Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

ObjectiveTo analyze the epidemic characteristics of foodborne disease outbreaks in Mengla County， Yunnan Province， so as to provide basis for formulating corresponding prevention and control measures. MethodsThe data of foodborne disease outbreaks in Mengla County， Yunnan Province from 2017 to 2021 in the national "foodborne disease outbreak monitoring system" were collected. The time， population， region， place， pathogenic factors and inducing links of the events were statistically analyzed. ResultsFrom 2017 to 2021， a total of 68 incidents were reported， including 526 cases and 5 deaths. The total incidence rate was 23.40% and the case fatality rate was 0.95%. The peak period was from May to July， with the largest number of reported events in July. The reporting areas were mainly Mengla Town （35.29%）， Guanlei Town （11.76%） and Mengpeng Town （10.29%）. The main place of the incident was family （76.47%）. The main pathogenic factors were plant toxins （79.41%）， mainly through the ingestion of wild mushrooms （68.52%）， improper processing of green beans （12.96%） and aconitum （9.26%）. ConclusionAccording to the epidemiological characteristics of Mengla County， we should focus on the public education of health knowledge in key areas and places， especially on the identification of wild mushrooms， to prevent accidental eating. At the same time， we should strengthen the monitoring and risk assessment of foodborne diseases， find potential risks as soon as possible， issue early warning and forecast in time， and constantly improve the clinical treatment ability of poisoned patients.

In order to explore the effect of peptidoglycan hydrolase on the viable cell counts of Bacillus amyloliquefaciens and the yield of alkaline protease, five peptidoglycan hydrolase genes (lytC, lytD, lytE, lytF and lytG) of B. amyloliquefaciens TCCC111018 were knocked out individually. The viable cell counts of the bacteria and their alkaline protease activities before and after gene deletion were determined. The viable cell counts of the knockout mutants BA ΔlytC and BA ΔlytE achieved 1.67×10⁶ CFU/mL and 1.44×10⁶ CFU/mL respectively after cultivation for 60 h, which were 32.5% and 14.3% higher than that of the control strain BA Δupp. Their alkaline protease activities reached 20 264 U/mL and 17 265 U/mL, respectively, which were 43.1% and 27.3% higher than that of the control strain. The results showed that deleting some of the peptidoglycan hydrolase genes effectively maintained the viable cell counts of bacteria and increased the activity of extracellular enzymes, which may provide a new idea for optimization of the microbial host for production of industrial enzymes.
Bacillus amyloliquefaciens/genetics* ; Bacterial Proteins ; Cell Count ; Endopeptidases/genetics* ; N-Acetylmuramoyl-L-alanine Amidase/genetics*

