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.

Functional experiment is an important part of training program of basic medical experiment technolo-gy in medical colleges,and a scientific laboratory management system is a prerequisite for ensuring the progress and training outcomes of the education.Based on the school-running concept of"small-scale elite edu-cation"in Peking Union Medical College,this paper expounds the progress of the construction of medical functional experiment teaching system in Peking Union Medical College from many aspects,such as the reform of medical functional experiment teaching,the construction of functional laboratory and so on,and puts forward some ideas for building of a qualified training laboratory,so as to provide reference for further deepe-ning the reform of experimental teaching and supporting sustainable development of teaching laboratory of medi-cal schools.

Political and value education of curriculum is necessary for universities to implement the fundamental task of cultivating morality and talents.Physiology and pharmacology are bridge courses connecting basic medicine and clinical medicine,and the nervous system is an important component of them.The exploration and practice of ide-dogical-political elements in the courses of nervous system physiology and pharmacology are of great significance in the curriculum of basic medical education and are essential for the cultivation of top-notch innovative talents.Our research group explored the integration of political and value education cases in the courses of neurophysiology and pharmacology,and conducted preliminary practice and summary thinking,providing reference for future research on political and value education in other courses.

Objective To analyze the prevalent characteristics,sequence type(ST),and blaOXA gene distribution of global Acineto-bacter pittii,and provide reference for prevention and clinical medication against this infection.Methods All the sequences of A.pittii genomes were downloaded in batch from NCBI by using Aspera software with deadline of November 30,2023,and perl script was used to extract the meta information of strains in batch from the downloaded GBK file.A self-made Perl program was utilized to extract the nucleotide coding sequence of the gene from each genome sequence file of A.pittii as the analysis database.BLASTN comparative analy-sis was implemented by using the allelic sequences of 7 housekeeping genes of the genus Acinetobacter Sp downloaded from the website as a query database to determine the ST of each genome.The nucleotide sequences of the blaOXA genes were downloaded from the NCBI pathogen resistance gene database and the self-written AMRG software was utilized to analyze the distribution of blaOXA gene among A.pittii.Results A total of 305 A.pittii genomes were obtained,which were mainly isolated from 1990 to 2020.The isolation rates showed an increasing trend of year by year with the highest isolation rate in 2015.The separation rates of the United States,China and Germany ranked in the top three positions,with the separation rates of 29.5％(90 strains),15.7％(48 strains),and 13.4％(41 strains),respectively.A total of 180(59.0％)specimens were sourced from humans,of which 42(23.3％)were from sputum,27(15.0％)from blood,and 15(8.3％)from skin and soft tissues.The 305 strains of A.pittii were assigned into 79 STs,among which ST93(14.4％),ST64(12.1％)and ST63(11.8％)accounted for the highest proportion.In the United States,China and Germany,the infections were mainly affected by ST64,ST63 and ST93,respectively.The 305 A.pitti carried the blaOXA gene except 6 strains,while the remained 299 strains carried 31 blaOXA variants,of which,252 blaOXA genes were found to own the carbapenemase hydrolysis activity and 146 strains carried blaOXA-500 gene.Conclusion There should be regional differences in the global distribution of A.pittii,and the high prevalence of the carbapenemase gene blaOXA suggested a potential trend of multi-drug resistance,which is worthy to be monitored.

Sudden unexpected death in epilepsy (SUDEP) refers to the sudden, unexpected and unexplained death of epilepsy patients, which is an important reason for the significant increase of the death risk of epilepsy patients. The risk factors of SUDEP are related to poor control of seizures, nocturnal seizures, prone position, antiepileptic drugs, comorbidity, etc. Epilepsy death caused by SUDEP has become a major public health problem. The latest progress in neuropathology and cardiopulmonary pathology of SUDEP was reviewed in this article.

Objective:To summarize the prenatal ultrasound features of fetal cleidocranial dysplasia (CCD) and provide references for clinical consultation.Methods:A retrospective analysis was conducted on the prenatal ultrasound features, genetic testing results, and prognosis of a CCD fetus diagnosed at Qingdao Women and Children's Hospital in June 2023. Relevant literature on CCD was retrieved from the CNKI, Yiigle, Wanfang, and PubMed databases including cases confirmed by genetic testing or postnatal clinical phenotype and imaging with relatively complete prenatal ultrasound information. The prenatal ultrasound features of CCD fetuses were summarized using descriptive statistical analysis.Results:(1) In this case, prenatal ultrasound at 25 weeks of gestation indicated widened cranial sutures with clear near-field intracranial structures, absence of the nasal bone, shortened and rigid bilateral clavicles, and mildly shortened bilateral femurs and humeri. Chromosomal karyotyping and chromosomal microarray analysis showed no abnormalities, but whole exome sequencing detected a RUNX2 gene mutation, leading to a diagnosis of CCD combined with the ultrasound phenotype. At 36 weeks of gestation, the mother experienced premature rupture of membranes and delivered a male infant vaginally. Bedside X-rays indicated bilateral wet lungs and bilateral clavicular dysplasia in the newborn. Telephone follow-up at 9 months showed no abnormalities in growth and development. (2) Literature review: Thirteen cases from 13 articles were included, along with this case, totaling 14 CCD fetuses. The main ultrasound phenotypes of CCD fetuses were clavicular dysplasia (12/14), incomplete cranial ossification (10/14), absence of the nasal bone (8/14), and shortening of the femur (12/14). Other ultrasound phenotypes included scapular dysplasia, short ribs, and increased interocular distance. Conclusion:Clavicular dysplasia and incomplete cranial ossification are the most specific signs of fetal CCD, while absence of the nasal bone and mild femoral shortening are secondary features of CCD.

