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Esophagogastric variceal bleeding is the most common lethal factor for patients with cirrhotic portal hypertension. We firstly developed a laparoscopic splenectomy and azygoportal disconnection (LSD) with intraoperative endoscopic variceal ligation (LSDL) technique. In this study, we aimed to evaluate whether LSDL is feasible and safe and whether LSDL can effectively prevent esophagogastric variceal re-bleeding (EVR), as compared with single LSD.In this randomized controlled single-center study, 88 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism were randomly assigned to receive either LSD (n = 44) or LSDL (n = 44) between January 2020 and December 2021. The primary outcome was EVR.No patients withdrew from the study. There were no significant differences in estimated blood loss, incidence of blood transfusion, time to first flatus and off-bed activity, or postoperative hospital stay between the two groups. Compared with that in the LSD group, operation time was significantly longer in the LSDL group (138.5 ± 19.4 min vs. 150.3 ± 19.0 min, P 0.05); however, LSDL was associated with a significantly decreased EVR rate at 1-year follow-up (8/44 vs. 1/44, P 0.05). Univariate analysis and multivariate logistic regression revealed that LSDL was a significant independent protective factor against EVR in comparison with LSD (relative risk: 0.105, 95% confidence interval 0.012-0.877; P = 0.037).Our newly developed LSDL procedure is not only technically feasible and safe; it also contributed to lowering the EVR risk more so than single LSD.We registered our research at https://www.gov/ . The name of research registered is "Laparoscopic Splenectomy and Azygoportal Disconnection with Intraoperative Endoscopic Variceal Ligation." The trial registration identifier at clinicaltrials.gov is NCT04244487.

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Purpose:Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear.Experimental Design:A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study.Results:A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone.Conclusions:Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

In Asia, laparoscopic splenectomy and azygoportal disconnection (LSD) has been widely regarded as a preferential treatment modality for cirrhotic portal hypertension (PH). However, LSD involves high surgical risk, technical challenges, and many potential postoperative complications. Technology optimization and innovation in LSD aiming to solve to these difficulties has scarcely been reported. In this retrospective study, we aimed to evaluate the clinical therapeutic effect of our cluster technology optimization and innovation on LSD for PH.From February 2012 to January 2020, 500 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism underwent LSD in our department. According to different operation periods, patients were divided into the early-, intermediate-, and late-period groups. We collected information regarding clinical characteristics of all patients as well as their preoperative and postoperative follow-up data.Compared with the early-period group, operation time and postoperative hospital stay were all significantly different and gradually declined from the intermediate- and late-period groups, respectively (all P lt; 0.05). Intraoperative blood loss of these three groups was gradually decreased, with significant differences (P lt; 0.05). The incidences of delayed gastric emptying and diarrhea in the late-period group were all significantly lower than those in the early- and intermediate-period groups, respectively (all P lt; 0.05). Compared with the early-period group, the incidence of variceal re-bleeding was significantly lower in the intermediate- and late-period groups (all P lt; 0.05).Our cluster technology optimization and innovation of LSD not only contributed to faster recovery and fewer complications but also enhanced surgical safety for patients. It is worth promoting this approach among patients with EVB and hypersplenism secondary to cirrhotic PH.

The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus. From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP. Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222–25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466–9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively. Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively. We registered our research at https://www.clinicaltrials.gov/ . The name of research registered is “Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection.” The trial registration identifier at clinicaltrials.gov is NCT02247414.

