Effects of diisononyl phthalate on lipid metabolism in HepG2 cells / 环境与职业医学

Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L−1). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L−1), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L−1 after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L−1, respectively (P<0.05). After exposure to 30 mmol·L−1 and 100 mmol·L−1 DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L−1 DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L−1 group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L−1 DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L−1 and 100 mmol·L−1 can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.

Source analysis and health risk assessment of polycyclic aromatic hydrocarbons in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021 / 环境与职业医学

Background Polycyclic aromatic hydrocarbons (PAHs), one of the main components of fine particulate matter (PM2.5), have a certain impact on ambient air quality, and long-term exposure to PAHs may pose potential health risks to human beings. Objective To identify the distribution characteristics and sources of PAHs in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021, and to evaluate the health risks of PAHs to the population in the area through the inhalation pathway. Methods From 2019 to 2021, air PM2.5 sampling was carried out at a state-controlled surveillance point in a district of Taizhou City for 7 consecutive days on the 10th-16th of each month, the sampling time was 24 h·d−1, and the sampling flow rate was 100 L·min−1. PM2.5 mass concentration was calculated by gravimetric method. A total of 16 PAHs were determined by ultrasonic extraction-liquid chromatography. Kruskal-Wallis H test was used to compare the distribution charac teristics of PAHs concentrations by years and seasons, characteristic ratio and principal component analysis (PCA) was used to analyze their sources, and a lifetime carcinogenic risk (ILCR) model was used to assess the health risk of PAHs. Results From 2019 to 2021, the annual average concentrations [M (P25, P75)] of ∑PAHs in atmospheric PM2.5 in the selected district of Taizhou City were 6.52 (2.46, 10.59), 8.52 (4.56, 12.29), and 3.72 (1.51, 7.11) ng·m−3, respectively, and the annual benzo[a]pyrene (BaP) excess rates (national limit: 1 ng·m−3) were 27.38% (23/84), 47.62% (40/84), and 19.04% (16/84), respectively, both presenting 2020> 2019 > 2021 (P<0.001, P<0.05). The ∑PAHs concentration distribution showed a seasonal variation, with the highest value in winter and the lowest value in summer (P<0.05). Among the atmospheric PM2.5 samples, the proportion of 5-ring PAHs was the highest, the proportion of 2-3-ring PAHs was the lowest; the proportion of 2-4-ring PAHs showed a yearly upward trend, and the proportion of 5-6-ring PAHs showed yearly downward trend (P<0.05). The characteristic ratio and PCA results suggested that the sources of sampled PAHs were mainly mixed sources such as dust, fossil fuel (natural gas), coal combustion, industrial emissions, and motor vehicle exhaust emissions. The ILCR (RILCR) of PAHs by inhalation for men, women, and children were 1.83×10−6, 2.35×10−6, and 2.04×10−6, respectively, and the annual average RILCR was 2.07×10−6, all greater than 1×10−6. Conclusion For the sampled time period, the main sources of PAHs pollution in atmospheric PM2.5 in the target district of Taizhou City are dust, fossil fuel (natural gas), coal combustion, industrial emissions, motor vehicle emissions, etc., and PAHs may have a potential carcinogenic risk to local residents.

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

Factores determinantes del éxito en la carrera de enfermeras actuantes en tecnología de reproducción asistida / Factors that affect career success of nurses who practice in assisted reproductive technology / Fatores que afetam o sucesso profissional de enfermeiros que atuam na área de tecnologia de reprodução assistida

Objetivo: examinar la relación entre éxito en la carrera y ambiente de trabajo con enfermeras actuantes en tecnología de reproducción asistida (TRA), e identificar factores que afectan su éxito en la carrera. Método: estudio transversal realizado en 53 centros de fertilidad de 26 provincias en la China Continental. Datos recolectados utilizando cuestionario de datos demográficos, un Cuestionario de Competencias de TRA para Enfermeras Especializadas, la Career-Success Scale (Escala de éxito profesional) y la Nursing Work Environment Scale (Escala del entorno de trabajo de enfermería). Se aplicó estadística inferencial y descriptiva. Resultados: 597 enfermeras actuantes en TRA participaron en nuestra encuesta, entregando 555 cuestionarios válidos. Los puntajes generales promedio de éxito en la carrera y ambiente de trabajo fueron 3,75 (desviación estándar, [DE]=1,01) y 3,42 (DE=0,77) respectivamente. Se observó fuerte correlación positiva entre éxito en la carrera y ambiente de trabajo (r=0,742; p<0,01). La regresión múltiple mostró que la concurrencia a conferencias académicas, atención psicológica, desarrollo profesional, apoyo y cuidado, salario y bienestar constituyeron factores significantes con influencia en el éxito en la carrera. Conclusión: la concurrencia a conferencias académicas, atención psicológica y ambiente de trabajo guardan relación positiva con el éxito en la carrera. Los gestores deberían considerar formas de abordar tales factores.

