Critical Values of Daily Sedentary Time and Its Longitudinal Association with Mild Cognitive Impairment Considering APOE ε4: A Prospective Cohort Study.

BACKGROUND: Long sedentary time and physical inactivity are negatively related to cognition, but the cut-off value remains unclear, and apolipoprotein E polymorphism ε4 (APOE ε4) is a known genetic risk factor of mild cognitive impairment (MCI). OBJECTIVES: To explore longitudinal association of sedentary time and MCI, and to identify a cutoff value that increases the risk of developing MCI, taking into account APOE ε4 stratification and its interactions. DESIGN: A prospective cohort study. SETTING: Population-based study. PARTICIPANTS: We included 4932 older adults from Tianjin Elderly Nutrition and Cognition (TENC) cohort study recruited from March 2018 to June 2021 with 3.11 years of median follow-up time. MEASUREMENTS: The primary outcome was newly diagnosed MCI, which was diagnosed by a modified version of the Petersen's criteria. The information of sedentary time (hours/day) and physical activity (MET-h/week) were obtained by questionnaire. Cox proportional hazard regression models and restricted spline curve were conducted. RESULTS: A total of 4932 participants were included (mean [SD] age, 67.85 [4.96] years; 2627 female [53.3%] and 2305 male [46.7%]), 740 newly onset MCI patients were identified. Longer sedentary time was associated with higher risk of MCI for all participants (HR:1.069, 95%CI: 1.034, 1.105), especially in APOE ε4 non-carriers (HR:1.083, 95%CI: 1.045, 1.123) whether adjusted potential confounders. Sedentary time had synergistic interactions with APOE ε4 (ß:1.503, 95%CI: 1.163, 1.942) and physical activities (ß: 1.495, 95%CI: 1.210, 1.846). Restricted spline curve showed a cut-off value of 3.03 hours/day. CONCLUSIONS: Long sedentary time (≥3.03 hours/day) could increase MCI risk, especially in APOE ε4 non-carriers, people with higher PA, aged 65 and above.

Grading Cytological Epithelial Atypia in Pancreatic Mucinous Cysts Predicts Patient Survival: Correlation with Histological, Molecular, and Clinical Follow-Up.

Cytological examination of epithelial cells in cyst fluids from pancreatic mucinous cysts is the optimal method for identifying high-grade atypia (HGA), which may represent histological high-grade dysplasia (HGD) or invasive carcinoma, and thereby classify the cyst as high-risk, warranting surgical resection. Cytological features of HGA were previously described at our institution in 2013 and implemented thereafter, but performance of grading with these criteria has not yet been reported. 1322 pancreatic cyst fluid specimens (2014-2021) were identified; all pathology reports and relevant clinical data were reviewed in detail. 230 unique cysts (217 patients) contained neoplastic mucinous epithelium. Of the 230 cysts, 178 had low-grade atypia (LGA), and 52 had HGA. 97 cysts had histologic follow-up: 77 (79%) were resections and 20 (21%) were diagnostic surgical biopsies only. 92 (95%) were confirmed neoplastic mucinous cysts, 3 were adenocarcinomas, and 2 were benign entities. Among histologically confirmed neoplastic mucinous cysts, 58 had low-grade dysplasia (LGD); 34 had HGD, of which 14 also had invasive carcinoma. A significantly higher proportion of cysts with HGA (63%) demonstrated at least HGD on follow-up compared to those with LGA (26%, p<0.001). The sensitivity and specificity of HGA for accurately classifying a high-risk cyst were 54% and 81%, respectively. 146/230 (64%) cysts had corresponding next-generation sequencing results. 31% of HGA cysts harbored a high-risk mutation (TP53, CDKN2A, and/or SMAD4) vs. 7% of LGA cysts (p<0.001). Among cysts without histologic confirmation, 25% of HGA cysts had a high-risk mutation vs. 7% of LGA cysts. The grade of cytological atypia was predictive of overall survival and recurrence-free survival (p<0.001 and p=0.020, respectively). Implementation of cytological criteria for HGA in pancreatic mucinous cysts has relatively low sensitivity but modest specificity for classifying a high-risk cyst. Though high-risk mutations were more commonly found in cysts with HGA, their frequency is overall low. Thus, evaluating the degree of cytologic atypia, which is predictive of patient survival, provides significant value and informs patient outcomes.

The Effects of Different Exercise Interventions on Patients with Subjective Cognitive Decline: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND OBJECTIVE: Exercise is a promising non-pharmacological therapy for subjective cognitive decline, but it is unclear which type of exercise is most effective. The objective was to assess the comparative effects and ranks of all exercise-based interventions on cognitive function in patients with subjective cognitive decline (SCD). METHOD: In this network meta-analysis, Online databases for Web of Science, PubMed, Embase, Medline, Cochrane Library and PsycINFO were searched from inception to April 30, 2023. The included studies are randomized controlled trials assessing the efficacy of exercise interventions for individuals with SCD. The primary outcome measure is memory, while secondary outcome measures encompass executive function, attention, verbal fluency, and global cognitive function. Represented using Standardized Mean Differences (SMDs) along with their 95% Confidence Intervals (CIs). Bias assessment was conducted in accordance with the 'Cochrane Risk of Bias Assessment Tool, 2nd Edition' (RoB 2). Pairwise meta-analysis was carried out using the 'meta-analysis' module within STATA 14.0, and network meta-analysis was performed using the 'mvmeta' and 'network' packages available in STATA 14.0. Registration number CRD42023289687. RESULT: This study included a total of 11 randomized controlled trials, encompassing 1,166 patients. Mind-body exercise was found to be efficacious in enhancing or sustaining memory (SMD: 0.58, 95%CI: 0.06 ~ 1.10) and executive function (SMD: 0.41, 95%CI: 0.09 ~ 0.73) in individuals with subjective cognitive decline. Furthermore, mind-body exercise exhibited the highest probability of being the most effective measures for improving or preventing the decline in memory (surface under cumulative ranking curve (SUCRA) value: 90.4) and executive function (SUCRA value: 91.8). The second-ranked moderate-intensity aerobic exercise has also shown a positive effect on the improvement of executive function in patients with subjective cognitive decline (SMD: 0.23, 95%CI: 0.03 ~ 0.43, SUCRA value: 68.2). However, we did not observe a significant effectiveness of exercise interventions on verbal fluency, attention, and overall cognitive function in subjective cognitive decline. CONCLUSION: Mind-body exercise may potentially be the optimal strategies for enhancing memory and executive function in individuals with subjective cognitive decline. Additionally, moderate-intensity aerobic exercise has shown a modest positive effect on executive function in subjective cognitive decline. When resources permit, practical application of these findings may be considered. Nevertheless, further support for the conclusions of this study is warranted through larger sample sizes and well-designed multicenter trials.

[Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway].

OBJECTIVE: To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. METHODS: We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2, 4, 6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. RESULTS: The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P < 0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P < 0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P < 0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P < 0.05). CONCLUSION: KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.

[Expert consensus on the application of critical care ultrasonography in invasive procedures].

The evolution of critical care medicine is inextricably linked to the development of critical care procedures. These procedures not only facilitate diagnosis and treatment of critically ill patients, but also provide valuable insights into disease pathophysiology. While critical care interventions offer undeniable benefits, the potential for iatrogenic complications necessitates careful consideration. The recent surge in critical care ultrasound (US) utilization is a testament to its unique advantages: non-invasiveness, real-time bedside availability, direct visualization of internal structures, elimination of ionizing radiation exposure, repeatability, and relative ease of learning. Recognizing the need to optimize procedures and minimize complications, critical care utrasound study group of Beijing critical care ultrasound research assocition convened a panel of critical care experts to generate this consensus statement. This document serves as a guide for healthcare providers, aiming to ensure patient safety and best practices in critical care.

[Introduction to Guidelines for public health protection against high temperature and heatwaves].

In recent years, the high temperature and heatwaves have seriously affected the health of Chinese residents, and there is an important need for public health protection guidelines for high temperature and heatwaves in China. The National Bureau of Disease Control and Prevention has organized experts to fully investigate the evidence from epidemiological research on the health of populations in high temperature and heatwaves globally and in China, analyze the health hazards and protection needs of different populations, and put forward practical and effective individual protection measures and health recommendations. For this reason, the "Guideline for Public Health Protection against High Temperature and Heatwaves" (referred to as the "Guideline") was officially issued in June 2023. This article interprets the background and significance of the Guideline, the principles of compilation, the main considerations, the main contents, the implementations and promotions and other aspects, to improve the understanding of the content of the Guideline and strengthen the publicity and implementations.

[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

[A case of acute inhalation dinitrogen tetroxide poisoning].

Dinitrogen tetroxide is often used as an oxidant in rocket propellant and has strong irritant and corrosive properties. This paper analyzes the clinical data of a patient with dinitrogen tetroxide poisoning admitted in the 63710 Army Hospital of Chinese People's Liberation Army, so as to further explore the poisoning mechanism, clinical characteristics and key points of acute inhaled dinitrogen tetroxide poisoning.

[Detection of EWSR1 gene rearrangement by fluorescence in situ hybridization in bone and soft tissue tumors: clinical application evaluation and atypical signal analysis].

Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.

[Analysis of clinical characteristic of children with progressive familial intrahepatic cholestasis type 3].

Objective: To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods: This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity. Results: Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment. Conclusions: Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas.

AIMS: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. METHODS: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. RESULTS: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. CONCLUSIONS: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

[Metformin ameliorates PM2.5-induced functional impairment of placental trophoblasts by inhibiting ferroptosis].

