The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective To investigate the influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in patients with severe acute pancreatitis(SAP), and to establish a predictive model. Methods A retrospective analysis was performed for the clinical data of 163 patients who were admitted to the intensive care unit and the emergency intensive care unit due to SAP in The First Affiliated Hospital of Guangxi Medical University from May 2012 to May 2022, and according to the diagnostic criteria for PICS, these patients were divided into PICS group (65 SAP patients with PICS) and non-PICS group (98 SAP patients without PICS). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Variance inflation factor and correlation matrix heatmap were used to evaluate multicollinearity between variables, and Lasso regression and multivariate logistic regression were used to identify independent risk factors and establish a nomogram predictive model. The receiver operating characteristic (ROC) curve, the calibration curve, and the Hosmer-Lemeshow goodness-of-fit test were used for the internal validation of the model, and the decision curve was used to evaluate the clinical practicability of the model. Results The univariate analysis showed that there were significant differences between the PICS group and the non-PICS group in mean arterial pressure, hemoglobin, hematocrit (HCT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), blood urea nitrogen, creatinine, Glasgow coma score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, acute respiratory distress syndrome, acute kidney injury (AKI), acute liver injury, hypovolemic shock, sepsis, intra-abdominal hypertension, intra-abdominal hemorrhage, and multiple organ dysfunction syndrome (all P < 0.05). The Lasso regression analysis showed that related predictive variables included PLR, HCT, APACHE Ⅱ, SOFA, mechanical ventilation, AKI, hypovolemic shock, and intra-abdominal hypertension, and the multivariate logistic regression analysis showed that PLR (odds ratio [ OR ]=1.006, P < 0.05), mechanical ventilation ( OR =4.324, P < 0.05), AKI ( OR =3.432, P < 0.05), and hypovolemic shock ( OR = 6.910, P < 0.05) were independent risk factors for PICS in patients with SAP. Model fitting was performed for the above factors, and bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.874 (95% confidence interval: 0.822-0.925); the calibration curve of the model was close to the reference curve, and the Hosmer-Lemeshow goodness-of-fit test showed that the model was well fitted ( χ 2 =8.895, P =0.351). The decision curve analysis showed that the predictive model had good clinical practicability. Conclusion PLR, mechanical ventilation, AKI, and hypovolemic shock are independent risk factors for PICS in patients with SAP, and the nomogram model established has good discriminatory ability, calibration, and clinical practicability.

Objective    To assess the feasibility and safety of ultra-micro 5 mm single-port endoscopic thoracic sympathicotomy in selected patients with primary palmar hyperhidrosis. Methods    From March 1, 2018 to February 1, 2021, 90 patients with primary palmar hyperhidrosis who underwent ultra-micro 5 mm single-port endoscopic thoracic sympathicotomy at the Thoracic Surgery Department of the University of Hong Kong-Shenzhen Hospital. There were 47 males and 43 females, with a median age of 26.0 (22.0, 31.0) years. During the operation, T3 and/or T4 thoracic sympathetic nerve chain was transected using an ultra-micro 5 mm single-port incision near the areola or under the axilla. The surgical data of the patients were retrospectively reviewed and analyzed. Results     All patients successfully completed the operation without major bleeding during the operation and no conversion to thoracotomy. There was no death or serious complication during the perioperative period. The operation time was 43.0 (23.0, 60.0) min, and the intraoperative blood loss was 2.0 (1.0, 2.0) mL. In the perioperative period, only one patient needed a tiny chest tube indwelling. The symptoms of hyperhidrosis on the hands all disappeared after the operation. The pain score on the postoperative day was 2.0 (2.0, 2.0) points. The hospital stay after surgery was 1.0 (1.0, 1.0) d. In the first month after the operation, the symptoms of hyperhidrosis on the hands were significantly relieved compared with those before the operation. The surgical incisions healed well, the wounds were concealed, and there was no wound infection or poor healing. The patients' satisfaction with the surgical incisions was 100.0%. After the operation, 14 (15.6%) patients had mild compensatory hyperhidrosis, 5 (5.6%) patients had moderate compensatory hyperhidrosis, and no patient had severe compensatory hyperhidrosis. Overall satisfaction rate was 94.0%. Conclusion     The clinical application of ultra-micro 5 mm single-port endoscopic thoracic sympathicotomy in selected patients with primary palmar hyperhidrosis is safe and feasible. The surgical wound is extremely small and hidden, the operation time is short, the pain is very slight, and the clinical outcome is good. It can fully meet the patients' pursuit of beauty.

