Genotypic and phenotypic features of 39 Chinese patients with glycogen storage diseases type I, VI, and IX.

Glycogen storage diseases (GSDs) are abnormally inherited glycogen metabolism mainly affecting the liver, muscles, and heart. Deficiency of proteins involved in glycogen metabolism caused by genetic mutations are responsible for different subtype of GSDs. However, there are still some challenges in diagnosing GSD. This study includes 39 suspected GSDs patients from unrelated families in China. Next-generation sequencing (NGS) was used to investigate the reason for their diseases at the genetic level. Finally, all 39 patients were diagnosed with GSDs, including 20 GSD-Ia, 4 GSD-VI, and 15 GSD IX (12 GSD-IXa patients and 3 GSD-IXb patients). Thirty-two mutations in G6PC1, PYGL, PHKA2, and PHKB genes were identified, with 14 of them being novel variants. The pathogenicity of novel variants was classified according to ACMG guildlines and predicted by in slico algorithms. Mutations p.L216L and p.R83H in G6PC1 gene may be the hot spot mutation in Chinese. Hearing impairment is a rare clinical feature of GSD Ia, which has also been observed in our cohort. The severity of GSD VI and IX was indicated by our patients. Close follow-up should be applied to GSD VI and IX patients. Our findings provided evidence for building the phenotype-genotype of GSDs and expanded the mutation spectrum of related genes.

Application of the ankle pump method in a sitting position to evaluate calf perforating veins by color Doppler ultrasound.

OBJECTIVE: We investigated the feasibility and efficacy of assessing calf perforating veins (PVs) using the ankle pump in a sitting position (AP-sit) method by color Doppler ultrasound. METHODS: We performed a multicenter prospective clinical trial between November 2022 and October 2023. Eligible patients with chronic venous disease and healthy controls were enrolled. The calf PVs were assessed using three different methods: manual compression in a standing position, manual compression in a sitting position, and AP-sit method. The reflux durations and detection rate of incompetent PVs (IPVs) were compared among the three methods. The number and diameter of calf PVs and distribution of IPVs were analyzed. RESULTS: A total of 50 patients with chronic venous disease and 50 healthy controls were included. There were 173 calves analyzed, including 97 healthy calves and 76 calves with chronic venous disease. The number of PVs per calf was higher in the diseased calves (median, 7.0; interquartile range [IQR], 6.0-8.0) than in the healthy calves (median, 5.0; IQR, 3.0-6.0; P < .001). The diameter of IPVs (median, 2.3 mm; IQR, 2.0-3.1 mm) was larger than that of competent PVs (median, 1.4 mm; IQR, 1.2-1.7 mm). Most of the IPVs (78.8%) were located in the medial and posterior middle of the calf. The reflux duration induced by the AP-sit method was greater than that induced by the manual compression methods (P < .001). Although the AP-sit method had a higher detection rate (92.0%) of IPVs than the manual compression methods (71.7% and 74.3% for standing and sitting, respectively; P < .001), especially in the distal lower leg, the manual compression methods found IPVs not found using the AP-sit method. CONCLUSIONS: Diseased calves with chronic venous disease have more PVs than do healthy calves. IPVs are commonly larger than competent PVs, with most IPVs located in the medial and posterior middle of the calf. Most importantly, the AP-sit method provides a convenient and effective approach for assessing the calf PVs, especially those located in the distal calf, as an alternative or complementary method to traditional manual compression, which is valuable in the daily practice of sonographers.

Dietary factors and patterns in relation to risk of later-onset ulcerative colitis in Chinese: A prospective study of 0.5 million people.

