A Clinic Study on Long-term Efficacy and Safety of Autologous Peripheral Blood Stem Cell Transplantation in Patients with Decompensated Hepatitis B Cirrhosis.

Objective: To investigate the long-term safety and efficacy of autologous peripheral blood stem cell transplantation (APBSCT) in treating decompensated hepatitis B cirrhosis. Methods: In this study, a retrospective analysis was conducted on a cohort of 84 patients diagnosed with decompensated hepatitis B cirrhosis between January 2011 and December 2012. The patients were categorized into two groups based on their treatment approach: the transplantation group, consisting of 34 cases who received APBSCT in addition to medical treatment, and the comprehensive medical treatment (CMT) group, comprising 50 cases who solely received CMT. EPI Data software was used for data input and verification. Survival curves were drawn by Kaplan-Meier method and analyzed by log-rank test. Paired t test and independent sample t test were used for intra-group and inter-group mean comparison of measurement data, respectively. The Mann-Whitney U test is used for non-normally distributed data. Results: After the ten-year follow-up period, it was found that overall survival (OS) in the transplantation group was markedly higher than that in the CMT (56% vs. 16%, P < .001). Albumin (ALB), prothrombin time (PT), and indocyanine green retention at 15 min (ICG R15) were significantly improved in sequence at 4 to 12 weeks of early treatment in APBSCT group; subsequently, the Acoustic radiation force impulse (ARFI) index and spleen length significantly decreased at 48 weeks. Compared with the CMT group, ALB and PT levels in the APBSCT group continued to recover and eventually stabilize at normal or low-risk levels at subsequent follow-ups up to 8 years. The ten-year prevalence of hepatocellular carcinoma (HCC) in the APBSCT group was markedly lower than that in the CMT group (26% vs. 62%; P = .025). Moreover, APBSCT significantly reduced ascites (χ2 = 6.997, P = .041) and was not associated with any significant adverse events during APBSCT. Based on clinical evidence, APBSCT is a safe and effective treatment for decompensated hepatitis B cirrhosis, resulting in a favorable long-term prognosis with no significant adverse events. Conclusions: APBSCT is a relatively safe and effective treatment for decompensated hepatitis B cirrhosis.

Effectiveness and Safety of Stem Cell Therapy in Liver Cirrhosis: A Meta-Analysis of Randomized Controlled Trials.

Objective: In recent years, stem cell transplantation (SCT) has been applied to the clinical treatment of patients with cirrhosis. The specialist clinic of the SCT clinic provides regular and effective interventions for cirrhosis, helping to improve patient management and compliance. The aim of this study was to determine the efficacy and safety of SCT in the treatment of cirrhosis. Methods: This systematic review adhered to the guidelines outlined in the PRISMA statement. The National Library of Medicin (MEDLINE), Excerpt Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials.gov databases were searched to screen liver cirrhosis-related articles with stem cell therapy from 2000 to 2022. The articles were then filtered and extracted for clinical outcomes including MELD score, Child-Pugh score, platelets, creatinine, bilirubin, albumin, international normalized ratio (INR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), α fetoprotein (AFP), prothrombin time (PT). The data were normalized and analyzed using the standardized mean difference (SMD) and 95% confidence interval (CI). Results: A total of 1209 articles were searched, and from these, ten studies were selected for analysis regarding the association between SCT and the clinical outcomes of liver cirrhosis. The findings revealed that SCT therapy, in comparison to conventional treatment, resulted in a reduction in MELD score and INR after 1 month, a decrease in Child-Pugh score at 3 months, an increase in platelet count at 3 months, and an elevation in ALB levels after 1 month. However, no significant beneficial effects were observed on creatinine, bilirubin, PT, ALT, AST, GGT, ALP, and ASP levels. Conclusion: This study suggested that SCT therapy could elevate the ALB levels and alleviate the MELD score and INR, short-term decreasing the Chile-Pugh score and increasing the platelet levels. It could be a potential therapeutic alternative for patients with cirrhosis.

