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 compare the efficacy and safety of low-dose and standard-dose radiotherapy (LD-RT vs. SD-RT) in the treatment of oropharyngeal cancer patients with positive human papillomavirus (HPV). Methods:All comparative studies of low-dose versus standard-dose radiotherapy in the treatment of HPV-positive oropharyngeal cancer were searched from PubMed, Web of Science, Cochrane Library, EMbase, Chinese Biomedical Literature Database (CBM), CNKI, Chongqing VIP, and Wanfang databases from January 1, 2000 to February 9, 2023. According to the inclusion and exclusion criteria, the data were strictly screened, and the RevMan 5.4 software was used for meta-analysis.Results:A total of 8 studies were included. The pooled results showed that the overall survival (OS) and progression-free survival (PFS) of patients in the LD-RT group were similar to those in the SD-RT group ( HR=0.83, 95% CI=0.59-1.18, P=0.31; HR=0.97, 95% CI=0.53-1.78, P=0.92), but the rate of percutaneous endoscopic gastrostomy (PEG) insertion was significantly reduced ( RR=0.45, 95% CI=0.28-0.72, P=0.001). Conclusion:LD-RT yields similar efficacy and lower rate of PEG insertion compared with SD-RT in HPV-positive oropharyngeal neoplasm patients.

BACKGROUND:Bioactive glass is a multifunctional synthetic composite material that releases active ions slowly and exhibits certain biological activities after affinity with tissues.Their versatility stems from the versatility of their preparation processes and components,allowing them to be applied in different clinical scenarios. OBJECTIVE:To review the main application forms,application fields of bioactive glass,as well as the influence of doping different elements on its function. METHODS:A literature search was conducted across WanFang Medical Database,CNKI Database,PubMed Database,and Web of Science Database,using the search terms"bioactive glass,slow-release ions,bone tissue engineering,composite scaffold,tissue regeneration and repair,biomedical engineering"in Chinese and English.The timeframe was limited from 2000 to 2023.Finally,88 articles were included for review. RESULTS AND CONCLUSION:(1)In terms of application forms,bioactive glass can be fabricated as coatings,particles,bone cements,and scaffolds according to needs.Coatings have the potential to enhance the biological activity of implants,yet they are susceptible to instability as a result of degradation.Particles offer a viable solution for the repair of irregular bone defects;however,particles produced through traditional methods often possess limited functionality.Bone cement provides the benefits of minimal invasiveness and injectability,yet its application is restricted to smaller bone defects.Scaffolds exhibit excellent mechanical properties and are commonly used for larger-sized bone defects,yet they have limited toughness.(2)In terms of applications,bioactive glass can be used in a variety of tissue regeneration and repair and disease treatment fields,including dentistry,orthopedics,soft tissue engineering,and cancer.(3)In terms of element doping,the addition of specific elements to bioactive glass not only improves its mechanical properties but also endows it with special biological functions such as bioactivity,degradability,and antibacterial properties.(4)Biologically active glass is a versatile material that can be used in different forms and functions by adjusting the preparation process and element doping to meet various clinical needs in bone tissue engineering and is widely used in the field of biomedical engineering.

Objective:To study the dosimetry effects of differently selected values of control point(CP)in Monaco radiotherapy planning system on dynamic intensity modulated radiation therapy(dIMRT)for esophageal cancer of middle and lower segment.Methods:Thirteen patients with esophageal cancer at middle and lower segment who received dIMRT in Shangluo Central Hospital from January to June 2023 were selected.In the Monaco radiotherapy planning system,nine groups of dIMRT plans were designed for each patient according to the 9 kinds of CP limit values(10,20,30,40,50,60,70,80 and 90).There were not changes in other optimized parameters except CP parameter.The differences of the dosimetry between target region and organs at risk(OAR)included lung,heart and spinal cord were analyzed.Results:With the increase of the CP limit value,the maximum dose of the target region which was radiation dose(D2%)of 2%volume of target region,the mean dose,which was radiation dose(D50%)of 50%volume of target region,and the homogeneity index(HI)appeared a trend of gradual stability after reduction,and the radiation dose(D98%)of 98%volume of target region which was the minimum dose of target region and the conformance index(CI)appeared a trend of gradual stability after increase.There was not significant in each dose indicator of OAR(P>0.05).The variation ranges of lung at 5,10,20,30 Gy dose(V5,V10,V20 and V30)were respectively 1.13%,0.75%,0.29%and 0.19%,and the maximum deviation of mean dose(Vmean)of lung was 18.7 cGy.The variation ranges of V10,V20,V30 and V40 in the heart were respectively 2.2%,1.23%,1.39%and 1.12%,and the maximum deviation of Vmean in the heart was 63.85 cGy,and the maximum deviation of Dmax in the spinal-cord was 70.78 cGy.There were statistically significant differences in the actual CP number(CPs),execution time(DT)of plan,and ratio value of machine unit(MU)of the complexity of plan to CPs(MU/CPs)among the plans of 9 groups(F=2.857,25.145,135.467,P<0.05),respectively.Conclusion:In the dIMRT plan of esophageal cancer of middle and lower segment,the maximum CP value is set at between 40-50,which can reduce the optimization time of the plan,the number of subfields and the treatment time of patients under the premise of meeting the dose of the target region and the OAR.

