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.

Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To investigate the status quo and influencing factors of social isolation of parents of children with autism spectrum disorder in order to provide theoretical basis for clinical intervention measures.Methods:A total of 340 parents of children with autism spectrum disorder who visited the Children′s Developmental Behavior Center of Third Affiliated Hospital of Sun Yat sen University were selected by the convenience sampling method as research objects during July to November 2023. A cross-sectional survey was investigated by a general information questionnaire, General Alienation Scale, Social Avoidance and Distress Scale, Affiliate Stigma Scale, Family APGAR Index, Chinese Simplified Version of Social Support Scale, and Social Responsiveness Scale.Results:A total of 323 valid questionnaires were collected, including 235 mothers and 88 fathers; 33 individuals aged 25-29 years, 233 individuals aged 30-39 years, and 57 individuals aged 40-60 years. The subjective social isolation score of parents of children with autism spectrum disorder was 33.24 ± 4.92 and the objective social isolation score was 4.00(2.00,7.00). The results of multiple linear regression analysis showed that the subjective social isolation of parents of children with autism spectrum disorder was influenced by factors including self-assessed health status, whether they worked full-time or not, whether they were satisfied with the division of labor in the family caring for their children, affiliate stigma, family care, and social support (all P<0.05); and the objective social isolation of parents was influenced by factors including the severity of autism symptoms, self-assessed health status, affiliate stigma, and family care (all p<0.05). Conclusions:Parents of children with autism spectrum disorder had some degree of social isolation, and the level of subjective social isolation was higher than objective social isolation. Healthcare professionals should pay attention to parents of autistic children who have high levels of symptom severity, poor self-rated health, do not work full-time, and are dissatisfied with the division of labor in the family caring for their child, and take measures to reduce the affiliate stigma, and to increase the level of family care and social support, so as to improve the social isolation of parents of children with autism spectrum disorder.

Objective:To analyze the clinical data and to screen the mortality risk factors of necrotizing fasciitis (NF) secondary to intestinal fistulas (NFsIF).Methods:This study was a retrospective observational study. The data of all NFsIF cases who met the inclusion criteria and were admitted into Shandong Provincial Hospital Affiliated to Shandong First Medical University (hereinafter referred to as our unit) from January 2000 to October 2023, and in PubMed, Web of Science, Scopus, China National Knowledge Infrastructure, and Chinese Medical Journal Network databases from its establishment to October 2023 were retrieved and screened. Based on clinical outcomes, the cases were divided into survival group (47 males and 24 females) and death group (16 males and 7 females), and the mortality rate was calculated. Clinical data of patients in the two groups including age, underlying diseases (most related to NF), symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement, and intestinal management and wound management measures were compared and analyzed to screen the risk factors of death in 94 patients with NFsIF.Results:A total of 94 valid cases were collected, including 90 patients reported in the literature and 4 patients admitted to our unit, with the mortality rate of patients being 24.5% (23/94). Univariate analysis showed that there were no statistically significant differences in age, underlying diseases, symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement between patients in the two groups ( P>0.05); there were statistically significant differences in intestinal treatment and wound treatment between the two groups (with χ2 values of 17.97 and 8.33, respectively, P<0.05). Multivariate logistic regression analysis showed that both intestinal treatment measures and wound treatments measures were independent risk factors for death in 94 NFsIF patients, among which first-stage colostomy+late-stage reconstruction and negative presssure therapy had higher protective effects (with odds ratios of 0.05 and 0.27, respectively, 95% confidence intervals of 0.01-0.33 and 0.08-0.88, respectively, P<0.05). Conclusions:The mortality risk of patients with NFsIF is high. Based on comprehensive treatments, active intestinal and wound treatment may be the key to avoid death, with first-stage colostomy+late-stage reconstruction and negative pressure therapy having higher protective effects.

Objective:To explore the effects of intermittent oro-esophageal tube feeding (IOE) on the swallowing function, incidence of aspiration pneumonia, and nutritional status in patients with dysphagia after stroke.Methods:Randomized controlled trials (RCTs) published from the establishment of the database to October 1, 2020 were retrieved from PubMed, Embase, Web of Science, EBSCO, Elsevier, OVID, ProQuest, CNKI, VIP, and Wanfang database. Two researchers independently conducted literature search, screening, data extraction and quality evaluation based on systematic reviews using Cochrane 5.11. RevMan 5.3 was used for the Meta-analysis of the included literature.Results:A total of 21 articles were included, with a total sample size of 1 616, including 809 patients receiving IOE and 807 patients with nasal indwelling gastric tube feeding. The Meta-analysis showed that IOE could enhance the swallowing function of patients ( RR=1.31, 95% CI: 1.21-1.43, P<0.01) , reduce the incidence of aspiration pneumonia ( RR=0.43, 95% CI: 0.28-0.65, P<0.01) , increase hemoglobin content ( MD=6.73, 95% CI: 5.89-7.57, P<0.01) , serum total protein content ( MD=4.44, 95% CI: 3.69-5.20, P<0.01) , serum prealbumin content ( MD=17.45, 95% CI: 7.29-27.62, P<0.01) , and serum albumin content ( MD=1.72, 95% CI: 1.33-2.10, P<0.01) . Conclusions:IOE can improve the swallowing function, reduce the incidence of aspiration pneumonia, and improve the nutritional level of patients with dysphagia after stroke, which has positive significance in clinical practice.

Objective:To analyze the 99 Tcm-methylene diphosphonate single photon emission computed tomography/spiral computed tomography (SPECT/CT)fusion imaging of bone metastases in patients with lung cancer and to evaluate the value of SPECT/CT in differentiating metastases from benign bone lesions.Methods:A total of 113 patients with bone metastases from lung cancer confirmed by pathology underwent bone scintigraphy and SPECT/CT imaging.Metastatic bone sites,quantity,up-take of radiotracer,and CT manifestations of each lesion were analyzed via bone scintigraphy imaging and SPECT/CT fusion imaging.Results:A total of 482 lesions from 113 patients were analyzed in this study.Among them,429 lesions were metasta-ses.Metastatic sites included spine(50.6%),thorax (29.1% ),pelvis (17.0%),extremities (2.1%),and skull(2.1%).CT manifestations were osteoblastic (41.0%),osteolytic (50.3%),mixed (4.0%),and normal (4.7%).Among these lesions, the proportion of hot spots displayed on SPECT/CT pictures was 90.7%(389/429),and the proportion of lesions with normal uptake of radiotracer was 9.3%(40/429).There were 53 benign lesions in 23 patients with bone metastasis.Conclusions:The most frequent metastatic sites in patients with lung cancer are spine and thorax.Bone metastasis from squamous carcinoma is more com-mon than from other types of lung cancer.The common CT manifestations are osteoblastic.The sensitivity and specificity of SPECT/CT fusion images for the diagnosis of bone metastatic lesions of lung cancer are high.