TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.

Transarterial Chemoembolization Plus Tyrosinkinase Inhibitors and PD-1 Inhibitors for Spontaneously Ruptured Hepatocellular Carcinoma.

PURPOSE: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with tyrosinkinase inhibitors (TKI) and PD-1 inhibitors, versus TACE monotherapy for the treatment of ruptured hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study included 104 patients with ruptured HCC receiving either combination therapy or TACE monotherapy at two centers between June 2015 and June 2022. Propensity score matching (PSM) analysis was used at a 1:2 ratio to reduce bias between the two groups. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were the occurrence of adverse events (AEs, Common Terminology Criteria for AEs, version 5.0.) and the peritoneal metastasis rate. RESULTS: A total of 69 patients were enrolled after PSM, including 23 patients in the combination group and 46 patients in the monotherapy group. The combination group exhibited a significantly longer median OS (553 days, 95% confidence interval [CI] 222.6-883.9) compared to the monotherapy group (105 days, 95% CI 81.2-128.7; P < 0.001). Similarly, the combination group showed a better median PFS (356 days, 95% CI 299.5-412.4) compared to the monotherapy group (97 days, 95% CI 75.9-118.1; P < 0.001). Moreover, there was no significant difference in the peritoneal metastasis rate (combination group: 8.6% vs. monotherapy group: 26.1%, P = 0.119). Grade 3 AEs occurred at a rate of 21.7% and 13% in combination and monotherapy groups, respectively. No Grade 4/5 AEs were observed in either group. CONCLUSIONS: Our study demonstrated that the combination of TACE with TKI and PD-1 inhibitors significantly enhances OS and PFS compared to TACE monotherapy in ruptured HCC patients. Furthermore, this combined approach exhibited an acceptable safety profile.

Epidemiological characteristics and temporal-spatial clustering analysis on human brucellosis in Jiangsu Province, 2006-2021.

The marked increase in the incidence rate of brucellosis is a serious public health concern in Jiangsu Province. However, its temporal and spatial distribution has not been studied in depth. The main purpose of this study is to depict the demographic, temporal and spatial distribution patterns and clustering characteristics of brucellosis cases in Jiangsu Province, China, from 2006 to 2021 to develop and implement effective scientific prevention and control strategies. Data for human brucellosis cases in Jiangsu Province from 2006 to 2021 were obtained from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS). Spatial autocorrelation analysis and temporal-spatial scan statistics were used to identify potential changes in the spatial and temporal distributions of human brucellosis in Jiangsu Province. During the years 2006-2021, 1347 brucellosis cases were reported in Jiangsu Province, with an average annual incidence rate of 0.1036 per 100,000 individuals. Middle-aged and elderly individuals (aged 40-69 years) were the main infected populations, accounting for 69.72% (939/1347) of all reported cases. The incidence of brucellosis in Jiangsu showed a long-term increasing trend and displayed pronounced seasonal variations, with the peak occurring between April and June annually. The incidence gradually expanded from the northern and southern areas to the central areas between 2006 and 2021. Global spatial autocorrelation analysis demonstrated a positive correlation in the incidence of brucellosis between 2008 and 2012-2021. Temporal-spatial clustering analysis showed that the primary cluster was detected in the northern, highly endemic regions of Jiangsu, and the three secondary clusters were in areas where there had been outbreaks of brucellosis. Human brucellosis remains a serious public health issue in Jiangsu Province. Northern and southern Jiangsu regions, with high rates of brucellosis, may require special plans and measures to monitor and control the disease. Additionally, the capacity to respond to outbreaks in high-incidence areas should be improved to prevent further brucellosis outbreaks.

On-board measurements of OC/EC ratio, mixing state, and light absorption of ship-emitted particles.

Carbonaceous aerosols play important roles in environmental impacts and climate effects. The characteristics of ship-emitted carbonaceous aerosols keep unclear under the latest global low sulfur fuel oil policy. This study selected four ocean-going vessels burning low sulfur fuel oils for on-board exhaust testing. The emission factors of ship carbonaceous aerosols were obtained under different engine types (main and auxiliary engines), fuel types, and engine loads. Our results showed that fuel and engine types were both important factors affecting carbonaceous aerosol emissions for ship engines. The emission factors of OC and EC from main engines were 1.18 ± 0.62 and 0.06 ± 0.04 g/kg burning heavy fuel oil (HFO), while 0.52 ± 0.35 and 0.04 ± 0.03 g/kg burning marine gas oil (MGO), respectively. The OC/EC ratios of ship-emitted particles were within a large range of 2 to 23. The OC/EC ratios from the main engines were significantly higher than those from the auxiliary engines by a factor of 6.3. The result of chemical mixing states of ship-emitted particles observed by a single particle mass spectrometer (SPAMS) showed that OC and EC were internally mixed and existed as the ECOC-bonded forms in single particles. The measured light absorption of ship-emitted particles with higher OC/EC ratios showed an evident short-wave absorption enhancement based on the aethalometer AE-33. Our results implied that ship-emitted carbonaceous aerosols (especially with high OC/EC ratios) could not be uniformly treated regarding the optical properties to more precisely estimate their potential environmental impacts and climate effects in model systems in the future.

