Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

[A cross-sectional survey on the types of antiviral treatment plans for patients with chronic hepatitis B].

Objective: To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B. Methods: A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022. Results: A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303). Conclusion: Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

Workplace bullying and suicidal ideation and behaviour: a systematic review and meta-analysis.

OBJECTIVES: Suicidal ideation and behaviour are potential outcomes of workplace bullying. This review aimed to determine the extent of the association between workplace bullying and suicidal ideation and behaviour. STUDY DESIGN: The study incorporated a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed to conduct a comprehensive systematic review and meta-analysis. A combination of subject terms and free words was used to search nine electronic databases. Two reviewers independently screened articles and extracted information according to the inclusion criteria. A meta-analysis was performed with averaged weighted correlations across samples using the STATA software (version 16.0) from pooled estimates of the main results from all studies. RESULTS: In total, 25 articles of high or medium quality were included in the systematic review; 15 of these were included in the meta-analysis. The prevalence of suicidal ideation and behaviour was 18% and 4%, respectively. Individuals who experienced workplace bullying had 2.03-times and 2.67-times higher odds of reporting suicidal ideation and behaviour, respectively, after adjustment for confounding factors. Moderating and mediating factors may help reduce the risk of suicidal ideation and behaviour for individuals experiencing workplace bullying. CONCLUSION: This study indicated that exposure to workplace bullying significantly increased the risk of suicidal ideation and behaviour.

[Application of methylene blue near-infrared fluorescence imaging for oral sentinel lymph node mapping in rats].

OBJECTIVE: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer. METHODS: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro, and the presence of lymphoid tissue was confirmed by pathological examination after resection. RESULTS: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence. CONCLUSION: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

MiR-20a Promotes kidney injury in sepsis rats through autophagy.

The aim of this work was to study the effects of micro ribonucleic acid (miR)-20a on acute kidney injury (AKI) in sepsis rats and its key molecular mechanism. Sprague-Dawley rats were randomly divided into healthy rat group (H group, n=3), sham group (S group, n=3), sepsis rat group (D group, n=3), sepsis rat + negative control transfection group (N group, n=3) and sepsis rat + miR-20a inhibitor transfection group (M group, n=3). At 6 h, 12 h and 24 h, serum creatinine (Scr) and blood urea nitrogen (BUN) were detected, the changes in miR-20a expression in kidney tissues were determined via reverse transcription-polymerase chain reaction (RT-PCR), the expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) was measured via Western blotting, and the inflammatory cell infiltration in kidney tissues was detected using hematoxylin-eosin (HE) staining. There was no obvious change in each index in S group compared with H group. D group, N group and M group had higher levels of Scr, BUN and LC3 in kidney tissues than S group. The levels of Scr, BUN and LC3 in kidney tissues were lower in M group than those in N group. MiR-20a may cause AKI in sepsis rats via activating autophagy.

miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2.

MicroRNAs (miRNAs) have pivotal roles in the initiation and progression of gastric cancer (GC), and miR-92a-3p has been proved to act as an oncogene in multiple malignancies. However, the molecular mechanisms by which miR-92a-3p contributes to GC remain unclear. The differentially expressed miRNAs were screened by GEO dataset, and the association of miR-92a-3p expression with clinicopathological characteristics and prognosis in patients with GC was analyzed by TCGA dataset. The target genes of miR-92a-3p were identified by bioinformatic analysis, and their interaction was confirmed by luciferase reporter assay. MTT, EdU and Transwell assays were conducted to determine the role of miR-92a-3p in GC cells. As a result, it was found that the expression levels of miR-92a-3p were increased in GC tissues and were associated with tumor size, lymph node infiltration and distant metastasis, acting as an independent prognostic factor of poor survival in patients with GC. Restored expression of miR-92a-3p facilitated cell proliferation, DNA synthesis and cell invasion, but its inhibitor reversed these effects. KLF2 was further identified as a direct target of miR-92a-3p, indicating a negative correlation with miR-92a-3p expression and harboring a favorable prognosis in GC. In addition, KLF2 repressed cell proliferation and invasion and attenuated the tumor-promoting effects of miR-92a-3p in GC cells. Altogether, our findings demonstrated that miR-92a-3p promoted the proliferation and invasion of GC cells by targeting KLF2.

