Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease.Methods 7-8 week-old,baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected,and randomly divided into two groups:control group (n=6) and WT DM group (n=6).In the same way,male A1AR knock-out C57BL/6J mice were selected as A1AR-/-DM group (n=6).DM model was established by intraperitoneal injection of streptozocin.The blood glucose (BG),body weight (BW),kidney weight (KW),24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks.The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry.The expression of caspase-1,IL-18 and A1AR were detected by Western blotting.Results At 4th week,compared with WT control mice,the BG,BW,KW and 24hUP of WT DM mice were increased significantly (n=6,P ＜ 0.01),with the pathological glomerular enlargement,mesangial cell proliferation,extracellular matrix accumulation and renal tubule hypertrophy being observed.Immunohistochemistry revealed decreased expression of megalin,an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice,which was correlated with 24hUP (r=-0.645,P ＜ 0.01).Compared with the control mice,the expressions of caspase-1,IL-18 and A1AR were significantly increased in WT DM mice (P ＜ 0.05).For A1AR-/-DM mice,more serious pathological lesion and megalin defect,together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice.Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease,in which the mechanism may be associated with caspase-1 related pyroptosis pathway.The details need further exploration.

OBJECTIVEHypothesis showed that women have higher risks of lung cancer than men when given similar levels of tobacco exposure, implying that sex-related hormones might have a role to play. The study is to identify the influence of female hormones on risk of lung cancer.

METHODSWe evaluated the association between lung cancer risk and menstrual/reproductive factors on a subset of self-responding females in a population based case-control study in Eastern Gansu, 1994 - 1998. The analysis included 109 lung cancer cases and 435 controls selected from the census list and matched to cases on age and prefecture.

RESULTSOdds ratios were lower for later ages at menarche (trend, P = 0.015) and later ages at menopause (trend, P = 0.074).

CONCLUSIONDespite limitations, these findings suggested a possible role related to hormones in the etiology of lung cancer in females.

Adult ; Age Factors ; Aged ; Carcinoma, Small Cell ; epidemiology ; etiology ; Case-Control Studies ; China ; epidemiology ; Contraception Behavior ; Female ; Humans ; Incidence ; Logistic Models ; Lung Neoplasms ; epidemiology ; etiology ; Menarche ; Menopause ; Middle Aged ; Odds Ratio ; Parity ; Risk Factors

Objective To evaluate the feasibility of biodegradable flow-diverting stent for treatment of intracranial wide-neck aneurysm.Methods Twenty adult New Zealand rabbits were used to induce wide-neck aneurysm models by elastase,and then,these models were divided into 3 groups:in group one (n=7),biodegradable polyglycolic acid flow-diverting stents (PGA-FDs) were implanted into parent arteries and covered the necks of aneurysms;in group 2 (n=7),the bare metal FDs replaced PGA-FDs;the observation period of animals in group one and group 2 was 3 months;in group 3 (n=6),the PGA-FDs were implanted into parent arteries with 6 weeks of observation period.The status of aneurysm occlusion and patency of side branches covered by the stent were assessed,and all animals were sacrificed:HE staining was used to observe the thrombosis in the aneurysms,Elastic fiber staining was used to observe the neointimal thickness of parent arteries,and immuohistochemical staining was employed to detect the expressions of CD34,CD68 and alpha-actin (αSMA) in the parent arteries.Results Complete aneurysm occlusion rate in groups one,2 and 3 was 83.3％ (5/6),0％ (0/6) and 66.7％ (4/6),respectively.The neointimal thickness in parent artery of groups one,2 and 3 was (111±69) μm,(70±48) μm and (190±52) μm,respectively;that in group 3 was significantly higher than that in group one and 2 (P＜0.05).The neointima comprised predominantly smooth muscle cells and collagen fibers.Some CD34 positive vascular endothelial cells could be seen in the neointima of parent arteries of groups one and 2.Conclusion The PGA-FD is an effective device to occlude aneurysms without inducing obvious neointimal thickness and side branch stenosis in the 3-month follow-up.

