eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell lymphoma. Despite the scarcity of reported BIA-ALCL cases in Asia, it is imperative to research early diagnosis. The crucial diagnostic criteria for BIA-ALCL include the presence of ALK - and CD30 + T cells exceeding 10% in the delayed seroma fluid. Furthermore, laboratory tests, such as histological examination of capsulectomies and analysis of clonal T-cell receptor (TCR) gene rearrangements, serve as important auxiliary diagnostic indicators. This article reported the case of a 56-year-old female patient who underwent bilateral breast augmentation with implants over 20 years ago. She presented with hardness, enlargement, and mild discomfort in her left breast. She was admitted to Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine in January 2023. MRI suggested implant rupture. Therefore, bilateral implant removal surgery was performed on February 2, 2023. Pathological examination of the fluid within the capsule of the left implant revealed a small number of ALK - and CD30 + T cells, with monoclonality observed in TCRγ gene rearrangement, indicating early changes suggestive of BIA-ALCL. Long-term follow-up is needed. The authors suggest that patients suspected of BIA-ALCL should undergo TCR gene rearrangement testing in addition to cytological and immunological examinations, which can provide guidance for the diagnosis, treatment, and necessary long-term follow-up of these patients.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell lymphoma. Despite the scarcity of reported BIA-ALCL cases in Asia, it is imperative to research early diagnosis. The crucial diagnostic criteria for BIA-ALCL include the presence of ALK - and CD30 + T cells exceeding 10% in the delayed seroma fluid. Furthermore, laboratory tests, such as histological examination of capsulectomies and analysis of clonal T-cell receptor (TCR) gene rearrangements, serve as important auxiliary diagnostic indicators. This article reported the case of a 56-year-old female patient who underwent bilateral breast augmentation with implants over 20 years ago. She presented with hardness, enlargement, and mild discomfort in her left breast. She was admitted to Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine in January 2023. MRI suggested implant rupture. Therefore, bilateral implant removal surgery was performed on February 2, 2023. Pathological examination of the fluid within the capsule of the left implant revealed a small number of ALK - and CD30 + T cells, with monoclonality observed in TCRγ gene rearrangement, indicating early changes suggestive of BIA-ALCL. Long-term follow-up is needed. The authors suggest that patients suspected of BIA-ALCL should undergo TCR gene rearrangement testing in addition to cytological and immunological examinations, which can provide guidance for the diagnosis, treatment, and necessary long-term follow-up of these patients.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

Objective:To explore the levels of programmed death receptor 1 (PD-1) and lymphocyte activating gene 3 (LAG-3) in the immune microenvironment of diffuse large B-cell lymphoma (DLBCL), their relationship with clinicopathological features, and their impact on prognosis.Methods:The tumor tissue sections and formaldehyde fixed paraffin embedded tissues from 174 DLBCL patients diagnosed at the First Affiliated Hospital of Xinjiang Medical University from February 2012 to August 2017 were retrospectively collected. The tissue chips were prepared, and the immunohistochemistry (IHC) method was used to detect the expressions of PD-1 and LAG-3 proteins in tumor infiltrating lymphocytes (TIL) of tissue chips [including whether they were positive (positive for IHC score 1-9 points, negative for 0 point) and expression level (high expression was 4-9 points on IHC score, low expression was 0-3 points)]. The relationship between the expression levels of PD-1 and LAG-3 and the clinicopathological characteristics of patients was analyzed. Spearman correlation coefficient was used to analyze the correlation between the expression levels of PD-1 and LAG-3. Kaplan-Meier method was used to draw overall survival (OS) and progression free survival (PFS) curves of patients with different expression levels of PD-1 and LAG-3, and log-rank test was used for comparison between the groups. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of OS and PFS in patients.Results:Of the 174 DLBCL patients, 95 (54.6%) were male and 79 (45.4%) were female; the median age was 60 years old (5-87 years old). The proportions of patients with PD-1 and LAG-3 positive in TIL of tumor tissues were 79.3% (138/174) and 78.8% (137/174), and the proportions of patients with high expression were 35.6% (62/174) and 37.9% (66/174), respectively. Among patients with bone marrow involvement, the proportion of patients with high expression of PD-1 [62.5% (15/24) vs. 32.5% (39/120), P= 0.006], the proportion of patients with high expression of LAG-3 [54.2% (13/24) vs. 32.5% (39/120), P= 0.050] were higher than those without bone marrow involvement. The expression levels of PD-1 and LAG-3 were not associated with gender, age, clinical stage, international prognostic index score, functional status (PS) score, lactate dehydrogenase level, whether there were B symptoms, whether it was intranodal, tumor length, whether it was germinal center B cell type, number of extranodal involvement sites, and whether it was treated with R-CHOP regimen (all P > 0.05). There was a positive correlation between PD-1 and LAG-3 expression levels in TIL of tumor tissues ( r = 0.202, P = 0.008). Multivariate Cox regression analysis showed that PS score (>2 points vs. ≤2 points: HR = 5.458, 95% CI 2.082-14.307, P = 0.001), R-CHOP regimen treatment (no vs. yes: HR = 2.181, 95% CI 1.086-4.379, P = 0.028) were independent influencing factors of OS, and PS score (>2 points vs. ≤2 points: HR = 3.913, 95% CI 1.579-9.698, P = 0.003), R-CHOP regimen treatment (no vs. yes: HR = 2.609, 95% CI 1.412-4.819, P = 0.024), LAG-3 expression level (low expression vs. high expression: HR = 0.531, 95% CI 0.283-0.995, P = 0.048) were independent influencing factors of PFS. There were no statistical differences in PFS and OS between patients with high and low PD-1 expression levels in TIL (both P > 0.05). PFS and OS in patients with high LAG-3 expression were worse than those in patients with low expression (both P < 0.05). OS in patients with high expressions of PD-1 and LAG-3 was worse than that in patients with low expressions of PD-1 and LAG-3 ( P = 0.044). Conclusions:The expression levels of PD-1 and LAG-3 in TIL of DLBCL patients' tumor tissues are related to bone marrow involvement, which are not related to most other clinicopathological features, and the prognosis of patients with high expressions of PD-1 and LAG-3 is poor.