[Novel coronavirus pneumonia (COVID-19) CT distribution and sign features].

Objective: To investigate the imaging findings of 2019 novel coronavirus pneumonia (COVID-19). Methods: From January 20 to February 5, 2020, a total of 130 patients diagnosed with COVID-19 from seven hospitals in China were collected. The imaging data were reviewed and analyzed in detail. Results: (1) Distribution: the lesion detected in the lung unilaterally in 14 cases (10.7%) and bilaterally in 116 cases (89.3%). According to the distribution in the lobes of the lung, all cases could be classified into subpleural distribution (102 cases, 78.4%), centrilobular distribution (99 cases, 76.1%) and diffused distribution (8 cases, 6.1%). (2) Number of lesions: single lesion 9 cases (6.9%); multiple lesions 113 cases (86.9%), diffuse lesions 8 cases (6.1%). (3) Imaging density: 70 cases (53.8%) of ground-glass opacity (GGO), 60 cases (46.2%) of GGO+consolidation. (4) Accompanying signs: 100 cases (76.9%) with vascular thickening, 98 cases (75.3%) with "pleural parallel sign" ; " intralobular septal thickening" in 100 cases (76.9%); "halo sign" in 13 cases (10%); "reversed-halo sign" in 6 cases (4.6%); pleural effusion in 3 cases (2.3%), and pneumatocele in 2 cases (1.5%); no case with pulmonary cavity. Among 35 patients that underwent follow-up CT, 21 patients (60%) improved while 14 (40%) exacerbated. Conclusions: COVID-19 imaging characteristic mainly has subpleural, centrilobular and diffused distribution. The first two distributions can overlap or progress to diffused distribution. In the later period, it was mainly manifested as organizing pneumonia and fibrosis. The most valuable characteristic is the pleural parallel sign.

A comprehensive study of risk factors for post-operative pneumonia following resection of meningioma.

BACKGROUND: Post-operative pneumonia (Pop) following meningioma surgery is the dominant systemic complication which could cause serious threats to patients. It is unclear whether hematological biochemical markers are independently associated with the Pop. This study attempted to perform a more comprehensive study of taking both clinical factors and hematological biomarkers into account to promote the management of patients after meningioma surgery. METHODS: We collected clinical and hematological parameters of 1156 patients undergoing meningioma resection from January 2009 to January 2013. According to whether the symptoms of pneumonia had manifested,patients were divided into the Pop group and the Non-Pop group. We analyzed the distinctions of clinical factors between the two groups. We successively performed univariate and multivariate regression analysis to identify risk factors independently associated with the Pop. RESULTS: 4.4% patients infected with the Pop (51 of 1156). The median age at diagnosis of the Pop patients was significantly older than the Non-Pop group (p = 0.002). There were strike distinctions of post-operative hospital stays between two groups, with 21 days and 7 days each (p < 0.001). On multivariate analysis, tumor relapse (p < 0.001), skull base lesions (p = 0.001), intra-operative blood transfusion (p = 0.018) and cardiovascular diseases (p = 0.001) were linked with increased risk of the Pop following meningioma resection. For hematological biochemical markers, it was the factor of Red blood cell distribution width-standard deviation (RDW-SD) (OR 5.267, 95%CI 1.316, 21.078; p = 0.019) and Neutrophils lymphocytes ratio (NLR) (OR 2.081, 95%CI 1.063, 4.067; p = 0.033) that could appreciably predict the Pop. CONCLUSIONS: Apart from tumor recurrence, localizations, intra-operative blood transfusion and cardiovascular diseases are independent risk factors for the Pop. We initially found hematological RDW-SD and NLR are also important predictors.

Effects of neuroblastoma breakpoint family member 1 (NBPF1) gene on growth and Akt-p53-Cyclin D pathway in cutaneous squamous carcinoma cells.

