Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

Purpose To investigate the clinicopathological characteristics of the gastric oxyntic gland adenoma(GOGA).Methods We collected 18 samples of GOGA,histopathological features and immunohistochemical staining were assessed.Main features of pathological diagnosis,treatment methods and follow-up were retrospectively analyzed.Results There were 18 patients,including 9 females and 9 males,aged from 36 to 86 years old.The endoscopic im-age showed a flat lesion with whitish in color or a polypoid protrusions.The size ranged from 0.3 cm to 0.8 cm.Hema-toxylin and eosin staining showed irregular glandular structures in the mucosal lamina propria,with branched and anas-tomosed patterns.The tumour demonstrating composed of chief cells hyperplasia with mild nuclear atypia.All lesions were confined to the mucous lamina propria.There was no atrophic within the peripheral gastic mucosa.Immunohisto-chemical examination showed positive for Pepsinogen-Ⅰ and MUC6.Gene mutation were analyzed in 2 cases using next generation sequence technology,and no KRAS and GNAS mutation had been detected.Endoscopic surgical treatment was performed in 11 cases,and biopsy forceps removal was carried out in 7 cases.No recurrence or metastasis was ob-served during the follow-up period of 1 to 58 months.Conclusion GOGA is a rare lesion,and appears to behave bio-logically benign.A full understanding of its histological morphology and biological behavior can improve the diagnostic ability of clinincans,and facilitate further research in the future.

Objective To establish a research protocol to clarify the characteristic changes in major functional activities and cellular processes involved in bone marrow during aging using RNA sequencing,and to identify potential targets for aging prediction and intervention.Methods Bone marrow cells were extracted from the bilateral tibiae and femurs of three C57BL/6J male mice aged 2,10,and 18 months,respectively.After red blood cell lysis,RNA was extracted for sequencing analysis.Results The result of gene expression and Venn analysis showed that gene expression levels were predominantly down-regulated from 2～10 months,but mainly up-regulated from 10～18 months.Gene expression thus changed from mainly down-regulation to mainly up-regulation during maturation and development in mice.Kyoto encyclopedia of genes and genomes and gene set enrichment analyses indicated that bone marrow tissues in mice at different ages showed significant expression differences in the"immune system""development and regeneration""transport and catabolism""cell growth and death"and other pathways.Specifically,inflammatory,cytoskeletal,and DNA repair pathways showed sustained activation,contrasting with progressive hematopoietic decline and fluctuating immune regulation.Enriched pathway screening revealed interactions among differentially expressed genes,such us upregulated genes Bmpr1a and Inhba,downregulated genes Dntt and Ccnd1,and downregulated genes Col1a1,Col1a2,Fcgr1,Fyn,Lgmn,Ctsl,Ctsk,Ctss,Gnail,Myl4,and Ccr5,involved in HSCs homeostasis,cell cycle,DNA repair,immune regulation,and apoptosis.Conclusions This study provides data on gene expression changes at the transcriptional level and offers a research strategy to explore the major characteristic changes in bone marrow during aging in mice.The result identify aging-related genes and signaling pathways,thus providing new strategies for delaying aging and preventing aging-related diseases.

Objective To establish a research protocol to clarify the characteristic changes in major functional activities and cellular processes involved in bone marrow during aging using RNA sequencing,and to identify potential targets for aging prediction and intervention.Methods Bone marrow cells were extracted from the bilateral tibiae and femurs of three C57BL/6J male mice aged 2,10,and 18 months,respectively.After red blood cell lysis,RNA was extracted for sequencing analysis.Results The result of gene expression and Venn analysis showed that gene expression levels were predominantly down-regulated from 2～10 months,but mainly up-regulated from 10～18 months.Gene expression thus changed from mainly down-regulation to mainly up-regulation during maturation and development in mice.Kyoto encyclopedia of genes and genomes and gene set enrichment analyses indicated that bone marrow tissues in mice at different ages showed significant expression differences in the"immune system""development and regeneration""transport and catabolism""cell growth and death"and other pathways.Specifically,inflammatory,cytoskeletal,and DNA repair pathways showed sustained activation,contrasting with progressive hematopoietic decline and fluctuating immune regulation.Enriched pathway screening revealed interactions among differentially expressed genes,such us upregulated genes Bmpr1a and Inhba,downregulated genes Dntt and Ccnd1,and downregulated genes Col1a1,Col1a2,Fcgr1,Fyn,Lgmn,Ctsl,Ctsk,Ctss,Gnail,Myl4,and Ccr5,involved in HSCs homeostasis,cell cycle,DNA repair,immune regulation,and apoptosis.Conclusions This study provides data on gene expression changes at the transcriptional level and offers a research strategy to explore the major characteristic changes in bone marrow during aging in mice.The result identify aging-related genes and signaling pathways,thus providing new strategies for delaying aging and preventing aging-related diseases.

