The mechanism of cancer-depression comorbidity.

Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients.

Comparison of laparoscopic common bile duct exploration plus cholecystectomy and endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy for elderly patients with common bile duct stones and gallbladder stones.

BACKGROUND: Common bile duct (CBD) stones commonly occur in cholecystectomy cases. The management options include laparoscopic CBD exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Although ERCP is fully developed, it has complications, and LCBDE is a proven alternative. This study aimed to evaluate the safety and efficacy of these treatments in elderly individuals aged ≥70 years. METHODS: A retrospective study between January 2015 and July 2022 included 160 elderly patients (aged ≥70 years) diagnosed with cholelithiasis and choledocholithiasis. The patients were divided into 1-stage (LCBDE [n = 80]) or 2-stage (ERCP followed by LC [n = 80]) treatment groups. Data collected encompassed comorbidities, symptoms, bile duct clearance, postoperative complications, and long-term outcomes for systematic analysis. RESULTS: This study analyzed 160 patients treated for CBD stones, comparing 1-stage and 2-stage groups. The 1-stage group had more female patients than the 2-stage group (57.5% vs 37.5%, respectively). The 1-stage group had a mean age of 80.55 ± 7.00 years, which was higher than the mean age in the 2-stage group. American Society of Anesthesiologists classification, Charlson Comorbidity Index, and laboratory findings were similar. Pancreatitis and cholangitis occurred after ERCP in the 2-stage group. Stone clearance rates (92.35% [1-stage group] vs 95.00% [2-stage group]) and biliary leakage incidence (7.5% [1-stage group] vs 3.0% [2-stage group]) were similar, as were postoperative complications and long-term recurrence rates (13.0% [1-stage group] vs 12.5% [2-stage group]). CONCLUSION: Our research indicates that both the combination of LCBDE and LC and the sequence of ERCP followed by LC are equally efficient and secure when treating CBD stones in elderly patients. Consequently, the 1-stage procedure may be considered the preferred treatment approach for this demographic.

FOXM1-CD44 Signaling Is Critical for the Acquisition of Regorafenib Resistance in Human Liver Cancer Cells.

Regorafenib is a multikinase inhibitor that was approved by the US Food and Drug administration in 2017. Cancer stem cells (CSCs) are a small subset of cancer-initiating cells that are thought to contribute to therapeutic resistance. The forkhead box protein M1 (FOXM1) plays an important role in the regulation of the stemness of CSCs and mediates resistance to chemotherapy. However, the relationship between FOXM1 and regorafenib resistance in liver cancer cells remains unknown. We found that regorafenib-resistant HepG2 clones overexpressed FOXM1 and various markers of CSCs. Patients with hepatocellular carcinoma also exhibited an upregulation of FOXM1 and resistance to regorafenib, which were correlated with a poor survival rate. We identified a close relationship between FOXM1 expression and regorafenib resistance, which was correlated with the survival of patients with hepatocellular carcinoma. Thus, a strategy that antagonizes FOXM1-CD44 signaling would enhance the therapeutic efficacy of regorafenib in these patients.

Single-incision versus four-incision laparoscopic transfistulous bile duct exploration for Mirizzi syndrome type II.

BACKGROUND: We developed laparoscopic transfistulous bile duct exploration (LTBDE) for Mirizzi syndrome (MS) McSherry type II in September 2011. Then, single-incision LTBDE (SILTBDE) was adopted as a preferred technique since August 2013. This retrospective study aims to analyze the outcome of LTBDE in 7.7 years and to compare SILTBDE with four-incision LTBDE (4ILTBDE). METHODS: Seventeen consecutive patients underwent LTBDE for MS McSherry type II from September 2011 to May 2019. Transfistulous removal of the impacted stone(s), choledochoscopic bile duct exploration, and primary closure of the gallbladder remnant were performed without biliary drainage. RESULTS: The sex ratio is 12:5 (male: female) with an average age of 39.4 ± 10.3 (24-56) years. Ten patients (58.8%) had their diagnoses of MS established by preoperative imaging. According to the Csendes classification, three type II (17.6%), nine type III (52.9%), and five type IV (29.4%) were identified. The operative time was 264.8 ± 60.3 min (156-358 min). The stone clearance rate was 100%. The postoperative hospital stay was 4.7 ± 1.9 (2-10) days. No procedure was converted to an open operation. Two postoperative transient hyperamylasemia (11.8%) and one superficial wound infection (5.9%) occurred and all recovered well under conservative treatment (Clavien-Dindo grade I). During an average 2.2-year follow-up period, no biliary stricture or stone recurrence occurred. No significant difference exists between the SILTBDE and 4ILTBDE groups. Nevertheless, an insignificant trend of shorter postoperative hospital stay was observed in the former. A diagnosis of MS Csendes type IV implicates prolonged total and postoperative hospital stays (p < 0.01). CONCLUSIONS: LTBDE is safe and efficacious for MS McSherry type II. It provides a simple solution for various types of MS and avoids undesirable complications following bilioenteric anastomosis. SILTBDE is comparable to 4ILTBDE for selected patients. Patients with MS Csendes type IV need more time to recover after surgery.

Change in the Oligomeric State of α-Synuclein Variants in Living Cells.

The accumulation of ß-sheet-rich α-synuclein (α-Syn) protein in human brain cells is a pathological hallmark of Parkinson's disease (PD). Moreover, it has been reported that familial PD mutations (A30P, E46K, H50Q, G51D, and A53T) accumulate at an accelerated rate both in vivo and in vitro. In addition, accumulations of various C-terminal α-Syn truncations, such as C-terminal-truncated N103 α-synuclein (N103), were found in an aggregated form in the brain tissue of PD patients. Fluorescent protein-tagged wild-type α-Syn, A30P, E46K, H50Q, G51D, A53T, and N103 were transfected into HEK293T and SHSY5Y cells, and their diffusion behaviors were investigated with a custom-built fluorescence microscope system. Based on our experimental results, the oligomerization of α-Syn is a time-dependent process in both HEK293T and SHSY5Y cells, and the oligomer state approaches a plateau after 48 h of transfection. The change in the oligomeric state of E46K, H50Q, and G51D exhibited a similar trend to the wild type at a lower concentration but became intense at a higher concentration. A53T and N103 possess smaller diffusion coefficients than wild-type α-synuclein and other family PD mutations, indicating that these two mutants could form higher oligomeric states or stronger interactions in HEK293T and SHSY5Y cells. In contrast, the smallest oligomer and the lowest intracellular interaction among all investigated α-Syn variants were found for A30P. These phenomena indicated the presence of different pathogeneses among familial PD mutants and C-terminal α-Syn truncations.

The experience of use of percutaneous transhepatic biliary drainages for early biliary complications after liver transplantation.

This study aimed to describe our experience and discuss the results, controversies, and the use of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary complications after liver transplantation (LT). Between November 2009 and August 2020, 76 consecutive patients who underwent 77 LTs (44 deceased donor LTs and 33 living donor LTs [LDLT]) were enrolled retrospectively. Endoscopic therapy as initial approach and PTBD as rescue therapy were used for patients with biliary complications. There were 31 patients (31/76, 40.8%) with biliary complications, and two of them died (2/31, 6.5%). Clinical success rate of endoscopic therapy alone was 71.0% (22/31). The remaining nine patients received salvage PTBD and their clinical results were observed according to whether their intrahepatic bile ducts (IHBDs) was dilated (group A, n = 5) or not (group B, n = 4). In group A, the technical and long-term clinical success rates of PTBD were 100% and 20%, respectively. These five patients received PTBD ranging from 75 to 732 days after their LTs, and no procedure-related complications were encountered. In group B, the technical and long-term clinical success rates of PTBD were 50% and 25%, respectively. Three group B patients (75%) underwent PTBD within 30 days after LDLT and had lethal complications. One patient had graft laceration and survived after receiving timely re-transplantation. The other two patients died of sepsis due to PTBD-related bilioportal fistula or multiple liver abscesses. Our experience showed salvage PTBD played a limited role in biliary complications without dilated IHBDs within 1 month after LT.

Comparison of Manual and Automated Nucleic Acid Extraction Methods in Virus Transport Medium.

BACKGROUND: The implementation of an automated nucleic acid extraction system has many advantages over the manual methods. The purpose of this study was to evaluate the validity of two different methods for nucleic acid extraction in virus transport medium. METHODS: We collected 20 nasopharyngeal swabs in viral transport medium from the emergency department of the Asia University Hospital for the detection of SARS-CoV-2. The performance of the MaelstromTM 8 (Taiwan Advanced Nanotech) and the QIAamp Viral RNA Mini Kit (Qiagen) were compared for the extraction of nucleic acid from viral transport medium. The extracts were used for the validation of the RNA extraction procedures. The RNase P target was amplified in a one-step reverse transcription-quantitative PCR (RT-qPCR) reaction, as internal control for the extraction method. RESULTS: In this study, the agreement between the two methods was good and Pearson's correlation coefficient (r) was 0.919 (p < 0.001). The mean cycle threshold value of the two methods was 29.1. CONCLUSIONS: Overall, the performance values of the MaelstromTM 8 and the QIAamp Viral RNA Mini Kit were comparable to each other. In summary, the MaelstromTM 8 provides a standardized procedure, avoidance of sample-to-sample cross contaminations, is easy to use, improves turnaround time and requires less hands-on time as compared to the manual extraction method. The MaelstromTM 8 is more suitable for clinical laboratories that carry small or medium-sized samples for nucleic acid extraction.