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective:To investigate the clinical effect of Jiedu Limai decoction in septic patients with syndrome of heat-toxin exuberance.Methods:A prospective randomized controlled trial was conducted. From March 2019 to April 2020, septic patients with syndrome of heat-toxin exuberance admitted to intensive care unit (ICU) of Shanghai General Hospital and Songjiang Branch of Shanghai General Hospital were enrolled as the research objects, and they were divided into routine treatment group and Jiedu Limai decoction group by the random number table method. Patients in both groups were given standard treatment in accordance with the guidelines, and patients in the Jiedu Limai decoction group were given Jiedu Limai decoction in addition to the standard treatment, once a day for 14 days. The 28-day survival of patients of the two groups were recorded, the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, coagulation indexes, infection indexes, inflammatory cytokines and organ function indicators before treatment and 7 days after treatment in both groups were recorded, and the prognosis of the two groups were recorded.Results:A total of 259 patients with infection or clinical diagnosis of infection admitted during the experimental observation period were included, and those who did not meet the Sepsis-3 diagnostic criteria, more than 80 years old or less than 18 years old, with multiple tumor metastases, autoimmune system diseases, with length of ICU stay less than 24 hours, with acute active gastrointestinal bleeding and with incomplete data were excluded. One hundred patients were finally enrolled, with 50 patients in the routine treatment group and 50 patients in the Jiedu Limai decoction group. There were no statistically significant differences in coagulation indexes, infection indicators, inflammatory cytokines and organ function indicators before treatment between the two groups. After 7 days of treatment, the coagulation indexes, infection biomarkers and inflammatory cytokines in the Jiedu Limai decoction group were significantly lower than those in the routine treatment group [D-dimer (mg/L): 2.2 (1.8, 8.5) vs. 4.0 (1.5, 8.7), fibrinogen (Fib, g/L): 3.7 (3.4, 4.3) vs. 4.2 (3.7, 4.3), fibrinogen degradation product (FDP, mg/L): 7.2 (5.4, 10.2) vs. 13.2 (9.2, 15.2), procalcitonin (PCT, μg/L): 0.4 (0.2, 2.9) vs. 0.5 (0.2, 0.9), C-reactive protein (CRP, mg/L): 50.1 (9.5, 116.0) vs. 75.1 (23.5, 115.2), interleukin-6 (IL-6, ng/L): 31.6 (21.6, 81.0) vs. 44.1 (14.0, 71.3), all P < 0.05], and the levels of B-type brain natriuretic peptide (BNP) and kidney injury molecule-1 (KIM-1) were significantly lowered [BNP (ng/L): 261.1 (87.5, 360.3) vs. 347.3 (128.8, 439.4), KIM-1 (μg/L): 0.86 (0.01, 1.40) vs. 1.24 (1.05, 1.57), both P < 0.05]. Compared with the routine treatment group, the number of new organ failure in the Jiedu Limai decoction group was decreased (30.0% vs. 50.0%, P < 0.05). Although there was no significant difference in 28-day mortality between the two groups ( P > 0.05), the 28-day mortality in the Jiedu Limai decoction group was lower than that in the routine treatment group (18.0% vs. 24.0%). Conclusion:Combining Jiedu Limai decoction to the sepsis guideline in treating syndrome of heat-toxin exuberance can effectively improve patients' coagulation function, the situation of heart and renal injury, reduce the level of inflammatory cytokines, and fewer people develop new organ failure after treatment.

OBJECTIVE：To es tablish the HPLC fingerprint of Arnebia euchroma ，analyze them with chemical pattern recognition technology ， and determine the contents of 3 components. METHODS ： HPLC method was adopted. Using acetylshikonin as reference ，HPLC fingerprint of 34 batches of A. euchroma from different sources were drawn. Similarity Evaluation System for TCM Chromatographic Fingerprint （2012A edition ）was used to evaluate the similarity of the samples ，and common peaks were determined. SPSS 19.0 and SIMCA 14.1 statistical software was used for cluster analysis ，principle component analysis and orthogonal partial least squares-discriminate analysis. According to the standard of the variable importance in the project greater than 1，the differential markers affecting the quality difference of A. euchroma were screened. Meanwhile ，the contents of 3 components were determined by the same HPLC method. RESULTS ：There were 12 common peaks in HPLC fingerprints for 34 batches of A. euchroma . The similarity of other samples were more than 0.86，except that t he three （No.2016A3005-5） batches of medicinal herbs on the market were less than 0.72；3 common peaks were identified ， such as shikonin ，acetylshikonin， β ，β ′-dimethylacrylic acanine. These 34 batches of samples could be classified into two categories . S 1， qq.com S4-S6，S13，S15-S20，S22，S26-S34 were clustered into one category，and others clustered into the other category. By principal component analysis ，the contribution rates of three principle components were 52.834％ ，18.600％ and 8.387％ . Accumulative contribution rate was 79.821％ . Six constituents，such as shikonin，acetylshikonin and β，β'-dimethylacrylic acanine were screened as differential markers，representing the major differences of A. euchroma . The linear range of above three components were 0.72-90，2.05-410，2.50-500 µg/mL（r all more than 0.999）， respectively. The limits of quantification were 0.132，0.135，0.118 µg/mL，respectively. The limits of detection were 0.040，0.041， 0.036 µg/mL，respectively. RSDs of precision ，stability（24 h），reproducibility and durability tests were all lower than 3％. Recoveries were 95.959％-100.201％（RSD＝1.669％，n＝6），97.818％-102.698％（RSD＝1.788％，n＝6），95.831％-99.344％ （RSD＝1.600％，n＝6）. The contents of above three components were 0.002％-0.134％，0.025％-1.388％，0.022％-0.881％. CONCLUSIONS：Established HPLC fingerprint and content determination method are simple and stable ，can be used for quality evaluation and quantitative analysis of A. euchroma . Shikonin ，acetylshikonin and β，β'-dimethylacrylic acanine are different in the content and are differential markers of A. euchroma from different source.