OBJECTIVE：To analyze the metabolites of tetrahydroxystilbene glucoside （THSG）and speculate its metabolism pathway in rats. METHODS ：Male SD rats were randomly divided into plasma group （n＝3），urine group （n＝3），bile group （n＝3），and tissue group （n＝9）. Each group was given single dose of THSG 200 mg/kg intragastrically. Plasma samples 10，30 min and 1，1.5，2，4 h after medication ，the unrine 0-6 h after medication ，the bile 0-4 h after medication ，the tissue of heart ， liver，spleen，lung，kidney and stomach 30 min and 1，2 h after medication （3 at each time point ）were collected respectively.After precipitated with methanol ，the metabolites of samples were analyzed and identified by UHPLC-Q-Exactive Orbitrap MS and mass loss filtration （MDF）. Its metabolism pathway was speculated. RESULTS：In the blood ，urine，bile，heart，liver，spleen， lung，kidney，stomach samples ，6，7，11，1，5，1，3，4，4 metabolites were detected ，including two phase Ⅰ（hydrolysis， hydrogenation and hydroxylation ）metabolites，18 phase Ⅱ（glucuronic acid binding and sulfation ）metabolites. There were 12 glucuronic acid binding products. CONCLUSIONS：Most of the metabolites of THSG are found in bile ，mainly glucuronic acid binding products of phase Ⅱ metabolite THSG ； main metabolic pathways involve glucose hydrolysis ， hydrogenation， hydroxylation，glucuronic acid binding and sulfation.

Acute pancreatitis (AP) is a common gastrointestinal disease and may lead to local complications and even multiple organ failure, and the pathogenesis of AP involves self-digestion of trypsin, inflammatory response, and microcirculation disturbance. This article introduces the role of pyroptosis in the pathogenesis of AP and briefly describes the activation pathway of pyroptosis, inflammasome, and the mechanism of action of effector molecules in inducing damage to the pancreas and extra-pancreatic organs. It is believed that the regulation of pyroptosis plays an important role in the pathogenesis of AP, which provides new ideas for the prevention and treatment of AP.

Objective:To evaluate the role of synapsin-Ⅰ phosphorylation in herkinorin-induced reduction of oxygen-glucose deprivation/restoration (OGD/R)-caused damage to cortical neurons and the relationship with conventional protein kinase C (cPKC)γ in newborn mice.Methods:Primary cortical neurons of cPKCγ + /+ and cPKCγ -/- mice (within 24 h after birth) were cultured for 7 days.Each type of neurons were then divided into 3 groups ( n=5 each) using a random number table method: control group (group C), OGD/R group and herkinorin group (group H). The neurons were subjected to oxygen-glucose deprivation (OGD) for 1 h followed by restoration of oxygen-glucose supply for 24 h. Herkinorin 10 μmol/L was added immediately after onset of OGD, the neurons were then incubated for 1 h, and herkinorin was washed out at the end of OGD in group H. At 24 h of oxygen-glucose restoration, cells were collected for measurement of the cell survival rate by methyl thiazolyl tetrazolium assay, and immunofluorescence was used to measure the number of neurites and the length of dendrites.Western blot was applied to detect the expression of phosphorylated synapsin-Ⅰ (p-synapsin-Ⅰ). Results:Compared with group C, the cell survival rate and the number of neurites were significantly decreased, the length of dendrites was shortened, and the expression of p-synapsin-Ⅰ was down-regulated in cPKCγ + /+ and cPKCγ -/- mice in group OGD/R and group H ( P<0.05). Compared with group OGD/R, the cell survival rate and the number of neurites were significantly increased, the length of dendrites was prolonged, the expression of p-synapsin-Ⅰ was up-regulated in cPKCγ + /+ mice in group H ( P<0.05), and no significant change was found in the parameters mentioned above in cPKCγ -/- mice in group H ( P>0.05). There was no significant differences in the expression of synapsin-Ⅰ in neurons among the three groups of cPKCγ + /+ mice and among the three groups of cPKCγ -/- mice ( P>0.05). Conclusion:Herkinorin can reduce OGD/R-caused damage to cortical neurons through decreasing cPKCγ membrane translocation and inhibiting synapsin-Ⅰ phosphorylation in newborn mice.