BACKGROUND: There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults. AIMS: To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese. METHODS: The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79. Dietary habits were assessed using food frequency questionnaires. Dietary patterns were derived by factor analysis with a principal component method. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.1 years, 312 cases of newly diagnosed UC were documented (median age of diagnosis 60.1 years). Egg consumption was associated with higher risk of UC (HR for daily vs. never or rarely: 2.29 [95% CI: 1.26-4.16]), while spicy food consumption was inversely associated with risk of UC (HR: 0.63 [0.45-0.88]). The traditional northern dietary pattern, characterised by high intake of wheat and low intake of rice, was associated with higher risk of UC (HR for highest vs. lowest quartile of score: 2.79 [1.93-4.05]). The modern dietary pattern, characterised by high intake of animal-origin foods and fruits, was associated with higher risk of UC (HR: 2.48 [1.63-3.78]). Population attributable fraction was 13.04% (7.71%-19.11%) for daily/almost daily consumption of eggs and 9.87% (1.94%-18.22%) for never/rarely consumption of spicy food. CONCLUSIONS: The findings highlight the importance of evaluating dietary factors and patterns in the primary prevention of later-onset UC in Chinese adults.

Emerging role of N6-methyladenosine RNA modification in regulation of SARS-CoV-2 infection and virus-host interactions.

Since December 2019, the infection caused by Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) has posed an enormous threat to human health security worldwide. Constant mutation of viral genome and varying therapeutic responses of patients infected with this virus prompted efforts to uncover more novel regulators in the pathogenesis. The involvement of N6-methyladenosine, a modified form of RNA, plays a crucial role in viral replication, viral pathogenicity, and intricate signaling pathways connected with immune responses. This review discusses research advances revealing the regulation of the life cycle of SARS-CoV-2 and antiviral responses of host cells by RNA m6A modification, highlights the biological functions of N6-methyladenosine components in SARS-CoV-2 infection and virus-host interactions, and outlines current challenges and future directions for exploring the potential clinical value of m6A modification in COVID-19.

A promising Artemisia capillaris Thunb. Leaf proteins with high nutrition, applicable function and excellent antioxidant activity.

The nutritional and functional properties of leaf proteins is a decisive factor for their use in food. This work was aimed to extract defatted Artemisia capillaris Thunb. (ACD) leaf proteins (ACLP), and assess ACLP nutritional quality, functional properties and in vitro antioxidant activity, as well characterize the structure. ACLP had a balanced amino acid profile and high bioavailability (protein digestibility corrected amino acid score (PDCAAS) 99.29 %). Solubility, foaming capacity and emulsifying ability of ACLP correlated positively with pH. Water and oil holding capacity were increased with temperature. Gel electrophoresis shown the protein molecular size was mainly ∼25 kDa, and random coil was the mainly secondary structure while ß-sheet was dominant regular conformation as indicated by circular dichroism (CD). ACLP performed in vitro antioxidant activity which was better after digestion. All data implied ACLP met the WHO/FAO protein quality expectations and had application potential in food.

Somatostatin receptor subtype 2A expression and genetics in 184 paragangliomas: a single center retrospective observational study.

PURPOSE: Adrenal and extra-adrenal paragangliomas (PGLs) are a group of neuroendocrine tumors (NETs) with strong heterogeneity, which often express somatostatin receptor subtype 2 A (SSTR2A). However, the association between SSTR2A expression and genetic status of PGLs remains unclear. The purpose of the study was to identify whether various pathogenic variants (PVs) had an impact on SSTR2A expression in PGLs. METHODS: This retrospective study included 184 patients with pathologically confirmed PGLs. The immunohistochemical expression of SSTR2A were studied in 184 tumors and PVs were tested in 159 tumor samples. Clinical and genetic data were compared in SSTR2A positive and negative PGLs. RESULTS: SSTR2A was positive in 63.6% (117/184) of all tumors. PGLs with negative SSTR2A were more likely to be extra-adrenal (37.0% vs 18.0%; P = 0.005) and exhibited a considerably greater proportion of PVs (75.4% vs. 49.0%; P = 0.001) than those with positive SSTR2A. Compared to those without PVs, a higher proportion of PGLs with PVs in cluster 1B (P = 0.004) and cluster 2 (P = 0.004) genes, especially VHL (P = 0.009), FGFR1 (P = 0.010) and HRAS (P = 0.007), were SSTR2A negative. SSTR2A was positive in all tumors (4/4) with SDHx PVs and in 87.5% (7/8) of metastatic PGLs. CONCLUSIONS: SSTR2A negativity was correlated with extra-adrenal tumor location and PVs in cluster 1B and cluster 2 genes such as VHL, FGFR1 and HRAS. Immunohistochemistry of SSTR2A should be taken into consideration in the personalized management of PGLs.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

