HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective:To understand the incidence of HIV infections and associated factors among men who have sex with men (MSM) in Jiangsu province.Methods:Based on national AIDS sentinel surveillance in 2019, MSM from 13 cities in Jiangsu were recruited for questionnaire interview and laboratory testing during April to July, 2019. Seropositive samples were tested with Limiting-antigen avidity enzyme immunoassay to detect recent HIV infections. The incidence of HIV infection in MSM were calculated according to the formula and parameters from China CDC. Multivariable logistic regression analysis was used to identify factors associated with recent infection of HIV.Results:A total of 4 469 MSM were subjects and the incidence of HIV infection were 4.5% (95% CI: 3.4%-5.5%).Multivariate logistic regression analysis results showed that compared with these aged ≥40 years, recruitment ways from MSM venues, awareness of AIDS knowledge, non-unprotected anal sex in the past 6 months and non-syphilis infection, those who aged 18-24 years (a OR=2.083,95% CI:1.087-3.990), recruitment ways from VCT clinics (a OR=2.125,95% CI:1.175-3.843), unawareness of AIDS knowledge (a OR=2.456,95% CI:1.109-5.437), unprotected anal sex in the past 6 months (a OR=3.553,95% CI:2.143-5.889) and syphilis infection (a OR=2.414,95% CI:1.033-5.462) were higher risk of HIV infection. Conclusion:The new infection rates of HIV were high in MSM in Jiangsu province. Health education, condom use and HIV/syphilis screening promotions should therefore be top priority in the prevention and control of HIV infection in MSM.

Objective To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients undergoing selective surgeries.Methods The traumatic patients undergoing selective surgeries from November 2016 to January 2017 at our department were selected for this prospective cohort study.They were divided into an intervention group (69 patients) and a control group (121 patients) according to the wards where they stayed.The intervention group was fasted for solids 6 hours prior to surgery and received oral solution with maltodextrin 2 hours prior to surgery.After surgery,they were allowed to drink liquids as soon as they were awakened.Normal food was allowed 2 hours later.The control group was fasted for either liquids or solids the night before surgery.After surgery,the patients who had received brachial plexus block only were allowed liquids with no limitation while the other patients were allowed liquids 6 hours after surgery and then were free for solids and liquids if no discomfort was observed.The time periods for preoperative liquids and solids fasting and for postoperative intake of liquids and solids were recorded and compared between the 2 groups.The perioperative well-beings (including anxiety,thirst,hunger,nausea,fatigue,dizziness,sweating and stomach discomfort) and serum glucose levels were compared between the 2 groups.Adverse reactions were observed.Results The preoperative fasting time for liquids for the intervention group (4.5 ± 2.9 hours) was significantly shorter than that for the control group (14.3 ±3.9 hours) (P ＜ 0.05).The preoperative fasting time for solids for the intervention group (17.6 ± 3.0 hours) were significantly longer than that for the control group (16.1 ±3.8 hours) (P ＜ 0.05).The postoperative fasting time periods for both liquids [1 (0,3) h] and solids [2 (1,4) h] for the intervention group were significantly shorter than those for the control group [6(6,6) h] hours and [6(6,6) h] (P ＜ 0.05).Compared with the control group,the perioperative anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort were significantly improved in the intervention group (P ＜ 0.05).The average serum glucose level was similar in both groups upon admission (P ＜ 0.05);it was significantly higher in the intervention group immediately before surgery (P ＜ 0.05) but was gradually decreased after surgery until there was no significant difference between the 2 groups (P ＞ 0.05).No major adverse reaction was observed in either group.Conclusion The protocol of perioperative fasting abbreviation may be safe and feasible in traumatic patients for selective surgeries,showing benefits of decreased anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort.

