Photogenerated chlorine radicals activate C(sp3)-H bonds of alkylbenzenes to access quinazolinones.

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

The application of specialised management assistants in demand forecasting of human resources.

Objective: Based on a theoretical analysis and through working practice, this paper presents the experience of the scientific use of the manpower demand prediction method and practical process of specialised business assistants in clinical departments. Methods: A spot observation, interview and public information inquiry were conducted, and SPSS20.0 Chinese software was used to make a statistical prediction of the business growth (P & LT; 0.05). Results: The specialist management assistant prepared the manpower needs assessment report for the department, and the hospital organization personnel department adopted the recommendation in the manpower needs assessment report and put it into the hospital's recruitment plan for the following year. Conclusion: The blood purification centre of specialised business assistants in patients in the medical market, service people, workload and equipment operation efficiency analysis data analysis. It was found that an effective prediction model that supports decisions regarding the hospital's scientific allocation of human resources is advantageous to the hospital's human resource optimisation, improves both operation equipment efficiency and patient satisfaction and is worthy of application and popularisation.

Risk factors for hospital-acquired and community-acquired pressure injuries: a multicentre mixed case-control study.

OBJECTIVES: To separately examine and comprehensively compare the risk factors for hospital-acquired (HAPIs) and community-acquired pressure injuries (CAPIs). DESIGN: A mixed case-control study. SETTING: Four medical centres in China. PARTICIPANTS: Inclusion criteria included patients who were (1) aged ≥18 years on admission; (2) admitted between January 2014 and December 2018, and (3) diagnosed with HAPIs (cases) or with no HAPIs (controls) during hospitalisation in the HAPIs study, and confirmed with CAPIs (cases) or with no PIs (controls) on admission in the CAPIs study. The exclusion criteria were as follows: (1) admitted for childbirth, psychiatric reasons or rehabilitation; (2) admitted for observation; (3) transferred from another hospital and (4) confirmed to have suffered PIs from previous hospitalisations in the CAPIs study. In total, 320 cases and 1657 controls were included in the HAPIs study, and 1763 cases and 1786 controls were included in the CAPIs study. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome variable was the occurrence of PIs. RESULTS: The existence of PIs or scars from previous PIs on admission, presence of forced posture, use of medical devices and surgery during hospitalisation were found to be independent risk factors for HAPIs, as evidenced by the corresponding OR and 95% CI values of 51.931 (34.241 to 78.763), 2.006 (1.405 to 2.864), 3.226 (1.709 to 6.089) and 2.161 (1.452 to 3.215), respectively. Age, sex, Braden rating and diabetes were found to be independent risk factors for CAPIs, as evidenced by the corresponding OR and 95% CI values of 1.031 (1.026 to 1.036), 0.810 (0.698 to 0.941), 1.235 (1.167 to 1.307) and 2.059 (1.332 to 3.184), respectively. CONCLUSIONS: The existence of PIs or scars from previous PIs on admission, presence of forced posture, use of medical devices and surgery during hospitalisation are suggested to be included as independent items for the risk assessment of PIs, together with the Braden scale. The Braden rating plays different roles in the development of CAPIs and HAPIs.

Inhibitory effects of Coptidis Rhizoma on the intestinal absorption and metabolism of Scutellariae Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: The Scutellariae Radix (SR) and Coptidis Rhizoma (CR) herb couple is widely used in traditional Chinese medicine prescriptions for the treatment of diabetes mellitus due to its interaction and synergistic effect compared to either herb alone, but the underlying mechanism of interaction between these herbs is unclear. This study aimed to investigate the effects of CR on the metabolism and absorption of SR. MATERIALS AND METHODS: After rats were treated with normal saline (NS group) or the CR extract (CR-treated group) for seven consecutive days, the intestinal flora was extracted from rat faeces for a co-incubation with the SR extract to investigate the metabolism of SR flavonoids, and a non-everted gut sac was prepared in vitro to evaluate the intestinal absorption of the SR extract. The components of the SR extract, the metabolites of the SR extract that was co-incubated with intestinal flora, and the dialysate acquired from non-everted gut sacs were identified and determined by an HPLC-MS/MS method. The absorption rate constant (Ka) and the apparent permeability (Papp) of each compound were calculated, and the effects of CR on the metabolism and absorption of flavonoids in SR were evaluated, by comparison the Ka and Papp between two groups using Student's t-test. RESULTS: Twenty-nine flavonoids were detected and identified in the SR extract, including 16 glycosides and 13 aglycones. In the co-incubation with the intestinal flora, differences in metabolite classes were not observed between the NS group and CR-treated group; however, the metabolic rates of 17 flavonoids in the CR-treated group were significantly higher than the NS group. The Papp of 11 compounds (4 glycosides and 7 aglycones) across the gut sac were greater than 2 × 10-5 cm/s in both groups, while the Papp values of 7 compounds including wogonoside (WG) and other aglycones were significantly decreased in the CR-treated group. CONCLUSION: Based on these results, CR decreased the metabolism and absorption of SR flavonoids, and exerted much greater inhibitory effects on aglycones than glycosides, which may be one of the potential mechanisms underlying the therapeutic effects of the combination of SR and CR on diabetes mellitus.