Objective To evaluate the safety of biodegradable flow-diverting devices (FDs) for treatment of intracranial aneurysms in rabbits.Methods Biodegradable polyglycolic acid FDs (PGA-FDs) were implanted into the abdominal aorta in 12 New Zealand rabbits,covering the ostium of a lumbar artery.Animals underwent angiography at 3,6,and 12 weeks after device implantation;and 3 animals were sacrificed at 3 and 6 weeks for pathology by HE staining,Veigert resorcinol (VG) staining,and CD34,CD68 and α smooth muscle actin (αSMA) immunohistochemistry.The diameter of abdomen arota and the patency of side branches covered by the devices were assessed.All animals were sacrificed after angiography for pathology at 12 weeks.Results No side branch occlusions were noted,either immediately after implantation or at follow-ups.Abdominal aorta neointimal hyperplasia was minimal,and there were no differences immediately after device implantation,or at 3,6,and 12 weeks after device implantation (abdominal aorta diameter:[3.35±0.24] mm,[3.33 ±0.12] mm,[3.23±0.16] mm,[3.12±0.10] mm and [3.30±0.11] mm).Pathology results showed the neointima covered the strips of PGA-FD,and minial inflammation was abserved around the strips.The PGA strips were obsorbed completely at 12 weeks follow up with no apparent inflammation.The neointima predominantly comprised of smooth muscle cells and collagen fibers.Conclusion The PGA-FD is safe for abdominal aorta and normal side branches at short-term follow-up.

Objective To analyze the application value of modified anterior pelvic floor reconstruction operation in pelvic organ prolapse.Methods A retrospective analysis was adopted.A total of 141 patients with pelvic floor reconstruction surgery in the obstetrics and gynecology department of Chongqing Municipal Ma-ternal and Child Health Care Hospital from January 2020 to December 2021 were included.The patients were divided into the observation group(modified anterior pelvic floor reconstruction operation,n=78)and control group(classic anterior pelvic floor reconstruction operation,n=63)according to the operation methods.The perioperative indicators,pelvic organ prolapse quantitation(POP-Q)score before and after operation,objective cure rate after operation,recurrence situation and pelvic floor quality of life score before and after operation were compared between the two groups.Results There was no significant difference in the surgical time,bleeding volume,duration of antibacteriakl drug use,and length of hospital stay between the two groups(P＞0.05).The POP-Q scores after surgerynin the two groups were signbificantly increase compared with before operation,and the objective cure rate in postoperative 12 months in the observation group was significantly higher than that in the control group at 12 months after surgery(91％.0 vs.81.0％,P＜0.05).There was no recurrence in the observation group after one year follow-up,while there were two cases of recurrence in the control group.The scores of the pelvic floor distress inventory short form 20(PFDI-20),pelvic floor impact questionnake,short form 7(PFIQ-7),and pelvic organ prolapse/incontinence sexual function questionnaire-12(PISQ-12)in 1 month after surgery in the two groups had statisticallyu significant differences compared with those before surgery(P＜0.05).After one year of follow-up,the patient global impression of improvement(PGI-I)score in the observation group was significantly lower than that in the control group(P＜0.05).Con-clusion The modified anterior pelvic floor reconstruction operation can effectively improve the quality of life in the patients,moreover the patients are not easy to relapse,so which is a new type of operation worthy of promotion.

OBJECTIVE To investigate the protective effect of artesunate(Art)against apoptosis and mitophagy induced by NaF in osteocytes MLO-Y4,and to explore the molecular mechanism.METHODS MLO-Y4 cells were treated with NaF(2 mmol·L-1)for 48 h to establish an in vitro model of osteocytes injuries,and the cells were divided into the cell control group,NaF(2 mmol·L-1)group and NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups.The cells were pretreated for 2 h and NaF was added for 48 h.The cell survival of MLO-Y4 cells was detected by MTT assay.The cell viability of MLO-Y4 cells was measured by Calcein-AM staining.The lactate dehydrogenase(LDH)content in the supernatant was examined by the LDH detection kit.The level of intracellular reactive oxygen species(ROS)was examined by DCFH-DA staining.The malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were detected by chemical colorimetry.Apoptosis was measured by Hoechst33342 staining and Annexin-V/PI staining.The level of mitochondrial membrane potential(MMP)was measured by JC-1 staining.The formation of autophagic vacuoles and morphological mitochondrial changes were observed via Lyso-tracker staining and Mito-Tracker staining.The ATP content was detected with the luciferase method.The expression of microtubule-associated protein light chain 3(LC-3)in mitochon-dria was examined by immunofluorescence staining.Protein expressions of LC-3,P62,E3 ubiquitin-ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)were detected by Western blotting.RESULTS Compared with the cell control group,the cell survival rate and cell viability were significantly reduced in the NaF group(P<0.01),LDH content in the supernatant,the level of intracellular ROS,the MDA content,apoptosis rate and autophagic vesicle formation were remarkably increased(P<0.01),protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly upregulated along with the elevation of LC-3 in damaged mitochondria(P<0.01),while P62 levels,SOD activity,MMP and ATP contents were reduced in NaF cells(P<0.05,P<0.01).Compared with NaF group,the cell viability and survival rate of MLO-Y4 cells in NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups were significantly increased(P<0.01);the content of LDH in supernatants was decreased obviously(P<0.01);the levels of intracellular ROS and MDA content were markedly reduced(P<0.05,P<0.01);the apoptosis rate and autophagic vesicle formation were remarkably decreased(P<0.05,P<0.01);protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly down-regulated along with the accumulation of LC-3 in damaged mitochondria(P<0.01);MMP and ATP content were also reduced(P<0.05,P<0.01);while SOD activityand P62 levelwere significantly increased(P<0.05,P<0.01).CONCLU-SION Art has a protective effect against oxidative damage induced by NaF in MLO-Y4 cells,which might be related to the inhibition of apoptosis and mitophagy.