Acute Pancreatitis After Percutaneous Metallic Stent Insertion for Malignant Biliary Obstruction: A Retrospective 2-Center Study.

BACKGROUND/AIMS: The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction. MATERIALS AND METHODS: From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis. RESULTS: On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened. CONCLUSION: Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.

Prognostic value of des-γ-carboxyprothrombin in patients with AFP-negative HCC treated with TACE.

In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease.

Survival prediction for patients with malignant biliary obstruction caused by pancreatic cancer undergoing biliary drainage: the COMBO-PaS model.

BACKGROUND: Patients with pancreatic cancer-caused biliary obstruction (PC-BO) have poor prognosis, but we lack of tools to predict survival for clinical decision-making. This study aims to establish a model for survival prediction among patients with PC-BO. METHODS: A total of 172 patients with PC-BO treated with percutaneous biliary drainage were randomly divided into a training group (n = 120) and a validation group (n = 52). The independent risk factors for overall survival were selected to develop a Cox model. The predictive performance of M stage, hepatic metastases, cancer antigen 199, and the Cox model was determined. Naples prognostic score (NPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for 1-month mortality risk were compared with the Cox model. RESULTS: The Cox model was developed based on total cholesterol, direct bilirubin, hepatic metastases, cancer antigen 199, stenosis type, and preprocedural infection (all P < 0.05), which named "COMBO-PaS." The COMBO-PaS model had the highest area under the curves (AUC) (0.801-0.933) comparing with other predictors (0.506-0.740) for 1-, 3-, and 6-month survival prediction. For 1-month mortality risk prediction, the COMBO-PaS model had the highest AUC of 0.829 comparing with NPS, PNI, and CONUT. CONCLUSION: The COMBO-PaS model was useful for survival prediction among patients with PC-BO.

Regional culture: The role of the invisible hand in shaping local family firms' top management team.

Research on family businesses has focused on the differences between family and non-family firms regarding the top management team (TMT), while this study further explores the difference within family firms from different regional culture based on the perspective of socio-emotional wealth (SEW) and evolutionary psychology. Using a sample comprised of all 625 family firms listed on the Small & Medium Enterprise Board and Growth Enterprise Board in Shenzhen Stock Exchange, this study finds that in regions of strong clan culture, family members are more willing to be involved in a family business and accept lower economic rewards. Particularly, when financial risk is high, these relationships mentioned above become more significant. Based on the results, this study proves that regional culture can affect the characteristics of top management teams in family firms, explains the heterogeneity of family firms' decision-making from a culture-based perspective and extends existing research on family business from the level of "family firm vs. non-family firm" to that of "family firms affected by different regional cultures".

Prognostic nomogram for acute pancreatitis after percutaneous biliary stent insertion in patients with malignant obstruction.

OBJECTIVE: This study aimed to develop and validate a nomogram to predict the risk of pancreatitis after percutaneous transhepatic biliary stent insertion (PTBS) in patients with malignant biliary obstruction (MBO). MATERIALS AND METHODS: We enrolled 314 patients who underwent PTBS for MBO from March 2016 to July 2021 in this retrospective study. We used univariate analysis to identify potential risk factors, while a multivariate logistic regression model was employed to establish a nomogram for predicting the risk of pancreatitis. The discrimination and calibration of the nomogram were evaluated by estimating the area under the receiver operator characteristic curve (AUC) and by bootstrap resampling and visual inspection of the calibration curve. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: After the procedure, 41 (13.1%) patients developed pancreatitis. Based on multivariate logistic regression analysis, young age (OR = 2.57, 95% CI 1.16 to 5.69), stent insertion across the papilla (OR = 6.47, 95% CI 2.66 to 15.70), and visualization of the pancreatic duct (OR = 15.40, 95% CI 6.07 to 39.03) were associated with an elevated risk of pancreatitis. Importantly, the performance of the nomogram was satisfactory, with an identical AUC (0.807, 95% CI 0.730 to 0.883) and high-level agreement between predicted and observed probabilities as suggested in calibration curves. The DCA curve subsequently confirmed the clinical utility. CONCLUSION: A predictive nomogram for pancreatitis after PTBS in patients with MBO was successfully established in the present study.

Novel prognostic signature based on HRAS, MAPK3 and TFRC identified to be associated with ferroptosis and the immune microenvironment in hepatocellular carcinoma.

OBJECTIVES: Ferroptosis, a programmed cell death, has been recognized recently. Several studies have shown the connection between ferroptosis and biological processes in cancer. However, the potential role and mechanism of ferroptosis-related genes in hepatocellular carcinoma (HCC) remain unclear, and understanding the crosstalk between the tumor immune microenvironment and ferroptosis is still a great challenge. METHOD: We retrospectively analyzed the transcriptomic and clinical data of HCC from TCGA database. 74 ferroptosis-related genes (FRGs), including 14 immune-ferroptosis-related genes (IFRGs), were identified with differential expression in tumor and normal tissues. Then, we screened and constructed a prognostic signature using survival analysis and the least absolute shrinkage and selection operator. Furthermore, we validated the performance of the signature for assessing survival prognosis and clinicopathological staging. In addition, we investigated the link between the prognostic features and tumor-infiltrating immune cells using CIBERSORT. RESULT: The results identified HRAS, MAPK3 and TFRC as prognostic IFRGs. The risk score was elevated when IFRGs were upregulated and patient outcomes worsened. In addition, the results show significant differences in tumor-infiltrating immune cells, especially immunosuppressive cells, including tumor-infiltrating macrophages cells and regulatory cells, implying that the expression of these three IFRGs may be an intrinsic barrier to strong ferritin-induced immune responses. Enrichment analysis revealed crosstalk between ferroptosis and tumor immunity. The effect of the risk score was validated in the ICGC cohort and the Human Protein Atlas database confirmed the high expression of IFRGs in tumor tissue. CONCLUSIONS: In our study, these IFRGs may provide some new ideas for the study of ferroptosis and the tumor immunity. These findings may also provide new strategies for treatment of HCC.

Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study.

Purpose: To compare the effectiveness and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab with those of TACE as well as apatinib among patients with unresectable hepatocellular carcinoma (HCC). Materials and methods: The data of patients with unresectable HCC (uHCC) who received TACE-apatinib-camrelizumab combination (TACE + AC group) and TACE-apatinib combination (TACE + A group) were collected from two centers between January 2018 and January 2022. Propensity score matching (PSM) was conducted to diminish the bias between the two groups. The primary outcome measures of the study were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: A total of 102 patients were enrolled in this study after PSM, with 34 patients in the TACE + AC group and 68 patients in the TACE + A group. Compared to the TACE + A group, TACE + AC had a significantly longer median OS (25.5 months, interquartile range [IQR], 23.5-33.0) than 18.5 months (IQR, 13.0-25.0; P = 0.001). Similarly, the PFS of the TACE + AC group was significantly improved (14.0 months, IQR, 9.0-NA) compared to that of the TACE + A group (5.0 months, IQR, 2.5-9.0; P = 0.001). The ORR rates (55.9% vs. 51.5%), and DCR rates (79.4% vs. 72.1%) were comparable between groups (P > 0.05). All treatment-related adverse events were tolerable and manageable, and no serious adverse events were observed. Conclusion: TACE combined with apatinib plus camrelizumab demonstrated superior efficacy to TACE plus apatinib for patients with unresectable HCC. The two combination therapies showed similar safety profiles.

Efficacy and safety of camrelizumab plus transarterial chemoembolization in intermediate to advanced hepatocellular carcinoma patients: A prospective, multi-center, real-world study.

