Integrin αvß6 mediates the immune escape through regulation of PD-L1 and serves as a novel marker for immunotherapy of colon carcinoma.

The immune escape of colon cancer and its role in the response to immunotherapies such as PD-1/PD-L1 checkpoint inhibitors have long been of great interest. The positive outcomes of immunotherapy are limited by the immunosuppressive nature of the tumor microenvironment. Integrin αvß6, which can regulate the progression of colon cancer, was recently reported to be involved in the immune suppression of colon cancer. In the present study, we explored the correlation between αvß6 and PD-L1 expression by immunohistochemistry of colon cancer tissues. Then, the regulation of PD-L1 signaling by αvß6 in colon cancer cells was demonstrated. We constructed an in vivo model and performed immunophenotyping experiments to analyze further the regulation of the immune response by αvß6. The role of αvß6 in the response to anti-PD-1 therapy in colon cancer was also verified. αvß6-positive tissues exhibited increased PD-L1 expression. Inhibition of αvß6 not only downregulated constitutive PD-L1 expression but also decreased IFN-γ-induced PD-L1 expression. In addition, αvß6-induced PD-L1 expression was suppressed by the ERK inhibitor PD98059, and knockdown of the ß6-ERK2 binding site had the equivalent effect. αvß6 decreased CD8+ T cell infiltration and granzyme B expression in CD8+ T cells in colon cancer patients. Furthermore, mice engrafted with αvß6-expressing colon cancer cells exhibited an unsatisfactory response to anti-PD-1 therapy, and anti-PD-1-induced increases in CD4+ and CD8+ T cell infiltration could be inhibited by αvß6. These results indicate that αvß6 mediates immune escape in colon cancer by upregulating PD-L1 through the ERK/MAPK pathway. Moreover, αvß6 could serve as a marker for the efficacy of anti-PD-1 therapy in colon cancer.

Antioxidant effects of Paeoniflorin and relevant molecular mechanisms as related to a variety of diseases: A review.

Paeoniflorin (PF), which is the main component of the Paeonia lactiflora Pall extract, is one of the traditional Chinese medicines. The pharmacological effects associated with PF include antioxidant, immunomodulatory, anti-inflammatory, anticancer, antidepressant-like and neuroprotective effects. Our previous studies had revealed that PF protected melanocytes and inhibited photodamage through the suppression of oxidative stress (OS). As OS plays a vital role in the progression of a variety of diseases, the capacity for PF to suppress OS may exert important effects upon them. However, no review exists on these antioxidant effects of PF as related to various diseases. Therefore, in this review we summarized studies involved with examining the antioxidant effects and molecular mechanisms of PF. Through its capacity to inhibit OS, PF has been shown to exert beneficial effects upon several systems including nervous, cardiac/vascular, digestive, and respiratory as well as specific diseases such as diabetes, autoimmune, pregnancy related, ocular, kidney, dermatology, along with suppression of distal flap necrosis, postoperative adhesions, and hearing loss. Such findings provide new insights and directions for future research directed at the development of PF as a natural antioxidant for the treatment of clinical diseases.

Primary pancreatic peripheral T-cell lymphoma: A case report.

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

Concurrence of dermatomyositis and psoriasis: a case report and literature review.

Dermatomyositis (DM) is a type of inflammatory myopathy with unknown causes. It is characterized by distinct skin lesions, weakness in the muscles close to the body, and the potential to affect multiple organs. Additionally, it may be associated with the presence of malignancies. The development of DM is influenced by genetic susceptibility, autoimmune response, and various external factors like cancer, drugs, and infectious agents. Psoriasis is a chronic, recurring, inflammatory, and systemic condition. Scaly erythema or plaque is the typical skin manifestation. The etiology of psoriasis involves genetic, immune, environmental and other factors. It is uncommon for a patient to have both of these diseases simultaneously, although individuals with DM may occasionally exhibit symptoms similar to those of psoriasis. Our patient was diagnosed with psoriasis in his 50s because of scalp squamous plaques, but he did not receive standard treatment. Ten years later, he developed symptoms of muscle pain and limb weakness. He was diagnosed with psoriasis complicated with dermatomyositis in our department and received corresponding treatment. Moreover, we reviewed the relevant literature to evaluate similarities and differences in clinical manifestation and treatment to other cases.

