One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects* ; Gene Editing/methods* ; Electroporation/methods* ; Plasmids/genetics* ; CRISPR-Cas Systems ; Genetic Engineering/methods*

Objective:To investigate the detection rate of nonalcoholic fatty liver disease(NAFLD)and its influencing factors among residents in western Chongqing of China during physical examination.Methods:Based on the clinical diagnostic criteria and ultra-sound examination results of NAFLD,the individuals who underwent physical examination in a grade A tertiary hospital in Western Chongqing from January 1,2020 to November 30,2023 were enrolled as subjects.The methods such as the t-test,the chi-square test,and the multivariate logistic regression analysis were used to clarify the detection rate of NAFLD and its influencing factors among the individuals undergoing physical examination.Results:The detection rate of NAFLD was 23.64%(12 872/54 067)among the individu-als undergoing physical examination.The detection rate of NAFLD in male individuals was significantly higher than that in female indi-viduals(39.22%vs.15.91%,χ2=2 197.112,P<0.001).The individuals in the age group of 50-59 years had the highest NAFLD detec-tion rate of 33.18%,and before the age of 60 years,the detection rate of NAFLD increased with age,while after the age of 60 years,the detection rate of NAFLD decreased with age(χ2=367.554,P<0.001),indicating the detection of NAFLD in younger populations in western Chongqing.The individuals with a body mass index in-dicative of overweight and obesity had a significantly higher detec-tion rate of NAFLD than those with a body mass index indicative of emaciation and normal weight(39.39%/71.40%vs.0.23%/9.68%,χ2=7 644.383,P<0.001).The multivariate logistic regression analy-sis showed that sex,age,body mass index,fasting blood glucose(FBG),systolic blood pressure(SBP),diastolic blood pressure(DBP),triglyceride(TG),uric acid(UA),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were risk factors for the detection rate of NAFLD in individuals undergoing physical examination(P<0.05),while total cholesterol(TC)was not a risk factor for the detection rate of NAFLD.Conclusion:The detection rate of NAFLD is 23.64%among the individuals aged 18 years or above who undergo physical examination in Western Chongqing,and there is a relatively high incidence rate of NAFLD in the age group of 50-59 years.Male individuals and overweight or obese individuals are at a high risk of NAFLD.FBG,SBP,DBP,TG,UA,HDL-C,and LDL-C are risk factors for NAFLD,while TC is not a risk factor for NAFLD.

Objective:To explore the key factors affecting health-related quality of life in children with brain tumors following initial diagnosis and to analyze its impact on survival and prognosis.Methods:Seventy-eight pediatric brain tumor patients who participated in a prospective cohort study between June 1st，2016 and June 30th，2021 were included for health-related quality of life assessment and long-term follow-up（median follow-up duration：52 months）.Results:The male-to-female ratio among the 78 children was 1.1：1，with a median age of 7.0（4.0，10.0）years. The scores of the Pediatric Quality of Life Inventory? 4.0 Generic Core Scales（PedsQL? 4.0）were（67.40±18.26）for parent proxy reports and（67.87±20.40）for child self-reports. Cronbach's α coefficients ranged from 0.790 to 0.927，with the intraclass correlation coefficient（ICC）was 0.673. According to the PedsQL? 4.0，impaired quality of life was observed in 50.0% of children by parent proxy report and 52.8% by child self-report，primarily affecting physical and role functioning. In addition，70% of caregivers reported impaired quality of life，with worry being the most prominent issue. Key factors affecting children's quality of life included radiotherapy，tumor stage，annual family income，and parents' marital status，while caregivers' quality of life was influenced by radiotherapy and the child's IgA levels（all P<0.05）. Children with decreased total scores，impaired physical functioning，or impaired emotional functioning on the PedsQL? 4.0 parent proxy report exhibited an increased risk of mortality（all P<0.05）. In multivariate Cox regression analysis，independent prognostic factors included a decrease in the total score on the PedsQL? 4.0 parent proxy report（ HR=6.702，95% CI：1.442-31.151， P<0.05），presence of hydrocephalus（ HR=33.602，95% CI：4.354-259.333， P<0.05），tumor recurrence（ HR=16.846，95% CI：3.158-89.852， P<0.05），and absence of hydrocephalus shunt surgery（ HR=13.428，95% CI：1.761-102.394， P<0.05）. Conclusion:The quality of life of newly diagnosed children with brain tumors is lower than that of healthy children，and quality of life is an important prognostic factor. Quality of life assessment should be an integral component of a comprehensive management program for children with brain tumors.