OBJECTIVE：To establ ish the fingerprint of Sojae Semen Nigrum and content determination method of 5 kinds of isoflavones，so as to provide reference for controlling its quality better. METHODS ：HPLC method was adopted to establish the fingerprint and detect the contents of 5 kinds of isoflavones. The determination was performed on Phenomenex C 18 column with mobile phase consisted of acetonitrile- 0.12％ formic acid solution （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 260 nm；the column temperature was 30 ℃ and sample size was 10 μL. Using daidzin as reference，HPLC fingerprints of 12 batches of samples were determined. The similarity of 12 batches of samples was evaluated by TCM Chromatographic Fingerprint Similarity Evaluation System （2012A） to confirm common peak. Cluster analysis and principal component analysis were performed by using SPSS 20.0 software and SIMCA 13.0 software. RESULTS ：There were 19 common peaks in HPLC fingerprints of 12 batches of samples ，the similarity of which was higher than 0.94. Totally 5 components were identified，such as daidzin ，glycitin，genistin，daidzein，genistein. Cluster analysis showed that 12 batches of Sojae Semen Nigrum were clustered into 2 categories，i.e. S 1-S3 clustered into one category ，and S 4-S12 clustered into the other category. By principal component analysis ，the contribution rates of two principle components were 53.261％ and 40.715％；accumulative contribution rate was 93.976％. The linear range of above 5 components were 5.97-191.00 µg/mL（r＝0.999 9），1.05-33.46 µg/mL（r＝0.999 9）， 8.93-285.61 µg/mL（r＝0.999 5），0.82-26.33 µg/mL（r＝0.999 9），0.93-29.64 µg/mL（r＝0.999 7），respectively. The limits of quantitation were 0.881 1，0.611 6，0.078 6，0.243 3，0.511 6 μg/mL，respectively. The limits of detection were 0.264 3，0.244 7， 0.021 4，0.124 8，0.106 7 μg/mL，respectively. RSDs of precision ，stability，reproducibility and durability tests were all lower than 5％. Recoveries were 95.15％-96.56％（RSD＝0.51％，n＝6），98.52％-103.45％（RSD＝1.88％，n＝6），95.37％-97.91％ （RSD＝0.95％，n＝6），99.75％-102.00％（RSD＝0.78％，n＝6），100.26％-103.65％（RSD＝1.21％，n＝6）. Among 12 batches of Sojae Semen Nigrum ，the contents of above 5 components were 0.178 3-0.265 9，0.021 7-0.096 2，0.288 5-0.597 2，0.014 1- 0.058 8，0.012 9-0.082 9 mg/g. CONCLUSIONS ：Established HPLC fingerprint and content determination method of 5 kinds of isoflavones can be used for quality control of Sojea Semen Nigrum. The Isoflavone components are similar ，but the contents are different among Sojae Semen Nigrum from different producing areas.