The clinicopathologic and immunohistochemical features of 60 cutaneous glomus tumor: a retrospective case series study.

BACKGROUND: Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain. OBJECTIVES: To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1ß, IL-6, and CGRP in it, further, to explore the possible mechanism of pain. METHODS: The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1ß, IL-6 and CGRP. RESULTS: GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1ß and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT. STUDY LIMITATIONS: Low sample size and further research is needed to explore the specific mechanism. CONCLUSIONS: IL-1ß and IL-6 were highly expressed in GT cells, suggesting that IL-1ß and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1ß and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it's necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet.

The clinicopathologic and immunohistochemical features of 60 cutaneous glomus tumor: a retrospective case series study

Abstract Background Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain. Objectives To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1β, IL-6, and CGRP in it, further, to explore the possible mechanism of pain. Methods The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1β, IL-6 and CGRP. Results GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1β and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT. Study limitations Low sample size and further research is needed to explore the specific mechanism. Conclusions IL-1β and IL-6 were highly expressed in GT cells, suggesting that IL-1β and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1β and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it's necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet.

Recurrence of Local Kyphosis After Percutaneous Kyphoplasty: The Neglected Injury of the Disc-Endplate Complex.

Background: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures. Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors. Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81±8.60° postoperatively to 25.13±8.91° at the final follow-up which showed a statistically significant difference (p<0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p<0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc-endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p<0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis. Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc-endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.

Immunohistochemical Features of MMP-9 and pSTAT1 in Granuloma Annulare and Sarcoidosis: A Comparative Study of 62 Cases.

Background: Granuloma annulare (GA) and sarcoidosis are granulomatous inflammatory diseases that share similarities. Objective: To identify the histological and immunohistochemical (IHC) features of GA and sarcoidosis. Methods: A retrospective review of 36 patients with GA and 26 with sarcoidosis was performed. Results from hematoxylin and eosin (H&E) staining and IHC staining of MMP-9 and pSTAT1 within the skin lesions of GA and sarcoidosis were analyzed, and random forest was applied for developing a predictive model. Results: Significantly greater expressions of MMP-9 (especially in elastic fibers, EFs, P < 0.0001) and pSTAT1 (P = 0.0003) were observed in lesion samples of GA versus sarcoidosis patients. In GA patients, MMP-9 was significantly upregulated in the interstitial type (P = 0.0222), while staining of pSTAT1 was positively correlated with the area of mucinous collagen in palisading GA (R = 0.5356, P = 0.0484). In sarcoidosis patients, MMP-9 (R = -0.7127, P = 0.0009) and pSTAT1 (R = -0.5604, P = 0.0067) were found to show stronger expressions in lesions with less lymphocyte infiltration. The predictive model demonstrated an AUC of 0.9675. Conclusion: These results indicate that MMP-9 and pSTAT1 might exert roles in granulomatous inflammation in different modes, and the presence of more robust MMP-9 staining in EFs appears to be more suggestive of GA.

Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis.

BACKGROUND: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are two unexplained immune diseases. The golden standard for diagnosis of these diseases requires a liver biopsy. Liver biopsy is not widely accepted by patients because of its invasive nature, and atypical liver histology can confuse diagnosis. In view of the lack of effective diagnostic markers for PBC and AIH, combined with the increasingly mature metabolomics technologies, including full-contour metabolomics and target. AIM: To determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of PBC and AIH. METHODS: Serum samples from 54 patients with PBC, 26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry serum metabolomics. The metabolites and metabolic pathways were identified, and the metabolic changes, metabolic pathways and inter-group differences between PBC and AIH were analyzed. Fifteen kinds of target metabolites of bile acids (BAs) were quantitatively analyzed by SRM, and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis. RESULTS: We found the changes in the levels of amino acids, BAs, organic acids, phospholipids, choline, sugar, and sugar alcohols in patients with PBC and AIH. Furthermore, the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease. CONCLUSION: The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

Thalidomide combined with endoscopy in the treatment of Cronkhite-Canada syndrome: A case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease with a poor prognosis and a mortality rate of up to 55%. Currently, there is no standard treatment for CCS. The department of gastroenterology of our hospital admitted a patient with CCS whose symptoms improved significantly after treatment with thalidomide combined with endoscopy, and there was no obvious adverse reaction during the 2-year follow-up. CASE SUMMARY: A 47-year-old Chinese man presented with diarrhea for more than 4 mo, accompanied by loss of taste, fatigue, and weight loss. Physical examination demonstrated that the patient's skin and hands were hyperpigmented, the front edges of the nails of both hands were notably thickened and yellow, and the nails were partially atrophied. Gastrointestinal endoscopy identified a diffuse polypoid bulge, and the patient bore an albumin level of 27.3 g/L. The level of the calcium correction amount was (2.164 mM) which allowed for a comprehensive diagnosis of Cronkhite-Canada syndrome, combined with hypoalbuminemia and hypocalcemia. Thalidomide of 150 mg per day was administered to regulate immunity, and the symptoms were relieved after 1 wk. During the follow-up period, polyps were still found that had not been resolved by thalidomide treatment, and endoscopic therapy was performed. This resulted in further improvement of his condition and no particular discomfort during the 2 years of follow-up. CONCLUSION: The patient's symptoms were significantly relieved by thalidomide 2 years after treatment, proposing it as a potential treatment for CCS.

Relationship between MTHFR C677T, homocysteine, and ischemic stroke in a large sample of the Han Chinese population.

Ischemic stroke, one of the prevalent causes of death and disability worldwide, is linked to environmental and genetic factors, including polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism. The present study aimed to explore the relationship between the MTHFR C677T variant, plasma homocysteine, and risk of developing large-artery atherosclerotic ischemic stroke (LAAIS) among Han Chinese. A population-based case-control study, which included 1810 patients with LAAIS and 1765 unrelated control subjects, was conducted. Compared to the controls, LAAIS patients had a significantly higher prevalence of hypertension, diabetes mellitus, smoking, and alcohol consumption (P < .001), as well as significantly higher mean fasting blood glucose, triglyceride, total cholesterol, and plasma homocysteine levels (P < .001). The TT homozygous genotype correlated with increased risk of developing LAAIS, as indicated by a significantly higher odds ratio (OR) compared to the CT and CC genotypes, in both additive (OR = 3.215, P = .01) and recessive models (OR = 3.265, P = .01). The plasma homocysteine level was genotype-dependent according to the following trend: TT > CT > CC. In conclusion, our data demonstrate that, in spite of its low prevalence in both patients and controls (1.5% vs 0.8%), the MTHFR C677T variant could, at least in part, affect homocysteine levels and this, either alone or in combination with other factors, increases the risk of LAAIS.

Rare primary rectal mucosa-associated lymphoid tissue lymphoma with curative resection by endoscopic submucosal dissection: A case report and review of literature.

BACKGROUND: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurs in approximately 9% of non-Hodgkin B-cell lymphomas. The gastrointestinal tract is the most commonly affected site of the extranodal forms of primary non-Hodgkin's lymphomas. However, it rarely occurs within the rectum, and at present, there is no consensus on its diagnosis and treatment at this site. CASE SUMMARY: We report a rare laterally spreading tumour-like rectal MALT lymphoma case in which the diagnosis and the depth of infiltration were determined by magnifying endoscopy and ultrasonic endoscopy. Then, the lesion was en bloc resected by endoscopic submucosal dissection (ESD) alone. The lesion was confirmed as MALT lymphoma by haematoxylin and eosin staining, immunohistochemical staining and gene arrangement analysis. Surveillance exams have indicated a 2-year disease-free survival for this patient. CONCLUSION: We report a rare primary rectal MALT lymphoma that was curable with resection by ESD. ESD is a safe and effective therapeutic option for rectal MALT lymphoma.

Exosome-transmitted miR-3124-5p promotes cholangiocarcinoma development via targeting GDF11.

