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.

OBJECTIVE To analysis the clinical and pathological characteristics of lymph nodes metastasis in pediatric patients with differentied thyroid carcinoma(pDTC),and to develop a nomogram for predicting lymph nodes metastasis in patients with pDTC.METHODS Four cohorts were integrated in this study,including internal training cohort(1419 cases)and validation cohort(609 cases)from the Surveillance,Epidemiology,and End Results(SEER)database of the National Cancer Institute,TCGA-pDTC cohort(20 cases from the Cancer Genome Atlas Program)and YHD-pDTC cohort(39 cases from true world).The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to screen factors related to lymph nodes metastasis in the presence and exclusion of T stage in pDTCs based on internal training cohort and construct nomograms.Calibration curve,receiver operating characteristic(ROC)curve,area under the ROC curve(AUC)and decision curve analysis(DCA)were used to evaluate model performance in the other three cohorts.RESULTS Multivariate logistic regression results showed that pathology[OR(95%CI):0.020(0.010-0.060),P<0.001],M stage[OR(95%CI):29.550(3.190-273.490),P=0.003],and T stage[OR(95%CI):2.210(1.820-2.680),P<0.001]were independent factors affecting lymph nodes metastasis in pDTCs.Through the internal training set,internal validation set,YHD-pDTC cohort and TCGA-pDTC cohort,the AUC values were 0.734(0.709,0.758),0.752(0.716,0.788),0.969(0.920,1),and 0.600(0.342,0.858)in that order,and the calibration curves are close to the perfect reference line.T stage is a better predictor of lymph nodes metastasis than extraperitoneal intrusion and tumor size.CONCLUSION Pathology,M stage,and T stage are risk factors for predicting lymph nodes metastasis in pDTCs.The nomogram established on this basis can make individualized predictions of the probability of lymph nodes metastasis in pDTCs.

From the natural-philosophical model of medicine in ancient Greece to the modern bio-psycho-social par-adigm,the evolution of medical models has always been shaped by philosophy.In classical antiquity,medicine and philosophy were closely intertwined;the natural-philosophical model,exemplified by Hippocrates,emphasized the human body as an integrated whole.During the Renaissance,the rise of experimental science challenged traditional philosophical systems and pushed medicine toward empirical investigation.In the late twentieth century,the bio-psycho-social model emerged to address the limitations of the purely biomedical approach.In the twenty-first centu-ry,the advent of artificial intelligence is driving a new transformation in medicine and continually prompting reflec-tion on the future direction of medical models and their underlying philosophical significance.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Objective To develop a self-assessment scale for medication literacy in patients with coronary heart disease comorbidity diabetes and to test its reliability and validity.Methods According to medication literacy theory model,the initial scale was formed through literature review,the qualitative interview and expert inquiry.Cognitive interview was used to optimize the expression of item text.421 patients with coronary heart disease comorbidity diabetes in a tertiary hospital in Zhejiang province from November 2022 to April 2023 were selected to investigate the reliability and validity of the scale by convenience sampling.Results The self-assessment scale of drug literacy for coronary heart disease comorbidity diabetes mellitus included 23 items in 5 dimensions including acquisition,understanding,communication,evaluation and calculation.The total Cronbach's α coefficient of the scale was 0.911;the retest reliability was 0.948;the average content validity index was 0.997;the correlation coefficients between each dimension and total score of the scale and the calibration scale ranged from 0.485 to 0.926.The exploratory factor analysis was employed to extract 5 common factors,and the cumulative variance contribution rate was 73.753％.Confirmatory factor analysis showed that the scale factor structure was stable.Conclusion The scale has good reliability and validity,and it can be used as an effective tool to evaluate the self-rated medication literacy level of patients with coronary heart disease comorbidity diabetes.

