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 evaluate the clinical efficacy of non-invasive high-frequency oscillatory ventilation (nHFOV) and nasal continuous positive airway pressure ventilation (nCPAP) as transitional breathing modes after evacuation from invasive ventilation in neonatal respiratory distress syndrome (NRDS).Methods:A randomized controlled trial was conducted using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases to search for all published literature before July 2022 on the treatment of NRDS with nHFOV and/or nCPAP after invasive ventilation and weaning. We compared the success rates of the evacuation , as well as the incidence of pneumothorax, bronchopulmonary dysplasia, and intraventricular hemorrhage between the nHFOV group and the nCPAP group in newborns who underwent invasive ventilation with NRDS.Results:A total of 7 randomized controlled studies were included, including 598 newborns diagnosed with NRDS who underwent tracheal intubation mechanical ventilation. The success rates of evacuating invasive ventilators for children in the nHFOV and nCPAP groups included in the article were calculated. The success rates of evacuating invasive ventilators for children in the two groups were 88.5%(231/261) and 66.5%(171/257), respectively. Compared with the nCPAP group, the success rate of evacuating invasive ventilators for children with NRDS in the nHFOV group was higher ( OR=3.93, 95% CI: 2.47-6.23, P<0.001). However, there was no statistically significant difference in the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, and pneumothorax between the two groups after weaning (all P>0.05). Conclusions:After weaning NRDS patients with invasive ventilation, nHFOV has a higher success rate in weaning compared to nCPAP, which is worthy of clinical application.

Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related death worldwide, with anaplastic lymphoma kinase (ALK) fusion mutations accounting for approximately 4%-9% of cases. In recent years, there are increasing clinical evidences suggesting that the combination of ALK inhibitors with surgical treatment holds significant potential for clinical application in resectable early and locally advanced non-small cell lung cancer (NSCLC) patients. This review aims to summarize the advances in neoadjuvant targeted therapy for ALK fusion positive NSCLC and discuss its advantages and challenges in clinical practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Anaplastic Lymphoma Kinase/antagonists & inhibitors* ; Lung Neoplasms/enzymology* ; Neoadjuvant Therapy/methods* ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use*

Magneto-acoustic-electric tomography (MAET) boasts high resolution in ultrasound imaging and high contrast in electrical impedance imaging, making it of significant research value in the fields of early tumor diagnosis and bioelectrical monitoring. In this study, a method was proposed that combined high conductivity liquid metal and maximum length sequence (M sequence) coded excitation to improve the signal-to-noise ratio. It was shown that, under rotational scanning, the liquid metal significantly improved the signal-to-noise ratio of the inter-tissue magneto-acoustic-electric signal and enhanced the quality of the reconstructed image. The signal-to-noise ratio of the signal was increased by 5.6, 11.1, 21.7, and 45.7 times under the excitation of 7-, 15-, 31-, and 63-bit M sequence code, respectively. The total usage time of 31-bit M sequence coded excitation imaging was shortened by 75.6% compared with single-pulse excitation when the same signal-to-noise ratio was improved. In conclusion, the imaging method combining liquid metal and M-sequence coding excitation has positive significance for improving MAET image quality.
Contrast Media ; Electricity ; Electric Conductivity ; Acoustics ; Tomography

