HuaFu Shengji is the primary traditional Chinese medicine (TCM) therapy for treating chronic skin ulcer. The high activities of the protein enzyme in the wound fluids is one of the main cause of healing delay. In order to investigate the effect of TCM Zhuhong ointment for promoting wound healing. This research focused on its influence on matrix metalloproteinase (MMP) activities in wound fluids with TCM Yang syndromes, directly on the activated MMP-1,2 activities in vitro and on MMP-1,-2,-9 production by HSF. 8 wound fluid samples were collected, which were diagnosed Yang Syndromes in TCM. Wound fluid activities of MMP-2 and MMP-9 were measured by gelatin zymogram assay. MMP-1 and MMP-2 activities in vitro were measured by substrate cleavage. CCK-8 was used to observe the toxicity of Zhuhong ointment on HSF. MMP-1,-2,-9 production by HSF were detected by confocal microscope. Zhuhong ointment from 1 to 25 g x L(-1) obviously inhibited MMP-2 activity in wound fluid. When Zhuhong ointment was over 5 g x L(-1), it showed significantly inhibitory effect on wound fluid MMP-9 activity. In vitro study, when the mercury concentration was 320 mg x L(-1), Zhuhong ointment solution directly inhibited both MMP-1 activity and MMP-2. But mercury concentration from 0.51-2.56 mg x L(-1), it could activate MMP-1 activity, and from 0.51-64 mg x L(-1), activate MMP-2 activity instead. The mercury concentration when Zhuhong ointment saturated in DMEM was 39.6 mg x L(-1). When the mercury concentration was over 1.23 mg x L(-1), Zhuhong ointment showed toxicity to HSF. At 1.23, 0.62, 0.31 mg x L(-1) of mercury concentration, it increased MMP-1 expression by HSF, and at 1.23, 0.62 mg x L(-1), decreased MMP-2 expression. However, at 1.23, 0.62, 0.31 mg x L(-1), it decreased MMP-9 expression. At higher concentration, Zhuhong ointment can inhibit MMP-2, MMP-9 activities in wound fluid with dose-dependent way and show a direct inhibitory effect on activated MMP-1 and MMP-2 in vitro. But at a lower concentration, it showed two-way adjustment, with increased MMP-1, MMP-2 activities and its expression by HSF and decreased MMP-9 activity.
Body Fluids ; enzymology ; Cells, Cultured ; Dermatitis ; drug therapy ; enzymology ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Fibroblasts ; drug effects ; enzymology ; physiology ; Humans ; Matrix Metalloproteinase 1 ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Wound Healing ; drug effects

BACKGROUNDThe elevated matrix metalloproteinase (MMP) activity is an important cause of chronic wound healing failure. Arsenolite, whose main component is arsenic trioxide (As2O3), is a common traditional Chinese medicine wildly used in treating chronic wounds; it can remove necrotic tissue and promote tissue regeneration. This research was designed to evaluate the effects of As2O3 on production and activities of MMP-1, MMP-2 and MMP-9, and on regulation of its signal transduction pathway in human skin fibroblasts (HSFb) and human monocyte line (THP-1 cells) that were in an inflammatory state.

METHODSWe established three cell models; HSFb activated by TNF-α, THP-1 cells activated by phorbol 12-myristate 13-acetate (PMA) and an HSFb-THP-1 co-culture system. Three cell models was cultured with As2O3 for 24 hours. The levels of MMP-1, MMP-2, MMP-9, TNF-α and IL-1β in the cell culture supernatants were assayed by ELISA. The mRNA expressions of MMP-1, MMP-2 and MMP-9 were determined by RT-PCR. The activities of MMP-2 and MMP-9 were tested by Gelatin zymography assays. The phosphorylation levels of ERK1/2 and p38MAPK were assayed by Western blotting.

RESULTSAs2O3 inhibited the expression of MMP-1, MMP-2 and MMP-9 mRNA, the secretion and activity of MMP-1, MMP-2 and MMP-9 in HSFb and THP-1 cells in the inflammatory state (P < 0.05 and P < 0.01 respectively). It also inhibited the secretion of TNF-α and IL-1β in THP-1 cells and in the co-culture system (P < 0.05 and P < 0.01, respectively). It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFb and THP-1 cells (P < 0.05 and P < 0.01, respectively).

CONCLUSIONSAs2O3, as a main component of arsenolite, can inhibit the production of MMPs by HSFb and THP-1 cells in an inflammatory state through inhibiting the release of inflammatory factors and the activation of the MAPK cascade pathway. This may be a possible mechanism for arsenolite healing chronic wounds.