OBJECTIVE: To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism. METHODS: Sixteen pregnant Kunming mice were randomly assigned into two groups (n=8) for intratracheal instillation of PBS or PM2.5 suspension at 1.5, 7.5, and 12.5 days of gestation. The pregnancy outcome of the mice was observed, and placental zonal structure and vascular density of the labyrinth area were examined with HE staining, followed by detection of ferroptosis-related indexes in the placenta. In cultured human trophoblasts (HTR8/SVneo cells), the effects of PM2.5 exposure and treatment with metformin on cell viability, proliferation, migration, invasion, and tube formation ability were evaluated using CCK8 assay, EDU staining, wound healing assay, Transwell experiment, and tube formation experiment; the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting. RESULTS: M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight (all P<0.001). PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis. In cultured HTR8/SVneo cells, PM2.5 significantly inhibited proliferation, migration, invasion, and angiogenesis of the cells by causing ferroptosis. Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation, migration, invasion, and angiogenesis of the cells, and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity, reduced MDA and Fe2+ levels, and upregulated GPX4 and SLC7A11 protein expression (P<0.05 or 0.01). CONCLUSION: PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice, and metformin can effectively alleviate PM2.5-induced trophoblast impairment.

[Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children].

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

[Primary cardiac synovial sarcoma: a clinicopathological analysis of five cases].

Objective: To assess the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary cardiac synovial sarcoma (PCSS). Methods: Five cases of PCSS were collected at Guangdong Provincial People's Hospital from 2008 to 2023, and their clinicopathological features were summarized. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and relevant literatures were reviewed. Results: The cases were found in four males and one female, ranging in ages from 16 to 51 years (median 30 years). Two cases were located in the pericardium, two in the right ventricle, and one in the left ventricle. Follow-up data were available in four cases. All the four patients died of disease at 3, 7, 13 and 26 months, respectively, after diagnosis. The tumor maximum diameter ranged from 6.0 to 14.0 cm in (mean 10.0 cm). Microscopically, three cases were monophasic and two cases were biphasic. Immunohistochemically, all cases were immunoreactive for EMA, vimentin, bcl-2 and CD56. The tumor cells were variably positive for pan-cytokeratin, SS18-SSX, SOX2, TLE1, CD99, synaptophysin, calretinin and calponin. FISH showed the presence of SS18 rearrangement in all the cases. NGS detected SS18-SSX gene fusion in three cases (SS18-SSX1 in one and SS18-SSX2 in two). Conclusions: PCSS is an exceedingly rare neoplasm, and should be distinguished from other various malignant epithelial and mesenchymal tumors. The clinical history, histopathological and immunohistochemical features, and molecular findings are all essential to the definitive diagnosis of PCSS.

[Analysis of changes in intrinsic neural timescales in male smoking addicts based on whole brain resting-state functional magnetic resonance imaging].

Objective: To investigate the abnormal changes of intrinsic neural time scale (INT) in male smoking addicts based on whole brain resting state functional magnetic resonance imaging (rs-fMRI). Methods: A case-control study. The clinical data and whole brain rs-fMRI data of 139 male subjects, aged (34.1±8.8) years, recruited through the online platform from January 2019 to December 2021 were retrospectively analyzed. According to the existence of smoking addiction, they were divided into smoking addiction group (n=83) and healthy control group (n=56).INT was calculated to reflect the brain neural activity dynamics. Single sample t test was used to obtain the whole brain spatial distribution maps of INT in smoking addiction group and the control group. Then two-sample t test was conducted to explore the difference of INT between the smoking addition group and the healthy control group, with age and years of education as covariates. Finally, Spearman correlation analysis was used to explore the relationship between INT and nicotine dependence scale score and smoking index. Results: Subjects with smoking addiction and healthy control group showed a similar pattern of hierarchical neural timescales, namely shorter INT in sensorimotor areas and longer INT in parietal lobe, posterior cingulate cortex. In addition, in the smoking addiction group, the left medial occipital gyrus (peak t=-3.18), left suproccipital gyrus (peak t=-3.66), bilateral pericalar cleft cortex (left: peak t=-3.02, right: peak t=-3.22), bilateral lingual gyrus (left: peak t=-3.10, right: t peak=-3.04), left cuneus (peak t=-2.97), default network associated brain region [left anterior cuneus(peak t=-3.23), left angular gyrus (peak t=-3.07), and left posterior cingulate cortex (peak t=-3.54) were significantly lower than those of healthy controls (gaussian random field correction, voxel level all P<0.005, mass level all P<0.05). However, there was no significant correlation between INT and nicotine dependence scale score and smoking index (both P>0.05 after Bonferroni correction). Conclusion: Compared with healthy controls, smoking addicts showed abnormal changes in the dynamics of neural activity in the visual cortex and the default network.