Purpose To investigate the clinicopathological characteristics of the gastric oxyntic gland adenoma(GOGA).Methods We collected 18 samples of GOGA,histopathological features and immunohistochemical staining were assessed.Main features of pathological diagnosis,treatment methods and follow-up were retrospectively analyzed.Results There were 18 patients,including 9 females and 9 males,aged from 36 to 86 years old.The endoscopic im-age showed a flat lesion with whitish in color or a polypoid protrusions.The size ranged from 0.3 cm to 0.8 cm.Hema-toxylin and eosin staining showed irregular glandular structures in the mucosal lamina propria,with branched and anas-tomosed patterns.The tumour demonstrating composed of chief cells hyperplasia with mild nuclear atypia.All lesions were confined to the mucous lamina propria.There was no atrophic within the peripheral gastic mucosa.Immunohisto-chemical examination showed positive for Pepsinogen-Ⅰ and MUC6.Gene mutation were analyzed in 2 cases using next generation sequence technology,and no KRAS and GNAS mutation had been detected.Endoscopic surgical treatment was performed in 11 cases,and biopsy forceps removal was carried out in 7 cases.No recurrence or metastasis was ob-served during the follow-up period of 1 to 58 months.Conclusion GOGA is a rare lesion,and appears to behave bio-logically benign.A full understanding of its histological morphology and biological behavior can improve the diagnostic ability of clinincans,and facilitate further research in the future.

Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

Objective To establish interferon-induced transmembrane protein 3(Ifitm3)knockout mice and to explore the effects of Ifitm3 on the proliferation and differentiation of adult neural stem cells of mice(aNSCs).Methods IFITM3 knockout mice were established by the CRISPR/Cas9 method and identified by genotype identification and Western Blot.The differences between Ifitm3-knockout mice and wild-type mice were analyzed by hematoxylin-eosin(HE)staining and flow cytometry.The aNSCs of wild-type mice and Ifitm3-knockout mice were isolated and cultured,the number and size of neurospheres were detected,The ability of aNSCs to proliferate and differentiate were detected by quantitative reverse-transcription polymerase chain reaction,Western Blot,and immunofluorescence.Results Ifitm3-knockout mice were successfully established.The mice developed normally,and there were no obvious abnormalities either histopathologically or the immune system.In vitro experiments showed that Ifitm3 knockout inhibited the self-renewal potential of aNSCs,led to a decrease in the proliferation ability of aNSCs,and inhibited the differentiation of aNSCs into immature neurons and astrocytes.Conclusions This study finds that a lack of IFITM3 result in the ability of aNSCs to proliferate and differentiate decreased,IFITM3 may regulate the function of aNSCs.

The pathogenesis of stroke is complex, with genetic risk factors as one of the main factors. The genetic variants of phosphodiesterase 4D (PDE4D) was significantly associated with the susceptibility to ischemic stroke (IS) in Caucasian population, but its association with the susceptibility to stroke in Chinese population is unclear. This article is intended to review the research on the association between PDE4D genetic variants and stroke susceptibility in Chinese population, aiming to further optimize the relevant research programs and provide reference for the prevention and treatment of stroke in China.
Humans ; Brain Ischemia/genetics* ; Genetic Predisposition to Disease ; East Asian People ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics* ; Stroke/genetics* ; Polymorphism, Single Nucleotide ; Risk Factors

