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.

Myeloid derived suppressor cells (MDSCs) are a type of immature, differentiated, heterogeneous cells derived from the bone marrow. MDSC plays a dual role in parasitic infections. On the one hand, the cells can induce helper T cell 1/2 (Th1/Th2) immune responses by inducing host secretion of interferon-γ (IFN-γ), interleukin (IL)-4, and IL-13. On the other hand, they can also secrete IL-10, IL-17 and transforming growth factor-β (TGF-β) to induce regulatory T cells (Treg)/Th17 immune responses, thereby exerting immune protection or immune escape. This article provides a review of the research progress on the immune regulation of host T cells by MDSC in parasitic infections.

Radiation-induced brain injury (RBI) is one of the complications after radiotherapy for head and neck malignant tumors, which seriously affects the quality of life of patients. The pathophysiological mechanism of RBI is not completely clear. Current studies suggest that it is involved in a variety of cells in the central nervous system (CNS), whereas astrocyte, as the largest number of glial cells in the CNS, plays an important role in maintaining the CNS homeostasis and responding to CNS injury. In this article, the role of astrocytes in RBI was reviewed.

In order to improve the operation difficulties in the narrow space of the nasal maxillary sinus, the nasal continuum minimally invasive surgical robot system is designed. The ball-and-socket joints and NiTiNol tubes are used as the main body of the continuum structure to improve the degree of freedom. The hardware systems and software systems are designed. The security control policies are planned. Finally, the robot confirmed prototype experiments are conducted and the feasibility of continuum robot confirmed through master-slave control experiment and animal experiment.
Animals ; Biomechanical Phenomena ; Equipment Design ; Minimally Invasive Surgical Procedures ; Robotic Surgical Procedures ; Robotics ; Software

To optimize the process of hydrogenation reduction in the synthesis of apremilast (APST), 3-nitrophthalic anhydride (4) and (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethanamine-(S)-2-acetamido-4-methylpentanoate (7) were used as starting materials to synthesize (S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-4-nitroisoindoline-1,3-dione (8) by amination.Then compound 8 was reduced to (S)-4-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethyl) isoindoline-1,3-dione (9) with ammonium formate as hydrogen source and palladium hydroxide as catalyst.Finally, apremilast was obtained by the acetylation reaction with acetic anhydride.The structure of the products were verified by optical rotation, 1H NMR, 13C NMR, MS and elemental analysis.And the total yield of three steps was increased to 67.0%.The improved reduction process can avoid the special reaction of hydrogenation and pressurization, and reduce the safety risk and production costs with high commercial value.

Objective:To determine the characteristics of hospitalized newly diagnosed systemic lupus erythematosus (SLE) patients with high disease activity, and identify the risk factors.Methods:Data from 194 newly diagnosed SLE patients at Shanghai Renji Hospital between May 2013 and December 2018 were collected retrospectively. All patients were followed up for 1 year or until death. Patients' demographic, clinical, and laboratory characteristics on admission and medication history were retrospectively collected as baseline data. Patients were divided into two groups, lupus patients with infection (51 cases) and lupus patients without infection (143 cases). The method of univariate analysis of data depended on the data distribution type. Variables that suggested association in the univariate analysis ( P<0.05) were entered into Cox regression model. Results:Among 194 patients with newly diagnosed SLE, 21 cases (11%) died and 51 cases (26%) were infected during 1-year follow-up. Regarding the infection site, 34 cases (67%) had lung infection, 9 cases (18%) had central nervous system infection and 9 cases (18%) had blood stream infection. Common bacteria were identified in 19 cases (45%), followed by fungal infection in 18 cases (43%) and mycobacterium infection in 7 cases (17%). Among the 51 patients with infection, 38 patients (75%) had infection within the first 3 months after diagnosis, and mortality in this group was significantly higher than that in the uninfected group (39%, 15/38 vs 2%, 3/143 , P<0.01). Comparing baseline parameters between patients with 3-month infection and without, significant differences ( P<0.05) were detected in age (≥40 years), systemic lupus erythematosus disease activity index (SLEDAI) score (>10 points), Systemic Lupus International Collaborating Clinic (SLICC)/American College of Rheumatology(ACR) systemic lupus erythematosus damage index (SDI) (≥1 point), pericardial effusion, nephritis, gastrointestinal vasculitis, diabetes, lymphocyte count <0.8×10 9/L platelet count <100×10 9/L, serum creatinine >104 mmol/L and serum globulin level <20 g/L. Finally, clinically meaningful candidate predictors were included in the Cox regression model and it showed that lymphocyte count <0.8×10 9/L, nephritis and gastrointestinal vasculitis were independently predictive for 3-month infection in new-onset lupus patients. Conclusion:Understanding disease spectrums and risk factors of infection in newly diagnosed SLE patients will help clinicians to manage those patients with infection effectively to achieve favorable prognosis.

