[The role of fluorescent cholangiography in preventing biliary tract injury and finding bile leakage].

The study investigated the clinical value of fluorescence cholangiography using indocyanine green (ICG) in laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) in preventing bile duct injury (BDI) and detecting bile leakage. A total of 300 patients who underwent fluorescent navigation LC and LCBDE in the Second Department of General Surgery, Shengjing Hospital Affiliated to China Medical University from June 2020 to September 2022 were selected as the research objects for observation and analysis. There were 114 males and 186 females, and aged (50.7±14.0) years with the body mass index (BMI) of (23.6±1.6) kg/m². All 300 cases of fluorescence navigation surgery were successfully completed, of which 5 patients received fluorescence-guided LCBDE and primary suture. The results showed that the application of fluorescence cholangiography with ICG can effectively avoid and detect the occurrence of BDI and bile leakage. Meanwhile, it is reasonable to hypothesize that ICG can be used for rapid localization and the final check to prevent the recurrence of bile leakage when bile leakage is suspected in the second operation.

[Research on the standard limits for vinyl chloride and trichloroethylene in the "Standards for Drinking Water Quality（GB5749-2022）" in China].

The usage of vinyl chloride and trichloroethylene in China has been increasing year by year, and they have been detected in both drinking water and environmental water, making them important environmental pollutants. Based on the latest research results on the health effects of vinyl chloride and trichloroethylene, the newly issued, "Standards for Drinking Water Quality (GB5749-2022)" in China has adjusted the standard limit of vinyl chloride from 0.005 mg/L to 0.001 mg/L and the standard limit of trichloroethylene from 0.07 mg/L to 0.02 mg/L. This article analyzed and discussed the relevant technical contents for determining the above standard limits, including the levels and exposure conditions of vinyl chloride and trichloroethylene in the water environment, health effects, derivation of safety reference values, and determination of hygiene standard limits. Suggestions were also made for the implementation of this standard.

[Methodological study on the establishment of limit values in the Standards of Drinking Water Quality].

The establishment of limit values for standards of drinking water quality is an important and complex process. This study systematically introduced the methodology of the establishment of standard limit values for drinking water quality and elaborated on the workflow of setting limit values of water quality indicators, principles and methods of selecting water quality indicators, derivation of safety reference values, and establishment of limit values. It also aimed to provide reference and support for the future revision of relevant standards.

[Research on the establishment of standard limits for perfluorooctanoic acid and perfluorooctane sulfonate in the "Standards for Drinking Water Quality（GB5749-2022）"in China].

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

[Influencing factors of Legionella reproduction in secondary water supply operation and management].

Objective: To analyze the pollution status and influencing factors of Legionella pneumophila in a secondary water supply facility in a city. Methods: From June to August 2020, a survey on the level of Legionella pneumophila in secondary water supply unit was carried out in a city in northern China, and 304 sets of secondary water supply facilities were included in the study. A total of 760 water samples were collected from the inlet and outlet water of the secondary water supply facilities and some water samples in the water tank were collected for the detection of Legionella pneumophila, standard plate-count bacteria and related physical and chemical indicators. Through questionnaire survey, the basic information of secondary water supply facilities and daily management of water quality were collected. Multivariate logistic regression model was used to analyze the influencing factors of Legionella pneumophila contamination. Results: Among 304 sets of secondary water supply facilities, most of them were located in residential buildings [57.24% (174/304)]. High and low water tank water supply, low water tank variable frequency conversion water supply and non-negative pressure water supply accounted for 26.6% (81/304), 36.8% (112/304) and 36.5% (111/304), respectively. About 25.7% of facilities (78/304) were positive for Legionella pneumophila. Among them, the positive rates of Legionella pneumophila in high and low water tank water supply, low water tank variable frequency conversion water supply and non-negative pressure water supply facilities were 38.3% (31/81), 29.5% (33/112) and 12.6% (14/111), respectively. The results of multivariate logistic regression model analysis showed that the disinfectant residue could reduce the risk of Legionella pneumophila contamination in water samples, and the OR (95%CI) value was 0.083 (0.022-0.317). The increase of the standard plate-count bacteria and conductivity might increase the risk of Legionella pneumophila contamination in water samples. The OR (95%CI) values were 3.160 (1.667-5.99) and 1.004 (1.001-1.006), respectively. Compared with the non-negative pressure water supply, the risk of Legionella pneumophila contamination of secondary water supply facilities was increased by water supply from high and low water tanks and variable frequency conversion water supply from low water tanks, with OR (95%CI) values of 4.296 (2.096-8.803) and 2.894 (1.449-5.782), respectively. Conclusion: The positive rate of Legionella pneumophila in secondary water supply in the study city is high. Disinfectant residue, conductivity and method of water supply are associated with the positive rate of Legionella pneumophila.

