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 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 predictive value of serum uric acid(UA),homocysteine(Hcy)and the product index of UA and Hcy in patients with stable coronary artery disease(SCAD).Methods A total of 783 patients with suspected coronary heart disease were collected,all of whom underwent coronary angiography.Patients were divided into coronary heart disease(CHD)group and non-coronary heart disease(NCHD)group.The CHD group was further divided into low score group(≤35 points)and high score group(>35 points)according to Gensini scores.Baseline data,blood lipids,Hcy,UA,left ventricular function ultrasound indicators,and comorbidities were collected.Logistic regression analysis was used to evaluate the risk factors associated with the onset of SCAD and severe coronary artery disease,while the Receiver Operating Characteristic(ROC)curve was conducted to assess the predictive efficacy of the product index of UA and Hcy,and related risk factors,for SCAD onset and severe coronary artery disease.Results 1.In CHD group,UA,Hcy and the product index of UA and Hcy were all higher than in the NCHD group(P<0.001);the high-score group had higher UA,Hcy and the product index of UA and Hcy than the low Gensini score group(P<0.001).2.Multivariate logistic regression analysis showed that female age,sex,body mass index(BMI),product index of UA and Hcy,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),type 2 diabetes mellitus(T2DM)and hypertension(HTN)were independent risk factors for SCAD(P<0.05).BMI,the product index of UA and Hcy,HDL-C,LDL-C and LVEF were independent risk factors for severe coronary artery disease(P<0.05).3.There was a positive correlation between UA and Hcy product index and Gensini scores(r=0.433,P<0.05).4.Receiver operating characteristic curve analysis showed that the product index of UA and Hcy and combined detection of coronary heart disease risk factors had predictive value for the occurrence of SCAD(P<0.05),and the predictive value of combined detection was higher(area under the curve 0.808);both the product index of UA and Hcy and the combined detection of coronary heart disease risk factors had predictive value for severe coronary artery lesions(P<0.05),with a higher predictive value for combined detection(area under the curve 0.771).Conclusion As an independent predictor of the risk of SCAD and severe coronary stenosis,the product index of UA and Hcy has a high predictive efficacy regarding disease risk and the severity of coronary artery in patients with SCAD.

Objective To evaluate the predictive value of changes in serum homocysteine(Hcy),high-density lipoprotein cholesterol(HDL-C),and the homocysteine-to-HDL-C ratio(HHR)for the incidence and short-term prognosis of patients with premature coronary heart disease(PCHD).Methods Between January 2022 and December 2023,301 patients with the suspected coronary heart disease(males≤55 years,females≤65 years)were retrospectively selected from the Department of Cardiology at the Third People's Hospital of Yunnan Province.All patients who underwent coronary angiography(CAG)were divided into the premature coronary heart disease(PCHD)group(n=98)and the non-coronary heart disease(NCHD)group(n=203).Patients with PCHD were followed up six months after the discharge and were further classified into the good prognosis group(n=55)and the poor prognosis group(n=43)based on the presence of worsening clinical symptoms such as chest tightness,chest pain,arrhythmias,heart failure,or death.Data collected included general patient information,blood lipid levels,Hcy levels,left ventricular function ultrasound indicators,and the presence of hypertension and type 2 diabetes.Results Hcy and HHR levels were significantly higher in the PCHD group compared to the NCHD group,while HDL-C levels were lower(P<0.001).In the poor prognosis group,Hcy and HHR levels were elevated,and HDL-C levels were reduced compared to the good prognosis group(P<0.001).The Hcy and HHR levels in the severe coronary artery stenosis group were markedly higher than those in the normal coronary artery group and the mild to the moderate stenosis group,with HDL-C levels being lower(P<0.001).Multivariate logistic regression analysis identified that male sex,HHR,Hcy,low-density lipoprotein cholesterol(LDL-C),and left ventricular ejection fraction(LVEF)were independent factors influencing premature coronary heart disease(P<0.05).HHR was found to be an independent risk factor for the poor short-term prognosis in PCHD.The analysis of the operating characteristic curve of the subjects showed that serum Hcy and HHR had the predictive value for the occurrence of PCHD(P<0.05),with HHR showing higher predictive value(area under the curve[AUC]=0.713).HHR also had the substantial predictive value for the short-term prognosis of PCHD(AUC=0.715).Conclusion Elevated HHR levels are associated with the severe coronary artery disease in patients with PCHD.HHR serves as a significant predictor for both the occurrence and short-term prognosis of PCHD.

