Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To analyze the influencing factors of unplanned extubation(UE)occurrence of peripherally inserted central catheter(PICC)in the patients with hematological diseases.Methods A retro-spective cohort study method was adopted.The data of 7 298 patients with hematological diseases implanted with PICC catheter and followed up to its removal from January 1,2016 to December 31,2020 in the Hematol-ogy Hospital of Chinese Academy of Medical Sciences were collected,including the demographic information,catheterization records,maintenance and extubation records.According to whether UE occurring,they were divided into the UE group(n=262)and normal extubation group(n=7 036).The general data were com-pared between the two groups.The COX regression was used to analyze the influencing factors of UE in pa-tients with hematological diseases.The dose-effect relationship between age and PICC UE occurrence risk was studied by the restrictive cubic spline method.Results The incidence rate of UE was 3.6％(262/7 298).The COX regression analysis results showed that the gender,disease diagnosis,fibrinogen,prothrombin time,PLT,catheter material,number of punctures during catheterization,positioning method of catheter tip,num-ber of catheter-related complications occurrence were related to PICC UE occurrence in the patients with he-matological diseases(P＜0.05).The results of restricted cubic spline showed that there was a"U"-type non-linear relationship between age and UE risk(X2=17.710,P＜0.05),and the risk of UE was the lowest when the age was 30 years old.Conclusion In PICC,the emphasis should be paid to the male patients with hemato-logical malignancies who have repeated punctures during catheterization,no intracardiac electrocardiographic positioning during catheterization,bleeding tendency,indwelling polyurethane catheters and repeated catheter-related complications in order to decrease the UC occurrence probability.

Objective To investigate CT features of Chlamydia psittaci(C.psittaci)pneumonia patients.Methods Ten patients with C.psittaci pneumonia were collected retrospectively based on macro gene second-generation sequencing(mNGS).The radiological manifestations of the disease were analyzed.Results Seven patients(70%)had contact history with birds(poultry)or their feces.Chest CT on the day of admission was mainly mass patchy consolidation,all of which were located in single lung,involving 8 cases(80%)with one lobe and 2 cases(20%)with two lobes.All of them were accompanied by air bronchogram,9 cases(90%)with ground glass shadow and 8 cases(80%)with interstitial changes.One case(10%)showed a reversed halo sign,and 1 case(10%)showed fan-shaped consolidation.Nine cases(90%)showed progress with increased fusion or new lesions within nine days.Conclusion CT findings of C.psittaci pneumonia have certain characteristics,and combining with history of contacting birds(poultry)can suggest diagnosis.

Objective To investigate the status of application of the central venous access in the departments of hematology to develop targeted administrative strategies and provide evidence for management.Methods A self-de-signed questionnaire was applied and convenience sampling was adopted in 93 hematology departments from 48 hospitals in 19 provinces(autonomous regions,municipalities).Results A total of 91 valid questionnaires were col-lected,with a valid questionnaire response rate of 97.85％.Among the 91 hematology departments,91(100％),73(80.22％),and 68(74.73％)carried out PICC,central venous catheter,and totally implantable access port catheteriza-tion,respectively.In the evaluation of blood test indicators before central venous access,the items with a higher e-valuation proportion were platelet count(100％)and D-dimer concentration(87.91％),while the evaluation proportion of other items was＜85％.When PICC catheterization,97.80％of hematology departments prefer basilic vein;83.52％of hematology departments used zone insertion method;95.60％of hematology departments had a skin disinfection range of ≥20 cm;98.90％of hematology departments had catheterization under ultrasound guidance;67.03％and 96.70％of hematology departments used the intracardiac electrocardiogram method or ultrasound assisted localiza-tion,postoperative X-ray localization;12.09％and 53.85％of hematology departments carried out tunnel catheteriza-tion and blunt separation expansion techniques,respectively.In terms of maintenance of central venous access de-vices,82.42％of hematology departments used disposable specialized maintenance kits;61.54％of hematology de-partments used transparent patches to fix PICC;45.21％of hematology departments used suture to fix central venous catheters;24.18％of hematology departments used cotton swabs to disinfect infusion joints;60.44％of hematology departments did not use disposable infusion joint disinfection cap;74.73％of hematology departments used gauze compression to prevent puncture site bleeding;only 6.59％hematology departments used antibacterial dressings con-taining chlorhexidine to prevent puncture site infections.In terms of quality management of central venous access devices,94.51％and 86.81％of hematology departments regularly conducted quality inspections of central venous access,and collected,calculated and analyzed relevant data.50.55％of hematology departments conducted complica-tion risk assessments,and 10.99％of hematology departments had established information management systems for venous therapy.Conclusion The implementation rate of PICC catheterization in the hematology department was relatively high,and the insertion operation basically meets the standard requirements.The evaluation before central venous access catheterization was relatively completed,and the maintenance and management are relatively stan-dardized.However,the evaluation of blood test indicators before the placement of central venous access urgently needs to be standardized and unified.When PICC catheterization,attention should be paid to the application of new technologies,and the information management of venous therapy needs to be improved.