As an online and offline mixed teaching method,the"1233"ideological and political teaching reform in Medical Immunology can improve students'independent learning ability,thinking ability,practical ability,ideological and political literacy.It has been piloted on a large scale at Fenyang College of Shanxi Medical University.Moreover,the quality course on the Wisdom Tree online platform has been recognized as the second batch of national first-class quality course.Currently,thirty universities have chosen this quality course.Starting from the actual development of the current"1233"ideological and political teaching reform,this paper uses the SWOT analysis method to systematically analyze the internal advantages and weaknesses,as well as the opportunities and threats of the external competitive environment of the course.Based on this,propose some relevant improvement suggestions and directions,and provide important support for the subsequent optimization and improvement of"1233"ideological and political teaching reform in Medical Immunology.

Objective To compare the safety and efficacy of endovascular treatment(EVT)transradial approach and transfemoral approach in patients with acute ischemic stroke with large vessel occlusion in the posterior circulation.Methods Patients with acute ischemic stroke with large vessel occlusion in the posterior circulation admitted to the Stroke Center of Linyi People's Hospital,Shandong Second Medical University from February 2022 to April 2024 were retrospectively recruited.The baseline and clinical data were collected,including age,sex,past medical history(hypertension,diabetes mellitus,hyperlipidemia,atrial fibrillation,coronary artery disease,myocardial infarction and stroke),smoking,blood pressure at admission,National Institutes of Health stroke scale(NIHSS)score at admission,modified Rankin scale(mRS)score before the onset of stroke,Alberta stroke program early CT score(ASPECTS),whether intravenous thrombolysis was performed,volume of core infarct zone,volume of hypoperfused zone,occlusion location,etiology of stroke,time indexes(including time from onset to door,time from door to arterial puncture,arterial puncture to recanalization,and time from onset to revascularization),anesthesia modality,EVT first-line strategy,number of passes and whether with vascular access conversion.Clinical data included 90-day postoperative mRS scores,postoperative puncture site complications in 24 hours,symptomatic intracranial hemorrhage at 72 hours postoperatively,modified thrombolysis in cerebral infarction(mTICI)grade at the last angiography introperative and length of stay.The groups were categorized into transradial(TRA)and transfemoral(TFA)groups according to the final access route for EVT.The baseline and clinical data of the two groups were compared.Results A total of 129 patients underwent EVT with acute ischemic stroke with large vessel occlusion in the posterior circulation were finally included,including 47 patients in TRA group and 82 patients in TFA group.The differences about sex,age,past medical history,smoking,blood pressure at admission,NIHSS score at admission,mRS score before the onset of the stroke,ASPECTS,whether intravenous thrombolysis was performed,volume of core infarct zone,volume of hypoperfused zone,occlusion location,etiology of stroke,anesthesia modality,EVT first-line strategy,number of passes,mTICI grade at the last angiography introperative and other aspects were not statistically significant(all P＞0.05).The good prognosis rate at 90 d after surgery(53.2％[25/47]vs.48.8％[40/82],P=0.630),distribution of mRS scores at 90d postoperatively(P=0.991),all-cause mortality at 90 days after surgery(27.7％[13/47]vs.28.0％[23/82],P=1.000),rate of good recanalization(mTICI grade≥2b)on intraoperative last angiogram(97.9％[46/47]vs.95.1％[78/82],P=0.436),rate of complication of puncture site(4.3％[2/47]vs.12.2％[10/82],P=0.209)between the two groups were not statistically significant.The time from door to arterial puncture was significantly longer in the TRA group than in the TFA group,and the difference between the two groups was statistically significant(122.00[95.00,153.00]min vs.105.00[80.25,118.00]min,Z=-2.937,P=0.03);average length of stay in the TFA group was significantly longer than that of the TRA group,and the difference between the two groups was statistically significant(6.00[4.95,7.05]d vs.7.00[6.95,8.88]d,Z=-2.573,P=0.010).Conclusions Patients who underwent EVT via radial or femoral artery approach with acute ischemic stroke with large vessel occlusion in the posterior circulation had similar safety and efficacy,and the number of days of hospitalization was shorter via the TRA.However,more large prospective randomized controlled clinical trials are needed to validate the results of this study.

