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.

ObjectiveTo assess the coverage and effectiveness of COVID-19 vaccines in the elderly. MethodsThis study was conducted in Changning District of Shanghai， targeting people aged 60 years and above. Vaccination data between 21 December 2020 and 28 February 2022 was retrieved from the Shanghai Collective Immunization System. Information on confirmed cases of COVID-19 from March 2022 through May 2022 was collected from the National Notifiable Diseases Reporting System. Vaccine effectiveness was calculated using the screening method. ResultsAs of 28 February 2022， 69.89% of people aged ≥60 years had received ≥1-dose vaccine， 63.80% had received full primary vaccination and 31.91% had received a booster dose. Vaccination coverage declined over age， with the lowest coverage in the elderly aged ≥80 years. Moreover， COVID-19 vaccination provided the highest protection against severe/critical illness and death due to the Omicron variants in the elderly aged ≥60 years. Full primary vaccination showed 96.15%（95%CI：84.15‒99.06）of vaccine effectiveness and booster vaccination showed 100% of the effectiveness against severe/critical COVID-19 and death. ConclusionsFull primary and booster vaccination coverage in the elderly is low， especially in those aged 80 and above. Our study finds high protection against COVID-19 associated severe/critical illness and death from both full primary and booster vaccination of inactivated COVID-19 vaccines in the elderly aged ≥60 years.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L^-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.
Animals ; Anti-Inflammatory Agents/pharmacology* ; Biological Products/pharmacology* ; Indole Alkaloids/pharmacology* ; Porifera ; Structure-Activity Relationship

This review aims to interpret the interventions to improve physical function for children and young people with cerebral palsy, thus providing relevant suggestions.Relevant literatures published before November 2018 were systematically searched in Cochrane library, CINAHL, and Embase MEDLINE using the Grading of Recommendations Assessment, Development and Evaluation method.Consult with international experts and patients to assess evidence and recommend it.Based on 3 systematic reviews, 30 randomized clinical trials, and 5 pre-and post-treatment studies, a total of 13 recommendations were given.The guidelines recommend that, in order to achieve functional stan-dards, intervention measures should include, patient-selected goals, full-task practice in real-life settings, support for family empowerment, and a team approach.The age, ability, and child/family preferences were all needed to be considered.In order to improve walking ability, ground walking and treadmill training can be carried out.Various methods can promote the realization of hand use goals hand use, including the two-hand exercise training, constraint-induced moverment therapy, goal-oriented training and cognitive therapy.In terms of patient self-care, the guideline proposed that, the combination of full-task practice and auxiliary equipment can improve the independence of self-care and reduce the burden of care givers.Leisure goals could be achieved by the combination of the practice of the entire task with strategies to address environmental, personal, and social barriers.The intervention of children and adolescents with cerebral palsy should take into consideration of patient selection and the goal of full-task practice.The child/family preference, age and ability should be considered when clinical workers selecting specific interventions.

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ² test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology* ; Blood Transfusion ; Female ; Gastrointestinal Neoplasms/surgery* ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVE: To analyze the proliferation potential of bone marrow-derived mesenchymal stem cells (MSC) in patients with myelodysplastic syndrome (MDS). METHODS: The MSC derived from the 24 patients with newly diagnosed MDS (MDS-MSC group) and MSC derived from 15 patients with nutritional anemia (control group) in the Affiliated Hospital of Hebei University were used as the research objects. The proliferation potential of MSC was analyzed by colony-forming unit assay, doubling time, cumulative passaging, cell number after 10 days of culture with equal amount of MSC and MTT experiment. The mechanism of abnormal proliferation was analyzed by cell cycle experiment, apoptosis experiment and p21 gene expression assay. RESULTS: In the colony forming unit assay, the number of MDS-MSC colonies was 4.44±2.51, which was significantly lower than that of the control group (12.44±2.55)(P<0.01); the doubling time of MDS-MSC group was significantly longer than that of the control group (7.80±3.26 vs 3.63±0.85) (P<0.01); the number of MDS-MSC in 5×10 CONCLUSION The proliferative capability of MDS-MSC is significantly reduced, which relates with the arrest of cell cycle in G
Apoptosis ; Bone Marrow Cells ; Cell Proliferation ; Humans ; Mesenchymal Stem Cells ; Myelodysplastic Syndromes

