A nomogram to predict conversion of laparoscopic surgery to laparotomy for Choledocholithiasis.

BACKGROUND: Laparoscopic surgery is effective for treating common bile duct (CBD) stones. However, it has high requirements for surgeons and the risk of conversion to laparotomy cannot be ignored. However, when conditions during surgery are not favorable, persisting with laparoscopic procedures blindly can lead to serious complications. Our study aimed to establish a nomogram model for predicting conversion of laparoscopic to laparotomy for choledocholithiasis. MATERIALS AND METHODS: A total of 867 patients who were diagnosed with choledocholithiasis and underwent laparoscopic surgery were randomly divided into a training group (70%, n = 607) and a validation group (30%, n = 260). A nomogram was constructed based on the results of logistic regression analysis. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram. RESULTS: Previous upper abdominal surgery, maximum diameter of stone ≥12 mm, medial wall of the duodenum stone, thickening of the gallbladder wall, thickening of CBD wall, stone size/CBD size ≥0.75, and simultaneous laparoscopic hepatectomy were included in the nomogram. The AUC values were 0.813 (95% CI: 0.766-0.861) and 0.804 (95% CI: 0.737-0.871) in the training and validation groups, respectively. The calibration curve showed excellent consistency between the nomogram predictions and actual observations. DCA showed a positive net benefit for the nomogram. CONCLUSIONS: We constructed a nomogram with a good ability to predict conversion to open surgery in laparoscopic surgery for choledocholithiasis, which can help surgeons to make a reasonable operation plan before surgery and timely convert to laparotomy during operation to reduce potential harm to the patient.

Chondroitin polymerizing factor (CHPF) contributes to malignant proliferation and migration of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the human digestive system, and has been recognized as a serious threat to public health worldwide. This study explored the role of chondroitin polymerizing factor (CHPF) in the development and metastasis of HCC. Immunohistochemistry analysis was performed to detect CHPF expression in HCC tissues and para-carcinoma tissues. qRT-PCR and Western blot analysis were used to determine the mRNA and protein expression of CHPF. MTT assays, colony formation assays, and flow cytometry were used to evaluate the cell proliferation, colony formation, and cell apoptosis, respectively. Wound-healing and Transwell assays were performed to evaluate cell migration. The results show that CHPF was not only up-regulated in HCC tissues compared with para-carcinoma tissues, but was also related with more advanced stages of HCC. Further studies revealed that CHPF knockdown significantly inhibited cell proliferation and colony formation, and induce cell apoptosis of HCC cells. Moreover, suppressing the expression of CHPF reduced the migration and invasiveness of HCC cells. In conclusion, we demonstrated that CHPF plays important roles in the development and progression of HCC, and high expression levels of HCC may be related with poorer prognosis. The results from this study may provide a potential therapeutic target for HCC treatment.

Neutrophil to lymphocyte ratio may be a helpful marker to evaluate disease activity in NMOSD.

Neutrophil to lymphocyte ratio (NLR) was introduced to assess the activity in autoimmune diseases. Neuromyelitis optica spectrum disorder (NMOSD) has been defined as a chronic inflammatory disease with a course of relapse-remission. Therefore, the relationship between NLR and NMOSD was assessed in this article. Data of NMOSD patients was extracted. NLR is calculated as the absolute count of neutrophil divided by the absolute count of lymphocytes. Correlations between NLR and characteristics of NMOSD patients were evaluated. Effect of treatments on NLR was also analyzed. Increased level of NLR was observed in patients with NMOSD compared healthy individuals (p < 0.001); moreover, patients who were experiencing acute attack had a higher level of NLR compared with those who in remission (p < 0.001). NLR was correlated with RDW (r = 0.288, p = 0.021), ΔEDSS (r = 0.301, p = 0.016). NLR may be a helpful marker to assess the disease activity of NMOSD. Meanwhile, NLR may reflect the aggravated degree of neurological disability.

Effects of early using azathioprine in the acute phase in neuromyelitis optica spectrum disorder.

