Apolipoprotein B mRNA editing enzyme catalytic polypeptide like 3A(APOBEC3A)mutation is a major driver of cervical cancer.APOBEC3A and human papilloma virus(HPV)is closely related.On the one hand,APOBEC3A can effectively inhibit HPV infection;on the other hand,it can promote the integration of HPV DNA into cervical keratinocytes.This paper reviews the complex interaction between HPV and APOBEC3A,and analyzes the involved viral mechanism and cellular signal pathway.A large number of studies have confirmed that APOBEC3A gene can effectively induce the evolution and development of a variety of malignant tumors,including cervical cancer.However,APOBEC3A protein level is not so high in cancer cells in clinic.This paper also discusses the significance and the potential therapeutic value of APOBEC3A activity in cervical cancer.

Objectives:To compare the efficacy of the combination of excimer laser coronary angioplasty(ELCA)and drug-coated balloon(DCB)for in-stent restenosis(ISR)and to evaluate the impact of neointimal tissue characteristics on treatment outcomes. Methods:A total of 96 ISR lesions from 86 patients who underwent optical coherence tomography(OCT)evaluation and DCB with or without ELCA treatment at The First Medical Center of Chinese PLA General Hospital from January 2019 to May 2023 were retrospectively analyzed.ISR lesions were divided into ELCA+DCB group(n=30)and DCB group(n=66).Additionally,ISR lesions were classified as homogeneous and non-heterogeneous patterns based on the OCT characteristics of the neointimal tissue,and the impact on acute lumen gains was compared between different ISR patterns.Acute lumen gain(ΔMLA)was defined as the changes in minimum lumen area before and after the intervention. Results:The ELCA+DCB group had a significantly greater ΔMLA than the DCB group([3.2±0.8]mm2 vs.[2.6±1.4]mm2,P=0.015).Among the ISR with a homogeneous pattern,the ΔMLA of the ELCA+DCB group was significantly greater than that of the DCB group([3.0±0.9]mm2 vs.[2.2±1.1]mm2,P=0.030).There was no significant difference in ΔMLA between the two ISR groups with the non-homogeneous pattern([3.4±0.7]mm2 vs.[3.2±1.5]mm2,P=0.533).There was no death,the rate of target lesion revascularization was similar between the patients with lesions receiving DCB treatment and patients receiving ELCA +DCB treatment(7.4%vs.4.2%,P＞0.05). Conclusions:The combination of ELCA and DCB is an effective strategy for treating ISR,which can achieve greater acute lumen gain compared to DCB treatment alone,especially for the treatment of homogenous ISR pattern characterized by OCT.

This paper mainly discusses the practical significance of the internal quality assurance system of graduate students in a military medical university based on training process management. The integrated internal quality assurance system follows the direction of three core steps—course learning, scientific research practice training, and dissertation writing, and highlights nine key points—learning foundation in admission education and training, knowledge acquisition in course learning, application ability in teaching and scientific research practice, innovation ability in academic activities and innovation competitions, topic selection quality in thesis proposal, training quality in mid-term assessment, paper quality in dissertation writing, output quality in thesis defense, and comprehensive quality in diploma awarding. Our exploration and practical experience is shared in this article.

Objective To explore the relationship between phenotypic changes of retinal microglia and retinal ganglion cells(RGCs)death after optic nerve injury.Methods Male C57BL/6J mice(6 to 8 weeks old)were randomly divided into 1-,3-,7-,and 14-day injury groups and sham operation group,with 4 mice in each group.The eyes in the injured groups were inflicted with optic nerve crush(ONC),while the eyes of the sham operation group were treated with the same operation procedure but without optic nerve clamp.Flash visual evoked potential(fVEP)and immunofluorescence staining were employed to evaluate the impact of optic nerve injury on visual function and number of RGCs.RT-qPCR and immunofluorescence staining were applied to detect the effecy of optic nerve injury on phenotypic changes in retinal microglia.Results fVEP results showed that the visual conduction of the injured eye was gradually decreased over time when compared with that of the sham group(P＜0.01).Immunofluorescence staining revealed that the number of RGCs was lost mainly within 7 d after injury(P＜0.01).At the same time,the number of retinal microglia reached its peak at 7 d after injury(P＜0.01).RT-qPCR indicated that the expression of disease-associated microglia(DAM)and interferon-responsive microglia(IRM)specific genes were significantly increased when compared with the sham group at 7 d after ONC(P＜0.01).Immunofluorescence staining displayed that the number of DAM peaked at 3 d after ONC(P＜0.01),but the proportion was decreased gradually with the progress of time(P＜0.05).The number and proportion of IRM peaked 7 d after ONC(P＜0.01).Correlation analysis suggested that the number of IRM was strongly correlated with the loss of ganglion cells(P＜0.01).Conclusion The conversion of retinal microglia from DAM type to IRM type after optic nerve injury may be an important cause of ganglion cell loss.