Objective:To explore the effects and mechanisms of polycaprolactone-cellulose acetate (PCL-CA) nanofiber scaffold loaded with rat epidermal stem cells (ESCs) on wound healing of full-thickness skin defects in rats.Methods:The experiment research method was applied. The primary ESCs were isolated from 1-3 d old Sprague-Dawley (SD) rats (undefined gender) by rapid adherent method and cultured by rapid adherent method. ESCs of the first passage were used for the subsequent experiments after the positive expressions of integrin β 1 and cytokeratin 19 (CK19) in primary cells were identified respectively by flow cytometey and immunofluorescence method. PCL-CA nanofiber scaffolds with polycaprolactone and cellulose acetate as components were prepared by electrospinning technique. The topological structure of the nanofiber scaffolds was determined and the diameter of 25 fibers was measured by scanning electron microscope. The constructed PCL-CA nanofiber scaffolds were used as the culture substrate for ESCs, which were cultured in keratinocytes (KCs) medium to construct ESCs-nanofiber scaffold complex (hereinafter referred to as ESCs scaffold). After 3 days of culture, the morphology of ESCs in the scaffold and their relationship was observed by scanning electron microscopy. The ESCs in ESCs scaffold were set as PCL-CA nanofiber scaffold group, and the ESCs cultured with KCs medium in culture dishes coated with type Ⅳ collagen were set as type Ⅳ collagen group. Western blotting was used to detect the protein expression level of CK19 in ESCs in the two groups after 3 days of culture ( n=3). The protein expressions of CK19 and proliferating nuclear antigen (PCNA) in ESCs in the two groups were detected by immunofluorescence method after 7 days of culture. A circular full-thickness skin wound of about 2 cm in diameter was prepared on both left and right sides of the back of 15 male SD rats aged 6-8 weeks. The rats were then equally divided into blank control group without implantation, scaffold alone group implanted with PCL-CA nanofiber scaffold, and ESCs scaffold group implanted with ESCs scaffold which were constructed after 3 days of culture according to the random number table. The percentage of wound areas on post injury day (PID) 3, 7, 14, and 21 was calculated ( n=5). The new skin tissue at the wound edge was collected on PID 21, the wound healing quality was evaluated by Masson staining, and the protein expression levels of Notch1, Jagged1, and Hes1, which are key proteins of Notch signaling pathway, were detected by Western blotting ( n=3). Data were statistically analyzed with one-way analysis of variance, one-way analysis of variance, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results:The constructed PCL-CA nanofiber scaffolds had a porous, mesh-like, and multilayered three-dimensional structure, in which the surface of the fibers was smooth and non-porous, and the fiber diameter was (383±24) nm. The ESCs in ESCs scaffold showed intact cellular structures and were tightly attached to the scaffold after 3 days of culture. The cells were interconnected and fully extended on the surface of the scaffold to form a membrane. After 3 days of culture, the protein expression level of CK19 of ESCs in PCL-CA nanofiber scaffold group was significantly higher than that in type Ⅳ collagen group ( t=24.56, P<0.01). After 7 days of culture, compared with those in type Ⅳ collagen group, there was no significant change in the proportion of PCNA positive cells of ESCs in PCL-CA nanofiber scaffold group, while the proportion of CK19 positive cells was higher. On PID 3, 7, 14, and 21, the percentages of wound areas of rats in ESCs scaffold group were (78.0±1.8)%, (40.9±2.0)%, (17.9±1.1)%, and (5.0±1.0)%, respectively, which were significantly lower than (84.2±1.9)%, (45.4±2.6)%, (21.8±1.7)%, and (10.1±1.1)% in blank control group ( t=5.42, 3.09, 4.33, 7.58, P<0.05 or P<0.01) and (82.7±1.2)%, (44.8±2.0)%, (22.4±2.4)%, and (10.3±2.4)% in scaffold alone group ( t=4.98, 3.11, 3.84, 4.57, P<0.05 or P<0.01), while the percentages of wound areas of rats between blank control group and scaffold alone group were similar ( t=1.47, 0.39, 0.47, 0.22, P>0.05). On PID 21, the layer of new skin at the wound edge of rats in each group was intact; compared with that in blank control group or scaffold alone group, the new skin tissue at the wound edge of rats in ESCs scaffold group had more orderly collagen arrangement; the scaffolds in the new skin at the wound edge of rats were completely degraded in ESCs scaffold group and scaffold alone group. On PID 21, the protein expression levels of Notch1, Jagged1, and Hes1 in the new skin tissue at the wound edge of rats in scaffold alone group were similar to those in blank control group ( t=1.70, 1.94, 0.18, P>0.05), while the protein expression levels of Notch1, Jagged1, and Hes1 in the new skin tissue at the wound edge of rats in ESCs scaffold group were significantly higher than those in scaffold alone group ( t=13.31, 22.07, 20.71, P<0.01). Conclusions:PCL-CA nanofiber scaffolds can inhibit the differentiation of ESCs of rats without affecting their proliferation in vitro. ESCs scaffolds constructed through using PCL-CA nanofiber scaffolds as the carrier to culture ESCs of rats can significantly promote the wound healing of full-thickness skin defects in rats, and the mechanism may be related to the activation of Notch signaling pathway.

