Objective:To investigate the expression of Toll-like receptor 4(TLR4)and extracellular signal-regulated protein kinase 1/2(ERK1/2)in decidua tissue of patients with unexplained spontaneous abortion and their correlation.Methods:The expres-sions of TLR4,ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion(abortion group)and 32 normal pregnancy(control group)were detected by immunohistochemistry and Western blot,respectively.The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis.Results:In immunohistochemical experiments,the cytoplasm of decidua cells in the two groups is the expression locus of TLR4,ERK1/2 and p-ERK1/2,the expression of the three proteins were different,and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group(P<0.01).There was no significant difference in ERK1/2 expression between abortion group and control group(P>0.05);In decidua tissue samples of abortion group,the protein level of TLR4 was higher than that of control group(P<0.05);the pro-tein level of p-ERK1/2 was significantly higher than that of control group(P<0.01),and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group(P>0.05).TLR4 was positively correlated with p-ERK1/2 expression in abortion group(r=0.890,P<0.01).Conclusion:Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion.

Objective:To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods:Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison.Results:Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P＜0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions:Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.

Objective:To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods:Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison.Results:Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P＜0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions:Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.

Objective:To determine the expression and diagnostic value of peripheral blood lymphocytes and functional activation status in non-Hodgkin lymphoma with hemophagocytic lymphohistiocytosis (NHL-HLH) .Methods:We retrospectively analyzed clinical data from 30 newly diagnosed NHL-HLH patients admitted to Jiangsu Province Hospital from September 2022 to September 2023. We assessed peripheral blood lymphocytes and activation status by flow cytometry. Forty newly diagnosed patients with NHL who received treatment at our hospital during the same period and had lymphocyte and functional activation indexes were selected as the control group. The differences in relative and absolute lymphocyte counts and functional activation indexes between the two groups were compared. The optimal cutoff values for continuous variables were calculated from the receiver operating characteristic curve and logistic regression analysis was used to evaluate the risk factors in NHL patients with HLH.Results:A total of 30 NHL-HLH patients were evaluated, including 12 T-cell lymphoma and 18 B-cell lymphoma patients. Forty individuals were in the control group, which included 19 T-cell lymphoma and 21 B-cell lymphoma patients. The absolute counts of CD3 + T, CD4 + T, CD8 + T, and NK cells, along with the relative count of NK cells, were significantly lower in the HLH group compared with that in the control group (all P values<0.01) . The expression of CD38 and HLA-DR on CD8 + T-cell activated subgroups was significantly higher in the NHL-HLH group compared with that in the control group (CD8 +CD38 +/CD8 + T expression median: 57.4% vs 21.5%, P<0.001; CD8 +CD38 +/CD8 + T expression median: 49.7% vs 33.5%, P=0.028, respectively) . In addition, CD28 expression on CD4 + and CD8 + T cells was significantly higher in NHL-HLH patients ( P<0.01) . ROC curve and multivariate logistic regression analyses revealed that absolute NK cell count ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were risk factors for predicting the occurrence of NHL-HLH patients. The sensitivity and specificity of the regression model were 86.7% and 86.1%, respectively, with an area under the curve of 0.94 ( P<0.001) . Conclusions:In NHL patients with HLH, there was a significant reduction in the absolute number of peripheral blood lymphocyte subpopulations, whereas T-cell function was notably activated. Specifically, absolute counts of NK cells ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were identified as risk factors for predicting the development of NHL-HLH patients. This will assist in early clinical diagnosis and treatment.

OBJECTIVE: To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction. METHODS: This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T₁WI, T₂WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques. RESULTS: The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high-risk areas of MVI. CONCLUSION The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction.
Humans ; Carcinoma, Hepatocellular ; Retrospective Studies ; Liver Neoplasms ; Magnetic Resonance Imaging ; Algorithms

The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl₂) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl₂ was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl₂ in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.
Animals ; Male ; Mice ; Antioxidants/pharmacology* ; Apoptosis ; Endoplasmic Reticulum Stress ; Melatonin/pharmacology* ; Mice, Inbred C57BL ; Nickel/adverse effects* ; Selenoproteins/genetics* ; Heart/drug effects*