[Feasibility of radiofrequency ablation for cancer patients with atrial fibrillation].

Objective: To analyze the impact of cancer on the recurrence rate of atrial fibrillation (AF) after AF radiofrequency ablation and further evaluate the feasibility of radiofrequency ablation therapy in cancer patients with AF. Methods: This study was a single-center, retrospective study. Cancer patients with AF undergoing radiofrequency ablation for the first time in the First Affiliated Hospital of Dalian Medical University from May 30, 2008 to September 30, 2018 were included (cancer group). AF patients without cancer undergoing radiofrequency ablation for the first time during the same period served as non-cancer group. Clinical data including age, gender, past history, cancer and AF-related parameters, etc. were analyzed. Patients were followed up after radiofrequency ablation. The primary endpoints were AF recurrence or all-cause death. Kaplan-Meier survival analysis was used to analyze the effect of cancers on the recurrence after AF ablation. The multivariate cox regression analysis was further applied to correct for other confounding factors to analyze whether the impact of cancers on the recurrence of atrial fibrillation was statistically significant. Results: A total of 90 patients were enrolled, there were 30 patients in the cancer group (mean age (64.8±6.6) years, 16 (53.3%) males) and 60 patients in the non-cancer group (mean age (63.6±6.2) years, 32 (53.3%) males). Clinical data, such as age, gender, and cancer treatment, were similar between the two groups. During an average follow-up period of (328.7±110.2) days, there were 6 AF recurrences (recurrence rate 20.0%) in the cancer group, and 17 AF recurrences (recurrence rate 28.3%) in the control group. AF recurrence rate was similar between the two groups (P>0.05). During the follow-up period, there was no all-cause death in the two groups. Kaplan-Meier survival analysis showed that cancer was not related to AF recurrence after radiofrequency ablation (P = 0.383). After adjusting for other confounding factors, the multivariate Cox regression analysis showed that cancer was not an independent predictor of AF recurrence after radiofrequency ablation (HR=0.508, 95%CI: 0.192-1.342, P = 0.172). Conclusions: The combination of cancer has no impact on the recurrence of AF after radiofrequency ablation. For cancer patients with AF, radiofrequency ablation therapy can be considered as a feasible heart rhythm control treatment strategy.

Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial.

BACKGROUND: Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3%-4% of non-small-cell lung cancer (NSCLC) and is associated with unfavorable prognosis. While MET is a validated drug target in lung cancer, the best biomarker strategy for the enrichment of a susceptible patient population still remains to be defined. Towards this end we analyze here primary data from a phase I dose expansion study of the MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC. PATIENTS AND METHODS: Eligible patients [≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2] with MET-dysregulated advanced NSCLC, defined as either (i) MET status by immunohistochemistry (MET IHC) 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2.0 or gene copy number (GCN) ≥5, or (ii) epidermal growth factor receptor wild-type (EGFRwt) and centrally assessed MET IHC 3+, received capmatinib at the recommended dose of 400 mg (tablets) or 600 mg (capsules) b.i.d. The primary objective was to determine safety and tolerability; the key secondary objective was to explore antitumor activity. The exploratory end point was the correlation of clinical activity with different biomarker formats. RESULTS: Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received two or more prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69.1%). The median treatment duration was 10.4 weeks. The overall response rate per RECIST was 20% (95% confidence interval, 10.4-33.0). In patients with MET GCN ≥6 (n = 15), the overall response rate by both the investigator and central assessments was 47%. The median progression-free survival per investigator for patients with MET GCN ≥6 was 9.3 months (95% confidence interval, 3.8-11.9). Tumor responses were observed in all four patients with METex14. The most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%). CONCLUSIONS: MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC (NCT01324479).

Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis.

BACKGROUND: In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis. PATIENTS AND METHODS: Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum-pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points. RESULTS: A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum-pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum-pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67-1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5-31.5) versus 22.5 months (95% CI 20.2-28.8) for osimertinib and platinum-pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18-1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16-0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinum-pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3, <1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum-pemetrexed arm. CONCLUSIONS: In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum-pemetrexed, which possibly reflects the high crossover rate of patients from platinum-pemetrexed to osimertinib. CLINICAL TRIALS NUMBER: ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.