OBJECTIVE To explore the effect and safety of dapagliflozin on cardiac function and renal function， blood glucose， and quality of life in patients with heart failure （HF） combined with chronic kidney disease （CKD）. METHODS A total of 156 patients with HF combined with CKD admitted to Shangqiu First People’s Hospital from January 1， 2021 to January 1， 2023 were included. According to the random number table， the patients were randomly divided into conventional treatment group （n＝80） and dapagliflozin group （n＝76）. Conventional treatment group was given conventional treatment； dapagliflozin group was additionally given Dapagliflozin tablets 10 mg orally， once a day， based on conventional treatment group. Both groups were treated for 6 months. Cardiac function [left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， N-terminal pro-brain natriuretic peptide （NT-proBNP）]， renal function [blood creatinine， urea nitrogen， urinary albumin excretion rate （UAER）， glomerular filtration rate （GFR）， creatinine 806731979@qq.com clearance rate （CCR）]， glycosylated hemoglobin， and the quality of life were observed in 2 groups before and after treatment. The occurrence of ADR was recorded. RESULTS After treatment， LVESD， LVEDD， NT-proBNP， blood creatinine， urea nitrogen， UAER in 2 groups as well as the level of glycosylated hemoglobin in dapagliflozin group were significantly lower than before treatment； the dapagliflozin group was significantly lower than the conventional treatment group. LVEF， GFR， CCR and Kansas City Cardiomyopathy Questionnaire score were significantly higher than before treatment， and the dapagliflozin group was significantly higher than the conventional treatment group （P＜0.05）. There was no statistical significance in glycosylated hemoglobin of conventional treatment group before and after treatment （P＞ 0.05）. There was no statistically significant difference in the incidence of dizziness， rash， liver dysfunction， urinary system infection， new dialysis and hypotension between the two groups （P＞0.05）. CONCLUSIONS Dapagliflozin can improve the cardiac function and renal function of patients with HF complicated with CKD， improve patients’ quality of life and lower blood sugar levels without increasing the risk of adverse events.

Objective:To investigate the chemotherapy pass rate and interleukin(IL)-17/IL-23 axis of Kanglaite injection combined with anlotinib and DC chemotherapy in the treatment of non small cell lung cancer (NSCLC).Methods:The clinical data of 103 NSCLC patients admitted to Suzhou Hospital Affiliated to Anhui Medical University (Suzhou Municipal Hospital) from January 2021 to December 2022 were selected retrospectively, and they were divided into observation group (52 cases) and control group (51 cases) based on the treatment plan. The patients in the two groups were given DC chemotherapy, and on this basis, the control group was given arotinib, while the observation group was given arotinib combined with Kanglaite injection. Three weeks′treatment was one cycle, and the two groups were treated for 3 consecutive cycles. The total clinical response rate, chemotherapy delay rate and chemotherapy pass rate after treatment were compared between the two groups, and the levels of neuron-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), IL-17 and IL-23 were compared between the two groups before chemotherapy and at the end of each chemotherapy cycle. The incidence of adverse reactions after treatment was compared between the two groups, and the improvement rate of Karnofsky Performance Status Score (KPS score) after chemotherapy was compared.Results:The total clinical response rate in the observation group was higher than that in the control group: 61.54%(32/52) vs. 41.18%(21/51), there was statistical difference ( χ2 = 4.27, P<0.05). At the third cycle of chemotherapy, the delay rate of chemotherapy in the observation group was lower than that in the control group : 1.92% (1/52) vs. 15.69% (8/51), and the chemotherapy pass rate was higher than that in the control group: 92.31% (48/52) vs. 76.47% (39/51), there were statistical differences ( χ2 = 4.51, 4.92, P<0.05). The serum levels of NSE, CYFRA21-1, CEA, IL-17 and IL-23 in the observation group were lower than those in the control group at the first, second and third cycles of chemotherapy ( P<0.05). The incidence of myelosuppression and gastrointestinal adverse reactions in the observation group were lower than those in the control group: 19.23% (10/52) vs. 45.10% (23/51), 59.62% (31/52) vs. 86.27% (44/51), there were statistical differences ( χ2 = 7.91, 9.24, P<0.05). The improvement rate of KPS score in the observation group was higher than that in the control group after chemotherapy: 51.92% (27/52) vs. 29.41% (15/51), there was statistical difference ( χ2 = 5.40, P<0.05). Conclusions:Anlotinib and DC chemotherapy combined with Kanglaite injection can effectively regulate tumor related cytokine levels, reduce adverse reactions, improve chemotherapy pass rate and treatment effect. It may be related to downregulating the IL-17/IL-23 axis.

At present,in medical academic circle there is no consensus on the optimal diameter of the stent used in transjugular intrahepatic portosystemic shunt(TIPS).In 2021,the Advancing Liver Therapeutic Approaches Consortium(ALTAC)recommended the use of controllable diameter TIPS covered stent system in the performance of TIPS,the stent diameter of this system can be adjusted within the range of 8 mm to 10 mm,and its stability can be maintained for a long time.This system carries several advantages such as accurately regulating portal venous pressure gradient(PPG),optimizing hemodynamic target,protecting liver blood perfusion,reducing shunt-related complications,etc.,indicating that this system has a promising clinical application prospect.Through reviewing the relevant literature,this paper summarizes the research progress of controllable diameter TIPS covered stent system,aiming to better help clinicians engaged in related fields to gain a further understanding of this new technology.