ObjectiveTo investigate the value of early fluid resuscitation endpoints in evaluating blood volume in patients with acute pancreatitis. MethodsA retrospective analysis was performed for the clinical data of 445 previously untreated patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Guangxi Medical University from 2003 to 2016 and had an onset time of less than 24 hours, and according the fluid resuscitation endpoints of mean arterial pressure (MAP), hematocrit (HCT), and blood urea nitrogen (BUN), the patients were divided into standard-reaching group (MAP ＞65 mm Hg, BUN ＜7.14 mmol/L, and HCT ≥0.35 and ≤044, n=219) and non-standard-reaching group (MAP ≤65 mm Hg or BUN ≥7.14 mmol/L or HCT ＞0.44 or ＜0.35, n=226). The standard-reaching group represented normal volume, while the non-standard-reaching group represented insufficient volume. The two groups were compared in terms of symptoms, signs, etiology, severity, complication, and prognosis. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of continuous data between two groups. ResultsCompared with the standard-reaching group, the non-standard-reaching group had significant increases in white blood cell count, BUN, and Computed Tomography Severity Index of the pancreas (Z=-2.85, -6.725, and -2.293, all P＜0.01). As for local complications, compared with the non-standard-reaching group, the standard-reaching group had significantly lower incidence rates of peripancreatic exudation (45.2% vs 54.9%, χ2=4.15, P＜0.05) and pancreatic necrosis (10.0% vs 186%, χ2=6.59, P＜0.05). As for systemic complications, compared with the non-standard-reaching group, the standard-reaching group had significantly lower incidence rates of acute respiratory distress syndrome (ARDS) (0.5% vs 4.4%, χ2=7.26, P＜0.05) and renal dysfunction (1.4% vs 6.6%, χ2=7.95, P＜0.05). The standard-reaching group had significantly lower proportion of patients with severe pancreatitis and hospital costs than the non-standard-reaching group (both P＜0.05). ConclusionFluid resuscitation endpoints can be used to evaluate the blood volume of patients with acute pancreatitis in the early stage after admission, and the patients not reaching the standard of fluid resuscitation tend to develop the complications such as peripancreatic exudation, pancreatic necrosis, ARDS, and renal dysfunction and may have higher hospital costs.

ObjectiveTo investigate the clinical features of severe acute hypertriglyceridemic pancreatitis (HTGP). MethodsA retrospective analysis was performed for the clinical data of 179 patients with moderate severe pancreatitis (MSAP) or severe acute pancreatitis (SAP) who were admitted to The First Affiliated Hospital of Guangxi Medical University from January 2013 to June 2016. According to the etiology, these patients were divided into severe biliogenic acute pancreatitis (biliogenic AP) group with 68 patients, severe alcoholic acute pancreatitis (alcoholic AP) group with 39 patients, severe acute HTGP group with 45 patients, and severe acute pancreatitis group with other causes (other group) with 27 patients. Related data of the patients with clear causes in the former three groups were recorded, including demographic data, blood triglyceride (TG) level on the first day of admission, cause, pancreatic necrosis, systemic complications ［acute respiratory distress syndrome (ARDS), acute renal injury, hypotension, and disseminated intravascular coagulation (DIC)］, and related clinical outcomes (admission to the intensive care unit, length of hospital stay, and mortality rate). In order to investigate the influence of TG concentration on the prognosis of AP patients, the patients were divided into normal blood lipid group with 82 patients, mild dyslipidemia group with 52 patients, moderate dyslipidemia group with 28 patients, and severe dyslipidemia group with 17 patients, according to the TG level on the first day of admission, and the incidence rates of systemic complications, pancreatic necrosis, and clinical outcomes were analyzed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, the chi-square test was used for comparison of categorical data between groups, and the Spearman rank correlation test was used for correlation analysis. ResultsBiliary tract disease remained the leading cause of SAP (38%), followed by hypertriglyceridemia (25%). As for systemic complications, the HTGP group had a significantly higher incidence rate of ARDS than the biliogenic AP group and the alcoholic AP group (P=0.014 and 0022). In the groups with different TG levels, the incidence rates of ARDS and acute renal injury were positively correlated with TG level (r=0.966 and 0.982, P=0.004 and 0.019). ConclusionThe HTGP group has a higher incidence rate of ARDS than the biliogenic AP group and the alcoholic AP group, and the risk of ARDS and acute renal injury tends to increase with the increasing TG level.

Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.