Objective To Analyze the expression profiles of LncRNAs and mRNAs in ovarian epithelial cancer cell lines by gene mi-croarray, and then provide experimental evidences for investigating the function of LncRNAs associated with ovarian cancer. Methods The differentially expressed LncRNAs and mRNAs in ovarian epithelial cancer cell lines, such as A2780, HO8910 and SKOV3, and ovarian epithelial cell line HOSEpiC were analyzed by gene microarray. The differentially expressed mRNAs were further performed the KEGG pathway enrichment analysis. The expression levels of six candidate LncRNAs, which had significant difference between the o-varian epithelial cancer cell line and the ovarian epithelial cell line, were further verified by qRT-PCR. Results There were 227 up-regulated LncRNAs and 483 down-regulated LncRNAs in A2780, HO8910 and SKOV3 cell lines. The differentially expressed mRNAs in A2780, HO8910 and SKOV3 cell lines were mainly enriched in the tumor-related pathways such as PI3K-AKT, mTOR and TNF-α( P<0.05) . The expression levels of PTPRG-AS1, CCNT2-AS1, XLOC 009869 and LINC01138 in ovarian epithelial cancer A2780, SKOV3 and OVCR3 cell lines were up-regulated (P<0.05), while those of RP11-252P19.2 and RP11-744I24.2 in ovarian epithelial cancer A2780, SKOV3, OVCR3 and 3AO cell lines were down-regulated ( P<0.05) . Conclusion The differentially expressed LncR-NAs and mRNAs in ovarian epithelial cancer cell lines may be obtained by gene microarray, and the differentially expressed mRNAs are associated with the tumor-related pathways such as PI3K-AKT, mTOR and TNF-α, which may provide new targets for the diagnosis and treatment of ovarian cancer.

OBJECTIVETo evaluate the efficacy and safety between endoscopic and microscopic surgery for transsphenoidal pituitary adenoma.

METHODSRandomized or semi-random controlled trials comparing endoscopic with microscopic surgery for transsphenoidal pituitary adenoma and published between January 2000 and July 2013 were recruited. This meta-analysis (RevMan 5.1 software) was conducted to estimate short-term and long-term complications. Fixed random effect model or semi-random effect model was established to analyse the data.

RESULTSTwelve randomized or semi-random controlled trials were included in this study. Among 848 patients studied, 380 of them were treated with endoscopic and 468 were treated with microscopic. The analysis of the basic characteristics of these patients included in these studies showed that: compared with microscopic, the follow-up of patients in endoscopic group was shorter [OR = -2.29, 95%CI (-4.18, -0.39), P = 0.02], while there were no significant difference in gender proportion and the age of patients between the two groups (P > 0.05) . Also, compared with endoscopic, there was a significant addition in the incidence of diabetes insipidus [OR = 0.45, 95%CI(0.30,0.66), P < 0.0001] and other complications [OR = 0.26, 95%CI ( 0.12, 0.57), P = 0.0008] in the microscopic group, the blood loss during surgery was more [OR = -0.62, 95%CI(-1.19, 0.05), P = 0.03], the rate of complete tumor resection lower [OR = 0.61, 95%CI(0.39, 0.96), P = 0.03], and the hospitalization [OR = -1.53, 95%CI(-2.18, -0.88), P < 0.00001] was also significantly longer, there was no significant difference in the incidence of cerebrospinal fluid leakage, operation time and vision improvement rate (P > 0.05).

CONCLUSIONFor patients with pituitary tumors, endoscopic surgery may be more suitable compared with microscopic.

Adenoma ; Endoscopy ; Evidence-Based Medicine ; Humans ; Microsurgery ; Neurosurgical Procedures ; methods ; Pituitary Neoplasms ; surgery ; Randomized Controlled Trials as Topic ; Treatment Outcome

Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixed-duration experiments (500 ms as the Short Group and 1500 ms as the Long Group) and random-duration experiments (500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from 15 Hz to 25 Hz. The beta power was higher during the hold period than the movement (reach and grasp) period. Further, in the fixed-duration experiments, the mean power as well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention.

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of