ObjectiveTo further understand the clinic manifestations of childhood primary Sjogren's Syndrome(pSS) and enhance early diagnosis. MethodsFive cases of pSS from Renji Hospital, Shanghai, were reported and their clinical features were analysoed. And literatures from Medline database and Weipu database were reviewed and discussed. Results①Childhood pSS had various clinic presentations that were non-specific and sicca symptoms were absent or occur late in most cases. ② The most common presentations were recurrent parotiditis and cutaneous manifestations with various locations and forms. ③ American-European Criteria for SS were not suitable for the diagnosis of childhood pSS. ConclusionRecurrent parotiditis and cutaneous manifestations in children can be used as clues for the diagnosis of childhood pSS but needs to be further confirmed by the positive results of salivary gland biopsy and autoantibodies examination, particularly SSA/SSB.

Objective To study the correlation between clinicopathological characteristics and lymph node metastasis and prognosis of rectal neuroendocrine tumors (NET),and try to explore the choice of surgical approach.Methods The clinicopathological data of 48 postoperative rectal NET patients were collected.The univariate and multivariate analysis of the correlation between clinicopathologic characteristics and lymph node metastasis were performed by chi-square test and Logistic regression.The prognosis single factor survival analysis was analyzed by Kaplan-Meier method.The survival rates were compared by Log-rank test.The prognosis multivariate survival analysis was performed by the use of Cox model.Results The results of univariate analysis indicated that clinicopathological characteristics related with lymph node metastasis were tumor distance from anal verge less than six cm,tumor diameter over two cm,muscularis invasion,distant metastasis and histological grade 3.The results of multivariate analysis showed that histological grade 3 was an independent risk factor of lymph node metastasis (OR=9.333,95 ％CI:1.054 to 82.635,P=0.045).The results of univariate survival analysis suggested that factors correlated with poor prognosis were tumor distance from anal verge less than six cm,tumor diameter over two cm,muscularis invasion,lymph node metastasis,distant metastasis and histological grade 3.The results of multivariate survival analysis indicated that tumor distance from anal verge less than six cm (HR=0.215,95 ％CI:0.047 to 0.980,P=0.047),distant metastasis (HR=8.788,95％CI:2.612 to 29.571,P＜0.01) and histological grade3 (HR=5.510,95％CI:1.692-17.944,P=0.005) were independent factors associated with poor prognosis.Conclusions For histological grade 1 and 2 rectal NET patients without distant metastasis,radical surgery is recommended when tumor diameter over two cm or muscularis invasion exists.For histological grade 3 rectal NET patients without distant metastasis,radical surgery is recommended.

Objective:To review the treatment of life threatening head and neck space infection.Methods:Retrospective was con-ducted to analyse the patient characterization,signs and symptoms at the time of presentation,presence of concomitant systemic co-morbidities,treatment,prognosis and bacteriology.Results:32 patients from 2007.01 to 2013.01(mean age was 57.71 years)were included.The cases were increased year by year.1 1 (34.37%)patients had breathing difficulty requiring tracheostomy and 19 (59.3%)had concomitant systemic comorbidities.23 cases recovered completely,8 with severe mediastinal infection were trans-ferred to the department of thoracic surgery or the department of respiratory medicine.1 patient died.Pus submission rate was 96.87%,the bacteria detection rate was 37.50%.Pus culture showed mixed infection dominated by streptococci.Staphylococcus au-reus,pseudomonas aeruginosa,enterococcus faecalis,prevotella and neisseria were detected.Conclusion:Annually incidence of life threatening head and neck space infection is increasing.Treatment of the infection should include:①Ensuring the airway patency;②Surgical incision and drainage as early as possible;③ Hypoglycemic control,maintenance of hemodynamic,nutritional support,and multi-disciplinary approach are the key points in the management of such infections;④ Systemic antibiotics.

Objective To investigate the differentiation of neuroendocrine component (NEC) in colorectal adenocarcinoma in relation to its significance by comparing the outcome between patients with or without NEC.Methods The paraffin sections from patients with pathologically confirmed colorectal adenocarcinoma were retrospectively collected and screened for those with NEC by morphological examination and immunohistochemistry with neuroendocrine markers.Control patients (n=54) without NEC were selected from colorectal cancer database and 2: 1 matched on the basis of clinical features with NEC positive patients (n=27).Relative analysis was performed between two groups.Results With a median follow-up of 72 months,the 5-year disease free survival was 58.0% (16/27) in NEC positive group and 79.1% (43/54) in control group (P=0.036).Similarly,the 5-year cancer-specific overall survival was significantly lower in NEC positive group than in control group (58.3% versus 81.1%,P=0.037).Cox regression showed that the 5-year cumulative risks of disease recurrence and cancer-caused death in NEC positive patients were 2.38 and 2.41 times higher than those in control patients,respectively.Conclusions NEC appears to bear a poor prognosis in patients with colorectal adenocarcinoma.

Objective:To compare the effects of low-carbohydrate diet (LCD) and low-fat diet (LFD) in the lifestyle intervention of non-alcoholic fatty liver disease (NAFLD) through a meta-analysis of randomized controlled trials.Methods:PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang were searched for relevant studies and study references and conference proceedings were manually searched. Two authors independently screened the items retrieved, extracted the data and assessed the quality of included studies. Meta-analysis was performed using R4.4.1 and RevMan5.4.1. Data were pooled using random-effects models and potential sources of heterogeneity were investigated using stratified meta-analysis. Funnel plots and Peters' test were used to assess publication bias.Results:Nine studies with a total of 510 participants met our inclusion criteria. Meta-analysis results showed that LCD and LFD interventions had similar effects on the reduction of intrahepatic lipid content in NAFLD patients ( SMD: -0.31,95% CI: 0.97 to 0.35, P = 0.36). There were no significant differences in changes of alanine aminotransferase ( SMD: -0.25, 95%CI: 0.91 to 0.41, P = 0.45) and aspartate aminotransferase ( SMD: -0.45, 95%CI: 1.63 to 0.72, P = 0.45) levels, either. Subgroup analyses implied that the duration of different interventions might be the cause of heterogeneity across studies. No significant publication bias was showed in the meta-analysis. Conclusion:Current evidence from randomized controlled studies does not support the superiority of LCD over LFD in the treatment of NAFLD.

ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Mesenchymal Stem Cells/physiology* ; Cellular Senescence ; Homeostasis ; Cell Cycle Proteins/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; Mitochondria/metabolism* ; Electron Transport Complex III/metabolism* ; Humans ; Cells, Cultured

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Animals ; Chloroquine/pharmacology* ; Longevity ; Rats