Objective To evaluate the significance of human papillomavirus L1 capsid protein (HPVL1) and human telomerase RNA component (hTERC) gene in the cytologic specimens of cervix which was infected by the high-risk types of human papillomavirus (HR-HPV),and to expose their relationship with cervical lesions.Methods The fluorescence signal of cytologic samples of cervix were detected by interphase FISH in chromosome enumeration double-color DNA probes TERC.The expression of HPVL1 capsid protein was detected by MaxVision immunohistochemistry method.300 samples were analyzed with HR-HPV positive from the cervical biopsy.The diagnoses as normal or chronic inflammation (n =45),cervical intraepithelial lesions Ⅰ grade (CIN Ⅰ,n =95),CIN Ⅱ (n =58),CIN Ⅲ (n =64),and squamous cervical cancer (SCC,n =37).Results The percentage of HPVL1 positive rates in normal or chronic inflammation,CIN Ⅰ,CIN Ⅱ,CIN Ⅲ and SCC groups were 58.70 ％ (27/46),63.16 ％ (60/95),37.93 ％ (22/58),10.94 ％ (7/64) and 0 (0/37),respectively.The percentage of HPVL1 decreased along with the increase of severity of the cervical intraepithelial lesions.Genomic amplification of hTERC positive rates in normal or chronic inflammation,CIN Ⅰ,CIN Ⅱ,CIN Ⅲ and SCC groups were 6.52 ％ (3/46),11.58 ％ (11/95),51.72 ％ (30/58),85.94 ％ (55/64) and 100.00 ％ (37/37),respectively.The percentage of hTERC increased along with the severity of the cervical intraepithelial lesions (rs =0.302,P ＜ 0.01).The percentage of HPVL+/hTERC-was 57.89 ％ in CIN Ⅰ group and 4.69 ％ in CIN Ⅲ group.The percentage of HPVL-/hTERC+ was 6.32 ％ in CIN Ⅰ group and 79.69 ％ in CIN Ⅲ group.Conclusion The detection of HPVL1 and hTERC are important for assisting cervical lesions screening and monitoring of disease progression in the HR-HPV positive cytologic specimens.

PURPOSE: Information on the possible role of the ribosomal protein S15a (RPS15a) in gastric cancer is scarce. The aim of this study was to evaluate the impact of RPS15a gene expression on the growth and cell cycle of gastric cancer cells in vitro and in vivo. MATERIALS AND METHODS: RPS15a mRNA expression was examined in cancer tissues and their corresponding adjacent normal tissues of 40 gastric adenocarcinoma patients. Next, RPS15a was knocked down using a lentivirus-mediated RNA interference (short hairpin RNA) system in the gastric cancer cell line BGC823. The effect of RPS15a knockdown was examined using CCK-8 assay, cell scratch test, colony formation assay, and flow cytometry. Finally, in nude mice, a tumorigenicity test was performed, and the tumor volume and weight were measured. RESULTS: RPS15a expression in tumor tissue was significantly greater than that in the adjacent normal tissue of gastric cancer patients. After RPS15a silencing, the BGC823 cell proliferation rate decreased significantly; most cells were arrested in the G0/G1 phase, cell growth was inhibited, and the migration rate was decreased. Colony formation assay showed that the number and size of clones in the RPS15a-silenced cells were fewer and smaller, compared to control cells. The nude mouse tumorigenicity test showed that RPS15a silencing had an inhibitory effect on tumor volume and mice weight. CONCLUSION: The present study found RPS15a expression to be higher in gastric tumors and its silencing in gastric cancer cells to inhibit the proliferation, growth, and migration thereof. Accordingly, RPS15a may be considered as a potential therapeutic target in gastric cancer.
Adenocarcinoma ; Animals ; Carcinogenicity Tests ; Cell Cycle ; Cell Line ; Cell Proliferation* ; Clone Cells ; Flow Cytometry ; Gene Expression ; Gene Silencing ; Humans ; In Vitro Techniques ; Mice ; Mice, Nude ; Ribosomal Proteins ; RNA Interference ; RNA, Messenger ; Sincalide ; Stomach Neoplasms* ; Tumor Burden

Clinical data of a child with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) diagnosed in the First Affiliated Hospital of Zhengzhou University in June 2020 were retrospectively analyzed.A female patient with 1 year and 2 months old presented with 10 months of developmental delay and 1 month of recurrent seizures.Physical examinations showed grade Ⅲ muscle strength of limbs, slightly higher muscle tone, active reflex of bilateral knee tendons, normal reflex of bilateral achilles tendons, and positive Babinski sign.Brain magnetic resonance imaging (MRI) showed bilateral cerebral hemisphere atrophy and diffuse abnormal signals.The whole exome sequencing test showed two heterozygous mutations of the DARS2 gene in the present case.There are no reports of early-onset LBSL gene mutation in Chinese population.A total of 6 related foreign literatures have been reported.All affected cases present psychomotor development disorders and other encephalopathy manifestations.Brain MRI involvement and DARS2 gene mutations are found in previous reports.Therefore, for children with developmental retardation, epilepsy, and diffuse abnormal signals in both cerebral hemispheres examined by brain MRI, genetic testing is recommended to confirm the diagnosis, guide prenatal diagnosis and genetic counseling.