BACKGROUND: Azathioprine is widely used for neuromyelitis optica spectrum disorder (NMOSD) patients, while a consensus of timing to receive azathioprine has not been proposed. OBJECTIVE: The objective of this paper was to evaluate the efficacy of early access of azathioprine in NMOSD patients. METHODS: We conducted a retrospective review of NMOSD patients based on medical records. Included patients were divided into three groups: group IVMT + AZA, group AZA after IVMT and group IVMT. Time to next relapse was adopted as the endpoint. RESULTS: Patients from group IVMT + AZA had a longer duration of remission compared with patients from group AZA after IVMT ( p = 0.025) and group IVMT ( p < 0.001), and longer duration showed in the group AZA after IVMT when compared with group IVMT ( p = 0.005). We found that older age of initial attack was a risk factor for NMOSD patients (HR: 1.235; p = 0.022), and younger age of receiving treatment was a protect factor (HR: 0.804; p = 0.023). Partial patients have used azathioprine before this study in group IVMT + AZA, result showed there was no significance between the patients who had or had not used azathioprine ( p = 0.299). CONCLUSION: Azathioprine could prolong the duration of remission after treatment, especially given within two weeks after attack. Patients who received azathioprine combined with glucocorticoids had a preferable effect than glucocorticoids alone in the remission.

Machine learning models and nomogram based on clinical, laboratory profiles and skeletal muscle index to predict pancreatic fistula after pancreatoduodenectomy.

Background: Postoperative pancreatic fistula (POPF) is a perilous complication that may arise subsequent to pancreaticoduodenectomy (PD). In recent times, there has been an escalating interest in employing machine learning (ML) techniques to aid in treatment decision-making. The purpose of this research is to assess the effectiveness of ML in comparison to conventional models, while also conducting an initial evaluation of the predictive capability of skeletal muscle index (SMI) concerning POPF. Methods: This retrospective observational study was carried out at The First Affiliated Hospital of Wenzhou Medical University from January 2012 to January 2021, encompassing data from 269 patients who underwent PD. After identifying independent factors associated with the condition, a logistic regression model was employed to construct a nomogram, alongside the establishment of five ML models. To assess their effectiveness, the best-performing ML model and nomogram were evaluated on a separate test group comprising 77 additional patients. The evaluation involved comparing the area under the curve (AUC) and Brier score. Results: Among the 269 patients studied, the incidence of POPF was found to be 56.9%, with 106 patients (69.3%) experiencing clinically-relevant POPF. We identified six independent factors associated with POPF, including body mass index (BMI), SMI, pancreatic duct dilatation, tumor size, triglyceride levels, and the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) on the first postoperative day. When evaluated on the test set, the Gaussian Naive Bayes (GNB) model, which was the best-performing ML model, achieved an AUC of 0.824 and a Brier score of 0.175. The corresponding performance indicators for the nomogram were 0.844 for AUC and 0.165 for the Brier score. Conclusions: This study found that there is minimal difference between ML and the nomogram based on logistic regression in predicting POPF. Additionally, SMI shows promise as a potential and practical tool for assessing the risk of POPF.

A scoring system for gallbladder polyps based on the cross-sectional area and patient characteristics.

BACKGROUND: Current management guidelines for gallbladder polyps (GBPs) focus on a diameter more than 1 cm as an indication for cholecystectomy. Since most GBPs are not malignant, unnecessary cholecystectomies can lead to unnecessary complications and costs. We developed a score to identify true polyps focusing on their cross-sectional area (CSA). METHODS: We retrospectively analyzed the demographic, clinical, laboratory, and sonographic characteristics of 522 patients with GBPs who had undergone cholecystectomy at our hospital between January 2010 and July 2020 (reference group). We used univariate analysis to compare these parameters between 88 true polyps and 434 pseudopolyps and multivariate logistic regression analysis to identify parameters to include in our scoring model. Receiver operating characteristics and area under the curve were used to identify cut-off values. The model was tested on a validation group of 98 patients. RESULTS: In the multivariate analysis, a CSA >123 mm2, positive blood flow signal, age >55.5 years, alanine aminotransferase (ALT) levels > 50 U/L, and an ALT/aspartate aminotransferase ratio > 0.77 were significantly associated with true polyps (odds ratio 6.528, 2.377, 2.617, 2.445, and -0.372, respectively). A prediction model based on cut-off values was used to distinguish a low-risk and high-risk GBP group; true polyps accounted for 6.54% and 58.72%, respectively (p < 0.001). In the low-risk and high-risk validation groups, true polyps comprised 12.35% and 82.35%, respectively (p < 0.001). CONCLUSIONS: Our scoring system shows high accuracy and specificity in identifying true polyps and helps determine the need for surgical resection.