Ischemic stroke has a high rate of disability and mortality and is often accompanied by white matter injury(WMI).WMI patients often have cognitive disorders,emotional disorders,sensorimotor disorders,urinary incontinence and other symptoms,which seriously affect daily life.WMI can be detected early through imaging techniques,but there is a lack of appropriate intervention and specific treatment.Studying the pathological mechanism of WMI after ischemic stroke is helpful to prevent the occurrence of WMI,delay its progression,and contribute to the development of effective drugs or specific treatments.This article reviewed the research progress of WMI mechanism after ischemic stroke in order to provide scientific basis for clinical prevention and treatment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate factors related to non-variceal upper gastrointestinal bleeding(NVUGIB)in hospitalized elderly patients.Methods:A retrospective study was conducted to collect the medical records of 1 085 elderly patients at the Affiliated Hospital of Qingdao University from January 1, 2018 to January 1, 2019.According to whether NVUGIB occurred during hospitalization, they were divided into the bleeding group(173 cases)and the control group(912 cases). General information(age, sex, smoking and drinking), diseases, medications and laboratory test results for the two groups were compared and analyzed, and factors related to NVUGIB were analyzed via binary Logistic regression.Results:There were significant differences in age, smoking, drinking, peptic ulcer, tumor, coronary heart disease, atrial fibrillation, stroke, helicobacter pylori(HP)infection, acute respiratory failure, use of anti-coagulant, anti-platelet drugs, nonsteroidal anti-inflammatory drugs and glucocorticoids, leukocyte counts, hemoglobin, C-reactive protein, procalcitonin, prothrombin time and international normalized ratio(INR), D-dimer, triglycerides, albumin and glycosylated hemoglobin(all P<0.05). Multivariate Logistic regression analysis showed that history of tumor( OR=1.552, 95% CI: 1.028-2.344), peptic ulcer( OR=4.797, 95% CI: 2.263-10.165), HP infection( OR=7.199, 95% CI: 1.825-28.571), acute respiratory failure( OR=2.977, 95% CI: 1.314-6.757), use of anti-coagulant and anti-platelet drugs( OR=2.715, 95% CI: 1.769-4.167), prolonged INR( OR=21.314, 95% CI: 2.321-195.727), increased leukocyte count( OR=10.370, 95% CI: 6.521-16.493)and hypoproteinemia( OR=1.970, 95% CI: 1.304-2.976)were independent risk factors for NVUGIB in hospitalized elderly patients. Conclusions:For hospitalized elderly patients, attention should be paid to their history of tumor, peptic ulcer, HP infection, acute respiratory failure, prolonged INR, elevated leukocyte counts, hypoalbuminemia and the use of anti-coagulant and anti-platelet drugs.The occurrence of NVUGIB, early evaluation and intervention should be carefully monitored or carried out to reduce its incidence in hospitalized elderly patients.

Objective:The risk factors for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-positive cirrhosis patients were screened based on commonly used laboratory indexes for the purpose of establishing a predictive model and the prediction efficacy of established model was validated in a validation patient cohort.Methods:The clinical data of 661 male patients with HBV-positive cirrhosis (cirrhosis group) and 694 male patients with HBV-positive HCC admitted to the First Hospital of China Medical University from 2010 to 2020 were retrospectively analyzed, age and complete blood count,liver function index (aspartate transaminase/alanine transaminase,glutamine transpeptidase,total protein, prealbumin, total bile acid, total bilirubin,direct bilirubin,cholinesterase), HBV markers, alpha-fetoprotein (AFP), fibrinogen,calcium were compared between the two groups. Multivariate Logistic regression was used to analyze the independent risk factors of HCC. The prediction model of high risk HCC ( P<0.05) was constructed and validated by receiver operating characteristic (ROC) curve and calibration curve. Results:There was significant difference in complete blood count, liver function index, HBV core antibody, HBV core antibody IgM, alpha-fetoprotein, fibrinogen, calcium between the two groups ( P<0.05). Multivariate analysis showed that calcium ( OR=35.770,95% CI 13.39-99.304),HBV core antibody ( OR=0.878,95% CI 0.816-0.944), AFP ( OR=1.002, 95% CI 1.001-1.003), fibrinogen ( OR=1.369, 95% CI 1.202-1.564) were the independent risk factors for HCC ( P<0.05), and were used for the nomogram. The AUC of the nomogram was 0.750 (95% CI 0.720-0.781) and the AUC of the validation group was 0.752 (95% CI 0.705-0.798). Conclusions:Based on calcium, hepatitis B virus core antibody, AFP, fibrinogen, a nomogram of the HCC is established and verified by ROC curve, which could be used to predict the risk of HBV-positive HCC.