Objective: To explore the relationship among cognitive flexibility, depression and eating attitude of adolescents and the influencing factors of eating attitude. Methods: A total of 1 231 subjects were assessed using general information questionnaire, Kutcher Adolescent Depression Scale 11 item(KADS-11), Cognitive Flexibility Inventory(CFI), Eating Attitude Test 26(EAT-26). Data were analyzed by independent sample t-test, univariate linear regression, spearman correlation analysis and Logistic regression. Results: There were significant differences in EAT 26 among adolescents between genders and between those with or without depression(P<0.01). Statistically significant differences were observed in CFI, flexible control and KADS 11 among adolescents with or without eating disorders(P<0.01). The scores of EAT 26 was negatively correlated with CFI (r=-0.19, P<0.01) and flexible control(r=-0.23, P<0.01). And there was a significant positive correlation between EAT 26 and KADS 11(r=0.23, P<0.01). Female(OR=2.40, 95%CI=1.87-3.23), depression (OR=1.76, 95%CI=1.35-2.29) and poor flexible control (OR=1.94, 95%CI=1.48-2.54) were risk factors for eating disorders. Conclusion Female, individuals with depressive symptoms or with poor flexible control ability are more likely to have eating disorders which need more attention.

Objective To explore and compare the prognostic ability of the serum level of M2BPGi and MRI imaging technology for hepatic fibrosis. Methods 118 patients who were diagnosed as hepatitis C were enrolled from March 2014 to March 2015 in our hospital.Their baseline data were recorded,and they were texted by imaging examination of MRI.Then all patients were followed-up 2 years.The patients were divided into hepatic fibrosis group and control group according to the follow-up results.Univariate analysis and Cox model were used to show that the prognostic factors influencing the prognosis of hepatic fibrosis in patients;meanwhile,the statistical significance factors were calculated by ROC curve.Results The serological markers of IV-C,HA and serum level of M2BPGi in hepatic fibrosis group were higher than those in control group,but its ADC values of liver was lower than those in control group,and the difference was statistically significant(P < 0.05). COX regression analysis showed that the difference of M2BPGi(RR = 4.282,P = 0.003)and ADC values(RR = 0.654,P = 0.004). The ROC analysis of the hepatic fibrosis group and the control group showed that the AUC of the combination was 0.865,the sensitivity and specificity were 95.2%,60.5%,respectively.Conclusion The clinical value the com-bined prognostic of them is of high prognostic efficacy,which is hopeful to be used as an auxiliary prognostic meth-od in clinic.

Currently,although surgical aortic valve replacement (SAVR) is still the golden standard in treatment of severe aortic stenosis according to the guideline,transcatheter aortic valve implantation (TAVI) is gradually becoming a common treatment for patients who are prohibitive or in high risk for SAVR.Recently,the valve manufacturers,including medical companies in China,are making their utmost to develop valve device,leading remarkable results achieved by TAVI.With the complications being controlled,TAVI displays promising future.It is likely that TAVI is expected to become a substitute for SAVR to treat patients with aortic stenosis or even aortic regurgitation.

Objective To evaluate the efficacy of MRI-detected extramural venous invasion (mrEMVI) in predicting tumor responses to preoperative chemoradiatiotherapy (pre-CRT) in patients with locally advanced rectal cancer (LARC).Methods The clinicopathological data,tumor response and mrEMVI information of 47 LARC from February 2013 to December 2014 were retrospectively collected.mrEMVI was given 0-4 score according to the degree,3-4 score were defined as mrEMVI positive;patients with mrEMVI positive were divided into three subgroups according to vascular size (large,middle and small).Association between different mrEMVI subgroup and tumor response was analyzed using Fisher exact test.Result 26 patients were mrEMVI positive.18 and 8 patients scored 3 and 4 for mrEMVI positive,respectively;16,6 and 4 patients were small,middle and larger vessels of mrEMVI positive,respectively.Patients with mrEMVI positive had less TRG 0-1 than mrEMVI negative (P =0.019).Scored 4 and larger vessel of mrEMVI positive had less TRG 0-1 than mrEMVI negative (P =0.038 and 0.017).Conclusions mrEMVI positive score 4 or larger vessel predict poor tumor response to pre-CRT in patients of locally advanced rectal cancer.