hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components.

OBJECTIVES: Explore the therapeutic role of human umbilical mesenchymal stem cells (hUMSCs) transplantation for regeneration of ECM components and restoration of follicular development in mice. BACKGROUND: The extracellular matrix (ECM) is crucial to maintain ovary function and regulate follicular development, as it participates in important cell signaling and provides physical support to the cells. However, it is unknown how hUMSCs affect the expression of ECM-related genes in ovaries treated with cyclophosphamide (CTX) and busulfan (BUS). METHODS: In the present study, we used 64 six- to eight-week-old ICR female mice to established mouse model. The mice were randomly divided into four groups (n = 16/group): control, POI, POI + hUMSCs, and POI + PBS group. The premature ovarian insufficiency (POI) mouse model was established by intraperitoneal injection of CTX and BUS for 7days, then, hUMSCs or PBS were respectively injected via the tail vein in POI + hUMSCs or POI + PBS group. Another 7days after injection, the mice were sacrificed to harvest the ovary tissue. The ovaries were immediately frozen with liquid nitrogen or fixed with 4% PFA for subsequent experiments. To screen differentially expressed genes (DEGs), we performed transcriptome sequencing of ovaries. Thereafter, a Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the related biological functions. Retrieval of interacting genes for ECM-related DEGs was performed using the function of STRINGdb (version 2.6.5) to evaluate potential protein-protein interaction (PPI) networks. Furthermore, qRT-PCR and IHC were performed to assess the differential expression of selected DEGs in control, damaged, hUMSCs-transplanted and non-transplanted ovaries. RESULTS: Chemotherapy caused mouse ovarian follicular reserve depletion, and hUMSCs transplantation partially restored follicular development. Our results revealed that ECM-receptor interaction and ECM organization were both downregulated in the damaged ovaries. Further investigation showed that ECM-related genes were downregulated in the CTX and BUS treatment group and partially rescued in hUMSCs injection group but not in the PBS group. qRT-PCR and IHC verified the results: collagen IV and laminin gamma 3 were both expressed around follicle regions in normal ovaries, chemotherapy treatment disrupted their expression, and hUMSCs transplantation rescued their localization and expression to some extent. CONCLUSION: Our data demonstrated that ECM-related genes participate in the regulation of ovarian reserve, hUMSCs treatment rescued abnormal expression and localization of collagen IV and laminin gamma 3 in the damaged ovaries. The results suggest that hUMSCs transplantation can maintain ECM-stable microenvironments, which is beneficial to follicular development.

Clinicopathological characteristics and prognosis of idiopathic membranous nephropathy with or without C3 deposition / 中华全科医师杂志

Objective:To investigate the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with or without C3 deposition.Methods:Clinical and pathological data of 576 patients with IMN diagnosed in Affiliated Hospital of Qingdao University from January 2017 to January 2021 were retrospectively analyzed. The patients were divided into C3 deposition group and non-C3 deposition group according to the immunofluorescence staining of C3. The clinical and pathological characteristics were compared between the two groups. Kaplan-Meier survival curve was used to compare the prognosis of the two groups.Results:A total of 576 IMN patients (male 364 (63.20%)) were enrolled, including 400 patients (69.44%) with C3 deposition and 176 patients (30.56%) without C3 deposition. Compared with the non-C3 deposition group, the levels of total blood cholesterol ( t=0.94, P=0.002) and the proportion of phospholipase A2 receptor ( χ2=9.99, P=0.002), IgG ( χ2=10.67, P=0.001), IgM ( χ2=7.00, P=0.008), IgA ( χ2=7.87, P=0.005) and C1q ( χ2=8.28, P=0.004) depositions in renal tissues was higher in C3 deposition group, while the levels of serum C3 ( t=2.87, P=0.004), albumin ( t=3.57, P<0.001) and IgG ( Z=3.55, P<0.001) were lower in C3 deposition group. There were no significant differences in other clinicopathological indicators between the two groups. The survival analysis was performed in 460 patients who were followed for>6 months, including 319 cases (69.35%) of C3 deposition and 141 cases (30.65%) of non-C3 deposition. The end point event was defined as an eGFR decline>30% or entry into end stage renal disease (ESRD). There was no statistically significant difference in treatment method between the two groups ( P>0.05). The median follow-up time was 22 (13,32) months, 327 (71.09%) patients achieved remission, and 22 patients had renal end-point events. Compared with the non-C3 deposition group, the proportion of urinary protein remission was lower ( χ2=10.85, P<0.05), the incidence of renal end-point events was higher ( χ2=5.05, P<0.05). Kaplan-Meier survival analysis showed that patients with C3 deposition had a lower cumulative remission rate (Log-rank χ2=6.68, P=0.010), and a lower cumulative renal survival than those without C3 deposition had ( χ2=5.42, P=0.020). Conclusions:Compared with patients without C3 deposition, IMN patients with C3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rate, and are more likely to have poor prognosis.

