Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.

Objective To investigate how miR-30b regulates mitophagy independently of the PINK1/Parkin pathway by targeting ubiquitin specific peptidase 14(USP14)in neuronal oxygen-glucose deprivation/reoxygenation(OGD/R)injury,and to provide new insights for the treatment of neonatal hypoxic-ischemic encephalopathy.Methods Fetal rat cortical neurons were isolated and an OGD/R model was established.Experiments were conducted in two parts.In part 1,cells were randomized into control,OGD/R,OGD/R+microRNA(miR)-negative control(NC),OGD/R+miR-30b mimic,OGD/R+miR-30b mimic+oe-NC,and OGD/R+miR-30b mimic+oe-USP14 groups.In part 2,cells were randomized into control,OGD/R,OGD/R+miR-NC,OGD/R+miR-30b mimic,OGD/R+miR-30b mimic+si-NC,OGD/R+miR-30b mimic+si-Parkin,and OGD/R+miR-30b mimic+si-Drp1(dynamin-related protein 1)groups.miR-30b and USP14 mRNA levels were measured by real-time quantitative PCR.Cell viability was assessed using the CCK-8 assay and cell death by propidium iodide staining.Protein levels of USP14,microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ,translocase of outer mitochondrial membrane 20(TOMM20),PINK1,Parkin,and Drp1 were determined by Western blot.MitoTracker Green staining was used to evaluate mitochondrial morphology,and mitochondrial reactive oxygen species(ROS)were measured using the MitoSOX Red probe.AGO2-RNA immunoprecipitation and dual-luciferase reporter assays were performed to validate the targeting relationship between miR-30b and USP14.Results Compared with the OGD/R group,the OGD/R+miR-30b mimic group showed higher cell viability,miR-30b expression,LC3 Ⅱ/LC3 Ⅰ ratio,and Drp1 protein expression(P<0.05),and lower PI positivity,mitochondrial ROS,USP14 mRNA and protein expression,TOMM20 protein expression,mitochondrial fragmentation index,and mitochondrial volume(P<0.05).PINK1 and Parkin protein levels did not differ significantly between these two groups(P>0.05).Compared with the OGD/R+miR-30b mimic+oe-NC group,the OGD/R+miR-30b mimic+oe-USP14 group exhibited reduced cell viability,miR-30b expression,and LC3 Ⅱ/LC3 Ⅰ ratio(P<0.05),and increased PI positivity,mitochondrial ROS,USP14 mRNA and protein expression,TOMM20 protein expression,mitochondrial fragmentation index,and mitochondrial volume(P<0.05).miR-30b was confirmed to target USP14.In addition,no significant differences were observed between the OGD/R+miR-30b mimic+si-NC and OGD/R+miR-30b mimic+si-Parkin groups in LC3 Ⅱ/LC3 Ⅰ ratio,fragmentation index,or average mitochondrial volume(P>0.05).Compared with the OGD/R+miR-30b mimic+si-NC group,the OGD/R+miR-30b mimic+si-Drp1 group showed a decreased LC3 Ⅱ/LC3 Ⅰ ratio and increased fragmentation index and average mitochondrial volume(P<0.05).Conclusions miR-30b regulates mitophagy by targeting USP14 independently of the PINK1/Parkin pathway,and confers protection against neuronal OGD/R injury.

