The stereoselective synthesis of privileged epimer of C-10 carba artemisinins and the effect of substituted groups with different acid-base properties on the antimalarial activity / 药学学报

Artemisinin is a sesquiterpene lactone natural product that contains an endoperoxide bond. Artemisinin has various biological activities including antimalarial, anti-tumor, antiviral and anti-fibrotic activity. Owing to the poor pharmacokinetic properties of artemisinin, its derivatives are currently used in clinic and frequently reported in literature. Although numerous derivatives of artemisinin have been reported, no study has been carried out yet to study the effect of substituted groups with different acid-base property on the antimalarial activity. Among these derivatives, the C-10 carbon artemisinin derivatives are often reported, and their corresponding 10β epimer show much better antimalarial activity than 10α epimer with large-sized substitute. However, there is currently no stereoselective synthesis to efficiently prepare the privileged 10β epimer of C-10 carba artemisinin. To address these two scientific questions, we herein first report an optimized method to stereoselectively synthesize the 10β epimer of C-10 carba artemisinin (98∶2 d.r.). Second, we employed the optimized method to synthesize a series of C-10 carba artemisinin derivatives with different acid-base properties. The antimalarial examination indicated that those derivatives with neutral groups or basic group of short chain showed similar antimalarial activity as dihydroartemisinin (DHA). The acidic group could dramatically decrease the antimalarial effect and was more than 22-fold less effective than DHA or the neutral ones. This study will shed light on the development of new generation of artemisinin derivatives with potent activity.

Protective Effect of Tangshen Formula () on Interstitial Cells of Cajal in Colon of Diabetic Rats / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Tangshen Formula (, TSF), a Chinese herbal medicine, on interstitial cells of Cajal (ICC) in the colon of diabetic rats.@*METHODS@#Fifty-four male Wistar rats were randomly divided into normal control (NC, n=14) and high-fat diet (HFD) groups (n=40). After 6 weeks, the rats in the HFD group were injected intraperitoneally streptozotocin once (30 mg/kg). Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes (DM) and TSF groups, 15 rats in each group. Rats in the NC and DM groups were intragastrically administered with saline, and those in the TSF group were given with TSF (2.4 g/kg) once daily for 20 weeks. Expression levels of Bax, Bcl-2, and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical staining. The number of ICC was determined by immunohistochemical staining. Immunofluorescence was used for analyzing the ratio of classically activated macrophages (M1) and alternatively activated macrophages (M2) to total macrophages. Electron microscopy was used to observe the epithelial ultrastructure and junctions.@*RESULTS@#TSF appeared to partially prevented loss of ICC in DM rats (P<0.05). Compared with the NC group, expression levels of Bcl-2, Bax, caspase-3, and TNF-α as well as the ratio of M1 to total macrophages increased in DM rats (all P<0.05), and the ratio of M2 to total macrophages decreased (P<0.05 or P<0.01). Compared with the DM group, TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio (P<0.05 or P<0.01). TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM rats.@*CONCLUSION@#Reduced number of ICC in DM rats may be associated with damage of the intestinal barrier. The protective effects of TSF on ICC may be through repair of the epithelial junctions, which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.

Evaluation of porcine urine-derived cells as nuclei donor for somatic cell nuclear transfer

