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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ObjectiveTo identify the active components in Maimendong decoction (MMDD) against pulmonary fibrosis (PF) and validate their molecular effects in vitro, while focusing on the role of methylophiopogonanone B in regulating fibrosis.MethodsData on MMDD components and targets were gathered from databases including BATMAN-TCM and PubMed, whereas the PF gene data were sourced from GeneCards, OMIM, and TTD. Shared targets were determined using the STRING database, and molecular docking was used to analyze the essential molecules associated with fibrosis. To simulate PF conditions, human embryonic lung fibroblasts (HPF) and A549 cells were exposed to transforming growth factor-β1 (TGF-β1). Various assays were used to determine the effects of MMDD and methylophiopogonanone B on signaling pathways, apoptosis, and epithelial–mesenchymal transition.ResultsWe identified 11 active components from MMDD extracts that targeted 511 shared proteins associated with PF, revealing 10 key targets in network analysis. Gene ontology analysis indicated that processes and pathways such as apoptosis regulation and PI3K/Akt signaling were involved. In vitro experiments revealed that MMDD downregulated the expression of α-smooth muscle actin (α-SMA), collagen type I (COL-I), and collagen type III and regulated Bcl-2/Bax signaling pathways to promote apoptosis. The flow cytometry apoptosis assay revealed that MMDD promoted the TGF-β1-induced apoptosis of myofibroblasts. The primary active ingredient in MMDD, methylophiopogonanone B, reduced α-SMA, COL-I, and PI3K/Akt/mTOR-related protein levels in TGF-β1-treated HPF cells, decreased Bcl-2 and cleaved caspase 3, and increased Bax. Moreover, methylophiopogonanone B increased E-cadherin levels and reduced α-SMA, fibronectin, N-cadherin, vimentin, and snail in TGF-β1-treated A549 cells.ConclusionMethylophiopogonanone B demonstrated the potential to treat PF by inducing myofibroblast apoptosis and inhibiting EMT. However, despite encouraging initial results, further clinical research is warranted to verify the safety and efficacy of methylophiopogonanone B in the management of PF

AIM:To investigate the challenges and needs of individual ophthalmologists participated in the training and their countries in the prevention and treatment of blindness and visual impairment, sum up the training effects, and discuss how to promote the development of eye health in the Belt and Road countries in the future.METHODS:A total of 48 ophthalmologists from 6 countries, including Kenya, Zambia, Nigeria, South Africa, Malawi, Botswana between August 1 and August 30, 2022, were trained and anonymous questionnaire survey was conducted. The questionnaire consists of 15 questions covering three aspects: challenges and strategies related to vision impairment and blindness in the country, training satisfaction, and recommendations for establishing optometric centers in Africa.RESULTS: A total of 48 questionnaires were distributed and 47 valid questionnaires were collected. The ophthalmologists hold the view that the biggest challenge of their countries in prevention and treatment of ocular diseases was high nursing costs, accounting for 36.17%, the biggest challenge faced by ophthalmologists was low wages, accounting for 29.79%. Building more eye specialist hospitals(38.30%)and providing more training opportunities(65.96%)can effectively help the countries and the ophthalmologists. The organizational satisfaction with the training courses reached 98%, the content and the lecturers' satisfaction were 100%.CONCLUSION:There are urgent needs to build more ophthalmic hospitals and provide more professional training opportunities to solve the difficulties in the prevention and treatment of eye diseases of the countries and the ophthalmologists. This training program has high satisfaction and good feedback.

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 construct a rational and efficient bed resource allocation management model to reduce pre-hos-pital waiting times,ensure patient safety,and improve satisfaction.Methods Based on lean management principles,a bed re-source allocation management model was developed and continuously optimized.The study compared bed turnover rates and effi-ciency indices,as well as preoperative waiting times for surgical patients,average length of stay,patient satisfaction,and anxiety incidence before and after the implementation of the lean model to evaluate its effectiveness.Results After implementing the lean bed resource allocation model,the bed efficiency index increased by 14.29％,and bed turnover rates improved by 3.34％.The average preoperative waiting time for surgical patients decreased by 100％,and the average length of stay reduced by 87.71％.Patient satisfaction increased by 2.4％,while anxiety incidence dropped by 28.1％.Conclusion The implementa-tion of a lean bed resource allocation model can enhance hospital bed efficiency,shorten preoperative waiting times for surgical patients,reduce average length of stay,and improve patient satisfaction.