Objective Clinical efficacy was compared among single injections of different doses of long acting gonadotropin releasing hormone agonist (GnRH-a),and daily injections of short-acting GnRH-a in order to evaluate different methods of ovarian stimulation for in vitro fertilization (IVF) cycles.Methods A retrospective study of 214 patients who underwent IVF assisted fertility treatments was conducted.Patients were allocated into four study groups:the short protocol (group A),in which daily injections of 0.1 mg GnRH-a was administered in the mid-luteal phase until the day of human chorionic gonadotropin (hCG) administration (see below);or the long protocol (group B,C & D),in which single injections of 3.75mg,2.0mg,or 0.9mg of long-acting GnRH-a was given in the mid-luteal phase,respectively.Stimulation with gonadotropins (Gn) started when pituitary down-regulation was established.When vaginal ultrasonographic scans showed that at least two follicles had reached 16-20mm in diameter,Gn stimulation was withdrawn,and serum estradiol (E2),progesterone (P),and luteinizing hormone (LH) were determined.Additionally,human chorionic gonadotropin (hCG) was administered that evening.Egg collection was performed 38 hours after hCG injection and the standard IVF procedure was performed.Results There were no statistically significant differences amongst the four groups when measuring serum LH levels,number of oocytes,number of fertilized eggs,number of good quality embryos,and clinical pregnancy rate.The total amount of Gn administered was almost identical when comparing group A and group D,as well as when comparing group B and group C.However,Group A and D required less Gn stimulation to exhibit follicles of 16-20mm in diameter,compared to group B and C (P ＜0.005).Moreover,there was a significant difference in the time required for ovulation induction between group A and group C,where group A had a shorter time to ovulation.The fertilization rate was statistically different between group B and other groups (P ＜ 0.005).Conclusion Through our data analysis,we conclude based on outcome,cost,side-effects,and simplification of treatments,that the 0.9mg long-acting GnRH-a treatment is eminent for ovarian stimulation for IVF.

Objective To compare the perioperative characteristics and long term outcomes between extracorporeal membrane oxygenation (ECMO)-conventional cardiopulmonary switch (experimental group,26 cases) and off-pump high-risk coronary artery bypass grafting (OPCABG group,24cases).Methods Perioperative characteristics and survival rate were retrospectively analyzed between experimental group and OPCABG group.Long term survival rates without major cardiovascular adverse events (MACE) were comparatively analyzed via Kaplan-Meier curves.Results The average Euroscore value were 11.7 ± 2.4 and 10.9 ± 2.0,respectively(P =0.208).The experimental group had a higher complete revascularization rate (96.2％ vs.66.7％,P =0.009),a shorter length of postoperative ECMO support [(33.1±23.6)h vs.(80.8±18.5)h],an intensive care unit stay[(4.8±1.1)d vs.(10.2±9.0)d]and a hospital stay [(17.7±6.3)d vs.(28.2±17.5)d] (all P＜0.05) as compared with OPCABG group.Preoperative New York Heart Association (NYHA) grading of cardiac function (r =0.511,P =0.008) and intraoperative ultrafiltration volume (r =-0.442,P =0.024) were significantly correlated with postoperative ECMO continuation in the experimental group.The follow-up period was (45.4 ± 15.2) months.The experimental group had a higher survival rate without MACE than had the OPCABG group (Log-rank test:x2=4.828,P=0.028).Conclusions The ECMO-conventional cardiopulmonary switch mode might facilitate a higher complete revascularization,a lower incidence of postoperative morbidities and improve the longterm survival rate without MACE for patients with high risks.

No abstract available.
Neodymium* ; Onychomycosis* ; Pilot Projects*

OBJECTIVETo understand the compliance of highly active anti-retroviral therapy (HAART) and influencing factors in people living with HIV/AIDS (PLWHA) in Nanjing.

METHODSPLWHA receiving HAART in No. 2 Hospital of Nanjing during May-June 2014 were recruited in this study. Self-administrated questionnaire was used to collect the data about HAART compliance and socio-demographic characteristics of PLWHA surveyed. Descriptive and multivariate statistical analysis were conducted to examine the effects of the factors on self-reported HAART adherence.

RESULTSA total of 276 PLWHA were surveyed, According to the evaluation criterion of Center for Adherence Support Evaluation (CASE), 252 cases showed good compliance (91.3%). logistic regression analysis revealed that smoking, progress of the disease and side effects, reminding of taking drug and age were correlated with self-reported HAART adherence.

