Tetrodotoxin（TTX）is a potent neurotoxin known for its specific sodium channel blocking effects, widely used in biomedical research. While TTX has been identified in various marine organisms, its true origin remains unclear, and the specific biosynthetic pathways are yet to be elucidated. The reported sources of TTX and the progress in research on TTX biosynthesis were summarized, with a focus on potential microbial sources of TTX, which could provide scientific reference for the production and biosynthesis studies of TTX.

Objective:To explore the movement patterns and factors influencing lung tumors tracked using the M6 cyberknife stereotactic radiotherapy(SRT)system and to provide a reference for the implementation of precise stereotactic radiotherapy for lung tumors.Method:A retrospective analysis was conducted on 29 patients with lung tumors who were treated using x-sight lung tracking technology and the M6 cyberknife SRT system at Tianjin Medical University Cancer Institute&Hospital,from January 2022 to August 2024.The tumor location and volume,irradiation dose,isodose line,and number of divisions were recorded.Lung tumor location and SPSS 26.0 software were used to analyze the movement amplitude of tumors in the left and right(LFT/RGT,LR)directions,the anterior-posterior(ANT/POS,AP)direction,and the superior-inferior(SUP/INF,SI)direction.The results are expressed as the mean±standard deviation((x)±s)mm,and a t-test was used for inter-group comparisons.Multiple linear regression was used to analyze the effects of factors such as age,gender,tumor location(upper and lower lungs),and tumor volume on the amplitudes of the lung tumor movements.Result:The average motion amplitudes in the LR direc-tions,AP direction,and SI direction of the tumor target areas were(3.5±1.8)mm,(5.3±1.7)mm,and(7.3±5.4)mm for the upper lung,based on 19 cases,and(3.1±1.6)mm,(4.5±2.2)mm,and(12.2±4.4)mm for the lower lung,based on 10 cases,respectively.There was a statistic-ally significant difference(P=0.015 3)in the amplitude of movements between the lower and upper lung tumors in the SI direction.The lung tumor movement amplitude in the SI direction was influenced by tumor location(P=0.035),and the movement amplitudes in the LR direc-tions and the AP direction were not related to factors such as gender,age,tumor location,and tumor volume.Conclusions:The lung tumor movement amplitudes for the different locations varied depending on the respiratory movement shown by the patient.In the SI direction,the movement amplitude of the lower lung tumors was greater than that of upper lung tumors,and this was due to tumor location effects.The movement amplitudes of the lower and upper lung tumors were similar in the LR directions and AP directions.Furthermore,movement amplitude was not affected by gender,age,tumor location,and tumor volume.

Objective:To explore the movement patterns and factors influencing lung tumors tracked using the M6 cyberknife stereotactic radiotherapy(SRT)system and to provide a reference for the implementation of precise stereotactic radiotherapy for lung tumors.Method:A retrospective analysis was conducted on 29 patients with lung tumors who were treated using x-sight lung tracking technology and the M6 cyberknife SRT system at Tianjin Medical University Cancer Institute&Hospital,from January 2022 to August 2024.The tumor location and volume,irradiation dose,isodose line,and number of divisions were recorded.Lung tumor location and SPSS 26.0 software were used to analyze the movement amplitude of tumors in the left and right(LFT/RGT,LR)directions,the anterior-posterior(ANT/POS,AP)direction,and the superior-inferior(SUP/INF,SI)direction.The results are expressed as the mean±standard deviation((x)±s)mm,and a t-test was used for inter-group comparisons.Multiple linear regression was used to analyze the effects of factors such as age,gender,tumor location(upper and lower lungs),and tumor volume on the amplitudes of the lung tumor movements.Result:The average motion amplitudes in the LR direc-tions,AP direction,and SI direction of the tumor target areas were(3.5±1.8)mm,(5.3±1.7)mm,and(7.3±5.4)mm for the upper lung,based on 19 cases,and(3.1±1.6)mm,(4.5±2.2)mm,and(12.2±4.4)mm for the lower lung,based on 10 cases,respectively.There was a statistic-ally significant difference(P=0.015 3)in the amplitude of movements between the lower and upper lung tumors in the SI direction.The lung tumor movement amplitude in the SI direction was influenced by tumor location(P=0.035),and the movement amplitudes in the LR direc-tions and the AP direction were not related to factors such as gender,age,tumor location,and tumor volume.Conclusions:The lung tumor movement amplitudes for the different locations varied depending on the respiratory movement shown by the patient.In the SI direction,the movement amplitude of the lower lung tumors was greater than that of upper lung tumors,and this was due to tumor location effects.The movement amplitudes of the lower and upper lung tumors were similar in the LR directions and AP directions.Furthermore,movement amplitude was not affected by gender,age,tumor location,and tumor volume.

