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There are urgent calls for new approaches to map the global urban conditions of complexity, diffuseness, diversity, and connectivity. However, existing methods mostly focus on mapping urbanized areas as bio physical entities. Here, based on the continuum of urbanity framework, we developed an approach for cross-scale urbanity mapping from town to city and urban megaregion with different spatial resolutions using the Google Earth Engine. This approach was developed based on multi-source remote sensing data, Points of Interest – Open Street Map (POIs-OSM) big data, and the random forest regression model. This approach is scale-independent and revealed significant spatial variations in urbanity, underscoring differences in urbanization patterns across megaregions and between urban and rural areas. Urbanity was observed transcending traditional urban boundaries, diffusing into rural settlements within non-urban locales. The finding of urbanity in rural communities far from urban areas challenges the gradient theory of urban-rural development and distribution. By mapping livelihoods, lifestyles, and connectivity simultaneously, urbanity maps present a more comprehensive characterization of the complexity, diffuseness, diversity, and connectivity of urbanized areas than that by land cover or population density alone. It helps enhance the understanding of urbanization beyond biophysical form. This approach can provide a multifaceted understanding of urbanization, and thereby insights on urban and regional sustainability.

Bhutan remains a largely non-industrialized country, making minimal contributions to global warming and climate change. Yet, the country suffers from the clutches of the adverse effects of climate change. Among them, the impact of climate change on mental health including psychological distress, acute stress disorder, post-traumatic stress disorder, major depressive disorder and anxiety disorder is well known. In this article, we aim to describe the various mental health issues that the country is facing or is likely to face in the future as a result of climate change.

Equal access to social infrastructures is a fundamental prerequisite for sustainable development, but has long been a great challenge worldwide. Previous studies have primarily focused on the accessibility to social infrastructures in urban areas across various scales, with less attention to rural areas, where inequality can be more severe. Particularly, few have investigated the disparities of accessibility to social infrastructures between urban and rural areas. Here, using the Changsha–Zhuzhou–Xiangtan urban agglomeration, China, as an example, we investigated the inequality of accessibility in both urban and rural areas, and further compared the urban-rural difference. Accessibility was measured by travel time of residents to infrastructures. We selected four types of social infrastructures including supermarkets, bus stops, primary schools, and health care, which were fundamentally important to both urban and rural residents. We found large disparities in accessibility between urban and rural areas, ranging from 20 min to 2 h. Rural residents had to spend one to two more hours to bus stops than urban residents, and 20 min more to the other three types of infrastructures. Furthermore, accessibility to multiple infrastructures showed greater urban-rural differences. Rural residents in more than half of the towns had no access to any infrastructure within 15 min, while more than 60% of the urban residents could access to all infrastructures within 15 min. Our results revealed quantitative accessibility gap between urban and rural areas and underscored the necessity of social infrastructures planning to address such disparities.

Gut-liver axis and cellular homeostasis play key roles in alcohol liver disease (ALD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis. We investigated whether the beneficial effects and underlying mechanisms of Jia-ga-song Tang (JGST) against ALD were associated with gut-liver axis and cellular homeostasis. A predictive network depicting the relationship between Jia-Ga-Song-Tang (JGST) and alcoholic liver disease (ALD) was designed by Network pharmacology. Next, 5% v/v Lieber-DeCarli alcohol liquid diet was used to establish the ALD. JGST protected the liver damage, repaired the intestines to alleviate the Two-hit on the liver, and balanced the cellular homeostasis. It was manifested in repairing the liver and intestinal pathological structure, reducing serum ALT, AST, and liver TG, TC, MDA, CAT, and increasing liver GSH, and intestine GSH-Px. JGST mainly inhibited the liver mRNA levels of HO-1, NQO1, GCLC, FASN, and PPARα and activated the intestinal mRNA levels of HO-1 and NQO1, while inhibiting the liver protein levels of HO-1, NQO1. Furthermore, LPS and LBP in the plasma and the expression of inflammatory factors such as IL-1β, TNF-α, IL-6, TGFβ1, CD14, and Myd88 were reduced after treatment to prove that JGST protects the liver from Two-hit. Ethanol was used to intervene in HepG2 and IEC-6 to establish an ALD cell model and treated by Germacrone, ML385, and TBHQ. repaired the intestinal barrier, and inhibited Nrf2 in IEC-6, but protect the HepG2 by activating Nrf2 to balance cellular homeostasis. Our results reinforce that JGST provides an effective protective method for alcoholic liver disease (ALD) by regulating Gut-liver axis and cellular homeostasis.

Immunoassay is a diagnostic tool based on the specific binding of antibodies and antigens with widespread applications. Nonetheless, several research obstacles, like poor specific antibodies, the poisonous reagents and unstable results, still remain challenges. Herein, we innovatively reported a colorimetric and fluorescent dual-mode immunoassay based on the bifunctional nanobody for SEA detection. Benefiting from the advantages of nanobodies, the bifunctional protein with both recognition and catalysis was built to identify and catalyze with efficiency to generate the first colorimetric signal. Meanwhile, the introduction of quinine as the natural source of the second fluorescent signal greatly improved the stability and safety of detection. In addition, the proposed method was successfully applied to detecting SEA in food samples with high accuracy and stability. This study integrated the bifunctional nanobody with eco-friendly fluorescent product to provide a specific and green platform for the detection of foodborne toxins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

HEV infection has become a global health concern. The study of HEV pathogenicity has been hindered by the lack of a suitable in vitro culture system. In the present research, we systematic demonstration of efficient replication of swine GT4 HEV in A549 cells, Huh-7 cells, and HepG2/C3A cell lines. The results of the immunofluorescence assay and immunofluorescence confocal assay showed that swine GT4 HEV is efficiently replicated in three cell lines at 72 h postinoculation. Meanwhile, we also detected the virus titer quantified were increased at 2-, 6,- and 11-days postinoculation. Moreover, we successfully observed HEV virus particles in the cell suspension at 6 days postinoculation. This finding holds significance for advancing in vitro HEV studies., (© 2024 Wiley Periodicals LLC.)

Background: Pulmonary fibrosis, a progressive and fatal lung disease with no effective treatment medication, is characterized by lung remodeling and fibroblastic foci caused by an oxidative imbalance with an overloading deposition of collagen. Trichodelphinine A, a hetisine-type C20-diterpenoid alkaloid, was found anti-fibrotic activity in vitro, but its effect and mechanism on pulmonary fibrosis still unknown., Purpose: Our study aimed to investigate and validate the anti-fibrotic properties of trichodelphinine A in pulmonary fibrosis animals induced by bleomycin (BLM), and its mechanism whether via NOX4-ARG1/TGF-β signaling pathway., Methods: The anti-fibrotic effects of trichodelphinine A were evaluated using BLM-induced rats through indicators of lung histopathology and collagen synthesis. Dynamic metabolomics evaluated the metabolic disorder and therapeutic effect of trichodelphinine A. The interaction between trichodelphinine A and NOX4 receptor was confirmed using CETSA and molecular dynamics experiments. Molecular biology experiments were conducted in NOX4 gene knockout mice to investigate the intervention effect of trichodelphinine A., Results: Trichodelphinine A could suppress histopathologic changes, collagen deposition and proinflammatory cytokine release pulmonary fibrosis in bleomycin induced rats. Dynamic metabolomics studies revealed that trichodelphinine A could correct endogenous metabolic disorders of arachidonic acid, arginine and proline during fibrosis development, which revealed that the regulation of oxidative stress and amino acid metabolism targeting NOX4 and ARG1 may be the main pharmacological mechanisms of trichodelphinine A on pulmonary fibrosis. We further determined that trichodelphinine A inhibited over oxidative stress and collagen deposition by suppressing Nrf2-keap1 and ARG1-OAT signaling pathways, respectively. Molecular dynamics studies showed that trichodelphinine A was directly binds with NOX4, in which PHE354 and THR355 residues of NOX4 are critical binding sites for trichodelphinine A. Mechanistic validation in cells or mice with NOX4 knockout or silencing suggested that the anti-fibrotic effects of trichodelphinine A depended on inhibition of NOX4 to suppress ARG1/OAT activation and TGF-β/Smads signaling pathway., Conclusion: Collectively, our findings indicate a powerful anti-fibrotic function of trichodelphinine A in pulmonary fibrosis via targeting NOX4. NOX4 mediates the activation of ARG1/OAT to regulate arginase-proline metabolism, and promotes TGF-β/Smads signaling pathway, thereby affecting the collagen synthesis in pulmonary fibrosis, which is a novel finding and indicates that inhibition of NOX4 is a novel therapeutic strategy for pulmonary fibrosis., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these., (Copyright © 2024. Published by Elsevier GmbH.)