This paper analyzes the current situation of constructing postgraduate education quality assurance systems worldwide, and explores the specific path of constructing a "seven-in-one" medical postgraduate education quality assurance system. The system should be constructed according to the education practice in military medical universities and consider the following aspects: first-class students, first-class teaching, first-class tutors, first-class disciplines, first-class management, first-class culture, and first-class achievements. The system should be constructed by enrollment reform and innovation, teaching method reform, tutor team construction, discipline construction, cultural atmosphere creation, and emphasis on cultivating achievements.

OBJECTIVE: To explore whether the differentiation of vascular stem cells (VSC) into smooth muscle cells (SMC) in aortic dissection (AD) is dysregulated, and to verify the role of Notch3 pathway in this process. METHODS: Aortic tissues were obtained from AD patients undergoing aortic vascular replacement and heart transplant donors at Department of Cardiovascular Surgery, Guangdong Provincial People's Hospital Affiliated to Southern Medical University. VSC were isolated by enzymatic digestion and c-kit immunomagnetic beads. The cells were divided into normal donor-derived VSC group (Ctrl-VSC group) and AD-derived VSC group (AD-VSC group). The presence of VSC in the aortic adventitia was detected by immunohistochemical staining, and VSC was identified by stem cell function identification kit. The differentiation model of VSC into SMC established in vitro was induced by transforming growth factor-β1 (10 μg/L) for 7 days. They were divided into normal donor VSC-SMC group (Ctrl-VSC-SMC group), AD VSC-SMC group (AD-VSC-SMC group) and AD VSC-SMC+Notch3 inhibitor DAPT group (AD-VSC-SMC+DAPT group,DAPT 20 μmol/L was added during differentiation induction). The expression of contractile marker Calponin 1 (CNN1) in SMC derived from aortic media and VSC were detected by immunofluorescence staining. The protein expressions of contractile markers α-smooth muscle actin (α-SMA), CNN1 as well as Notch3 intracellular domain (NICD3) in SMC derived from aortic media and VSC were detected by Western blotting. RESULTS: Immunohistochemical staining showed there was a population of c-kit-positive VSC in the adventitia of aortic vessels, and VSC from both normal donors and AD patients had the ability to differentiate into adipocytes and chondrocytes. Compared with normal donor vascular tissue, the expressions of SMC markers α-SMA and CNN1 of tunica media contraction in AD were down-regulated (α-SMA/β-actin: 0.40±0.12 vs. 1.00±0.11, CNN1/β-actin: 0.78±0.07 vs. 1.00±0.14, both P < 0.05), while the protein expression of NICD3 was up-regulated (NICD3/GAPDH: 2.22±0.57 vs. 1.00±0.15, P < 0.05). Compared with Ctrl-VSC-SMC group, the expressions of contractile SMC markers α-SMA and CNN1 were down-regulated in AD-VSC-SMC group (α-SMA/β-actin: 0.35±0.13 vs. 1.00±0.20, CNN1/β-actin: 0.78±0.06 vs. 1.00±0.07, both P < 0.05), the protein expression of NICD3 was up-regulated (NICD3/GAPDH: 22.32±1.22 vs. 1.00±0.06, P < 0.01). Compared with AD-VSC-SMC group, the expressions of contractile SMC markers α-SMA, CNN1 were up-regulated in AD-VSC-SMC+DAPT group (α-SMA/β-actin: 1.70±0.07 vs. 1.00±0.15, CNN1/β-actin: 1.62±0.03 vs. 1.00±0.02, both P < 0.05). CONCLUSIONS Dysregulation of VSC differentiation into SMC occurs in AD, while inhibition of Notch3 pathway activation can restore the expression of contractile proteins in VSC-derived SMC in AD.
Humans ; Actins ; Platelet Aggregation Inhibitors ; Signal Transduction ; Aortic Dissection ; Cell Differentiation ; Myocytes, Smooth Muscle ; Stem Cells

Objective:To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.