[The Function of CD40/CD40L Pathway in Silicosis Fibrosis].

Objective: To investigate the role of CD40/CD40L Pathway in the formation of silicosis fibrosis. Methods: Totally 64 inpatients were recruited and assigned to the silicosis group and the control group, 23 in each group. The alveolar lavage fluid was collected from all patients and isolated. The expression of CD40L protein was detected by Flow Cytometry. The level of IL-8、The IL-6、INF-γ and MCP-1 was detected by ELISA. Two groups of BALF were co-cultured with HFL-1 cells, the expression of Collagen I and α-SMA was detected by Immunohistochemistry. Results: Compared with the control group, CD40L was highly expressed on T lymphocyte cells in silicosis group (P<0.05) , and the contents of IL-8、The IL-6、INF-γand MCP-1 in Silicosis group were significantly higher than those in control group (P<0.05) . After co-culture of BALF and HFL-1 cells, the expression levels of Collagen I and α-SMA in Silicosis group were significantly higher than those in control group (P<0.05) . Conclusion: CD40-CD40L cross-linking system can promote the activation of T cells, release inflammatory factors, promote the synthesis of collagen I and α-SMA by fibroblasts, make the lung fibrous tissue proliferate, and lead to the formation of silicosis fibrosis.

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial.

BACKGROUND: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis. RESULTS: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01905657.

MicroRNA miR-252 targets mbt to control the developmental growth of Drosophila.

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.

Optimization of broth recovery for repair of heat-injured Salmonella enterica serovar Typhimurium and Escherichia coli O157:H7.

AIMS: The purpose of this research was to determine optimum conditions for broth recovery of heat-injured Salmonella Typhimurium and Escherichia coli O157:H7. METHODS AND RESULTS: Exposure to 55°C for 15 and 25 min, respectively, induced cellular injury to those pathogens. Comparison was made with the commonly used overlay method using selective medium for recovering sublethally injured cells of S. Typhimurium. For E. coli O157:H7, phenol red agar base with 1% sorbitol was used. After cell suspensions were heated at 55°C for selected time intervals, microbes were 10-fold diluted with brain heart infusion (BHI), tryptic soy broth (TSB) and TSB with 0·6% yeast extract (TSBYE) and incubated at 37°C for up to 3 h. At hourly intervals, diluents were plated onto selective medium for recovery. Simultaneously, diluents were plated onto tryptic soy agar (TSA) for recovery of sublethally injured cells. For overlays, diluents were plated onto TSA and overlaid with selective agar after a resuscitation interval. Broth recovery conditions for S. Typhimurium and E. coli O157:H7 were determined to be 1 h in any of the following broth media: BHI, TSB or TSBYE. When liquid resuscitation was applied to sublethally injured cells in food samples (milk), 1 h was also sufficient time for recovery. CONCLUSIONS: The broth recovery method is a convenient alternative to conventional recovery methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Cells sublethally injured by control interventions might not grow on selective medium because they have no resistance to several selective compounds. However, injured cells can recuperate and multiply under conditions sufficient for recovery. To repair and detect heat-injured cells, the overlay method is commonly used but this method has some limitations. This study confirms the effectiveness of liquid resuscitation method on recovery of injured cells. The broth recovery can replace the overlay method due to greater convenience and timesaving.

Influence of exposure to summer environments on skin properties.

BACKGROUND: Although cosmetic companies have launched products to combat extreme environments (hot or cold) and various pollutants, research into the effects of these conditions on skin properties is lacking. We aimed to investigate the influence of exposure to outdoor environments during summer on skin properties. METHODS: We enrolled 20 women in their 20s and 40s. They were exposed to outdoor and indoor environments for 90 min each in July 2016. Skin evaluations were performed on the face (forehead and cheek) and forearm. Skin hydration level, sebum secretion, trans-epidermal water loss (TEWL), pH and greasiness were evaluated. RESULTS: Skin hydration levels, sebum secretion, TEWL and greasiness in all examined regions were higher after outdoor exposure than after indoor exposure; however, skin pH decreased after outdoor exposure. Hydration levels on the forearm and sebum secretion on the face increased, whereas hydration levels and TEWL on the cheek, greasiness in all regions except the cheek, and pH in all regions decreased during the 90-min outdoor exposure. The hydration levels in all regions except the cheek, sebum secretion and greasiness on the face increased, but the TEWL and the pH declined after being indoors. CONCLUSION: Hot environments cause the production of more sweat, increasing hydration levels, sebum secretion, TEWL, and greasiness and reducing skin pH. After acclimatization, skin hydration on the cheek decreases because of sweat evaporation. Cosmetics that are marketed for use in summer should control sweat and sebum secretion, solve related inconveniences, and provide moisture, especially on the cheeks.