Rapid Cobas Liat SARS-CoV-2 Assay in Comparison with the Laboratory-Developed Real-Time RT-PCR Test.

BACKGROUND: The objective of this study was to compare the validity of two different assays for the detection of SARS-CoV-2. METHODS: We collected 50 nasopharyngeal swabs in universal transport medium from the emergency department of Asia University Hospital for the detection of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). The samples for the Liat SARS-CoV-2 influenza A/B test were stored at -70℃ after SARS-CoV-2 testing using the RT-PCR in order to assess method comparison. RESULTS: In this study, the Limit of detection (LOD) of the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test is 12 copies/µL and the assay obtained 100% positive agreement and negative percent agreement with RT-PCR. CONCLUSIONS: In summary, a prefect agreement exists between the detection of SARS-CoV-2 conducted with the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test and the RT-PCR. The cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test is a reliable method for the detection of SARS-CoV-2, and it only requires 20 minutes to obtain the results. On the other hand, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test is accurate, easy to use, and provides a faster turnaround time than testing performed in the high-throughput platform.

The association between oral health status and the clinical outcome of cirrhotic patients on the waiting list for liver transplantation.

Liver transplantation (LT) candidates often present with poor oral hygiene, which could potentially lead to systemic infections and sepsis owing to their cirrhotic state. In this study, we investigated the oral health status of LT candidates and propose guidance for the detection and treatment of encountered oral lesions among these patients. The decayed, missing, and filled teeth (DMFT) index was determined through oral examination. The presence of dental calculus was detected using panoramic radiography and defined by the radiopaque dental calculus (RDC). From January 2011 to August 2018, 56 LT candidates were enrolled with a median follow-up of 39 months. The overall mean numbers of decayed, missing, and filled teeth among these patients were 2.7 ± 2.8, 10.9 ± 8.3, and 5.4 ± 4.5, respectively. Eighteen patients (32.1%) had RDC. The 5-year survival rates of all 56 patients was 57.7%, while that of those who either received LT (23 patients) or not were 82.1% and 39.8%, respectively. A Cox regression model revealed better overall survival of patients after LT (adjusted hazard ratio [aHR] = 0.067, p = 0.001), worse survival among patients with RDC (aHR = 3.468, p = 0.010), at Child-Pugh stages B and C (aHR for stage B = 11.889, p = 0.028; aHR for stage C = 19.257, p = 0.013) compared to patients at Child-Pugh stage A, and those with a model for end-stage liver disease (MELD) score ≥25 (aHR = 13.721, p = 0.018). This study demonstrates that RDC was associated with worse prognosis in LT candidates. We therefore recommend that interprofessional collaboration should be a routine preoperative procedure for the evaluation of oral hygiene among LT candidates.

Exploring the Impact of Glyoxal Glycation on ß-Amyloid Peptide (Aß) Aggregation in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the presence of extracellular senile plaques formed by ß-amyloid (Aß) peptides in the patient's brain. Previous studies have shown that the plaques in the AD brains are colocalized with the advanced glycation end products, which is mainly formed from a series of nonenzymatic reactions of proteins with reducing sugars or reactive dicarbonyls. Glycation was also demonstrated to increase the neurotoxicity of the Aß peptides. To clarify the impact of glycation on Aß aggregation, we synthesized two glycated Aß42 peptides by replacing Lys16 and Lys28 with Nε-carboxymethyllysine respectively to mimic the occurrence of protein glycation. Afterward, we monitored the aggregation kinetics and conformational change for two glycated peptides. We also used fluorescence correlation spectroscopy to probe the early stage of peptide oligomerization and tested their abilities in copper binding and reactive oxygen species production. Our data show that glycation significantly slows down the aggregation process and induces more cytotoxicity especially at position 28. We speculated that the higher toxicity might result from a relatively stable oligomeric form of peptide and not from ROS production. The data shown here emphasized that glycated proteins would be an important therapeutic target in AD treatments.

Evaluation of the association between vitamin D and lung cancer skin metastasis: A protocol for systematic review.

BACKGROUND: This study aims to investigate the association between vitamin D (VD) and lung cancer skin metastasis (LCSM). METHODS: The following databases will be retrieved from the beginning to the present of each database without language limitation: PUBMED, EMBASE, Cochrane Library, Web of Science, CBM, and CNKI. The reference lists of included trials and other sources will also be checked. Two researchers will independently undertake literature selection, data collection, and study quality evaluation. We will utilize a fixed or random-effect model to pool the data according to the heterogeneity test. The RevMan 5.3 software will be used to analyze the data and perform meta-analysis. RESULTS: This study will summarize high quality study to explore the association between VD and LCSM. CONCLUSION: The findings of this study will help to judge whether there is association between VD and LCSM. ETHICS AND DISSEMINATION: No research ethical approval is required in this study, because it will only analyze published data. It is expected to disseminate through a peer-reviewed journal. STUDY REGISTRATION: osf.io/ph2au.

Expression of FOXM1 and Aurora-A predicts prognosis and sorafenib efficacy in patients with hepatocellular carcinoma.

BACKGROUND: Effective prognostic biomarkers and powerful target-therapeutic drugs are needed for improving the treatment of Hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to evaluate the expression of FOXM1 and Aurora-A and their prognostic value in HCC. METHODS: We determined the differentially expressed genes signature in HCC using the Gene Set Enrichment Analysis (GSEA), and then evaluated the expression of FOXM1 and Aurora-A in TCGA and KMUH cohort. Associations between co-expression of FOXM1 and Aurora-A and clinical variables were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated with different FOXM1 and Aurora-A expression status. RESULTS: FOXM1-related gene sets were mostly associated with cell cycle regulation in HCC tissues. We found a positive correlation between the expression of FOXM1 and Aurora-A. Overexpression of FOXM1 and Aurora-A was associated with larger tumor size, advanced stage, higher grade, and double-positive for HBV and HCV. The coordinated overexpression of FOXM1 and Aurora-A was the most significant independent prognostic factor for OS and RFS. Furthermore, the concomitant high expression of FOXM1 and Aurora-A predicted the worst OS of sorafenib-treated patients with HCC. CONCLUSIONS: The co-expression of FOXM1 and Aurora-A could be a reliable biomarker to predict the sorafenib response and prognosis of HCC patients.

Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice.

Imbalance of lipid metabolism is a main cause of metabolic syndrome leading to life-threatening metabolic diseases. Angiopoietin-like protein 8 (Angptl8) was recently identified as a liver and adipose tissue-released hormone that is one of the molecules involved in triglyceride metabolism. However, the regulatory mechanism of Angptl8 is largely unknown. A high fat diet (HFD)-fed mouse model, which showed high cholesterol, high triglyceride, and high insulin in the blood, revealed the upregulation of hepatic and plasma Angptl8 and the downregulation of hepatic glycine N-methyltransferase (GNMT). The inverse correlation of hepatic Angptl8 and GNMT expression in the livers of HFD-fed mice was also confirmed in a publicly available microarray dataset. The mechanistic study using primary hepatocytes showed that the Angptl8 expression could be induced by insulin treatment in a dose- and time-dependent manner. Inhibition of PI3K/Akt pathway by the specific inhibitors or the dominant-negative Akt blocked the insulin-induced Angptl8 expression. Moreover, knockout of GNMT promoted the Akt activation as well as the Angptl8 expression. These results suggested that GNMT might be involved in insulin-induced Angptl8 expression in HFD-mediated metabolic syndrome.

Alternative Laparoscopic Intracorporeal Pringle Maneuver by Huang's Loop.

AIM: This paper aims to describe an intracorporeal tourniquet method for laparoscopic Pringle maneuver (PM). METHODS: One shortened Foley tube with side-hole on the tip was put into the abdomen. Then, the tail was pulled out through the side-hole to make a loop to encircle porta hepatis for inflow control. RESULT: It is easy to keep the tension by a metallic clip, and when released, the clip can be removed and the loop loosened. CONCLUSION: Therefore, PM could be performed inside the abdomen without special instrument nor extra trocar port. The intracorporeal Pringle maneuver with Huang's loop could be routinely used during laparoscopic liver resection even for a laparoscopic beginner because it is so easily learnt, safe, and effective.

Activation of G protein coupled estrogen receptor (GPER) promotes the migration of renal cell carcinoma via the PI3K/AKT/MMP-9 signals.

Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. However, the mechanisms responsible for RCC metastasis are still needed further illustration. Our present study revealed that a seven-transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The activation of GPER by its specific agonist G-1 significantly promoted the in vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP-9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration, which suggested that MMP-9 is the key molecule mediating G-1 induced RCC progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059), significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC-2 cells. Generally, our data revealed that activation of GPER by its specific agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals, which might be a promising new target for drug discovery of RCC patients.

Comparison study of clinical outcomes between single-site robotic cholecystectomy and single incision laparoscopic cholecystectomy.

BACKGROUND: Multiport laparoscopic cholecystectomy is the standard surgical procedure for symptomatic gallbladder diseases. The latest evolution is single incision laparoscopic cholecystectomy (SILC). Single-site robotic cholecystectomy (SSRC) overcomes several limitations of manual SILC. The aim of this study is to present our initial experiences in SSRC and to compare its clinical outcomes with those of SILC. METHODS: This study retrospectively reviewed data for patients who received SSRC or SILC from February 2014 to September 2015. The following variables were analyzed: age, sex, body mass index, indications, pain scale, length of stay, and complications. The data were analyzed with Student t test or by Fisher exact test. RESULTS: The analysis included 51 SSRC (33 women, 18 men) and 63 SILC patients (40 women, 23 men). Patients in both groups had similar demographic features and indications for surgery. The SSRC group required no conversions to conventional laparoscopy and no additional trocars, whereas the SILC group had two (3.17%) cases. Length of stay did not significantly differ between the SSRC and SILC groups (4.29 ± 0.72 vs. 4.13 ± 0.93 days, respectively; p = 0.823). However, the SSRC group had shorter operative time (71.30 ± 48.88 vs. 74.70 ± 30.16 minutes; p = 0.772), less perioperative bile spillage (9.81% vs. 19.05%; p = 0.189), and less postoperative bile leakage (0% vs. 3.17%; p = 0.501). However, the parameters mentioned above were not statistically significant, whereas pain scale scores were significantly lower in the SSRC group (2.11 ± 0.76 vs. 3.98 ± 0.84; p < 0.01). CONCLUSIONS: Both SSRC and SILC are safe and feasible procedures for performing single incision cholecystectomy. SSRC, however, has the advantage of significantly decreased postoperative pain.

The value of primary vascular stents in management of early portal vein stenosis after liver transplantation.

If portal vein stenosis (PVS) occurs within 1 month after liver transplantation (LT), especially within 1 week, it can be catastrophic and result in rapid loss of the grafts and mortality. Although surgical treatments have been considered standard treatment for PVS, patients are usually unable to receive operations or re-transplantations, because of their critical conditions and a shortage of grafts. Recently, primary percutaneous transhepatic portal vein stents (PTPS) were suggested as alternative and less-invasive treatments of PVS. However, because lethal complications may follow these primary stent placements for patients in early stages after LT, primary PTPS placements for patients suffering PVS 1 month after LT has been suggested. From November 2009 to July 2015, 38 consecutive adult patients underwent LT at our institution. Among them, six recipients suffered PVS within 1 month after LT. Technical success was achieved in all six patients. Clinical success was obtained in two of the four patients suffering PVS within 1 week after LT, and in the other two patients suffering PVS>1 week after LT. All surviving patients and their grafts were in good condition, and their stents remained patent. Our experience showed that primary PTPS placements can be used to effectively treat patients with PVS encountered within 1 month, and even within 1 week, after LT with acceptable short-term results. However, possible fatal complications should be kept in mind. Long-term results of these procedures need further follow-up.

[Relationship between hepatitis B virus X protein and hepatic cellular cancer].

Hepatic cellular cancer (HCC) is one of the most common cancers in the world, which is a serious threat to human health and life quality. More than 700,000 people die of HCC each year on average, and its incidence increases in many countries. Chronic hepatitis B virus (HBV) infection has been identified as a dominant risk factor for HCC. The pathogenesis of HBV-induced hepatocarcinogenesis is, however, incompletely understood. Evidence currently available supports a key role of the HBV X protein (HBx) in the cancer transformation and malignant tumor metastasis. HBx is a multifunctional regulator that may cooperate with the host factors to exert its effects on transcription, signal transduction, cell cycle progression, apoptosis, protein degradation, expression of oncogene and anti-oncogene. This review presents the current knowledge in the molecular pathogenesis of HBx in the induction of HCC.