OBJECTIVE To explore the safety， effectiveness， and cost-effectiveness of elderly patients with sarcopenia receiving Shenling baizhu powder combined with nutrition and exercise intervention， providing a reference for rational clinical drug use. METHODS A total of 237 elderly sarcopenia patients were randomly assigned to an observation group （118 cases） and a control group （119 cases）. Both groups of patients received nutrition and exercise intervention； the observation group added Shenling baizhu powder （6 g each time， three times daily） on this basis. The safety， effectiveness， and cost-effectiveness of the two plans were compared after 3 months. RESULTS Both groups of patients completed the follow-up. Before intervention， no significant difference was observed in skeletal muscle index （SMI）， grip strength， and 6-minute walk test （6MWT） speed between the two groups （P＞0.05）. After intervention， the grip strength of the patients in the observation group was significantly greater than that of the control group （25.05 kg vs. 23.18 kg， P＜0.01）； the treatment response rate of sarcopenia， SMI， and 6MWT speed were higher than those of the control group， butthe differences were not statistically significant （P＞0.05）. The adverse reaction/event rate of the patients in the observation group was lower than that of the control group （14.41% vs. 16.81%， P＝0.611）， but the difference was not statistically significant. Compared with the control group’s plan， the cost of the observation group’s plan was higher （981.25 yuan vs. 913.94 yuan）， and the effect was better （effectiveness rate： 0.618 6 vs. 0.563 0）， with an incremental cost-effectiveness ratio of 1 210.61 yuan. The results of the sensitivity analysis were consistent with the cost-effectiveness analysis results. CONCLUSION Elderly patients with sarcopenia who receive Shenling baizhu powder combined with nutrition and exercise intervention can significantly strengthen grip strength without increasing the incidence of adverse reactions/events. Compared with the control group plan， the observation group needs to spend an additional 1 210.61 yuan for each additional effective patient with sarcopenia.

Objective To analyze the effects of early staged lung rehabilitation on lung function,cancer-related fatigue and physical activity of patients with severe lung cancer after lobectomy.Methods A total of 112 patients with severe lung cancer who underwent pulmonary lobectomy in the Affiliated Cancer Hospital of Xinjiang Medical University from June 2019 to May 2020 were selected as study objects.They were divided into control group and observation group in the order of enrollment,with 56 cases in each group.There was no significant difference in baseline information between the two groups(P>0.05).The control group was given routine rehabilitation nursing,and the observation group was additionally given early staged lung rehabilitation on the basis of routine rehabilitation nursing.A follow-up study was conducted for 18 months.Pulmonary function indexes,such as forced expiratory volume in one second(FEV1)and forced expiratory volume in one second/forced vital capacity(FEV1/FVC),the incidence of cancer-related fatigue,daily physical activity time,Self-rating Anxiety Scale(SAS)scores and Self-rating Depression Scale(SDS)scores were compared between the two groups before intervention 1,6 and 18 months after intervention.Results The incidence of cancer-related fatigue in the observation group was significantly lower than that in the control group(44.64%vs.64.29%,P=0.037).Repeated measurement analysis of variance showed that there were significant differences in the FEV1,FEV1/FVC,daily physical activity time,SAS scores,and SDS scores between intra-subject effect and inter-subject effect(P<0.05),suggesting that FEV1,FEV1/FVC,daily physical activity time,SAS scores,and SDS scores had a trend of change over time,and there were differences between groups.At 1,6 and 18 months after intervention,FEV1,FEV1/FVC and daily physical activity time in the observation group were significantly higher than those in the control group,while SAS scores and SDS scores in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Early staged pulmonary rehabilitation on the basis of conventional rehabilitation nursing can improve the long-term pulmonary function and negative emotions,reduce the incidence of cancer-related fatigue,and increase physical activity in patients with severe lung cancer after lobectomy.