Objective: Camrelizumab is a newly developed program-death receptor one inhibitor; the real-world evidence about its application in hepatocellular carcinoma (HCC) treatment is lacking. Therefore, this prospective, multi-center, real-world study evaluated the efficacy and safety of camrelizumab plus transarterial chemoembolization (TACE) in treating intermediate-to-advanced HCC patients. Methods: This study consecutively enrolled 101 intermediate to advanced HCC patients. All patients received camrelizumab-based treatment within 30 days of the perioperative period of the TACE operation. The primary outcome was progression-free survival (PFS), and the secondary effects were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and AEs. Results: Specifically, the median PFS was 9.7 (95% confidence interval: 7.4-12.0) months, with a 1-year PFS rate of 30.6%. Meanwhile, the median OS was not reached (NR) yet, with a 1-year OS rate of 61.9%. Besides, the CR, PR, SD, and PD rates were 12.8%, 44.9%, 29.5%, and 12.8%, respectively. The ORR and DCR were 57.7% and 87.2%, respectively. More cycles of camrelizumab were independently correlated with prolonged PFS (hazard ratio (HR): 0.415, P = 0.002), whereas longer intervals between camrelizumab administration and TACE were independently associated with unfavorable PFS (HR: 1.873, P = 0.032). The incidence of total AEs was 90.1%; most AEs were grade 1 (20.8%), grade 2 (28.7%) and grade 3 (37.6%), while only 3 (3.0%) patients had grade 4 AEs. Conclusion: The camrelizumab plus TACE regimen is effective and safe, indicating its potential to serve as a promising treatment choice for intermediate to advanced HCC patients.

Transcatheter arterial chemoembolization alone versus combined with microwave ablation for recurrent small hepatocellular carcinoma after resection: a retrospective comparative study.

PURPOSE: To compare the efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) versus TACE alone for the treatment of recurrent small hepatocellular carcinoma (sHCC) after resection. MATERIALS AND METHODS: From June 2015 to January 2020, a total of 45 patients with recurrent sHCC (size ≤ 3 cm) treated by TACE-MWA or TACE were included in this study. The radiological response at 1-, 3-, 6-month after initial treatment [modified Response Evaluation Criteria in Solid Tumors (mRECIST)], progression-free survival (PFS), overall survival (OS), and complications were evaluated. RESULTS: The TACE-MWA group showed better 1-, 3-, 6-month tumor response rates than TACE group. The corresponding 1-, 3-, and 5-year PFS rates were 76.5%, 70.6%, and 70.6% for the TACE-MWA group, and 56.1%, 15.0%, and 15.0% for the TACE group (P = 0.003). The 1-, 3-, and 5-year OS rates were 100.0%, 82.1%, and 61.5% for the TACE-MWA group, and 89.0%, 58.1%, and 50.8% for the TACE group (P = 0.389), respectively. Moreover, no major complications related to treatment were observed in either of the groups. Compared with the TACE group, the TACE-MWA group had a significantly lower number of re-TACE sessions (P = 0.003). CONCLUSIONS: Although TACE alone provides equivalent effectiveness for recurrent sHCC in terms of OS rates, TACE-MWA had better 1-, 3-, 6-month tumor response rates and may prolong tumor PFS time.

Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization.

OBJECTIVES: Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS: A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS: Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS: ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS: • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.

Metallic stent placement versus catheter drainage for malignant bilioenteric anastomotic stricture.

PURPOSE: The purpose of the study was to compare self-expandable metallic stent placement with catheter drainage for malignant bilioenteric anastomotic stricture in terms of efficacy and safety. MATERIALS AND METHODS: This study included 54 patients with malignant bilioenteric anastomotic stricture treated from March 2016 to February 2021. Twenty-seven patients underwent insertion of self-expandable metallic stent (Stent group); the remaining twenty-seven patients underwent internal-external catheter drainage (Catheter group). Technical success was defined as successful placement of stent or drainage catheter in the appropriate position; clinical success was defined as a 20% reduction in serum bilirubin within 1 week after the procedure, compared with baseline. Complications, duration to stent/catheter malfunction, and overall survival were evaluated. RESULTS: Technical success was achieved in all patients in both groups. In the Stent group, 21 patients received one stent and the other 6 patients required two stents. Clinical success rates were similar between the groups [Stent group, 92.6% (25/27); Catheter group, 88.9% (24/27)]. There were no major complications. The median duration to stent/catheter malfunction was significantly longer in the Stent group (130 days) than in the Catheter group (82 days; P = 0.010). The median overall survival was also significantly longer in the Stent group (187 days) than in the Catheter group (118 days; P = 0.038). CONCLUSION: Self-expandable metallic stent placement might be better than internal-external catheter drainage for malignant bilioenteric anastomotic stricture in terms of the duration before stent/catheter malfunction and patient survival.

Hepatic arterial infusion chemotherapy following simultaneous metallic stent placement and iodine-125 seed strands for advanced cholangiocarcinoma causing malignant obstructive jaundice: a propensity score matching study.