Psoriasis may increase the risk of idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study.

BACKGROUND: Although some studies have indicated that Psoriasis could contribute to the risk of idiopathic pulmonary fibrosis (IPF), no study has reported a clear causal association between them. Our aim was to explore the potential relationship between Psoriasis and IPF using Mendelian randomization (MR) design. METHODS: To explore a causal association between Psoriasis and IPF, we used genetic instruments from the largest available genome-wide association study (GWAS) of European ancestry, including psoriasis (5314 cases, 457,619 controls) and IPF (1028 cases, 196,986 controls). Our main analyses were conducted by inverse-variance weighted (IVW) method with random-effects model, with the other complementary four analyses: weighted median method, weighted mode, multivariable MR and MR-Egger approach. RESULTS: The results of IVW methods demonstrated that genetically predicted psoriasis was significantly associated with higher odds of IPF, with an odds ratio (OR) of 1.09 (95%CI, 1.01-1.18; P = 0.02). Weighted median method, weighted mode and multivariable MR also demonstrated directionally similar results (P < 0.05), while the MR-Egger regression did not reveal the impact of psoriasis on IPF (OR = 1.09, 95%CI, 0.98-1.21; P = 0.11). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between psoriasis and IPF. CONCLUSIONS: Our study provided potential evidence between genetically predicted psoriasis and IPF, which suggests that understanding the mutual risk factors between psoriasis and IPF can facilitate the clinical management of both diseases.

In vitro and in vivo immunomodulatory activity of acetylated polysaccharides from Cyclocarya paliurus leaves.

In this study, we aimed to investigate the immunomodulatory effects of polysaccharides from Cyclocarya paliurus leaves after acetylation modification (Ac-CPP0.1) on dendritic cells (DCs) and immunosuppressed mice. In vitro, Ac-CPP0.1 promoted phenotypic and functional maturation of DCs. Specifically, it increased the expression of costimulatory molecules (CD80, CD86, and MHC II) and the secretion of cytokines (TNF-α, IL-6, IL-1ß, IL-10, IL-12p70) of DCs. In vivo, Ac-CPP0.1 significantly improved immunosuppression of mice, which was manifested by increased body weight and immune organ index, up-regulated cytokines (IL-4, IL-17, TGF-ß3, and TNF-α), and restored short-chain fatty acid (SCFAs) levels of intestinal. The immunoactivation of Ac-CPP0.1 in DCs and in mice is linked to the activation of the TLR4/NF-κB signaling pathway. Furthermore, Ac-CPP0.1 reversed intestinal flora imbalance caused by cyclophosphamide. At the species level, Ac-CPP0.1 increased the abundance of unclassified_Muribaculaceae, unclassified_Desulfovibrio, Bacteroides_acidifaciens and Faecalibaculum_rodentium, decreased the level of Lactobacillus_johnsonii, unclassified_g_Staphylococcus and Staphylococcus_nepalensis. In summary, Ac-CPP0.1 has considerable immunomodulatory potential, which is beneficial to the future utilization and development of Cyclocarya paliurus.