Dissecting the novel abilities of aripiprazole: The generation of anti-colorectal cancer effects by targeting Gαq via HTR2B

Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo, but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (Gαq) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of Gαq to HTR2B was decreased after Ari treatment. Knockdown of Gαq not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and Gαq was found in that the mutation at amino acid 190 of Gαq reduced the efficacy of Ari. Thus, these results confirm that Gαq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.

Efficacy and safety of 4 kinds of hemocoagulases combined with proton pump inhibitor for nonvariceal upper gastrointestinal bleeding：a network meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the difference of efficacy and safety of four kinds of commonly used haemocoagulases combined with proton pump inhibitor （PPI） for nonvariceal upper gastrointestinal bleeding （NVUGIB）， and to provide evidence-based basis for clinical decision-making. METHODS Retrieved from PubMed， Web of Science， Wanfang data， VIP and CNKI databases， randomized controlled trials （RCTs） or cohort studies about Hemocoagulase agkistrodon blomhoffii， Haemocoagulase agkistrodon， hemocoagulase and Hemocoagulase bothrops atrox combined with PPI were collected during the inception to Dec. 2021. Two researchers independently screened the literature， extracted data and evaluated the quality of included studies. ADDIS 1.16.8 software was used to conduct a Bayesian network meta-analysis. RESULTS A total of 33 studies were included， involving 3 602 patients. Results of network meta-analysis showed that： in terms of hemostatic efficacy， compared with PPI monotherapy， four kinds of haemocoagulases combined with PPI could significantly improve the hemostatic efficacy of patients （P＜0.05）； there was no statistical significance in the pairwise comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： Hemocoagulase agkistrodon blomhoffii combined with PPI＞ Hemocoagulase bothrops atrox combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞hemocoagulase combined with PPI＞PPI alone. In terms of the incidence of adverse drug reactions （ADR）， compared with PPI monotherapy， there was no statistical difference in the incidence of ADR among four kinds of haemocoagulases combined with PPI （P＞0.05）. There was no statistical significance in the pairwise 88325750。E-mail：fengyufei@126.com comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： hemocoagulase combined with PPI＞Hemocoagulase bothrops atrox combined with PPI＞Hemocoagulase agkistrodon blomhoffii combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞PPI alone. CONCLUSIONS Compared with PPI monotherapy， four different sources of hemocoagulases combined with PPI have better efficacy and similar safety in the treatment of NVUGIB. There is no significant difference in efficacy and safety among different hemocoagulases.

Clinical characteristics and risk factors of antineutrophil cytoplasmic antibody-associated vasculitis complicated with infection / 中华肾脏病杂志

Objective:To investigate the characteristics and risk factors of infection in newly diagnosed patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods:The clinical data of AAV patients (followed up for at least 6 months) in Affiliated Hospital of Qingdao University from September 2012 to September 2020 were retrospectively collected. According to whether infection occurred during follow-up, the patients were divided into infection group and non-infection group. The clinical characteristics and infection status of the two groups were analyzed, and the Cox regression analysis model was used to explore the influencing factors of infection.Results:A total of 236 AAV patients were enrolled in this study, including 128 females (54.2%) and 108 males (45.8%), with a median age of 66.00 (59.76, 71.99) years. There were 202 patients (85.6%) with positive myeloperoxidase (MPO)-ANCA and 34 patients (14.4%) with positive protease 3 (PR3) -ANCA. There were 77 cases in the infection group and 159 cases in the non-infection group. A total of 121 infections occurred in 77 patients, and 54 infections (44.6%) occurred within 6 months after initial diagnosis. In the infection group the proportion of patients with hypertension history, pulmonary underlying diseases and patients who received hormone pulse therapy or plasma exchange, the incidence of lung, kidney, heart and gastrointestinal involvement, the level of serum creatinine and five factors score (FFS) at initial diagnosis were significantly higher than those in the non-infection group (all P<0.05), while the estimated glomerular filtration rate (eGFR) was significantly lower ( P<0.05). Lung (73.6%) was the main infection organ of AAV patients. The most common pathogenic microorganisms were bacteria (64.0%), mainly Pseudomonas aeruginosa and Staphylococcus aureus, followed by fungi (33.7%, mainly Candida albicans). Multivariate Cox regression analysis showed that lung involvement ( HR=1.682, 95% CI 1.034-2.734, P=0.036) and gastrointestinal involvement ( HR=2.976, 95% CI 1.219-7.267, P=0.017) were the independent influencing factors for infection in AAV patients. Conclusions:AAV patients have a higher incidence of infection within 6 months after initial diagnosis. The most common organ of infection in AAV patients is the lung, and the common pathogens are Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Lung involvement and gastrointestinal involvement are the independent risk factors for infection in AAV patients.

