Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Objective To explore the clinical significance of nucleolar antinuclear antibodies(ANA)in re-lated diseases.Methods This study was a retrospective study.Clinical samples of 71780 patients who visited the hospital from January 2017 to May 2022 were collected.Indirect immunofluorescence was used to detect ANA in clinical samples.Statistical analysis was conducted on the positivity rate of nucleolar ANA in clinical patients,as well as the relevant clinical information and laboratory characteristics of patients with autoimmune diseases(AID)with nucleolar ANA positivity.Results Among 71780 patients who underwent routine ANA testing,16778 were positive for ANA,with a positive rate of 23.37％.Among them,there were 1 708 cases of nucleolar type,accounting for 2.38％of all routine ANA tests,and the proportion of ANA positive cases was 10.18％.There was a statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the＞20-＜50 year old group and the ≥ 50 year old group(P＜0.05),while there was no statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the ≤ 20 year old group(P＞0.05).There was a statistically significant difference in the positivity rate of nucleolar ANA among women of different age groups(P＜0.05),among them,the highest positive rate of nucleolar ANA was found in women aged between 20 and 50 years old.There was no statistically significant difference in the positive rate of nucleolar ANA among males of different age groups(P＞0.05).The positivi-ty rate of ANA was the highest among patients in the Department of Rheumatology and Immunology(70.35％),but nucleolar ANA positivity was mainly seen in departments such as Reproductive Medicine Cen-ter(12.90％),Respiratory Medicine(12.40％),and Neurology(11.29％),and the difference in positivity rates between departments was statistically significant(P＜0.05).Out of 1 708 nucleolar ANA positive indi-viduals,420 underwent ANA titers,including 34 AID patients and 386 non AID patients.There was no statis-tically significant difference in nucleolus positive titers between non AID patients and AID patients(P＞0.05).Conclusion The nucleolus type is a common fluorescence pattern in ANA positive individuals,and there are gender and age differences in ANA positive individuals.The positive rate and titer of nucleolar ANA vary among different AID diseases.Combined with other immune function indicators,and it is helpful for early differential diagnosis of AID.

【Objective】 To investigate the influencing factors behind the follow-up compliance of patients with low/no phenylketonuria (PKU) for special medical use, in order to provide a basis for regulating the follow-up of PKU patients and ensuring the effectiveness of special diet treatment. 【Methods】 A survey was conducted on PKU patients treated in Urumqi Maternal and Child Health Hospital for over 1 year, from January 2010 to December 2020. Interviews and questionnaires were conducted with their caregivers to collect and analyze the current status of PKU patients undergoing special diet treatment, and to identify the influencing factors behind their compliance with follow-up treatment. 【Results】 Patients who had received neonatal disease screening, neonatal gene diagnosis, and maternal Down′s screening during pregnancy had better compliance, with statistically significant differences (χ²=5.753, 10.993, 9.189, P<0.05). PKU children with parents who had a college education or above showed significantly higher adherence to special diet treatment (χ²=8.321, 7.415, P<0.05). PKU children with parents having a fixed occupation also showed higher compliance, with a statistically significant difference (χ²=20.626, 7.895, P<0.05). Patient age, interval of buying special diet, number of blood samples sent and enrollment of normal age, all had a significant impact on the follow-up compliance of PKU patients with special diet (χ²=19.443, 8.090, 69.482, 12.001, P<0.05). 【Conclusions】 PKU is a treatable genetic metabolic disease. Strengthening health education, formulating standardized follow-up plans and procedures, and improving follow-up treatment compliance are crucial in enhancing the treatment and follow-up effectiveness of PKU patients.