Morphology of immune-mediated hepatitis: A comparison between immune checkpoint inhibitor therapy and combined immune checkpoint inhibitor/anti-angiogenic therapy.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) with anti-angiogenic drugs has shown promising anticancer effects. However, ICIs can trigger immune-mediated hepatitis (IMH). We aimed to clarify whether the combined use of anti-angiogenic drugs and ICIs would increase the severity of IMH. METHODS: One hundred IMH patients (ICI monotherapy vs. ICI plus anti-angiogenic therapy 30 vs. 70) were retrospectively enrolled. Clinicopathological parameters were compared between the two groups. RESULTS: IMH mainly showed variable degrees of panlobular hepatitis (84 %), while some cases presented mixed cholangio-hepatitic (14 %) or cholangitic (2 %) pattern. The incidence of moderate-severe injury was not significantly different between the two groups (combination vs. monotherapy 38.6 % vs. 20.0 %, p = 0.109). Specifically, the rates of marked lobular injury and portal inflammation were higher in the combination group than in the monotherapy cohort (p < 0.005), while the frequencies of interface hepatitis, bile duct injury, histiocytosis aggregates, and endothelialitis were comparable between the two groups (p > 0.05). Compared to mild IMH cases, severe IMH cases showed higher immunostaining expression levels of PD-L1 (60.7 % vs. 19.4 %, p < 0.0001). Treatments and outcomes of IMH were not significantly different between the two groups (p > 0.05). CONCLUSIONS: Compared to ICI monotherapy, the administration of anti-angiogenic drugs in combination with ICIs was not associated with increased hepatotoxicity.

Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol.

Florfenicol (FLO) has been shown to elicit diverse toxic effects in plants, insects, and mammals. Previously, our investigations revealed that FLO induced abnormal cardiac development and early embryonic mortality in chicken embryos. However, the effect of FLO on mitochondrial responses in stem cells remains unclear. In this study, we show that FLO significantly diminishes proliferation viability and obstructs the directed differentiation of P19 stem cells (P19SCs) into cardiomyocytes. Proteomic analysis revealed 148 differentially expressed proteins in response to FLO. Functional analysis has pinpointed FLO interference with biological processes associated with oxidative phosphorylation within the mitochondria. In alignment with the results of proteomic analysis, we confirmed that FLO inhibits the expression of both nuclear DNA-encoded and mitochondrial DNA-encoded subunits of the electron transport chain. Subsequent experiments demonstrated that FLO disrupts mitochondrial dynamics and induces the mitochondrial unfolded protein response to maintain mitochondrial homeostasis. These findings collectively highlight the significance of mitochondrial dynamics and the mitochondrial unfolded protein response to mediate the decreased proliferation viability and directed differentiation potential in P19SCs treated with FLO. In conclusion, this study provides a comprehensive overview of mitochondrial responses to FLO-induced cytotoxicity and enhances our understandings of the molecular mechanisms underlying FLO-induced embryonic toxicity.

The Hippo pathway in endometrial cancer: a potential therapeutic target?

Endometrial cancer, one of the most prevalent malignant cancers tumors of the female reproductive tract, has been increasing in incidence and mortality rates around the world. The Hippo pathway, one of the eight traditional human cancer signaling pathways, is an intricate signaling network that regulates cell proliferation, differentiation, and migration as well as restricting organ size in response to a range of intracellular and extracellular signals. Inhibiting the Hippo pathway results in aberrant activation of its downstream core component YAP/TAZ, which can enhance cancer cells' metabolism and maintain their stemness. Additionally, the Hippo pathway can modulate the tumor microenvironment and induce drug resistance, where tumorigenesis and tumor progression occur. However, the Hippo pathway has been little researched in endometrial cancer. Here, we aim to review how the Hippo pathway contributes to the onset, development and the potential treatment of endometrial cancer with the aim of providing new therapeutic targets.

Characterization, antioxidant and antibacterial activities of gelatin-chitosan edible coated films added with Cyclocarya paliurus flavonoids.