How to precisely protect and preserve anterior and posterior vagal trunks and all their branches during the procedure of splenectomy and azygoportal disconnection is studied rarely. We firstly developed a vagus nerve-guided robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VGRSD). The aim of this study was to evaluate whether VGRSD is feasible and safe and to determine whether VGRSD can effectively eliminate postoperative digestive system complications by protecting vagal nerve precisely.In this prospective clinical study, 10 cirrhotic patients with oesophagogastric variceal bleeding and hypersplenism who underwent VGRSD between January 2022 and March 2022 were gathered, and compared with a retrospective cohort who received a part of the vagus nerve-preserving robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VPRSD). They were all followed up for 6 months.In VGRSD group, the operation time was 173.5 ± 16.2 min, blood loss was 68.0 ± 39.1 ml, VAS pain score on the first day was 1.9 ± 0.7, and the postoperative hospital stay was 7.7 ± 0.7 days. There was no incisional complications, pneumonia, gastric fistula, pancreatic fistula, and abdominal infection. No patients suffered from diarrhoea, delayed gastric emptying, and epigastric fullness. Compared with VPRSD, operation time was significantly longer for VGRSD (p 0.05). However, VGRSD was significantly associated with less diarrhoea and shorter postoperative hospital stay (all p 0.05).VGRSD procedure is not only technically feasible and safe, it also effectively eliminate postoperative digestive system complications.We registered our research at https://www.gov/. The name of research registered is 'Vagus Nerve-guided Robotic-assisted Splenectomy and Azygoportal Disconnection'. The trial registration identifier at clinicaltrials.gov is NCT05300516.

Hepatocellular carcinoma (HCC) progresses fast and has a poor prognosis, but the growth rate in different TNM stages is not clear. The present study was to estimate the growth rate of HCC with different TNM stages at diagnosis.Baseline demographics and tumor characteristics were analyzed for 10145 patients in Surveillance, Epidemiology, and End Results (SEER) Program-registered HCC. Multiple linear regression models were used for age adjustment with patient race, sex, marital status, and HCC grade.The age at diagnosis was younger in Caucasians and males. The adjusted average age of patients with stage I HCC was 65.26 years. The adjusted age of patients with stage II, IIIA, IIIB, and IIIC was -0.17, -0.25, -0.29, and -0.55 adjusted-year younger compared with patients with stage I HCC (all P 0.001). The adjusted average age of patients with T1 was 65.26 years. The age adjustment was -0.17, -0.26, and -0.55 respectively (all P 0.001) for T2, T3 or T4 tumors without distant metastases.These findings demonstrated that the more advanced the HCC stage at diagnosis, the younger the age at diagnosis and the faster the HCC growth from tumor occurrence.

About 10%-20% of all individuals who develop hepatocellular carcinoma (HCC) do not have cirrhosis. Comparisons are rarely reported regarding the effectiveness of radiofrequency ablation (RFA) and liver resection (LR) in survival of HCC without cirrhosis and stratification by tumor size ≤ 5 cm.We used the Surveillance, Epidemiology, and End Results (SEER) database and identified 1505 patients with a solitary HCC tumor ≤ 5 cm who underwent RFA or LR during 2004-2015. Patients were classified into non-cirrhosis and cirrhosis groups and each group was categorized into three subgroups, according to tumor size (≤ 30 mm, 31-40 mm, 41-50 mm).In patients without cirrhosis, LR showed better 5-year HCC cancer-specific survival than RFA in all tumor size subgroups (≤ 30 mm: 82.5% vs. 56.4%; 31-40 mm: 71.3% vs. 46.8%; 41-50 mm: 74.7% vs. 37.5%; all P0.05). Compared with RFA, LR was an independent protective factor for HCC cancer-specific survival in multivariate Cox analysis [≤ 30 mm: hazard ratio (HR) = 0.533, 95% confidence interval (CI): 0.313-0.908; 31-40 mm: HR = 0.439, 95% CI: 0.201-0.957; 41-50 mm: HR = 0.382; 95% CI: 0.159-0.916; all P0.05]. In patients with cirrhosis, for both tumor size ≤ 30 mm and 31-40 mm groups, there were no significant survival differences between RFA and LR in multivariate analysis (all P0.05). However, in those with tumor size 41-50 mm, LR showed significantly better 5-year HCC cancer-specific survival than RFA in both univariate (54.7% vs. 23.1%; P0.001) and multivariate analyses (HR = 0.297; 95% CI: 0.136-0.648; P = 0.002).RFA is an inferior treatment option to LR for patients without cirrhosis who have a solitary HCC tumor ≤ 5 cm.

Background Our purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer‐specific survival (CSS). Methods We extracted eligible data of relevant patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Further, we divided all patients into two groups (training and validation cohorts) at random (7:3). Nomogram was established using effective risk factors based on univariate and multivariate analysis. The effective performance of nomogram was evaluated using concordance index (C‐index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC). Results We selected 3620 patients with early HCC including the training cohort (70%, 2536) and the validation cohort (30%, 1084). The nomogram‐related C‐indexes were 0.755 (95% CI: 0.739–0.771) and 0.737 (95% CI: 0.712–0.762), in the training and validation cohorts, respectively. The calibration plots showed good consistency of 3‐and 5‐year CSS between the actual observation and the nomogram prediction. The 3‐, 5‐year DCA curves also indicated that the nomogram has excellent clinical utility. The 3‐, 5‐year area under curve (AUC) of ROC in the training cohort were 0.783, 0.779, respectively, and 0.767, 0.766 in the validation cohort, respectively. With the establishment of nomogram, a risk stratification system was also established that could divide all patients into three risk groups, and the CSS in different groups (i.e., low risk, intermediate risk, and high risk) had a good regional division. Conclusions We developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management., Our purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer‐specific survival (CSS). We developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management.

Background The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC. Materials and methods Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitative realtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods. Results RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and migration in hepatoma cells. Conclusion RNF128 promotes HCC progression by activating EGFR/MEK/ERK signaling pathway, which might function as a novel prognostic molecular signature with the potential to be a candidate therapeutic target for HCC patients.

A typical feature of hepatocellular carcinoma (HCC) is growth with metastasis to distant organs, which is associated with poor survival. Whether tumor size can predict distant metastases in HCC remains unclear.We identified 29,170 HCC patients with or without distant metastases between 2010 and 2016 in the Surveillance, Epidemiology and End Results database. According to an optimal cutoff value of tumor size (58 mm) for predicting distant metastases using Youden's index, patients were categorized into groups of tumor size ≤30 cm, 30-58 mm, and ≥58 mm.Tumor size had a significantly positive correlation with distant metastases (r = 0.245, P 0.001). Among patients with distant metastasis, the most common metastasis site was lung (39.3%), followed by bone (30.0%), and brain (2.0%). Incidence of distant metastases in patients with tumor ≥58 mm was 5.7 times (22.8%/4.0%) that of patients with tumors ≤30 mm and 2.9 times (22.8%/7.9%) that of patients with tumors 30-58 mm. Multivariate analyses showed that compared with ≤30 mm, tumor size ≥58 mm was an independent risk predictor of overall distant metastases (OR, 5.200; 95% CI, 4.635-5.834; P0.001), lung (OR, 6.036; 95% CI, 5.006-7.278; P0.001); bone (OR, 3.365; 95% CI, 2.781-4.071; P0.001); and brain metastasis (OR, 1.905; 95% CI, 1.023-3.547; P0.05).Tumor size ≥58 mm is significantly associated with HCC distant metastases. In clinical practice, patients with tumors ≥58 mm may benefit from timely identification of distant metastases.

Digestive system complications are among the most important causes of postoperative poor quality of life after open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD). We firstly developed a modified vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (MVLSD). In this study, we aimed to evaluate whether MVLSD is feasible and safe and to determine whether MVLSD can effectively eliminate postoperative digestive system complications, in comparison with CLSD. In this randomized controlled single-center study, 60 patients with cirrhosis were randomly assigned to undergo either CLSD (n = 30) or MVLSD (n = 30) between April and December 2018. The primary outcome was delayed gastric emptying (DGE). Endoscopic physicians were blinded to group assignments. One patient who received MVLSD withdrew from the study. There were no significant differences in intraoperative blood loss, incidence of blood transfusion, time to off-bed activity, time to first flatus, and postoperative hospital stay between the two groups. Compared with CLSD, operation time and incidences of DGE, diarrhea, epigastric fullness, and overall postoperative complications were all significantly reduced in the MVLSD group (all P

A regioselective Wacker-Tsuji oxidation of internal olefins in tBuOH has been developed using oxygen as the terminal oxidant and tert-butyl nitrite as the simple organic redox cocatalyst without the involvement of hazardous cocatalysts or harsh reaction conditions. A series of internal olefins bearing various functional groups can be oxidized to the corresponding substituted ketones in generally good yields with high regioselectivities.

On 28 July 2021, the first indigenous case of novel coronavirus pneumonia (COVID-19) emerged in Yangzhou, marking the beginning of a public health crisis caused by the new coronavirus pneumonia. It is a significant challenge for hospitals to carry out prevention and control measures to ensure the safety of medical professionals and patients when facing the changes in an epidemic situation. Subei People's Hospital, as one of the first group of "Grade III-class A" hospitals in Jiangsu Province and the Yangzhou Regional Medical Centre, responded quickly and scientifically to prevent and control the disease. A closed-loop management system was implemented at the hospital entrance (consisting of the outpatient clinic, emergency clinic, fever clinic, and buffer ward) and an epidemic prevention and control group was established with the assistance of multiple departments. This group optimized the pre-screening and triage system, standardized the fever clinic consultation process, and improved the construction of an information-based prevention and control network so that patients were detected, diagnosed, isolated, and treated early. The emergency management capability was improved to achieve zero missed consultations of patients attending for COVID-19 and to effectively maintain medical order during this critical period. This current report systematically summarizes the operational practices and the effectiveness achieved by implementation of the entrance closed-loop management in the hospital and analyzed the key operational issues for future reference by medical institutions and management departments.

Robotic surgery has been widely accepted in many kinds of surgical procedures. Little is known about clinical effects of robotic-assisted splenectomy and azygoportal disconnection (RSD) for gastroesophageal variceal bleeding and secondary hypersplenism owing to cirrhotic portal hypertension. The aim of this study was to evaluate whether RSD is feasible and safe for patients with cirrhotic portal hypertension and whether RSD is superior to laparoscopic splenectomy and azygoportal disconnection (LSD). We retrospectively investigated the clinical effects of 50 patients with cirrhosis who underwent vagus nerve-preserving RSD (n = 20) and LSD (n = 30) between September 2020 and October 2021. We compared patients' demographic, intraoperative, and perioperative variables. RSD and LSD were successful in all patients. Operative time did not differ significantly between the RSD group and LSD group (151.15 ± 21.78 min vs. 144.50 ± 24.30 min, P 0.05), but intraoperative blood loss were significantly reduced in the RSD group (61.00 ± 34.93 mL vs. 105.00 ± 68.77 mL, P 0.05). No statistically significant differences were found regarding intraoperative allogeneic transfusion rate, visual analog scale pain score on the postoperative first day, time to first oral intake, initial passage of flatus, initial off-bed activity, postoperative hospital stay, and overall perioperative complication rate (all P 0.05). In conclusion, RSD is not only a technically feasible and safe procedure but it was associated with less blood loss than LSD for cirrhotic portal hypertension with gastroesophageal variceal bleeding and secondary hypersplenism. Registered at researchregistery.com: trial registration number is researchregistry7244, date of registration October 10, 2021, registered retrospectively.

BACKGROUND: The prognosis for patient survival using the tumor–node–metastasis (TNM) staging system may be imperfect, as it based only on biological factors and does not include the socioeconomic factors (SEFs). We integrated the SEFs into the TNM system (TNM-SEF), and evaluated whether the novel TNM-SEF staging system showed better prediction capacity and improved clinical guidance in hepatocellular carcinoma (HCC). METHODS: We selected data of 12 514 cases with HCC between 2010 and 2015 from the SEER database. The Kaplan–Meier survival curves and Cox proportional hazards regression were used to analyze cancer-specific survival (CSS) among the TNM-SEF stages. RESULTS: Multivariate Cox analyses showed that insurance status, marital status, year of diagnosis, and income were prominent prognostic SEFs (all P < .05). When compared with the SEF0 stage, the SEF1 stage was significantly associated with a 36.1% increased risk of cancer-specific mortality in HCC overall, a 22.2% increased risk of metastatic HCC, and a 41.8% increased risk of non-metastatic HCC (all P < .001). The concordance index of the TNM-SEF stage (0.768) was better than that of the TNM stage (0.764). Furthermore, patients with SEF0 stage showed higher 5-year CSS than those with SEF1 stage (I: 48.7% vs. 28.1%; II: 41.0% vs. 25.1%; IIIA: 12.8% vs. 5.0%; IIIB: 7.8% vs. 6.0%; IIIC: 6.4% vs. 6.7%; IVA: 8.4% vs. 2.5%; IVB: 2.1% vs. 0.8%; all P < .05). CONCLUSION: We have proved that the SEF stage is an independent predictor for HCC. The combined SEF stage with TNM staging warrants more clinical attention, for improved prognostic prediction and clinical guidance.

Circular RNAs are known to regulate the biological processes of hepatocellular carcinoma (HCC), and humans with Down syndrome are at low risk of developing solid tumors due to the amplification of several tumor suppressor genes on human chromosome 21 (HSA21). Here, we aimed to investigate the potential role of circRNAs originating from HSA21 in the progression of HCC. CircRNA-sequencing was performed to analyze differentially expressed circRNAs in 4 HCC and peritumor tissues, and circRNAs originating from HSA21 were further analyzed. Circ_0061984 (circPTTG1IP) was chosen for further study because it showed the lowest expression in HCC tissues, and qRT-PCR was used to confirm the expression of circPTTG1IP in HCC patient tissues. The biological function of circPTTG1IP was detected in HCC cells both in vivo and in vitro. Moreover, luciferase reporter assays, circRNA immunoprecipitation, and fluorescence in situ hybridization (FISH) were used to investigate the potential mechanism of circPTTG1IP. Finally, the possible mechanisms of filgotinib in circPTTG1IP-driven HCC were assessed. CircPTTG1IP expression was decreased in HCC compared to peritumoral tissues. Moreover, low circPTTG1IP expression was revealed to be associated with a poor prognosis of HCC patients. Elevation of circPTTG1IP was revealed to inhibit HCC development both in vitro and in vivo. Mechanistically, circPTTG1IP was shown to function as a competing endogenous RNA (ceRNA) of RNF125 by binding miR-16-5p to increase the level of the E3 ubiquitin ligase RNF125, which further ubiquitinated and degraded JAK1 protein. Finally, we demonstrated that administration of filgotinib, a JAK1 inhibitor, restricted HCC progression induced by low circPTTG1IP expression. Thus, we revealed that circPTTG1IP is a novel tumor suppresser circRNA in HCC and that a low circPTTG1IP level promotes HCC development via the miR-16-5p/RNF125/JAK1 axis. Patients with low circPTTG1IP may benefit from filgotinib treatment.

The dynamic behaviors of two beams connected by a joint with clearance are investigated. A new equivalent joint model using the transverse and torsion spring systems is developed to describe the dynamics of two jointed beams with clearance. Based on the finite element method (FEM), the equations of motion of the two jointed beams with clearance are established using Hamilton's principle. A modified numerical solution method is presented based on the Newmark integration method to solve the equations with the nonlinearity due to clearance. The contributions of the clearance size and stiffness on the amplitude-frequency response are discussed. The effects of the clearance on the vibration transfer between the two connected beams and the impact force of the joint are investigated.

BACKGROUND/AIMS In patients who survive the first esophageal variceal bleeding (EVB) resulting from portal hypertension, the probability of fatal esophageal variceal re-bleeding (EVR) is high. We have developed a sandwich-style sequential therapy combining laparoscopic splenectomy and azygoportal disconnection (LSD) with preoperative and postoperative endoscopic intervention (LSDE). The aim of the present study was to investigate whether LSDE is safe and effective and to evaluate whether the postoperative EVR rate for LSDE was lower than that for LSD without periodical postoperative endoscopic intervention (NLSDE). MATERIALS AND METHODS We retrospectively investigated the outcomes of 226 patients with cirrhosis with EVB and secondary hypersplenism who all received preoperative endoscopic variceal ligation (EVL) to manage emergency EVB then underwent NLSDE (n=106) or LSDE (n=120) between February 2012 and April 2016. The perioperative and follow-up variables of the two groups were evaluated. RESULTS Between the two groups, there were no differences in number of blood transfusions, intraoperative blood loss, postoperative complications, and hospital stay. LSDE showed shorter operation time (p=0.001) and lower EVR rates during the periods ranging from 1 to 12 months, 4 to 6 months, 4 to 12 months, and 7 to 12 months (all p

Background Coronavirus disease 2019 (COVID-19) is closely associated with physical and mental health problems; however, little is known about the severity of stigma caused by COVID-19 among its survivors. Thus, the aim of this study was to compare differences in stigma experiences of COVID-19 survivors versus healthy controls after the COVID-19 outbreak peak in China. Methods This cross-sectional study comprised 154 COVID-19 survivors and 194 healthy controls recruited through consecutive and convenience sampling methods, respectively. COVID-19 related stigma was measured by the Social Impact Scale (SIS). Stigma differences between the two groups were compared with analysis of covariance (ANCOVA) and a generalized linear model (GLM) was used to identify independent correlates of COVID-19-related stigma in this study. Results Compared with healthy controls, COVID-19 survivors reported more overall stigma (F(1,347) = 60.82, p F(1,347) = 56.54, p F(1,347) = 19.96, p F(1,347) = 71.40, p F(1,347) = 34.73, p p values Conclusion COVID-19-related stigma is commonly experienced among COVID-19 survivors even though the outbreak has been well-contained in China. Routine assessment of stigma experiences should be conducted on COVID-19 survivors and appropriate psychological assistance, public education, and anti-stigma campaigns and policies should be enforced to reduce stigma within this vulnerable subpopulation.

The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus.From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP.Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222-25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466-9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively.Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively.We registered our research at https://www.gov/ . The name of research registered is "Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection." The trial registration identifier at clinicaltrials.gov is NCT02247414.

Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Some E3 ubiquitin-protein ligases play essential roles in HCC development. We aimed to explore a hub E3 ubiquitin-protein ligase gene and verify its association with prognosis and immune cell infiltration in HCC. We identified cell division cycle 20 (CDC20) as a hub E3 ubiquitin-protein ligase in HCC by determining the intersecting genes in a protein-protein interaction (PPI) network of differentially expressed genes (DEGs) in HCC data from the International Cancer Genome Consortium (ICGC) and 919 E3 ubiquitin-protein ligase genes from the Integrated annotations for Ubiquitin and Ubiquitin-like Conjugation Database (IUUCD). DEGs and their correlations with clinicopathological features were explored in The Cancer Genome Atlas (TCGA), ICGC, and Gene Expression Omnibus (GEO) databases via the Wilcoxon signed-rank test. The prognostic value of CDC20 was illustrated by Kaplan-Meier (K-M) curves and Cox regression analyses. Subsequently, the correlation between CDC20 and immune infiltration was demonstrated via the Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). CDC20 expression was significantly higher in HCC than in normal tissues (all P P

An iron-catalyzed α,β-dehydrogenation of carbonyl compounds was developed. A broad spectrum of carbonyls or analogues, such as aldehyde, ketone, lactone, lactam, amine, and alcohol, could be converted to their α,β-unsaturated counterparts in a simple one-step reaction with high yields.