Meibomian gland dysfunction and expressions of inflammatory factors and lipid metabolic factors in diabetic mice / 中华实验眼科杂志

Objective:To explore the changes in morphology and function of meibomian gland and the expressions of inflammatory factors and lipid metabolic factors in meibomian gland of diabetic mice.Methods:Fifty 8-week-old male C57BL/6 mice of clean degree were divided into normal control group ( n=20) and diabetes model group ( n=30) according to a random table.Diabetes model was established by the intraperitoneal injection of streptozotocin (60 mg/kg, 10 mg/ml). Mouse tail vein blood glucose ≥16.7 mmol/L was considered as successful modeling.Blood glucose was measured weekly, and body weight was compared between the two groups.Ten mice were randomly selected for fluorescein sodium staining of the cornea to evaluate the integrity of the corneal epithelium from both groups at an interval of 4 weeks.Five mice were randomly selected from the two groups and were sacrificed via anesthesia to collect meibomian gland tissue for hematoxylin and eosin staining in order to observe morphological changes at 8 and 16 weeks after modeling, respectively.At 16 weeks following modeling, mebomian gland of 5 mice randomly selected from both groups was stained with oil red O staining to observe the distribution of lipid.Real-time fluorescence quantitative-PCR was performed to detect the relative expressions of tumor necrosis factor (TNF)-α, pigment epithelium derived factor (PEDF), peroxisome proliferators-activated receptor γ (PPARγ), and adipose differentiation-related protein (ADFP) mRNA in meibomian gland.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University Eye Hospital (No.TJYY20190630009). Results:The successful modeling rate of diabetes in mice was 100%, and the survival rate was 83.3% (25/30). The weight was significantly lower and the blood glucose level was higher in diabetes model group at 8 and 16 weeks after modeling in comparison with normal control group (all at P<0.05). There were significant differences in corneal fluorescein staining score among different time points in diabetes model group ( F=27.155, P<0.05). In diabetes model group, thinner wall of meibomian gland duct, enlarged lumen of the duct, dilated acini and oil red-stained lipid deposition in most acini were observed.At 16 weeks after modeling, the expressions of TNF-α, and PPARγ mRNA in meibomian gland of diabetes model group were 3.33±0.91 and 1.55±0.25, which were significantly higher than 1.00±0.16 and 1.00±0.27 of normal control group (both at P<0.05). The expression of PEDF mRNA in diabetes model group was 0.42±0.08, which was significantly lower than 1.00±0.34 in normal control group ( P<0.05). There was no significant difference in the ADFP mRNA expression between the two groups ( t=0.943, P=0.38). Conclusions:Inflammatory factors and lipid metabolic factors such as TNF-α, PEDF, and PPARγ may be involved in the pathogenesis of meibomian gland dysfunction induced by diabetes.

Efficacy of plasma exchange in the treatment of autoimmune hemolytic anemia in children / 中国小儿急救医学

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.

Efficacy of plasma exchange in the treatment of autoimmune hemolytic anemia in children / 中国小儿急救医学

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.

Relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity / 中华内分泌代谢杂志

Objective:Explore the relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity(baPWV) in community population.Methods:Questionnaire, physical examination, blood tests, and baPWV detection were applied to a community based population. Finally, 3 912 subjects with complete data were included in the study. The relationship between sleep duration, time to fall asleep and PWV was evaluated with binary logistic regression analysis. Results:Being adjusted for age, sex, prevalence of diabetes, sleep condition, body mass index, blood glucose, blood pressure, dyslipidemia, ankle-brachial index, sleep duration and time to fall asleep were correlated with PWV. The risk of PWV abnormalities was increased in the≥8 h group compared to the 6-8 h group( OR=1.155, 95% CI 0.995-1.367, P=0.037). The risk of abnormalities PWV was higher in the group with sleep time after 00: 00 than in the group -23: 00( OR=1.482, 95% CI 1.008-2.179, P=0.045). Conclusion:Long sleep duration(≥8 h) and late sleep time(after 00: 00) may be associated with higher risk of atherosclerosis.