Transjugular intrahepatic portosystemic shunt for pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of patients with pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). METHODS: Patients diagnosed with PA-HSOS and treated in Ningbo No.2 Hospital between November 2017 and October 2022 were enlisted in this retrospective cohort study. RESULTS: This cohort comprised a total of 22 patients with PA-HSOS, of which 12 patients received TIPS treatment and 10 patients experienced conservative treatment. The median follow-up duration was 10.5 months. Baseline characteristics existed with no significant difference between the two groups. No operation failures or any TIPS-associated intraoperative complications were observed after TIPS. In the TIPS group, the portal venous pressure was substantially decreased from 25.3 ±â€…6.3 mmHg to 14.4 ±â€…3.5 mmHg after TIPS ( P  = 0.002). Compared with preoperative, the ascites after TIPS were significantly subsided ( P  = 0.001) and there existed a considerable decrease in Child-Pugh score. At the end of follow-up, 5 patients died, involving 1 in the TIPS group and 4 in the conservative treatment group. The median survival time was 13 (3-28) months in the TIPS group and 6.5 (1-49) months in the conservative treatment group, respectively. The survival analysis demonstrated that the total survival time of TIPS group was longer than that of the conservative treatment group, no statistical significance was observed ( P  = 0.08). CONCLUSION: TIPS may be a secure and effective therapeutic strategy for PA-HSOS patients who do not respond to conservative treatment.

Enhancing the osmotic energy conversion of a nanoporous membrane: influence of pore density, pH, and temperature.

Salinity gradient power, which converts Gibbs free energy of mixing to electric energy through an ion-selective pore, has great potential. Towards practical use, developing membrane-scaled nanoporous materials is desirable and necessary. Unfortunately, the presence of a significant ion concentration polarization (ICP) lowers appreciably the power harvested, especially at a high pore density. To alleviate this problem, we suggest applying an extra pressure difference ΔP across a membrane containing multiple nanopores, taking account of the associated power consumption. The results gathered reveal that the application of a negative pressure difference can improve the power harvested due to the enhanced selectivity. In addition, if the pore density of a membrane is high, raising its pore length is necessary to make the energy harvested economic. For example, if the pore length is 2000 nm and the pore density is 2.5 × 109 pores per cm2, an increment in the power density of 213 mW m-2 can be obtained by applying ΔP = -1 bar at pH 11 and 323 K, where a net positive power density can be retrieved. The performance of the system considered under various conditions is examined in detail, along with associated mechanisms.

The Role of Hepatic Arterial Infusion Chemotherapy in the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). METHODS: The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). RESULTS: A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients' OS (HR, 0.49; 95% CI: 0.37-0.61) and PFS (HR, 0.52; 95% CI: 0.36-0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27-0.88) and DFS (HR, 0.49; 95% CI: 0.31-0.68). CONCLUSION: HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.

Prognostic factors in stage I gastric cancer: A retrospective analysis.

PURPOSE: The purpose of this research is to investigate the prognostic factors of patients with stage I gastric cancer (GC) and to determine whether adjuvant chemotherapy improves the prognosis for high-risk patients. METHODS: We performed a retrospective analysis at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences from January 2001 to December 2015. Cox regression and Kaplan-Meier were used to evaluate the relationship between the patients' clinicopathologic characteristics and prognosis. RESULTS: A total of 1,550 patients were eligible for the study. The 5-year disease-free survival (DFS) rate of all enrolled patients was 96.5%. The pT and pN stages were significantly associated with the prognosis. The 5-year DFS rates of the three subgroups (T1N0, T2N0, and T1N1) were 97.8%, 95.7%, and 90.5%, respectively (p < 0.001). In the T1N1 subgroup, patients not undergoing chemotherapy showed a lower 5-year DFS rate compared to those undergoing chemotherapy, although the difference was not statistically significant. CONCLUSIONS: Both the pT and pN stages were closely associated with the prognosis of patients with stage I GC. We also found that the danger coefficient of the pN stage was higher than that of the pT stage, and that postoperative adjuvant chemotherapy might be a reasonable approach to improve outcomes of high-risk patients, particularly in the T1N1 group.