Objective:To explore the relationship between somatic symptoms of major depressive disorder(MDD)and cortisol(COR) rhythm, C-reactive protein(CRP) and other immune-metabolism-related indicators, and understand its mechanism from the perspective of endocrine and immune regulation.Methods:A case-control study was conducted in hospitalized patients with MDD who met DSM-5 diagnostic criteria.According to the Patient Health Questionnaire (PHQ-15), PHQ-15 ≥10 were classified as the somatic major depressive disorder group(S-MDD group) and 73 patients were enrolled.PHQ-15 <5 was classified as the non-somatic depressive disorder group (NS-MDD group) and 70 patients were enrolled.Plasma cortisol (COR8, COR16 and COR24) levels were measured at 8∶00, 16∶00 and 24∶00 on the same day, plasma CRP and interleukin-6 (IL-6) level, serum uric acid (UA), blood glucose (GLU), blood lipid (TC, TG, HDL, LDL) level were detected at 8∶00.Independent sample t test, non-parametric test, chi-square test, repeated ANOVA, covariance analysis, and multivariate Logistic regression were used for statistical analysis. Results:①Time effect, grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant ( P<0.05). Covariance analysis excluded age as an influential factor, COR16, AUC(total cortisol output/area under the curve, AUC) and COR8-16 in S-MDD group ((90.50±40.57)μg/L, (1 425.12±564.78), (-6.43±5.76))were higher than those in NS-MDD group((68.74±31.51)μg/L, (1 251.57±456.61), (-8.77±5.48)), and the difference was statistically significant ( F=8.971, 4.320, 8.731, P<0.05). ②CRP in S-MDD group ((1.41±1.06)mg/L) were higher than that in NS-MDD group((0.61±0.53)mg/L), and the difference was statistically significant ( F=25.436, P<0.05). The proportion of patients with higher CRP level(CRP≥1 mg/L) in S-MDD group(58%) was higher than that in NS-MDD group(23%), and the difference was statistically significant(χ 2=17.824, P<0.01). ③Multivariate logistic regression analysis found that CRP ( OR=4.953, 95% CI: 2.407-10.193), COR8-16 ( OR=3.451, 95% CI: 1.380-8.633) were main risk factors of somatic symptoms of MDD ( P<0.05). Conclusion:Cortisol rhythm disturbance and high CRP level may be the biological basis of somatic symptoms in patients with MDD.

This article reported a case of malignant pheochromocytoma and paraganglioma with cranial metastasis. The patient was a 25-year-old man. At the age of 10, he was diagnosed with retroperitoneal paraganglioma. He received radiotherapy after partial resection of the tumor. At the age of 15, when he consulted for headache and hypertension, a space occupying lesion was found on the right adrenal without further diagnosis and treatment. His headache and hypertension were aggravated at the age of 25. Then he visited our medical center and diagnosed with right adrenal pheochromocytoma. He undertook an operation to remove the right adrenal lesion, and his blood pressured could be controlled in the normal range with oral antihypertensive medication. One year after the surgery, a cranial lesion with positive 131I-metaiodobenzylguanidine imaging was found following the increase of norepinephrine and dopamine in both blood and urine. The diagnosis of malignant pheochromocytoma with cranial metastasis was confirmed. The cranial lesion was treated with cyberknife therapy for 4 times, and the lesion was slightly reduced. Four year after the removal of right adrenal tumor, he developed multiple bone metastasis in the right ribs and left ilium, and then he received 131I-metaiodobenzylguanidine radiotherapy. Additionally, the results of gene test indicated a pathogenic mutation of SDHB. During the follow-up period of one year after the treatment, his blood pressure fluctuated to about 140/90mmHg with 10mg of phenoxybenzamine once a day. The case is a malignant pheochromocytoma with multiple bone metastasis characterized by a long course with an ideal prognosis in a way. Consequently, we suggested the diagnostic pathway with genetic testing based on clinical phenotype to approach more timely diagnosis and reasonable evaluation of the prognosis in pheochromocytoma and paraganglioma. Furthermore, clinicians should pay more attention to the long-term surveillance.

Objective::Based on gene array technology, gene set enrichment analysis (GSEA) and immune infiltration analysis were performed on chip data of intracranial aneurysm (IA) mRNA expression profile, in order to provide theoretical basis for understanding the formation mechanism of IA. Method::The GSE75436 raw data were obtained from the gene expression omnibus (GEO). GSEA of biological process (BP) in gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) signaling pathways were analyzed for gene expression profile by R software. The CIBERSORT deconvolution method was used to analyze the infiltration ratio of 22 types of immune cells in the expression profile. And COREMINE database was used to predict traditional Chinese medicines (TCMs), which were significant correlation with the enrichment result. Result::The GSEA results showed that the changes in gene expression of IA samples mainly involved in the regulation of cytokines, activation and differentiation of leukocyte, inflammatory immune response and other processes. The infiltration matrix analysis of immune cells showed that mast cells resting and neutrophils were significantly reduced in IA samples. The comparison of paired samples showed that mast cells and natural killer cells (NK cells) were significantly activated in the IA samples of the same individual, while neutrophils and T cells CD4 naive were significantly reduced. Through COREMINE prediction, it was found that Stephaniae Tetrandrae Radix was correlated with the activation of granulocytes, Sapindi Mukorossi Semen and Pistaciae Chinensis Cortex were correlated with the activation of neutrophils, Trichosanthis Semen, Paeoniae Radix Alba and Ligustri Lucidi Fructus were correlated with the cytotoxicity mediated by NK cells. Conclusion::Activation of mast cells and NK cells are closely associated with the occurrence and development of IA. The inflammatory immune processes and pathways such as nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway and cytotoxicity mediated by NK cells may be important factors in the pathogenesis of IA, and TCMs such as Stephaniae Tetrandrae Radix may be the potential molecular drug sources.