Phytochemical Investigation and in Vitro Antioxidant Activity of Panchavalkala Bark Extracts

Natural antioxidants have an important role in the prevention of many age-related diseases and promotion of health. Among natural antioxidants from plants, flavonoids and other phenolic compounds are potent antioxidants and chelating agents. Panchavalkala the barks of five trees i.e. Nyagrodha (Ficus benghalensis L.), Udumbara (Ficus racemosa L.), Ashwatha (Ficus religiosa L.), Plaksha (Ficus virens Aiton) and Parisha (Thespesia populnea (L.)Sol.ex Correa) are also known as Pancha Ksheeri Vrikshas in use since Vedic period. Barks of these trees are dried in shade and are used for different formulations (Pancha Kashaya Kalpanas), in different pathological conditions, especially as wound healing, gynecological disorders and etc. The plant samples were extracted using ethanol and water, and subjected for the phytochemical analysis. It was confirmed that samples contain many biologically active compounds like flavonoids, polyphenols, tannins, alkaloids, glycosides and terpinoids etc. The marker compound of each trial drug and the quantitative analysis has been carried out by high performance liquid chromatography. The antioxidant study was done by using in vitro method 1, 1­-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. The marker compounds caffeic acid and gallic acid were quantified in each extract for their quality and efficacy. PVK barks showed high free radical scavenging activity as evidenced by the low IC50 values in DPPH (EE PVK- 20.46µg/ml, AE PVK-37.79µg/ml, EE T.poulenea-22µg/ml, AE T. poulenia- 23.31µg/ml AE F. benghalensis- 25.53µg/ml, EE F. benghalensis- 26.23µg/ml, EE F. religiosa - 34µg/ml). Quercetin- IC50 value 4.026µg/ml is used as standard. The results of the study demonstrated that PVK barks possess phyto-constituent’s viz. tannins, flavonoids, polyphenols etc. and has potential antioxidant activity. Thus these barks have good therapeutic potential as natural antioxidant and might be used in life style related conditions like hyperlipidemia, diabetes, obesity, cardiovascular disorders and etc.

Characteristics of HIV-1 CRF01_AE molecular network in Yunnan Province / 中华微生物学和免疫学杂志

Objective:To investigate the molecular network of HIV-1 CRF01_AE in Yunnan Province and the factors influencing it.Methods:Demographic data and plasma samples of HIV/AIDS patients in Yunnan drug resistance monitoring database from 2018 to 2021 were collected. HIV-1 pol gene fragments (protease and reverse transcriptase region) were amplified using RT-PCR and then sequenced. The optimal gene distance was selected and a molecular network was constructed based on the sequences of CRF01_AE genotype. Results:In this study, a total of 967 sequences of CRF01_AE genotype were obtained by sequencing. At the optimal gene distance threshold of 1.75%, a total of 320 sequences were involved in the network with a rate of 33.1%, and 84 clusters were identified. In the regional distribution, one cluster dominated by multiple regions, one cluster dominated by Zhaotong, one cluster dominated by Honghe and five clusters dominated by Wenshan were formed in the network. In the network, 75.8% of heterosexual men were connected with other heterosexual men and 54.1% were connected with heterosexual women. There was potential transmission among 66.7% of men who have sex with men (MSM). HIV/AIDS patients in Chuxiong, Dali, Dehong, Honghe, Lincang, Pu′er, Wenshan, Yuxi and Zhaotong were more likely to be involved in the network that those in Kunming. People who were 50 years old and above were more likely to be involved in the network than those less than 25 years old. Factors influencing HIV/AIDS patients with HIV-1 CRF01_AE infection to become high-risk transmitters in Yunnan were not found and further study on this subject was needed.Conclusions:HIV-1 CRF01_AE strains had spread actively in different regions of Yunnan Province and the transmission network was complex. Dynamic monitoring of CRF01_AE strains should be strengthened and a precise intervention for high-risk transmitters should be performed to reduce new infections.

Safety of human papilloma virus vaccine based on Vaccine Adverse Event Reporting System from 2006 to 2021 / 中国生物制品学杂志

@#Objective To investigate the characteristics of distribution of adverse event(AE)associated with human papillomavirus(HPV)vaccine by analysis of data on AE collected from the Vaccine Adverse Event Reporting System(VAERS).Methods The data on AE reported in VAERS from January 1st,2006 to December 31st,2021 were analyzed and compared by using Pearson Chi-square test and Mann-Whitney U test.Results A total of 53 571 cases of AE were included in the study,in which the ratio of male to female was 0. 25∶1,and the median age of vaccinees was 15 years. A portion of 36. 1%of AE occurred after the first dose,while 90. 7% occurred within 3 d after vaccination. Both the gender ratios(χ~2=72. 570,P < 0. 001) and the median ages(Z = 4. 255,P < 0. 001)of vaccinees in non-serious and serious adverse event(SAE)showed significant difference. In terms of classification of SAE,hospitalization,prolonged hospitalization and disability were more common in females than in males,of which the percentages decreased with the increasing age. Among the AE,syncope was the most common clinical symptom. In the SAE,the highest proportion of deaths was caused by HPV2 vaccine,which was 19. 0%. The proportion of prolonged hospitalization caused by HPV4 vaccine was higher than that by HPV9vaccine. In general,HPV4 vaccine was more prone to cause SAE than HPV9 vaccine(χ~2=183. 267,P < 0. 001).Conclusion In all the AE,the largest proportion occurred in the age group of 9 ～ 17 years,followed by those in the groups of 18 ～ 26 and 27 ～ 45 years. Most of the AE occurred after the first dose. The clinical symptoms of AE caused by three vaccines were different. The analysis of distribution characteristics of AE may provide a reference for the study on clinical safety of HPV vaccine and optimization of vaccination.

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Late effects of Beauveria bassiana on larval stages of Aedes aegypti Linneo , 1762 (Diptera: Culicidae) / Efeitos tardios de Beauveria bassiana nos estágios larvais de Aedes aegypti Linneo, 1762 (Diptera: Culicidae)

Aedes aegypti is a culicide that has gained relevance over the years due to its ability to transmit various viruses that cause diseases in humans that all the years cause high mortality rates in the world population. The main problem is that Ae. aegypti has managed to establish and maintain a close relationship with humans and their habitat, which is why the search for alternatives to control vector populations becomes imperative. The objective of the present work was to study the effects of two Beauveria bassiana strains on Aedes aegypti. Third instar larvae of Ae. aegypti in 250 mL plastic containers were inoculated with the GHA and NB3 strains at different concentrations (1.5 × 104 , 1.5× 105 , 1.5 × 106 and 1.5 × 107 conidia/mL). The NB3 strain presented highest mortality values with 63% in the highest concentration i.e., 1.5 × 107 , while for the GHA strain the highest mortality value was 30.7% at the same concentration. The results showed significant difference in mortality with respect to the strain and days post treatment (P = 0.0001), but not with respect to the conidial concentration (P = 0.634). The average mortality of larvae per day for the NB3 for different concentrations ranged from 20 to 25 larvae per day, while for the GHA daily mortality ranged from 5 to 12 larvae. In post-treatment mortality, the highest mortality was recorded in the third stage larvae for the NB3, while for GHA the highest percentage mortality was observed in individuals who managed to reach the adult state. The findings of the current research depicted the noteworthy role of B. bassiana for the management of an important vector of human disease.

O Aedes aegypti é um culicida que vem ganhando relevância ao longo dos anos devido à sua capacidade de transmitir diversos vírus causadores de doenças em humanos que ao longo dos anos ocasionam altas taxas de mortalidade na população mundial. O principal problema é que Ae. aegypti tem conseguido estabelecer e manter uma relação próxima com o homem e seu habitat, por isso a busca por alternativas para o controle das populações de vetores torna-se imperativa. O objetivo do presente trabalho foi estudar os efeitos de duas cepas de Beauveria bassiana sobre Ae. aegypti. Larvas de terceiro instar de Ae. aegypti em recipientes plásticos de 250 mL foram inoculados com as cepas GHA e NB3 em diferentes concentrações (1.5 × 104, 1.5 × 105, 1.5 × 106 e 1.5 × 107 conídios/mL). A cepa NB3 apresentou os maiores valores de mortalidade com 63% na concentração mais alta, ou seja, 1.5 × 107, enquanto para a cepa GHA o maior valor de mortalidade foi 30.7% na mesma concentração. Os resultados mostraram diferença significativa na mortalidade com relação à cepa e dias pós-tratamento (P = 0.0001), mas não com relação à concentração de conídios (P = 0.634). A mortalidade média de larvas por dia para o NB3 para diferentes concentrações variou de 20 a 25 larvas por dia, enquanto para o GHA a mortalidade diária variou de 5 a 12 larvas. Na mortalidade pós-tratamento, a maior mortalidade foi registrada nas larvas de terceiro estágio para o NB3, enquanto para o GHA o maior percentual de mortalidade foi observado em indivíduos que conseguiram atingir o estado adulto. Os resultados da pesquisa atual retratam o papel notável de B. bassiana no manejo de um importante vetor de doenças humanas.

Distribution modelling of Aedes aegypti in three dengue-endemic areas in Sumatera, Indonesia

@#Ae. aegypti is a dengue virus vector and a public health threat in Indonesia. Furthermore, the Dengue Haemoragic Fever (DHF) has spread to all cities in the country, including Bandar Lampung. A species distribution model, Maximum Entropy (MaxEnt), was used to predict the geographic distribution of this vector in three dengue-endemic areas, namely Sukarame, Kemiling, and Tanjung Seneng. Previously, surveillance was conducted to determine the presence of Ae. aegypti. Therefore, this study suggested that environmental variables such as rainfall, temperature, land cover, and population density have influenced the widespread of Ae. aegypti and facilitate its proliferation in the study areas. The influence of the environmental variables was analyzed using a response curve. The model performance was measured by percent contribution, the importance of permutations, and the jackknife test. This study’s evaluation indicates that the certainty models for the presence of Ae. aegypti in Sukarame, Kemiling, and Tanjung Seneng were developed extremely well, with respective values of 0.989, 0.993, and 0.969. The results showed that Ae. aegypti is widespread in the three endemic areas. The high population density and land conversion into settlements are influential environmental variables essential in determining the distribution of the vector in three areas of Bandar Lampung. Climatic factors such as rainfall and temperature are supporting aspects in maintaining the habitat of Ae. aegypti in the area. Mapping areas at risk of this dengue vector can aid in planning disease management strategies and identifying priority locations for entomological surveys to control epidemics.

Late effects of Beauveria bassiana on larval stages of Aedes aegypti Linneo, 1762 (Diptera: Culicidae) / Efeitos tardios de Beauveria bassiana nos estágios larvais de Aedes aegypti Linneo, 1762 (Diptera: Culicidae)

Aedes aegypti is a culicide that has gained relevance over the years due to its ability to transmit various viruses that cause diseases in humans that all the years cause high mortality rates in the world population. The main problem is that Ae. aegypti has managed to establish and maintain a close relationship with humans and their habitat, which is why the search for alternatives to control vector populations becomes imperative. The objective of the present work was to study the effects of two Beauveria bassiana strains on Aedes aegypti. Third instar larvae of Ae. aegypti in 250 mL plastic containers were inoculated with the GHA and NB3 strains at different concentrations (1.5 × 104, 1.5× 105, 1.5 × 106 and 1.5 × 107 conidia/mL). The NB3 strain presented highest mortality values with 63% in the highest concentration i.e., 1.5 × 107, while for the GHA strain the highest mortality value was 30.7% at the same concentration. The results showed significant difference in mortality with respect to the strain and days post treatment (P = 0.0001), but not with respect to the conidial concentration (P = 0.634). The average mortality of larvae per day for the NB3 for different concentrations ranged from 20 to 25 larvae per day, while for the GHA daily mortality ranged from 5 to 12 larvae. In post-treatment mortality, the highest mortality was recorded in the third stage larvae for the NB3, while for GHA the highest percentage mortality was observed in individuals who managed to reach the adult state. The findings of the current research depicted the noteworthy role of B. bassiana for the management of an important vector of human disease.