Myrtenol alleviates oxidative stress and inflammation in diabetic pregnant rats via TLR4/MyD88/NF-κB signaling pathway.

Gestational diabetes mellitus (GDM) is a special kind of diabetes that arises only during pregnancy. A woman with GDM has a higher risk of developing type-2 diabetes and other metabolic diseases. In this exploration, we intended to scrutinize the therapeutic actions of Myrtenol against the streptozotocin (STZ)-provoked GDM in rats. GDM was provoked in the pregnant rats via injecting the 1% of STZ (25 mg/kg) and then treated with the 50 mg/kg of myrtenol. The glucose level and bodyweight of animals were noted. The lipid profile, that is, total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) was determined by respective kits. The lipid peroxidation and antioxidants status were examined using assay kits. The status of proinflammatory markers was investigated by assay kits. The messenger RNA (mRNA) expressions of TLR4/MyD88/NF-κB signaling proteins were studied by reverse transcription polymerase chain reaction analysis. The hepatic and pancreatic tissues were examined microscopically. Myrtenol treatment notably decreased the status of blood glucose and lipid profile and improved the HDL in the GDM rats. The status of lipid peroxidation and inflammatory markers were substantially reduced by the myrtenol and it enhanced the antioxidants status of GDM animals. Myrtenol treatment remarkably downregulated the mRNA expressions of TLR4/MyD88/NF-κB signaling proteins. The histological findings also proved the therapeutic actions of myrtenol. Altogether, the findings of this investigation unveiled the therapeutic actions of the myrtenol against the STZ-provoked GDM in rats. Myrtenol could be a promising therapeutic agent to treat GDM in the future.

The methodological framework of surgical innovation: The interpretation of IDEAL reporting guideline / 中国胸心血管外科临床杂志

@#Adherence to reporting guidelines contributes to report methodology and outcomes of research distinctly and transparently. There are some checklists with specific study types related to surgery on the EQUATOR Network’s website. However, the IDEAL framework focuses on stepwise evaluation of surgical innovation through all stages with some key elements, which those existing guidelines may not mention. This likely results in the inaccuracy in reporting in studies attempting to follow the IDEAL recommendations and suggests a pressing need for IDEAL reporting guidelines. Considering these limitations, the IDEAL developed the IDEAL reporting guidelines between October 2018 and May 2019. The paper aimed to provide interpretation of IDEAL reporting guideline, and promote its understanding and use among Chinese researchers.

The methodological framework of surgical innovation: the introduction of IDEAL framework and recommendation / 中国胸心血管外科临床杂志

@#Surgical innovation is an important part of surgical research and practice. The evaluation of surgical innovation through the stages is similar to those for drug development, but with important differences. The Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) Framework and Recommendations represent a new paradigm for the evaluation of surgical intervention and devices which was developed in 2009. The IDEAL is a five-stage framework involving the nature stages of surgical innovation, together with recommendations for surgical research pathway. The Framework and Recommendations were updated and published in 2019, which added a pre-IDEAL stage if necessary. The updated IDEAL also underlines the purpose, key question and ethical issues for each stage. In the first paper of IDEAL Framework and Recommendations series, we conducted a comprehensive introduction of IDEAL (e.g. the development, updates and application of IDEAL) to promote the dissemination and application of IDEAL in China.

Clinicopathological characteristics and prognosis of IgA nephropathy patients with gross hematuria / 中华全科医师杂志

