From NAFLD to MASLD: When metabolic comorbidity matters.

INTRODUCTION AND OBJECTIVES: In a recent development, a cohort of hepatologists has proposed altering the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated steatotic liver disease (MASLD), accompanied by modified diagnostic criteria. Our objective was to investigate the effect of the revised definition on identifying significant hepatic fibrosis. PATIENTS AND METHODS: From Jan 2009 to Dec 2022, a total of 428 patients with biopsy-proven hepatic steatosis were diagnosed with NAFLD. Patients were classified into subgroups according to MASLD and Cryptogenic-SLD diagnostic criteria. The clinical pathological features were compared between these two groups. Risk factors for significant fibrosis were analysed in the MASLD group. In total, 329 (76.9 %) patients were diagnosed with MASLD, and 99 (23.1 %) were diagnosed with Cryptogenic-SLD. RESULTS: Those with MASLD exhibited a higher degree of disease severity regarding histology features than Cryptogenic-SLD. The prevalence of significant fibrosis increased from 13 % to 26.6 % for one and two criteria present to 42.5 % for meeting three or more cardiometabolic risk factor (CMRF) criteria (p = 0.001). ALB (aOR:0.94,95 %CI:0.90-1.00; p = 0.030), lower levels of PLT (aOR:0.99, 95 %CI:0.99-1.00; p < 0.001), and more metabolic comorbidities (aOR:1.42,95 %CI:1.14-1.78; p = 0.012) were independent risk factors of significant fibrosis in MASLD. CONCLUSIONS: The new nomenclature of MASLD and SLD is more applicable to identifying significant fibrosis than NAFLD. Patients with three or more cardiometabolic risk factors are at higher risk of fibrosis.

Prognostic biomarker CCR6 and its correlation with immune infiltration in cutaneous melanoma.

Background: Cutaneous melanoma (CM) is an aggressive type of skin cancer. Even after standard treatment, the recurrence and malignant progression of CM were almost inevitable. The overall survival (OS) of patients with CM varied widely, making it critical for prognostic prediction. Based on the correlation between CCR6 and melanoma incidence, we aimed to investigate the prognostic role of CCR6 and its relationship with immune infiltration in CM. Methods: We obtained RNA sequencing data from The Cancer Genome Atlas (TCGA) to analyze the CM expression. Functional enrichment analyses, immune infiltration analyses, immune checkpoint analyses, and clinicopathology analyses were performed. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram model had been developed. Kaplan-Meier survival analysis and log-rank test were used to estimate the relationship between OS and CCR6 expression. Results: CCR6 was significantly upregulated in CM. Functional enrichment analyses revealed that CCR6 was correlated with immune response. Most immune cells and immune checkpoints were positively correlated with CCR6 expression. Kaplan-Meier analyses showed that high CCR6 expression was associated with a good outcome in CM and its subtypes. Cox regression showed that CCR6 was an independent prognostic factor in patients with CM (HR = 0.550, 95% CI = 0.332-0.912, p<0.05). Conclusions: CCR6 is considered to be a new prognostic biomarker for patients with CM, and our study provides a potential therapeutic target for CM treatment.

[Efficacy Evaluation of Three Endoscopic Therapies of Isolated Gastric Varices with Modified Tissue Adhesive].

Objective: To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive. Methods: A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated. Results: In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies ( P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods ( P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year ( P<0.05). Conclusion: The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

Functional Surgery for Subungual Melanoma: Surgical Tips Based on Histological Analysis of 21 Cadavers.

