Objective:To analyze the clinical and genetic characteristics of a family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) caused by a new locus of HTRA1 mutation. Methods:The medical history and clinical data of a patient with CARASIL were collected, and genetic test was performed on some family members to observe the HTRA1 mutation. Results:The proband presented with cognitive impairment, suspicious lumbar lesions, and alopecia. Cranial imaging revealed extensive blank brain lesions and multiple microbleeding foci. The mother of the proband had psychiatric symptoms and stroke once, and the sixth younger sister had history of dementia and hypertension. Genetic test revealed that the proband and his two sons carried HTRA1 heterogenic mutation c.888C>G (p.I296M), and the two sons had alopecia. Conclusion:The c.888C>G(p.I296M) may be a new pathogenic mutation site of CARASIL.

Objective:To investigate the effect of miRNA (miR) -193b-5p on melanogenesis and its possible mechanisms.Methods:Human primary melanocytes were isolated from discarded normal foreskin tissues of healthy males after circumcision, and cultured in vitro. miR-NC mimics (miR-NC mimic group) and miR-193b-5p mimics (miR-193b-5p mimic group) were transfected into human primary melanocytes and human MNT1 melanoma cells, separately. After transfection, real-time quantitative PCR (RT-qPCR) was performed to determine the overexpression efficiency of miR-193b-5p at 48 hours, Western blot analysis to determine the expression of melanogenesis-related proteins tyrosinase (TYR) and microphthalmia-associated transcription factor (MITF) in human primary melanocytes and human MNT1 melanoma cells at 72 hours, and the melanin content in the above cells was determined by a sodium hydroxide solubilization method at 1 week. The target gene of miR-193b-5p was predicted by using Targetscan algorithms and verified by dual-luciferase reporter assay, and RT-qPCR and Western blot analysis were performed to analyze changes in mRNA and protein expression of the target gene respectively after the overexpression of miR-193b-5p. Two-independent-samples t test was used for comparisons between two groups. Results:In human primary melanocytes and human MNT1 melanoma cells, the miR-193b-5p expression levels were significantly higher in the miR-193b-5p mimic groups than in the miR-NC mimic groups ( t = 65.57, 22.49, respectively, both P < 0.001) , and the melanin content was significantly lower in the miR-193b-5p mimic groups (0.091 ± 0.007, 0.130 ± 0.004, respectively) than in the miR-NC mimic groups (0.117 ± 0.002, 0.188 ± 0.032, t = 5.98, 3.24, P < 0.01, < 0.05, respectively) . Western blot analysis showed that the expression of melanogenesis-related proteins TYR and MITF in both human primary melanocytes and human MNT1 melanoma cells was significantly lower in the miR-193b-5p mimic groups than in the miR-NC mimic groups (all P < 0.01) . TargetScan analysis and dual-luciferase reporter assay revealed a binding site for miR-193b-5p in the 3′ untranslated region of the transcriptional regulator CITED2. After up-regulation of miR-193b-5p expression in human primary melanocytes and human MNT1 melanoma cells, the CITED2 mRNA and protein expression levels significantly decreased compared with the miR-NC mimic groups (all P < 0.05) . Conclusion:miR-193b-5p overexpression can down-regulate the expression of melanogenesis-related proteins TYR and MITF, and then inhibit melanogenesis, which may be related to the targeted inhibition of CITED2 expression.

Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis.

Objective:To evaluate the effect of unilateral pediatric kidney donation for adult kidney transplantation.Methods:Retrospective analysis was conducted on the cases of children who donated unilateral donor kidney for adult kidney transplantation recipients in our hospital, and those who were followed up for more than three years were included in this study. The body weight of the recipients in group A was ≤50 kg, and the body weight of the recipients in group B was ≤70 kg.The recipients were divided into 0-5 year old donor group (group A) and 6-17 year old donor group (B group). Clinical data, recipient/kidney survival, graft function and growth, and complications of the recipient were analyzed.Results:A total of 45 adult recipients were enrolled, including 12 in group A and 33 in group B. The renal survival rate at 3 years after operation was (100%, 96.9%)/(91.6%, 93.9%). One week after the operation, the early postoperative recovery of renal function in group B was better than that in group A, and the difference of serum creatinine was statistically significant ( P<0.05), while the difference of serum creatinine in other postoperative follow-up time points was not statistically significant ( P>0.05). Within a year, both groups of grafts continued to grow, reaching adult levels in one year. There was no statistical significance in the incidence of complications between the two groups ( P>0.05). The incidence of protein in the two groups was 33.3% and 6.1%, respectively, 1 case in each group still had proteinuria at 1 year after surgery, and only 1 case in the infant donor kidney recipient in group A had proteinuria at 3 years after surgery. Conclusions:Unilateral donor kidney transplantation from children can provide good results for adult patients with uremia by selecting suitable donors according to the weight of the recipient.

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.

Objective:To explore the current situation of the use of assistive devices for mobility in patients with knee osteoarthritis and analyze its influencing factors.Methods:Using the convenient sampling method, patients with knee osteoarthritis who were admitted to the Orthopedics Department of a Class Ⅲ Grade A general public hospital in Zhengzhou from January to July 2019 were selected as the research objects. The general information questionnaire, the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) Scale and other scales were used to conduct surveys. Univariate analysis and binary Logistic regression analysis were used to investigate the influencing factors of the use of assistive devices for mobility in patients with knee osteoarthritis. In this study, a total of 347 questionnaires were distributed and 340 valid questionnaires were returned. The effective recovery rate was 97.98%.Results:The usage rate of assistive devices for mobility in patients with knee osteoarthritis was 26.47% (90/340) , 5.55% (5/90) of the patients were recommended using assistive devices for mobility by medical staff, 2.22% (2/90) of the patients obtained assistive devices for mobility through professional adaptation, and 81.11% (73/90) of the patients did not receive health education on assistive devices for mobility. The total mean score of the QUEST Scale for 90 patients with knee osteoarthritis using assistive devices for mobility was (3.17±0.34) . Binary Logistic regression analysis showed that age, education level, monthly income, pain intensity, the activity of daily living status and social support were influencing factors for the use of assistive devices for mobility in patients with knee osteoarthritis ( P<0.05) . Conclusions:Patients with knee osteoarthritis have a lower usage rate of assistive devices for mobility, receive fewer professional assistive devices for mobility services, and have lower satisfaction with them. There are many factors affecting whether or not to use assistive devices for mobility. Medical staff should pay more attention to and guide the use of assistive devices for mobility for patients with knee osteoarthritis.

Objective:To analyze the clinical characteristics and possible causes of familial spontaneous pneumothorax in combination with literatures.Methods:The detailed clinical information of 8 cases of FSP were retrospectively reviewed, and the clinical characteristics of FSP were analyzed combined with literatures.Results:Among 265 FSP patients in 76 families, the ratio of male to female is 1.55∶1, age of onset over 40 years old was 48.30%, 17.11%(13/76)of the cases occurred in the same generation, 67.10%(51/76)in two generations, 14.47%(11/76)in three generations and 1.31%(1/76)in four generations, and no intergenerational phenomenon was found. The proband had the mutation in the FLCN gene. The recurrence rates of observation, thoracentesis, chest tube drainage and operation were 21.62%(8/37), 48.39%(30/62), 38.89%(35/90)and 4.00%(4/100), respectively.Conclusion:Compared with sporadic cases of PSP, the clinical characteristics of FSP are as follows, the incidence of pneumothorax in man is higher than women, but women is significantly higher, and the age of pneumothorax is later, most of them are two generations, which may be related to heredity. And the effect of surgical treatment is the best.