Background@#Somatic cell nuclear transfer (SCNT) is used widely in cloning, stem cell research, and regenerative medicine. The type of donor cells is a key factor affecting the SCNT efficiency. @*Objectives@#This study examined whether urine-derived somatic cells could be used as donors for SCNT in pigs. @*Methods@#The viability of cells isolated from urine was assessed using trypan blue and propidium iodide staining. The H3K9me3/H3K27me3 level of the cells was analyzed by immunofluorescence. The in vitro developmental ability of SCNT embryos was evaluated by the blastocyst rate and the expression levels of the core pluripotency factor. Blastocyst cell apoptosis was examined using a terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. The in vivo developmental ability of SCNT embryos was evaluated after embryo transfer. @*Results@#Most sow urine-derived cells were viable and could be cultured and propagated easily. On the other hand, most of the somatic cells isolated from the boar urine exhibited poor cellular activity. The in vitro development efficiency between the embryos produced by SCNT using porcine embryonic fibroblasts (PEFs) and urine-derived cells were similar.Moreover, The H3K9me3 in SCNT embryos produced from sow urine-derived cells and PEFs at the four-cell stage showed similar intensity. The levels of Oct4, Nanog, and Sox2 expression in blastocysts were similar in the two groups. Furthermore, there is a similar apoptotic level of cloned embryos produced by the two types of cells. Finally, the full-term development ability of the cloned embryos was evaluated, and the cloned fetuses from the urine-derived cells showed absorption. @*Conclusions@#Sow urine-derived cells could be used to produce SCNT embryos.

A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy / 中华医学杂志(英文版)

BACKGROUND@#Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS).@*METHODS@#A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score.@*RESULTS@#A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.@*CONCLUSIONS@#PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.

Research status of the formulas for calculating the degree of intraocular lens / 国际眼科杂志(Guoji Yanke Zazhi)

@#With the progress in refractive cataract surgery, the refractive effects after cataract surgery are more accurate and predictable. Various types of intraocular lens have been applied to clinical practice and there is an increasingly higher demand on the precision of intraocular lens(IOL)calculation formula. According to calculation principles and different parameters required, this article aims to give a review on the research progress of IOL calculation formula.

Effect of Huoxue Jiedu Runzao Prescription on Expression of Apoptosis Inhibitor Survivin in Submandibular Gland Cells of Sjögren's Syndrome Mice / 中国实验方剂学杂志

Objective:To investigate the effect of Huoxue Jiedu Runzao prescription on the morphology， apoptosis， and function of submandibular gland in the mouse model of Sjögren's syndrome （SS） and its functioning mechanism， we analyzed the expression of the apoptosis inhibitor Survivin in the submandibular gland cells of SS mice. Method:Female BALB/c57 mice were selected as the normal group. The naive non-obese diabetic （NOD/Ltj） female mice were selected as the SS model， which were randomly assigned into the model group， Paeoniae Radix Alba total glucosides capsule （0.234 g·kg^-1） group， and low-， medium-， and high-dose （15.6， 31.2， 62.4 g·kg^-1， respectively） Huoxue Jiedu Runzao prescription groups. Each group had 15 mice. The morphological and functional changes of submandibular gland and the Survivin expression were observed and measured after 8 weeks of drug intervention. Survivin expression was determined by immunohistochemistry （IHC）， Western blot， and reverse transcription-polymerase chain reaction （RT-PCR）. Result:Compared with normal group， salivary flow and submandibular gland index in model group were significantly decreased （<italic>P</italic><0.01）， and histopathological score of submandibular gland was significantly increased （<italic>P</italic><0.01）. Western blot showed that Survivin protein expression was significantly decreased （<italic>P</italic><0.05）. IHC showed that， Survivin mRNA expression was significantly decreased （<italic>P</italic><0.01）， and RT-PCR results showed that Survivin mRNA expression was significantly decreased （<italic>P</italic><0.01）. Compared with model group， salivary flow and submandibular gland index of mice in Huoxue Jiudu Runzao prescription groups and Paeoniae Radix Alba total glucosides capsules groups were significantly increased （<italic>P</italic><0.05）， histopathological score of submandibular gland was significantly decreased （<italic>P</italic><0.05）， IHC results showed that Survivin expression was significantly increased （<italic>P</italic><0.01）. Western blot and RT-PCR results showed that Survivin protein and mRNA expression of Huoxue Jiudu Runzao prescription high-dose group and Paeoniae Radix Alba total glucosides capsule group were significantly increased （<italic>P</italic><0.05）. Conclusion:Huoxue Jiedu Runzao prescription can improve the secretion function of submandibular acinus， increase the submandibular gland index， and saliva secretion of SS mice by up-regulating survivin in submandibular gland cells of SS mice.

