OBJECTIVETo examine the vesicular glutamate transporters (VGluTs: VGluT1-VGluT3) in the peripheral vestibular system.

METHODSThe vestibular structures, including Scarpa's ganglion (vestibular ganglion, VG), maculae of utricle and saccule, and ampullary cristae, from normal Sprague-Dawley rats were processed immunohistochemically for VGluTs, by avidin-biotinylated peroxidase complex method, with 3-3'-diaminobenzidine (DAB) as chromogen.

RESULTS(1) VGluT1 was localized to partial neurons of VG and to the putative primary afferent fibers innervating vestibular end-organs. (2) Intense VGluT3 immunoreactivity was detected in large number of sensory epithelia cells, and weak labeling of VGluT3-positive afferent fibers was in the maculae and ampullary cristae. (3) No or very weak VGluT2 immunoreactivity was observed in the VG and acoustic maculae.

CONCLUSIONThese results provide the morphological support that glutamate exists in the peripheral vestibular system, and it may play an important role in the centripetal vestibular transmission.

Acoustic Maculae ; metabolism ; Animals ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vesicular Glutamate Transport Proteins ; classification ; metabolism ; Vestibule, Labyrinth ; metabolism ; Vestibulocochlear Nerve ; cytology ; metabolism

Objective To explore whether autoreactive antibody presents in patients with sporadic idiopathic hypoparathyroidism(sIHP).Methods The subjects including 26 patients with sIHP and 112 genealogical members as well as 60 age-and sex-matched healthy controls.Anti-parathyroid antibodies in the sera were assayed by indirect immunofluorescence.The levels of calcium,phosphorus and magnesium as well as intact parathyroid hormone(iPTH)in the sera were tested.Results Positive autoantibodies against parathyroid tissue were demonstrated in 10 patients(38%)with sIHP,significantly higher than that of in genealogical members(10%,?~2=13.42,P

Objective To investigate the rehabilitation promoting factors in stroke patients and to provide references for the design and implementation of effective intervention for rehabilitation of stroke patients.Methods In-depth interviews were conducted among eight stroke patients,and interview data were collected and analyzed.Results Five themes were identified through analysis and classification of the interview data:practical rehabilitation goals,effective rehabilitation training behaviors,overcoming abandonment behaviors and negative emotions,suitable support system,and proper self-adjustment.Conclusion The rehabilitation promoting factors for stroke patients are performing effective rehabilitation training towards effective rehabilitation goals.In this process,patients need to rely on appropriate social support and patients' self-adjustment to overcome abandonment behaviors and negative emotions.These factors form a force to promote rehabilitation during the process of rehabilitation.

BACKGROUNDThe postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.

METHODSThe outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.

RESULTSOverall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15 th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).

CONCLUSIONSThis study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.

Adolescent ; Adult ; China ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm, Residual ; mortality ; therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; mortality ; therapy ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Transplantation, Homologous ; Young Adult

ObjectiveTo investigate the clinical efficacy and possible mechanism of Erzhi Tiangui prescription on repeated implantation failure （RIF） of kidney deficiency syndrome. MethodSeventy patients with RIF of kidney deficiency syndrome who underwent natural cycle frozen-thawed embryo transfer （FET） in the Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were enrolled and randomly divided into a treatment group （35 cases） and a control group （35 cases）. Patients in the treatment group took oral Erzhi Tiangui prescription from the third day of each menstrual cycle two months before the FET cycle and continued to take it until the day of transplantation from the third day of the menstrual cycle in the month of transplantation. Those in the control group did not accept traditional Chinese medicine （TCM）. In addition，10 patients who successfully achieved clinical pregnancy after the first natural cycle FET were screened from the reproductive medical record bank of this hospital and assigned to the normal group. Peripheral blood samples of patients in the three groups on the day of embryo transfer were collected from the specimen bank of the Reproductive and Genetic Center. Serum soluble programmed death molecule-1 （sPD-1），soluble programmed death molecule-ligand 1 （sPD-L1），transforming growth factor-β （TGF-β），interleukin-17 （IL-17）， and interleukin-10 （IL-10） levels were measured by enzyme-linked immunosorbent assay （ELISA）. The changes in kidney deficiency syndrome scores， the final biochemical pregnancy rates， clinical pregnancy rates， and embryo implantation rates of the treatment group and the control group before and after treatment were observed. ResultCompared with the normal group，the model group showed increased serum levels of sPD-1 and IL-17（r=0.347，P<0.05），decreased levels of IL-10 and TGF-β （P<0.01），and non-significant change in sPD-L1 level. Serum sPD-1 was positively correlated with IL-17 （P<0.05） and negatively correlated with IL-10（r=-0.521，P<0.01） and TGF-β（r=-0.457，P<0.01） in RIF patients with kidney deficiency syndrome. After TCM treatment，compared with the control group， the treatment group showed improved TCM syndrome score （P<0.05） and increased clinical pregnancy rate and embryo transfer rate（P<0.05），but there was no statistically significant difference in the biochemical pregnancy rate between the two groups. ConclusionAbnormal expression of sPD-1 in patients with RIF of kidney deficiency syndrome breaks the balance of T helper 17 （Th17）/regulatory T cell （Treg），which is not conducive to embryo implantation and pregnancy maintenance. Erzhi Tiangui prescription，a TCM for tonifying the kidney，can significantly improve the symptoms of kidney deficiency in patients with RIF of kidney deficiency syndrome，reduce the concentrations of sPD-1 and IL-17 in the peripheral serum，increase the levels of TGF-β and IL-10，regulate the peripheral Th17/Treg immune balance，and increase the implantation rate and clinical pregnancy rate，which has a high clinical value.

Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms. In recent years, the incidence of dry eye has been increasing year by year, and the diagnosis and treatment of dry eye are constantly evolving and innovating. However, due to the corresponding drawbacks of traditional examination methods and the lack of a large number of clinical trial studies on new examination methods, there is still no unified standard for the diagnosis and treatment of dry eye. In this review, we have performed a broad search for articles discussing different examination methods for dry eye, including promising diagnostic tools and technique, the latest advances, and contradictions, in order to provide a review of dry eye examination methods including the tear volume, the tear film, the eyelid and meibomian gland, and the degree of damage to the epithelial cells of the ocular surface, and provide a reference for the diagnosis and treatment of dry eye.

The alphaherpesvirus envelope glycoprotein I,encoded by the non-essential gene US7,plays an important role in the pathogenic mechanism of the virus.Recent studies have shown that envelope glycoprotein gI is important in the assembly of alpha herpesvirus particles and the diffusion of viral particles,by participating in secondary envelope coating and promoting in-tercellular transmission.The protein also has essential roles in promoting the axonal transport of the virus along neurons and the anti-host immune response,thereby affecting virulence.This article discusses the molecular mechanism through which gI affects the virulence of alpha herpes virus,thus providing a theoretical basis for in-depth study of the function of this protein.

Objective:To explore the multi-component， multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy （IgAN） by network pharmacology， aiming to provide evidence for its basic research and clinical application. Method:The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards， Traditinal Chinese Medicine Integrated Database （TCMID）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis， cell experiments in vitro were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53 （PI3K/Akt/p53） signaling pathway of human mesangial cells. Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items， which were related to nuclear hormone receptor binding， nuclear receptor activity， deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways， which were closely related to PI3K/Akt signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， advanced glycation end product/receptor of advanced glycation end product （AGE/RAGE） signaling pathway and others. Cell experiments in vitro confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB （PDGF-BB）-induced proliferation of human mesangial cells by regulating PI3K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis， oxidative stress， inflammation response and others， providing ideas and directions for the new drug development and mechanism study of IgAN.

OBJECTIVETo investigate the association between the rs2274223 and rs3765524 polymorphism of phospholipase C epsilon 1 (PLCE1) gene and the susceptibility to develop esophageal squamous cell carcinoma (ESCC) in a pure Kazakh Chinese population.

METHODSMatrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was utilized to genotype the potentially functional single nucleotide polymorphism rs2274223 A>G and rs3765524 C>T of PLCE1 in an ongoing hospital-based and case-control study of 200 ESCC cases with 300 cancer-free age ( ± 5 years) and sex matched controls. Statistical analyses were performed with Statistical Products and Services Solutions software (version 13.0). Adjusted odds ratios (OR) and 95% confidence evaluation intervals (95%CI) measured by multivariate logistic regression analysis were adopted to study the correlation of the gene polymorphism with the susceptibility to ESCC.

RESULTSThe genotype frequencies observed for rs2274223 was consistent with Hardy-Weinberg equilibrium in controls. Univariate analysis revealed significant differences between cases and controls with respect to genotype distribution for rs2274223 (P = 0.006). The variants of rs2274223 were found to confer significantly increased risk of ESCC (GG vs AA: OR = 3.17, 95%CI = 1.45-6.93; AG/GG vs AA: OR = 1.55, 95%CI = 1.08-2.22) in the Kazakh Chinese population. Moreover, AG/GG genotype of rs2274223 was found to be significantly associated with poorly-differentiated ESCC (OR = 2.48, 95%CI = 1.10-5.60). When the ESCC patients were divided into two subgroups, stage I/II and stage III/IV according to the AJCC TNM classification, the GT/GG genotype of rs2274223 was significantly associated with stage III/IV ESCC (OR = 1.85, 95%CI = 1.05-3.25). No significant association was found between rs3765524 and Kazakh ESCC.

CONCLUSIONSThese results indicate that rs2274223 site polymorphism of the PLCE1 gene is strongly associated with risk of ESCC in a Kazakh Chinese population, especially the poorly-differentiated and stage III/IV ESCC.

Alleles ; Carcinoma, Squamous Cell ; ethnology ; genetics ; Case-Control Studies ; China ; epidemiology ; Confidence Intervals ; Esophageal Neoplasms ; ethnology ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kazakhstan ; ethnology ; Male ; Middle Aged ; Odds Ratio ; Phosphoinositide Phospholipase C ; genetics ; Polymorphism, Single Nucleotide ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases