Objective The aim of this study was to develop a method for the determination of nine vulcanizing agents and accelerators in pharmaceutical rubber stoppers by headspace gas chromatography with sulfur chemiluminescence detector(HS-GC-SCD).Methods A DB-1 capillary column(30 m×0.32 mm×0.25 μm)was used with He as the carrier gas.The injection port temperature was 220 ℃,the split ratio was 10∶1,and the carrier gas flow rate was 1.5 mL·min-1.The temperature program was as follows:the starting temperature was 40 ℃,and it was increased to 60 ℃ at a rate of 5 ℃ per minute,and then to 260 ℃ at a rate of 15℃per minute.SCD detector parameters:base temperature was 280℃,combustion chamber temperature was 800 ℃,air flow rate was 60 mL·min-1,and hydrogen flow rate was 40 mL·min-1.Results The sample pretreatment method was simple and convenient,and it effectively reduced the extraction loss.The methodological results showed that all sulfides showed good linear relationships within the concentration range(r2≥ 0.990).The RSD was less than 2％;and the average recovery rate was 86.4％-97.5％.From the analysis of the sample test results,free sulfur is commonly found in rubber stoppers.Among all the samples of the vulcanization system,the free sulfur detected in the sulfur vulcanization system is higher than the free sulfur produced by degradation of other vulcanization systems.Conclusions This method is simple to operate,compared with other existing detection methods.HS-GC-SCD has a smaller matrix effect,higher sensitivity and selectivity,and is appropriate for quantifying the concentrations of sulfide present in various rubber stoppers.

Objective The aim of this study was to develop a method for the determination of nine vulcanizing agents and accelerators in pharmaceutical rubber stoppers by headspace gas chromatography with sulfur chemiluminescence detector(HS-GC-SCD).Methods A DB-1 capillary column(30 m×0.32 mm×0.25 μm)was used with He as the carrier gas.The injection port temperature was 220 ℃,the split ratio was 10∶1,and the carrier gas flow rate was 1.5 mL·min-1.The temperature program was as follows:the starting temperature was 40 ℃,and it was increased to 60 ℃ at a rate of 5 ℃ per minute,and then to 260 ℃ at a rate of 15℃per minute.SCD detector parameters:base temperature was 280℃,combustion chamber temperature was 800 ℃,air flow rate was 60 mL·min-1,and hydrogen flow rate was 40 mL·min-1.Results The sample pretreatment method was simple and convenient,and it effectively reduced the extraction loss.The methodological results showed that all sulfides showed good linear relationships within the concentration range(r2≥ 0.990).The RSD was less than 2％;and the average recovery rate was 86.4％-97.5％.From the analysis of the sample test results,free sulfur is commonly found in rubber stoppers.Among all the samples of the vulcanization system,the free sulfur detected in the sulfur vulcanization system is higher than the free sulfur produced by degradation of other vulcanization systems.Conclusions This method is simple to operate,compared with other existing detection methods.HS-GC-SCD has a smaller matrix effect,higher sensitivity and selectivity,and is appropriate for quantifying the concentrations of sulfide present in various rubber stoppers.

Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.

Female ; Humans ; Pregnancy ; Septate Uterus ; Uterus/surgery* ; Hysteroscopy/methods* ; Estrogens ; Tissue Adhesions/surgery* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

BACKGROUND: To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study. RESULTS: Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9-16.3) months for patients with HPS and 15.1 (95% CI, 7.3-22.9) months for patients without HPS, which is not a significant difference ( P  = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0-12.8] vs. 8.4 [95% CI, 3.6-13.1] months; P  = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003-1.064]; P  = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011-3.260]; P  = 0.046) were identified to be the independent prognostic factors of OS. CONCLUSION Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Prospective Studies ; Liver Neoplasms/pathology* ; Prognosis ; Hepatopulmonary Syndrome/therapy* ; Prevalence ; Treatment Outcome ; Retrospective Studies

Purpose: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective:To investigate the preventive efficacy of pirfenidone in esophageal stent-related restenosis and the related underlying mechanisms.Methods:Twenty-four rats underwent esophageal stent placement were included in this study. The rats were randomly assigned to three groups, with 8 rats in each group. The three groups were set to receive placebo, 150 mg/kg pirfenidone and 300 mg/kg pirfenidone daily by oral administration for 28 days, respectively. Twenty-eight days after stent placement, the stented esophagi were harvested for histological examinations. The number of epithelial layers, the thickness of submucosal fibrosis, the percentage of granulation tissue area, the degree of inflammatory cell infiltration, the degree of collagen deposition, and the α-SMA staining scores were evaluated. One-way ANOVA was performed for the statistical comparison of the number of epithelial layers, the degree of inflammatory cell infiltration, the degree of collagen deposition and the α-SMA staining scores among these three groups. The Kruskal-Wallis H test was used for comparison of the thickness of submucosal fibrosis and the percentage of granulation tissue area among the three groups. Results:Gross pathological findings showed that both pirfenidone groups had significantly less luminal fibrotic tissue formation and restenosis than placebo group. The percentage of granulation tissue areas in placebo group, 150 mg/kg and 300 mg/kg pirfenidone groups were 57.23%±25.68%, 21.80%±6.65% and 12.18%±6.37%, respectively. Both pirfenidone groups showed significantly less granulation tissue areas than placebo group ( P<0.01). The degree of inflammatory cell infiltration, the degree of collagen deposition and the α-SMA staining scores were 3.28±0.55, 3.38±0.63 and 2.75±0.38 in placebo group, 2.30±0.46, 2.36±0.58 and 2.00±0.42 in 150 mg/kg pirfenidone group, and 1.86±0.38, 1.91±0.41 and 1.57±0.28 in 300 mg/kg pirfenidone group, respectively. Both pirfenidone groups showed significantly less inflammatory cell infiltration, collagen deposition and α-SMA staining scores than placebo group ( P<0.01). Conclusion:Pirfenidone can suppress esophageal stent-related restenosis in rats by significantly inhibiting inflammation, myofibroblast activation and proliferation, and fibrotic tissue formation.