Objective: to examine the relationship between career success and work environment of nurses who practice in assisted reproductive technology and to identify factors that affect career success. Method: a cross-sectional study conducted in 53 fertility centres in 26 provinces in mainland China. Data were collected using a demographic data questionnaire, a specialised nursing competence questionnaire, the Career-Success Scale, and the Nursing Work Environment Scale. Descriptive and inferential statistics were applied. Results: 597 assisted reproductive technology nurses participated in our survey, and 555 valid questionnaires were collected. Theoverall mean scores for career success and work environment were 3.75 [standard deviation (SD) = 1.01] and 3.42 (SD = 0.77) respectively. There was a strong positive correlation between career success and work environment (r = 0.742, p < 0.01). Multiple regression showed that attending academic conferences, psychological care, professional development, support and care, salary, and welfare were significant factors that influence career success. Conclusion: attending academic conferences, psychological care, and work environment are positively related to career success. Administrators should consider ways to address these factors.

Objetivo: examinar a relação entre o sucesso profissional e o ambiente de trabalho de enfermeiros da área de tecnologia de reprodução assistida e identificar os fatores que afetaram tal sucesso. Método: estudo transversal conduzido em 53 centros de fertilidade em 26 províncias da China Continental. Os dados foram coletados por meio de um questionário demográfico, um questionário sobre competências de enfermagem especializada em tecnologias de reprodução assistida, da Career-Success Scale (Escala de Sucesso Profissional) e da Nursing Work Environment Scale (Escala do Ambiente de Trabalho na Enfermagem). Aplicaram-se análises de estatística descritiva e inferencial. Resultados: participaram do estudo 597 enfermeiros da área de tecnologia de reprodução assistida, e 555 questionários válidos foram coletados. As pontuações globais médias para o sucesso profissional e o ambiente de trabalho foram 3,75 [desvio padrão (DP) = 1,01] e 3,42 (DP = 0,77), respectivamente. Verificou-se forte correlação positiva entre o sucesso profissional e o ambiente de trabalho (r = 0,742; p < 0,01). A análise de regressão múltipla mostrou que a participação em eventos acadêmicos, a assistência psicológica, o desenvolvimento profissional, o apoio e os cuidados, e o salário e o bem-estar foram fatores que influenciaram significativamente o sucesso profissional. Conclusão: a participação em eventos acadêmicos, a assistência psicológica e o ambiente de trabalho mostraram correlação positiva com o sucesso profissional. Os gestores deveriam considerar formas de abordar esses fatores.

miR-9500 Regulates Migration and Invasion of Lung Adenocarcinoma Cells by Targeting SMAD2 / 肿瘤防治研究

Objective To explore the molecular mechanism underlying miR-9500 regulating the migration and invasion of lung adenocarcinoma cells by targeting SMAD2. Methods The core target genes of miR-9500 were screened out by bioinformatics analysis, and their GO function analysis, KEGG signaling pathway enrichment, and survival analysis were performed. The targeted binding sites between miR-9500 and SMAD2 were predicted, and the direct targeting relationship between miR-9500 and SMAD2 was verified by dual-luciferase reporter assay. qRT-PCR and Western blot were used to assess the effect of miR-9500 on the mRNA and protein expression levels of SMAD2. Wound healing assay, Transwell assay, and Matrigel invasion assay were used to determine the effect of miR-9500 on the migration and invasion of lung adenocarcinoma cells. Results The core target genes of miR-9500 were mainly enriched in the cancer pathway, TGF-β signaling pathway, and focal adhesion. However, only the expression levels of VAMP2, SMAD2, and RXRA among the top 10 core target genes were significantly correlated with the overall survival of patients with lung adenocarcinoma. miR-9500 targeted SMAD2 and down-regulated the expression levels of SMAD2, and overexpression of miR-9500 significantly inhibited the migration and invasion of lung adenocarcinoma cells and markedly decreased the expression levels of MMP2 and MMP9. Conclusion miR-9500 can inhibit the migration and invasion of lung adenocarcinoma cells by targeting SMAD2, which may play an important role in the tumorigenesis and development of lung adenocarcinoma as a tumor suppressor.

