Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0～7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100％)and Pepsinogen Ⅰ(83％),focally positive for H+/K+-ATPase(58％).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human/genetics* ; Humans ; Immunophenotyping ; Killer Cells, Natural ; Lymphoproliferative Disorders ; Male

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective To investigate the role of zinc finger protein 36,C3H type-like 1 (ZFP36L1) mediating astrocytes activation in the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). Methods Superoxide dismutase 1 (S0D1)-G93A transgenic mice were used as animal models, the wild-type littermates as the control (13 mice were taken from mutant and wild-type mice at each time point) . The ZFP36L1 mRNA and protein levels of the spinal cord in the early, middle and late stage were detected by Real-time PGR and Western blotting. The expression and distribution of ZFP36L1 in the spinal cord were detected by immunofluorescence. Primary astrocyte model was established from 15 postnatal 1-2 day mice. The ZFP36L1 mRNA and protein levels in astrocytes were detected by Real-time PCR and Western blotting. Si-ZFP36L1 was transfected into SOD1-G93A mutant primary astrocytes. The transfection efficiency was detected by Western blotting. Tumor necrosis factor a (TNF-a) and interleukin-18 (IL-18) secreted from astrocytes after transfection were assessed by Western blotting and ELISA. After silencing ZFP36L1 in SOD1-G93A mutant primary astrocytes, it was cocultured with SOD1-G93A mutant NSC34 cells. 5 ' -ethynyl-2' deoxyuridine (EdU) test and the level of proliferating cell nuclear antigen (PCNA) were used to determine the effect of ZFP36L1 on NSC34 cell proliferation. TUNEL test and the level of cleaved-Caspase-3 were used to determine the effect of ZFP36L1 on NSC34 cell apoptosis. Blank small interfering RNA(siRNA) was transfected as the control group. Results Compared with the wild-type mice, the mRNA and protein levels of ZFP36L1 were downregulated in the spinal cord of SOD1-G93A transgenic mice. In wild type mice, ZFP36L1 positive cells were mainly [^-tubulin IE positive. In SOD1-G93A mutant mice, ZFP36L1 positive cells were mainly glial fibrillary acidic protein (GFAP) positive. The expression of ZFP36L1 in SOD1-G93A mutant primary astrocytes increased, and si-ZFP36Ll reduced the level of ZFP36L1 in SOD1-G93A mutant primary astrocytes significantly. Inflammatory factors including TNF-a, IL-18 decreased significantly after silencing ZFP36L1. In addition, after silencing ZFP36L1 expression, SOD1-G93A mutant primary astrocytes enhanced the proliferation activity of NSC34 cells and inhibited NSC34 cell apoptosis significantly. Conclusion Astrocytes are activated in the process of ALS. ZFP36L1 promotes the degeneration of motor neurons in ALS through the inflammatory factors secreted by astrocytes.

A fungal strain WXF1904, was isolated from a starfish sample corrected in the South China Sea. According to its internal transcribed spacer (ITS) analysis, the strain was identified as a member of the genus Aspergillus and designated as Aspergillus sp. WXF1904. One new isocoumarin containing halogennamed 6-chloro-5,7-dihydroxy-3,8-dimethylisocoumarin (1), along with six known compounds pilobolusate (2), p-hydroxybenzaldehyde (3), methyl orsellinate (4), catechol (5), vanillic acid (6), and wasabidienone E (7), were isolated from the cultures of Aspergillus sp. WXF1904 by silica gel column chromatography, ODS gel column chromatography, and high performance liquid chromatography (HPLC). Their structures were elucidated by high resolution mass spectrometry (HR-MS), nuclear magnetic resonance (NMR) as well as literature comparison. The new compound 5-chloro-6,7-dihydroxy-3,8-dimethylisocoumarin and compound 2 showed weak acetylcholinesterase inhibitory activity.

Objective:To investigate characteristics and differences of cerebral glucose metabolism in patients with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis from the perspective of different trigger factors of antibodies. Methods:A total of 15 patients (8 males, 7 females, age (30.5±17.7) years) with anti-NMDAR encephalitis between January 2016 and January 2019 in Huashan Hospital, Fudan University were recruited retrospectively. All patients underwent resting state cerebral 18F-FDG PET imaging. The characteristics of brain glucose metabolism were analyzed, and the SUV ratio (SUVR) was semi-quantitatively compared with that in 12 healthy subjects (HS; 7 males, 5 females, age (51.5±9.6) years). Independent-sample t test was used to analyze the data. Results:Among 15 patients, 5 patients were viral encephalitis-related anti-NMDAR encephalitis, showing focal decreased metabolism in unilateral temporal lobe or basal ganglia (SUVR: patients: 0.659±0.219; HS: 1.754±0.203; t=-9.58, P<0.001), with increased metabolism in contralateral temporal lobe or basal ganglia (SUVR: patients: 2.275±0.244; HS: 1.960±0.227; t=2.55, P=0.022) in 18F-FDG PET imaging. Six patients were cryptogenic anti-NMDAR encephalitis, showing asymmetric increased metabolism in frontal, temporal, parietal and basal ganglia (SUVR: patients: 2.482±0.395; HS: 1.754±0.203; t=5.23, P<0.001), with decreased metabolism in bilateral occipital lobes. The remaining 4 cases were paraneoplastic origin accompanied by teratoma, showing increased metabolism in bilateral temporal and basal ganglia (SUVR: patient: 2.359±0.181; HS: 1.960±0.227; t=3.16, P=0.007), with mild decreased metabolism in bilateral occipital lobe. Conclusions:The abnormal changes of cerebral glucose metabolism in patients with anti-NMDAR encephalitis can be divided into at least three patterns according to different trigger factors. A comprehensive understanding of these characteristic metabolic changes is helpful for detecting disease, and may provide potential value in indicating different causes.