Background Alpha-fetoprotein (AFP) has been widely used as a tumor marker in the treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, a large number of HCC patients are diagnosed without cirrhosis, and the prognostic capability of AFP was unclear in HCC patients without cirrhosis. Our purpose was to investigate the prognostic efficiency of AFP in patients with non-cirrhosis, single, and small HCC who were treated with surgical resection. Methods Among the 111 374 liver cancer patients included in the Surveillance, Epidemiology, and End Results database, we selected 224 patients without cirrhosis with a single HCC ≤3 cm in diameter who were identified at diagnosis and treated with surgical resection. The AFP test results were recorded as AFP-positive and AFP-negative levels. Results Kaplan-Meier method showed that there was no significant survival difference between the AFP-positive and AFP-negative groups (P = .566). The same results were found in the subgroups of patients with tumor size ≤2 cm and 2-3 cm (P = .710 and .687, respectively). Receiver operating characteristic (ROC) curve analysis showed that AFP had inadequate accuracy to discriminate survivors and deceased patients in subgroups of patients with tumor size ≤3 cm, 2-3 cm, or ≤2 cm (area under the ROC curve = 0.449, 0.458, 0.443; 95% confidence interval = 0.366-0.533, 0.346-0.571, 0.317-0.569, respectively). Conclusion AFP levels have no predictive value in well-compensated non-cirrhosis patients with single, small HCC (≤3 cm) treated with surgical resection for curative intent.

Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

Macrophage differentiation is associated with tumorigenesis, including the tumorigenesis of hepatocellular carcinoma (HCC). Herein, we explored the value of macrophage differentiation-associated genes (MDGs) in the prognosis of HCC using data from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. We performed multivariate Cox regression analyses to identify the hub genes affecting HCC patient prognoses. The correlations between hub genes and macrophage differentiation and immune checkpoint inhibitors (PD-1, PD-L1, and CTLA4) were investigated. Finally, the potential mechanism was examined with gene set enrichment analysis (GSEA). In total, seventeen differentially expressed MDGs were obtained after intersecting data from the two databases. Multivariate analysis indicated that CDC42 expression was an independent prognostic indicator in both databases. Furthermore, CDC42 showed a strong correlation with the tumor infiltration levels of immune cells in HCC tissue. Correlation analysis revealed that CDC42 expression was positively associated with M2 macrophage markers and immune checkpoint inhibitors, which indicated that CDC42 expression might be related to M2 macrophage differentiation and HCC cell immune tolerance. Finally, GSEA showed that CDC42 expression was most significantly related to the Wnt signaling pathway. In conclusion, this study showed that CDC42 expression might be an important MDG in HCC and may prove to be a new gene for studying macrophage differentiation in HCC. Abbreviations: HCC: hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; ICGC: International Cancer Genome Consortium; GSEA: gene set enrichment analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; ROC: receiver operating characteristic; K-M: Kaplan-Meier; AUC: the area under the ROC curve; TNM: Tumor size/lymph nodes/distance metastasis, Graphical abstract