Effect of Lactate on Immune Cells in Tumor Microenvironment and Progress of Related Target Therapy / 肿瘤防治研究

The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.

Clinical study on early predictors of concurrent bile duct injury following TACE in patients with liver cancer / 中华肝脏病杂志

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.

Application of pathological feature clustering in oral pathology teaching / 中华口腔医学杂志

To propose a new student-guided teaching method, in which students carried out the clustering of different diseases with the same pathological characteristics, and differentiated diagnosis of these diseases. This method was named pathological feature clustering (PFC). Seventy-seven undergraduates of School of Stomatology, Wuhan University were enrolled. Stratified random sampling method was adopted to divide the students into 4 groups with 18-20 students in each group. Each group of students selected a disease from the following four topics as the theme and summarize the histological characteristics of the disease: ①oral mucosal disease;②odontogenic tumors and tumor-like lesions, oral and maxillofacial cysts; ③salivary gland diseases;④epithelial-derived tumors and tumor-like lesions (referred to as topics 1, 2, 3, and 4, respectively). When discussing a specific type of disease, the group which select the topic was the summary group (SG), and the other groups were the non-summary group (NSG). After summarizing, students shared the summary results through PPTs, and teachers made comments and supplements. The teaching effect was evaluated by comparing the results of the pre-class test and the final examination. Students' acceptance of PFC teaching method was evaluated through a questionnaire, which included 8 objective questions and 1 subjective question. Likert-scale was used to design the questionnaire, with 1 to 5 points for each question. Students rated each question according to their own situation. Differences among groups were compared by Mann-Whitney U nonparametric test. The pre-class test results showed that the scores of students in SG group in subjects 1, 2, 3 [(5.6±0.8), 5.0(1.0) and (2.9±1.0) points for subjects 1, 2 and 3, respectively] were higher than those in NSG group [(5.1±1.0), 4.0(2.5) and 1.5(2.5) points] (U=402.50, P=0.047; U=392.00, P=0.026; U=295.00, P=0.003). The final examination results showed that there was no significant difference between the scores of the SG group and the NSG group in subjects 1, 2, 3 and 4 (P>0.05). These results showed that the differences between SG and NSG groups were reduced after the summarizing and share between groups, further demonstrating the effectiveness of the PFC teaching method. The results of questionnaire showed that 81.8%(63/77) students were completely satisfied with PFC teaching method, 13.0%(10/77) students were satisfied and 5.2%(4/77) students were basically satisfied. According to the feedback of Likert scale objective evaluation questionnaire, the mean score of each question ranged from 4.19 to 4.77, indicating that students believed that PFC teaching method had a positive impact on the learning of oral pathology. The PFC teaching method proposed in this study could improve the ability of pathological differential diagnosis of undergraduates.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Clinical Features and Prognostic Factors of Patients with Primary Cutaneous Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the clinical characteristics and prognostic factors of patients with primary cutaneous lymphoma.@*METHODS@#The clinical data of 22 patients with primary cutaneous lymphoma admitted to Xinjiang Hotan District People's Hospital, Heji Hospital affiliated to Changzhi Medical College and the Fifth Medical Center of PLA General Hospital from January 2013 to June 2021 were retrospectively analyzed.@*RESULTS@#The incidence of primary cutaneous T cell and NK/T cell lymphoma was about 91.9/100 000, and the incidence of primary cutaneous B cell lymphoma was about 14.5/100 000. The overall survival (OS) of patients aged ≥65 years was significantly shorter than that of patients younger than 65 years (P <0.05). Patients with elevated β2-microglobulin (β2-MG) had shorter OS and progression-free survival (PFS) (both P <0.05). Patients who achieved complete/partial response after initial treatment had longer OS than those with stable or progressive disease (P <0.05). There were significant differences in OS and PFS among patients with different pathological types of primary cutaneous lymphoma that originated from T and NK/T cells, the OS and PFS of patients with mycosis fungoides were longer than those of patients with other pathological types (both P <0.05). In addition, disease stage might also affect the PFS of the patients (P =0.056).@*CONCLUSION@#The age, disease stage, β2-MG level, pathological type and remission state after treatment of the patients were related to the clinical prognosis.