In this study, gelatin-chitosan (GEL-CS) composite films added with 0.1 %, 0.2 %, and 0.3 % Cyclocarya paliurus flavonoids (CPF) were prepared. Then their appearance properties, mechanical properties, barrier properties, microstructure, thermal stability properties, antioxidant activity, and antibacterial properties were investigated. As compared with GEL-CS film, the GEL-CS films with CPF were darker in color, had higher water vapor barrier, higher elongation at break, and higher thermal stability. Additionally, microstructure analysis with Fourier infrared spectroscopy, scanning electron microscopy, and X-ray diffraction demonstrated that hydrogen bonding was the main force for cross-linking CPF with other membrane substrates. Moreover, the addition of CPF strengthened the antioxidant and antimicrobial properties of the membranes. These results indicated that the CPF addition could endow membranes with more excellent functional properties and bioactivity, accompanied by environmentally friendly and edible features. The GEL-CS-CPF composite film would be a potential and prospective packing material for food preservation applications.

Compound AC1Q3QWB upregulates CDKN1A and SOX17 by interrupting the HOTAIR-EZH2 interaction and enhances the efficacy of tazemetostat in endometrial cancer.

Endometrial cancer (EC) is a common malignancy of the female reproductive system, with an escalating incidence. Recurrent/metastatic EC presents a poor prognosis. The interaction between the long non-coding RNA (lncRNA) HOTAIR and the polycomb repressive complex 2 (PRC2) induces abnormal silencing of tumor suppressor genes, exerting a pivotal role in tumorigenesis. We have previously discovered AC1Q3QWB (AQB), a small-molecule compound targeting HOTAIR-EZH2 interaction. In the present study, we unveil that AQB selectively hampers the interaction between HOTAIR and EZH2 within EC cells, thus reversing the epigenetic suppression of tumor suppressor genes. Furthermore, our findings demonstrate AQB's synergistic effect with tazemetostat (TAZ), an EZH2 inhibitor, significantly boosting the expression of CDKN1A and SOX17. This, in turn, induces cell cycle arrest and impedes EC cell proliferation, migration, and invasion. In vivo experiments further validate AQB's potential by enhancing TAZ's anti-tumor efficacy at lower doses. Our results advocate AQB, a recently discovered small-molecule inhibitor, as a promising agent against EC cells. When combined with TAZ, it offers a novel therapeutic strategy for EC treatment.

The MR Imaging of Primary Intrahepatic Lymphoepithelioma-like Cholangiocarcinoma: A Diagnostic Challenge.

PURPOSE: To characterize the magnetic resonance imaging features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). MATERIALS AND METHODS: Thirty-four patients with 38 histologically confirmed LELCCs were enrolled retrospectively from January 2014 to August 2022. We evaluated the clinical features, histologic findings, and imaging manifestations on dynamic enhanced MRI. RESULTS: 74% (25/34) of the cases were associated with EBV infection. Moreover, patients infected with EBV exhibited a lower level of Ki-67 proliferation. The serum CA199 level was elevated in 10 patients. The median tumor diameter was 2.8 cm (range, 1.1-8.7 cm). Most tumors were well-defined with a smooth or lobulated margin and showed peripheral hyperintensity and central hypointensity on T2-weighted imaging (T2WI). T2 hyperintense foci were recognized in 8 patients. In the dynamic enhanced MRI, 21 tumors demonstrated Type A enhancement pattern (rim enhancement), 10 demonstrated Type B (rapid wash-in and wash-out), and seven demonstrated Type C (rapid wash-in without wash-out). Capsular enhancement in PVP or DP was found in 22 tumors. A few patients had satellite lesions, portal vein thrombosis, bile duct dilatation, and distal metastasis. Lymph node metastases were discovered pathologically in 11 patients. CONCLUSIONS: MRI findings of LELCC vary and are non-specific. While a majority of LELCCs exhibit typical features of intrahepatic cholangiocarcinoma (iCCA), unique findings like T2 hyperintense foci or capsular enhancement could suggest LELCC. EBV infection and elevated tumor markers can aid in differentiation. However, given the mimics of some cases of liver hypervascular lesions, histological examination remains essential for definitive diagnosis.