Objective:To systematically review the medical decision-making for children with autism spectrum disorder (ASD) from the perspective of caregivers.Methods:It was a systematic review. Using search terms as “Autism”“loneliness disorder”“autism spectrum disorder”“parents”“caregiver”“medical decision making”, etc., qualitative studies on medical decision-making of ASD caregivers in the databases of PubMed, Web of Science, Cochrane Library, Embase, Scopus, CNKI.com, Wanfang Database, VIP database, and Chinese Biomedical Literature database were searched. The search was conducted from the inception of the databases to July 31, 2022, and the data was organized from August 1 to September 1, 2022. The literature quality was evaluated by two researchers according to the quality evaluation criteria for qualitative research at the Centre for Evidence-based Health Care, Joanna Briggs Institute, Australia. Pooled integration method was used to integrate the study results and evaluate the medical decision-making of children with ASD from the perspective of caregivers.Results:Seventeen studies were included, with two studies rated as quality grade A and fifteen studies rated as quality grade B. A total of 36 research findings were extracted. These findings were grouped into ten new categories based on similarities, which were further synthesized into three overarching results: the symptom-driven medical decision-making process, delays in medical decision-making due to individual, family, and societal factors, and the influence of personal experiences and multiple external pressures on medical decision-making.Conclusion:The factors that lead to the delay or promotion of medical decision of caregivers of children with ASD are complicated, and comprehensive intervention measures should be taken at individual, family and social levels to promote early medical diagnosis and intervention of the children with ASD.

Remnant lipoprotein cholesterol(RLP-C)are composed of very low-density lipoprotein 3 cho-lesterol(VLDL3-C)and intermediate density lipoprotein cholesterol(IDL-C),which are the remnants produced by the hydrolysis of triglyceride-rich lipoproteins(TRLs).RLP-C levels are significantly related to the occur-rence of atherosclerotic cardiovascular disease(ASCVD)and are the remaining risk factors for ASCVD other than low-density lipoprotein cholesterol(LDL-C).Subintimal accumulation of atherogenic lipoprotein particles causes chronic inflammatory responses,including innate immune responses and adaptive immune responses.Unlike LDL-C,RLP-C is more likely to remain under the arterial endothelium and is directly phagocytosed by macrophages without oxidative modification,leading to the formation of foam cells and inflammatory reaction in the arterial wall endothelium,thereby forming atherosclerotic plaques.This review summarizes the concept of RLP-C,the relationship and quantitative detection method of RLP-C and ASCVD,and the mechanism of in-flammatory in ASCVD caused by RLP-C.

Based on the resutls of literature review and interviews of experts, two rounds of Delphi surveys were conducted. The mean, importance ratio, coefficient of variation and coordination coefficient were used for assessment of survey from multiple perspectives, and finally form a framework model of factors affecting the efficacy of Tuina therapy. A total of 37 experts were selected for questionnaire surveys, the positive coefficients of experts' participatation in the first round and second round were 92.5% and 80.0%, respectively. The overall coordination coefficient in the second round is 0.68. The items were included into the consensus meeting if the importance ratio of items were equal to and more than 80%. After the expert consensus meeting, 22 items were included to form a framework model of factors affecting the efficacy of Tuina therapy, and summarized as 5 major influencing factors, including diagnostic factors, treatment factors, prognostic factors, patient factors, and doctor-patient communication. This framework can guide and help young Tuina practitioners to improve clinical efficacy. It is also clearly pointed out that the effect of Tuina for pain is not only related to disease diagnosis or manipulation, but also related to home exercise, health care, and doctor-patient communication.