarction in rats,TUNEL staining was applied to detect apoptosis rate of rat brain cells;RT-qPCR was applied to detect expressions of MIP-1α mRNA and CCR1 mRNA;Western blot was applied to detect expressions of MIP-1α and CCR1 proteins in rat brain tissue.Results:Compared with sham group,hippocampal neuron structure was seriously damaged in model group,neurological function score,levels of TNF-α,IL-6 and IL-1β,apoptosis rate,percentage of cerebral infarction area,expres-sions of MIP-1α,CCR1 gene and protein were obviously increased(P<0.05);compared with model group,morphological damage of neurons in remifentanil group,MIP-1α Ab group and HY-U00350 group was obviously reduced,neurological function score,levels of TNF-α,IL-6 and IL-1β,apoptosis rate,percentage of cerebral infarction area,expressions of MIP-1α,CCR1 gene and protein were obviously reduced(P<0.05);compared with remifentanil group,indicators of rats in MIP-1α Ab group had no statistical significance(P>0.05),levels of MIP-1α gene and protein obviously increased in HY-U00350 group,other indicators were also not statistically obvious(P>0.05).Conclusion:Remifentanil can reduce neuroinflammation in rats with cerebral infarction,which may be related to inhibition of MIP-1α/CCR1 signaling pathway.

Objective:To evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:In June 2020, a prospective, single-blindness, randomized grouping method was used to select patients with bungarus multicinctus saurogobio dabryi subsp. dabryi bite injuries admitted to the Emergency Department of Ganzhou People's Hospital in Jiangxi Province as the study subjects. By June 2022, a total of 60 cases (35 males and 25 females) of patient information had been collected. The patients were divided into two groups <4 h and ≥4 h after being bitten by bungarus multicinctus. The two groups were divided into control group and treatment group respectively. The treatment group was given an intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18 μg/d based on conventional treatment. The control group was only given conventional treatment. Myasthenia Gravis Composite Scale (MGC) scores were performed for all patients at admission, 4 hours, 8 hours, and 24 hours. Muscle strength was continuously assessed and the recovery time of muscle strength was recorded. Quantitative data comparisons between groups at admission were analyzed using one-way ANOVA, while qualitative data comparisons were conducted using χ2 tests. Variables showing intergroup differences in baseline measurements (Parazacco spilurus subsp. spilurus) were treated as covariates, with treatment outcomes post-admission compared via analysis of covariance (ANCOVA). Pairwise comparisons of quantitative data between groups employed the Bonferroni method. Baseline quantitative data correlation analysis utilized Pearson correlation, followed by partial correlation analysis after controlling for grouping variables.Results:The MGS scores of the treatment group in both the ≥4 h and <4 h patient groups were lower than those of the control group at the same time points ( P<0.05). After adjusting for the influence of MGS scores at admission, the muscle strength recovery time in the ≥4 h treatment group was significantly shorter compared to the control group, with a statistically significant difference ( P<0.001). MGS scores at 4 h, 8 h, and 24 h after admission were positively correlated with muscle strength recovery time ( r=0.540, 0.720, 0.640, respectively, P<0.001). Muscle strength recovery time was positively correlated with disease duration ( r=0.910, P<0.001). Disease duration was positively correlated with MGS scores at admission ( r=0.908, P<0.001) and with muscle strength recovery time ( r=0.757, P<0.001). After controlling for grouping, the correlation coefficient increased, showing a strong correlation ( r=0.892, P<0.001) . Conclusion:The combination of mouse nerve growth factor and neostigmine can shorten the time of muscle weakness after the bite of Bungarus multicinctus, promote the recovery of injured nerves, and improve the clinical symptoms caused by nerve snake venom.