Objective:To investigate the clinicopathological features and prognosis of IgA nephropathy (IgAN) patients with gross hematuria.Methods:The clinical and pathological data of 490 primary IgAN patients admitted in the Affiliated Hospital of Qingdao University from January 2010 to June 2019 were analyzed. Patients were divided into gross hematuria group and non-gross hematuria group. The clinical and pathological features and prognosis were compared between the two groups. All patients were diagnosed by kidney biopsy, and followed up until June 30, 2020. Kaplan-Meier survival curve was used to examine the renal survival,and Cox regression model was used to analyze the risk factors affecting renal survival in two groups.Results:Among 490 patients there were 111 patients (22.7%) in the gross hematuria group and 379 patients (77.3%) in the non-gross hematuria group. Age, hypertension, 24-h urine protein, serum creatinine, blood uric acid, blood triglycerides, total blood cholesterol level, mesangial cell hyperplasia (M1), the proportion of renal tubular atrophy or renal interstitial fibrosis (T1/2) in gross hematuria group were lower than those in non-gross hematuria group ( P<0.05), while the estimated glomerular filtration rate (eGFR) in gross hematuria group was higher than those in non-gross hematuria group ( P<0.05). Four hundred and twenty six patients (86.9%) were followed up for at least 6 months, including 93 patients in gross hematuria group and 333 patients in non-gross hematuria group. There was no statistically significant difference in treatment method between the two groups ( P>0.05). The incidence of end-point events in non-gross hematuria group was higher than that in gross hematuria group [18.6%(62/333) vs. 6.5%(6/93), χ2=8.023, P<0.05]. Kaplan-Meier survival analysis showed that the cumulative renal survival rate of the gross hematuria group was higher than that of the non gross hematuria group (χ2=11.44, P<0.001). Multivariate Cox regression analysis showed that urine protein>1 g/24 h, eGFR<60 ml·min -1·(1.73 m 2) -1, hypertension, hyperuricemia and the elevated serum IgA/C3 were risk factors for renal survival [ HR(95% CI)=3.457(1.137-10.514),2.736(1.073-6.977),2.720(1.144-6.465),2.789(1.102-7.060),1.070(1.009-1.135), all P<0.05]. Conclusions:IgAN patients with gross hematuria has less severe kidney damage and higher cumulative renal survival rate than non-gross hematuria patients. Urinary protein>1.0 g/d, hypertension, hyperuricemia and the elevated serum IgA/C3 are risk factors for adverse end-point events, to which timely attention and corresponding treatment should be given.

Impaired Parahippocampal Gyrus-Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease / 神经科学通报·英文版

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

Re-investigation after 8 years on the publication of Chinese clinical trials after registration / 中华医学科研管理杂志

Objective To investigate the publication status and quality in registration centers and journals of Chinese clinical trials after registration.Methods The Chinese clinical trials registered on the US Clinical Trial Registration website (www.clinicaltrials.gov) before July 24,2009 were searched.China Knowledge Network (CNKI),Wanfang Database,VIP Database,PubMed,and EMbase Database were searched by computer from inception to December 31,2017,to investigate the outcome publication of these clinical trials in the registration center and journals.Results A total number of 654 clinical trials were included in this study.Only 25 clinical trials,accounted for 3.8％,published trial outcome on the US Clinical Trials Register,74 clinical trials,accounted for 11.3％,were published in the journals (effective literature).Most of the trials took 2 to 3 and in both from registration to completion and study closure to outcome publication.Conclusions The proportion and quali ty of clinical trial outcome publication in China were low,which alerting us that researcher should pay more attention to the trial outcome publication.

Research progress of open scientific ecosystem based on the block chain / 中华医学科研管理杂志

Objective To provide comprehensive background reference for the application of block chain technology in scientific research ecology.Methods The related literatures of block chain and open science were retrieved and analyzed from the mainstream databases and network resources.Results According to the analysis of weak points of the traditional scientific system,as well as the crisis of open science movement,it alerted the urgency and necessity of establishing a truly open scientific ecosystem.This article also introduced the basic knowledge of block chain,demonstrated the feasibility of its application and potential advantages of block chain for constructing an open scientific ecosystem.The preliminary practice of block chain applied in open scientific systems is also summarized.Conclusions The block chain technology allows for the construction of an open,reliable,decentralized and collaborative environment infrastructure that changes the whole process of scientific research.

