[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

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: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective To investigate the effects of dynamic lung compliance(Cdyn)-guided indi-vidual positive end-expiratory pressure(PEEP)titration on pulmonary function in elderly patients undergoing laparoscopic colorectal cancer surgery.Methods Sixty-eight elderly patients were selected for laparoscopic radical resection of colorectal cancer,37 males and 31 females,aged 65-79 years,BMI<30 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using the random number table method:individualized PEEP group(group P)and control group(group C),34 patients in each group.In group P,the patients received recruitment maneuvers and PEEP titration test at immediately after intubation,immediately after establishing pneumoperitoneum-Trendelenburg position and immediately after pneumoperitoneum.The patients in group C received PEEP 5 cmH2 O during procedure.The three best titra-tion PEEP and the actual tidal volume(VT)in group P were also recorded.PaO2,PaCO2,PETCO2 10 mi-nutes after the tracheal intubation(T1),10 minutes(T2)and 1 hour(T3)after establishing pneumoperito-neum-Trendelenburg position,at the end of the surgery but before extubation(T4)were recorded,and the oxygenation index(OI),physiological dead space to tidal volume(Vd/VT),alveolar arterial oxygen differ-ence(A-aDO2),driving pressure,and Cdyn were calculated.Concentrations of interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),Clara cell secretoyr protein(CC16)and lung alveolar surface active sub-stances-D(SP-D)in the serum samples were determined by ELISA before anesthesia induction(T0)and 10 minutes after extubation(T5).Postoperative pulmonary complications(PPCs)were also recordrd.Results The individualized PEEP of Cdyn?guided PEEP titration was 4 cmH2O. Compared with group C, the PaO2 and OI in group C were significantly increased at T4, the Cdyn was significantly increased at T1,T3, and T4, the driving pressure was significantly decreased at T1 -T4, the serum concentration of CC16 was significantly decreased at T5 ( P < 0. 05). There were no significant differences in PaCO2, PET CO2,A?aDO2, and Vd/ VT between the two groups. There was no severe PPCs in the two groups. Conclusion Pressure?controlled ventilation modes combined with Cdyn?guide PEEP titration can increase the Cdyn, reduce thedriving pressure, and improve OI at the end of the operation, reduce the concentrations of CC16 at postop?eration, improve pulmonary function in elderly patients undergoing laparoscopic colorectal cancer surgery.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objective To develop a low-oxygen mixed gas generator to make up for the deficiencies of low-pressure chambers and load-resistant hypoxia trainers during pilot hypoxia tolerance testing.Methods The device prepared the low-oxygen gas with the principle of gas separation,which was composed of a Sunsource OLF1100D-220AF air compressor,a SMC IDG75SAM4-03 filter,a buffer tank,an AIR Products PA3010 integrated assembly,a control box,sensors and regulators.The sensors included the pressure sensor,flow sensor,concentration sensor and dew point temperature sensor,and the control box consisted of a main control board,a power supply module,a transmission module,a communication module,a display and a housing.The embedded control software of the device was developed with KEIL 5 and C++.Results The device developed prepared the low-oxygen gas with the volume fraction being 4％to 18％and the maximum error of volume fraction being 0.05％,and the main components of the prepared gas met the technical requirements of medical oxygen as stipulated in GB 8982-2009 Oxygen supplies for medicine and aircraft breathing.Conclusion The low-oxygen gas prepared by the device has its volume fraction precisely controlled and can be used for hypoxia tolerance testing and acclimation training for pilots.[Chinese Medical Equipment Journal,2024,45(7):24-28]

Aim To study the apoptosis of human hep-atoma cell line ( HepG2 ) induced by different polar parts of Arnebia euchroma ( Royle ) Johnst ( AE ) and to verify its anti-hepatoma effect by a mouse orthotopic liver cancer model so as to explore the anti-cancer effect of AE extract. Methods Firstly, MTT method and Annexin V-FITC/PI double staining method were used to detect the anti-proliferative and pro-apoptotic effects of each polar part of AE on HepG2 cells, and Western blot was used to detect the expression of Bcl-2 apoptosis family proteins incells. Based on the above experimental results, the effective parts with significant pro-apoptotic effect were screened out for anti-in situ liver cancer experiments in mice, and the organ indexes, liver function indexes and tissue sections of mice with orthotopic liver cancer before and after administration were evaluated. Results With the decrease of the polarity of AE extract,the anti-proliferation and pro-apoptotic effects on HepG2 cells were enhanced, and the anti-proliferation and apoptosis-inducing effects of AE petroleum ether fraction ( AEP) were the most significant. When AEP dose was 1.56 (μg • L

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*