Objective To investigate how miR-30b regulates mitophagy independently of the PINK1/Parkin pathway by targeting ubiquitin specific peptidase 14(USP14)in neuronal oxygen-glucose deprivation/reoxygenation(OGD/R)injury,and to provide new insights for the treatment of neonatal hypoxic-ischemic encephalopathy.Methods Fetal rat cortical neurons were isolated and an OGD/R model was established.Experiments were conducted in two parts.In part 1,cells were randomized into control,OGD/R,OGD/R+microRNA(miR)-negative control(NC),OGD/R+miR-30b mimic,OGD/R+miR-30b mimic+oe-NC,and OGD/R+miR-30b mimic+oe-USP14 groups.In part 2,cells were randomized into control,OGD/R,OGD/R+miR-NC,OGD/R+miR-30b mimic,OGD/R+miR-30b mimic+si-NC,OGD/R+miR-30b mimic+si-Parkin,and OGD/R+miR-30b mimic+si-Drp1(dynamin-related protein 1)groups.miR-30b and USP14 mRNA levels were measured by real-time quantitative PCR.Cell viability was assessed using the CCK-8 assay and cell death by propidium iodide staining.Protein levels of USP14,microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ,translocase of outer mitochondrial membrane 20(TOMM20),PINK1,Parkin,and Drp1 were determined by Western blot.MitoTracker Green staining was used to evaluate mitochondrial morphology,and mitochondrial reactive oxygen species(ROS)were measured using the MitoSOX Red probe.AGO2-RNA immunoprecipitation and dual-luciferase reporter assays were performed to validate the targeting relationship between miR-30b and USP14.Results Compared with the OGD/R group,the OGD/R+miR-30b mimic group showed higher cell viability,miR-30b expression,LC3 Ⅱ/LC3 Ⅰ ratio,and Drp1 protein expression(P<0.05),and lower PI positivity,mitochondrial ROS,USP14 mRNA and protein expression,TOMM20 protein expression,mitochondrial fragmentation index,and mitochondrial volume(P<0.05).PINK1 and Parkin protein levels did not differ significantly between these two groups(P>0.05).Compared with the OGD/R+miR-30b mimic+oe-NC group,the OGD/R+miR-30b mimic+oe-USP14 group exhibited reduced cell viability,miR-30b expression,and LC3 Ⅱ/LC3 Ⅰ ratio(P<0.05),and increased PI positivity,mitochondrial ROS,USP14 mRNA and protein expression,TOMM20 protein expression,mitochondrial fragmentation index,and mitochondrial volume(P<0.05).miR-30b was confirmed to target USP14.In addition,no significant differences were observed between the OGD/R+miR-30b mimic+si-NC and OGD/R+miR-30b mimic+si-Parkin groups in LC3 Ⅱ/LC3 Ⅰ ratio,fragmentation index,or average mitochondrial volume(P>0.05).Compared with the OGD/R+miR-30b mimic+si-NC group,the OGD/R+miR-30b mimic+si-Drp1 group showed a decreased LC3 Ⅱ/LC3 Ⅰ ratio and increased fragmentation index and average mitochondrial volume(P<0.05).Conclusions miR-30b regulates mitophagy by targeting USP14 independently of the PINK1/Parkin pathway,and confers protection against neuronal OGD/R injury.

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

This study analyzed the effects of male age and abstinence time on semen quality and explored the best abstinence time for Chinese males among different age groups. Semen parameters, including sperm kinetics, morphology, and DNA fragmentation index (DFI), were reviewed from 2952 men. Samples were divided into six age groups (≤25 years, 26-30 years, 31-35 years, 36-40 years, 41-45 years, and >45 years) and were divided into six groups according to different abstinence time (2 days, 3 days, 4 days, 5 days, 6 days, and 7 days). The differences in semen quality between the groups were compared, and the effect of age and abstinence time on semen quality was analyzed. Significant differences were observed in semen volume, progressive motility (PR), and DFI among the age groups (all P < 0.05), and no significant differences were observed in sperm morphological parameters (all P > 0.05). There were significant differences in semen volume, PR, and DFI among different abstinence time groups (all P < 0.05) and no significant differences in sperm morphological parameters (all P > 0.05). Pearson analysis showed that male age and abstinence time were both significantly correlated with sperm kinetics and DFI (both P < 0.05), while no significant correlation was found with sperm morphological parameters (all P > 0.05). The box plots and histograms of men's age, abstinence time, and semen quality show that most semen quality parameters differ significantly between the 2 days and 7 days abstinence groups and other groups at different ages. Except for the sperm morphology parameters, sperm kinetic parameters and sperm DFI are linearly related to male age and abstinence time.
Adult ; DNA Fragmentation ; Humans ; Male ; Retrospective Studies ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Pancreatic cancer is one of the most malignancy tumor in digestive system with extraordinarily poor prognosis owing to its difficulty in early diagnosis and complex treatments.Recently,great progress has been made in surgical techniques,adjuvant treatment and perioperative management of pancreatic cancer.However,the long-term survival of patients with pancreatic cancer has not been significantly improved. American Society of Clinical Oncology released clinical practice guidelines for potentially curable pancreatic cancer in 2016 and updated it for the first time in 2017.In2019,American Society of Clinical Oncology renewed its guidelines in order to modify the program of postoperative adjuvant therapy for pancreatic cancer and recommend FOLFIRINOX as the first choice for postoperative adjuvant therapy for patients with pancreatic cancer in order to improve the prognosis of patients with pancreatic cancer.