CONCLUSIONIt is suggested to strengthen the education about antiviral therapy compliance in PLWHA with mild infection and those who are smokers and young, suffer from side effects, have no reminding methods for taking drug.

Acquired Immunodeficiency Syndrome ; drug therapy ; Age Factors ; Antiretroviral Therapy, Highly Active ; Antiviral Agents ; adverse effects ; therapeutic use ; China ; Disease Progression ; HIV Infections ; drug therapy ; Humans ; Medication Adherence ; statistics & numerical data ; Reminder Systems ; Smoking ; Surveys and Questionnaires

Objective To understand the compliance of highly active anti-retroviral therapy (HAART) and influencing factors in people living with HIV/AIDS (PLWHA) in Nanjing. Methods PLWHA receiving HAART in No. 2 Hospital of Nanjing during May-June 2014 were recruited in this study. Self-administrated questionnaire was used to collect the data about HAART compliance and socio-demographic characteristics of PLWHA surveyed. Descriptive and multivariate statistical analysis were conducted to examine the effects of the factors on self-reported HAART adherence. Results A total of 276 PLWHA were surveyed,According to the evaluation criterion of Center for Adherence Support Evaluation (CASE),252 cases showed good compliance (91.3%). logistic regression analysis revealed that smoking,progress of the disease and side effects,reminding of taking drug and age were correlated with self-reported HAART adherence. Conclusion It is suggested to strengthen the education about antiviral therapy compliance in PLWHA with mild infection and those who are smokers and young,suffer from side effects,have no reminding methods for taking drug.

Objective To evaluate the role of complement receptor 3 (CR3) on murine macrophages in the recognition of Penicillium marneffei.Methods RAW264.7 murine macrophage cells were cultured in vitro,and divided into four groups to be cocultured with inactivated and live Penicillium mameffei yeast cells as well as inactivated and live Penicillium marneffei conidia respectively at 37 ℃ in 5％ CO2 for one hour.The RAW264.7 cells incubated with phosphate-buffered saline (PBS) served as the blank control group.Then,reverse transcription-PCR was conducted to detect CR3 mRNA expression,Western blot to measure CR3 protein expression,flow cytometry to determine phagocytosis rate,enzyme-linked immunosorbent assay (ELISA) to quantify cytokine levels in culture supernatant.Some RAW264.7 macrophages were transfected with a specific siRNA targeting CR3 gene and cocultured with inactivated Penicillium marneffei conidia,subsequently,phagocytosis rate and supematant cytokine levels were determined.Data were processed by the SPSS 16.0 software,and one-way analysis of variance (ANOVA) was conducted for inter-group comparisons of these parameters.Results No significant differences were observed in the mRNA or protein expressions of CR3 among the four groups of RAW264.7 cells cocuhured with different forms of Penicillium marneffei (both P ＞ 0.05).The phagocytosis rate was 95.14％,89.56％,91.03％ and 90.78％ in RAW264.7 cells cocultured with inactivated conidia and yeast cells,as well as live conidia and yeast cells of Penicillium marneffei,respectively (P ＞ 0.05).The levels of interleukin (IL)-2,interferon (IFN)-γ,IL-4 and IL-10 in culture supernatant were increased at different degrees after one-hour coculture in the four coculture groups compared with the blank control group,but no statistical difference was noted among the four coculture groups in the supernatant levels of these cytokines (all P ＞ 0.05).After coculture with inactivated Penicillium marneffei conidia,the siRNA-transfected RAW264.7 cells showed a statistical decrease in phagocytosis rate (10.89％ vs.92.78％,P ＜ 0.05) and supernatant levels of IL-2,IFN-γ IL-4 and IL-10 compared with untransfected RAW264.7 cells.Conclusions In early stage of innate immunity,CR3 on macrophages may be one of the pattern recognition receptors participating in the recognition and mediation of phagocytosis of Penicillium marneffei.It's possible that both Thl-and Th2-type cytokines,such as IL-2,IFN-γ,IL-4 and IL-10,are involved in the immune response of macrophages against Penicillium marneffei.