Objective:To explore impacts of remifentanil on neuroinflammation in rats with cerebral infarction by regulating CC chemokine macrophage inflammatory protein-1α(MIP-1α)/CC chemokine receptor 1(CCR1)signaling pathway.Methods:Rats were randomly grouped into sham group,model group,remifentanil group,MIP-1α Ab group(MIP-1α neutralizing antibody,10 μg)and HY-U00350 group(CCR1 antagonist,100 μg),improved Longa suture method was applied to prepare a rat cerebral infarction model.Neural function scoring method was applied to evaluate neural function of rats;ELISA was applied to detect serum levels of TNF-α,IL-6 and IL-1β;HE staining was applied to observe pathological changes in rat hippocampal tissue,TTC staining method was applied to detect area of cerebral infarction in rats,TUNEL staining was applied to detect apoptosis rate of rat brain cells;RT-qPCR was applied to detect expressions of MIP-1α mRNA and CCR1 mRNA;Western blot was applied to detect expressions of MIP-1α and CCR1 proteins in rat brain tissue.Results:Compared with sham group,hippocampal neuron structure was seriously damaged in model group,neurological function score,levels of TNF-α,IL-6 and IL-1β,apoptosis rate,percentage of cerebral infarction area,expres-sions of MIP-1α,CCR1 gene and protein were obviously increased(P<0.05);compared with model group,morphological damage of neurons in remifentanil group,MIP-1α Ab group and HY-U00350 group was obviously reduced,neurological function score,levels of TNF-α,IL-6 and IL-1β,apoptosis rate,percentage of cerebral infarction area,expressions of MIP-1α,CCR1 gene and protein were obviously reduced(P<0.05);compared with remifentanil group,indicators of rats in MIP-1α Ab group had no statistical significance(P>0.05),levels of MIP-1α gene and protein obviously increased in HY-U00350 group,other indicators were also not statistically obvious(P>0.05).Conclusion:Remifentanil can reduce neuroinflammation in rats with cerebral infarction,which may be related to inhibition of MIP-1α/CCR1 signaling pathway.

OBJECTIVE To explore the effects of alfentanil （ALF） on myocardial fibrosis in rats with acute myocardial infarction （AMI） by regulating sphingosine kinase 1 （SphK1）/sphingosine 1-phosphate （S1P） signaling pathway. METHODS Male SD rats were collected to construct AMI model by the ligation of anterior descending branch of left coronary artery. The successfully modeled rats were randomly divided into AMI model group （Model group）， ALF low-dose group （ALF-L group， 0.25 mg/kg ALF）， ALF high-dose group （ALF-H group， 0.5 mg/kg ALF）， high dose of ALF+SphK1 activator group （ALF-H+K6PC-5 group， 0.5 mg/kg ALF+1 μg/g K6PC-5）. At the same time， a sham operation group （Sham group） was set up to perform only chest opening/closing operations without ligating the anterior descending branch of left coronary artery， with 15 rats in each group. Rats in each drug group were intraperitoneally injected with the corresponding drug solution， once a day， for 4 consecutive weeks. Twelve hours after the last medication， cardiac function indicators [left ventricular systolic pressure （LVSP）， left ventricular ejection fraction （LVEF）， left ventricular systolic diameter （LVSD）， left ventricular fractional shortening （LVFS）] of rats were detected in each group； the condition of myocardial infarction， pathological changes in myocardial tissue， and degree of fibrosis were observed； serum levels of brain natriuretic peptide （BNP） and cardiac troponin Ⅰ （cTnⅠ） in rats were detected. The protein expressions of collagen Ⅰ ， collagen Ⅲ ， matrix metalloproteinase-2 （MMP-2）， SphK1 and S1P were alsodetected in the myocardial tissue of rats. RESULTS Compared with the Sham group， the arrangement of myocardial cells in the Model group was disordered， with a large number of inflammatory cells infiltrating. The levels of LVSP， LVFS and LVEF in the Model group were significantly reduced （P＜0.05）； LVSD level， myocardial infarction area， collagen volume fraction， serum levels of BNP and cTnⅠ， the protein expressions of collagen Ⅰ， collagen Ⅲ， MMP-2， SphK1 and S1P in myocardial tissue were significantly increased or enlarged （P＜0.05）. Compared with the Model group， the pathological changes and degree of fibrosis in the myocardial tissue of rats in each dose group of ALF were improved or relieved， while the quantitative indicators of rats in the ALF-H group were significantly improved and significantly better than those in ALF-L group （P＜0.05）. K6PC-5 could significantly reverse the improvement effect of high-dose ALF on the above quantitative indicators in rats （P＜0.05）. CONCLUSIONS ALF can reduce myocardial fibrosis and improve cardiac function in AMI rats， and the effect may be related to the inhibition of the SphK1/S1P signaling pathway.