BACKGROUND:3D bioprinting has been used to print a variety of tissues including skin,vascular tissues,liver,cartilage,cardiac tissues,ear,and adipose tissues.OBJECTIVE:To review the application of 3D bioprinting technology in printing tissues or organs and its research progress in oral medicine.METHODS:A computer-based retrieval of PubMed and CNKI was performed to search articles concerning the application of 3D bioprinting technology in printing tissues,organs and stomatology which were published from 2006 to 2016,using the keywords of 3D bioprinting,3D pinting,organs,tissues,tissue engineering,stomatology,oral,cranio-maxillofacial in English and Chinese,respectively.RESULTS AND CONCLUSION:Direct cell-bioprinting is still in its early stage,even though 3D bioprinting has been applied to print various tissues such as skin,vascular tissues,liver,cartilage and cardiac tissues,etc.Although additive manufacturing technology has been widely used for printing different scaffolds of tissues and organs nowadays,there are no successful bioprinted tissues with biological functions in clinical practice.Even in oral medicine,most of the studies still remain in the stage of printing biological scaffolds.It is a long way to solve the problems such as source of cells,materials of biological scaffolds and types of extracellular matrix in the future,due to the complexity of human organism structure and the function expression of various tissues and organs.

Objective To investigated the etiologic characteristics of Shigella (S.) sonnei strains causing outbreaks and sporadic cases in some areas of Guangdong province and Guangxi Zhuang Autonomous Region during 2014-2016. Methods Fourteen S. sonnei strains isolated from outbreaks and 6 S. sonnei strains from sporadic cases from Guangdong and Liuzhou of Guangxi Zhuang Autonomous Region were tested for antimicrobial resistance and analyzed by pulsed-field gel electrophoresis (PFGE). Six typical strains were selected for whole genome sequencing typing and compared with 51 strains isolated both at home and abroad from NCBI genome database. Results The antibiotic resistance test indicated the isolates had high resistance rate to ampicillin, tetracycline, gentamicin, trimethoprim/sulfamethoxazole and nalidixic acid, while sensitive to azithromycin, chloromycetin and imipenem. PFGE showed high similarity (93.2%) among the strains isolated from different areas. The whole genome sequencing analysis also revealed that all the typical strains wereclustered into a same evolution branch, close to some strains from Korea. Conclusions The S. sonnei strains isolated from some areas of Guangdong and Guangxi Zhuang Autonomous Region showed high resistance to commonly used antibiotics, but they were sensitive to azithromycin, chloramphenicol and imipenem. The isolates in this study also showed similar PFGE patterns and close phylogenic evolution.

Objective To synthetize a novel MR molecular imaging probe named USPIO?PEG?tLyP?1,and to evaluate its value in detecting U87 cells by MR imaging. Methods USPIO?PEG?tLyP?1 was synthetized by conjugating USPIO?PEG with tLyP?1. Neuropilin?1 expression levels of glioma cell lines were detected by Western blot. The cytotoxicity of USPIO?PEG and USPIO?PEG?tLyP?1 were assessed by MTT colorimetric assay. The uptake efficiency of USPIO?PEG?tLyP?1 was measured by Prussian blue staining, transmission electron microscope and MR imaging in vitro. Results The novel MR molecular imaging probe was synthetized with an average diameter of 43.84 nm. U87 glioma cell line was screened as test subject for the highly expression of NRP?1(P<0.05). USPIO?PEG?tLyP?1 group showed much more intracellular blue particles than USPIO?PEG group after Prussian blue staining. After incubation,USPIO?PEG?tLyP?1 mainly existed in lysosme,endoplasmic reticulum and mitochondria. In vitro MRI showed that USPIO?PEG?tLyP?1 significantly enhanced the negative contrast effect compared with USPIO?PEG(P<0.01). Conclusion The decoration of tLyP?1 enhanced targeting ability of USPIO?PEG to glioma cells and MR molecular imaging can be a promising method for early diagnosis of gliomas.

OBJECTIVETo investigate the prevalence of hypertension in women with a history of preeclampsia (PE) and to estimate related risk factors.

METHODSIn this prospective case-control study, we collected clinical data from 809 women with a history of PE and 3 421 women with normal pregnancy from January 2008 to June 2012. Between November 2012 and April 2013, 651 women in PE group and 2 684 women with normal pregnancy group were recruited at the same time for collecting postpartum data including blood pressure, blood glucose and blood lipid. Binary logistic regression analysis was applied to analyze the relative factors of postpartum blood pressure.