Improved Rectification and Osmotic Power in Polyelectrolyte-Filled Mesopores.

Ample studies have shown the use of nanofluidics in the ionic diode and osmotic power generation, but similar ionic devices performed with large-sized mesopores are still poorly understood. In this study, we model and realize the mesoscale ionic diode and osmotic power generator, composed of an asymmetric cone-shaped mesopore with its narrow opening filled with a polyelectrolyte (PE) layer with high space charges. We show that, only when the space charge density of a PE layer is sufficiently large (>1×106 C/m3), the considered mesopore system is able to create an asymmetric ionic distributions in the pore and then rectify ionic current. As a result, the output osmotic power performance can be improved when the filled PE carries sufficiently high space charges. For example, the considered PE-filled mesopore system can show an amplification of the osmotic power of up to 35.1-fold, compared to the bare solid-state mesopore. The findings provide necessary information for the development of large-sized ionic diode and osmotic power harvesting device.

Autophagy flux inhibition augments gastric cancer resistance to the anti-human epidermal growth factor receptor 2 antibody trastuzumab.

The autophagy involved in the occurrence, development and prognosis of human epidermal growth factor receptor 2 (HER2) gene-amplified cancer also controls the resistance of this type of cancer to the monoclonal antibody, trastuzumab (Tzb). In the present study, Tzb resistance was established in HER2-positive NCI-N87 cell lines (Tzb-refractory cells). The cell viability, clonogenic assay, ratios of light chain 3 II/I, sequestosome 1 expression, and the phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) were investigated in the parental and Tzb-refractory cells. The viability of parental NCI-N87 and Tzb-refractory cells with an autophagy inhibitor or inducer was also examined. The results of the present study indicated that autophagic flux may have an important function in the resistance of HER2-positive human gastric cancer NCI-N87 cells to Tzb. Tzb resistance in NCI-N87 cells prevents cell apoptosis via autophagic flux inhibition. Tzb may activate the Akt/mTOR pathway to inhibit autophagic flux in gastric cancer cell lines. Everolimus, an mTOR inhibitor, may inhibit cell viability, indicating that the mTOR pathway may serve a function in HER2-positive gastric cancer and that the resistance of HER2-positive gastric cancer to Tzb may, at least partially, be due to activation of the mTOR pathway.

Long non-coding RNA UCA1 promotes the tumorigenesis in pancreatic cancer.

The contribution of long non-coding RNAs (lncRNAs) to tumorigenesis and metastasis of pancreatic cancer (PC) remains largely unknown. Urothelial cancer-associated 1 (UCA1), which is an originally identified lncRNA in bladder cancer, has be proved to play a pivotal role in bladder cancer progression and embryonic development. In this study, we detected the mRNA expression of UCA1 in 128 PC patients by qRT-PCR, and found that UCA1 expression was significantly, up-regulated in tumor tissues than that in matched adjacent non-tumor tissues (p<0.05). Clinicopathological analysis demonstrated that UCA1 expression in PC significantly correlated with malignant potential factors such as tumor size (p=0.021), depth of invasion (p=0.033), CA19-9 level (p=0.034) and tumor stage (p=0.013). Cox proportional hazards regression analysis also confirmed that high UCA1 expression was an independent prognostic biomarker of PC (p=0.046), which led to an obviously shorter 5-year overall survival (OS) compared to those patients with low UCA1 expressions (p=0.018). Furthermore, we effectively down-regulated UCA1 mRNA expression by transfecting RNA interfere fragments into SW-1990 cells, and our results in vitro indicated that down-regulation of UCA1 could effectively inhibit the cell proliferative activities, induce apoptotic rate and cause cell cycle arrest in PC cells (p<0.05). Meanwhile, UCA1 expression negative-correlated with p27 in PC tissues (r2=0.46, p<0.01), and knockdown of p27 partly abrogated the cell proliferative activities caused by UCA1 (p<0.05). Our results raised the possibility of using UCA1 as a potential prognostic biomarker and therapy target of PC, and down-regulation of UCA1 might be considered to be a novel molecular treatment strategy for patients with PC.

miR-203 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting oncogene ADAM9 and oncogenic long non-coding RNA HULC.