In the original publication of the article the keywords are incorrectly online published. The correct keywords should read as α-Conotoxin; Nicotinc acetylcholine receptor; Acetylcholine binding protein; X-ray crystallography".

OBJECTIVE:To investigate the effects of NOS1AP rs12742393 A/C gene polymorphism on lipid-regulating re-sponse of rosuvastatin calcium. METHODS:Two hundred and tuirty six patients with coronary heart disease(CHD)were selected from cardiology department of our hospital during Jan. 2014-Jun. 2015,and then given rosuvastatin calcium and other symptomatic treatment for 12 weeks. Polymorphism of NOS1AP rs12742393 A/C was detected by PCR-RFLP. The levels of TG,TC,HDL-C and LDL-C were detected by photoelectric colorimetry before treatment and 4,12 weeks after treatment. The serum relationship of genotype with the level of blood lipid was analyzed. RESULTS:Among 236 CHD patients,there were 131 cases of AA genotype (55.5%),98 cases of AC genotype(41.5%) and 7 cases of CC genotype(3.0%);genotype and allele frequencies met the Har-dy-Weinberg balance(P>0.05). There were 132 patients with normal blood lipid and 104 patients with hypercholesterolemia;there was statistical significance in genotype and allele frequencies (P<0.05). Among 104 CHD patients with hypercholesterolemia be-fore treatment,there was no statistical significance in the levels of TG,TC,LDL-C and HDL-C between AA genotype and AC+CC genotype(P>0.05). 4th and 12th week after treatment,the levels of TG,TC and LDL-C in different genotypes were all de-creased significantly;4th week after treatment,the level of LDL-C in AC+CC genotype was significantly lower than AA genotype, and the change compared to before treatment was significantly more than AA genotype,with statistical significance (P<0.05). There was no statistical significance in the level of HDL-C among different genotypes compared to before treatment;there was no statistical significance in the levels of TG,TC and HDL-C 4th,12th week after treatment and their changes compared to before treatment between AA genotype and AC+CC genotype;there was no statistical significance in the level of LDL-C 12th week after treatment and their changes between AA genotype and AC+CC genotype(P>0.05). CONCLUSIONS:NOS1AP rs12742393 A/C gene polymorphism is associated with CHD complicated with hypercholesterolemia;the C allele of NOS1AP rs12742393 may strengthen the response of CHD patients with hy-percholesterolemia to rosuvastatin calcium through influencing the level of LDL-C.

The α3* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The α-conotoxin (α-CTx) LvIA has been identified as the most selective inhibitor of α3β2 nAChRs known to date, and it can distinguish the α3β2 nAChR subtype from the α6/α3β2β3 and α3β4 nAChR subtypes. However, the mechanism of its selectivity towards α3β2, α6/α3β2β3, and α3β4 nAChRs remains elusive. Here we report the co-crystal structure of LvIA in complex with Aplysia californica acetylcholine binding protein (Ac-AChBP) at a resolution of 3.4 Å. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvIA plays an important role in the selectivity of LvIA towards α3β2 and α3/α6β2β3 nAChRs by making a salt bridge with Lys-155 of the rat α3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat β2 subunit in the α3β2 nAChR model, revealing the reason for its more potent selectivity towards the α3β2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target α3β2 nAChRs, with significant implications for the design of new therapeutic α-CTxs.
Animals ; Aplysia ; Binding Sites ; Conotoxins ; chemistry ; Crystallography, X-Ray ; Humans ; Protein Structure, Quaternary ; Receptors, Nicotinic ; chemistry