Objective:To assess the efficacy and safety of programmed death-1 (PD-1) inhibitor combined with radiotherapy in advanced and relapsed / refractory extranodal NK/T cell lymphoma (ENKTL).Methods:Clinical data of 26 patients with advanced and recurrent / refractory ENKTL admitted to Sun Yat-sen University Cancer Center from January 2019 to December 2021 were retrospectively analyzed. All patients were treated with the PD-1 inhibitor combined with radiotherapy. The treatment responses, survival rate and and adverse reactions of the regimen were analyzed. The Kaplan-Meier method was used to estimate the 1- and 2-year progression-free survival (PFS) rate and overall survival (OS) rate, and the Cox proportional risk model was used for univariate prognostic factorial analysis for PFS and OS.Results:The median follow-up time of 26 patients was 29 months (10-49 months). The objective response rate (ORR) was 85%. The complete and partial remission rates were 77% and 8%. The median PFS time was 25 months. The 1- and 2- year PFS rates were 73.1% and 53.3%. The 1- and 2- year OS rates were 88.5% and 75.3%. The main adverse reaction was acute mucositis with an incidence rate of 31% (8/26), followed by hematological toxicity. The incidence of immune-related adverse events in lung, liver and thyroid were low. Only 1 patient developed grade 3 acute mucositis, 1 patient developed grade 4 immune pneumonitis, and the remaining patients had grade 1-2 toxicities. All patients showed good tolerance. The univariate analysis showed that elevated lactate dehydrogenase, Epstein-Barr virus DNA positive after treatment, and less than 6 cycles of anti-PD-1 immunotherapy were prognostic factors for poor OS.Conclusion:The regimen of PD-1 inhibitor combined with radiotherapy demonstrates promising efficacy and well tolerance in patients with advanced and relapsed / refractory ENKTL.

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.

Objective:To analyze the clinical efficacy and prognostic factors of intracranial primary diffuse large B-cell lymphoma (DLBCL).Methods:Clinical data of 205 patients pathologically diagnosed with intracranial primary DLBCL at Sun Yat-sen University Cancer center from March 2001 to September 2020 were retrospectively analyzed. Among them, 101 patients were male and 104 female, the median age was 54 years old. Non-germinal center B cell (GCB) subtype accounted for 74.1%(126/170). A total of 177 patients received high-dose methotrexate (HD-MTX) and 91 patients received rituximab. After induction chemotherapy, 59 patients (30.4%) achieved complete response (CR), 112 patients (57.7%) achieved partial response (PR) or stable disease (SD). A total of 83 patients received consolidation or salvage radiotherapy, and only 14 patients received autologous stem cell transplantation (ASCT). The influence of pathological type, chemotherapy, rituximab treatment, radiotherapy and radiotherapy mode, ASCT and other factors on the overall survival (OS) and progression free survival (PFS) was evaluated. The survival rate was calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by COX model.Results:The median follow-up time was 34 months. The 5-year OS and PFS rates were 55.6% and 44.2%, respectively. GCB subtype, chemotherapy with HD-MTX, rituximab treatment, remission status after induction chemotherapy, and radiotherapy were favorable prognostic factors for OS or PFS, in which the last three were the independent prognostic factors. Consolidation radiotherapy in patients who obtained CR after induction chemotherapy did not significantly improve survival, while salvage radiotherapy in patients who achieved PR/SD after induction chemotherapy significantly improved both OS and PFS(both P<0.01). Consolidation radiotherapy showed no significant survival difference compared with consolidation ASCT. Conclusions:The non-GCB subtype of intracranial primary DLBCL is related to poor prognosis. The addition of rituximab to HD-MTX based induction chemotherapy can improve survival. Radiotherapy is still an important treatment for intracranial primary DLBCL, and there are limitations of ASCT in practical clinical application.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.