Neuroblastoma breakpoint family member 1 (NBPF1) is involved in the occurrence and development of tumors. However, only a limited number of studies were conducted on NBPF1 and cutaneous squamous cell carcinoma (SCC). This study mainly explored the expression and mechanism of NBPF1 in SCC. SCC tissue and adjacent tissues samples were randomly selected. NBPF1 gene was overexpressed in the A431 cell line using plasmid transfection technique. Cell viability was tested by cell counting kit-8 (CCK-8) assay. Flow cytometry was used to determine cell cycle and apoptosis. Western blot and RT-qPCR were respectively performed to determine the expression levels of proteins and mRNAs. The NBPF1 gene was lowly expressed in SCC tissues. The expression level of NBPF1 gene was the lowest in A431 cell line. The cell viability of A431 was reduced after transfection. Overexpression of NBPF1 not only arrested A431 cells in G1 phase and promoted apoptosis, but also up-regulated the expressions of Bax and p53 mRNA and protein and down-regulated the expressions of Bcl-2, Survivin and Cyclin D1. Akt-p53-Cyclin pathway was inhibited when NBPF1 gene expression was up-regulated. Upregulation of NBPF1 might promote apoptosis of A431 cells and block cell cycle via inhibiting the activation of Akt-p53-Cyclin signaling pathway.

Identification of two novel anti-HCV E2 412-423 epitope antibodies by screening a Chinese-specific phage library.

The hepatitis C virus (HCV) E2 412-423 linear epitope has been found to be highly conserved across multiple HCV genotypes. The antibodies against this epitope have broadly neutralizing activity. Considering the poor immunogenicity of the epitope in humans and significant diversity in the global distribution of HCV genotypes, the aim of this study was to construct an anti-HCV phage library by using a series of optimal strategies to screen novel broadly neutralizing antibodies from Chinese donors. mRNA was isolated from peripheral blood samples of 39 patients who were anti-HCV positive. A phage library was constructed by inserting a single-chain variable fragment (scFv) gene repertoire into the T7Select10-3b vector. A synthetic peptide representing the HCV E2 N-terminal 412-423 region was used as "bait" for bio-panning. The binding affinities of phage clones to the synthetic peptide were evaluated through peptide-ELISA. Two scFv clones (R3-19 and R4-85) showing the strongest binding affinities were selected. The complementarity-determining regions (CDRs) of these clones were aligned with those of other previously reported broadly neutralizing anti-HCV antibodies, and multiple conserved amino acid sites were found. The optimized procedures ensured that two novel scFv antibodies were isolated from a constructed phage library and showed specific binding to the poorly immunogenic HCV E2 412-423 linear epitope. Keywords: phage antibody library; hepatitis C virus; broadly neutralizing antibody; synthetic peptide.

[Diversity analysis of luminal and mucosa-associated microbial communities in obese mice].

Objective: Gut microbiota have been reported to be able to regulate host metabolism and is closely associated to obesity. The purpose of this study was to explore the differences between the diversity of luminal and mucosa-associated microbial communities in obese mice. Methods: Colonic luminal contents and colonic mucosa were separately collected from 10 obese mice fed with high-fat diet for 12 weeks. DNA of gut microbiota was extracted and micro flora populations were analyzed by Illumina sequencing. Species annotation, diversity analysis, and species difference analysis were conducted. Results: The microbial flora from colonic contents had similar richness, evenness and overall structure to those from colonic mucosa (ACE index 250 vs. 285, Chao index 257 vs. 291, Shannon index 3.84 vs. 3.97, Simpson index 0.05 vs. 0.06, all P>0.05). However, there were differences in the microbial composition on specific levels. At the phylum level, colonic contents had higher abundance of Bacteroidetes (56.08% vs. 27.25%, P=3.21×10(-5)), while colonic mucosa had higher abundance of Firmicutes (49.09% vs. 34.27%, P=0.03) and proteobacteria (18.48% vs. 3.62%, P=0.000 9). At the genus level, butyrate-producing bacteria-Lactobacillus was more abundant in colonic content (LDA score=3.89), whereas gram-negative genus Helicobacter, Sphingomonas and Desulfovibrio were relatively abundant in colonic mucosa (LDA score=4.78, 3.59 and 4.11, respectively). Conclusion: There were differences in microbial composition at the phylum and genus levels between microbial flora from colonic contents and colonic mucosa, although they had similar richness, evenness and overall structure.

Entecavir maleate versus entecavir in Chinese chronic hepatitis B predominantly genotype B or C: Results at week 144.