Background/Aims: Some inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS. Methods: Forty-seven patients with Crohn’s disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot. Results: Prevalence of IBS-like symptoms in Crohn’s disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity. Conclusion IBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.

OBJECTIVE: To study the effect of silencing LncRNA SNHG7 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its targeted regulation on miR-181b-5p. METHODS: Rat cardiomyocytes H9c2 were cultured in vitro and randomly divided into control group, H/R group, H/R + si-NC group, H/R + si-SNHG7 group, H/R + si-SNHG7 + anti-miR-NC group and H/R + si-SNHG7 + anti-miR-181b-5p group. The content of lactate dehydrogenase (LDH), malondialedhyde (MDA) and the activity of superoxide dismutase (SOD) were detected. Flow cytometry was carried out to detect the rate of apoptosis. qRT-PCR was used to detect the expression of SNHG7 and miR-181b-5p. Dual luciferase report experiment was used to verify the targeting relationship between SNHG7 and miR-181b-5p. Western blotting was used to detect the expression of Bax and Bcl-2. RESULTS: Compared with the control group, the H/R group showed significantly increased SNHG7 expression in cardiomyocytes, reduced miR-181b-5p expression, higher levels of LDH and MDA, reduced activity of SOD, increased cell apoptosis rate, higher level of Bax protein, and reduced level of Bcl-2 protein (all P< 0.05). Compared with the H/R and H/R + si-NC groups, the H/R + si-SNHG7 group had significantly reduced level of LDH and MDA, increased activity of SOD, reduced apoptosis rate, reduced level of Bax protein, increased level of Bcl-2 protein (all P< 0.05). The dual luciferase report experiment confirmed that SNHG7 could target miR-181b-5p. Interference with the expression of miR-181b-5p could reduce the effect of silencing SNHG7 on H/R-induced cardiomyocyte oxidative stress and apoptosis. CONCLUSION Silencing SNHG7 may inhibit H/R-induced cardiomyocyte oxidative stress and apoptosis by up-regulating the expression of miR-181b-5p, thereby exerting a protective effect on cardiomyocytes.
Animals ; Apoptosis ; Hypoxia ; MicroRNAs/genetics* ; Myocardial Reperfusion Injury ; Myocytes, Cardiac ; RNA, Long Noncoding/genetics* ; Rats

Background/Aims: Some inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS. Methods: Forty-seven patients with Crohn’s disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot. Results: Prevalence of IBS-like symptoms in Crohn’s disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity. Conclusion IBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.