O Aedes aegypti é um culicida que vem ganhando relevância ao longo dos anos devido à sua capacidade de transmitir diversos vírus causadores de doenças em humanos que ao longo dos anos ocasionam altas taxas de mortalidade na população mundial. O principal problema é que Ae. aegypti tem conseguido estabelecer e manter uma relação próxima com o homem e seu habitat, por isso a busca por alternativas para o controle das populações de vetores torna-se imperativa. O objetivo do presente trabalho foi estudar os efeitos de duas cepas de Beauveria bassiana sobre Ae. aegypti. Larvas de terceiro instar de Ae. aegypti em recipientes plásticos de 250 mL foram inoculados com as cepas GHA e NB3 em diferentes concentrações (1.5 × 104, 1.5 × 105, 1.5 × 106 e 1.5 × 107 conídios/mL). A cepa NB3 apresentou os maiores valores de mortalidade com 63% na concentração mais alta, ou seja, 1.5 × 107, enquanto para a cepa GHA o maior valor de mortalidade foi 30.7% na mesma concentração. Os resultados mostraram diferença significativa na mortalidade com relação à cepa e dias pós-tratamento (P = 0.0001), mas não com relação à concentração de conídios (P = 0.634). A mortalidade média de larvas por dia para o NB3 para diferentes concentrações variou de 20 a 25 larvas por dia, enquanto para o GHA a mortalidade diária variou de 5 a 12 larvas. Na mortalidade pós-tratamento, a maior mortalidade foi registrada nas larvas de terceiro estágio para o NB3, enquanto para o GHA o maior percentual de mortalidade foi observado em indivíduos que conseguiram atingir o estado adulto. Os resultados da pesquisa atual retratam o papel notável de B. bassiana no manejo de um importante vetor de doenças humanas.

Late effects of Beauveria bassiana on larval stages of Aedes aegypti Linneo, 1762 (Diptera: Culicidae)

Abstract Aedes aegypti is a culicide that has gained relevance over the years due to its ability to transmit various viruses that cause diseases in humans that all the years cause high mortality rates in the world population. The main problem is that Ae. aegypti has managed to establish and maintain a close relationship with humans and their habitat, which is why the search for alternatives to control vector populations becomes imperative. The objective of the present work was to study the effects of two Beauveria bassiana strains on Aedes aegypti. Third instar larvae of Ae. aegypti in 250 mL plastic containers were inoculated with the GHA and NB3 strains at different concentrations (1.5 × 104, 1.5× 105, 1.5 × 106 and 1.5 × 107 conidia/mL). The NB3 strain presented highest mortality values with 63% in the highest concentration i.e., 1.5 × 107, while for the GHA strain the highest mortality value was 30.7% at the same concentration. The results showed significant difference in mortality with respect to the strain and days post treatment (P = 0.0001), but not with respect to the conidial concentration (P = 0.634). The average mortality of larvae per day for the NB3 for different concentrations ranged from 20 to 25 larvae per day, while for the GHA daily mortality ranged from 5 to 12 larvae. In post-treatment mortality, the highest mortality was recorded in the third stage larvae for the NB3, while for GHA the highest percentage mortality was observed in individuals who managed to reach the adult state. The findings of the current research depicted the noteworthy role of B. bassiana for the management of an important vector of human disease.

Resumo O Aedes aegypti é um culicida que vem ganhando relevância ao longo dos anos devido à sua capacidade de transmitir diversos vírus causadores de doenças em humanos que ao longo dos anos ocasionam altas taxas de mortalidade na população mundial. O principal problema é que Ae. aegypti tem conseguido estabelecer e manter uma relação próxima com o homem e seu habitat, por isso a busca por alternativas para o controle das populações de vetores torna-se imperativa. O objetivo do presente trabalho foi estudar os efeitos de duas cepas de Beauveria bassiana sobre Ae. aegypti. Larvas de terceiro instar de Ae. aegypti em recipientes plásticos de 250 mL foram inoculados com as cepas GHA e NB3 em diferentes concentrações (1.5 × 104, 1.5 × 105, 1.5 × 106 e 1.5 × 107 conídios/mL). A cepa NB3 apresentou os maiores valores de mortalidade com 63% na concentração mais alta, ou seja, 1.5 × 107, enquanto para a cepa GHA o maior valor de mortalidade foi 30.7% na mesma concentração. Os resultados mostraram diferença significativa na mortalidade com relação à cepa e dias pós-tratamento (P = 0.0001), mas não com relação à concentração de conídios (P = 0.634). A mortalidade média de larvas por dia para o NB3 para diferentes concentrações variou de 20 a 25 larvas por dia, enquanto para o GHA a mortalidade diária variou de 5 a 12 larvas. Na mortalidade pós-tratamento, a maior mortalidade foi registrada nas larvas de terceiro estágio para o NB3, enquanto para o GHA o maior percentual de mortalidade foi observado em indivíduos que conseguiram atingir o estado adulto. Os resultados da pesquisa atual retratam o papel notável de B. bassiana no manejo de um importante vetor de doenças humanas.

Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injury

Drug-induced liver injury (DILI) is a leading reason for preclinical safety attrition and post-market drug withdrawals. Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI, especially in idiosyncratic liver injury. This study examined liver injury reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for drugs associated with hepatotoxicity

ADR/AE early warning analysis of Shujin Jianyao Pills based on spontaneous reporting system / 中国中药杂志

To explore the general characteristics of adverse drug reactions/adverse events(ADR/AE) in patients after using Shujin Jianyao Pills, and explore risk warning signals, this study analyzed 166 cases of ADR/AE reports of Shujin Jianyao Pills collected from 2005 to 2017 based on the National Center for ADR Monitoring spontaneous reporting system(SRS). And the descriptive statistical method was used to analyze general characteristics. The results showed that among the 166 ADR/AE cases, 106 cases were female patients, accounting for 63.86%. Middle-aged and elderly people aged 45 to 64 accounted for the largest proportion(82 cases, 49.40%), which were followed by elderly aged 65 and over(48 cases, 28.91%). ADR/AE involved a wide range of systems and organs, of which skin and its accessories were the most damaged(30 cases, 12.93%), which were followed by systemic damage(27 cases, 11.64%). The top 10 ADR/AE manifestations were rash(15 cases, 6.33%), nausea(14 cases, 5.91%), dizziness(14 cases, 5.91%), abdominal pain(12 cases, 5.06%), pruritus(11 cases, 4.64%), low back pain(11 cases, 4.64%), vomiting(10 cases, 4.22%), hepatocyte damage(9 cases, 3.80%), headache(9 cases, 3.80%), and diarrhea(7 cases, 2.95%). Bayesian confidence propagation neural network(BCPNN) was used to mine the ADR/AE risk early warning signal of Shujin Jianyao Pills, and the propensity score method was used to control the balance of confounding factors. The results suggested warning signs for nausea, diarrhea, rash, and dizziness, vomiting, abdominal pain, headache, liver cell damage. This study provides a basis for the post-marke-ting safety evaluation of Shujin Jianyao Pills, and can provide guidance for its rational clinical use and risk management.

Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014 / 中华流行病学杂志

Objective To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China,and to provide guidance for the implementation of precise intervention.Methods A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014.Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters.Transmission network was constructed by Cytoscape 3.6.0,which was further used for exploring of the major risk factors.Results Of the 2 094 sequences,12.18％ (255/2 094) were in clusters.A total of 82 transmission clusters were identified.The numbers of clusters and contained sequences in intra-provincial transmission (61,173) were significantly more than those in inter-provincial transmission (21,82).The ratio of transmission clustering in MSM increased over time from 2.41％ (2/83) during 1996-2008 to 23.61％ (72/305) during 2013-2014,showing a significant upward trend (x2 =27.800,df=1,P =0.000).The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters,which increased from 0.67％ (2/297) during 1996-2008 to 6.36％(30/472) during 2013-2014,showing a significant upward trend (x2=20.276,df=1,P=0.000).The transmission rate in homosexuals of the inter-transmission clusters (86.59％,71/82) was higher than that of intra-provincial transmission clusters (56.65％,98/173),and the difference was statistically significant (x2=22.792,P=0.000).The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33％,7/21) was higher than that of intra-provincial clusters (13.11％,8/61),and the difference was statistically significant (x2=4.273,P=0.039).Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22％,42/82) was significantly higher than that with intra-provincial transmission clusters (26.59％,46/173),and the difference was statistically significant (x2=14.932,P=0.000).Inter-provincial clusters were mainly detected in and and MSM.Conclusions Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China.Inter-provincial transmission clusters increased rapidly,MSM played an important role in the wide spread of the strain.More researches in transmission networks are needed to guide the precision intervention.

Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014 / 中华流行病学杂志

Objective To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China,and to provide guidance for the implementation of precise intervention.Methods A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014.Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters.Transmission network was constructed by Cytoscape 3.6.0,which was further used for exploring of the major risk factors.Results Of the 2 094 sequences,12.18％ (255/2 094) were in clusters.A total of 82 transmission clusters were identified.The numbers of clusters and contained sequences in intra-provincial transmission (61,173) were significantly more than those in inter-provincial transmission (21,82).The ratio of transmission clustering in MSM increased over time from 2.41％ (2/83) during 1996-2008 to 23.61％ (72/305) during 2013-2014,showing a significant upward trend (x2 =27.800,df=1,P =0.000).The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters,which increased from 0.67％ (2/297) during 1996-2008 to 6.36％(30/472) during 2013-2014,showing a significant upward trend (x2=20.276,df=1,P=0.000).The transmission rate in homosexuals of the inter-transmission clusters (86.59％,71/82) was higher than that of intra-provincial transmission clusters (56.65％,98/173),and the difference was statistically significant (x2=22.792,P=0.000).The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33％,7/21) was higher than that of intra-provincial clusters (13.11％,8/61),and the difference was statistically significant (x2=4.273,P=0.039).Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22％,42/82) was significantly higher than that with intra-provincial transmission clusters (26.59％,46/173),and the difference was statistically significant (x2=14.932,P=0.000).Inter-provincial clusters were mainly detected in and and MSM.Conclusions Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China.Inter-provincial transmission clusters increased rapidly,MSM played an important role in the wide spread of the strain.More researches in transmission networks are needed to guide the precision intervention.

Sulfur-enriched alkaloids from the root of

Five new sulfur-enriched alkaloids isatithioetherins A-E (-), and two pairs of scalemic enantiomers (+)- and (-)-isatithiopyrin B ( and ) and isoepigoitrin and isogoitrin and ), along with the known scalemic enantiomers epigoitrin and goitrin ( and ), were isolated and characterized from an aqueous extract of the roots. Their structures were determined by extensive spectroscopic data analysis, including 2D NMR and theoretical calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory (TDDFT). Compounds - represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Isolation and structure characterization of and support the postulated biosynthetic pathways for the diastereomers and a rare thio-Diels-Alder reaction. Compounds and showed antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2, IC 0.60 and 1.92 μmol/L) and the herpes simplex virus 1 (HSV-1, IC 3.70 and 2.87 μmol/L), and also inhibited Coxsackie virus B3 (IC 0.71 μmol/L).

The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity

Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from and a steroidal glycoside acyltransferase (SGA) from and their application in the biosynthesis of acylated steroidal glycosides (ASGs). Initially, an gene, designated as OsSGT1, was isolated from . OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3- and 17-hydroxyl steroids. Unexpectedly, in an effort to identify OsSGT1, we found the bacteria gene in operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-glucosides (AT-17-Gs) and acetylated estradiol-17-glucosides (AE-17-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 3'-acetylated testosterone17-glucoside towards seven human tumor cell lines were thus observable.

Crystalloid or colloid for goal-directed fluid therapy in cesarean section under combined spinal epidural anesthesia / 中国医师杂志

Objective This study will compare crystalloid to colloid for goal-directed fluid therapy (GDFT) in cesarean section under combined spinal epidural anesthesia,and to discuss which type of fluid is more effective to prevent perioperative hypotention.Methods We randomly assigned 60 patients (ASA Ⅰ-Ⅱ) scheduled undergoing cesarean section into two groups:colloid group and crystalloid group.The colloid group received balanced 6％ HES (130/0.4,Volulyte) and Lactated Ringer's solution (LR),while the crystalloid group just received LR as haemodynamic optimization fluid.The primary outcomes included the incidence of maternal hypotension,and vasopressor doses prior to delivery.The secondary outcomes included umbilical blood gas abnormalities,neonatal Apgar grade and adverse events.Results The impact fluid volume,total liquid volume and urine volume in the crystalloid group were more than those in the colloid group (P ＜ 0.05).No statistical difference was seen in the number of patients who showed hypotension,vomiting and nausea between two groups.And there was no significant difference in the incidence of neonatal adverse effects between two groups.Conclusions No evidence showed that colloid had more advantages in GDFT for patients received cesarean section under combined spinal epidural anesthesia,except that the volume of colloid input was less than crystalloid.

