[ ABSTRACT] AIM:To investigate the effects of microRNA-378*( miR-378*) on the survival and apoptosis of human mesenchymal stem cells ( hMSCs ) .METHODS: The expression of miR-378* was determined by microRNA arrays and quantitative real-time PCR ( qRT-PCR) .H2 O2 was used to induce hMSCs apoptosis.By transfection of miR-378*mimic or inhibitor, we up-regulated or down-regulated miR-378* expression in hMSCs.The effect of miR-378*and connective tissue growth factor ( CTGF) on hMSC survival and apoptosis were detected by MTT, LDH, caspase-3/7 and TUNEL assays.RESULTS:The expression of miR-378*was up-regulated in the old hMSCs compared with the young hMSCs.H2 O2 increased the expression of miR-378*, decreased the expression of CTGF.Up-regulation of miR-378*re-sulted in increasing apoptosis and decreasing survival of hMSCs.Conversely, down-regulation of miR-378*resulted in de-creasing cell apoptosis and increasing survival.The regulation of miR-378*on hMSC apoptosis and survival was attenuated by inhibiting the expression of miR-378* and CTGF together.Direct repression of CTGF expression inhibited the hMSC survival and increased apoptosis.CONCLUSION:miR-378*enhances apoptosis of hMSCs by repressing the expression of CTGF.

AIM: To investigate the effect of microRNA-708-5p (miR-708-5p) on the migration of human mesenchymal stem cells (hMSCs).METHODS:The expression of miR-708-5p was determined by miRNA arrays and re-al-time PCR.By transfection of miR-708-5p mimic or inhibitor, the up-regulation or down-regulation of miR-708-5p ex-pression in hMSCs was evaluated .The cell scratch and Transwell tests were used to detect the migration capability of hM-SCs.The effects of transmembrane protein 88 (TMEM88), a miR-708-5p target gene, onβ-catenin expression and migra-tion of hMSCs were detected .RESULTS:The expression of miR-708-5p was down-regulated in the old hMSCs compared with the young hMSCs.Up-regulation of miR-708-5p resulted in increasing migration of hMSCs.Conversely, down-regula-tion of miR-708-5p resulted in decreasing cell migration .The expression of TMEM88 was up-regulated in the old hMSCs compared with the young hMSCs , while the expression of β-catenin was down-regulated.Directly repression of TMEM88 expression increased the β-catenin expression and migration of hMSCs .The regulation of miR-708-5p on hMSCs was atten-uated by inhibiting the expression of miR-708-5p and TMEM88 together.CONCLUSION:miR-708-5p increases β-cate-nin expression and Wnt/β-catenin activity by repressing TMEM 88, thus enhancing the migration of hMSCs .

AIM:To investigate the effects of microRNA-486-5p (miR-486-5p) on the senescence of human mesenchymal stem cells ( hMSCs).METHODS: The expression of miR-486-5p was determined by miRNA arrays and real-time PCR.By transfection of miR-486-5p mimic or inhibitor, up-regulation or down-regulation of miR-486-5p expres-sion in hMSCs was established.The effect of miR-486-5p and silence information regulator 1 (SIRT1) on hMSC telomerase activity and senescence were detected byβ-galactosidase staining.RESULTS:The expression of miR-486-5p was up-regu-lated in the old hMSCs compared with the young hMSCs.Up-regulation of miR-486-5p resulted in increasing senescence of hMSCs.Conversely, down-regulation of miR-486-5p resulted in decreasing cell senescence.The expression of SIRT1 and telomerase reverse transcriptase ( TERT) was down-regulated in the old hMSCs compared with the young hMSCs.Directly repression of SIRT1 expression inhibited the hMSC TERT protein expression and telomerase activity, but increased cell se-nescence.The regulation of miR-486-5p on hMSC senescence was attenuated by inhibiting the expression of miR-486-5p and SIRT1 together.CONCLUSION:miR-486-5p enhances senescence of hMSCs by decreasing the expression of SIRT1 and telomerase activity.

AIM:To investigate the role of microRNA-486-5p (miR-486-5p) in the apoptosis of human bone marrow mesenchymal stem cells (hMSCs) induced by hydrogen peroxide (H2O2).METHODS: The hMSCs were cul-tured in vitro and exposed to serum-free medium and H2O2(10 mmol/L).The changes of miR-486-5p expression in oxida-tive stress-related apoptosis of hMSCs were measured by real-time PCR.The hMSCs were transfected with miR-486-5p mimic or inhibitor at concentration of 30 nmol/L by Lipofectamine RNAiMAX.The effect of miR-486-5p on H2 O2-induced decrease in cell viability was evaluated by MTT assay.Hoechst 33342 staining and flow cytometry were applied to determine the role of miR-486-5p in the apoptosis of hMSCs.The protein expression was evaluated by Western blotting.Caspase-3 ac-tivity was determined using a caspase-3 activity kit.RESULTS:Compared with control group, the expression of miR-486-5p significantly decreased after treated with H2O2(P<0.05).In addition, over-expression of miR-486-5p in the hMSCs reduced the cell viability, accelerated apoptosis, down-regulated Bcl-2/Bax ratio, caspase-3 enzyme precursor content and phosphorylation of Akt, and activated caspase-3 activity.Conversely, down-regulation of miR-486-5p significantly inhibited H2 O2-induced cell apoptosis and the caspase-3 activity, increased cell viability and up-regulated Bcl-2/Bax ratio and phos-phorylation level of Akt.CONCLUSION:Over-expression of miR-486-5p promotes H2 O2-induced hMSCs apoptosis, and repression of miR-486-5p protects hMSCs from H2 O2-induced cellular apoptosis, which may be mediated by regulating Akt signaling pathway.

Objective:To analyze the characteristics of nerve injury in patients with diabetic peripheral neuropathy (DPN) and explore the diagnostic value of current perception threshold (CPT) and nerve conduction velocity (NCV) for DPN.Methods:One hundred and thirty-six DPN patients admitted to Beijing Puren Hospital from June 2017 to December 2019 were selected, and 130 diabetic non-DPN patients admitted during the same period were used as controls. All the subjects were tested by CPT and NCV. Among them, the detection of NCV included sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV). Statistical analysis was performed on the relevant indicators of the two groups of subjects.Results:The CPT values of the upper limb median nerve and ulnar nerve at 2 000 Hz, 250 Hz, and 5 Hz, the superficial peroneal nerves at 250 Hz, and 5 Hz, and the CPT values of the sural nerve at 2 000 Hz and 250 Hz were higher than those of non-DPN patients, DPN injury mainly occurred in myelinated nerve fibers in the lower extremities [60.29%(82/136)], and the difference were statistically significant ( P<0.05). The SCV and MCV of the median nerve, ulnar nerve, and common peroneal nerve in the DPN group were lower than those in the non-DPN group, the SCV abnormal rate was higher than the MCV: 55.88%(76/136) vs. 37.50%(51/136); 58.82%(80/136) vs. 41.18% (56/136); 67.65%(92/136) vs. 50.00%(68/136), and the differences were statistically significant ( P<0.05). The area under the predictive value curve (AUC) of CPT for DPN was 0.815 (95% CI 0.735 ~ 0.895). The AUC of NCV for DPN was 0.875 (95% CI 0.813 ~ 0.944). The AUC of CPT and NCV for DPN was 0.923 (95% CI 0.876 ~ 0.970). Conclusions:DPT patients have abnormal CPT and NCV, and nerve damage occurs mostly in myelinated nerve fibers and SCV. Diagnosing DPN by combining CPT and NCV is helpful to improve the detection rate of DPN.

Objective:To study the clinicopathological features, diagnosis, treatment and prognosis of patients with solid pseudopapillary neoplasm of the pancreas (SPN).Methods:From Jan 2008 to Dec 2017, 112 pathology confirmed SPN patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University were followed up. The clinicopathological characteristics and diagnosis were analyzed.Results:Most SPN patients were young women, the ratio of male to female is 1∶7. SPN patients have no typical clinical symptoms. The preoperative diagnostic accuracy of SPN was 57.14% with imaging examination. Pathological diagnosis depends mainly on immunohistochemical staining. All patients underwent surgical resection. Follow-up ranged from 4 to 123 months. The mean follow-up time was 49 months. All patients were doing well and no recurrence or metastasis was found.Conclusions:SPN is a rare tumor with low malignant potential. Surgical resection is effective.

Total thoracoabdominal aortic aneurysmrepair is one of the most complex operations in cardiac surgery. Patients may have spinal cord injury, disturbance of consciousness, hypoxemia, arrhythmia, acute renal injury, abdominal organ ischemia and so on after operation. Postoperative complications may occur in patients with neurological, respiratory, circulatory, digestive, urinary and coagulation systems. This paper summarizes the experience of prevention and treatment of postoperative complications based on the medical literature at home and abroad and the experience of diagnosis and therapeutic schedule in our hospital, in order to improve the prognosis.

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

A young female patient presented with fever, arthralgia, and rash was diagnosed with adults still's disease. When treated with glucocorticoid steroid, the above patient progressed to anuria, sudden, and confusion. After a teamwork involving different departments, the patient was finally diagnosed with atypical hemolytic uremic syndrome (aHUS) and treated with good outcome. aHUS is a rare disease, while Eculizumab is an orphan drug. The diagnosis and treatment of the patient reveals the importance of multidisciplinary team on the diagnosis and treatment of rare and difficult diseases.