Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

This study aims to investigate the potential of oncolytic nanoparticles encapsulating Coxsackievirus A21 (CVA21) full-genome mRNA (CVA21@ONP) to resurrect CVA21 and induce apoptosis in host cells, as well as the antitumor immune effects of CVA21@ONP in immunocompetent tumor-bearing BALB/c mice. We used lipid nanoparticles (LNPs) to encapsulate CVA21 full-genome mRNA, thus preparing CVA21@ONP. The killing efficacy of CVA21@ONP was determined by the plaque assay and cell counting kit-8 (CCK-8), and the apoptosis in HT29 and CT26-iRFP cells was evaluated by flow cytometry. Mice were administrated with CVA21@ONP at high and low doses intratumorally, and the growth of tumors expressing infra-red fluorescent protein (iRFP) was monitored. Additionally, the types and changes of immune cells in the spleen were analyzed by flow cytometry. The results demonstrated that CVA21@ONP successfully resurrected CVA21 in both HT29 and U87MG cells. The plaque assay revealed robust killing effects of CVA21@ONP against both human and murine cell lines, and flow cytometry results showed increased early and late apoptotic cells. Notably, intratumoral detection revealed significantly down-regulated expression of iRFP in both high- and low-dose CVA21@ONP groups. Flow cytometry results further indicated that CVA21@ONP treatment effectively reduced the levels of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), in the spleen, while enhancing T cell-dependent antitumor immune responses. These findings suggest that CVA21@ONP can replicate and survive extensively both in vitro and in vivo, activating the immune system of mice administrated with CVA21@ONP to target cells at the tumor site, thereby remodeling the tumor immune microenvironment and accelerating the suppression or even complete regression of tumors. The oncolytic performance of CVA21@ONP has been verified through intratumoral injection administration in this study, aimed at further exploring its therapeutic potential and promoting the development of the field of tumor treatment.
Animals ; Nanoparticles/chemistry* ; Mice ; Mice, Inbred BALB C ; Humans ; Apoptosis ; Oncolytic Viruses/genetics* ; Oncolytic Virotherapy/methods* ; Cell Line, Tumor ; RNA, Messenger/genetics* ; HT29 Cells

OBJECTIVE T o explore the values of body temperature,white blood cells(WBC),neutrophils(NEUT),platelets(PLT),red blood cell distribution width(RDW),procalcitonin(PCT)and C-reactive procal-citonin(PCT)in early diagnosis of postoperative nosocomial infections in the intensive care unit(ICU)patients undergoing surgical procedures.METHODS The clinical data that were collected from the surgery patients who were hospitalized in ICU of Affiliated Hospital of Nantong University from Mar.2021 to May 2022 were retro-spectively analyzed,and the enrolled patients were divided into the infection group with 45 cases and the non-infection group with 130 case according to the status of nosocomial infections.The highest body temperature and the levels of WBC,NEUT,PLT,RDW,PCT and CRP were observed and compared between the infection group within 48 hours before diagnosis with nosocomial infections and the non-infection group after ICU stay for 48 hours.The values of the single and joint detection of the indexes in prediction of postoperative nosocomial infec-tions in the ICU patients were analyzed.RESULTS The body temperature,WBC,NEUT,RDW,PCT and CRP of the infection group were 38.30(37.80,38.80)℃,14.10(10.90,17.30)× 109/L,12.22(9.32,15.12)×109/L,14.10(12.70,15.50)％,1.20(0.10,2.30)ng/ml and 55.00(40.00,70.00)mg/L,respectively,high er than those of the non-infection group(P＜0.05).CRP,body temperature,PCT,NEUT and WBC showed remarkable diag-nostic effects;the area under the curves(AUCs)of the above indexes were 0.968,0.952,0.939,0.896 and 0.886,respectively.The sensitivity of the joint detection of PCT and CRP was 0.978,with the specificity 0.985 and AUC 0.980;the sensitivity of the joint detection of body temperature,PCT and CRP was 0.978,with the specificity 0.992,AUC 0.991.CONCLUSIONS The ICU patients with postoperative nosocomial infections show high levels of body temperature,WBC,NEUT,PCT and CRP.The body temperature,PCT and CRP have high sensitivity and specificity,showing certain values in prediction of postoperative nosocomial infection in the ICU pa-tients;the joint detection of the indexes has higher diagnostic efficiency.