The contents recorded in the rotation registration manual is not only the quantitative indicators for evaluating the quality of residency training, but also the important basis for training assessment and issuance of training certificates. In order to solve the problems of data authenticity, information delay, and repeated entry in the rotation registration manual for residency training, Shanghai East Hospital, Tongji University, launched a project to dock the electronic rotation registration manual with the hospital information system. Through the establishment of the project team, the development of working mechanisms, and the implementation of the project, data analysis was used for process reformation and system optimization, so as to continuously improve management efficiency and medical safety while solving problems and form a set of implementation system with reference significance in practice.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective:To investigate the risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction (IBD) in patients with severe traumatic brain injury (sTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 101 patients with sTBI admitted to Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from May 2020 to February 2023, including 63 males and 38 females, aged 21-81 years [(53.4±14.2)years]. All the patients underwent emergency surgery. The patients were divided into IBD group ( n=67) and non-IBD group ( n=34) according to whether or not they had IBD after surgery. The gender, age, basic diseases (hypertension and diabetes), types of intracranial hematoma (subdural, epidural, and intracerebral hematoma), preoperative Glasgow Coma Scale (GCS), cerebral hernia, intraoperative initial intracranial pressure (iICP), operation time, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were recorded in the two groups. Univariate and multivariate binary Logistic regression analyses were conducted to assess the correlations between above-mentioned indicators and incidence of postoperative IBD in sTBI patients and determine the independent risk factors for sTBI. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the warning effectiveness of each risk factor for IBD. Results:The results of the univariate analysis showed that preoperative GCS, cerebral hernia, intraoperative iICP, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were significantly correlated with the incidence of IBD in sTBI patients ( P<0.05 or 0.01), while there were no correlations of IBD with gender, age, basic diseases, types of intracranial hematoma and operation time ( P>0.05). The results of the multivariate binary Logistic regression analysis showed that preoperative GCS≤5 points ( OR=2.49, 95% CI 1.17, 5.32, P<0.05), intraoperative iICP>23 mmHg (1 mmHg=0.133 kPa)( OR=1.20, 95% CI 1.03, 1.39, P<0.05), and initiation time of enteral nutrition>24 hours ( OR=10.03, 95% CI 1.26, 80.21, P<0.05) were highly correlated with postoperative IBD in sTBI patients. The results of the ROC curve analysis showed that intraoperative iICP had the highest warning value (AUC=0.91, 95% CI 0.85, 0.96), followed by preoperative GCS (AUC=0.88, 95% CI 0.82, 0.95), and initiation time of enteral nutrition had the lowest warning value (AUC=0.78, 95% CI 0.69, 0.87). Conclusions:Preoperative GCS≤5 points, intraoperative iICP>23 mmHg, and initiation time of enteral nutrition>24 hours are independent risk factors for postoperative IBD in sTBI patients. The warning value of intraoperative iICP ranks the highest for postoperative IBD in sTBI patients, followed by preoperative GCS, with initiation time of enteral nutrition having the lowest warning value.

Objective To screen the distribution frequency of Mur blood group among voluntary blood donors in Hezhou,Guangxi,and further analyze the molecular basis of of Mur antigen positive samples.Methods The Mur pheno-type of voluntary blood donors in Hezhou was serologically screened using microplate method,and the distribution frequency of Mur antigens in different ethnic groups was analyzed.Genetic typing was performed on these positive samples with PCR-SSP method to verify the accuracy of the serological method,and the genetic background was sequenced and analyzed.Re-sults Among 3 298 samples from voluntary blood donors in Hezhou,432(13.10%,432/3 298)were screened positive for Mur antigen,and PCR-SSP genotyping validation showed that all 432 samples were electrophoretic positive.Among them,the proportion of Han blood donors with positive Mur antigen was12.79%(331/2 587),Yao ethnic group was13.25%(64/483),Zhuang ethnic group was 16.51%(36/218),and no statistically significant difference was found in the three groups(P＞0.05).Further sequencing results showed that 428 samples were GYP(B-A-B)Mur,also known as GYP.Mur type(12.98%,428/3 298),the other 4 samples were GYP(B-A-B)Bun,also known as GYP.Bun type(0.12%,4/3 298).Conclusion The Mur blood type frequency is high in the voluntary blood donors in Hezhou,Guangxi,and is predominant characterized by GYP.Mur genotype.Due to ethnic integration,no significant difference was noticed in the frequency of Mur blood type distribution between Han,Zhuang and Yao population.Therefore,conducting extensive Mur blood group antigen and antibody testing in Hezhou is of great significance for ensuring clinical blood transfusion safety.

This article describes the experience of implementing the informatization construction of teaching supervision for standardized residency training in Shanghai East Hospital, Tongji University, and discusses the means to improve teaching activity supervision, such as management informatization and internet technology. This study aims to ensure the efficiency and work quality of supervision, optimize the process and resource allocation of supervision, and lay a solid foundation for improving the quality of residency training and teaching in the hospital (especially the key indicators for residency training and teaching quality, including the supervision rate of teaching activities and the completion rate of teaching activities) and establishing a sound system and the assets of teaching data in residency training.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

The integrated use of health insurance funds and public health funds is the driving force for promoting service integration and continuously advancing the construction of a"Healthy China".Based on the synergistic advantage theory and the PCIC theory,this paper proposes three paths to promote the integrated use:rationalizing the functional position and service supply of the two parties,optimizing the payment and incentive mechanism,and strengthening the capacity building of service buyers.Based on the above path perspective,this paper finds that the current domestic exploration and practice of coordinated use has achieved certain results,but there are also problems such as unclear funding sources,unclear scope of purchased services,insufficient coordination of multi-subject assessment incentives,weak correlation with health outputs,insufficient cost accounting and health measurement assessment capabilities,and imperfect information system interconnection.It is recommended to improve the top-level design,establish an assessment and payment incentive mechanism related to health outcomes,and realize the dynamic construction of fund expansion and informatization.