Calycosin inhibits viability, induces apoptosis, and suppresses invasion of cervical cancer cells by upregulating tumor suppressor miR-375.

Calycosin, a functional phytoestrogen isoflavone isolated from Radix astragali, has been shown to possess multiple pharmacological properties including anti-cancer activity. However, up to now, the anti-cancer effect and the related mechanism of calycosin on cervical cancer (CC) cells have not been explored. It has been demonstrated that tumor suppressor miR-375 was downregulated in CC and calycosin upregulated miR-375 expression in cerebral ischemia/reperfusion. Thus we supposed that calycosin exerted anti-cancer effect by upregulating miR-375 expression in CC cells. Effects of calycosin or combined with miR-375 on cell viability and lactate dehydrogenase (LDH) release were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetra zoliumromide (MTT) and LDH release assay. Apoptosis, caspase-3 activity, and cell invasion were determined by flow cytometry, caspase-3 activity assay, and Transwell assay, respectively. miR-375 expression was detected by quantitative real-time PCR (qRT-PCR). Our results showed that Calycosin dose-dependently inhibited cell viability and increased LDH release in CC cells, suggesting the cytotoxic effect of calycosin on CC cells. Calycosin enhanced the apoptotic rate and caspase-3 activity and decreased the number of invaded cells in CC cells. In addition, we found that miR-375 expression was decreased in CC cells but was upregulated in response to calycosin. Mechanistically, knockdown of miR-375 significantly reversed the anti-cancer effect of calycosin on CC cells. In conclusion, calycosin inhibited viability, induced apoptosis, and suppressed invasion of CC cells by upregulating tumor suppressor miR-375.

A network meta-analysis of comparison of operative time and complications of laparoscopy, laparotomy, and laparoscopic-assisted vaginal hysterectomy for endometrial carcinoma.

BACKGROUND: The endometrial carcinoma (EC) is the most frequently occurring female genital cancer. The authors performed this network meta-analysis to compare operative time and the incidence of bowel injury and wound infection of 3 operative approaches (laparoscopy, laparotomy, and laparoscopic-assisted vaginal hysterectomy [LAVH]) in the treatment of EC. METHODS: The Cochrane Library, PubMed, and Embase databases were searched. Randomized controlled trials (RCTs) for EC from the day of databases establishment to February 2017 were included. Direct and indirect evidences were combined to calculate the combined weighted mean difference (WMD) or odd ratio values and the surface under the cumulative ranking curve (SUCRA) value of 3 operative approaches in the treatment of EC. RESULTS: A total of 9 qualified RCTs were included into the study. The results showed that laparotomy had a shorter-operative time than LAVH (WMD = -40.36, 95% confidence interval = -75.03 to -2.57). However, there was no significant difference in the incidence of bowel injury and wound infection among 3 operative approaches. Besides, the SUCRA values indicated that laparotomy had the shortest operative time but the incidence of bowel injury and wound infection was relatively higher. CONCLUSION: The results from this study indicate that laparotomy had highest incidence of bowel injury and wound infection but shortest operative time among 3 operative approaches in the treatment of EC.

WITHDRAWN: Up-regulation of RIP3 alleviates cervical cancer progression through inducing necroptosis.

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Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer: A network meta-analysis.

BACKGROUND: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. METHODS: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. RESULTS: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. CONCLUSION: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which was clinically significant for the treatment of AOC.

Long non-coding RNA ANRIL indicates a poor prognosis of cervical cancer and promotes carcinogenesis via PI3K/Akt pathways.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are playing critical roles in tumorgenesis. LncRNA ANRIL has been reported to promote tumor progression in types of cancers. However, the expression and function of ANRIL in cervical cancer are still largely unclear. We measured the expression of ANRIL in cervical cancer tissues and cell lines and analyzed its association with clinicopathological features and prognosis. Loss-of-function experiments were used to identify the biological function of ANRIL. Our results showed that the expression of lncRNA ANRIL was significantly increased both in cervical cancer tissues and cell lines. Patients with high ANRIL expression had advanced FIGO stage, lymph node metastasis and poor overall survival than those with low ANRIL expression. Multivariable Cox proportional hazards regression analysis suggested that high ANRIL expression was an independent prognostic factor of prognosis. Loss-of-function experiments showed that decreased expression of ANRIL inhibited cell proliferation, migration and invasion of cervical cancer. Finally, western blot indicated that the PI3K/Akt pathway was found to be inactivated in cervical cancer cells after ANRIL inhibition. These results indicated that lncRNA ANRIL might play an important role in cervical cancer progression and could serve as a novel prognostic biomarker and therapeutic target in cervical cancer.