Objective:To investigate the molecular mechanism of the disease based on the clinical characterization and genetic mutation analysis in a family with intellectual disability.Methods:The proband with intellectual disability was diagnosed at Luohe Central Hospital in December 2019. Peripheral blood samples were collected from four family members. Whole exome sequencing (WES) was used to screen the pathological mutations. Then the PCR and Sanger sequencing were used to verify the selected mutations and combine the relevant database to analyze variation loci.Results:We infer that the ARX c.1162 A>G was co-segregated with the phenotype of the family based on the results of WES. The results of sanger sequencing and WES are consistent. The mother of the proband is the carrier of the mutation. There is no mutation frequency reported in the healthy population. The mutation of the ARX c.1162A>G is harmful inferred by a variety of bioinformatics software. Combined with the phenotypic analysis of OMIM database, we infer the phenotype caused by the mutation is consistent with the patients in the family.Conclusion:The mutation of the ARX c.1162 A>G may be the cause of the intellectual disability in the family affected. And the variant has not been reported in China.

Objective:To investigate the effects of olanzapine versus risperidone on cognitive function, serum complement C3 and C4 levels and high sensitivity C-reactive protein (hs-CRP) level in patients with schizophrenia. Methods:Eighty patients with schizophrenia who received treatment in Lishui Second People's Hospital, China between September 2018 and September 2019 were included in this study. They were randomly assigned to receive treatment either with olanzapine (olanzapine group, n = 40) or risperidone (risperidone group, n = 40). Before and after treatment, the Positive and Negative Syndrome Scale (PANSS) score and the Wisconsin Card Sorting Test score were evaluated in each group. Before and after treatment, serum levels of dopamine, serotonin, norepinephrine, complement C3 and C4 and hs-CRP levels were compared between the olanzapine and risperidone groups. Results:Before treatment, there were no significant differences in PANSS and WCST scores between the two groups (both P > 0.05). After treatment, PANSS score, the number of perseverative errors and the number of random errors in each group were significantly decreased compared with before treatment [olanzapine group: (56.23 ± 9.37) points, (13.06 ± 6.26) points, (16.23 ± 6.35) points, t = 12.334, 5.885, 3.840, all P < 0.05; risperidone group: (55.98 ± 10.21) points, (13.97 ± 6.54) points, (16.31 ± 6.32) points, t = 12.044, 6.213, 3.321, all P < 0.05]. After treatment, the number of correct sorts and the number of categories in each group were significantly increased compared with before treatment [olanzapine group: (29.21 ± 2.24) points, (3.79 ± 1.12) points, t = 3.323, 2.087, both P < 0.05; risperidone group: (29.33 ± 2.35) points, (3.81 ± 1.15) points, t =2.750, 2.085, both P < 0.05]. After treatment, there were significant differences in these indexes between the two groups (all P > 0.05). Before treatment, there were no significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups (all P > 0.05). After treatment, serum levels of dopamine, serotonin and norepinephrine in each group were significantly decreased compared with before treatment [olanzapine group: (5.02 ± 0.13) μg/L, (66.24 ± 6.05) μg/L, (27.32 ± 4.05) μg/L, t = 67.800, 9.977, 5.082, all P < 0.05; risperidone group: (4.18 ± 0.12) μg/L, (63.12 ± 6.21) μg/L, (24.81 ± 4.13) μg/L, t = 99.761, 12.296, 6.882, all P < 0.05]. After treatment, there were significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups ( t = 30.029, 2.276, 6.882, all P < 0.05). Before treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups (all P > 0.05). After treatment, complement C3 and C4 and hs-CRP levels in each group were significantly increased compared with before treatment [olanzapine group: (1.12 ± 0.18) g/L, (0.24 ± 0.06) g/L, (1.09 ± 0.11) mg/L, t = 5.129, 4.049, 32.452, all P < 0.05; risperidone group: (1.13 ± 0.17) g/L, (0.25 ± 0.07) g/L, (1.10 ± 0.12) mg/L, t = 5.147, 5.164, 29.227, all P < 0.05]. After treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups ( t = 0.255, 0.686, 0.389, all P > 0.05). Conclusion:Olanzapine and risperidone have the same effects on improving the mental symptoms and cognitive function of patients with schizophrenia, but risperidone has more obvious effects on improving the body function than olanzapine.