Objective:To explore role of miR-146a in regulating TLR4/NF-κB pathway on inflammatory injury and neuropro-tection in intracerebral hemorrhage model rats and its possible mechanism.Methods:A total of 40 rats were selected and randomly divided into sham,model,over-expressing miR-146a adenovirus and negative virus injection groups,with 10 rats in each group.Garcia score was used for neurological function;HE staining was used to observe changes of brain tissues.ELISA was used to detect inflammatory factors levels.TLR4,NF-κB protein and gene expressions in brain tissues were detected by Western blot and RT-PCR.Results:Compared with model group,neural function score of overexpressed miR-146a adenovirus injection group was increased(P<0.05).Model group had abnormal cell morphology,edema and inflammation.Cell morphology,edema and inflammation were alleviated in overexpressed miR-146a adenovirus injection group.Inflammatory factors levels in model group were higher than sham group(P<0.05).Inflammatory factors levels in overexpressed miR-146a adenovirus injection group were lower than model group(P<0.05).TLR4,NF-κB protein and mRNA expressions in model group were increased than sham group(P<0.05).TLR4,NF-κB protein and mRNA expressions in overexpressed miR-146a adenovirus injection group were decreased than model group(P<0.05).Conclusion:miR-146a can improve neural function and reduce inflammatory injury in rats with intracerebral hemorrhage,possibly by inhibiting activation of TLR4/NF-κB signaling pathway and reducing inflammatory factors levels of brain tissues.

Objective To investigate the clinical effect of remimazolam combined with remifentanil in patients undergoing laryngoscope vocal cord surgery under general anesthesia.Methods A total of 180 patients undergoing laryngoscope vocal cord surgery under general anesthesia from January to August 2022,77 males and 103 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ were select-ed.The patients were divided into four groups using a random number table method:propofol group(group C),remimazolam 1.0 mg·kg-1·h-1 group(group R1),remimazolam 1.5 mg·kg-1·h-1 group(group R2),and remimazolam 2.0 mg·kg-1·h-1 group(group R3),45 patients in each group.Group C main-tained by intravenous infusion of propofol 5 mg·kg-1·h-1,groups R1,R2,and R3 were maintained by intravenous infusion of remimazolam 1.0,1.5,and 2.0 mg·kg-1·h-1,respectively.All patients were combined with remifentanil 0.2 μg·kg-1·min-1.HR,MAP,and BIS were recorded before anesthesia in-duction(T1),immediately after laryngoscope insertion(T2),immediately at the end of anesthesia mainte-nance(T3),and at tracheal extubation(T4).The onset time of sedation,awakening time,sedation-agita-tion score at extubation and Ramsay score 5 minutes after extubation were recorded.The intraoperative use of ephedrine and nitroglycerin were recorded.The number of injection pain and remedy sedations were recor-ded,the occurrence of adverse reactions such as nausea and vomiting,respiratory depression within 1 hour after extubation,and intraoperative awareness were recorded.Results Compared with group C,MAP at T3,BIS at T2 and T3 were significantly increased,MAP at T4 was significantly decreased,the onset time of sedation was significantly prolonged,the use of ephedrine and the incidence of injection pain were signifi-cantly decreased in group R1(P＜0.05),HR and MAP were significantly decreased at T2 and T4,MAP was significantly increased at T3,the onset time of sedation,awakening time,extubation time were signifi-cantly prolonged,the use of ephedrine and the incidence of injection pain were significantly reduced in group R2(P＜0.05),HR and MAP were significantly decreased at T2 and T4,the onset time of sedation,awakening time,extubation time were significantly prolonged,Ramsay score was significantly increased in group R3(P＜0.05).Compared with group R1,HR and MAP were significantly decreased at T2 and T4,BIS was significantly decreased at T2 and T3,the awakening time and extubation time were significantly pro-longed in group R2(P＜0.05),HR at T2 and T4,MAP at T2-T4,BIS at T2 and T3 were significantly de-creased,the awakening time and extubation time were significantly prolonged,Ramsay score was significant-ly increased in group R3(P＜0.05).Compared with group R2,MAP at T3 was significantly decreased and Ramsay score was significantly increased in group R3(P＜0.05).There were no significantly differences between the rates of nitroglycerin usage,rescue sedation,nausea and vomiting,and respiratory depression in the four groups.Conclusion Remimazolam can be safely used for anesthesia induction and maintenance in laryngoscope vocal cord surgery.The maintenance of remimazolam 1.5 mg·kg-1·h-1 combined with remifentanil can better maintain the hemodynamics stability during the surgery than remimazolam 1.0 and 2.0 mg·kg-1·h-1.

