[Difference analysis of somatic mutations between deficient mismatch repair and proficient mismatch repair gene related with colorectal cancer].

Objective: To analyze the difference of somatic mutation of DNA mismatch repair (MMR) protein deletion (dMMR) /integrity (pMMR) in colorectal cancer (CRC). Methods: A total of 93 cases of paraffin pathological tissue derived from CRC patients underwent surgical treatment and postoperative routine immunohistochemical diagnosed as dMMR in the Second Affiliated Hospital of Zhejiang University Medical College from January 2015 to January 2017 were collected and conducted the second-generation sequencing test. The expressions of 4 MMR proteins (MLH1, MSH2, MSH6 and PMS2) in CRC tissue were detected by immunohistochemistry method, and the immunohistochemistry results were re-interpreted according to the American Association of Pathologists (CAP) standard. Second-generation sequencing technology was used to detect somatic mutations of 41 genes in 93 cases of paraffin pathological CRC tissue, and Fisher's exact test was used to analyze the gene mutation differences between groups. Results: After re-evaluation according to CAP standard, 31 cases were divided into pMMR group and 62 cases in dMMR group among the 93 CRC patients. The medium number of gene mutations in the dMMR group was 9.5, higher than 3.0 of the pMMR group (P<0.001). Somatic mutation differences were found in 17 genes between the dMMR and pMMR groups, including breast cancer susceptibility genes 1 (BRCA1), BRCA2, MLH1, PDGFRA, PIK3CA, APC, ATM, KIT, MET, PMS2, MSH6, POLE, MSH2, PTCH1, epidermal growth factor receptors (EGFR), TP53 and ERBB2 genes. The pathogenic somatic mutation rates of BRAF, MLH1, MSH2 and MSH6 in the dMMR group were higher than those in the pMMR group [21.0% (13/62) vs 9.7% (3/31), 9.7% (6/62) vs 0 (0/31), 21.0% (13/62) vs 0 (0/31), 22.6% (14/62) vs 0 (0/31), P<0.05]. The mutation rate differences of BLM N515fs, BRAF V600E, PTCH1 R1308fs and KRAS G13D sites were statistically different between the dMMR group and the pMMR group [22.6% (14/62) vs 0 (0/31), 19.4% (12/62) vs 3.2% (1/31), 11.3% (7/62) vs 0 (0/31), 16.1% (10/62) vs 3.2% (1/31), P<0.05]. The mutation rates of 3 uncommon sites including BLM N515fs, MSH6 F1088fs and PTCH1 R1308fs were 28.2% (11/39), 15.4% (6/39) and 15.4% (6/39) in patients with dMMR who were missing MLH1 and PMS2 together, statistically different from all of 0 (0/31) in pMMR patients (P<0.05). Conclusions: CRC Patients with dMMR have more related gene somatic mutations. The BRAF V600E mutation is closely related to dMMR. KRAS G13D, BLM N515fs and PTCH1 R1308fs mutation sites are also associated with the expression of MMR proteins.

Atrazine contamination in agricultural soils from the Yangtze River Delta of China and associated health risks.

Atrazine is one of the most widely applied and persistent herbicides in the world. In view of limited information on the regional contamination of atrazine in soils in China, this study investigated the spatial distribution and environmental impacts of atrazine in agricultural soils collected from the Yangtze River Delta (YRD) as an illustrative analysis of rapidly developing regions in the country. The results showed that the concentrations of atrazine in the YRD agricultural soils ranged from <1.0 to 113 ng/g dry weight, with a mean of 5.7 ng/g, and a detection rate of 57.7 % in soils. Pesticide factory might be a major source for the elevated levels of atrazine in Zhejiang Province. The contamination of atrazine was closely associated with land use types. The concentrations and detection rates of atrazine were higher in corn fields and mulberry fields than in rice paddy fields. There was no significant difference in compositions of soil microbial phospholipids fatty acids among the areas with different atrazine levels. Positive relationship (R = 0.417, p < 0.05, n = 30) was observed between atrazine and total microbial biomass. However, other factors, such as soil type and land management practice, might have stronger influences on soil microbial communities. Human health risks via exposure to atrazine in soils were estimated according to the methods recommended by the US EPA. Atrazine by itself in all the soil samples imposed very low carcinogenic risks (<10-6) and minimal non-cancer risks (hazard index <1) to adults and children.

Chinese herbal medicine for functional constipation: a randomised controlled trial.

1. This was an 18-week prospective, randomised, double-blind, placebo-controlled clinical study on a Chinese herbal medicine--ma zi ren wan (MZRW)--for the treatment of functional constipation. 2. 120 subjects with functional constipation (Rome III criteria) were randomised (60 per arm) into the MZRW and placebo groups. Respective responder rates for the two groups were 43.3% and 8.3% during treatment, and 30.0% and 15.0% in the follow-up period (p<0.05). The MZRW group was superior to the placebo group in terms of increased complete spontaneous bowel movement as well as reduction in severity of constipation, straining at evacuation, and use of rescue therapy. No serious adverse effects were reported. 3. The dose of MZRW (7.5 g bid) was determined in a separate clinical trial. This study entailed a dose determination study and then a placebo-controlled clinical trial and can be a good reference for future studies.

Prediction of active ingredients and mechanism of Siwei Jianbu decoction in the treatment of atherosclerosis by network pharmacology.

OBJECTIVE: Siwei Jianbu Decoction (SJD) has been shown to be effective in treating atherosclerosis (AS). However, its mechanism is still unclear. MATERIALS AND METHODS: The active compounds and targets of SJD were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The target genes of AS were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, DrugBank, and Therapeutic Target (TTD) databases. Interactions between drug and disease targets were analyzed to obtain common targets. Subsequently, "herb-compound-target" and protein-protein interaction (PPI) networks were constructed and analyzed using the Cytoscape software. Thereafter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed by DAVID online database. Then, the results were visualized by R software. Finally, molecular docking was performed using AutoDockTools and PyMOL software. RESULTS: A total of 61 active compounds and 377 target genes were identified for SJD, as well as 726 target genes for AS. Interactive analyses revealed 126 common genes between SJD and AS. Quercetin, ellagic acid, baicalein, and kaempferol were the 4 key compounds in SJD. Moreover, eight key targets, namely TNF, SRC, RELA, AKT1, STAT3, JUN, MAPK1 and FOS were found. Results from enrichment analysis indicated that the MAPK pathway may play an important role. The analysis of molecular docking revealed that the key compounds formed strong bonds with their corresponding key targets. CONCLUSIONS: These findings indicate that SJD could prevent AS by inhibiting the expression of genes associated with MAPK pathway such as MAPK1, RELA, and FOS.

Percutaneous revascularization for atherosclerotic renal artery stenosis: a meta-analysis.

OBJECTIVE: This study investigates whether medication therapy alone is as effective and safe as percutaneous revascularization (PR) in patients with atherosclerotic renal artery stenosis (ARAS). MATERIALS AND METHODS: The Embase, PubMed, and Cochrane Library databases were searched from their inception to July 31, 2021, for randomized controlled trials (RCTs) reporting PR for ARAS. RevMan 5.3 was employed to analyze the retrieved articles. RESULTS: Eight studies with a total of 2,225 ARAS patients were included in this analysis, demonstrating that PR and medication therapy alone had a similar effect on both systolic [mean difference (MD)= 0.19, 95% CI: -1.64- 2.02] and diastolic blood pressure (MD= -0.44, 95% CI: -1.68-0.80). Meanwhile, there were no differences in all-cause mortality [Odds ratio (OR) = 0.89, 95% CI: 0.70-1.14], stroke (OR = 0.84, 95% CI: 0.55-1.31), congestive heart failure (OR = 0.89, 95% CI: 0.67-1.19), and perioperative complications (OR = 0.87, 95% CI: 0.68-1.12). CONCLUSIONS: Medication therapy alone is as effective and safe as PR.

[A prognostic nomogram for metastasized colorectal cancer patients treated with cetuximab].

Objective: To identify the prognostic factors in metastatic colorectal cancer (mCRC) patients treated with cetuximab and establish a prognostic nomogram and validate its accuracy. Methods: A retrospective case-control study was conducted. Patients were selected as following criteria: patients with metastatic colorectal cancer(mCRC), which primary site confirmed by pathology and metastatic lesions confirmed by CT or MRI with at least one measurable and evaluable target lesion; patients' expected survival longer than 3 months; Eastern Cooperative Oncology Group (ECOG) score between 0 to 2; patients have signed informed consent; both KRAS and NRAS genes were wild-type; and at least 2 cycles of cetuximab combined with chemotherapy as the first-line regimen. Patients who met the following criteria were excluded: patients with incomplete clinicopathological and follow-up data; patients with severe diseases of vital organs such as heart, brain, lung, kidney, or other advanced malignant tumors; patients without informed consent. According to the above criteria, clinicopathological data of 95 patients with mCRC admitted in the Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine for first-line treatment with cetuximab from January 2010 to January 2017 were analyzed retrospectively. The Cox proportional hazards model was used to analyze the clinicopathological factors to determine the independent prognostic factors for progression-free survival(PFS). The R software was adopted to establish a prognostic nomogram model. Then, the nomograms of 6-month, 12-month and 18-month progression-free survivals (PFS) were drawn, and compared with the reality. The internal validation and accuracy of the nomogram were determined by the Bootstrap method and also the calculated concordance index (C-index). Results: The median follow-up time was 16.5 (2-43) months and the median PFS was 8.5 months. PFS at 6-,12- and 18-month was 73.7%, 35.8%, and 17.9%, respectively. ECOG score of 1-2 (HR=5.733, 95% CI:2.408-13.649, P<0.001), primary tumor was located in the ileocecal region (HR=5.880, 95% CI:1.645-21.023, P=0.006), Ki-67 index ≥45% (HR=3.574,95% CI:1.403-9.108,P=0.008), baseline D-dimer level ≥345 mg/L (HR=2.536,95% CI:1.531-7.396, P=0.012), NLR≥2.8 (HR=5.573,95% CI:2.107-14.740,P=0.001) and the combined treatment for FOLFOX (HR=0.465, 95% CI: 0.265-0.817, P=0.008) were independent risk factors for PFS of mCRC patients (all P<0.05). These independent risk factors were taken into account to construct a nomogram prediction model. The bootstrap method was used to perform internal validation, and the C-index of the nomogram prediction model in this study was 0.67 (95% CI: 0.64~0.71). The 6-, 12- and 18-month PFS predicted by the nomogram were consistent with the actual values. Conclusion: The nomogram model constructed by ECOG score, primary tumor site, Ki-67 index, baseline D-dimer level, baseline NLR and chemotherapy regimen may predict the prognosis of mCRC patients treated with cetuximab more accurately and individually, which can assist clinicians in making treatment decisions.

Antibiotics in the agricultural soils from the Yangtze River Delta, China.

This study focused on the occurrence and spatial distribution of 13 common antibiotics in the agricultural soils of the Yangtze River Delta (YRD), China. Antibiotics were detected in all the 241 soil samples (i.e., 100% detection rate) with the total concentrations ranging from 4.55 to 2,010 ng/g dry weight. The concentrations of three antibiotic classes decreased in the order: quinolones (mean 48.8 ng/g) > tetracyclines (mean 34.9 ng/g) > sulfonamides (mean 2.35 ng/g). Ciprofloxacin was the prevalent compound with a mean concentration of 27.7 ng/g, followed by oxytetracycline (mean of 18.9 ng/g). A distinct spatial distribution was observed, where high concentrations of antibiotics were detected in the sites adjacent to the livestock and poultry farms. The potential sources of antibiotics in the agricultural soils were the application of manure and wastewater irrigation in this region. Risk assessment for single antibiotic compound indicated that tetracyclines and quinolones could pose a potential risk, in which doxycycline and ciprofloxacin had the most severe ecological effect in the agricultural soils. Antibiotic resistance genes (ARGs), such as tetA, sulI, and qnrS, were detected in 15 analyzed soil samples, and sulI showed significant correlations with quinolones, tetracyclines, copper, and zinc. Further studies on the distribution of other ARGs in agricultural soil at a region-scale are needed for the risk management of extensively used antibiotics and major ARGs.

Accumulation and distribution of polycyclic aromatic hydrocarbons in rice (Oryza sativa).

Various tissues of rice plants were sampled from a PAH contaminated site in Tianjin, China at different growth stages of the ripening period and analyzed for PAHs. PAHs were much higher in roots than in the exposed tissues. Grains and internodes accumulated much smaller amounts of PAHs than leaves, hulls or ear axes. No specific gradient trends along roots, stem, ear axes, and grains were observed, suggesting that systematic translocation among them is unlikely. Over the ripening period, PAH concentrations were increased in rice roots and decreased in most above-ground tissues. Significant correlations between PAH and lipid contents can only be observed during full mature stage. The spectra of individual PAH compounds in rice organs including roots were similar to those in air, rather than those in soil. There was also a significant correlation between bioconcentration factor (BCF, plant over air) and octanol/air partitioning coefficient (Koa).

Diamagnetic measurements based on the compensation of TF current diffusion in J-TEXT.

Due to the existence both of toroidal ripples and toroidal field (TF) current diffusion, the toroidal flux changes with time when the TF current is at the flat-top. A diamagnetic measurement based on the compensation of TF current diffusion has been built in J-TEXT to solve this problem. The measurement system includes a double-loop installed in the vacuum vessel and an array of small printed circuit board (PCB) magnetic probes placed on the mid-plane of one TF coil. A model was proposed to analyze and compensate the effect of TF current diffusion. Experiment results show that the residual flux is about 1 × 10-4 Wb after the compensation and it can meet the need of diamagnetic measurement in J-TEXT.

Spectrophotometric determination of trace amounts of cadmium and zinc in waste water with 4-(2-pyridylazo)-resorcinol and mixed ionic and non-ionic surfactants.

A spectrophotometric method for determination of trace amounts of cadmium and zinc in waste water with PAR and mixed ionic and non-ionic surfactants is described. The interferences of foreign ions can be eliminated by masking with a mixture of triethanolamine, potassium fluoride, ethylenediamine and sodium hexametaphosphate. By virtue of the difference between the absorbances before and after addition of a little sodium diethyldithiocarbamate, cadmium and zinc can be determined directly in aqueous solution without separation. Beer's law is obeyed for 0-20 microg of Cd or 0-12 microg of Zn in 25 ml of solution. The apparent molar absorptivities at 505 nm are 8.65 x 10(4) l.mole(-1).cm(-1) for Cd and 8.21 x 10(4) l.mole(-1).cm(-1) for Zn. Results obtained by applying the proposed method to waste-water samples agree well with those obtained by atomic-absorption spectrophotometry.

Spectrophotometric determination of chromium in waste water and soil.

The reaction of Cr(VI) with o-nitrophenylfluorone (NPF) in presence of cetyltrimethyl-ammonium bromide (CTMAB) to form a purplish red complex at pH 4.7-6.6 by heating at 50 degrees for 10 min has been investigated. The composition of the complex is 1:2:2 [Cr(VI):NPF:CTMAB], the wavelength of maximum absorbance is 582 nm. The molar absorptivity is 1.11 x 10(5)1.mole(-1).cm(-1). Beer's law is obeyed up to 0.2 microg ml Cr(VI) concentration. The interference of several ions, including Cu(2+), Fe(3+) and Al(3+), is eliminated by addition of a masking mixture containing KF, DCTA and tartrate. A new sensitive method for determination of chromium in waste water and soil is presented.

Biochemical and morphological changes in the lenses of selenium and/or vitamin E deficient rats.

The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and free radicals were measured, and the morphological changes were observed in the lens of control rats, selenium-deficient (SeD) and/or vitamin E deficient (VED) rats. The activities of GSH-Px in the lens of SeD rats decreased significantly. The GSH-Px activities of lens were positively related to erythrocytes selenium level. There was a free radical at g = 2.0015 in the rat lens of all groups, but the content of free radicals in the lens of SeD group was significantly higher than that of the control group. The free radical content of lens was negatively related to erythrocytes selenium level, as well as the GSH-Px activities in the lens. In vitro, ultraviolet radiation caused the generation of another kind of free radical (g = 2.0097) in the lens of all groups, but the amount of the free radical in the lens of the SeD group was also significantly higher than that of the control group. The activities of SOD and GSSG-R in VED rat lens were significantly decreased. The amount of MDA in the lens of SeD and/or VED rats were significantly increased. The results showed that the decrease of antioxidative capability in the lenses of SeD and/or VED rats accelerated the lipid peroxidation and generation of free radicals. Although only early morphological changes in SeD and/or VED rat lens were observed, it is considered that selenium and vitamin E deficiency may be involved in the occurrence of cataract.

Water solubility enhancements of pyrene by single and mixed surfactant solutions.

Water solubility enhancements of pyrene by both single-surfactant and mixed-surfactant solutions were compared and evaluated. The solubility of pyrene in water was greatly enhanced by each of Triton X-100 (TX100), Triton X-405 (TX405), Brij 35 and SDS, in which the water solubility enhancements increased with increasing surfactant concentrations. The extent of solubility enhancements at surfactant concentrations below the CMC is the order of TX100 > Brij 35 > TX405 > SDS; the sequence at surfactant concentrations above the CMC is TX100 > Brij 35 > SDS > TX405. Pyrene was solubilized synergistically by anionic-nonionic mixed surfactant solutions, especially at low surfactant concentrations. The synergistic power of the mixed surfactants is SDS-TX405 > SDS-Brij 35 > SDS-TX100. The synergism as noted is attributed to increasing Kmc is and/or decreasing the CMC of the mixed surfactant solution. For SDS-TX405 and SDS-Brij 35 mixed surfactant solutions, an increase in Kmc is coupled with a decrease in the CMC; for SDS-TX100, only a decreased in the CMC value is noted. Mixed-surfactant solutions may improve the performance of the surfactant-enhanced remediation (SER) of soils by increasing the bioavailability and biodegradation of non-aqueous-phase organic pollutants and reducing the level of surfactant pollution and remediation expenses.

Survey of polycyclic aromatic hydrocarbons (PAHs) in arterial street air of Hangzhou.

The presence of particulate and vapor PAHs, SO2 and NOx and other interrelated conditions (temperature, traffic intensity and wind velocity) were investigated in the arterial street air of Hangzhou. The concentration of the nine PAHs in the air was mean to 11.7 micrograms/m3, and the content of benzo(a) pyrene was up to 0.108 microgram/m3. The contents of PAHs in the sampling sites were in good relation to the traffic intensity, and would be also affected by the terrain and meteorological conditions. The occurrences of PAHs in ambient air were mainly affected by their physical, chemical characters and temperature. The three- and four-ring PAHs (MW < or = 228) mainly existed in the vapor phase and the five-ring PAHs (MW > 228) existed predominately in the particulate phase. The fraction of vapor PAHs in the total nine PAHs was 84.2% in the air of the sampling sites. In the morning and evening, the concentrations of PAHs in the arterial street air were higher than that on the noon and the diurnal variation of PAHs was similar to that of the traffic gas NOx. A conclusion would be drawn that the major source of PAHs in the arterial street air was the traffic. And the results indicated that 75% of BaP would come from traffic source and remaining 25% of BaP would come from non-traffic source.

Partition of polycyclic aromatic hydrocarbons on organobentonites from water.

A series of organobentonites synthesized by exchanging organic cation such as dodecyltri-methylammonium (DTMA), benzyldimethyltetradecylammonium (BDTDA), cetyltrimethyl-ammonium (CTMA), octodeyltrimethylammonium (OTMA) on bentonite. The optimal condition, properties and mechanisms for the organobentonites to sorb phenanthrene, anthracene, naphthalene, acenaphthene in water were investigated in detail. The partition behavior was determined for four polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, phenanthrene, anthracene and acenaphthene, from water to a series of organobentonites. The interlayer spacings and organic carbon contents of organobentonites, removal rate and sorption capacities for organobentonites to treat phenanthrene, anthracene, naphthalene, acenaphthene were correlated to the length of alkyl chains and the amounts of cation surfactant exchanged on the bentonite. Phenanthrene, anthracene, naphthalene, and acenaphthene sorption to organobentonites were characterized by linear isotherms, indicating solute partition between water and the organic phase composed of the large alkyl functional groups of quaternary ammonium cations. PAHs distribution coefficients (Kd) between organobentonites and water were proportional to the organic carbon contents of organobentonites. However, the partition coefficients (Koc) were nearly constants for PAHs in the system of organobentonite-water. The Koc of phenanthrene, anthracene, naphthalene, acenaphthene were 2.621 x 10(5), 2.106 x 10(5), 2.247 x 10(4), 5.085 x 10(4), respectively. The means Koc values on the organobentonites are about ten to twenty times larger than the values on the soils/sediments, what is significant prerequisite for organobentonite to apply to remediation of pollution soil and groundwater. The sorption mechanism was also evaluated from octanol-water partition coefficients and aqueous solubility of PAHs. The correlations between 1gKoc and 1gKow, 1gKoc and 1gS for PAHs in the system of water/organobenotonites are also discussed.

[Clinical study on effect of tongyu no. I in improving prethrombotic state of senile diabetes mellitus].

OBJECTIVE: To explore the therapeutic mechanism of Tongyu No. I (TY-1) in improving prethrombotic state of senile diabetes mellitus. METHODS: Sixty-two patients of diabetes mellitus with prethrombotic state and blood-stasis Syndrome were selected and divided randomly into two groups, 32 in the treated group and 30 in the control group. The two groups were treated by conventional therapy, combined with additional TY-1 (treated group) and aspirin (control group) respectively for 2 months. And the clinical effect as well as relevant criteria in both groups before and after treatment were observed. RESULTS: In the treated group, treatment showed markedly effective in 14 cases, effective in 16 and ineffective in 2, the total effective rate being 93.8%. In the control group, the corresponding values were 6, 14, 10 and 66.7% respectively. Comparison of the total effective rate in the two groups showed significant difference (P < 0.01). After treatment, the treated group showed lowering in plasma TXB2 similar to that in the control group, while the decrease of GMP-140 and fasting blood glucose levels was significant as compared with before treatment (P < 0.01) and the difference was significant between the two groups (P < 0.05) after treatment. CONCLUSION: TY-1 could improve the prethrombotic state and blood-stasis Syndrome in patients of diabetes mellitus, the main therapeutic mechanism might be correlated to the lowering of GMP-140 content.

Organochlorine pesticides in agricultural soil and vegetables from Tianjin, China.

Samples of eight types of vegetables, the rhizosphere soils, and bulk soils were collected from two sites (A and B) in Tianjin, China for the determination of hexachlorocyclohexane isomers (HCHs) and dichlorodiphenyltrichloroethane and metabolites (DDXs). The average concentrations of total HCHs and DDXs in the bulk soils were 3.6 and 80.1 ng/g for site A and 102 and 235 ng/g for site B, respectively. Relative accumulations of HCHs and DDXs in the rhizosphere soil from site A but not site B were demonstrated. The concentrations of total HCHs and DDXs in vegetable roots were 3.6-60 and 4.2-73 ng/g for site A and 15-152 and 7.1-136 ng/g for site B, respectively. Difference in bioaccumulation among various vegetables, especially between tuber and fibrous vegetables was significant. DDXs in spinach and cauliflower from site B and lindane (gamma-HCH) in cauliflower from both sites and violet from site B exceeded the maximum residual limits. Linear correlation of log-transformed HCHs and DDXs contents between the vegetable roots and the rhizosphere soils suggests the direct uptake of HCHs and DDXs.