Reports on the efficacy and safety of long-term entecavir treatment in chronic hepatitis B (CHB) predominantly genotype B or C are insufficient. This study presents the efficacy and safety of entecavir maleate in Chinese CHB patients. Patients were randomly assigned to receive 48-week treatment with either 0.5 mg/day entecavir (group A) or 0.5 mg/day entecavir maleate (group B), and then all patients received treatment with 0.5 mg/day entecavir maleate from week 49. Two hundred and seventy-five patients with CHB (HBeAg-positive: 218) were analysed, predominantly (98.5%) with genotype B or C. Baseline characteristics were balanced. For the HBeAg-positive CHB patients, the mean HBV DNA level decreased similarly (A: by 6.36 log10 IU/mL vs B: by 6.31 log10 IU/mL) between groups at week 144. The percentages of patients who achieved undetectable HBV DNA were similar (A: 70.59% vs B: 66.67%) between groups. Similar HBeAg loss rates (A: 43.53% vs B: 40.23%; P>.05) and HBeAg seroconversion rates (A: 21.52% vs B: 21.18%) were achieved. For the HBeAg-negative CHB patients, similar reductions in HBV DNA levels from baseline (A: by 6.13 log10 IU/mL vs B: by 5.65 log10 IU/mL) and percentages of patients who achieved undetectable HBV DNA (A: 100% vs B: 100%) were achieved. The overall incidence of adverse events was comparable between groups. In conclusions, 48-week administration of entecavir maleate and entecavir showed similar efficacy and safety in Chinese patients with CHB. Long-term entecavir maleate treatment was effective and safe in CHB patients.

Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir.

Studies regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) in patients with chronic hepatitis B receiving first-line nucleos(t)ide analogues is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with entecavir. This was a retrospective cohort study consisting of 139 Chinese patients enrolled in a multicenter clinical trial treated with entecavir or entecavir maleate for up to 240 weeks. Anti-HBc evaluation was conducted for all the available samples using a newly developed double-sandwich anti-HBc immunoassay. At week 240, 35 (25.2%) patients achieved a serological response (HBeAg seroconversion) and these patients at week 240 had significantly higher levels of anti-HBc (P<.01). We defined 4.65 log10  IU·mL-1 , with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict seroconversion. Patients with baseline anti-HBc ≥4.65 log10  IU·mL-1 had 28.0% (26/93) and 35.5% (33/93) chance of seroconversion at weeks 144 and 240, respectively. The baseline anti-HBc level was the strongest predictor for seroconversion at week 144 (OR: 5.78, 95% confidence interval [CI]: 2.05-16.34, P=.001). The baseline anti-HBc level was a strong predictor for seroconversion at week 240 (OR: 5.36, 95% CI: 2.17-13.25, P<.001). Hence, baseline anti-HBc titre is a useful predictor of long-term entecavir therapy efficacy in HBeAg-positive CHB patients, which could be used to optimize antiviral therapy.

[Clinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients].

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion: In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

[Efficacy and safety of pegylated interferon α-2b injection (Y shape, 40 kD) in treatment of patients with genotype 1/6 chronic hepatitis C].

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion: In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

Combined Anti-CD154/CTLA4Ig Costimulation Blockade-Based Therapy Induces Donor-Specific Tolerance to Vascularized Osteomyocutaneous Allografts.

Tolerance induction by means of costimulation blockade has been successfully applied in solid organ transplantation; however, its efficacy in vascularized composite allotransplantation, containing a vascularized bone marrow component and thus a constant source of donor-derived stem cells, remains poorly explored. In this study, osteomyocutaneous allografts (alloOMCs) from Balb/c (H2(d) ) mice were transplanted into C57BL/6 (H2(b) ) recipients. Immunosuppression consisted of 1 mg anti-CD154 on day 0, 0.5 mg CTLA4Ig on day 2 and rapamycin (RPM; 3 mg/kg per day from days 0-7, then every other day for 3 weeks). Long-term allograft survival, donor-specific tolerance and donor-recipient cell trafficking were evaluated. Treatment with costimulation blockade plus RPM resulted in long-term graft survival (>120 days) of alloOMC in 12 of 15 recipients compared with untreated controls (median survival time [MST] ≈10.2 ± 0.8 days), RPM alone (MST ≈33 ± 5.5 days) and costimulation blockade alone (MST ≈45.8 ± 7.1 days). Donor-specific hyporesponsiveness in recipients with viable grafts was demonstrated in vitro. Evidence of donor-specific tolerance was further assessed in vivo by secondary donor-specific skin graft survival and third-party graft rejection. A significant increase of Foxp3(+) regulatory T cells was evident in tolerant animals. Donor cells populated peripheral blood, thymus, and both donor and recipient bone marrow. Consequently, combined anti-CD154/CTLA4Ig costimulation blockade-based therapy induces donor-specific tolerance in a stringent murine alloOMC transplant model.