Clinical study of gynecological endoscopic surgery in the combined treatment of previous cesarean scar diverticulum / 中国医师杂志

Objective To investigate the clinical value of hysteroscopy and combined laparoscopic surgery in the treatment of previous cesarean scar diverticulum (PCSD).Methods 36 cases of PCSD in our hospital from January 2013 to January 2015 were selected.Among them,13 cases were treated with hysteroscopy diverticulum incision (hysteroscopic surgery group),and 23 cases underwent hysteroscopy combined with laparoscopy diverticulectomy repair (combined operation group).The diagnosis and surgical treatment of PCSD patients were recorded and the pregnancy outcome was followed up.Results The operation time [(39.5 ± 17.1) min vs (92.3 ± 30.8) min],the amount of bleeding [(18.2 ± 5.6) ml vs (98.6 ± 24.4) ml] and the length of hospital stay [(2.3 ± 0.6) days vs (5.2 ± 1.1) days] in hysteroscopic surgery group were less than those of hysteroscopy combined with laparoscopy (P ＜ 0.05).The time of vaginal bleeding after operation [(6.3 ± 1.7) days vs (13.4 ± 2.7) days] & [(6.9 ± 2.2) days vs (14.0 ± 3.1) days] was significandy less than that before operation in two operation methods (P ＜ 0.05).8 cases effective,1 cases partially effective,3 cases invalid were in the hysteroscopy group,while 16 cases effective,5 cases partially effective,2 cases invalid were in the combined operation group.The difference of curative effect between the two surgical methods was not statistically significant (P ＞0.05).17 cases of fertility requiring patients underwent hysteroscopy combined with laparoscopy diverticulectomy repair,of which 8 eases were successfully delivered after operation.Conclusions Individualized clinical decision-making should be made for PCSD patients.Hysteroscopy and combined hysteroperitoneal surgery have the same effect,but the latter should be chosen for those with severe clinical symptoms or reproductive needs.

The protective effect of dexmedetomidine on acute lung injury induced by lipopolysaccharide / 中国医师杂志

Objective To investigate whether dexmedetomidine (Dex) has a protective effect against acute lung injury (ALI) in lipopolysaccharide (LPS) induced mice model.Methods Mice were randomly allocated into three groups as follows:LPS group (LPS administration),LPS + Dex group1 (LPS administration +50 μg/kg Dex),and LPS + Dex group2 (LPS administration +25 μg/kg Dex).Lung tissue sections were stained with hematoxylin and eosin (HE) to observe the pathological changes.The c-reactive protein was measured with automatic biochemical analyzer.The apoptotic marker Caspase-3 expression was detected by Western blot.Results HE staining showed pulmonary interstitial congestion,edema and inflammatory cell infiltration in LPS group.Intraperitoneal injection of dexmedetomidine could significantly improve the pathological changes of lung tissue.Compared with LPS group,C-reactive protein and Caspase3 were significantly reduced in dexmetomidine group.Conclusions Dexmedetomidine attenuates LPS-induced inflammatory reaction and apoptosis in mice.

Effects of ischemia-reperfusion on endothelial progenitor cell function and iNOS, eNOS expression / 中国医师杂志