Arsenicals ; pharmacology ; Cell Line ; Cells, Cultured ; Electrophoresis, Polyacrylamide Gel ; Fibroblasts ; drug effects ; enzymology ; Humans ; Interleukin-1 ; metabolism ; Matrix Metalloproteinase 1 ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Monocytes ; drug effects ; enzymology ; Oxides ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the diagnostic value of ThinPrep cytology test (TCT) in lung cancer.

METHODS353 cases of bronchoalveolar lavage fluid (BALF) and(or) bronchial brushing cytology (192 cases from lung cancer patients and 161 cases from benign lung disease patients) were detected with TCT and method of direct smear, respectively. The sensitivity and specificity of two methods was compared.

RESULTSThe sensitivity and specificity of TCT were 39.6% and 99.4%. And which of direct smear method were 8.3% and 100%, respectively. The sensitivity of TCT was significantly higher than that of method of direct smear in the diagnosis of lung cancer (P < 0.01). There were 71 patients who underwent BALF and bronchial brushing cytology simultaneously, the sensitivity of TCT of BALF was higher than that of bronchial brushing cytology (P < 0.05). Of the 69 cases which had both TCT and histopathological results, TCT and pathology concordance rate was 84.1%.

CONCLUSIONTCT has more diagnostic value in lung cancer; BALF is more preponderant than bronchial brushing cytology by TCT in the diagnosis of lung cancer.

Adenocarcinoma ; diagnosis ; pathology ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Bronchi ; pathology ; Bronchoalveolar Lavage Fluid ; cytology ; Bronchoscopy ; Carcinoma, Small Cell ; diagnosis ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; pathology ; Cytodiagnosis ; methods ; Cytological Techniques ; methods ; Female ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Male ; Middle Aged ; Pneumonia ; diagnosis ; pathology ; Sensitivity and Specificity ; Tuberculosis, Pulmonary ; diagnosis ; pathology ; Young Adult

Objective The IAEA report No.483 describes the latest method of small field dosimetry.The field output factor measurement and correction methods are used to improve the accuracy and consistency of the measurement results for different type detectors.Methods The field output factors from 0.6 cm×0.6 cm to 10 cm× 10 cm were measured using IBA's CC13 ionization chamber,CC01 ionization chamber,PFD semiconductor detector,EFD semiconductor detector and Razor semiconductor detector,respectively.The field output correction factors were used to correct the measurement result.Results Compared with the corrected data,the results of ionization chamber are mainly affected by the volume averaging and the fluence perturbation effect,lead to the measurement result which is 4.70％ lower at 0.6 cm × 0.6 cm;The results of Shielded semiconductors are mainly affected by fluence perturbation effect,lead to the measurement result which is 4.80％ higher at 0.6 cm × 0.6 cm.The results of unshielded semiconductors are mainly affected by energy response and fluence perturbation effect,resulting in lower measurement results at the field size＞0.8 cm×0.8 cm,2.10％ lower at field size of 1.5 cm× 1.5 cm,higher measurement results at field size＜0.8 cm×0.8 cm and 1.1％ higher at field size of 0.6 cm×0.6 cm.Before the correction,the measurement results from different types of detectors are quite different,average standard deviation is 0.016 6.After the correction,the difference among the detectors is significantly reduced,average standard deviation is 0.006 6.Conclusions For detectors such as ionization chambers and semiconductors,the field output correction factors can be used to correct the output factors of the small field to improve the accuracy and consistency of the measurement results.

Objective improve the accuracy of the measurement results by using the field output factor measurement method based on daisy-chaining.Methods The Varian Edge Accelerator 6 MV X-ray data were measured using the IBA CC13 ionization chamber, IBA CC01 ionization chamber, IBA Razor semiconductor detector , IBA EFD semiconductor detector and Gafchromic EBT 3 film , respectively. Results Compared with the daisy-chaining measurement method,the results obtained by the conventional measurement method using CC13 were smaller. The deviation value was 16. 71% in the 1 cm × 1 cm field. The measurement results in a larger field via CC01 were bigger with a deviation of 8. 39% in the 40 cm × 40 cm filed. The measurement results via Razor in a larger field were larger with a deviation of 9. 40% in the 40 cm × 40 cm field. The measurement results were similar between EFD and Razor with a deviation of 9. 14% in the 40 cm × 40 cm field. The results of the film measurement were equivalent to those obtained from the daisy-chaining method in a field of＞ 1 cm × 1 cm with a deviation within 1. 60%,whereas the deviation was increased to 3. 13% in the 1 cm× 1 cm field. The results were consistent with daisy-chaining measurement if the 3 cm × 3 cm or 4 cm × 4 cm fields were selected as the intermediate fields with the maximum deviation of 0. 29%. Conclusions For the detectors with changing response along with the field size,daisy-chaining measurement method can be utilized to extend the measurement range and improve the accuracy of the measurement results.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*