OBJECTIVE To understand the current status of antimicrobial agent usage intensity(AUD)of antibiot-ics,carbapenems(CB)and isolation rates of carbapenem-resistant gram-negative bacteria(CRGNB)and explore the effect of CB on hospital-associated CRGNB infections.METHODS A retrospective analysis was conducted on antimicrobial agent usage and clinical data of the patients who were hospitalized in Nantong University Affiliated Hospital from 2023 to 2024.The antimicrobial usage patterns,CB-AUD and isolation rates of CRGNB were sta-tistically analyzed.Additionally,the clinical data from 1933 confirmed hospital-acquired infection cases from 2023 to 2024 were retrospectively analyzed,and the patients were classified into two groups based on CRGNB resist-ance:the CRGNB-infected group with 376 cases and the non-CRGNB-infected group with 1557 cases.The risk factors for CRGNB infections were identified.RESULTS In the two years,the overall utilization rate of antimicro-bial drug and AUD fluctuated every six months(P＜0.05).The overall define daily dose system(DDDs)and AUD of the three CBs(meropenem,imipenem/cilastatin and biapenem)increased every six months(P＜0.05).The o-verall drug resistance rate of gram-negative bacilli to CB decreased every six months(P＜0.05).The logistic re-gression analysis showed that the duration of use of CB and combined use of antibiotics were the risk factors for the CRGNB infections(with the OR values,1.445,2.479,1.958,respectively,all P＜0.05).CONCLUSIONS The overall use of CB is on the rise.The use of CB,especially the duration of CB,increases the probability of CRGNB infection.Therefore,it is necessary for the hospital to strengthen the monitoring of CB-AUD and supervi-sion of CB.

Objective To investigate the effectiveness of continuous improvement projects based on FOCUS-PDCA on the pathogen sample submission rate before antimicrobial therapy for inpatients.Methods FOCUS-PDCA was used to improve the pathogen sample submission rate in Affiliated Hospital of Nantong University from Jun.to Jul.2023.The inpatients from Jan.to May 2023(before improvement)were enrolled as control group,and the inpatients from Aug.to Dec.2023(after improvement)were enrolled as improvement group.The utilization rate of antibiotics,the submission rate of pathogen samples,the submission rate of clinical microbial samples and the detection rate of multidrug-resistant organisms were compared between the 2 groups.Results The utilization rate of therapeutic antimicrobial agents(32.18％vs 32.93％,P=0.003)and antimicrobial consumption intensity(39.99 defined daily dose[DDD]/100 patient-days vs 44.19 DDD/100 patient-days)in the improvement group were significantly lower than those in the control group.The pathogen sample submission rates before antimicrobial therapy and key antimicrobial combination therapy in the improvement group were significantly higher than those in the control group(52.01％vs 23.64％,87.74％vs 77.71％;both P＜0.001).The qualified rate of microbial specimens in the improvement group was significantly higher than that in the control group(88.77％vs 80.11％,P＜0.001).The detection rates of multidrug-resistant organisms and carbapenem-resistant Klebella pneumoniae in the improvement group were significantly lower than those in the control group(40.45％vs 48.42％,29.65％vs 43.17％;both P＜0.001).Conclusion The continuous improvement projects based on FOCUS-PDCA can improve the pathogen sample submission rate,reduce the detection rate of multidrug-resistant organisms,and promote standardized hospital infection quality management.

