Review on hotspots, challenges, and the future of river management strategies in China

Aim: The study aimed to understand the status of pesticide residues in lactating mother’s milk, identify factors involved in the transfer of pesticide residues and health risk to infants.Methodology: A total of 153 lactating mothers were selected from four agro-climatic zones varying from subtropics to dry temperate high hills for residue analysis. The extraction and cleanup were performed by QuEChERS method. Residue were analysed by Shimadzu 2010 GC equipped with a 63Ni ECD and confirmed by Shimadzu QP 2010 Plus GC-MS through selected ion monitoring (SIM) mode. The EDI was compared with the ADI of Σ-DDT (0.02 mg kg-1 body wt d-1) established by FAO/WHO for neonate risk assessment from different pesticides. Results: The mean DDT levels in breast milk were 0.240 mg kg-1 fat (0.011 mg kg-1 milk), 0.171 mg kg-1 fat (0.010 mg kg-1 milk), 0.026 mg kg-1 fat (0.001 mg kg-1 milk) and below detectable limit (BDL) in Zones I (subtropical), II (sub-humid foothills), III (wet temperate high hills) and IV (dry temperate high hills), respectively. The residue levels decreased with an increase in parity and increased with the age or weight of the mothers. The Σ-DDT residues were higher in rural women (0.011 mg kg-1 milk) than urban (0.005 mg kg-1 milk), housewives (0.009 mg kg-1 milk) than working women (0.007 mg kg-1 milk) and lacto-vegetarians (0.007 mg kg-1 milk) than omnivorous mothers (0.005 mg kg-1 milk). The estimated daily exposure of neonates to Σ-DDT was considerably lower (0.001 mg kg-1 body weight) than the ADI (0.02 mg kg-1 body weight) indicating no appreciable risk to one-month-old infants. Interpretation: Mother's rural habitation, demography and primiparous parity seem to be the major cause for transfer of pesticide residues. The study also advocates a constant bio-monitoring of lactating mothers’ milk for pesticide residues owing to the continuous changes in the pesticide usage pattern.

Nonsteroidal anti-inflammatory drugs induced diaphragm disease: a report of 3 cases and literature review

Multiple strictures of small bowel induced by nonsteroidal anti-inflammatory drugs (NSAIDs), were known as diaphragm disease. The purpose of these case reports is to present 3 cases of diaphragm disease of small bowel and summarize the clinical features of this disease entity. A 34-year-old man, a 63-year-old man, and a 66-year-old woman were admitted to Daegu Catholic University Medical Center because of recurrent intestinal obstructions. Two of these patients had taken heavy NSAIDs use. Capsule endoscopy was performed in all cases and the all capsules were retained by circumferential strictures of the ileum. Segmental resection of the strictures was performed in 2 patients and 1 underwent just enterotomy and capsule removal. In conclusion, clinicians should be aware that diaphragm disease might be a cause of small bowel obstruction especially in patients receiving long term NSAIDs therapy.

A Rare Case of Intramural Müllerian Adenosarcoma Arising from Adenomyosis of the Uterus

Müllerian adenosarcomas usually arise as polypoid masses in the endometrium of post-menopausal women. Occasionally, these tumors arise in the cervix, vagina, broad and round ligaments, ovaries and rarely in extragenital sites; these cases are generally associated with endometriosis. We experienced a rare case of extraendometrial, intramural adenosarcoma arising in a patient with adenomyosis. A 40-year-old woman presented with sudden-onset suprapubic pain. The imaging findings suggested leiomyoma with cystic degeneration in the uterine fundus. An ill-defined ovoid tumor with hemorrhagic degeneration, measuring 7.5 cm in diameter, was detected. The microscopic findings showed glandular cells without atypia and a sarcomatous component with pleomorphism and high mitotic rates. There was no evidence of endometrial origin. To recognize that adenosarcoma can, although rarely, arise from adenomyosis is important to avoid overstaging and inappropriate treatment.

Prophylactic extended-field irradiation with concurrent chemotherapy for pelvic lymph node-positive cervical cancer