Objective: Cholangiocarcinoma (CHOL) is a deadly cancer worldwide with limited available therapies. The aim of this study was to investigate key exosomal miRNAs and their functions in CHOL development. Methods: Serum exosomes were isolated from patients with CHOL and healthy controls, followed by miRNA sequencing for identifying differentially expressed miRNAs (DEMs) and their functions. Then, the expression of key DEMs was experimentally validated in exosomes from clinical CHOL patients and CHOL cells. The effects of overexpression of key DEMs on CHOL cell migration and proliferation were investigated. A key exosomal DEM miR-3124-5p was identified. The effects of overexpression or knockdown of exosomal miR-3124-5p on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were investigated. Moreover, the function of exosomal miR-3124-5p on tumor growth in vivo was explored. Results: A total of 632 exosomal DEMs were identified between CHOL and control samples. Target genes of DEMs were significantly enriched in pathways, such as the p53 signaling pathway. miR-3124-5p was upregulated in serum exosomes from CHOL patients and exosomes from CHOL cells, and overexpression of miR-3124-5p promoted RBE cell migration and viability. Moreover, overexpression of exosomal miR-3124-5p promoted the proliferation, migration, and angiogenesis of HUVECs, while knockdown of miR-3124-5p had the opposite effect. miR-3124-5p could target growth differentiation factor 11 (GDF11) and downregulate GDF11 expression. Furthermore, exosomal miR-3124-5p promoted tumor growth in vivo. Conclusions: Our findings revealed that exosome-encapsulated miR-3124-5p promoted the malignant progression of CHOL by targeting GDF11. Exosomal miR-3124-5p and GDF11 could be promising biomarkers or therapeutic targets for CHOL.

PRMT5 confers lipid metabolism reprogramming, tumour growth and metastasis depending on the SIRT7-mediated desuccinylation of PRMT5 K387 in tumours.

The protein arginine methyltransferase 5 (PRMT5), which is highly expressed in tumour tissues, plays a crucial role in cancer development. However, the mechanism by which PRMT5 promotes cancer growth is poorly understood. Here, we report that PRMT5 contributes to lipid metabolism reprogramming, tumour growth and metastasis depending on the SIRT7-mediated desuccinylation of PRMT5 K387 in tumours. Mass spectrometric analysis identified PRMT5 lysine 387 as its succinylation site. Moreover, the desuccinylation of PRMT5 K387 enhances the methyltransferase activity of PRMT5. SIRT7 catalyses the desuccinylation of PRMT5 in cells. The SIRT7-mediated dessuccinylation of PRMT5 lysine 387 fails to bind to STUB1, decreasing PRMT5 ubiquitination and increasing the interaction between PRMT5 and Mep50, which promotes the formation of the PRMT5-Mep50 octamer. The PRMT5-Mep50 octamer increases PRMT5 methyltransferase activity, leading to arginine methylation of SREBP1a. The symmetric dimethylation of SREBP1a increases the levels of cholesterol, fatty acid, and triglyceride biogenesis in the cells, escaping degradation through the ubiquitin-proteasome pathway. Functionally, the desuccinylation of PRMT5 K387 promotes lipid metabolism reprogramming, tumour growth and metastasis in vitro and in vivo in tumours.

Nickel-Catalyzed anti-Markovnikov Hydrodifluoroalkylation of Unactivated Alkenes.

An efficient Ni-catalyzed hydrodifluoroalkylation of unactivated alkenes with bromodifluoroacetate by using PhSiH3 as hydride source was developed. The transformation affords aliphatic difluorides with anti-Markovnikov regioselectivity. A wide range of highly remote alkenes, simple alkenes, drug molecules, commercially available CF2 precursors, and even nonfluorinated substrates are competent in this reaction under mild conditions, demonstrating the practicability of the strategy. Moreover, mechanistic studies indicated that the difluoroalkyl radical might be a key intermediate to this transformation.

Toxic epidermal necrosis associated with afatinib: A case report and literature review.