Functional diversity of diterpene synthases in Aconitum plants.

Members of the Aconitum genus within the Ranunculaceae family are known to accumulate a broad array of medicinal and toxic diterpenoid alkaloids (DAs). Historically, ent-copalyl diphosphate (ent-CPP) was considered the sole precursor in DAs biosynthesis. However, the recent discovery of ent-8,13-CPP synthase in A. gymnandrum Maxim., which participates in ent-atiserene biosynthesis, raises the question of whether this gene is conserved throughout the Aconitum genus. In this study, RNA sequencing and PacBio Iso-sequencing were employed to identify diterpene synthases (diTPSs) in four additional Aconitum species with distinct DA compositions. In vitro and in vivo analyses functionally characterized a diverse array of 10 class II and 9 class I diTPSs. In addition to the identification of seven class II diTPSs as ent-CPP synthases, three other synthases generating ent-8,13-CPP, 8,13-CPP, and 8α-hydroxy-CPP were also discovered. Four class I kaurene synthases-like (KSLs) were observed to react with ent-CPP to yield ent-kaurene. Three KSLs not only reacted with ent-CPP but also ent-8,13-CPP to produce ent-atiserene. AsiKSL2-1 was found to react with 8α-hydroxy-CPP to produce Z-abienol and AsiKSL2-2 exhibited no activity with any of the four intermediates. This research delineates the known diterpene biosynthesis pathways in six Aconitum species and explores the highly divergent diterpene synthases within the genus, which are consistent with their phylogeny and may be responsible for the differential distribution of diterpenoid alkaloids in root and aerial parts. These findings contribute valuable insights into the diversification of diterpene biosynthesis and establish a solid foundation for future investigation into DA biosynthetic pathways in Aconitum.

Clinical Value of Combined Detection of Serum sTim-3 and CEA or CA19-9 for Postoperative Recurrence of Colorectal Cancer Diagnosis.

Purpose: The present study aimed to evaluate the clinical value of Combined Detection of serum soluble T-cell immunoglobulin 3 (sTim-3) with carcinoembryonic antigen (CEA) or glycotype antigen 19-9 (CA19-9) for Postoperative Recurrence of Colorectal Cancer (CRC) Diagnosis. Patients and Methods: The serum sTim-3 was measured by highly sensitivity TRFIA, and serum CEA and CA19-9 were obtained through the collection of clinical data. Quantitative detection of serum sTim-3, CEA, CA19-9 in 90 patients after the CRC surgery (52 postoperative recurrence and 38 no-postoperative recurrence), 21 patients with colorectal benign tumors, and 67 healthy controls. To analyze the clinical diagnostic value of combined detection of sTim-3 with CEA or CA19-9 to test whether patients have recurrence after CRC surgery. Results: The sTim-3 (15.94±11.24ng/mL) in patients after CRC surgery was significantly higher than in healthy controls (8.95±3.34ng/mL) and colorectal benign tumors (8.39±2.28ng/mL) (P < 0.05), and sTim-3 (20.33±13.04ng/mL) in CRC postoperative recurrent group was significantly higher than in the group without recurrence after CRC surgery (9.94±2.36ng/mL) (P < 0.05). In terms of detecting postoperative recurrence after CRC surgery, combined detection of sTim-3 and CEA (AUC: 0.819, sensitivity: 80.77%, specificity: 65.79%), sTim-3 and CA19-9 test (AUC: 0.813, sensitivity: 69.23%, specificity: 97.30%) was significantly better than the CEA single test (AUC: 0.547, sensitivity: 63.16%, specificity: 48.08%) and CA19-9 single test (AUC: 0.675 sensitivity: 65.38%, specificity: 67.57%), Delong test P < 0.05. Conclusion: The efficacy of CEA and CA19-9 single test was not optimal, and the combination of sTim-3 in serum could significantly improve the sensitivity and specificity of detecting patient recurrence after CRC surgery.