In vitro and in vivo identification of metabolites of magnoflorine by LC LTQ-Orbitrap MS and its potential pharmacokinetic interaction in Coptidis Rhizoma decoction in rat.

Magnoflorine, an important aporphine alkaloid in Coptidis Rhizoma, is increasingly attracting research attention because of its pharmacological activities. The in vivo and in vitro metabolism of magnoflorine was investigated by LC LTQ-Orbitrap MS. In vivo samples including rat urine, feces, plasma and bile were collected separately after both oral (50 mg kg(-1) ) and intravenous administration (10 mg kg(-1) ) of magnoflorine, along with in vitro samples prepared by incubating magnoflorine with rat intestinal flora and liver microsome. As a result, 12 metabolites were found in biological samples. Phase I metabolites were identified in all biological samples, while phase II metabolites were mainly detected in urine, plasma and bile. In a pharmacokinetic study, rats were not only dosed with magnoflorine via oral (15, 30 and 60 mg kg(-1) ) and intravenous administration (10 mg kg(-1) ) but also dosed with Coptidis Rhizoma decoction (equivalent to 30 mg kg(-1) of magnoflorine) by intragastric administration to investigate the interaction of magnoflorine with the rest of compounds in Coptidis Rhizoma. Studies showed that magnoflorine possessed lower bioavailability and faster absorption and elimination. However, pharmacokinetic parameters altered significantly (p < 0.05) when magnoflorine was administered in Coptidis Rhizoma decoction. Oral gavage of Coptidis Rhizoma decoction decreased the absorption and elimination rates of magnoflorine, which revealed that there existed pharmacokinetic interactions between magnoflorine and the rest of ingredients in Coptidis Rhizoma.

[Stability study in biological samples and metabolites analysis of astragaloside IV in rat intestinal bacteria in vitro].

To figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside IV ( AST), this research was done to explore the stability of AST in the artificial gastric juice. artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the artificial gastric juice, artificial intestinal juice and rat liver. Also, the metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was converted to its secondary etabolites (6-O-ß-D-glucopyranosyl- cycloastragenol, CMG) by removal of xylose moiety at C-3, then transformed into cycloastragenol (CAG) after hydrolytic removal of the glucose moiety at C-6. All the results suggested that the metabolism of AST in vivo occurs mainly in the intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal flora is the main reason that AST metabolizes.

[Identification of metabolites of epiberberine in rat liver microsomes and its inhibiting effects on CYP2D6].

Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 µmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.

[Effect of comparability of Coptis chinensis and Scutellaria baicalensis on five sub-enzymatic activities of liver microsomes in rats].

To study the mechanism of metabolic interaction between Coptis chinensis and Scutellaria baicalensis. Rats were given C. chinensis and S. baicalensis for 7 days to produce hepatic microsomal enzyme. Cocktail probe substrate and liver microsome in vitro temperature incubation method were adopted. Meanwhile, the metabolic elimination percentages of the five probe substrates were detected with HPLC, in order to evaluate the effect of each administration group on the enzymatic activity of rat liver microsome CYP450. Compared with the blank group, C. chinensis obviously inhibited CYP2D6 and CYP1A2, and S. baicalensis remarkably inhibited CYP1A2, CYP2E1 and CYP2C9. The compatibility of C. chinensis and S. baicalensis with the ratio of 1:1 not only inhibited CYP1A2, but also remarkably activated CYP2D6 and CYP3A4. However, their activation effect disappeared under the ratio of 2: 1, and turned into the inhibitory effect on CYP1A2 and CYP2C9. The results showed that C. chinensis and S. baicalensis had an inhibitory effect on CYP450, but their compatibility with certain ratio resulted in double effects of activation and inhibition, which was related to their compatibility ratio. It is speculated that the inhibitory and inducing effects of C. chinensis and S. baicalensis on metabolic enzymes are among causes for their attenuation and synergistic effects.

Expression and methylation status of the Syk gene in cervical carcinoma.

OBJECTIVE: Spleen tyrosine kinase (Syk), a non-receptor protein tyrosine kinase, has recently been recognized as a new candidate tumor suppressor. Decrease or loss of Syk expression has been associated with a malignant phenotype and poor prognosis in a variety of cancers. This study aimed to determine the precise role of Syk in cervical cancer. METHODS: Methylation-specific PCR (MSP) and RT-PCR were utilized to analyze the methylation status and Syk mRNA expression in tissue samples from 20 normal controls, 50 CIN patients and 60 cervical cancer patients. RESULTS: Syk expression was detected in all 20 normal cervical tissues, as well as in all 18 CIN1 samples. Syk expression was found in 18 of 32 (56%) of CIN2/3 samples. CONCLUSION: The results indicate a potential link between the loss of Syk expression and cervical carcinogenesis.