BACKGROUND: Amputation has been the standard treatment for subungual melanoma. Although there is growing attention toward a more conservative functional surgery, specific operative techniques are not yet available. OBJECTIVE: We aimed to provide objective measurements for use in functional surgery by analyzing the anatomy of the nail apparatus obtained from 21 cadavers. MATERIALS AND METHODS: Nailbed thickness was histologically measured in each subunit, and skin surface anatomy was evaluated to determine the proximal resection margin. Immunohistochemical staining was performed to analyze microvessel distribution according to the nail subunit. RESULTS: The nailbed thickness was the thinnest at the most proximal point of the nail matrix (thumbs, 1.10 ± 0.42 mm; big toes, 1.15 ± 0.37 mm) and the thickest at the hyponychium (thumbs, 2.86 ± 0.82 mm; big toes, 2.72 ± 0.84 mm). The distance from the eponychium to the skin surface closest to the bony cortex of extensor tendon insertion was 6.92 ± 5.13 mm in thumbs and 5.14 ± 1.59 mm in big toes. The median microvessel density was the highest at the hyponychium (25.74 vessels/mm2) and lowest at the germinal matrix (16.26 vessels/mm2) (p < .05). CONCLUSION: This histological study offers practical tips, including those to help decide the proximal and deep resection margins, in functional surgery.

Clinical Features and Outcomes of Repeated Endoscopic Therapy for Esophagogastric Variceal Hemorrhage in Cirrhotic Patients: Ten-Year Real-World Analysis.

OBJECTIVE: This study is aimed at evaluating the survival of cirrhotic patients with different etiologies after endoscopic therapy for acute variceal bleeding and the effect of repeated endotherapy on patients' prognosis. METHODS: We retrospectively evaluated the clinical features and outcomes between cirrhotic patients with chronic HBV or HCV infections and other etiologies. The 3-year and 5-year survival rates and rehemorrhage rate in one year between the viral and nonviral cirrhosis patients were compared by Kaplan-Meier curves and log-rank test. Cox analysis was used to identify the impact factors that affect the long-term survival of patients with cirrhosis and variceal bleeding after endotherapy. RESULTS: Out of 2665 patients with liver cirrhosis and variceal hemorrhage selected from our medical center between September 2008 and December 2017, a total of 1342 patients were included for analysis. The median follow-up duration was 32.9 months (range 0.16-111.4 months), the 3- and 5-year cumulative survival rates were 75.3% and 52.8%, respectively. The median survival time was significantly longer in viral cirrhosis patients (47.1 months [95% CI: 24.9-69.1]) compared with nonviral cirrhosis patients (37.0 months [95% CI: 25.0-56.0], p = 0.001). The 3-year and 5-year survival rates of the viral group were higher than the nonviral group. The rehemorrhage rate at one year was higher in nonviral patients than in viral patients (p < 0.001). CONCLUSION: Repeated endotherapy combined with effective antiviral therapy is helpful for long-term survival of cirrhotic population with variceal hemorrhage and HBV or HCV infection.

Antiviral therapy reduces rebleeding rate in patients with hepatitis B-related cirrhosis with acute variceal bleeding after endotherapy.

BACKGROUND: The preventive effects of antiviral therapy to reduce rebleeding rate in patients with hepatitis B-related cirrhosis undergoing endoscopic treatment have not yet been reported. METHODS: In this retrospective cohort study, 1139 patients with chronic hepatitis B with first acute variceal bleeding after endoscopic therapy from September 2008 to December 2017 were included. Among them, 923 who received and 216 who did not receive antiviral therapy were followed up for rebleeding. Cumulative rebleeding rate was calculated using the Kaplan-Meier method. Univariate and multivariate logistic regression analyses were performed to estimate the effects of antiviral therapy on rebleeding risk. The propensity score matched method and inverse probability of treatment weighting analysis were used to calculate the rebleeding rate between the antiviral and non-antiviral groups. RESULTS: The rebleeding rates were 40.5, 60.7, 72.6, and 89.2% in antiviral group at 1, 2, 3, and 5 years, respectively. The corresponding rebleeding rates in the non-antiviral group were 54.2, 72.4, 84.4, and 93.3%, respectively. The multivariate logistic regression analysis revealed that antiviral therapy was an independent protective factor associated with rebleeding. CONCLUSION: Antiviral treatment significantly reduced rebleeding rate in patients with HBV-related cirrhosis who received endoscopic treatment after the first variceal bleeding.

A new algorithm for predicting long-term survival in chronic hepatitis B patients with variceal bleeding after endoscopic therapy.

BACKGROUND AND AIMS: A predictive algorithm for survival is urgently needed in clinical practice. This study aimed to establish an algorithm to predict long-term survival in chronic hepatitis B (CHB) patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy. METHODS: This was a retrospective study in which 603 patients who followed-up for three years were randomly assigned into a training cohort and a validation cohort in a 2:1 ratio. A new score model was devised based on the result of Cox regression analysis in the training cohort, and was verified in the validation cohort. RESULTS: A prediction score model composed of age, neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase and MELD score was established. The score ranged from 0 to 11. Areas under the ROC curve of the score were 0.821 (p < 0.001, 95% CI: 0.769-0.873) and 0.827 (p < 0.001, 95% CI: 0.753-0.900) in the training cohort and validation cohort, respectively. Scores 0-4 and 5-11 identified patients as low-risk and high-risk categories, respectively. The cumulative 3-year survival rate was significantly higher in the low-risk group than in the high-risk group (p < 0.001). CONCLUSION: The new score model can be used to predict long-term survival in CHB patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy.

A Retrospective Analysis of Cyanoacrylate Injection versus Hemoclip Placement for Bleeding Dieulafoy's Lesion in Duodenum.

BACKGROUND: Duodenal Dieulafoy's lesion (DL) is a rare disease that may lead to lethal hemorrhage in the upper gastrointestinal tract. The best technique for endoscopic intervention still remains unclear. In the present study, we performed a retrospective analysis of cyanoacrylate injection versus hemoclip placement for treating bleeding DLs. MATERIALS AND METHODS: We retrospectively analyzed eighteen patients from three medical centers between October 2008 and February 2016; six patients received cyanoacrylate injection, while hemoclips were placed in 12 patients during the upper gastrointestinal endoscopy. RESULTS: All patients received first endoscopic examination and/or endotherapy within 12 hours of admission to hospital. No difference was observed in the primary hemostasis rate or the recurrent hemorrhage rate between the cyanoacrylate injection (CI) group and the hemoclip placement (HP) group, except that in one patient from the HP group melena was found three days after the first endotherapy. This patient received cyanoacrylate injection once again. CONCLUSION: Both cyanoacrylate injection and hemoclip placement are effective in treating duodenal DL, and neither of them causes significant side effects.

Sural Nerve Splitting in Reverse Sural Artery Perforator Flap: Anatomical Study in 40 Cadaver Legs.

BACKGROUND: The reverse sural artery perforator flap has been widely used in reconstruction of the lower extremity. However, along with the high rate of flap necrosis, sural nerve injury is one of the most frequent complications. This cadaveric study investigated a simple sural nerve preservation technique during reverse sural artery perforator flap surgery. METHODS: Cadaver dissection was performed on 40 cadaver lower legs, to investigate the pattern of sural nerve distribution. The points where the lateral and medial sural cutaneous nerves penetrate the deep fascia were measured. The converging point of these nerves into the sural nerve was also recorded. Furthermore, the sural nerve was split until no tethering was observed, to simulate the sural nerve-sparing reverse sural artery perforator flap. RESULTS: Twenty-nine legs (72.5 percent) showed the lateral and medial sural cutaneous nerves converging to become the sural nerve (combined pattern); seven (17.5 percent) and four legs (10.0 percent) demonstrated the diminished and parallel types, respectively. The distances between the lateral malleolus and the fascia-penetrating point of the lateral and medial sural cutaneous nerves were 29.9 ± 3.3 cm and 18.8 ± 5.6 cm, respectively. In the combined type, the point of convergence was 13.6 ± 4.2 cm from the lateral malleolus. Nerve splitting was successfully performed in all combined cases, without injuring the nerve fascicles. CONCLUSIONS: The medial sural cutaneous nerve enters the deep fascia significantly more distally than does the lateral sural cutaneous nerve. Furthermore, using nerve splitting, the medial sural cutaneous nerve can be kept intact during reverse sural artery perforator flap surgery.