Krüppel-like factor 2 suppresses growth and invasion of gastric cancer cells in vitro and in vivo.

Krüppel-like factor 2 (KLF2), a novel tumor-suppressor gene, is implicated in diverse cellular processes, including cell growth, apoptosis, and invasion. However, the role and action mechanisms of KLF2 in gastric cancer (GC) need be further elucidated. The expression of KLF2 was investigated by immunohistochemical assay in human GC tissues, and lentivirus-mediated KLF2 overexpression was transfected into GC cells (AGS and HGC-27) for assessing cell proliferation and invasion, respectively indicated by MTT and Transwell assays. Subcutaneous GC tumor models were constructed for estimating tumor growth in vivo. As a result, the expression level of KLF2 was decreased in GC tissues compared with the para-carcinoma tissues (31.03% vs 53.45%, P=0.035), and negatively correlated with the lymph node metastasis in GC patients (P=0.02). Moreover, overexpression of KLF2 inhibited the cell proliferation and invasive potential and downregulated the protein expression of PCNA, Bcl-2 and MMP-9 in GC cells. The result in vivo showed KLF2 overexpression reduced the xenograft tumor growth. In conclusion, our findings indicate that KLF2 may function as a tumor suppressor involved in the progression of human GC.

Long noncoding RNA, tissue differentiation-inducing nonprotein coding RNA is upregulated and promotes development of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the major causes of cancer death worldwide, especially in Eastern Asia. Due to the poor prognosis, it is necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recently, studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. Increasing evidence indicates that some lncRNAs are widely involved in the development and progression of ESCC, such as HOTAIR, SPRY4-IT1 and POU3F3. An emerging lncRNA, tissue differentiation-inducing nonprotein coding RNA (TINCR), has been studied in human cutaneous squamous cell carcinoma and has critical biological function, but its role in ESCC remains unknown. Here, we evaluated the expression profile of TINCR and its biological function in ESCC. In a cohort of 56 patients, TINCR was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues. Further, in vitro silencing TINCR via small interfering RNA (siRNA) inhibited the proliferation, migration and invasion of ESCC cells. Meantime, siRNA treatment induced apoptosis and blocked the progression of cell cycle. Taken together, our study suggests that TINCR promotes proliferation, migration and invasion of ESCC cells, acting as a potential oncogene of ESCC.

[Intertumoral heterogeneity of molecular phenotype and analysis of prognosis in multifocal and multicentric breast cancer].

Objective: This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer (MMBC). Methods: The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec. 2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed. We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype, and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade.The corresponding hazard ratio was calculated by Cox proportional-hazards regression. Results: Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients (6.8%), respectively. Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients (16.4%). There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0% vs. 77.3%, P=0.808). Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78.7% vs. 58.3%, P=0.037), and had a greater risk of recurrence (HR=2.130, 95%CI=1.027-4.420; P=0.042). Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients(11.0%). Conclusions: Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival. Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis, and improve the outcomes of the patients.

[Telescopic technique associated with mucosectomy in pancreaticoduodenectomy].

OBJECTIVE: To explore the feasibility of the telescopic technique associated with mucosectomy in preventing pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: The data of 39 patients who received PD in the Affiliated Hospital of Nantong University was retrospecively analyzed. We developed a safe and simple method of pancreaticojejunostomy in 39 patients, in whom approximately 3 cm of jejunal mucosa was cut to improve the adhesion between the loop and pancreatic parenchyma after end-to-end invagination. RESULTS: This procedure was proved to be much more expeditious, and only 2 of 39(5.1%)patients had pancreatic leakages, who were treated with drainage only. No hemorrhage or cholangitis was observed. No postoperative mortality was observed. CONCLUSION: The telescopic technique associated with mucosectomy is an acceptable and safe surgery for pancreaticojejunal anastomosis.