Objective:To explore the effect of holistic nursing combined with heat preservation nursing in patients undergoing thoracoscopic lung wedge resection.Methods:From April 2020 to March 2021, convenience sampling was used to select 196 patients who underwent thoracoscopic wedge resection for lung cancer in the First Affiliated Hospital of Xinjiang Medical University as the research object. The patients were divided into the observation group and the control group by the order of admission, 98 cases in each group. The patients in the control group were given routine nursing, and the patients in the observation group were given holistic nursing combined with heat preservation nursing on the basis of the control group. The visual analogue scale (VAS) was used to evaluate the postoperative pain of the two groups of patients, and the transfer time to and from the Resuscitation Room, postoperative recovery time and hospital stay were compared between the two groups. The incidence of postoperative adverse reactions in the two groups was recorded and compared.Results:The VAS scores of the observation group at 1 and 12 hours after operation were (2.06±0.52) and (2.46±0.81) respectively, which were lower than those of the control group [ (3.72±1.10) and (4.06±0.78) ], and the differences were statistically significant ( P<0.05) . The postoperative recovery time, hospital stay, and transfer time to and from the Resuscitation Room of the observation group were (56.34±10.10) min, (7.12±1.17) d, (2.10±0.32) min, and (2.52±0.50) min, respectively, lower than those of the control group, and the differences were statistically significant ( P<0.05) . The incidence of adverse reactions in the observation group (4.08%) was lower than that in the control group (22.45%) , and the difference was statistically significant ( P<0.05) . Conclusions:Holistic nursing combined with heat preservation nursing can speed up the postoperative recovery, reduce the incidence of adverse reactions, relieve postoperative pain, and facilitate postoperative recovery of patients undergoing thoracoscopic lung wedge resection.

Objective:To determine the characteristics of hospitalized newly diagnosed systemic lupus erythematosus (SLE) patients with high disease activity, and identify the risk factors.Methods:Data from 194 newly diagnosed SLE patients at Shanghai Renji Hospital between May 2013 and December 2018 were collected retrospectively. All patients were followed up for 1 year or until death. Patients' demographic, clinical, and laboratory characteristics on admission and medication history were retrospectively collected as baseline data. Patients were divided into two groups, lupus patients with infection (51 cases) and lupus patients without infection (143 cases). The method of univariate analysis of data depended on the data distribution type. Variables that suggested association in the univariate analysis ( P<0.05) were entered into Cox regression model. Results:Among 194 patients with newly diagnosed SLE, 21 cases (11%) died and 51 cases (26%) were infected during 1-year follow-up. Regarding the infection site, 34 cases (67%) had lung infection, 9 cases (18%) had central nervous system infection and 9 cases (18%) had blood stream infection. Common bacteria were identified in 19 cases (45%), followed by fungal infection in 18 cases (43%) and mycobacterium infection in 7 cases (17%). Among the 51 patients with infection, 38 patients (75%) had infection within the first 3 months after diagnosis, and mortality in this group was significantly higher than that in the uninfected group (39%, 15/38 vs 2%, 3/143 , P<0.01). Comparing baseline parameters between patients with 3-month infection and without, significant differences ( P<0.05) were detected in age (≥40 years), systemic lupus erythematosus disease activity index (SLEDAI) score (>10 points), Systemic Lupus International Collaborating Clinic (SLICC)/American College of Rheumatology(ACR) systemic lupus erythematosus damage index (SDI) (≥1 point), pericardial effusion, nephritis, gastrointestinal vasculitis, diabetes, lymphocyte count <0.8×10 9/L platelet count <100×10 9/L, serum creatinine >104 mmol/L and serum globulin level <20 g/L. Finally, clinically meaningful candidate predictors were included in the Cox regression model and it showed that lymphocyte count <0.8×10 9/L, nephritis and gastrointestinal vasculitis were independently predictive for 3-month infection in new-onset lupus patients. Conclusion:Understanding disease spectrums and risk factors of infection in newly diagnosed SLE patients will help clinicians to manage those patients with infection effectively to achieve favorable prognosis.

