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 analyze the current state of medication literacy among elderly patients with chronic diseases in urban areas of Beijing,identify its key influencing factors,and propose targeted improvement measures.Methods From February 1 to June 30,2023,a questionnaire survey was conducted among elderly chronic disease patients in 193 communities across 15 districts of Beijing using a convenience sampling method.Data was collected through face-to-face interviews,with a total of 787 questionnaires distributed and 755 valid responses received.The logistic regression analysis model was employed to systematically identify and evaluate the factors affecting patients'medication literacy.Results Among the 755 valid questionnaires collected,53.25%(402 cases)of patients met the medication literacy criteria.Regression analysis results showed that multiple factors significantly influenced medication literacy among elderly patients with chronic diseases,including using rural cooperative medical care or self-payment methods(OR=1.669,P=0.039),retaining medication instructions(OR=0.519,P=0.038),checking medication instructions before use(OR=1.993,P<0.01),and possessing the ability to understand medication instructions(partial understanding OR=2.805,P=0.038;fully understanding OR=3.084,P=0.022)as positive influencing factors;whereas having 2 to 3 chronic diseases(OR=0.574,P=0.039),taking 3 to 5 medications(OR=1.845,P=0.015),and experiencing drug-related problems(OR=1.993,P<0.01)were identified as negative influencing factors.Conclusion Multiple factors influence medication literacy among elderly patients with chronic diseases.To ensure the safety and efficacy of their medication use,It is recommended to implement targeted measures.These include revising patient medication guidance leaflets tailored to age,enhancing patients'understanding of drug instructions,and strengthening medication guidance and social support systems.

Objective To analyze the differences in aging-related information between Chinese and American drug instruction for common chronic disease in the elderly,and to propose policy recommendations for the aging-related drug instruction in China.Methods Ten common chronic disease treatment drugs for elderly patients were selected,and through the random sampling method,the drug manuals of one domestic manufacturer were randomly selected for each drug by the random number method,and one American drug manual was selected as a sample from the dailymed website,and the information related to elderly people in the various items of the drug manuals was statistically analyzed by using Excel for comparative analysis.The average reading level of the patient version of the U.S.drug instructions was calculated using the Readability Formulas Scoring System;the readability of the Chinese drug instructions was assessed by the Health Education Text Material Suitability Scale.Results Compared with the U.S.drug instruction,the drug instruction for common chronic diseases of the elderly in China were updated less frequently and at a slower pace;the drug instruction with information on medication for elderly patients were fewer than those of the U.S.drug instruction,and the content of the drug instruction was not well documented;and the drug instruction were poorly readable,which was not conducive to the comprehension of the elderly patients.Conclusion China is in urgent need of reforming the aging of drug instructions,and it is recommended that,for chronic disease medications for elderly patients,we should increase the number of clinical trials conducted on the elderly,improve and complete the drug information for the elderly in the drug instructions,and produce"drug instructions for elderly patients"that are suitable for the elderly to read and understand.

Objective To evaluate the status of home medication safety among elderly patients with chronic diseases and analyze its influencing factors in urban and rural areas of Henan Province.Methods Convenient sampling method was adopted.Data was collected through a designed and optimized questionnaire.Pharmacists conducted in-home surveys.Excel and SPSS 26.0 software were used for data analysis.Results A total of 352 valid questionnaires were analyzed.Most respondents were aged 60～70 years,with a female proportion of 56.2%,and 52.0%of them had a junior high school education or lower.The top-ranked chronic diseases were hypertension(62.2%)and hyperlipidemia(33.2%),and 61.1%of patients suffered from multiple chronic diseases.Antipyretic and analgesic drugs were most common in home medicine cabinets(90.1%).The proportion of drugs being stored in accordance with the instructions(46.9%)was slightly low,and 93.8%of the elderly handled expired drugs improperly.Awareness of medication guidance services was low(34.9%).Logistic regression analysis showed that factors such as education level and monthly income had significant effects on the understanding of drug package insert,rational drug storage,proper disposal of expired drugs,and awareness of medication guidance services(P<0.05).Conclusion There are still some potential safety risks in the home medication use of elderly patients with chronic diseases in urban and rural areas of Henan Province.It is necessary to enhance education on drug storage and medication guidance,particularly for low-income and less-educated groups,to improve the safety of home medication use.

Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that possess potential toxicity to the human body. The production and utilization of diverse emerging PFAS have resulted in widespread human exposure. Therefore, it is imperative to establish a quantitative methodology encompassing a wide range of PFAS for a comprehensive assessment of human exposure to these compounds. Objective To establish a high-throughput quantitative method for the simultaneous determination of 53 PFAS in human serum based on ultra-high-performance liquid chromatography-Q Exactive high resolution mass spectrometry (UPLC-Q Exactive HRMS). Methods The extraction recoveries of hydrophilic-lipophilic balance (HLB) column, weak anionexchange (WAX) column, and 96-well WAX μElution plate were compared to select the SPE column with the highest recovery. The retention time and peak shape of the target compounds were compared between ACQUITY UPLC BEH C₁₈ column and Accucore aQ column, and the more cost-effective column was chosen. The effects of adding different levels of ammonium formate (0, 2, 5 and 10 mmol·L⁻¹) in mobile phase on peak shape and target response were compared to determine the optimal buffer salt concentration. The optimal spray voltage was obtained by comparing −2 kV and −4 kV. The proposed method was validated from the aspects of selectivity, standard curve, limits of detection, precision, accuracy, and matrix effect. The method was applied to 142 umbilical serum samples. Results The best recovery rate (64%-118%) was achieved by using 96-well WAX μElution plate. The optimal separation and peak shape were obtained by utilizing Accucore aQ column with H₂O-methanol (containing 5 mmol·L⁻¹ ammonium formate) as the mobile phase. Less in-source collision and better target response were observed when the spray voltage was set to −2 kV. All target analytes had a good linearity, with R² > 0.99. The limits of detection ranged from 0.01 to 0.50 μg·L⁻¹, and the recovery ranged from 69% to 127% with the precision less than 26%. A total of 31 PFAS were detected in the 142 actual samples, among which 14 PFAS had a detection frequency over 50%. Perfluorooctanoic acid showed the highest median concentration of 4.16 μg·L⁻¹, followed by 6:2 chlorinated polyfluorinated ether sulfonate and perfluorooctane sulfonates (3.50 μg·L⁻¹ and 1.59 μg·L⁻¹, respectively). Conclusion In this study, we establish a UPLC-Q Excative HRMS method for simutanious determination of 53 PFAS concentrations in serum. This method has the advantages of wide coverage of PFAS, good selectivity, and easy operation, and is suitable for biological detection with a large sample size.

Objective: To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children. Methods: A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations. Results: The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05). Conclusion Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

Objective:To observe the changes of varicella zoster virus (VZV)-DNA load in aqueous humour samples in VZV-induced acute retinal necrosis (ARN) in the early stages of antiviral treatment.Methods:A retrospective observational clinical study. From April 2016 to April 2018, 24 patients with 24 eyes of VZV-induced ARN who were diagnosed by Department of Ophthalmology, Eye and ENT Hospital of Fudan University and received complete aqueous humor sampling were included in the study. Among them, there were 13 males with 13 eyes, 11 females with 11 eyes; 12 left eyes and 12 right eyes; the age was 52.0±9.5 years old (39-71 years old). The time from the onset of ocular symptoms to the diagnosis of ARN was 16.6±6.1 days (7-30 days). Best-corrected visual acuity (BCVA) and ultra-wide-field fundus imaging were performed in all affected eyes. The BCVA examination was carried out using the Snellen visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity. All patients were given intravitreal injection of 40 mg/ml ganciclovir 0.1 ml (including 4 mg of ganciclovir), 2 times a week, until the active necrotizing retinal lesions subsided, at most after the diagnosis 4 weeks, with a maximum of 9 injections. The follow-up period was 12.8±5.6 months. The aqueous humor samples were collected at presentation and 4, 7, 14, 21, 28 days after the initiation of antiviral therapy, and the VZV-DNA load was detected by real-time quantitative polymerase chain reaction. A plateau phase and a logarithmic reduction phase of the DNA load changes were observed after antiviral treatment began. Wilcoxon rank sum test was used to compare and analyze the differences in BCVA between the eyes at baseline and last follow-up.Results:The mean viral load at presentation was 8.6×10 7±1.3×10 8 copies/ml. The initial plateau phase last for an average of 7.4±2.4 days. In the following logarithmic reduction phase, the mean slope of the decline in viral load was -0.13±0.04 log/day, and the expected time for half reduction of the initial viral load was 2.5±0.7 days. After 28 days antiviral treatment, the viral load decreased to 1.7×10 5±1.8×10 5 copies/ml. In the course of the disease, rhegmatogenous retinal detachment occurred in 16 eyes. Before treatment and at the last follow-up, the logMAR BCVA of the affected eye was 1.1±0.6 and 0.8±0.7, respectively. The results of correlation analysis showed that the logMAR BCVA at the last follow-up was correlated with the initial VZV-DNA load ( r=0.467, P=0.033). Conclusion:The VZV-DNA load in the aqueous humor of eyes with VZV-induced ARN is significantly decreased after antiviral treatment, which is closely related to the clinical process of ARN.

Objective:To understand the evaluation of 90 pharmaceutical service posts by pharmacists in hospitals, so as to provide basis for rational allocation of pharmaceutical personnel in hospitals.Methods:A questionnaire survey was conducted among 2 582 hospital pharmacists in 31 provinces from August 2019 to April 2020. The survey contents included post classification, staffing qualification and scores related to drug safety.Results:Among the 90 pharmaceutical posts investigated, there were 39 posts with a safety correlation score of 5(the highest score), 36 with 4 and 15 with 3. There were 41 posts in advanced pharmaceutical care and 49 posts in basic pharmaceutical care. The minimum qualifications required was 21 posts with pharmacy related college degree or assistant pharmacist, 61 posts with pharmacy related or clinical pharmacy bachelor degree or pharmacist title, and 8 posts with higher qualification. Advanced pharmaceutical care posts had high drug safety relevance scores and high personnel qualification requirements, mainly involving drug treatment, scientific research and comprehensive management posts.Conclusions:Pharmacists with different qualifications should be allocated according to different levels of pharmaceutical care projects, which can reasonably allocate limited human resources and make the best of their talents.

By comparing the proportion of hospital pharmaceutical functions and work contents of different levels of pharmaceutical professionals at home and abroad, the authors divided pharmaceutical care in medical institutions into basic pharmaceutical care based on drug management and advanced pharmaceutical care based on drug treatment. Different pharmaceutical service levels created different pharmaceutical service values. Pharmaceutical classification service can stimulate the work potential of pharmaceutical professionals at all levels, improve the service level of pharmacists, and provide basis for the better distribution of medical costs in China.