Objective:To summarize and analyze the clinical and genetic characteristics of Chinese patients with adrenomyeloneuropathy (AMN).Methods:Clinical data were collected and analyzed retrospectively on AMN patients who were diagnosed by genetic testing in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from May 2008 to August 2022. Clinical characteristics of AMN patients with different types of gene mutations were compared. Loe score was used to evaluate the severity of white matter demyelinating, and the serum levels of very long-chain fatty acids (VLCFA) in patients with or without white matter demyelinating were compared. The motor function of the AMN patients was assessed using the Expanded Disability Status Scale (EDSS), and the association between EDSS scores and the course of disease was analyzed.Results:A total of 23 male patients with onset age of (29.52±9.91) years were included in this study. The first symptom of all patients was abnormal lower extremities, of which 17 patients showed stiffness and weakness in their lower limbs (73.9%, 17/23), and 6 patients showed numbness and pain in both lower limbs (26.1%, 6/23). The occurrence of symptoms was not related to the type of gene mutation. White matter demyelination occurred in 33.3% (7/21) of patients over a disease duration of (7.67±4.46) years. There was no statistically significant difference in serum VLCFA level between the white-matter demyelination group and the non-demyelination group. The EDSS score was positively correlated with the disease duration ( r=0.57, P=0.006). Sixteen ABCD1 gene mutations were found in this study, among which c.5_19delinsTCTCCAGG (p.P2Lfs *12) was reported for the first time. Four probands belonging to different families carried the c.1415_1416del (p.Q472Rfs *83) variant. Conclusions:Lower limb movement disorders and sensory dysfunction are the prominent clinical manifestations in AMN patients, with deterioration of motor function associated with the course of disease. AMN may be converted to cerebral type and VLCFA concentration is not associated with the phenotypic changes. The c.1415_1416del (p.Q472Rfs *83) mutation is a hot spot mutation of the disease.

OBJECTIVE To investigate the mechanism of Jianpi Yishen Huazhuo Recipe in regulating ovarian function in rats with polycystic ovary syndrome(PCOS) through the Bax/Bcl-2/Caspase-3 pathway. METHODS SD rats were fed with a high-fat diet combined with letrozole to establish a model of PCOS. The successfully modeled rats were randomly divided into blank control group, model group, high-, medium-, and low-dose Jianpi Yishen Huazhuo Recipe groups, as well as positive drug metformin group. ELISA was used to detect the serum levels of LH, T, and LH/FSH in each group of rats. HE staining was used to observe the morphology of ovarian tissue. Immunohistochemistry and Western blotting was used to detect the protein expression of Bax, Bcl-2, and Caspase-3 in ovarian tissues of rats. RESULTS ELISA results showed that the levels of LH, T, and LH/FSH in each dose group of Jianpi Yishen Huazhuo Recipe significantly decreased, while the level of FSH significantly increased. HE staining results showed that ovarian tissue in each dose group of Jianpi Yishen Huazhuo Recipe was significantly improved. Immunohistochemistry results showed that Bax expression increased in granulosa cells, interstitial cells, and luteal cells, while Bcl-2 expression increased in oocytes, luteal cells, and follicular fluid. Caspase-3 expression increased in granulosa cells, oocyte membranes, and interstitial cells. Western blotting results showed that the relative expression of Bax and Caspase-3 proteins decreased in each dose group of Jianpi Yishen Huazhuo Recipe, while the relative expression of Bcl-2 protein increased, and the ratio of Bax/Bcl-2 decreased. CONCLUSION Jianpi Yishen Huazhuo Recipe can improve ovarian ovulation function by downregulating the expression of Bax and Caspase-3 proteins in ovarian tissue of PCOS rats, reducing the ratio of Bax/Bcl-2, upregulating the expression of Bcl-2 protein, adjusting the process of ovarian cell proliferation and apoptosis, improving the ovarian microenvironment, regulating endocrine levels, and promoting follicular development and maturation.

Objective To evaluate the efficacy and safety of high intensity focused ultrasound(HFIU)combined with endometrial ablation in the treatment of adenomyosis(AM)patients with heavy menstrual bleeding(HMB).Method A total of 199 patients with AM combined with HMB who underwent HIFU treatment at the Obstetrics and Gynecology Center of Affiliated Hospital of Chengdu University of TCM from July 2020 to September 2022 were selected and divided into two groups according to the ablation range.The combined ablation group included 80 cases with lesion and endometrial ablation(endometrial ablation rate≥30%),while the lesion ablation group 119 cases with simple lesion ablation.A 1∶1 propensity score matching was performed on the two groups,resulting in 59 patients in each group.A 6-month follow-up was conducted.The clinical manifestations(menstrual volume,degree of dysmenorrhea,uterine and lesion volume),quality of life(MS-QOL,UFS-QOL),and postoperative adverse reactions between the two groups before and 6 months after surgery was compared.Results Menstrual volume,degree of dysmenorrhea,uterine and lesion volume,MS-QOL score,and UFS-QOL score of the both groups were improved 6 months after surgery,when compared to those before surgery(P<0.05).Significantly reduced menstrual volume,degree of dysmenorrhea,and lower MS-QOL score were observed in the combined ablation group when compared with the lesion ablation group(P<0.05),but there was no statistical significance in uterine and lesion volume and UFS-QOL score(P>0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05),but the combined ablation group had longer vaginal bleeding and fluid flow time(P<0.05).Conclusion The combined HIFU and endometrial ablation can effectively reduce menstrual flow,alleviate dysmenorrhea,and improve quality of life in patients with AM combined with HMB.Although it increases vaginal bleeding and fluid flow time,reasonable symptomatic management can effectively prevent the occurrence of adverse consequences such as infection.