OBJECTIVE: This study aims to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) following the simultaneous placement of self-expandable metallic stent (SEMS) and iodine-125 (125I) seed strands for the management of advanced cholangiocarcinoma (CCA) patients presenting with malignant obstructive jaundice (MOJ). METHODS: Data from 74 patients with MOJ caused by advanced CCA treated with stent placement with 125I seed strands with or without HAIC between November 2015 and October 2020 were analysed retrospectively. Eighteen patients received 5 sessions of HAIC after SEMS placement with 125I seed strands (HAIC group), and 56 patients only underwent SEMS placement with 125I seed strands and served as controls (control group). HAIC consisted of infusions of gemcitabine (600-1000 mg/m2 given over 30 min) followed by oxaliplatin (60-100 mg/m2 given over 2 h), with an interval of 4 weeks. Propensity score matching (PSM) analysis was used to adjust for differences in the baseline characteristics of the groups (including age, total bilirubin, and serum alanine aminotransferase level). Overall survival (OS), stent patency, and adverse events were compared between the two groups. RESULTS: OS and stent patency were significantly better in patients in the HAIC group than in those in the control group (median survival time: before PSM, 362 vs. 185 days, p = 0.005; after PSM, 357 vs. 183 days, p = 0.012; median duration of stent patency: before PSM, 294 vs. 156 days, p = 0.001; after PSM, 287 vs. 183 days, p = 0.039). All adverse reactions were controllable by temporary symptomatic treatment. Serious complications and treatment-related deaths were not observed. CONCLUSION: Our preliminary study showed that HAIC following SEMS placement with 125I seed strands is effective and safe for the management of advanced CCA patients presenting with MOJ and could improve stent patency and patient survival.

Risk factor for vital signs elevation during percutaneous microwave ablation of liver tumor under deep sedation.

PURPOSE: To evaluate the frequency and the degree of vital signs elevation, as well as to elucidate the risk factors for elevation of cardiopulmonary parameters. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 101 patients who received microwave ablation (MWA) under deep sedation with propofol. Univariate analysis followed by multivariate linear regression analysis was performed to determine the risk factors associated with the elevation of cardiopulmonary parameters. RESULTS: The heart rate (HR), mean blood pressure (BP) and respiratory rate (RR) were elevated in 53.5%, 45.5% and 30.7%. Hyperhemodynamic state (mean BP or HR increased > 30% of the baseline) and high RR (RR > 20 times/min) were detected in 23.8% and 13.9%. Age ≤ 50 years was signifiant for mean BP and HR elevation (p = 0.032; p = 0.027), ablation zone abutting the parietal peritoneum (p = 0.001; p = 0.001; p < 0.001) and the diaphragm (p = 0.001) were risk factors for BP and RR elevation. CONCLUSIONS: Elevations in HR and BP are common. Risk factors for vital signs elevation include ablation zone abutting the parietal peritoneum and the diaphragm, as well as young age. These findings help devise strategies for anesthetic management.

MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated death worldwide. MicroRNA (miRNA)-32-5p is as an important cancer-associated miRNA in different types cancer. To date, the role of miR-32-5p in the migration and invasion of NSCLC remains unknown. In the present study, a Transwell assay was performed to investigate the role of miR-32-5p in lung adenocarcinoma. miR-32-5p expression level was determined via reverse transcription-quantitative PCR in 24 pairs of NSCLC and adjacent normal tissues. SMAD family member 3 (SMAD3) was considered as a novel target gene by luciferase reporter assay and western blot in NSCLC. The present study demonstrated that miR-32-5p is frequently downregulated in NSCLC tissues. The overexpression of miR-32-5p resulted in the inhibition of migratory and invasive abilities in NSCLC cells. Thus, SMAD3 was identified as a target of miR-32-5p, and its expression was negatively correlated with miR-32-5p expression in clinical NSCLC tissues. Overall, these findings indicate that miR-32-5p serves as a tumor suppressor by targeting SMAD3. Thus, miR-32-5p may be a potential therapeutic target for the treatment of lung adenocarcinoma.

Establishment of an induced pluripotent stem cell line (WMUi016-A) from a patient with X-linked Dent disease (X-Dent) carrying the hemizygote mutation p.R718* (c.2152C > T) in the CLCN5 gene.

The gene mutations of the chloride channel gene (CLCN5) can lead to the inherited X-linked Dent disease (X-Dent). The urine cells of a 4-year-old male X-Dent patient with the hemizygous CLCN5 gene mutation p.R718* (c.2152C > T) were reprogrammed into induced pluripotent stem cells (iPSCs) using integration free Sendai virus reprogramming system. The generated iPSCs stably expressed pluripotent stem cell markers and can be induced to differentiate into three germ layers in vitro. The karyotype of the generated iPSCs was normal (46, XY).