ALK-positive anaplastic large cell lymphoma with a monomorphic small-cell pattern masquerading as inflammatory gastric lesions.

INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions. CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered. DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

Antineutrino Charged-Current Reactions on Hydrocarbon with Low Momentum Transfer.

We report on multinucleon effects in low momentum transfer (<0.8 GeV/c) antineutrino interactions on plastic (CH) scintillator. These data are from the 2010-2011 antineutrino phase of the MINERvA experiment at Fermilab. The hadronic energy spectrum of this inclusive sample is well described when a screening effect at a low energy transfer and a two-nucleon knockout process are added to a relativistic Fermi gas model of quasielastic, Δ resonance, and higher resonance processes. In this analysis, model elements introduced to describe previously published neutrino results have quantitatively similar benefits for this antineutrino sample. We present the results as a double-differential cross section to accelerate the investigation of alternate models for antineutrino scattering off nuclei.

[A preliminary study on the application of two-point traction with guidewire method in percutaneous transhepatic sinus tract dilation].

Objective: To explore the feasibility and effectiveness of the two-point traction with guidewire method to improve the safety of percutaneous transhepatic sinus tract dilation. Methods: The clinical data of 18 patients underwent the two-point traction guided by percutaneous transhepatic sinus dilation between January 2013 and July 2017 in Shengjing Hospital of China Medical University were analyzed retrospectively. The operation time, volume of intraoperative blood loss and postoperative complications were recorded. Results: All of the 18 patients were treated successfully. The mean size of the percutaneous transhepatic sinus tract was (18.6±2.3) Fr. The operation time was 15-45 min, with an average of 30 minutes, and the average intraoperative blood loss was about 11.7 ml. The incidence of postoperative complications was 22.2% (4/18), including cholangitis in 3 patients, pancreatitis in 1 case. All the complications were relieved after symptomatic treatment, no severe complications (biliary tract perforation or severe haemorrhage) occurred. A total of (3.3 ± 2.6) times cholangioscopic explorations for stone extraction were performed, with a overall clearance rate of 64.7% (11/17). Conclusions: From the results of limited patient data in this group, the two-point traction with guidewire can provide the exact guidance for percutaneous transhepatic sinus tract dilation, which is effective and easily conducted, but still need further clinical study to confirm.

Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma.

BACKGROUND: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). METHODS: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. RESULTS: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. CONCLUSIONS: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.

[Hyper-IgE syndrome in adulthood: a case report and literature review].

Objective: To describe the clinical features of hyper-IgE syndrome (HIES), with emphasis on refractory pulmonary cystic lesions as the initial presentation in adulthood. Methods: A case of HIES presenting with pulmonary cystic lesions in an adult patient was retrospectively analyzed. We used "hyper-IgE syndrome" as the Chinese keywords, "hyper-IgE syndrome, China" as the English keywords to retrieve the literature from Wanfang database/CNKI database and Pubmed database until April 2016. The clinical data were pooled and analyzed. Results: A 19 year old female patient was admitted to our hospital because of recurrent cough and expectoration as the chief complaint. Physical examination revealed broad nasal bridge and scoliosis, and chest CT showed gradually enlarged and increased cystic lesions. Laboratory studies demonstrated significantly increased blood eosinophils and serum level of total IgE, together with a definite chemotactic dysfunction of neutrophils. A further detection of STAT3 mutation was negative. The diagnosis of HIES was made and antibiotic treatment resulted in disease remission. Literature review found 45 reports including 37 in Chinese and 11 in English. Eight cases of adult HIES were reported, and all the patients were male, aging 18 to 31 years. Prolonged disease course, recurrent infection and formation of cystic lesions in the lungs were important features of HIES. Early diagnosis and treatment with specific antibiotics were important for improving outcome of the patients. Conclusion: Refractory pulmonary cystic lesions can be the initial presentation in adult HIES. Understanding of the clinical characteristics of HIES will be helpful to avoid misdiagnosis and improve prognosis.