Radiographic and α-fetoprotein response predict pathologic complete response to immunotherapy plus a TKI in hepatocellular carcinoma: a multicenter study.

BACKGROUND: Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear. METHODS: We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti-programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples. RESULTS: We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558-0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785-0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy. CONCLUSIONS: In patients with unresectable HCC receiving combined TKI/anti-PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.

Identifying Hub Genes and miRNA-mRNA Regulatory Networks in Mice Infected with H1N1 Influenza Virus.

H1N1 influenza virus is a major factor in seasonal influenza outbreaks. After the body is infected with the influenza virus, the expression of certain mRNAs, including miRNAs, could be affected. However, the association between these mRNAs and miRNAs remains unclear. This study is aimed at identifying differentially expressed genes (DEGs) and miRNAs (DEmiRs) caused by H1N1 influenza virus infection and constructing a miRNA-mRNA regulatory network. Nine GSE datasets were downloaded from the Gene Expression Omnibus database, of which seven were mRNA data and two were miRNA data. The limma package in R language package was used to analyze array data, and edgeR package was used to analyze high-throughput sequencing data. At the same time, the genes related to H1N1 infection were further screened by WGCNA analysis. DEGs were subjected to Gene Ontology and KEGG pathway enrichment analyses by DAVID database, while the STRING database predicted the protein-protein interaction (PPI) network. The correspondence between miRNA and target mRNA was analyzed by the miRWalk database. Cytoscape software was used to output PPI results, identify hub genes, and construct a miRNA-mRNA regulatory network. 114 DEGs and 37 candidate DEmiRs were identified for subsequent analysis. These DEGs were significantly enriched in response to the virus, cytokine activity, and symbiont-containing vacuole membrane. According to KEGG analysis, DEGs were enriched in PD-L1 expression and PD-1 checkpoint pathway. The key point Cd274 (PD-L1) was highly expressed in the H1N1-infected group. Finally, a potential miRNA-mRNA regulatory network (containing 8 candidate DEmiRs and 69 candidate DEGs) and a PPI network were constructed. After that, three hub genes were identified: Ifit3, Stat2, and Irf7. These hub genes and Cd274 were validated by another independent high-throughput dataset and were highly expressed pattern. This study will help researchers gain insights into the intrinsic effects of H1N1 influenza virus infection on the host and suggest a novel association of H1N1 virus with the host immune system.

Exposure to bisphenol A induces neurotoxicity associated with synaptic and cytoskeletal dysfunction in neuro-2a cells.

Bisphenol A (BPA) has been reported to injure the developing and adult brain. However, the underlying mechanism still remains elusive. This study used neuro-2a cells as a cellular model to investigate the neurotoxic effects of BPA. Microtubule-associated protein 2 (MAP2) and tau protein maintain microtubule normal function and promote the normal development of the nervous system. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic plasticity. Cells were exposed to the minimum essential medium (MEM), 0.01% (v/v) DMSO, and 150 µM BPA for 12, 24, or 36 h. Morphological analysis revealed that the cells in the BPA-treated groups shrank and collapsed compared with those in the control groups. CCK-8 and lactate dehydrogenase assay (LDH) assays showed that the mortality of neuro-2a cells increased as the BPA treatment time was prolonged. Ultrastructural analysis further revealed that cells demonstrated nucleolar swelling, dissolution of nuclear and mitochondrial membranes, and partial mitochondrial condensation following exposure to BPA. BPA also decreased the relative protein expression levels of MAP2, tau, and Dbn. Interestingly, the relative protein expression levels of SYP increased. These results indicated that BPA inhibited the proliferation and disrupted cytoskeleton and synaptic integrity of neuro-2a cells.