Role of innate immune cells in host immune responses against Aspergillus fumigatus / 中华微生物学和免疫学杂志

Aspergillus fumigatus ( A. fumigatus) is an environmental filamentous fungus and an opportunistic pathogen that can cause chronic and invasive aspergillosis. The development of aspergillosis is the result of the interaction between the host and the pathogen, and the symptoms of A. fumigatus infection varied in patients with different immune status. The host innate immune response to inhaled fungal spores is a key determinant of the development of aspergillosis. This review focused on the role of innate immune cells including macrophages, neutrophils, natural killer cells, natural killer T cells and mast cells in host defense against A. fumigatus, aiming to provide reference for further research on the pathogenesis, clinical prevention and treatment of aspergillosis.

Osteoprotective effect of denosumab on patients with chronic kidney disease / 中华肾脏病杂志

Osteoporosis is a comorbidity or complication of chronic kidney disease (CKD). Low bone mineral density, osteoporosis, and fractures are risk factors of poor prognosis in patients with CKD. Active prevention and treatment of osteoporosis is essential for patients with CKD. Denosumab is a fully human monoclonal antibody that targets receptor activator of nuclear factor-κB ligand (RANKL) and is not metabolized or excreted by the kidney. Clinical studies have shown that the use of denosumab in CKD (including dialysis and renal transplantation) patients with osteoporosis, can increase bone mineral density and reduce the incidence of fractures with acceptable safety. As hypocalcemia has been observed in patients with CKD, close monitoring and early supplementation of calcium and vitamin D are required before denosumab initiation, and serum calcium levels need to be monitored during treatment. The review summarized the published literature of denosumab in bone protection of CKD.

Long-term survival influencing and risk factors in peritoneal dialysis patients: a single center study in Southwest China / 中华肾脏病杂志

Patients who initiated peritoneal dialysis (PD) in Sichuan Provincial People's Hospital from January 1, 2001 to December 31, 2013 were enrolled in the single center and retrospective study. Clinical and laboratory data were collected to analyze the long-term survival rates, technique survival rates and associated influencing factors. Patients were followed up until December 31, 2021 or endpoints occurred (death or stopping PD treatment). Kaplan-Meier survival curves were used to estimate survival rates and technique survival rates. Cox proportional hazards regression model was used to analyze the risk factors of death and technique failure in PD patients. A total of 373 patients were enrolled in the study, with age of (52.1±15.8) years old and 199 (53.4%) males. During the follow-up, 154 (41.3%) patients died, 72 (19.3%) patients transferred to hemodialysis, and 40 (10.7%) patients received kidney transplant. Kaplan-Meier survival curves revealed that overall survival rates of PD patients at 1, 3, 5, 7, and 10 years were 92.2%, 76.6%, 66.0%, 52.4% and 38.6%, respectively. Technique survival rates were 93.5%, 84.8%, 74.2%, 62.8% and 44.5% at 1, 3, 5, 7, and 10 years, respectively. Multivariate Cox regression model results showed that age ( HR=1.055, 95% CI 1.039-1.073, P<0.001), transfer from hemodialysis ( HR=2.212, 95% CI 1.514-3.231, P<0.001), episodes of peritonitis ( HR=2.141, 95% CI 1.194-3.837, P=0.011), Charlson comorbidity index ( HR=1.525, 95% CI 1.305-1.783, P<0.001), and baseline albumin ( HR=0.951, 95% CI 0.925-0.978, P<0.001) were independent influencing factors of survival in PD patients. Episodes of peritonitis ( HR=2.327, 95% CI 1.274-4.250, P=0.006) and Charlson comorbidity index ( HR=1.244, 95% CI 1.035-1.496, P=0.020) were independent influencing factors of technique survival in PD patients. PD patients have good early survival rates and technical survival rates, but long-term outcomes need to be further improved. Peritonitis is a major risk factor for low long-term survival rates and technical survival rates in PD patients.

Research progress on the role and mechanism of ferroptosis in renal fibrosis / 中华肾脏病杂志

Ferroptosis is a recently identified type of non-apoptotic cell death, mainly caused by disruption of cellular metabolic pathways such as iron metabolism and reactive oxygen species metabolism, characterized by intracellular iron overload and reactive oxygen species accumulation leading to lipid peroxidation. Ferroptosis is closely related to renal diseases. The role of ferroptosis in diseases such as acute kidney injury and renal cell carcinoma has been extensively studied, and new discoveries and advances have been made in its relationship with renal fibrosis. The paper systematically reviews the relationship between ferroptosis and renal fibrosis in terms of the latest regulatory mechanisms of ferroptosis and its role in renal fibrosis, and explores the potential clinical application of targeted inhibition of ferroptosis to prevent renal fibrosis.