Objective To analyze the impact of Helicobacter pylori standard strain (Hp P12) and its virulence factor vacuolating cytotoxin A ( VacA) on DNA damage and homologous recombination ( HR) repair in a human gastric epithelial cell line (GES-1). Methods Strains of Hp P12 and vacA gene knock-out Hp P12 ( Hp P12 ΔvacA) were respectively used to infect GES-1 cells at a multiplicity of infection of 100. GES-1 cells treated with etoposide (50μmol/L) or mitomycin (0. 5μg/ml) for 2 h were used as posi-tive control. Western blot and immunofluorescence were performed to detect the expression of DNA damage marker protein γH2AX and key HR repair proteins (Rad51, pMRE11, CtIP and pCtIP) and the recruitment of them at DNA damage sites. Human embryonic kidney HEK-293 ( DR-GFP) cells were infected with Hp P12 and Hp P12 ΔvacA strains to verify the impact of VacA on HR repair efficiency. Results The expres-sion and recruitment of γH2AX and key HR repair proteins ( Rad51, pMRE11, CtIP and pCtIP) were in-creased in Hp P12-infected cells as compared with that in uninfected and Hp P12 ΔvacA-infected cells ( all P<0. 05). To evaluate the HR repair efficiency, I-SceⅠ plasmid-transfected HEK-293 (DR-GFP) cells were infected with Hp P12 and Hp P12 ΔvacA and the results showed that green fluorescent protein ( GFP)-positive cells were decreased after infection, especially in Hp P12 ΔvacA-infected cells (both P<0. 05). Conclusions Hp P12 infection could cause DNA damage and promote HR repair in GES-1 cells, in which the virulence factor VacA played an important role.

Objective To explore the mechanism of latent human immunodeficiency ciency virus type 1 (HIV-1) infection is unclear, especially in dendritic cells (DC).We hypothesized that DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) binds with HIV-1 may activate HIV-1 provirus.Methods We generated a model by transfecting 293T cells with a DC-SIGN expression plasmid and a HIV-1 5'long terminal repeat (LTR) reporter plasmid, and then stimulated the 293T cells with HIV-1 gp120 protein, wild-type HIV-1 and VSV-G-pNL4.3 pseudotype virus ( without gp120 protein).CEM-Bru cells were transfected with the DC-SIGN expression plasmid and stimulated by HIV-1 gp120 protein.Then HIV-1 replication was detected.The involvement of the ERK, p38 and NF-κB pathways signaling in this response were determined by inhibiting the pathways specifically and detecting the phosphorylation of the signaling kinase.Results The HIV-1 5'LTR was reactivated by HIV-1 gp120 in DC-SIGN-expressing 293T cells.After HIV-1 gp120 protein stimulation of the mold of CEM-Bru cells, the increasing expression of HIV-1 Tat mRNA and HIV-1 p24,which implies early and late HIV-1 provirus replication was reactivated by the HIV-1 gp120/DC-SIGN stimulation.HIV-1 gp120/DC-SIGN stimulation reactivates latent HIV-1 provirus via the NF-κB signal pathway.Conclusion HIV-1 gp120/DC-SIGN stimulation reactivates latent HIV-1 provirus via the NF-κB signal pathway.

Objective To understand the awareness of children snoring disease knowledge and demand of health education and appropriate health education methods from the parents whose children were in hospital by snoring, and provide basis for health education in clinic. Methods On the basis of literature search and expert consultation, 276 parents whose children in hospital by snoring were investigated by self-designed questionnaire. The questionnaire included the awareness of children snoring disease knowledge and demand of health education and appropriate health education methods were carried out. Results The awareness rate of children snoring disease knowledge was 2.54%-55.07% in parents whose children in hospital by snoring. The average demand rate of health education surpass 80%, major reason and symptom and main therapy and surgical outcomes of snoring were more concerned with 100.00%(276/276). The average demand rate of the impact on the intelligence was 96.38%(266/276). Acceptable methods of health education from high to low were as follows, consulting a doctor was 93.48%(258/276), posting publicity column in the halls or ward hallway was 74.28% (205/276), attending health education lecture was 66.30% (183/276), through QQ group or micro letter platform was 61.96%(171/276), through community healthy knowledge publicity column was 56.52%(156/276), through broadcast radio and television programs when see a doctor or in hospital was 53.62%(148/276), through telephone counseling was 36.96%(102/276), through hospital health prescription was 36.23% (100/276), through audiovisual teaching materials was 32.25% (89/276), communication between parents was 7.97%(22/276). Conclusions The awareness rate of children snoring disease knowledge from the parents whose children in hospital by snoring is low, the medical staff need take various ways of health education to improve snoring children′s parents′overall understanding level of children sleep apnea, effectively prevent various influencing factors of sleep apnea and snoring related complications, to reduce the dangers caused by snoring.