Objective:To analyze clinical characteristics and high-frequency ultrasound features of localized scleroderma, and to construct and validate a non-invasive prediction model for staging of skin lesions based on the high-frequency ultrasound features.Methods:Patients with localized scleroderma were retrospectively collected from the Department of Dermatology and Venereology, Second Xiangya Hospital of Central South University from February 1, 2021 to February 28, 2023, and clinical data as well as high-frequency ultrasound and pathologic features of 85 lesions from these patients were analyzed. Lesions were divided into modeling cohort and validation cohort according to the chronological order of patient enrollment. The univariate analysis and multivariable logistic regression models were used to analyze the independent influential factors in the staging of localized scleroderma lesions in the modeling cohort, construct the regression equation, and to build a nomogram prediction model. The Bootstrap validation method was used for internal validation, and the predictive performance of the nomogram model in the modeling cohort and validation cohort was further evaluated by the calibration curve and receiver operating characteristic (ROC) curve.Results:In the modeling cohort, 60 patients with localized scleroderma, including 16 males and 44 females, were enrolled, with the age [ M ( Q1, Q3) ] being 22.0 (10.0, 39.2) years, and there were 28 lesions in the oedematous phase and 32 lesions in the fibrotic and atrophic phase; in the validation cohort, 25 patients with localized scleroderma, including 8 males and 17 females, were enrolled, with the age being 18.0 (7.0, 30.0) years, and there were 9 lesions in the oedematous phase and 16 lesions in the fibrotic and atrophic phase. Univariate analysis in the modeling cohort showed no significant differences in the age and gender of patients or the location of lesions between the oedematous phase group and the fibrotic and atrophic phase group (all P > 0.05) ; compared with the oedematous phase group, the fibrotic and atrophic phase group showed an increased proportion of patients with disease duration ≥ 2 years (20/32 cases vs. 10/28 cases, χ2 = 4.29, P = 0.038), decreased thicknesses of the subcutaneous fat layer in skin lesions (1.4 [0.0, 26.0] mm vs. 1.8 [0.1, 14.3] mm, Z = -2.14, P = 0.032), increased decrements in the subcutaneous fat layer thickness in the lesional sites compared with non-lesional control sites (1.8 [0.5, 11.0] vs. 0.3 [-1.9, 8.0] mm, Z = -4.72, P < 0.001), increased ratios of the lesional elasticity values to control elasticity values (2.9 [1.8, 6.9] vs. 1.8 [1.1, 5.9], Z = -4.34, P < 0.001), and increased ultrasound-based lesional activity scores (5.0 [3.0, 8.0] points vs. 3.0 [0.0, 5.0] points, Z = -4.76, P < 0.001). Multivariable logistic stepwise regression analysis showed that the disease duration ≥ 2 years ( P = 0.032), increased ratios of the lesional elasticity values to control elasticity values ( P = 0.019), increased ultrasound-based lesional activity scores ( P = 0.013), and increased decrements in the subcutaneous fat layer thickness in the lesions compared with the controls ( P = 0.013) helped to confirm localized scleroderma lesions in the fibrotic and atrophic phase. Based on the results of regression analysis, a total of 4 factors were included in the nomogram prediction model, including the disease duration, the decrement in the subcutaneous fat layer thickness in lesions compared with controls, the ratio of the lesional elasticity values to control elasticity values, and the ultrasound-based lesional activity score; additionally, the constructed logistic regression model formula for predicting the probability (p) of skin lesions in fibrotic and atrophic phase was "ln (p/[1 - p]) = -9.595 + 2.204 × the disease duration + 0.784 × the decrement in the subcutaneous fat layer thickness in the lesions compared with the controls (mm) + 0.887 × the ratio of the lesional elasticity values to control elasticity values + 1.374 × the ultrasound-based lesional activity score". The calibration curve showed a good predictive performance of the model through the Bootstrap validation method, and the ROC curve demonstrated good discrimination and accuracy (modeling cohort: area under the curve = 0.936, 95% CI: 0.879 - 0.994; validation cohort: area under the curve = 0.889, 95% CI: 0.748 - 1.000) . Conclusions:High-frequency ultrasound could provide essential details for staging the localized scleroderma lesions. Based on the disease duration, subcutaneous fat layer thickness, skin elasticity values, and ultrasound-based lesional activity scores, the constructed prediction model could predict the stages of localized scleroderma lesions with excellent discrimination, accuracy, and predictive performance.

The delta-12 fatty acid desaturase (Δ¹² FAD or FAD2) is a key enzyme that catalyzes oleic acid to linoleic acid by dehydrogenation at Δ¹² position of fatty acid carbon chain. In peanut, reduction or loss of FAD2 activity could enhance the relative content of oleic acid in kernels, and improve the quality and oxidation stability of peanut kernels and products. RNA interference (RNAi) technology could lead to non-expression or down-regulated expression of AhFAD2 gene. We constructed two RNA interference expression vectors with the inverted repeat sequence of partial AhFAD2 gene, which were driven separately by cauliflower mosaic virus (CaMV) 35S promoter or soybean agglutinin lectin seed-specific promoter. Homozygous transgenic lines carrying the two constructs stably in genetics were developed by peanut genetic transformation. There were no significant differences between the transgenic lines and the control through investigating the main agronomic traits. We analyzed the transcriptional level expression of AhFAD2 gene in transgenic lines and the control by real-time fluorescence quantitative PCR (qRT-PCR). The results suggested that the target genes of transgenic lines were likely suppressed by RNA interference, but showed different transcriptional levels in different peanut transgenic lines. Compared with untransformed lines, the resulting down-regulation of AhFAD2 gene resulted in a 15.09% or 36.40% increase in oleic acid content in the seeds of transformed HY23 and FH1 lines respectively, and the content of linoleic acid decreased by 16.19% or 29.81%, correspondingly, the ratio of oleic acid and linoleic acid (O/L) improved by 38.02%, 98.10%. The oleic acid content had significant differences between the two transformation constructs, and also among different transgenic lines. Moreover, the inhibition effect of RNAi was more obvious in the transgenic lines with FH1 as the receptor, and with transformation structure driven by seed specific promoter. The suppressed expression of AhFAD2 gene enabled the development of peanut fatty acid, which indicated that RNA interference would be a reliable technique for the genetic modification of peanut seed quality and the potential for improvement of other traits as well.