Legius syndrome combined with central precocious puberty: a case report and literature review / 中华神经科杂志

Objective:To investigate the clinical phenotype and genotypic characteristics of Legius syndrome.Methods:The clinical data of a child with precocious puberty and scattered café-au-lait macules admitted to Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University in July 2021 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) was used for genetic analysis to confirm the molecular diagnosis of the family. The relevant literature was reviewed to summarize the clinical characteristics of the disease.Results:The proband was a 10-year and 9-month-old girl, presenting with more than 5 café-au-lait macules with diameter>5 mm on the face and trunk, freckles in the axillary, without Lisch tubercles of iris and tumor signs of neurofibromatosis type 1, diagnosed as central precocious puberty at the age of 8. trio-WES results of the family revealed a spontaneous heterozygous nonsense mutation c.751(exon7) C>T in SPRED1 gene, causing a nonsense mutation in the amino acid sequence p.Arg251Ter (p. Ter251 *). Literature review showed a total of 88 pathogenic mutations were reported in SPRED1 gene, including frameshift mutations (41/88), nonsense mutations (31/88), splice mutations (7/88), missense mutations (6/88), and others (3/88), and no mutational hotspots were found. Clinical phenotype was as follows:>5 café-au-lait macules accounted for 92.8% (168/181), armpit and inguinal freckles 43.5% (73/168), macrocephaly 21.4% (31/145), learning disability 18.0% (30/166), psychomotor retardation 13.8% (22/159), lipoma (adult) 13.7% (21/153), Noonan facial sign 12.1% (21/173), and tumor phenotype of neurofibromatosis type 1 was not reported. Conclusions:The central precocious puberty phenotype of Legius syndrome was not reported in China. The clinical phenotype of Legius syndrome was mild, with a large variation, but without neurofibromatosis type 1 tumor phenotype. Genetic testing can be beneficial for early diagnosis of Legius syndrome.

The value of surface sphenoidal electrode in detecting interictal abnormal discharge in temporal region / 中华神经科杂志

Objective:To compare the detection and amplitude of epileptiform discharges (EDs) between surface sphenoidal electrode and anterior temporal electrode in patients with interictal EDs in the temporal region, and to explore the value of surface sphenoidal electrode.Methods:A total of 1 356 outpatients with epilepsy who underwent 2-hour video electroencephalogram (EEG) monitoring in Xuanwu Hospital from October to December 2021 were retrospectively enrolled. All patients were hooked up with scalp electrode according to the international 10-20 system as well as surface sphenoidal electrode and anterior temporal electrode. The EEGs with EDs recorded by surface sphenoidal electrode and/or anterior temporal electrode were selected for analysis. The detection rate and the amplitude of EDs by surface sphenoidal electrode and anterior temporal electrode were compared.Results:Seventy-three EEGs were collected and 250 EDs were counted. The detection rate of the anterior temporal electrode and surface sphenoidal electrode were 88.0% (220/250) and 98.4% (246/250) respectively. The difference in detection rate was statistically significant (χ 2=18.38, P<0.001). For the EDs from anterior temporal regions (taking the discharges recorded by anterior temporal electrode as "gold standard"), the detection rate of surface sphenoidal electrode was 98.2% (216/220). There was no statistically significant difference in detection rate between the anterior temporal electrode and surface sphenoidal electrode (χ 2=2.27, P=0.132). There were 216 EDs recorded by these two kinds of electrode simultaneously. The average amplitude of the EDs on surface sphenoidal electrode and anterior temporal electrode was (77.1±38.9) μV and (80.2±44.9) μV, respectively. The difference was statistically significant ( t=2.28, P=0.031). Conclusions:The detection rate of surface sphenoid electrodes was higher than that of anterior temporal electrodes for the EDs in the temporal region, and surface sphenoidal electrodes can be used routinely in outpatient. The surface sphenoidal electrode had more chance to detect EDs originating from regions out of the anterior temporal regions.

