OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To investigate and analyze epidemiological characteristics of patients with mycoplasma pneumoniae pneumonia (MPP) from 2020 to 2023, and the risk factors for plastic bronchitis (PB), To provide data support for developing preventive measures. Methods The medical records of 2 257 patients with respiratory tract infection treated at Huai'an Hospital Affiliated to Xuzhou Medical University from 2020 to 2023 were collected. Count the number of MPP patients and analyze the MP detection rate. Multivariate logistic regression analysis and ROC curve was used to screen the risk factors for PB. Results A total of 858 cases were positive for MP antibodies, and the detection rate was 38.02%. There are statistically significant differences in MP detection rates among different genders, age groups, and years (P<0.05). Among the 286 patients diagnosed with MPP and undergoing bronchoscopy, 68 (23.78%) patients had PB. According to univariate and multivariate logistic regression analysis, small age, higher N%, D-D, LDH and AST levels were independent risk factors for PB (P<0.05). ROC curve analysis shows that age and combined detection are the most effective indicators for PB prediction, with areas under the curve of 0.998 and 0.961, respectively. Conclusion MP is the main pathogen of respiratory tract infections in the area from 2020 to 2023. Women and children are more susceptible to MP infection. Small age, high N%, DD, LDH and AST levels are independent risk factors for PB in patients with MPP. Targeted preventive measures should be taken for MP susceptible population, and close attention should be paid to PB related risk factors to prevent disease progression and the occurrence of PB.

Esophageal squamous cell carcinoma can easily penetrate into the esophageal wall and invade adjacent organs due to the lack of serosa. Stage cT4b tumors involving organs adjacent to the aorta, vertebral body, trachea, or bronchus were considered unresectable. For unresectable esophageal squamous cell carcinoma, radical chemoradiotherapy or chemotherapy is recommended. However, the therapeutic effect is poor. With the advent of conversion surgery, surgical resection is feasible after induction therapy for patients with esophageal tumors that are initially unresectable due to adjacent organ invasion or distant metastasis. This article reviews the research on conversion surgery for unresectable esophageal squamous cell carcinoma in recent years in order to explore the clinical application prospects of conversion surgery.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G^-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G^- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Neoadjuvant chemoradiotherapy or chemotherapy combined with surgery for locally advanced esophageal cancer has become the standard treatment, and despite the survival benefit, most patients still experience postoperative recurrence and distant metastasis. Immune checkpoint inhibitors play an anti-tumor role by activating T cells, and immunotherapy has become one of the important strategies for first-line and second-line treatment of advanced esophageal cancer with the continuous evolution of immunotherapy models. Regarding neoadjuvant immunotherapy for esophageal cancer, a large number of studies are being carried out and explored, which are expected to inject new vitality into neoadjuvant therapy for esophageal cancer. This article reviews the current clinical studies on neoadjuvant immunotherapy for esophageal cancer.

Objective To conduct a survey on students for their common needs for the course and the support to their research training,to provide reference for course reform and curriculum of ideology and politics.Methods A survey before and after course was conducted in 704 graduates who selected the course of"Experiments of Molecu-lar Biology"from the autumn of 2018 to the spring of 2024.After collecting the survey,they were summarized,counted,and analyzed.Results The students selected this course were mainly research-oriented graduate students.Their professional background was mainly in clinical medicine,and there was a relatively lack of training in tech-nology and laboratory skill in molecular biology experiment.The follow-up survey showed that experimental operation and implementation as well as analysis of experimental results were the two most helpful aspects for students;PCR,RNA extraction and detection,and Western blot were the most useful techniques for student learning and scientific research.Conclusions Through the survey,the professional background of students,dynamic changes in their course selection needs are well acknowledged and so thus able to optimize,provide good reference for teaching and learning in this field,and provide a basis for curriculum reform and construction of ideological and political courses.