Objective To construct a comorbidity network for medical expenses by analyzing the rele-vant medical records,and to construct a deep learning prediction model by combining with the disease net-works and long short-term memory neural networks in order to improve the accuracy of individual medical ex-pense prediction and provide the assistance for optimizing the medical policies and enhancing the patient health management level.Methods Based on the medical records of Taiwan,China Health Insurance Research Data-base during 2000-2013,the data of 5.84 million visits from 9 963 patients were analyzed,and a comorbidity network of medical expenses for 104 common diseases was constructed.The network structure was analyzed and the potential comorbidity was predicted,and the deep learning model of individual medical cost was con-structed by combining the input of patient's gender,age,medical history and other information.Results The constructed medical cost comorbidity network consists of 104 nodes,3 390 edges and 6 modules,and is a high-ly connected network with nodes,indicating that the medical costs possesses the high correlation between dis-eases.The constructed deep learning prediction model significantly improves the prediction accuracy compared to the traditional regression models and deep learning models that do not fully consider the comorbidity infor-mation.Conclusion The constructed model provides a new theoretical perspective for understanding the co-morbidity of diseases,as well as an effective tool for accurately predicting medical costs,optimizing medical re-source allocation and achieving the personalized medical services.

Objective Port-wine stains are a kind of dermatological disease of congenital capillary malformation.Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration,we intend to construct a nanodrug co-loaded with rapamycin(RPM),an anti-angiogenesis drug,and photochlor(HPPH),a photosensitizer,and integrate the nanodrug with dissolvable microneedles(MN)to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains.Methods First,RPM and HPPH co-loaded nanoparticles(RPM-HPPH NP)were prepared by the emulsification solvent-volatilization method,and its ability to generate reactive oxygen species(ROS)was investigated under 660 nm laser irradiation.Mouse hemangioendothelioma endothelial cells(EOMA)were used as the subjects of the study.The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry.The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays(with free RPM serving as the control).Then,hyaluronic acid(HA)dissolvable microneedles loaded with RPM-HPPH NP(RPM-HPPH NP@HA MN)were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method.The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine.The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment.Results The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation.At the cellular level,RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner.The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation.Under laser irradiation,RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant(P＜0.05).The height of the needle tip of RPM-HPPH NP@HA MN was 600 μm and the mechanical property of a single needle was 0.75048 N.Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum.Conclusion RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy,providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Objective To explore the efficacy of the geriatric interdisciplinary team(GIT)service for elderly patients with multimorbidity and malnutrition.Methods We selected 109 elderly patients with diabetes mellitus(DM),chronic obstructive pulmonary disease(COPD)or chronic heart failure(CHF)and multi morbidity to the Department of Geriatrics of The 2nd People's Hospital of Kunming City from January 2022 to January 2023.The patients were randomly divided into the control group of 53 cases and the observation group of 56 cases.The control group received routine management of multimorbidity and malnutrition,while the observation group used the GIT service model to manage multimorbidity and malnutrition.The disease,nutritional status,and quality of life outcomes of the two groups of elderly patients were evaluated before and 3 months after the intervention.(1)HbA1c was detected in patients with DM in both groups,and the aggravation of patients with COPD or CHF was observed and recorded.(2)Nutrition-related indicators(Tp,ALB and Hb)and Barthel index were evaluated in both groups.Results(1)The HbA1c of patients with DM in the two groups decreased after intervention(P＜0.001),and the decrease in the observation group was more significant than that in the control group(P＜0.001).(2)The number of AECOPEs in patients with COPD in the two groups decreased,and the observation group was less than the control group(P＜0.05).(3)The number of CHF acute exacerbations in patients with CHF in the two groups decreased and the observation group was fewer than the control group(P＜0.05).(4)The TP,ALB,Hb and Barthel index scores of the two groups increased compared with those before intervention,and the observation group increased more significantly than the control group(P＜0.05).Conclusion The geriatric interdisciplinary team service for the elderly has a good effect in the intervention of elderly patients with multimorbidity and malnutrition.

Objective:To understand the prevalence of arboviruses in mosquito samples in Xichang City, Sichuan Province, and enrich the data of arbovirus activity and genetic characteristics in southwestern Sichuan Province.Methods:In June 2018, the nucleic acid was extracted from Culex tritaeniorhynchus mosquitoes collected from different pigsties in three villages and suburbs of Xichang City. The specific primers of Yunnan orbivirus, Banna virus, Tibet orbivirus (S7, S10), Flavivirus and alphavirus were used for quantitative polymerase chain reaction examination, and the positive product was cloned for sequencing analysis. Results:A total of 9 012 mosquitoes were collected, of which Cx. tritaeniorhynchus was the dominant species. A number of 88 batches of these mosquitoes were amplified, and 2 strains of Japanese encephalitis virus (JEV), 7 strains of Banna virus (BAV), 7 strains of Tibet orbivirus (TIBOV) and 1 strain of Yunnan orbivirus virus (YOUV) were detected, respectively. By the results of cluster analysis and evolutionary tree analysis, the 17 newly found virus strains were close to the Yunnan isolates, and 2 JEV strains were located in the GI-b clade. The other 7 strains of BAV were A2 evolutionary clades. Of the 7 TIBOV plants, 6 were located in the same clade. One TOUV was in the same clade as the Yunnan strain. Conclusions:Culex tritaeniorhynchus mosquitoes in Xichang city might carry JEV, BAV, YOUV and TIBOV, among them JEV was GI-b type and BAV was A2 type. The results provide data supporting the detection and analysis of arboviruses in Xichang city.