Study on the sleep quality and its influencing factors in rural hypertensive patients in Xuanen country of Hubei Province / 中华疾病控制杂志

Objective To investigate sleep quality and it’s influencing factors of hypertensives among rural area in Hubei Province. Methods The method of stratified sampling by selecting 569 hypertensives in Xuanen county of Hubei was applied to perform the questionnaire survey, including the sociodemographic data, daily life habits and physical health data, as well as pittsburgh sleep quality index(PSQI) and compliance of hypertensive patients scale(CHPS). Results The average score of PSQI in 569 hypertensives was 7.25±3.61, of which 251(44.11%) hypertensives were poor sleep quality. The influencing factors of sleep quality for hypertensives are gender (P=0.006, OR=1.626), the number of other diseases(P=0.001, OR=1.520), regular exercise (P=0.033, OR=0.660) and the compliance of hypertensives (P=0.024, OR=1.707). Conclusions The sleep quality of rural hypertensives in Xuanen county, Hubei Province is poor, which is affected by different factors. Therefore effective measures should be taken to improve the sleep quality of hypertensives.

Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Single-center Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.</p><p><b>METHODS</b>In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.</p><p><b>RESULTS</b>The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28.</p><p><b>CONCLUSIONS</b>As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.</p>

Measurement and clinical significance of cervical lordosis / 中国骨伤

Measurement of cervical lordosis is the basic method for evaluating cervical function, and important reference for determine treatment decision. However, how to choose appropriate measurement in accordance with different situation, as well as the relationship among these methods is not clear. An increasing number of studies suggested that different measurements could directly affect the judgment of cervical lordosis. Therefore, comparative study of cervical vertebrae plays an important role in clinical treatment for cervical spondylosis under different cervical curvature conditions.

Active changes of lignification-related enzymes in pepper response to Glomus intraradices and/or Phytophthora capsici / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The activities of enzymes responsible for lignification in pepper, pre-inoculation with arbuscular mycorrhizal (AM) fungus of Glomus intraradices and/or infection with pathogenic strain of Phytophthora capsici, and the biological control effect of G. intraradices on Phytophthora blight in pepper were investigated. The experiment was carried out with four treatments: (1) plants pre-inoculated with G. intraradices (Gi), (2) plants pre-inoculated with G. intraradices and then infected with P. capsici (Gi+Pc), (3) plants infected with P. capsici (Pc), and (4) plants without any of the two microorganisms (C). Mycorrhizal colonization rate was reduced by about 10% in pathogen challenged plants. Root mortality caused by infection of P. capsici was completely eliminated by pre-inoculation with antagonistic G. intraradices. On the ninth day after pathogen infection, Peroxidase (POD) activity increased by 116.9% in Pc-treated roots but by only 21.2% in Gi+Pc-treated roots, compared with the control, respectively. Polyphenol oxidase (PPO) and Phenylalanine ammonia-lyase (PAL) activities gradually increased during the first 3 d and dramatically decreased in Pc-treated roots but slightly decreased in Gi+Pc-treated roots, respectively. On the ninth day after pathogen infection, PPO and PAL decreased by 62.8% and 73.9% in Pc-treated roots but by only 19.8% and 19.5% in Gi+Pc-treated roots, compared with the control, respectively. Three major POD isozymes (45,000, 53,000 and 114,000) were present in Pc-treated roots, while two major bands (53,000 and 114,000) and one minor band (45,000) were present in spectra of Gi+Pc-treated roots, the 45,000 POD isozyme was significantly suppressed by G. intraradices, suggesting that the 45,000 POD isozyme was induced by the pathogen infection but not induced by the antagonistic G. intraradices. A 60,000 PPO isozyme was induced in Pc-treated roots but not induced in Gi+Pc-treated roots. All these results showed the inoculation of antagonistic G. intraradices alleviates root mortality, activates changes of lignification-related enzymes and induces some of the isozymes in pepper plants infected by P. capsici. The results suggested that G. intraradices is a potentially effective protection agent against P. capsici.