Circular RNA circ_0089153 acts as a competing endogenous RNA to regulate colorectal cancer development by the miR-198/SUMO-specific peptidase 1 (SENP1) axis.

Increasing evidence has indicated the implications of circular RNAs (circRNAs) in the development of colorectal cancer (CRC). In this study, we investigated the functional role and mechanism of circ_0089153 in CRC pathogenesis. The expression levels of circ_0089153, microRNA (miR)-198, and SUMO-specific peptidase 1 (SENP1) were gauged by quantitative real-time PCR (qRT-PCR) or western blot. Cell proliferation, sphere formation, tube formation, and apoptosis abilities were detected by 5-Ethynyl-2'-Deoxyuridine (EdU), sphere formation, tube formation, and flow cytometry assays, respectively. The direct relationship between miR-198 and circ_0089153 or SENP1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The mouse xenograft assays were performed to evaluate the role of circ_0089153 in vivo. Our data showed that circ_0089153 was overexpressed in CRC tissues and cells. Depletion of circ_0089153 repressed cell proliferation, sphere formation ability, and enhanced cell apoptosis, as well as inhibited tube formation in vitro. Moreover, circ_0089153 depletion diminished tumor growth in vivo. Mechanistically, circ_0089153 targeted miR-198, and the effects of circ_0089153 were mediated by miR-198. SENP1 was identified as a direct and functional target of miR-198. Circ_0089153 worked as a competing endogenous RNA (ceRNA) to post-transcriptionally regulate SENP1 expression by miR-198. Our findings identify circ_0089153 as a novel regulator of CRC development through the regulation of the miR-198/SENP1 axis and establish a strong rationale for developing circ_0089153 as a promising therapeutic against CRC.

Berbamine Enhances the Efficacy of Gefitinib by Suppressing STAT3 Signaling in Pancreatic Cancer Cells.

BACKGROUND: Small molecular inhibitors such as gefitinib (Gefi), which target EGF receptor (EGFR), are considered to be a viable pathway for the selective inhibition of pancreatic cancer (PC) development. However, the large difference in Gefi response between PC patient individuals and PC cell lines severely limits the clinical efficacy of Gefi. Berbamine (BBM) is a well-known natural-derived antitumor agent. However, no study yet exists on whether BBM can enhance the sensitivity of PC cells to Gefi or its underlying mechanisms. METHODS: MTS assay and clonogenic assay were used to determine whether BBM could enhance the anti-PC activity of Gefi by. Flow cytometric analysis was performed to study the cell cycle progression and rate of apoptosis after combined treatment with BBM and Gefi. Surface plasmon resonance (SPR) and Western blot experiments were carried out to detect the STAT3 binding affinity and the STAT3 inhibitory effect of BBM. Molecular docking and Molecular dynamic simulation were used to predicting the dominant interaction between BBM and STAT3. RESULTS: This study found that BBM synergizes with Gefi to inhibit cell growth and induce cell cycle arrest and PC cell apoptosis. Mechanistically, our results showed that BBM and Gefi have synergistic inhibitory effects on STAT3 phosphorylation, but have little effect on other EGFR downstream pathways, suggesting that BBM may exert sensitization through the inhibition of STAT3. Besides, BBM has a high affinity for STAT3 and a good inhibitory effect on STAT3 activation, further indicating that BBM was a potent direct STAT3 inhibitor. Molecular modeling between STAT3 and BBM suggested that BBM formed several key hydrophilic interactions with STAT3. CONCLUSION: Our findings suggest that the combination of BBM and Gefi could be further developed as a potential PC therapy.

A Prediction Model for Recognizing Strangulated Small Bowel Obstruction.

INTRODUCTION: Early and accurate diagnosis of strangulated small bowel obstruction (SSBO) is difficult. This study aimed to devise a prediction model for predicting the risk of SSBO. MATERIALS AND METHODS: A database of 417 patients who had clinical symptoms of intestinal obstruction confirmed by computed tomography (CT) were evaluated for inclusion in this study. Symptoms and laboratory and radiologic findings of these patients were collected after admission. These clinical factors were analyzed using logistic regression. A logistic regression model was applied to identify determinant variables and construct a clinical score that would predict SSBO. RESULTS: Seventy-six patients were confirmed to have SSBO, 169 patients required surgery but had no evidence of intestinal ischemia, and 172 patients were successfully managed conservatively. In multivariate logistic regression analysis, body temperature ≥ 38.0°C, positive peritoneal irritation sign, white blood cell (WBC) count > 10.0 × 10^9/L, thick-walled small bowel ≥3 mm, and ascites were significantly associated with SSBO. A new prediction model with total scores ranging from 0 to 481 was developed with these five variables. The area under the curve (AUC) of the new prediction model was 0.935. CONCLUSIONS: Our prediction model is a good predictive model to evaluate the severity of SBO.

Genetically engineered recombinant adenovirus expressing interleukin­2 for hepatocellular carcinoma therapy.

Regulatory and effector T cells possess immunological cytotoxicity for tumor cells in the tumor microenvironment during tumor progression and are the primary suppressors inhuman cancer therapy. Interleukin­2 (IL­2) is an anticancer cytokine, which triggers human innate and adaptive immunity by stimulating T cell propagation and lymphocyte infiltration into tumor sites. IL­2 has been used successfully for cancer therapy. Recombinant adenovirus expressing IL­2 (rAd­IL­2) injection is a gene therapy agent that may improve prognosis of hepatocellular carcinoma (HCC) patients. In the present study, the ability of IL­2 to stimulate an immune response and the ability of recombinant adenovirus to inhibit tumor cell growth in HCC was investigated in a HCC tumor model. It was demonstrated that the regulatory and effector cell­mediated tumor suppression by antitumor cluster of differentiation (CD)4+ and CD8+ T cells stimulated by rAd­IL­2 is tumor­specific. Furthermore, rAd­IL­2 significantly stimulated tumor­specific cytotoxic T lymphocyte responses, increased interferon­Î³ release and enhanced antitumor immunity by inducing CD4+ and CD8+ T cell recruitment into the tumor, and additionally induced memory to protect tumor­bearing mice against tumor challenge. Treatment with rAd­IL­2 led to tumor regression and long­term survival of mice in the 120­day treatment period. Tumor challenge experiments demonstrated that rAd­IL­2 induced memory, protecting against reinfection. In conclusion, rAd­IL­2 may promote tumor­associated effector and regulatory T cell expansion and may be a potential therapeutic agent for clinical immunotherapy application in the treatment of cancer.

Clinical value of the neutrophil/lymphocyte ratio in diagnosing adult strangulated inguinal hernia.

BACKGROUND: Diagnosis of incarcerated inguinal hernia (IIH) is not difficult, but currently, there are no diagnostic criteria that can be used to differentiate it from strangulated inguinal hernia (SIH). This research aimed to evaluate the clinical value of the neutrophil/lymphocyte ratio (NLR) in diagnosing SIH. METHODS: We retrospectively analyzed 263 patients with IIH who had undergone emergency operation. The patients were divided into two groups according to IIH severity: group A, patients with pure IIH validated during operation as having no bowel ischemia; group B, patients with SIH validated during operation as having obvious bowel ischemia, including bowel necrosis. We statistically evaluated the relation between several clinical features and SIH. The accuracy of different indices was then evaluated and compared using receiver operating characteristic (ROC) curve analyses, and the corresponding cutoff values were calculated. RESULT: Univariate analysis showed eight clinical features that were significantly different between the two groups. They were then subjected to multivariate analysis, which showed that the NLR, type of hernia, and incarcerated organ were significantly related to SIH. ROC curve analysis showed that the NLR had the largest area under the ROC curve. CONCLUSION: Among the different clinical features, the NLR appears to be the best index in diagnosing SIH.

Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway.

The antidiabetic drug metformin has been shown to possess antitumor functions in many types of cancers. Although studies have revealed its beneficial effects on the prognosis of hepatocellular carcinoma (HCC), the detailed molecular mechanism underlying this event remains largely unknown. In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells. We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC.