BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.

Objective:To study the clinicopathologic features and the key points of differential diagnosis of appendiceal diverticulosis (AD) and low-grade mucinous neoplasm (LAMN) to avoid over-diagnosis.Methods:The clinical data, pathologic features and follow-up information of 20 patients with AD, who were diagnosed in the Peking University Third Hospital from January 2010 to November 2019 were collected and compared with 44 cases of LAMN which were diagnosed during the same period.Results:Among the 20 cases of AD, hypermucinous epithelium, filiform villi or undulating epithelium and mucosa atrophy were observed in 10 (50.0%), 4 (20.0%) and 14 (70.0%) cases, respectively, however, focally loss of lamina propria and mucosa/submucosa fibrosis were observed only in 1 (5.0%) and 4 (20.0%) cases, respectively. Extramural mucin deposits were seen in 11 (55.0%) cases, all were acellular mucin. Mucosal Schwann cell hyperplasia were present in 12 (60.0%) cases. Nine (45.0%) and 5 (25.0%) cases were associated with acute diverticulitis or acute suppurative appendicitis, respectively. In comparison with AD, LAMN cases more frequently showed hypermucinous epithelium (42/44, 95.5%), filiform villi or undulating epithelium (43/44, 97.7%), loss of lamina propria (43/44, 97.7%) and fibrosis and hyalinization of appendiceal wall (44/44, 100.0%), whereas mucosal atrophy (4/44, 9.1%) and Schwann cell hyperplasia(11/44, 25.0%) were less frequently seen ( P<0.05). Follow-up information was available for 10 AD patients and 27 LAMN patients; all were alive without evidence of recurrence. Conclusions:Epithelial hyperplasia, loss of lamina propria, fibrosis of the appendiceal wall and extramural mucin deposits may occur focally in AD and should be distinguished from LAMN. The preservation of normal appendiceal mucosa architecture, lack of diffuse appendiceal wall fibrosis and hyalinization, and no definite neoplastic epithelium are the key point for preventing over-diagnosis.

Objective To assess the short-term effects of bariatric surgery on body composition. Methods Fifty-seven patients who underwent bariatric surgery were assessed by dual-energy x-ray absorptiometry (DEXA) before surgery, and 1 and 3 months after surgery. The body composition indexes of whole body and different regions were compared. Results The body mass index (BMI) decreased by 10.61％ and 18.51％, and the lean mass (LM) by 13.22％ and 14.35％ at 1 and 3 months after surgery, respectively. The A/G far mass (FM) decreased significantly 3 months after surgery (P ＜ 0.05). The bone mineral density (BMD) of the spine increased, but that of the pelvis decreased at 1 and 3 months after the operation, and a reduction was observed in the BMD of the whole body by 1.23％ and 1.45％, respectively (P ＜ 0.05). Compared to the baseline, the bone mineral content (BMC) of the spine, pelvis, and whole body increased at 1 and 3 months post-surgery, with a statistically significant difference (P ＜ 0.05). The FM of the whole body (9.52％ and 22.77％) and four regions (legs, trunk, android, and gynoid) reduced. A significant loss of FM (P ＜ 0.05) was observed in the android region by 15.80％ and 31.86％ at the two follow-ups. Conclusion Bariatric surgery can effectively reduce the patient's BMI and FM in the short term, and promotes the redistribution of fat; however, it may be accompanied by a reduction in LM, while the BMD and BMC change trend of pelvis and whole body are opposite.

Objective To evaluate the left atrial(LA) function in patients with severe preeclampsia ( SPE) by full-volume imaging technology. Methods Forty-two patients of SPE were randomly chosen as SPE group,34 healthy pregnant women were selected as the control group. LA related function parameters including LA maximum volume( LAVmax),LA minimum volume( LAVmin),LA pre-atrium contraction volume(LAVpre),LA reservoir volume(LARV),LA passive emptying volume(LAPEV),LA contraction volume(LACV),LA expansion index(LAEI),LA passive emptying fraction(LAPEF),LA passive emptying fraction( LAAEF ) were separately required by biplane area-length method and full-volume imaging technology in antepartum and postpartum. Results Compared with control group before delivery,the parameters of SPE group before delivery such as LAVmax,LAVmin,LAVpre were higher,LAEI,LAPEF, LAAEF indexed to body surface area(BSA) were lower(all P ＜0.01).Compared with control group before delivery,the parameters of control group after delivery such as LAVmax,LAVmin,LAVpre were lower( all P ＜0.05),LAEI, LAAEF calculated as ratio to BSA were somewhat reduced,LAPEF calculated as ratio to BSA was relatively higher(all P ＞0.05).Compared with SPE group before delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were lower,LAEI,LAPEF,LAAEF indexed to BSA were higher( all P ＜0.01). Compared with control group after delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were still incresed ( all P ＜ 0.05 ), LAEI,LAPEF, LAAEF indexed to BSA were relatively lower( all P ＞0.05). Conclusions Full-volume imaging technology can quantitatively evaluate the LA function. LA reservoir function,conduit function and booster pump function are reduced in SPE before delivery,LA rereservoir function,conduit function and booster pump function are basically recovery in SPE after delivery.

Sub-health status in the occupational population showed high incidence. Thus, it is necessary to improve the occupational groups of sub-health status, improve the health level of occupational groups. Shanghai university of traditional Chinese medicine Shuguang hospital treatment center (hereinafter referred to as disease prevention center), based on traditional Chinese medicine disease theory, did a lot of practices on occupational sub-health groups with Chinese medicine prevention and health care. Since 2014, three-year commitment to the Shanghai action plan project, the hospital has constructed a sub-health platform. This article discussed the experience of construction of sub-health platform for the construction of sub-health management system with Chinese characteristics and provided reference for the construction of sub-health management model.

Objective To evaluate the surgical technique and the clinical effect of applying free superficial palmar branch of the radial artery flap to repair soft tissue defect of finger pulp.Methods From June,2011 to December,2013,12 cases of soft tissue defect of finger pulp and bone exposed were treated with free superficial palmar branch of the radial artery flap.The flap was designed from the proximal end of palmar wrist and the donor site was sutured directly.The size of the harvested flaps was between 2.5 cm × 1.0 cm and 6.2 cm × 3.8 cm,and the sensation of the flap was reconstructed via median nerve cutaneous branch.Results All transfering flaps survived and all cases were followed up for 4 to 17 months.The donor site got primary healing with a straight car.The appearance and texture of the flaps were satisfactory.2-point discrimination ranged from 6 to 11 mm.The pain sensation,warmth sensation and touch sensation of the flap got better.Conclusion The free superficial palmar branch of the radial artery flap is easy to harvest and anastomose,which is masked and a small incision for the donor site.The appearance and sensation of the flap which has sensory nerve branched for sensory reconstruction is satisfactory.It is an ideal method for the repairment of finger pulp defects.