This article elaborates how to facilitate the cultivation reform of medical graduate innovation ability from four perspectives: graduates, colleges or universities, supervisors and the society. Graduates should focus on studying high-quality academic papers, participate in various academic competitions, and actively apply for research projects; universities should innovate education philosophy, optimize curriculum system, create innovation-stimulating cultural atmosphere, establish quality supervision mechanism; supervisors should set a good example for their students, maintain a harmonious relationship with students, take the responsibility of fostering virtue though education and organize excellent supervisor team; and the society should support universities to realize "industry-education collaboration".

Objective:To investigate the clinical value of 3D-FLAIR MRI in the diagnosis of paroxysmal vestibular syndrome.Methods:The clinical data of 72 patients with suspected disease of paroxysmal vestibular syndrome diagnosed and treated in vertigo clinic of our hospital from July 2018 to December 2019 were analyzed retrospectively.All patients had a history of hearing loss, tinnitus and recurrent vertigo.They were divided into two groups: 37 patients suspected of Meniere and 35 patients suspected of vestibular migraine.3D-FLAIR MRI of inner ear was performed after 4 hours of intravenous injection of GD DTPA diluent.The results of diagnosis were compared with those of gadolinium radiography.The data were analyzed by SPSS 19.0.Results:Twenty-one patients with suspected Meniere's disease showed signs of water accumulation in the membranous labyrinth, 4 patients with suspected vestibular migraine showed signs of water accumulation in the membranous labyrinth ( P<0.01). Twenty-three patients with positive signs of water accumulation in the membranous labyrinth were finally diagnosed as Meniere's disease, while Meniere's disease was found in 2 cases of 47 patients with negative signs of membranous labyrinthine hydrops(the sensitivity, specificity and accuracy of the diagnosis of Meniere's disease were 92.0%, 95.9% and 94.6%, respectively). Three cases were complicated with vestibular migraine in the 25 cases with positive signs of membranous labyrinthine hydrops, and 29 cases were finally diagnosed as vestibular migraine in 47 cases with negative signs of membranous labyrinthine hydrocephalus (the sensitivity, specificity and accuracy of diagnosing vestibular migraine with signs of membranous labyrinthine hydrops were 90.6%, 52.4% and 68.9%, respectively). Conclusion:The 3D-FLAIR MRI technique of inner ear after gadolinium radiography has an important role in distinguishing the suspected diseases of paroxysmal vestibular syndrome, and is helpful to improve the diagnosis level of vestibular diseases.

Objective To investigate the effect of bevacizumab (BVZ) on cerebral vessel and blood brain barrier changes in whole-brain irradiation mice.Methods Seventy-five male mice aged 6-7 weeks were randomly divided into normal control group,BVZ group and radiation group (n=25).Mice firom normal control group were without whole-brain irradiation or drug administration.Mice from BVZ group and radiation group were accepted fractionated cranial irradiation at a total dose of 30 Gy by X-ray.Mice from BVZ group and radiation group were intraperitoneally injected with 10 mg/kg BVZ solution or equivalent normal saline (10 weeks continuously) at the beginning of the first X-ray whole-brain irradiation.Eleven weeks after the first irradiation,HE staining was used to observe cerebrovascular pathological changes;Western blotting was used to test vascular endothelial growth factor (VEGF) protein expression;Evan Blue (EB) staining was used to assess the blood-brain barrier damage,and immunofluorescence staining was used to test the yon willebrand factor (vWF) and tight junction protein-1 (ZO-1) expressions.Results The VEGF protein expression level and brain tissue EB content ([9.66±0.73] μg/mL) in the normal control group were significantly increased as compared with those in the radiation group and BVZ group ([16.90±2.15] μg/mL and [12.29±0.96] μg/mL,P＜0.05),but ZO-1/vWF ratio (0.92±0.08) in normal control group was significantly decreased as compared with that in the radiation group and BVZ group (0.46±0.18 and 0.75±0.11,P＜0.05).As compared with the radiation group,BVZ group had significantly reduced VEGF protein expression and EB level in the brain tissues,and had significantly increased ZO-1/vWF ratio (P＜0.05).Conclusion BVZ decreases the quantity of VEGF in brain tissues and alleviates the continuous damage of the brain vessels and blood brain barrier in whole-brain irradiation mice.