Objective To explore the effects of ischemia and ischemia reperfusion on the proliferation,apoptosis,migration ability,inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression of endothelial progenitor cells (EPCs).Methods Collection of peripheral blood from volunteers and culture of endothelial progenitor cells in vitro.The cells were divided into three groups:control group,hypoxia group and hypoxia reoxygenation group.Methyl thiazolyl tetrazolium (MTT) assay was used to detect cell proliferation.Transwell chamber method was used to detect cell migration.Cell apoptosis was detected by flow cytometry.Western blot was used to detect iNOS and eNOS expressions.Results A confocal microscope was used to observe the basic adherence of the cells to the wall for about 3 days,and the area became larger.After 7 d of single nucleus cell culture,the growth of colony-like pattern was more than that of spindle.The cell counts of the three groups in the microscope were (1.83 ± 0.92),(5.07± 0.84),(2.11 ± 0.74).Compared with the control group (0.24 ± 0.04),the hypoxia group (0.62± 0.06) could promote EPCs proliferation,and the difference was statistically significant (t =12.142,P ＜ 0.05);While there was no significant difference between the hypoxia reoxygenation group (0.39 ± 0.06) and the control group (P ＞ 0.05).The number of cell migration in the hypoxia group (18.28 ± 2.05) and hypoxic complex oxygen group (14.08 ± 2.11) was not statistically significant compared with the control group (15.14 ± 1.25) (P ＞ 0.05).The apoptosis rate in hypoxia group (34.57 ±0.42)％ and hypoxia reoxygenation group (41.08 ± 0.44)％ was significantly higher than that in control group (24.83 ± 0.38) ％ (x2 =13.427,15.084,P ＜ 0.05).The apoptosis rate of hypoxia reoxygenation group was significantly higher than that of hypoxia group (x2 =9.657,P ＜ 0.05).The expression of iNOS in hypoxia group and hypoxia reoxygenation group was significantly higher than that in control group,and the difference was statistically significant (P ＜ 0.05).Conclusions Ischemia could promote the proliferation of EPCs,and increase the expression of iNOS,but the expression of EPCs was down-regulated after reperfusion.

Effect of Yupingfeng granule on Th17/Treg balance in children with milk protein allergy / 中国医师杂志

Objective To observe Thl7 cells,Treg cells and their related factors in peripheral blood of children with milk protein allergy and explore the influence of Yupingfeng granule on Th17 / Treg imbalance and its clinical effect.Methods 40 children with milk protein allergy were divided into two groups randomly:the conventional treatment group (n =20),Yupingfeng granule group (n =20).The conventional treatment group received conventional treatment for 2 months.On the basis of routine treatment,Yupingfeng granule group was additionally treated with Yuping feng granule.The serum Th17,Treg cell counts,interleukin (IL)-17 and transforming growth factor-β1 (TGF-β1) levels were detected,and the eczema area and severity index (EASI) score of rash in children was recorded.Results The levels of Th17 cells and IL-17 in allergy children were obviously increased compared with those of the normal children,while the Treg cells,and the TGF-β1 level were lower than those of the normal children (P ＜ 0.05).After treatment,the Thl7 cells,the IL-17 levels and ESAI scores of the conventional treatment group and the Yupingfeng granule group were lowered,while the Treg cells and the TGF-β1 levels were increased (P ＜ 0.05).Compared with the conventional treatment group,these indexes increased and decreased more significantly in the Yupingfeng granule group (P ＜ 0.05).Conclusions Milk allergy children have obvious imbalance of Thl7/Treg;the Yupingfeng granule can adjust this imbalance and alleviate the allergic symptoms of milk protein.

Protective Effect of remote ischemic preconditioning on liver warm ischemia-reperfusion injury in aged rats / 中国医师杂志

Objective To investigate the effect of remote ischemic preconditioning on nuclear factor erythroid-2 related factor 2 (Nrf2) signaling in the liver of aged rats after warm ischemia reperfusion injury.Methods A 70％ hepatic warm ischemia-reperfusion model was established in aged rats (15-16 months old) (1 hour after ischemia and 2 hours after reperfusion).12 male Sprague-Dawley rats were divided into two groups:pretreatment group and control group.The level of serum alanine aminotransferase (ALT) was detected after operation and the liver tissues were harvested for the determination of malondialdehyde (MDA) content and the activity of antioxidant enzyme-superoxide dismutase (SOD).The pathological changes of liver were observed.The change of Nrf2 protein expression in liver tissue was examined by Western blot.Results Serum ALT and MDA in the pretreatment group were significantly lower than those in the control group.The liver pathological damage of pretreatment group rats were lighter than the control group (P ＜ 0.05).Compared with the control group,the Nrf2 protein expression and the activity of SOD increased in the liver of pretreatment group (P ＜ 0.05).Conclusions Remote ischemic preconditioning can reduce 70％ hepatic ischemia-reperfusion injury in aged rats,and its mechanism may be related to its activation of Nrf2 signaling pathway.