Objective　To compare pain in patients with young-onset (YOPD) and late-onset (LOPD) Parkinson’s disease and analyze influencing factors.Methods　Seventy participants who visiting outpatient and inpatient of the neurology department of the Provincial Hospital Affiliated to Anhui Medical University from October 2018 to July 2020 were selected and divided into YOPD and LOPD group according to age and Hoehn-Yahr (H-Y) Scale.General data were collected.The king’s Parkinson’s disease pain scale (KPPS)，part 3 of the Unified Parkinson’s disease rating scale (UPDRS-Ⅲ).The hamilton rating scale for depression (HAMD） were used to assess the item of pain,motor function and prevalence of depression.And further analyses of their effects on pain were made.Results　Compared with LOPD patients,YOPD patients had lower mean age,HAMA score and prevalence of hypertension and constipation,longer mean duration of disease,higher mean HAMD score,MMSE score,KPPS score and incidence of pain (P<0.05).Compared with LOPD patients with pain,YOPD patients with pain had higher prevalence of pain occurring in the waist,lower prevalence of pain occurring in the legs (P<0.05).YOPD patients with pain had higher mean UPDRS-Ⅲ score,HAMD score,HAMA score and dyskinesia stage than those without pain (P<0.05).LOPD patients with pain had higher mean HAMD score,HAMA score and dyskinesia stage than those without pain (P<0.05).Conclusion　Patients with YOPD have a higher incidence of PD pain and more severe pain than those with LOPD.The more severe the emotional disorders and motor symptoms are,the more likely they will suffer from pain.Clinicians should standardize the treatment of pain according to the type and location of pain in PD patients,so as to improve the quality of life of patients.

Objective:To evaluate the association between the efficacy and safety of metformin and the influence of variants in SLC47A1 rs2289669 G>A polymorphism in the treatment of systemic lupus erythematosus (SLE).Methods:A multicenter, randomized, double-blind, placebo-controlled trial was conducted. Patients were consented at enrollment for blood donation for genotyping, and their peripheral blood were used to detect the distribution frequency of SLC47A1 mutations. The major or mild/moderate flares defined by modified safety lupus erythematosus national assessment (SELENA)-systemic lupus erythematosus disease activity index (SLEDAI) Flare Index (SFI) and adverse events were recorded at 12 months of follow-up. The correlation between efficacy/safety and genotype was analyzed. Student's t test and χ2 test was used to assess the continuous variables and categorical variables. Results:Between May 24, 2016, and Dec 13, 2017, a total of 31 patients in the metformin group and 35 in the placebo group were detected. There were no statistical significant differences in the clinical manifestations, SELENA-SLEDAI scores, and therapy of the participants at baseline. There was no significant difference in the frequency of AA genotype, GA genotype, and GG genotype of SLC47A1 rs2289669 distribution between the metformin group and the placebo group. In the metformin group, patients who flared had a lower frequency of A alleles than those non-flared [25%(4/16) vs 61%(28/46), χ2=6.116, P=0.019 8]; the flare rate was significantly lower in patients with AA genotype than in GG genotype [0%(0/8) vs 57%(4/7), χ2=6.234, P=0.012 5]. The infection rate was lower in the metformin group than that in the placebo group [38%(12/31) vs 69%(24/35), χ2=5.913, P=0.015 0], but there was no significant difference among different genotypes in the metformin group. Compared to GG geno-type, AA genotype showed a trend of decrease in infection rate[38%(3/8) vs 72%(5/7), χ2=1.727, P=0.188 8]. Conclusion:Metformin has a favorable safety profile and may reduce the frequency of flares in SLE patients with low-grade lupus disease activity. The metformin therapeutic efficacy in SLE is relevant to the SLC47A1 gene polymorphism. Patients of the AA genotype may benefit most from metformin than those of the GG and GA genotypes.

Objective: To explore the relationship among cognitive flexibility, depression and eating attitude of adolescents and the influencing factors of eating attitude. Methods: A total of 1 231 subjects were assessed using general information questionnaire, Kutcher Adolescent Depression Scale 11 item(KADS-11), Cognitive Flexibility Inventory(CFI), Eating Attitude Test 26(EAT-26). Data were analyzed by independent sample t-test, univariate linear regression, spearman correlation analysis and Logistic regression. Results: There were significant differences in EAT 26 among adolescents between genders and between those with or without depression(P<0.01). Statistically significant differences were observed in CFI, flexible control and KADS 11 among adolescents with or without eating disorders(P<0.01). The scores of EAT 26 was negatively correlated with CFI (r=-0.19, P<0.01) and flexible control(r=-0.23, P<0.01). And there was a significant positive correlation between EAT 26 and KADS 11(r=0.23, P<0.01). Female(OR=2.40, 95%CI=1.87-3.23), depression (OR=1.76, 95%CI=1.35-2.29) and poor flexible control (OR=1.94, 95%CI=1.48-2.54) were risk factors for eating disorders. Conclusion Female, individuals with depressive symptoms or with poor flexible control ability are more likely to have eating disorders which need more attention.