Objective To explore the effect of high altitude exposure and short-term acclimation on the platelet-associated parameters by studying the changes of platelet-associated parameters in healthy young man.Methods Four hundred and sixtytwo young men were recruited from Chengdu (the elevation of 500m) during Jun.2012 to Aug.2013 according to the inclusion and exclusion criteria,of which 193 had been living in Chengdu (plain group),and 269 flew from Chengdu to Lhasa (3700m) in 2 hours,and then 147 of them were exposed in the high altitude for 1 day (acute high altitude exposure group),and another 122 for 7 days (short-term acclimation group).The demographic data were collected and the blood routine and platelet-associated parameters were measured of all the participants,and then the information collected were compared between the 3 groups.Results Compared to the plain group,the platelet count (PLT),platelet distribution width (PDW) and plateletcrit (PCT) reduced and the mean platelet volume (MPV) increased significantly (P＜0.05) in the acute high altitude exposure group;while all the indexes in short-term acclimation group returned to approach the levels in the plain group,but statistical differences still existed in PLT,PDW and PCT (P＜0.05).The platelet activating factor (PAF) and epinephrine (Epi) decreased markedly in acute high altitude exposure group than in plain group (P＜0.05);while in short-term acclimation group,the PAF returned to approach the level in plain group,and the Epi was further down (P＜0.05).In addition,no marked difference of 5-HT level was observed in the 3 groups (P＞0.05).Pearson correlation analysis indicated that high altitude-induced reduction of oxygen saturation (SpO2) was positively related to the changes of PLT.Conclusions Acute high altitude exposure may reduce PLT,PDW and PCT levels,but elevate MPV and enhance the platelet activity.The reduction of SpO2 might be associated with the changes of PLT,PDW and PCT.Platelet-associated parameters may be recovered to normal with a compensatory effect after short-term acclimation.

Objective To evaluate the change of left atrial function after mitral valvuloplasty in patients with mitral valve prolapse by measuring left atrial strain using two-dimensional speckle tracking echocardiography(2D-STE).Methods Study population consisted of 25 patients with mitral valve prolapse and 25 healthy subjects.High frame rate two-dimensional images were recorded from the apical four chamber view and two chamber view.Images of patients with mitral valve prolapse were respectively recorded at pre-operation,3 days and 3 months post-operation.Left atrial longitudinal strain was measured in two views using two-dimensional strain soft ware.Results ①Compared with the control group,global peak atrial longitudinal strain (PALS),peak atrial contraction strain (PACS) and atrial longitudinal strain during early diastole(ALSED) decreased (P ＜0.01) in patients with mitral valve prolapse,but global timeto-peak of peak atrial longitudinal strain(TPLS) increased(P ＜0.01).Regurgitant jet area/left atrium area (RJA/LAA) in patients with mitral valve prolapse correlated negatively with global PALS(r =-0.620,P ＜ 0.01).② Compared with preoperative group,global PALS,PACS,ALSED and TPLS decreased significantly at 3 days after surgery(P ＜0.01).Global PALS,ALSED(P ＜0.01) and PACS(P ＜0.05)increased at 3 months after surgery,but global TPLS did not differ significantly.Conclusions 2D-STE could accurately evaluate the change of left atrial function after mitral valvuloplasty.