To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

To standardize clinical treatment decisions and improve the comprehensive diagnosis and treatment of bipolar disorder in China, the Psychiatric Branch of the Chinese Medical Association initiated the Guidelines for the Prevention and Treatment of Bipolar disorder in China (2025 edition). This protocol summary describes the background and purpose of the guideline, the formulation method, working group members, division of responsibilities, guideline registration, conflicts of interest, collection and selection of clinical issues, the evidence-based foundation of the guideline, writing and external review, as well as publishing, dissemination, and other aspects.

To standardize clinical treatment decisions and improve the comprehensive diagnosis and treatment of bipolar disorder in China, the Psychiatric Branch of the Chinese Medical Association initiated the Guidelines for the Prevention and Treatment of Bipolar disorder in China (2025 edition). This protocol summary describes the background and purpose of the guideline, the formulation method, working group members, division of responsibilities, guideline registration, conflicts of interest, collection and selection of clinical issues, the evidence-based foundation of the guideline, writing and external review, as well as publishing, dissemination, and other aspects.