Objective: To report a case of afatinib-induced toxic epidermal necrosis (TEN), in a patient with metastatic non-small cell lung cancer (NSCLC) and compare these findings with that of evaluate similarities and differences to other cases reported in the literature. Methods: With use of the algorithm of drug causality for epidermal necrolysis (ALDEN), the effects of afatinib were evaluated in a NSCLC patient who developed TEN. In addition, previous case reports on this topic were included to provide a review of patients' clinical characteristics, treatment regimens and therapy outcomes in response to afatinib treatment. Results: In our case, toxic epidermal necrolysis was observed at five days after afatinib therapy, while other Stevens-Johnson syndrome/toxic epidermal necrolysis responses, as associated with afatinib, did not seem to be induced until a latency period of over thirty days post-afatinib. Treatment with corticosteroids resulted in significant improvements of these clinical symptoms, and eventually to a complete remission. Conclusion: Afatinib can result in grade four cutaneous adverse effects like SJS/TEN, with an uncertain latency period. The skin lesions which appear during this period of afatinib treatment should be closely monitored.

The miR-23-27-24 cluster: an emerging target in NAFLD pathogenesis.

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing globally, being the most widespread form of chronic liver disease in the west. NAFLD includes a variety of disease states, the mildest being non-alcoholic fatty liver that gradually progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Small non-coding single-stranded microRNAs (miRNAs) regulate gene expression at the miRNA or translational level. Numerous miRNAs have been shown to promote NAFLD pathogenesis and progression through increasing lipid accumulation, oxidative stress, mitochondrial damage, and inflammation. The miR-23-27-24 clusters, composed of miR-23a-27a-24-2 and miR-23b-27b-24-1, have been implicated in various biological processes as well as many diseases. Herein, we review the current knowledge on miR-27, miR-24, and miR-23 in NAFLD pathogenesis and discuss their potential significance in NAFLD diagnosis and therapy.

Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B.

BACKGROUND: Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application. AIM: The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA (pgRNA), cccDNA, and HBeAg seroconversion. METHODS: This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog (NUC)-based therapy (NCT03509688 and NCT03546530). Serum qHBcrAg, pgRNA, HBV DNA, hepatitis B core antigen, HBeAg, liver cccDNA, and HBV DNA were measured. The correlations of serum qHBcrAg with other biomarkers were analyzed. RESULTS: A total of 139 patients were included. The mean qHBcrAg levels were 5.32 ± 1.18 log10 U/mL at baseline and decreased during treatment (all P < 0.0001). Serum qHBcrAg levels were positively correlated with pgRNA (r = 0.597, P < 0.0001) and cccDNA (r = 0.527, P < 0.0001) levels. The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant (r = 0.399, P < 0.0001). HBcrAg predicted HBeAg seroconversion, with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk. Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion [odds ratio (OR) = 2.402, 95% confidence interval (CI): 1.314-4.391, P = 0.004; OR = 3.587, 95%CI: 1.315-9.784, P = 0.013]. CONCLUSION: Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.

Hyperglycemia Promotes Liver Metastasis of Colorectal Cancer via Upregulation of Integrin αvß6.

BACKGROUND Diabetes is related to higher risk of multiple cancers. This study aimed to explore the effect and mechanism of diabetes on liver metastasis of CRC. MATERIAL AND METHODS Overall and liver metastasis-free survival in diabetic and non-diabetic CRC patients were compared by Kaplan-Meier analysis. Expression of alphavß6 was detected by immunohistochemistry in clinical specimens. Effects of hyperglycemia on alphavß6 expression in colon cancer cells were assessed by western blot, real-time PCR, and flowcytometry. Effects of hyperglycemia on migration and invasion were demonstrated by Transwell assay. Expression and activity of MMP-9 and MMP-2 were determined by real-time PCR and gelatin zymography. Liver metastatic nodules were counted and b6 expression was detected by western blot in a liver metastasis mouse model. RESULTS CRC patients with diabetes had poorer overall and liver metastasis-free survival, and diabetes was associated with higher alphavß6 expression in CRC specimens. Hyperglycemia promoted the invasion and migration of colon cancer cells, and upregulated the expression and activity of MMP-9, which were attenuated by inhibition of alphavß6. Hyperglycemia upregulated the expression of ß6 and cell surface expression of avb6, which was reduced by ERK inhibitor. The in vitro results were confirmed in vivo in the mouse model. CONCLUSIONS Our study demonstrated the enhancing effect of hyperglycemia on liver metastasis of CRC, and showed that alphavß6 was involved in this process, suggesting that control of glucose levels and inhibition of alphavß6 can reduce the risk of liver metastasis in diabetic CRC patients.