Objective To explore the characteristics of functional connectivity based on cerebellum at resting state and the brain functions related to cognitive function on attention deficit hyperactivity disorder (ADHD).Methods Thirty ADHD children (ADHD group) were diagnosed at ADHD Specialist Clinic of Changzhou Children's Hospital,Nantong University from June 2015 to July 2017,and 33 healthy children (healthy control group) were selected from a normal school in Changzhou.Then,they received the functional and structural magnetic resonance imaging (MRI)scans.Finally,the differences of the characteristics of functional connectivity were compared between the 2 groups based on cerebellum which had been found with dysfunction on the previous study of amplitude of low-frequency fluctuation.Results It all showed positive activated brain regions when comparing ADHD group and healthy control group based on left cerebellum (-49.5,-58.5,-18.5) as ADHD children's functional connectivity scores were higher in left middle frontal gyrus [volume =835 mm3,coordinate (-27,-21,51)],right middle frontal gyrus [volume =755 mm3,coordinate(45,-3,6)],right superior temporal gyrus [volume =256 mm3,coordinate (45,-24,-6)],left limbic lobe[volume =513 mm3,coordinate (-15,-3,-18)],and there were statistically significant differences between the 2 groups (t =4.10,4.38,3.97,3.32,all P ＜ 0.05).Conclusions There exist abnormal functional connectivity between cerebellum and left middle frontal gyrus,right middle frontal gyrus,right superior temporal gyrus and left limbic lobe.It may be one of the brain mechanisms of the main clinical manifestations of the decreasing of attention,hyperactivity and impulsiveness and the dysfunction of cognitive function.

Retrospective analysis of the clinical data of a child with type 102 mental retardation caused by DDX3X gene mutation in the pediatric diagnosis of the First Affiliated Hospital of Zhengzhou University in April 2019.A 2 years and 3 months old girl with " delay for more than 1 year" , using second-generation sequencing technology for full exon detection, and the result is DDX3X gene 13 th exon c. 1463G>A hybridization mutation, this is a new mutation.There are no Chinese cases reported with DDX3X gene mutations, and there are 8 related cases were reported in foreign literature, all children have different degrees of intellectual disability.So patients with unexplained intellectual disability(especially female patients) need to be wary of the possibility of DDX3X gene mutation.

Objective:To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome.Methods:The data of 3 children with febrile infection-related epilepsy syndrome admitted to the First Affiliated Hospital of Zhengzhou University from May to June 2019 were collected retrospectively, and their clinical characteristics, diagnosis, treatments and prognosis were summarized in combination with relevant literature.Results:The age of onset was 6-9 years old.The time interval from fever to first convulsion was 4-7 days, and they progressed to status epilepticus within 24 hours.The seizures were mainly multifocal seizures.Cerebrospinal fluid laboratory examination was normal.Electrocardiogram shows diffuse slow wave activity as the background, and epileptic waves dominated by the temporal area.Cranial magnetic resonance imaging showed signs of edema in 2 cases during the acute phase.All patients were resistant to multiple (4-5) anti-epileptic drugs, but high-dose anesthetic drugs can effectively terminate status epilepticus.All cases developed into refractory epilepsy, 2 cases had cognitive impairment and 1 case had movement impairment after 1 year.Conclusion:Febrile infection-related epilepsy syndrome often occurs in school-age children who have been physically healthy, which was included by fever.The seizures are explosive and refractory in febrile infection-related epilepsy syndrome, and it lacked specific laboratory indicators.High-dose anesthetics can effectively terminate status epilepticus, but it always has a poor prognosis.

Objective: To analyze the clinical and pathological features and prognostic factors of neuroendocrine carcinoma of the cervix (NECC). Methods: The clinical data of 35 cases of NECC treated in Shanxi Provincial Cancer Hospital from January 2006 to May 2014 were retrospectively analyzed. Results: The median age of 35 cases of NECC was 43 years old. The infection rate of human papillomavirus (HPV) 18 type was 66.7% (10/15) in 15 NECC patients who were tested with HPV. The accuracy rate of diagnosis was 14.3% (5/35) before procedure. The positive detection rate of Syn, CgA, AE1/AE3, P63 and NSE were respectively 100.0% (35/35), 80.0% (28/35), 100.0% (35/35), 34.3% (12/35) and 57.1% (20/35). The 3-year overall survival rate of 35 NECC cases was 34.29% (12/35). The age, volume of local tumor and degrees of interstitial infiltration were the main prognostic factors of patients with NECC(all P < 0.05). Conclusions NECC is easily misdiagnosed by pathomorphological examination alone, the accuracy of diagnosis could be improved by detecting neuroendocrine carcinoma markers with immunohistochemical method. The infection rate of HPV18 is higher than the others in NECC. The volume of local tumor is one of the main prognostic factors for NECC patients.

OBJECTIVE: To explore the genetic basis for 7 patients with Alström syndrome. METHODS: DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4). CONCLUSION ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.
Alstrom Syndrome/genetics* ; Cell Cycle Proteins/genetics* ; Humans ; Mutation ; Pedigree ; Whole Exome Sequencing

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.
Asthma ; Humans ; Inflammation ; Respiratory System ; Rhinitis, Allergic ; Sinusitis