Objective To investigate the correlations of the expression levels of plasma long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) and microRNA-143-3p (miR-143-3p) with disease activity and prognosis in patients with rheumatoid arthritis (RA). Methods A total of 129 RA patients admitted to our hospital from April 2021 to April 2023 were selected as disease group. According to the 28-joint disease activity scores (DAS28), the patients were divided into stable disease group (n=28), mildly active group (n=42), moderately active group (n=35), and severely active group (n=24). According to the prognosis of the patients after 6 months of treatment, they were divided into good prognosis group (n=88) and poor prognosis group (n=41), and 110 healthy people who underwent physical examinations in our hospital during the same period were included as control group. The expression levels of plasma LncRNA PVT1 and miR-143-3p were detected using quantitative real-time fluorescent polymerase chain reaction (qRT-PCR). The targeting relationship between LncRNA PVT1 and miR-143-3p was predicted using the Target Scan Human website. Multivariate Logistic regression analysis was conducted to explore the factors influencing the prognosis of RA patients. Receiver operating characteristic (ROC) curve was performed to assess the predictive value of plasma LncRNA PVT1 and miR-143-3p for the prognosis of RA patients. Results The plasma LncRNA PVT1 level in the disease group was higher than that in the control group, while the plasma miR-143-3p level was lower (P < 0.05). The plasma LncRNA PVT1 levels decreased sequentially in the severe activity, moderate activity, mild activity, and disease stable groups, while the plasma miR-143-3p levels increased sequentially (P < 0.05).The proportion of patients positive for human leukocyte antigen-DR4 (HLA-DR4), DAS28, and plasma LncRNA PVT1 expression level were higher in the poor prognosis group than in the good prognosis group, while the plasma miR-143-3p level was lower (P < 0.05). Plasma LncRNA PVT1, miR-143-3p expression, HLA-DR4 positivity, and DAS28 were factors influencing the prognosis of RA patients (P < 0.05). LncRNA PVT1 and miR-143-3p had targeted binding sites, and there was a negative correlation between them (P < 0.05). The area under the curve (AUC) for the combined prediction of plasma LncRNA PVT1 and miR-143-3p for prognosis of RA patients was 0.914, which was superior to the individual diagnosis of LncRNA PVT1 or miR-143-3p (Z=2.159, P=0.031; Z=2.108, P=0.035). The sensitivity and specificity of the combined diagnosis were 95.12% and 78.41%, respectively. Conclusion The plasma LncRNA PVT1 level gradually increases, while the plasma miR-143-3p level gradually decreases with increasing RA disease activity. The combined detection of the two biomarkers has high predictive value for the prognosis of RA patients.

Objective:To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM).Methods:The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort.Results:A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area ( HR=1.258, 95% CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95% CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion:Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.

Objective·To establish the early symptom network of adult intensive care unit(ICU)patients after transfer(post-ICU patients),identify the core symptoms and bridge symptoms,compare the symptom networks of two subgroups,i.e.mixed ICU and coronary care unit(CCU),and analyze the occurrence of symptoms.Methods·From December 2022 to August 2023,a total of 328 adult patients transferred to wards from mixed ICU and CCU of Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine were selected by convenience sampling.The general situation and clinical data questionnaire,and symptom questionnaires(including Hospital Anxiety and Depression Scale,Fatigue Severity Scale,Richards-Campbell Sleep Questionnaire,and Pain Numeric Rating Scale)were used.Based on Spearman correlation analysis and GLASSO algorithm,contemporaneous symptom network was built,and centrality indices and differences between subgroup symptom networks were computed.The edge accuracy and the stability of centrality indices of the network were tested.Results·A total of 302 valid questionnaires were collected,and the effective rate was 92.1％.The results of the centrality indices computations showed that in the early symptom network of post-ICU patients,the highest strength was"feel cheerful"(rs=1.145),the highest closeness was"enjoy something"(rC=1.851×10-3),and the highest expected influence was"(fatigue)interferes with physical function"(rE=1.143).The top three highest bridge strengths of symptoms were"worrying thoughts"(rb=10.392),"enjoy something"(rb=10.359),and pain(rb=10.221).There were no significant differences in network structure(M=0.289)and overall connection strength(GSmixedICU=13.876,GSCCU=13.838;S=0.039)of the early symptom networks between mixed ICU and CCU patients after being transferred to wards.When comparing the centrality indices,apart from the strength and expected influence of five symptoms showing statistically significant differences(all P＜0.05),other indices were not significantly different.The edge accuracy and the stability of centrality indices in the early symptom network of post-ICU patients were fine.Conclusion·Anxiety and depression are the core symptoms of adult post-ICU patients,and pain is one of the bridge symptoms.There is no significant difference in the incidence of early symptoms between mixed ICU and CCU patients after being transferred out.Medical care personnel should pay attention to the discomfort symptoms of post-ICU patients,and carry out targeted interventions to improve patients'comfort and promote the rehabilitation process.