Objective    To explore the predictive value of CT signs of mixed ground-glass nodules in the pathological subtype and differentiation of lung adenocarcinoma. Methods    The clinical data of 66 patients with mixed ground-glass nodules pathologically diagnosed as invasive adenocarcinoma (IAC) in the Second Department of Thoracic Surgery, the First Affiliated Hospital of Xiamen University from May to December 2021 were retrospectively analyzed, including 20 males and 46 females, aged 35-75 years. The CT findings were analyzed before operation, and the lesion profile was cut after operation to distinguish the ground-glass and solid components, and the pathological results of different positions were obtained. According to the postoperative pathological results, the patients were divided into a low-risk group (containing adherent type and no components of micropapillary subtype and solid subtype, n=16), a medium-risk group (containing niple or acinar type and no components of micropapillary subtype and solid subtype, n=38), and a high-risk group (containing micropapillary or solid subtype, n=12). The relationships between CT features and the pathological subtype and degree of differentiation were analyzed and compared. Results    In 66 patients with IAC, the infiltration degree of solid components was greater than that of ground-glass components. When the solid component ratio (CTR) was≥25% (sensitivity 90.2%, specificity 64.0%, P=0.005), and the average CT value was>−283.95 HU (sensitivity 82.9%, specificity 64.0%, P=0.000), the histological grade was more inclined to medium and low differentiation. The CTR, Ki-67, average CT value and histological grade of IAC in the medium- and high-risk groups were higher than those of nodules in the low-risk group. Conclusion    The infiltration degree of solid components is higher than that of ground-glass components in IAC mixed ground-glass nodules. The pathological subtype, Ki-67 expression and histological grade of lung adenocarcinoma can be predicted according to its CT characteristics, which has important clinical significance for determining the timing of surgery.

Objective: To explore the relationship between body image and adverse childhood experiences (ACEs) in adolescents. Methods: A total of 1 701 adolescents in grade 6-8 in three middle schools in Shanghai were selected by stratified cluster sampling, and were investigated anonymously using computer assisted self interview approach. Information including demographic characteristics, body image satisfaction, and ACEs were collected. The Chi square test and multivariate Logistic regression were used to explore the relationship between adolescent body image satisfaction and types of ACEs. Results: About 60.73% of the respondents were satisfied with their body image, with higher satisfaction among boys(66.16%) than among girls(55.13%)( χ 2= 21.70 ， P <0.01). About 79.19% of the respondents had experienced at least one ACE, and respectively 61.61%, 65.14% and 21.58 % of them had experienced abuse, neglect and family dysfunction. Multivariate Logistic regression analysis indicated that experiencing at least one ACE, abuse, neglect and family dysfunction were all related with low body image satisfaction among girls( OR =0.33- 0.57 , P <0.01), while among boys neglect,having 3 or more than 4 ACEs were found to be associated with body image satisfaction ( OR =0.54-0.64, P <0.05). The cumulative effects of ACEs on adolescent body image were observed. Conclusion Different types of ACEs are associated with body image in adolescents, ACEs have cumulative effects on adolescent body image, which shows gender differences.Screen of ACEs and improvement of family nurturing environment should be highlighted among adolescents, especially among girls.

Intensity-modulated radiation therapy(IMRT) is currently the main treatment method for nasopharyngeal carcinoma. During radiotherapy for nasopharyngeal carcinoma, factors such as body mass reduction, tumor regression, and organ displacement at risk can affect the precise implementation of radiation therapy. Applying adaptive radiotherapy (ART) technology to optimize the treatment plan at the appropriate timing can reduce the adverse effects caused by the above factors and enhance the accuracy of radiotherapy. There are no uniform standards for the necessity, timing, and case selection of ART. In this review, the research progress of ART in the radiotherapy of nasopharyngeal carcinoma in recent years was reviewed to provide a reference for further clinical application of ART in nasopharyngeal carcinoma.

Purpose: The prevalence of multi-morbidities with colorectal cancer (CRC) is known to be increasing. Particularly prognosis of CRC patients co-diagnosed with metabolic syndrome (MetSyn) was largely unknown. We aimed to examine the death risk of CRC patients according to the multiple MetSyn morbidities. Materials and Methods: We identified CRC patients with MetSyn from the electronic medical records (EMR) systems in five independent hospitals during 2006-2011. Information on deaths was jointly retrieved from EMR, cause of death registry and chronic disease surveillance as well as study-specific questionnaire. Cox proportional hazards regression was used to calculate the overall and CRC-specific hazards ratios (HR) comparing MetSyn CRC cohort with reference CRC cohort. Results: A total of 682 CRC patients in MetSyn CRC cohort were identified from 24 months before CRC diagnosis to 1 month after. During a median follow-up of 92 months, we totally observed 584 deaths from CRC, 245 being in MetSyn cohort and 339 in reference cohort. Overall, MetSyn CRC cohort had an elevated risk of CRC-specific mortality (HR, 1.49; 95% confidence interval [CI], 1.07 to 1.90) and overall mortality (HR, 1.43; 95% CI, 1.09 to 1.84) compared to reference cohort after multiple adjustment. Stratified analyses showed higher mortality risk among women (HR, 1.87; 95% CI, 1.04 to 2.27) and specific components of MetSyn. Notably, the number of MetSyn components was observed to be significantly related to CRC prognosis. Conclusion Our findings supported that multi-morbidities of MetSyn associated with elevated death risk after CRC. MetSyn should be considered as an integrated medical condition more than its components in CRC prognostic management.