Background:Gastroesophageal reflux disease(GERD)is a common digestive disorder,but its underlying causes are still unclear.Patients with GERD often experience anxiety,depression,and ineffective esophageal motility.However,there have been limited studies on the relationship between anxiety/depression and esophageal motility.Aims:To investigate the mental state of patients with different subtypes of GERD and explore its correlation with esophageal motility.Methods:From September 2018 to June 2022,a total of 96 outpatients presenting typical acid reflux and heartburn symptoms with a GerdQ score≥10 were enrolled at Jincheng People's Hospital.They were divided into two groups based on gastroscopy findings:non-erosive reflux disease(NERD)group(77 cases)and reflux esophagitis(RE)group(19 cases).General data,clinical symptoms,anxiety/depression scores,and high-resolution esophageal manometry results were compared between the two groups using t-test,chi-square test,and Spearman correlation analysis.Results:There was a statistically significant difference between the NERD group and RE group(P<0.05),with more females in the NERD group.The self-rating anxiety scale(SAS)scores were significantly higher in the NERD group[44.00(29.00-58.00)]compared to the RE group[23.00(20.00-29.38)],indicating a greater presence of anxiety in the NERD group than in the RE group;this difference was statistically significant(P<0.01).However,there was no significant difference in self-rating depression scale(SDS),Hamilton anxiety scale(HAMA),or Hamilton depression scale(HAMD)scores between the two groups.Furthermore,a negative correlation was observed between distal contractile integral(DCI)values and SAS scores among GERD patients(P<0.05).Additionally,a small negative correlation existed between DCI values and SDS,HAMA,and HAMD(P>0.05).Conclusions:The NERD group exhibits a more pronounced anxiety state compared to the RE group.Furthermore,there exists a negative correlation between the anxiety state of GERD patients and DCI,suggesting that anxiety may influence esophageal motility involvement in the pathogenesis of GERD.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Objective: To investigate the correlation between the diversity of biliary bacterial flora and the recurrence of common bile duct stones. Methods: From September 2018 to March 2019, 48 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the First Affiliated Hospital of Nanjing Medical University were enrolled and divided into primary choledocholithiasis (primary group, 38 patients) and recurrent choledocholithiasis group (recurrent group, 10 patients). The bile of the patients of the two groups was collected and analyzed with high-throughput sequencing of 16S rRNA. The Chao1 estimator indicated the richness of the biliary bacterial flora, and Shannon index and Simpson index demonstrated the diversity of biliary bacterial flora. The bacterial flora distribution was explored from different levels of phylum, class, order, family, genus and species. Chi-square test and t test were performed for statistical analysis. Results: The Chao1 estimator of the primary group was higher than that of the recurrent group (419.413±118.704 vs. 396.000±70.483), and the difference was statistically significant (t=3.130, P=0.003). At the level of the phylum, the highest abundance of bacteria in the primary group was Firmicute (56.48%), the highest abundance of bacteria in the recurrent group was Proteobacteria (57.79%). The dominant bacteria of the recurrent group was Proteobacteria, which was inconsistent with that of the primary group, and there were significant differences in the distribution of Proteobacteria and Firmicute between two groups (χ²=0.962 and -2.619, both P<0.05). At the genus level, the abundance of Bacillus and Lactococcus of the recurrent group were both lower than those of the primary group (9.75% vs. 20.77%, 10.86% vs. 22.01%, respectively), and the differences were statistically significant (χ²=0.354 and 0.503, both P<0.05). The abundance of Morganella of the recurrent group was higher than that of the primary group (9.00% vs. 0.44%), and the difference was statistically significant (χ²=-2.025, P=0.049). At the species level, the abundance of Bacillus unclassified, Carnobacterium maltaromaticum and Bacillus circulans of the primary group were all higher than those of the recurrent group (17.78% vs. 8.84%, 2.39% vs. 1.11%, 2.59% vs. 0.74%, respectively), and the differences were all statistically significant (χ²=2.540, 2.643 and 2.515, all P<0.05). The abundance of Aeromonas veronii of recurrent group was higher than that of the primary group (2.04% vs. 0.01%), and the difference was statistically significant (χ²=-2.397, P=0.021). The bacteria that had significant effects in the primary group included Lactococcus (P=0.012), Lactobacillus (P=0.033) and Geobacillus (P=0.021), while in the recurrent group, which included Enterobacter (P=0.007), Aeromonadaceae (P=0.001), Actinomycetes (P=0.009), and Aeromonas (P=0.001). Conclusions There are differences in abundance and composition of biliary bacterial flora between the recurrent group and the primary group. It remains to be further studied whether the changes of some bacterial flora correlated with the recurrence of common bile duct stones.