PURPOSE: This study aimed to evaluate whether prophylactic extended-field pelvic radiotherapy (EF-PRT) yields better results than standard whole pelvic radiotherapy (WPRT) in patients with pelvic lymph node-positive cervical cancer treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 126 cases of stage IB-IVA cervical cancer that had pelvic lymph node involvement in magnetic resonance imaging and were treated with CCRT between 2000 and 2016 were reviewed. None of the patients had paraaortic lymph node (PALN) metastases. The patients were classified to two groups, namely, those treated with EF-PRT, including prophylactic para-aortic radiotherapy, and those treated only with WPRT. The median dose to the PALN area in patients treated with EF-PRT was 45 Gy. All patients received concurrent cisplatin-based chemotherapy. RESULTS: Overall, 52 and 74 patients underwent EF-PRT and WPRT, respectively. Patient characteristics and irradiated dose were not significantly different, except the dose to the para-aortic area, between the two groups. The median follow-up period was 75.5 months (range, 5 to 195 months). The 10-year cumulative recurrence rate of PALN for EF-PRT vs. WPRT was 6.9% and 10.1% (p = 0.421), respectively. The 10-year disease-free survival and overall survival for EF-PRT vs. WPRT were 69.7% vs. 66.1% (p = 0.748) and 71.7% vs. 72.3% (p = 0.845), respectively. Acute gastrointestinal complications were significantly higher in EF-PRT (n = 21; 40.4%) than WPRT (n = 26; 35.1%) (p = 0.046). Late toxicities were not significantly different in both groups. CONCLUSION: In this study, prophylactic radiotherapy for PALN does not have an additional benefit in patients with pelvic lymph node-positive cervical cancer treated with CCRT.

Molecular Testing for Gastrointestinal Cancer

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

Adult granulosa cell tumor presenting with massive ascites, elevated CA-125 level, and low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography

Adult granulosa cell tumors (AGCTs) presenting with massive ascites and elevated serum CA-125 levels have rarely been described in the literature. An ovarian mass, massive ascites, and elevated serum CA-125 levels in postmenopausal women generally suggest a malignant ovarian tumor, particularly advanced epithelial ovarian cancer. AGCT has low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography due to its low metabolic activity. In the present report, we describe a case of an AGCT with massive ascites, elevated serum CA-125 level, and low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography.

CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats

The efficacy of endothelin receptor antagonists in protecting against myocardial ischemia/reperfusion (I/R) injury is controversial, and the mechanisms remain unclear. The aim of this study was to investigate the effects of CPU0123, a novel endothelin type A and type B receptor antagonist, on myocardial I/R injury and to explore the mechanisms involved. Male Sprague-Dawley rats weighing 200-250 g were randomized to three groups (6-7 per group): group 1, Sham; group 2, I/R + vehicle. Rats were subjected to in vivo myocardial I/R injury by ligation of the left anterior descending coronary artery and 0.5 percent sodium carboxymethyl cellulose (1 mL/kg) was injected intraperitoneally immediately prior to coronary occlusion. Group 3, I/R + CPU0213. Rats were subjected to identical surgical procedures and CPU0213 (30 mg/kg) was injected intraperitoneally immediately prior to coronary occlusion. Infarct size, cardiac function and biochemical changes were measured. CPU0213 pretreatment reduced infarct size as a percentage of the ischemic area by 44.5 percent (I/R + vehicle: 61.3 ± 3.2 vs I/R + CPU0213: 34.0 ± 5.5 percent, P < 0.05) and improved ejection fraction by 17.2 percent (I/R + vehicle: 58.4 ± 2.8 vs I/R + CPU0213: 68.5 ± 2.2 percent, P < 0.05) compared to vehicle-treated animals. This protection was associated with inhibition of myocardial inflammation and oxidative stress. Moreover, reduction in Akt (protein kinase B) and endothelial nitric oxide synthase (eNOS) phosphorylation induced by myocardial I/R injury was limited by CPU0213 (P < 0.05). These data suggest that CPU0123, a non-selective antagonist, has protective effects against myocardial I/R injury in rats, which may be related to the Akt/eNOS pathway.

Gabapentin for overactive bladder and nocturia after anticholinergic failure

INTRODUCTION: We reviewed our experience with the use of gabapentin to treat symptoms of overactive bladder (OAB) and nocturia in patients who have failed conventional anticholinergic therapy. METHODS: Thirty-one patients referred to us with refractory (OAB) and/or nocturia were treated with oral gabapentin. All the patients had tried or remained on antimuscarinic drugs during treatment. Twenty-four of 31 complained of bothersome symptoms during day and night and the other seven had primary complaints of nocturia. Initial gabapentin doses ranged from 100-300 mg at bedtime. Dose was slowly titrated up to 3,000 mg based on patients' symptomatology and tolerability. RESULTS:The mean age was 51 years old (range 27-78). There were 13 men and 18 women. The median steady state dose chosen by the patient after initial titration was 600 mg/day. Fourteen of 31 patients reported subjective improvement of their frequency and 8 have been on the medication for over 12 months with persistent efficacy. For the 14 improved patients, mean frequency/24 hours decreased from 14.1 ± 2.2 to10.0 + 2.1. Three patients with primary nocturia reported improvement from a mean of 4.0 ± 1.3 to 1.0 ± 0.3 episodes/night. Six patients stopped taking the drug within one month due to side effects mostly described as drowsiness or lethargy. CONCLUSION: Fourteen of 31 patients with refractory (OAB) and nocturia improved with oral gabapentin. Gabapentin was generally well tolerated and can be considered in selective patients when conventional modalities have failed.