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.

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Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.

Objective:To investigate the current situation of coping styles in Crohn's disease patients and its related influencing factors.Methods:A total of 80 patients with Crohn's disease admitted to our hospital from Apri 2021 to Dec 2022 were selected to evaluate their coping styles with a simple coping style questionnaire,and relevant data were collected.The factors affecting the coping styles of Crohn's disease were analyzed by multivariable logistic regression.Results:Among the 80 patients,29 cases were negative coping,the incidence was 36.25% .There were 51 patients with positive coping(63.75% ).Educational level,simplified Crohn's disease activity index(CDAI)score,adverse psychology,social support and type D personality were associated with negative coping(P＜0.05).Gender,age,family history,working status,monthly family income,place of residence,and marital status were not associated with negative coping in patients with Crohn's disease(P＞0.05).Multivariable logistic regression analysis showed that education level of high school or below(OR=2.945,95% CI:1.139-7.614),higher CDAI score(OR=11.999,95% CI:4.387-32.815),poor psychology(OR=5.950,95% CI:2.180-16.239),low social support(OR=3.598,95% CI:1.370-9.448)and type D personality(OR=3.208,95% CI:1.118-8.904)were risk factors for negative coping in patients with Crohn's disease(P＜0.05).Conclusions:The incidence of negative coping in patients with Crohn's disease is higher,which is related to high school education or below,high CDAI score,poor psychology,low social support,and type D personality.Therefore,clinical measures can be taken to promote patients to actively cope with the disease.

In order to realize the diagnosis of slit lamp in cross-regional patients and improve the real-time and convenience of diagnosis,a remote slit lamp diagnosis platform based on Internet of Things(IoT)technology is designed.Firstly,the feasibility of remote slit lamp is analyzed.Secondly,the IoT platform architecture of doctor/server/facility(D/S/F)is proposed and a remote slit lamp is designed.Finally,the performance of the remote slit lamp diagnostic platform is tested.The platform solves the communication problem of distributed slit lamps and realizes respectively numerical control of multi-area slit lamp by multi-eye experts.The test results show that the remote control delay of the platform is less than 20 ms,which supports multiple experts to diagnose multiple patients separately.

Objective:To investigate the status quo of psychological contracts and influencing factors among members of the "1+N" family doctor teams in Shenzhen and to explore the impact of psychological contracts on job burnout.Methods:This cross-sectional study was conducted from September 30 to October 31, 2022 among 361 members of 92 family doctor teams from 92 community health service centers which provided family doctor team service in Shenzhen city. A self-designed general information questionnaire, an employee psychological contract questionnaire (including organizational responsibility and personal responsibility dimensions), and a job burnout scale (including emotional exhaustion, depersonalization, and personal accomplishment dimensions) were used in the study. T-tests, one-way ANOVA, Pearson correlation analysis, and multiple linear regression analysis were used to analyze the influencing factors of psychological contracts and job burnout.Results:Among 361 respondents, there were 299 females (82.8%) and 62 males (17.2%), and a higher proportion of general practitioners (37.5%, 129/361) and nurses (41.8%, 151/361). The total score of psychological contracts among the 361 respondents was (141.6±19.5), with organizational responsibility scoring (70.6±11.2) and personal responsibility scoring (71.0±9.3). On the job burnout scale, emotional exhaustion scored (17.89±6.82), depersonalization scored (6.51±2.54), and personal accomplishment scored (30.95±5.70). General practitioners scored lower in organizational responsibility and personal responsibility compared to other members ( F=7.341,3.119, all P<0.05), and higher in emotional exhaustion and depersonalization ( F=7.637, 2.415, all P<0.05). Members with≤5 years of work experience scored lower in personal responsibility and personal accomplishment ( F=3.656, 4.205, all P<0.05). Correlation analysis showed that scores of organizational responsibility and personal responsibility were negatively correlated with levels of emotional exhaustion and depersonalization ( r=-0.618, -0.526, all P<0.01), ( r=-0.404, -0.393, all P<0.01), and positively correlated with personal accomplishment ( r=0.500, 0.558, all P<0.01). Multiple linear regression analysis indicated that organizational responsibility negatively affected emotional exhaustion and depersonalization ( β=-0.554, -0.274, all P<0.01), and positively affected personal accomplishment ( β=0.172, P<0.05). Personal responsibility positively affected personal accomplishment ( β=0.404, P<0.01). Conclusions:The study demonstrates that general practitioners in family doctor teams in Shenzhen city have lower psychological contract levels and are more prone to emotional exhaustion and depersonalization; members with≤5 years of work experience have lower personal responsibility and accomplishment. The results indicate that enhancing organizational responsibility can reduce job burnout of members in family doctor teams.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective: To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). Materials and Methods: SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Results: Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC:0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). Conclusion FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective:To survey on the status quo of the role cognition and job burnout among family doctor team members in Shenzhen Futian district.Methods:A survey on the role cognition and job burnout of family doctor members was conducted in October 2022. One family doctor team was randomly selected from each of the 92 community health service centers in Futian district of Shenzhen city, and all members of the selected family doctor teams were included in the survey. The Chinese version of the Maslach Burnout Inventory-Human Services Survey was used in the study, and the influencing factors of role cognition and job burnout, as well as the impact of role cognition on job burnout were analyzed.Results:A total of 361 family doctor team members were included in the survey, The scores of the Role Ambiguity and Role Conflict Scale were (35.25±5.21) and (27.03±13.73), respectively. In the Occupational Burnout Scale, the scores of Emotional Exhaustion, Dehumanization, and Personal Achievement Scale were (17.89±6.82), (6.51±2.54), and (30.95±5.70), respectively. There were significant differences in role ambiguity and job burnout among family doctor team members with different ages, professions, and years of work ( P<0.05). Team members aged≤30, general practitioners, and working time ≤5 years had higher scores for role ambiguity, emotional exhaustion, dehumanization, and lower personal achievement ( P<0.05). The score of role ambiguity was negatively correlated with the degree of emotional exhaustion and dehumanization ( r=-0.544, -0.352), and positively correlated with personal achievement ( r=0.473). The score of role conflict was positively correlated with the degree of emotional exhaustion and dehumanization ( r=0.352, 0.376), and negatively correlated with personal achievement ( r=-0.440). Regression analysis showed that the role cognition was significantly associated with the emotional exhaustion, dehumanization, and personal achievement ( F=10.28-85.12, P<0.01). Conclusion:Active and effective measures should be taken to improve the role cognition and reduce job burnout of family doctor team members in primary health care institutions.