Correlation between carotid atherosclerosis and subclinical left ventricular dysfunction in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To investigate the relationship between carotid atherosclerosis(CAS)and subclinical left ventricular(LV)dysfunction in type 2 diabetes mellitus patients with preserved LV ejection fraction(LVEF).Methods:A total of 120 patients with type 2 diabetes mellitus who had LVEF≥50% were selected in the Department of Endocrinology, the First Affiliated Hospital of Air Force Medical University from June 2021 to October 2021. The global longitudinal strain(GLS)was obtained by two-dimensional speckle tracking echocardiography(STE)to assess subclinical LV systolic function. The mitral ratio of peak early to late diastolic filling velocity(E/A), and mitral velocity to early diastolic velocity of the mitral annulus(E/E′)ratio were obtained by pulsed tissue Doppler echocardiography to assess LV diastolic function. Acrroding to bilateral carotid ultrasound examination, the subjects were divided into normal carotid arteries group( n=46) and CAS group( n=74). Demographics and biochemical parameters were compared between two groups. Binary logistic regression and Pearson correlation analysis were used to evaluate the relationship between CAS and subclinical LV dysfunction. Results:The CAS group had a higher proportion of men, older age, and a longer duration of diabetes than the normal carotid arteries group(all P<0.05). There was no difference in LVEF and GLS between the two groups [normal carotid arteries group vs CAS group, LVEF: (60.72±4.73)% vs(60.07±4.28)%; GLS: (18.24±3.72)% vs(17.81±3.47)%, respectively; both P>0.05]. However, compared with normal carotid arteries group, E/A ratio was decreased and E/E′ ratio was significantly increased in CAS group(both P<0.01). Pearson correlation analysis showed that GLS was not correlated with carotid plaque thickness and carotid intima-media thickness(CIMT; both P>0.05). By contrast, E/E′ ratio was positively correlated with carotid plaque thickness and CIMT(both P<0.05). Binary logistic regression analysis showed that GLS and E/E′ ratio were not associated with CAS( both P>0.05). However, decreased E/A ratio was significantly associated with the existence of CAS( OR=0.09, 95% CI 0.01-0.67, P=0.018). Conclusions:In type 2 diabetes mellitus patients without overt heart failure and with preserved LVEF, the occurrence of CAS is not associated with subclinical LV systolic impairment assessed by GLS, but is significantly associated with LV diastolic dysfunction, and is independent of traditional cardiovascular risk factors.

Application of 99Tc m-MIBI SPECT/CT imaging in patients with primary cervical dystonia / 中华核医学与分子影像杂志

Objective:To evaluate the value of 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT imaging for the identification of dystonic muscles in patients with primary cervical dystonia (PCD). Methods:A total of 10 patients with PCD (3 males, 7 females, age (47.3±9.9) years) and 10 healthy subjects (4 males, 6 females, age (43.5±9.4) years; control group) between August 2019 and October 2021 in China-Japan Friendship Hospital were enrolled prospectively. All subjects underwent 99Tc m-MIBI SPECT/CT scan. The SUV max of 8 bilateral representative muscles, including rectus capitis posterior major, obliquus capitis inferior, splenius capitis, semispinalis, sternocleidomastoid, trapezius, musculus scalenus muscle and levator scapulae were evaluated in control group. In PCD group, muscles with abnormal uptake were determined. ROI was drawn and SUV max was measured. Independent-sample t test was used to analyze the differences of SUV max between normal and abnormal muscles. The detecting rates of neck MRI and SPECT/CT for abnormal muscles were analyzed by χ2 test. Results:Normal muscles of healthy subjects showed mild symmetrical radioactivity distribution, with the SUV max of 1.10±0.19. A total of 60 muscles with abnormal uptake in 10 patients were found, including 7 rectus capitis posterior major, 10 obliquus capitis inferior, 8 splenius capitis, 8 semispinalis, 10 sternocleidomastoid, 5 trapezius, 3 musculus scalenus muscle and 9 levator scapulae. The SUV max of muscles with abnormal uptake was 1.81±0.43, which was higher than that of normal muscles ( t=17.05, P<0.001). Only 30 pieces abnormal hypertrophy muscle were found by neck MRI, and the detecting rate was much lower than that of SPECT/CT (18.75%(30/160) vs 37.50%(60/160); χ2=28.03, P<0.001). Conclusion:99Tc m-MIBI SPECT/CT may be a useful method for identifying dystonic muscles and a guide to precision therapy in patients with PCD.