OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Objective:To explore the current status of readiness for young and middle-aged maintenance hemodialysis (MHD) patients to return to work and analyze its influencing factors, with the aim of providing reference for the evaluation and intervention of patients returning to work.Methods:From October to December 2022, convenience sampling was used to select 425 patients from six hospitals in the urban area of Yangzhou as the subject. A cross-sectional survey was conducted using the General Information Questionnaire, Readiness for Return-To-Work Scale (RRTWS), Distress Disclosure Index (DDI) and Perceived Social Support Scale (PSSS). Binary Logistic regression was used to analyze the influencing factors of returning to work.Results:Among 425 young and middle-aged patients undergoing MHD, 105 (24.7%) returned to work, of which 79 (75.2%) were in the uncertain maintenance stage and 26 (24.8%) were in the active maintenance stage. 320 did not return to work, including 148 (46.3%) in the pre-intention stage, 86 (26.9%) in the intention stage, 42 (13.1%) in the action preparation self-evaluation stage, and 44 (13.8%) in the action preparation behavior stage. Age, per capita monthly income of the family, number of comorbidities, level of self-disclosure, and level of perceived social support were factors that affected patients' readiness to return to work.Conclusions:The rate of young and middle-aged MHD patients returning to work needs to be improved. The return of patients to work is influenced by multiple factors. Medical and nursing staff should focus on patients who are old, have low per capita monthly income of the family, and have a large number of comorbidities. Targeted interventions and guidance should be provided to patients, such as self-disclosure training and improving their perceived social support, in order to increase the rate of patients returning to work rate.

Objective: To understand the prevalence of chronic kidney disease (CKD) and related factors in adults in Anhui province based on the data of Chinese Chronic Diseases and Nutrition Surveillance program (2018) in Anhui. Methods: Multi-stage stratified cluster random sampling was used to select participants aged ≥18 years. Moreover, questionnaire survey, body measurements and laboratory tests were conducted. The complex weighting method was used to estimate the prevalence of CKD in residents with different characteristics, and complex sampling data logistic regression model was used for multivariate analysis to identify related risk factors. Results: A total of 7 181 participants were included. The overall prevalence of CKD was 11.06% in adults in Anhui, and the prevalence was 12.49% in women and 9.59% in men (P<0.05). The moderate, high and very high risk for CKD progression were 8.66%, 2.02% and 0.38%, respectively. Multivariate analysis showed that age (OR=1.03, 95%CI: 1.00-1.05), BMI (OR=1.05, 95%CI: 1.01-1.09), being woman (OR=1.38,95%CI: 1.22-1.55), hypertension (OR=2.50, 95%CI: 1.76-3.56), diabetes (OR=2.28, 95%CI: 1.51-3.43), dyslipidemia (OR=1.26, 95%CI: 1.11-1.43) and hyperuricemia (OR=2.16, 95%CI: 1.68-2.78) were risk factors for CKD. Conclusion: The prevalence of CKD in adults in Anhui was relatively high and age, gender, BMI, hypertension, diabetes, dyslipidemia and hyperuricemia were found to be associated with the prevalence of CKD. To prevent CKD and its complications, attention should be paid to the management of related risk factors, including overweight and obesity, hypertension, diabetes, dyslipidemia and hyperuricemia.
Adult ; Male ; Female ; Humans ; Adolescent ; Cross-Sectional Studies ; Prevalence ; Hyperuricemia/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; Hypertension/epidemiology*

OBJECTIVE To intr oduce multidisciplinary collaborative blood glucose management mode （hereinafter referred as to blood glucose management mode of the whole hospital ）of the whole hospital with the participation of clinical pharmacists ，and to evaluation it effects on the blood glucose management of perioperative diabetes patients. METHODS The process of blood glucose management mode of the whole hospital in Drum Tower Hospital Affiliated to Medical School of Nanjing University and the work content of clinical pharmacists were introduced. Three hundred patients with type 2 diabetes mellitus who underwent elective surgery were included and randomly divided into general consultation group （control group ）and hospital-wide glucose management group （intervention group ）. The effect of glucose management and indicators such as preoperative waiting time and total length of stay were compared between 2 groups. RESULTS In the blood glucose management team of the whole hospital ，the physicians，clinical pharmacists and nurses of blood glucose management in endocrinology department were the core members ，and the management process was divided into initial management ，daily management ，discharge management and follow-up. As the team secretary ，the clinical pharmacists were mainly responsible for daily summarizing and managing the blood glucose level and special conditions of patients ，regularly evaluating the management effect ，carrying out pharmaceutical ward rounds ，medical order review， pharmaceutical care ， timely assessing the blood glucose of patients and guiding the rational use of drugs. Compared with before intervention ， after 3 days ofintervention，the levels of fasting plasma glucose （FPG）and postprandial blood glucose （PBG） were decreased significantly in 2 groups（P＜0.05）；intervention group was significantly lower than control group （P＜0.05）. Compared with control group ， the fluctuation of blood glucose in intervention group was significantly reduced （P＜0.05），standard deviation of blood glucose had reached the targeted control level ， and the postprandial glucose excursion and the largest amplitude of glycemic excursion were close to the targeted control level ；the rate of bl ood glucose reaching the standard before operation and at discharge were significantly increased （P＜0.05）；the preoperative waiting time and hospitalization days were significantly shortened （P＜0.05）. CONCLUSIONS The multidisciplinary collaborative blood glucose management mode of the whole hospital with the participation of clinical pharmacists can control the blood glucose level of diabetic patients in the perioperative period more stably and effectively ，and has practical significance for the disease treatment and prognosis of patients.