MicroRNAs (miRNAs) have been integrated into tumorigenic programs by regulating genes at post-transcriptional level. Long non-coding RNAs (lncRNAs) are novel targets for miRNAs. Here, we reported that miR-203 down-regulation was closely linked to advanced clinical features and poor overall survival (OS) of patients with hepatocellular carcinoma. We also confirmed that miR-203 and oncogene ADAM9 (a disintegrin and metalloproteinase 9)/oncogenic long non-coding RNA HULC (highly up-regulated in liver cancer) were inversely expressed in hepatocellular carcinoma (HCC) tissues or cell lines. More intriguingly, up-regulation of miR-203 diminished the expression of ADAM9 and HULC in HCC cancer cells. Over-expression of miR-203 could markedly inhibit cell proliferation, invasion and induce cell apoptosis. Furthermore, we identified that miR-203 modulated ADAM9 and HULC in a novel post-transcriptional regulatory mechanism. Over-expression of HULC partly rescued the miR-203-mediated antitumor effects. These results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment.

Distribution and clinical significance of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients.

This study was designed to investigate the distribution of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients, its clinical significance, and the expression profile of Th17 cell-associated cytokines. The percentage of Th17 cells detected by flow cytometry analysis (FACS) was significantly higher in 46 pancreatic tumor tissues (5.28 ± 1.65%) compared with corresponding adjacent normal tissues (2.57 ± 0.83%) (P = 0.031). In addition, the percentage of Th17 cells was significantly higher in stage III-IV tumors than stage I-II tumors (P = 0.039). The percentage of Th17 cells in peripheral blood of 20 pancreatic cancer patients (3.99 ± 1.15%) was significantly higher than 15 healthy volunteers (1.98 ± 0.57%) (P = 0.027). Immunohistochemistry (IHC) was performed to detect IL-17(+) cells in 46 pancreatic tumor tissues, as well as expression of CD34 in 24 tumor tissues. IL-17 was shown to mainly locate in cytoplasm, and the frequency of IL-17(+) cells in tumor tissues (39/46) was higher than control (29/46). The presence of IL-17(+) cells in tumor tissues was associated with tumor, node, and metastasis (TNM) stage, and lymph node metastasis (P = 0.012 and P = 0.009) but not with patient sex, age, tumor size, and histological grade (P > 0.05). Interestingly, distribution of Th17 cells in tumor tissues was positively correlated with microvessel density (MVD) (r = 0.86, P = 0.018). Furthermore, the median survival time of patients with high and low level of IL-17(+) cells frequency was 14.5 and 18.5 months respectively (P = 0.023). The serum levels of Th17 cell-associated cytokines, IL-17 and IL-23 in 20 pancreatic patients detected by enzyme-linked immunosorbent assay (ELISA) were 69.2 ± 28.5 pg/mL and 266.5 ± 98.1 pg/mL, respectively, which were significantly higher than 15 healthy volunteers (P = 0.015 and P = 0.02). Moreover, levels of IL-17 and IL-23 were significantly higher in stage III-IV tumors than stage I-II tumors (P = 0.04 and P = 0.036). This study suggests that increase in Th17 cells frequency and its related cytokines levels in pancreatic tumor tissues may indicate involvement in the invasion and metastasis of pancreatic cancer, which may thereby affect patient prognosis. Therefore, Th17 cells and related cytokines may be served as important immune indicators for predicting the prognosis of pancreatic cancer patients.