The improvement of food labeling can improve consumers' health awareness, reduce the burden of chronic diseases on the health and economy, and promote the development of the healthy food industry. Disease Risk Reduction Claim has been developed in European Union and the U.S. for over 20 years, with mature management methods and experience, but it is still lacking in China. Learning and drawing on the international management experience of food disease risk reduction claims can assist China to establish food disease risk reduction claims and improve the food health claims and labeling system.
Humans ; United States ; European Union ; Food Labeling ; Food Industry ; China/epidemiology*

The improvement of food labeling can improve consumers' health awareness, reduce the burden of chronic diseases on the health and economy, and promote the development of the healthy food industry. Disease Risk Reduction Claim has been developed in European Union and the U.S. for over 20 years, with mature management methods and experience, but it is still lacking in China. Learning and drawing on the international management experience of food disease risk reduction claims can assist China to establish food disease risk reduction claims and improve the food health claims and labeling system.
Humans ; United States ; European Union ; Food Labeling ; Food Industry ; China/epidemiology*

OBJECTIVE: To explore the clinical characteristics and molecular genetic mechanism of a fetus with recombinant chromosome 8 (Rec8) syndrome. METHODS: A fetus who was diagnosed with Rec8 syndrome at the Provincial Hospital Affiliated to Shandong First Medical University on July 20, 2021 due to high risk for sex chromosomal aneuploidy indicated by non-invasive prenatal testing (NIPT) (at 21st gestational week) was selected as the study subject. Clinical data of the fetus was collected. G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out on the amniotic fluid sample. Peripheral blood samples of the couple were also subjected to G banded karyotyping analysis. RESULTS: Prenatal ultrasonography at 23rd gestational week revealed hypertelorism, thick lips, renal pelvis separation, intrahepatic echogenic foci, and ventricular septal defect. The karyotype of amniotic fluid was 46,XX,rec(8)(qter→q22.3::p23.1→qter), and CMA was arr[GRCh37]8p23.3p23.1(158049_6793322)×1, 8q22.3q24.3(101712402_146295771)×3. The karyotype of the pregnant woman was 46,XX,inv(8)(p23.1q22.3), whilst that of her husband was normal. CONCLUSION The Rec8 syndrome in the fetus may be attributed to the pericentric inversion of chromosome 8 in its mother. Molecular testing revealed that the breakpoints of this Rec8 have differed from previously reported ones.
Humans ; Fetus/abnormalities* ; Chromosomes, Human, Pair 8 ; Female ; Pregnancy ; Karyotyping

Butyrate, normally produced by probiotics in the gut, not only provides energy for cells, but also changes the phosphorylation, acetylation and methylation levels of many proteins in cells. As a result, it affects the expression of many genes and the transmission of cell signals. Through G protein-coupled receptors, butyrate promotes the secretion of intestinal mucus and the formation of epithelial barriers, and attenuates the impacts of the pathogenic bacteria and their metabolites on human body. The Toll-like receptors (TLRs) are a group of pattern recognition receptors, and their activation causes the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus and eventually leads to expression and secretion of various pro-inflammatory factors and chemokines. The expression of TLRs is also involved in the pathogenesis of some inflammatory diseases and tumors. The purpose of this review is to summarize the effects of butyrate on TLRs and their downstream signaling pathways. We not only summarized the production of butyrate, the expression of TLRs and the influence of their interaction on the body under the conditions of inflammation and tumor, but also discussed the potential role of butyrate as a bacterial metabolite in the treatments of some human diseases.
Humans ; Butyrates ; Toll-Like Receptors ; Acetylation ; Phosphorylation ; Inflammation