OBJECTIVE T o explore the values of body temperature,white blood cells(WBC),neutrophils(NEUT),platelets(PLT),red blood cell distribution width(RDW),procalcitonin(PCT)and C-reactive procal-citonin(PCT)in early diagnosis of postoperative nosocomial infections in the intensive care unit(ICU)patients undergoing surgical procedures.METHODS The clinical data that were collected from the surgery patients who were hospitalized in ICU of Affiliated Hospital of Nantong University from Mar.2021 to May 2022 were retro-spectively analyzed,and the enrolled patients were divided into the infection group with 45 cases and the non-infection group with 130 case according to the status of nosocomial infections.The highest body temperature and the levels of WBC,NEUT,PLT,RDW,PCT and CRP were observed and compared between the infection group within 48 hours before diagnosis with nosocomial infections and the non-infection group after ICU stay for 48 hours.The values of the single and joint detection of the indexes in prediction of postoperative nosocomial infec-tions in the ICU patients were analyzed.RESULTS The body temperature,WBC,NEUT,RDW,PCT and CRP of the infection group were 38.30(37.80,38.80)℃,14.10(10.90,17.30)× 109/L,12.22(9.32,15.12)×109/L,14.10(12.70,15.50)％,1.20(0.10,2.30)ng/ml and 55.00(40.00,70.00)mg/L,respectively,high er than those of the non-infection group(P＜0.05).CRP,body temperature,PCT,NEUT and WBC showed remarkable diag-nostic effects;the area under the curves(AUCs)of the above indexes were 0.968,0.952,0.939,0.896 and 0.886,respectively.The sensitivity of the joint detection of PCT and CRP was 0.978,with the specificity 0.985 and AUC 0.980;the sensitivity of the joint detection of body temperature,PCT and CRP was 0.978,with the specificity 0.992,AUC 0.991.CONCLUSIONS The ICU patients with postoperative nosocomial infections show high levels of body temperature,WBC,NEUT,PCT and CRP.The body temperature,PCT and CRP have high sensitivity and specificity,showing certain values in prediction of postoperative nosocomial infection in the ICU pa-tients;the joint detection of the indexes has higher diagnostic efficiency.

OBJECTIVE To understand the current status of antimicrobial agent usage intensity(AUD)of antibiot-ics,carbapenems(CB)and isolation rates of carbapenem-resistant gram-negative bacteria(CRGNB)and explore the effect of CB on hospital-associated CRGNB infections.METHODS A retrospective analysis was conducted on antimicrobial agent usage and clinical data of the patients who were hospitalized in Nantong University Affiliated Hospital from 2023 to 2024.The antimicrobial usage patterns,CB-AUD and isolation rates of CRGNB were sta-tistically analyzed.Additionally,the clinical data from 1933 confirmed hospital-acquired infection cases from 2023 to 2024 were retrospectively analyzed,and the patients were classified into two groups based on CRGNB resist-ance:the CRGNB-infected group with 376 cases and the non-CRGNB-infected group with 1557 cases.The risk factors for CRGNB infections were identified.RESULTS In the two years,the overall utilization rate of antimicro-bial drug and AUD fluctuated every six months(P＜0.05).The overall define daily dose system(DDDs)and AUD of the three CBs(meropenem,imipenem/cilastatin and biapenem)increased every six months(P＜0.05).The o-verall drug resistance rate of gram-negative bacilli to CB decreased every six months(P＜0.05).The logistic re-gression analysis showed that the duration of use of CB and combined use of antibiotics were the risk factors for the CRGNB infections(with the OR values,1.445,2.479,1.958,respectively,all P＜0.05).CONCLUSIONS The overall use of CB is on the rise.The use of CB,especially the duration of CB,increases the probability of CRGNB infection.Therefore,it is necessary for the hospital to strengthen the monitoring of CB-AUD and supervi-sion of CB.

Sedentary bad habits and unhealthy diets in modern lifestyles have led to an upward trend in the incidence of obesity, and a series of diseases related to obesity have also gradually received attention. Multiple sclerosis is a chronic inflammatory disease of the central nervous system, and obesity has a common inflammatory component with most chronic diseases. Therefore, this paper reviews the research progress on the relationship between obesity and multiple sclerosis in order to better understand the role of obesity in the management of multiple sclerosis.

Psychotherapy is one of the widely used therapies for depression.Yet there are currently no definitive biological markers as indicators of effectiveness.Using functional magnetic resonance imaging(fMRI)to assess the neuroimaging biomarkers before and after different psychological treatments for depression reveals corresponding changes in brain region activation and functional connectivity.For example,after cognitive-behavioral therapy,the prefrontal cortex of patients may be activated and dynamic functional connectivity variability may change,while mindfulness therapy may show alterations in specific temporal lobe regions.Additionally,studies exploring special populations and internet-based psychological intervention have also found changes in brain region activation and functional connectivity,providing guidance for the efficacy evaluation of corresponding psychotherapies.This article reviews the characteristic brain region or network changes in fMRI activity after different psychotherapies in depressed patients,aiming to discuss future directions for research that integrates neuroimaging with psychological treatment for depression.

Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.