[Correlation of FOXA1 with the malignancy and progression of prostate cancer].

OBJECTIVE: To study the relationship of the expression of FOXA1 in the prostate cancer (PCa) tissue with the Gleason score and clinical staging of PCa and with castration-resistant PCa (CRPC). METHODS: Using the immunohistochemical method, we detected the expressions of FOXA1 and Ki-67 in the pathological sections of 35 cases of PCa and 21 cases of benign prostatic hyperplasia (BPH). Then we analyzed their correlation with the Gleason score and TNM staging of PCa and that with CRPC. RESULTS: The positive expression of FOXA1 was significantly higher in the PCa than in the BPH tissue (P < 0.001) and was positively correlated with that of Ki-67 (P < 0.001) as well as with the Gleason score (P = 0.027) and clinical staging of PCa (P = 0.002), but showed no correlation with CRPC (P = 0.391). CONCLUSION: The positive expression of FOXA1 is increased in PCa, most significantly in the advanced stage of the tumor.

[Effects of Klotho protein on proliferation, migration, adhesion and vascular endothelial growth factor expression of human umbilical vein cells].

OBJECTIVE: To explore the effects of anti-aging Klotho protein in the proliferation, migration and adhesiveness of human umbilical vein endothelial cell (HUVEC) and its influence of vascular endothelial growth factor (VEGF) expression in HUVEC. METHODS: HUVEC were treated for 24 h with various concentrations of Klotho protein (final concentrations of 0.1, 1, 10 nmol/L respectively). At the same time, HUVEC treated with PBS, 10 nmol/L VEGF and 10 nmol/L Klotho protein plus AKT inhibitors served as blank control, positive control and AKT signaling pathway inhibition group respectively. The effects of Klotho proteins on proliferation, migration and adhesiveness of HUVEC were determined by thiazolyl blue tetrazolium bromide (MTT), scratches, Transwell and cell adhesion assays respectively. After HUVEC exposed to Klotho protein, the induced function of VEGF expression was measured by Western blot analysis. RESULTS: The MTT results showed that the A values of 0.1, 1, 10 nmol/L Klotho protein group increased respectively to 0.63 ± 0.03, 0.71 ± 0.04, 0.80 ± 0.04, control to the blank group (0.59 ± 0.03, F = 9.32, all P < 0.05). The scratches tests showed that compared with the blank control (9.40 ± 2.07)%, the cell migration rates of 0.1, 1, 10 nmol/L Klotho protein group increased significantly to (12.28 ± 0.62)%, (31.66 ± 1.50)%,(36.69 ± 0.79)%, (F = 9.50, all P < 0.05). Transwell assay found that cell migration count of 0.1, 1, 10 nmol/L Klotho protein group increased to 95.88 ± 9.54, 143.13 ± 7.83, 178 ± 12.77, higher than the blank control group (80.13 ± 12.19), the difference was statistically significant (F = 11.51, all P < 0.05). In cell adhesion assays, the number of cell adhesion increased to 59.60 ± 5.13, 78.40 ± 7.16, 114.60 ± 5.55 at 0.1, 1, 10 nmol/L Klotho protein group versus the blank control (49.40 ± 6.23) and the difference was also statistically significant (F = 9.75, all P < 0.05). Using Western blot, the expressions of VEGF were significantly induced to 0.46 ± 0.02,0.71 ± 0.12,0.81 ± 0.16 at 0.1, 1, 10 nmol/L Klotho protein group versus blank control group (0.35 ± 0.08, F = 8.95, all P < 0.05). CONCLUSION: Klotho protein can promote the proliferation, migration and adhesiveness of HUVEC and induce a significant expression of VEGF, and its functions are related with the AKT signaling pathway.