RESULTSPrevalence of hypertension in PE group was higher than those with normal pregnancy (17.2% (112/651) vs. 1.1% (30/2 684), P < 0.01). Prevalence of hypertension in severe PE and mild PE patients was similar (20.1% (58/289) vs. 15.2% (55/362), P = 0.103). Binary logistic regression analysis indicated that progestational body mass index (OR = 1.379, 95% CI: 1.257-1.510, P < 0.05) , antepartum systolic blood pressure (OR = 1.025, 95%CI:1.012-1.040, P < 0.05) , antepartum triglyceride (OR = 1.002, 95% CI: 1.002-1.410, P < 0.05) , antepartum fasting blood glucose (OR = 1.733, 95% CI: 1.047-2.870, P < 0.05) , postpartum body mass index (OR = 1.279, 95% CI: 1.199-1.363, P < 0.05), postpartum fasting insulin (OR = 1.107, 95% CI: 1.055-1.162, P < 0.05) , systolic blood pressure difference between antepartum and postpartum (OR = 1.024, 95% CI :1.011-1.037, P < 0.05) , difference on triglyceride value between antepartum and postpartum (OR = 1.26, 95% CI: 1.069-1.486, P < 0.01), difference value of HOMA-IR between antepartum and postpartum (OR = 2.448, 95% CI: 1.330-4.500, P < 0.01) and difference value of high density lipoprotein cholesterol between antepartum and postpartum (OR = 1.699, 95% CI: 1.277-2.260, P < 0.05) were associated with hypertension after pregnancy.

CONCLUSIONSWomen with history of PE are associated with higher risk of postpartum hypertension. Increased blood pressure, abnormal glucose and lipid metabolism during pregnancy are major risk factors for postpartum hypertension.

Adult ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Case-Control Studies ; Cholesterol, HDL ; Female ; Humans ; Hypertension ; epidemiology ; Insulin ; Pre-Eclampsia ; epidemiology ; Pregnancy ; Prospective Studies ; Risk Factors ; Triglycerides

Objective To investigate the prevalence of hypertension in women with a history of preeclampsia ( PE) and to estimate related risk factors .Methods In this prospective case-control study , we collected clinical data from 809 women with a history of PE and 3 421 women with normal pregnancy from January 2008 to June 2012.Between November 2012 and April 2013, 651 women in PE group and 2 684 women with normal pregnancy group were recruited at the same time for collecting postpartum data including blood pressure , blood glucose and blood lipid.Binary logistic regression analysis was applied to analyze the relative factors of postpartum blood pressure .Results Prevalence of hypertension in PE group was higher than those with normal pregnancy ( 17.2%( 112/651 ) vs.1.1%( 30/2 684 ) , P<0.01 ).Prevalence of hypertension in severe PE and mild PE patients was similar (20.1%(58/289) vs.15.2%(55/362),P=0.103).Binary logistic regression analysis indicated that progestational body mass index ( OR =1.379, 95%CI:1.257-1.510,P <0.05), antepartum systolic blood pressure (OR =1.025,95%CI:1.012 -1.040,P<0.05), antepartum triglyceride (OR=1.002,95%CI:1.002 -1.410,P<0.05), antepartum fasting blood glucose(OR=1.733,95%CI:1.047-2.870,P<0.05), postpartum body mass index (OR=1.279,95%CI:1.199 -1.363,P <0.05), postpartum fasting insulin (OR =1.107,95%CI:1.055 -1.162,P <0.05), systolic blood pressure difference between antepartum and postpartum (OR =1.024,95%CI:1.011-1.037,P<0.05), difference on triglyceride value between antepartum and postpartum(OR=1.26,95%CI:1.069-1.486,P<0.01), difference value of HOMA-IR between antepartum and postpartum (OR=2.448,95%CI:1.330-4.500,P<0.01)and difference value of high density lipoprotein cholesterol between antepartum and postpartum (OR=1.699,95%CI:1.277 -2.260,P<0.05)were associated with hypertension after pregnancy .Conclusions Women with history of PE are associated with higher risk of postpartum hypertension.Increased blood pressure , abnormal glucose and lipid metabolism during pregnancy are major risk factors for postpartum hypertension .