As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To analyze the relationship between sedentary behavior and the force expiratory volume in 1 second (FEV₁) reduction in middle-aged and elderly people in communities. Methods: The participants aged ≥40 years were randomly selected from a natural population cohort in Songjiang District, Shanghai, for pulmonary function tests and survey by using international physical activity questionnaire, a generalized additive model was used to analyze the association between sedentary behavior and FEV₁ reduction in the study population and different sex-age subgroups. Results: A total of 3 121 study subjects aged ≥40 years were included. The prevalence of FEV₁ reduction was 14.8%, which was higher in men than in women. There were 24.8% participants were completely sedentary. The prevalence of FEV₁ reduction in women aged <60 years in complete sedentary group was 2.04 (95%CI: 1.11-3.72) times higher than that in non-complete sedentary group. In men aged <60 years, the prevalence of FEV₁ reduction increased with daily sedentary time (OR=1.16, 95%CI: 1.04-1.29), and the prevalence of FEV₁ reduction was also higher in those with sedentary time >5 hours/day than those with sedentary time ≤5 hours/day (OR=3.02, 95%CI: 1.28-7.16). The sensitivity analysis also found such associations. Conclusions: FEV₁ reduction rate in age group <60 years was associated with sedentary behavior. Complete sedentary behavior or absence of moderate to vigorous physical activity played important roles in FEV₁ reduction in women, while men were more likely to be affected by increased sedentary time, which had no association with physical activity. Reducing sedentary time to avoid complete sedentary behavior, along with increased physical activity, should be encouraged in middle-aged and elderly adults in communities to improve their pulmonary function.
Male ; Aged ; Middle Aged ; Humans ; Adult ; Female ; Infant ; Sedentary Behavior ; China/epidemiology* ; Exercise ; Surveys and Questionnaires ; Prevalence

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.
Female ; Humans ; Cancer-Associated Fibroblasts/pathology* ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/pathology* ; Prognosis ; STAT3 Transcription Factor/metabolism* ; Drug Resistance, Neoplasm

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Paraquat/pharmacology* ; Lung

Objective: To clarify the long-term characteristics of tinnitus following treatment of sudden deafness and its long-term physical and mental effects on patients. Methods: A retrospective analysis was performed on 88 patients (46 males and 42 females; Age from 11 to 89 years) with sudden deafness treated in Department of Otoscope Surgery of Peoples's Libration Army General Hospital in Beijing from April 2020 to January 2021, and the occurrence of tinnitus and treatment effect of all patients were analyzed. Follow-up was conducted for patients with residual tinnitus after treatment for more than 1 year by the investigation and filling in the survey information collection form, Tinnitus Evaluation Questionnaire (TEQ) and Tinnitus Handicap Inventory (THI). Descriptive statistics and SPSS 22.0 software were used for statistical data analysis. Results: In this study, 93.2% (82/88) of patients with sudden deafness were accompanied by tinnitus at the onset, and the proportion of long-term tinnitus after treatment was 90.2% (74/82). After 1 year of treatment for sudden deafness, the improvement of tinnitus was significant in low-frequency sudden deafness compared with those of high-frequency, flat and total deafness sudden deafness (χ2 value was 6.801, 4.568 and 4.038, all P<0.05). In patients with residual tinnitus, 9 (12.2%) patients felt minimal loudness or even no loudness, 34 (46.0%) patients felt slight loudness, 28 (37.8%) patients felt tinnitus was relatively loud, and 3 (4.1%) patients felt tinnitus was loud or noisy. Nine (12.2%) patients's sleep was often affected, 41 (55.4%) patients's sleep was sometimes affected, 9 (12.2%) patients's sleep was rarely affected, 15 (20.3%) patients's sleep was almost not affected. Twenty-eight (37.8%) patients basically completely adapted to tinnitus and 46 (62.2%) patients did not completely adapted to residual tinnitus. Eight (10.8%) patients had no impact on life, 39 (52.7%) patients had slight impact, 22 (29.7%) patients had moderate impact, and the other 5 (6.8%) patients had greater impact. According to tinnitus evaluation questionnaire(TEQ), there were 12 cases (16.2%) of grade Ⅰ, 26 cases (35.1%) of grade Ⅱ, 28 cases (37.8%) of grade Ⅲ, 7 cases (9.5%) of grade Ⅳ and 1 case (1.4%) of grade Ⅴ. According to tinnitus handicap inventory(THI), tinnitus disability was classified into grade Ⅰ, 22 cases (29.7%), grade Ⅱ, 14 cases (18.9%), Grade Ⅲ, 27 cases (36.5%) and grade Ⅳ, 11 cases (14.9%). Conclusion: The rate of residual tinnitus following treatment of sudden deafness is high. Some of the patients can completely adapt residual tinnitus after one year, but some of them will be affected when sleep, work and study. Residual tinnitus can lead to tinnitus disability in different degrees.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Hearing Loss, Sudden/therapy* ; Tinnitus/therapy* ; Retrospective Studies ; Deafness/complications* ; Audiometry

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.
Humans ; Dentistry, Operative ; Consensus ; Endodontics ; Root Canal Therapy ; Dental Care

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both