OBJECTIVE To establish and verify the risk prediction models for postoperative multidrug-resistant or-ganisms(MDROs)infections in the liver transplantation patients based on the machine learning algorithms so as to provide bases for identification of the population at high risk of postoperative MDROs infections.METHODS The liver transplantation patients who were retrospectively collected from intensive care Ⅳ database(MIMIC-Ⅳ)and eICU collaborative research database(eICU)were recruited as the research subjects,meanwhile,the patients who underwent liver transplantation in the First Hospital of Shanxi Medical University from Jan.2021 to Jul.2024 were assigned as the external verification group.The variables were selected by Lasso regression,and the models were established based on 7 types of machine learning algorithms such as extreme gradient boosting algorithm and random forest.The predictive performances of the models were evaluated by comparing the areas under receiver operating characteristic(ROC)curves and the accuracy,the characteristic variables were interpreted by Shapley additive explanations(SHAP),and the risk prediction calculator was established.RESULTS A total of 637 pa-tients were finally enrolled in the study,and the incidence of postoperative MDROs infections was 35.79％.Total-ly 15 variables were finally selected for construction of the model.The area under the receiver operating character-istic curve of XGBoost model was 0.82 for the internal test set,0.78 for the external test set;the predictive per-formance of XGBoost model was better than that of the rest of 6 models.SHAP algorithm indicated that the top 5 important predictive factors were as follows:hepatic encephalopathy,length of intensive care unit(ICU)stay,albumin,model of end-stage liver disease(MELD)and total length of hospital stay.CONCLUSION The risk pre-diction models that are established based on the machine learning algorithms have remarkable effect on prediction of the postoperative MDROs infections and can accurately identify the liver transplantation patients at high risk of postoperative MDROs infections,which may provide guidance for the identification of high-risk population and the development of prevention and treatment measures for infections.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

As a type of non-Hodgkin lymphoma,Burkitt lymphoma is characterized by unfixed location of disease,rapid progression,diverse symptoms,and clinical complexity in diagnosis and treatment.Professor Wang Xixing posits that Burkitt lymphoma manifests as a tangible mass,and its formation is associated with the invasion of exogenous pathogens,internal injury induced by seven emotions,and deficiency of healthy qi.The fundamental pathogenesis involves dysfunction of the liver,spleen and kidney,leading to liver qi stagnation,spleen-stomach deficiency in the middle energizer,and liver-kidney disharmony.The secondary manifestations were caused by the binding of phlegm-damp,toxin,and stasis.In general,the pathogenesis of Burkitt lymphoma presented deficiency in the origin and excess in the superficiality,and deficiency interweaved with excess.In clinical practice,Professor Wang emphasizes the regulation of the functions of liver,spleen and kidney,and maintains the body's yin-yang balance on the basis of the combination of disease differentiation and syndrome differentiation.Therapeutic strategies focus on soothing liver qi,replenishing qi to strengthen the spleen,and tonifying the kidney to regulate the liver,separately through the utilization of Chaihu Sanjie Decoction,Buzhong Yiqi Decoction,and Bushen Tiaogan Decoction.In this way,significant clinical efficacy is usually achieved.

Objective To investigate the mechanism by which angiopoietin-like protein 8(ANGPTL8)regulates vascular smooth muscle cell(VSMCs)apoptosis.Methods An in vitro abdominal aortic aneurysm cell model was established by stimulating human VSMCs(HUSMCs)with angiotensin Ⅱ(AngⅡ).Stable ANGPTL8 knockdown and over-expression VSMC cell strains were generated using lentiviral transfection.TUNEL staining was used to de-tect apoptosis.Western blot analysis was performed to measure the protein expression of ANGPTL8,caspase9,caspase3,Bcl-2,Bax,p53,and PUMA,while RT-qPCR was used to assess mRNA expression of ANGPTL8,Bcl-2 and Bax.Results AngⅡ significantly induced ANGPTL8 expression in HVSMCs in a time-and dose-de-pendent manner(P＜0.05).ANGPTL8 knockdown significantly reduced the expression of apoptosis-related proteins caspase9,caspase3,and Bax,while increased the expression of the anti-apoptotic protein Bcl-2(P＜0.05).Con-versely,ANGPTL8 over-expression markedly induced HVSMCs apoptosis,which was significantly suppressed by treatment with the p53 pathway inhibitor pifithrin-α(PFT-α).Conclusions ANGPTL8 may promote VSMC apop-tosis by activation of p53 signaling pathway.

Objective To investigate the applicability of D-dimer levels combined with the Tei index in assessing the volume load in patients with acute decompensated heart failure(ADHF).Methods Two hundred patients admitted to the Emergency Department of Taizhou TCM Hospital between 2022 and 2023 were selected as the subjects,who were divided into a low volume load group(n=121)and a high volume load group(n=79)based on plasma volume indices.The clinical indicators and parameters of cardiac function of these subjects were compared.Multivariate Logistic regression analysis was used for identification of potential risk factors for elevated volume loads.A model for prediction of elevated volume loads was developed via Chi-square automatic interaction detection,followed by internal validation via Bootstrapping.Logistic regression analysis was used to study the interactions between D-dimer levels and Tei indices in assessing the volume loads of patients with ADHF.Results Multivariate regression analysis showed that age,Tei index,D-dimer levels and B type natriuretic peptide(BNP)were risk factors for high volume loads in ADHF patients.The decision tree model established had 14 nodes and 8 terminal nodes.Four explanatory variables including age,Tei index,D-dimer levels and BNP were screened out.The area under curve(AUC),sensitivity,specificity and prediction accuracy of the classification tree model were higher than those of the regression model.When D-dimer levels ≥1.16 and Tei index ≥0.65 interacted and co-existed,ADHF patients were at higher risk of developing high volume loads(OR=6.526,95％CI:2.439-7.183).The results of restricted cubic spline analysis pointed to nonlinear dose response relationships in the correlation strength of D-dimer levels,Tei index and volume loads.Conclusion There are interactions between D-dimer levels and Tei index,and the risk of high volume loads in ADHF patients is significantly increased when D-dimer levels are 1.16 or above and Tei index is 0.65 or above.