Development and validation of a noninvasive diagnostic model for IgA nephropathy / 中华肾脏病杂志

Objective:To explore the development and clinical application value of Nomogram model, a noninvasive early diagnosis model, in IgA nephropathy.Methods:The clinical data of 712 patients with primary glomerular disease diagnosed by renal histopathological examination in Affiliated Hospital of Qingdao University during October 1, 2010 to August 31, 2019 were collected retrospectively, including 241 cases of IgA nephropathy and 471 cases of non-IgA nephropathy. According to the time of case inclusion, the patients were divided into the training set ( n=426, 156 cases of IgA nephropathy and 270 cases of non-IgA nephropathy) and the validation set ( n=286, 85 cases of IgA nephropathy and 201 cases of non-IgA nephropathy). Univariate and multivariate logistic regression equations were used to analyze the risk factors for diagnosing IgA nephropathy in patients of training set. Nomogram model for noninvasive diagnosis of IgA nephropathy was established according to the akichi information criteria (AIC) and applied to the validation set for validation. The discriminant degree, calibration degree and clinical practicability of the model were verified and evaluated by receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA), respectively. Results:Multivariate logistic regression results showed that the age ( OR=0.966, 95% CI 0.947-0.985, P=0.001), IgA/C3 ratio ( OR=1.889, 95% CI 1.468-2.432, P<0.001), serum albumin ( OR=1.091, 95% CI 1.047-1.136, P<0.001), total cholesterol ( OR=0.810, 95% CI 0.694-0.946, P=0.008), and gross hematuria ( OR=6.858, 95% CI 1.867-25.189, P=0.004) of patients with primary glomerular disease were independent factors for the diagnosis of IgA nephropathy. Nomogram diagnostic model was constructed based on the above indicators, and the areas under ROC curve were 0.880 and 0.887 respectively in the training set and the validation set. The calibration curve showed that the predicted probability of the model was in good agreement with the actual probability. DCA showed that the safety and clinical net benefit of the model were higher. Conclusions:The Nomogram model has high accuracy and clinical practicality in diagnosing IgA nephropathy, and can be used for noninvasive and early diagnosis of IgA nephropathy to enable patients to receive early treatment.

Effects of famine exposure in early life on bone mineral density measured by ultrasound in postmenopausal women / 中华内分泌代谢杂志

Objective:To explore the relationship between famine exposure in early life and bone mineral density measured by ultrasound in postmenopausal women.Methods:From May 2011 to October 2011, 10 140 residents over 40 years old in Yunyan District of Guiyang City were randomly selected, and followed up for 3 years, 7 493 subjects were selected and finally included a total of 1 504 subjects. Grouped by date of birth, the differences in bone mineral density measured by ultrasound, and risk of osteoporosis between the exposed and non-exposed groups were compared.Results:SOS, T-score, and QUI in infant- and preschool-exposed group were lower than those of non-exposed group. The medium/high risk of osteoporosis in non-exposed, fetal-exposed, infant-exposed, and preschool-exposed groups were 50%, 46.8%, 58.4%, and 62.8%, respectively ( P<0.01). Multivariate linear regression analysis showed that famine exposure in infant- and preschool-exposed groups were significantly negative correlated with SOS, T-score, and QUI, while fetal-exposed group was not significantly correlated with SOS, T-score, and QUI. Compared with the non-exposed group, the OR of the medium/high risk of osteoporosis in the infant- and preschool-exposed groups were( OR=1.41, 95% CI 1.02-1.96)、( OR=1.68, 95% CI 1.21-2.34), with statistically significance ( P<0.05), and there was no statistical significance in the fetal-exposed group. After adjusting for confounding factors, the medium/high risk of osteoporosis in infant- and preschool-exposed group were 1.64 and 1.90 as compared with the non-exposed group ( OR=1.64, 95% CI 1.16-2.32, P<0.05 and OR=1.90, 95% CI 1.35-2.70, P<0.05). Conclusion:In postmenopausal women, famine exposure in early life was significantly negatively correlated with bone mineral density measured by ultrasound (SOS, T-score, and QUI), and was associated with an increased risk of osteoporosis.

Molecular cytogenetic diagnosis of a case with ring chromosome 18 syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with developmental delay and congenital syndactyly.@*METHODS@#G-banding chromosomal karyotyping and chromosomal microarray analysis (CMA) were performed on peripheral blood sample from the child.@*RESULTS@#The child was ascertained as 46, XY, r(18)[52]/45,XY,?18[3]. A 18q21.32-q23 deletion was identified by CMA with a size of 19.85 Mb, which has encompassed 99 genes including CTDP1, TXNL4A, TSHZ1, PIGN, RTTN, TNFRSF11A, KDSR and CYB5A.@*CONCLUSION@#Clinical phenotype of the patient with ring chromosome 18 is associated with the size of the euchromatin loss and involved genes. As a useful complement to conventional karyotyping, CMA has provided an powerful tool for delineating complex chromosomal aberrations.

The Glutamatergic Postrhinal Cortex-Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval / 神经科学通报·英文版

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.