Background: Surgery for pancreatic cancer with liver metastases (PCL) is not recommended in the international guidelines, and investigation of its clinical significance in patients with PCL is very limited. This study explored whether surgery, especially synchronous resection of the primary tumor and liver metastases (SPL), could improve survival in PCL. Methods: Data of 14,248 patients with PCL from Surveillance, Epidemiology, and End Results database was analyzed. Patients were divided into following groups: SPL, synchronous primary site, and other resection (SPO), single resection of the primary site (SPS), and no resection (NR). Results: In this study, only 93 (0.7%) underwent SPL, 88 (0.6%) for SPO, and 232 (1.6%) for SPS. Multivariate Cox analysis showed surgical procedures of both the primary site and other sites were independent protective prognostic factors for pancreatic cancer cause-specific survival (PCSS) (all P < 0.001). Patients in the SPL group showed the most survival benefit, with a significant and gradually increased difference as compared with the SPO, SPS, and NR groups (median survival: 54, 34, 15, and 3 months, respectively, all P < 0.001). Compared with the NR group, mortalities were significant and gradually declining in the SPS, SPO, and SPL groups, with hazard ratio 0.329 (95% confidence interval [CI], 0.281 to 0.386), 0.220 (95% CI, 0.164 to 0.294), and 0.162 (95% CI, 0.118 to 0.222), respectively (all P < 0.001). Conclusions: Surgical procedures for both primary site and other sites improved survival. SPL, particularly, showed a considerable survival benefit in well-selected patients with PCL.

Esophagogastric variceal re-bleeding (EGVR) is a common and potentially lethal complication after open or laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension. Currently, noninvasive biomarkers for predicting EGVR are lacking. This prospective study focused on developing a noninvasive and convenient clinical model for predicting postoperative EGVR. Between September 2014 and March 2017, we enrolled 164 patients with cirrhosis who successfully underwent LSD. Based on the absence or presence of EGVR, patients were divided into EGVR and non-EGVR groups. We used correlation analysis to determine significant candidate variables among the liver fibrotic markers procollagen type III (PC-III), hyaluronidase (HA), laminin (LN), and type IV collagen (C-IV). Postoperative EGVR occurred in 22 (13.41%) patients. Correlation analyses showed that LN (r = 0.375; p

The clinical guidance of the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system is established only in biological factors and does not include nonbiological factors (NBFs). We assessed the clinical value of incorporating NBFs into the TNM staging system in point of the clinical management and prognostic prediction accuracy of rectal cancer.We used the Surveillance, Epidemiology and End Results (SEER) database and identified 12,515 patients with rectal cancer who were diagnosed between 1 January 2011 and 31 December 2015. Multivariate Cox proportional hazards regression analysis and Kaplan-Meier curves were used to determine the probabilities of cancer-specific survival (CSS) according to different TNM-NBF stages.Multivariate Cox regression analysis showed that county percentage with a bachelor's degree, insurance status, unemployment status, and marital status were all significant prognostic NBFs (p 0.05). The concordance index of TNM-NBF stages was 0.815 (95% confidence interval (CI) 0.8072-0.8228). Multivariate Cox analyses showed that, compared with NBF0-stage, NBF1-stage was contacted with a 54.5% increased risk of cancer-specific mortality in rectal cancer, which increased to 68.3% in non-metastatic rectal cancer (all p 0.001). NBF0-stage showed a CSS benefit as compared with NBF1-stage (p 0.001).We found that NBF-stage was an independent prognostic factor for survival in rectal cancer. The influence of NBFs on survival in rectal cancer warrants greater clinical attention. Furthermore, the consolidation of NBF-stage into the TNM staging system is crucial to better prognostic prediction accuracy and individualized risk-adaptive therapies.

Background: Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC). However, 10%-20% of patients with HCC do not have cirrhosis. The aim of this study was to explore the potential differences in tumour characteristics of HCC between patients with and without cirrhosis. Methods: In this study, we identified total 10,849 patients with HCC diagnosed between 2010 and 2016, from the SEER database. The degree of fibrosis was categorized as "no cirrhosis" (Ishak score 0-4) or "cirrhosis" (Ishak score 5-6). Among all patients with HCC, patients with no cirrhosis and with cirrhosis accounted for 1800 (16.6%) and 9049 (83.4%), respectively. Results: Significant negative correlations were observed between no cirrhosis/cirrhosis and pathological grade (r =-0.074, P