In humans, solitary renal involvement or primary renal echinococcosis is rare, accounting for about 2-4 % of cases. Usually, patients shpw no obvious symptoms, but they can manifest as renal pain, renal mass, gross hematuria, and hydatiduria in rare cases. We report a case of primary renal cystic echinococcosis, which was originally misdiagnosed as a tuberculous renal abscess., Competing Interests: We declare that we have no conflict of interest., (© 2024 The Authors.)

Objective: Health-related quality of life (HRQoL) was an important health outcome measure for evaluating an individual's overall health status. However, there was limited in the literature on HRQoL and its long-term changes of the Tibetan population. This study aimed to assess HRQoL of Tibetan and its changes over time, and explore the differences in HRQoL for residents at different altitudes., Design: Data for the cross-sectional study were extracted from the fifth and sixth waves of the National Health Services Surveys which were conducted in 2013 and 2018. A multistage stratified cluster random sampling strategy was used to select representative participants., Setting: Tibet Autonomous Region in China., Participants: This study recruited 14 752 participants in 2013 and 13 106 participants in 2018, and after excluding observations with missing values for key variables, 10 247 in 2013 and 6436 in 2018 were included in the study analysis., Primary and Secondary Outcome Measures: The EQ-5D-3L was used to measure participants' HRQoL., Results: The mean health state utility scores of the participants were 0.969±0.078 and 0.966±0.077 in 2013 and 2018, respectively. Pain/discomfort was the most frequently prevalent issue reported in 18.1% and 17.9% of the participants in 2013 and 2018, respectively. Tibetans living 3500-4000 m altitude had the best HRQoL. Age, sex, employment status, educational attainment, chronic disease and weekly physical exercise were influencing factors associated with HRQoL., Conclusions: The HRQoL of the Tibetan population was lower than the general Chinese population, and decreased over time between 5 years. There were differences in HRQoL among Tibetan at different altitudes, with residents living at 3500-4000 m having the best quality of life. More attention should be paid to those Tibetans who are older, female, unemployed and without formal education., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Providing equitable access to health care for all populations is an important sustainable development goal. China has made significant progress in achieving equity in healthcare utilization. However, research on equity in healthcare utilization in Tibet is sparse. This study aims to evaluate changes in income-related inequity in inpatient care utilization and unmet needs between 2013 and 2018 among the Tibetan population and identify the inequity source., Methods: Data for this cross-sectional study were obtained from the fifth and sixth waves of the National Health Services Survey in 2013 and 2018. After excluding observations with missing values for key variables, 11,092 and 10,397 respondents were included in this study, respectively. The outcome variables of interest were inpatient service utilization and unmet hospitalization needs. The concentration index and horizontal inequity index (HI) were used to assess income-related inequity. Non-linear decompositions were performed to identify the main contributors to inequity. In the decomposition method, need variables included sex, age, chronic diseases, and the EuroQol-Visual Analog Scale; non-need variables consisted of income, education, employment status, marital status, and health insurance schemes., Results: The probability of inpatient care utilization increased from 6.40% in 2013 to 8.50% in 2018. The HI for inpatient care utilization was 0.19 (P < 0.001) in 2013, whereas it decreased to 0.07 (P < 0.001) in 2018. The contribution of income to inequity in inpatient care utilization decreased from 87.09% in 2013 to 59.79% in 2018. As for unmet inpatient care needs, although its probability increased from 0.76 to 1.48%, the percentage of reasons for financial hardship decreased from 47.62 to 28.57%. The HI for unmet hospitalization need was - 0.07 in 2013 and - 0.05 in 2018, and neither was statistically significant. The New Rural Cooperative Medical Scheme made majority contributions to promote equity in unmet hospitalization need. Moreover, the female respondents reporting low EuroQol-Visual Analog Scale scores and patients with chronic disease were not only more likely to seek for inpatient care, but also have more unmet need than the reference groups., Conclusions: The inequity in inpatient care utilization in Tibet narrowed from 2013 to 2018, and there was no inequity in unmet hospitalization needs in 2013 and 2018. Income and the New Rural Cooperative Medical Scheme are the main drivers of equity promotion. To promote access to inpatient care utilization and decrease the probability of unmet hospitalization need in future, policymakers should target high-need residents in Tibet to improve accessibility, availability, and acceptability., (© 2023. The Author(s).)

Endometrial cancer (EC) is a complex disease that affects the reproductive health of females worldwide. Platycodin D (PD) is known to exert numerous anticancer effects, markedly inhibiting cell proliferation, inducing apoptosis and causing cell cycle arrest in several types of cancer. The present study aimed to explore the mechanisms underlying the effects of PD in EC cells. The viability and proliferation of human endometrial stromal cells (ESCs) and RL95-2 EC cells following treatment with PD were evaluated using Cell Counting Kit-8, MTT and colony formation assays. Wound healing and Transwell assays were also performed to assess the migration and invasion of EC cells following treatment with PD. The expression levels of α2A-adrenergic receptor (ADRA2A) were measured using reverse transcription-quantitative PCR and western blotting assays with and without PD treatment and following transfection with short hairpin (sh) RNAs targeting ADRA2A2. Moreover, western blot analysis was performed to measure the expression levels of Ki67, PCNA, MMP2 and MMP9 and the phosphorylation of proteins of the PI3K/Akt signaling pathway. The results demonstrated that treatment with PD markedly decreased the proliferation, invasion and migration of EC cells, and reduced activation of the PI3K/Akt signaling pathway in EC cells. Moreover, transfection with sh-ADRA2A attenuated the effects of PD. ADRA2A expression was downregulated in EC cells compared with ESCs, and ADRA2A expression was elevated in EC cells following treatment with PD. In conclusion, the present study indicates that PD blocked the PI3K/Akt signaling pathway via the upregulation of ADRA2A expression, thereby inhibiting the proliferation, invasion and migration of EC cells., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ni et al.)

Ethnopharmacological Relevance: Herba Delphinii Brunoniani, a Tibetan Material Medica, derived from the aerial parts of Delphinium brunonianum Royle, possesses efficacy of cooling blood to remove apthogentic heat, and dispelling wind to arrest itching, and has been used for the treatment for liver disease according to Tibetan Medicine Theories in Shel Gong Shel Phreng. However, the mechanisms of action remain unclear., Aim of the Study: This work aimed to investigate the efficacy mechanism of Delphinium brunonianum extract (DBE) on nonalcoholic steatohepatitis (NASH), a kind of liver disease by integrating serum metabolomics and network pharmacology analysis., Materials and Methods: In this study, NASH model mice were established by a high-fat diet. The indexes of lipid accumulation, insulin resistance, and inflammatory reaction were used to evaluate the efficacy of DBE. A combination of UHPLC-QTOF-MS based metabolomics and network pharmacology was established to illustrate the serum biomarkers of NASH mice and to demonstrate the anti-NASH mechanisms of DBE. Serum metabolomics demonstrated potential metabolites and the corresponding metabolic pathways in the efficacy of DBE. Network pharmacology screened the targets of DBE against NASH. Finally, the mechanisms of DBE against NASH were verified by in-vivo pharmacology., Results: Metabolomics revealed that DBE significantly regulated the abnormal levels of twenty-two metabolites, which involved the biosynthesis of unsaturated fatty acids and steroid hormone, linoleic acid metabolism, arachidonic acid metabolism, and alpha-Linolenic acid metabolism pathways. Network pharmacology showed that DBE exhibited anti-NASH effects through regulating the targets of PTGS2, PLA2, ALOX5, ALOX15, FASN, and CYP450. Finally, united pharmacological verification result, we found that the mechanisms of DBE against NASH may be related to the regulation of the unsaturated fatty acids biosynthesis and the arachidonic acid metabolism pathway., Conclusions: Integrating serum metabolomic and network analysis, we found that DBE might inhibit the pathological process of NASH by regulating the relative targets and the metabolic pathways, which may be a potential mechanism for the anti-NASH efficacy of DBE. This integrated strategy also provided a rational way for revealing the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine (TCM)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from Delphinium brunonianum . Four novel diterpenoid alkaloids, brunodelphinine B-E, were isolated from D. brunonianum together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids-brunodelphinine E ( 4 ), delbruline ( 5 ), lycoctonine ( 7 ), delbrunine ( 8 ), and sharwuphinine A ( 12 )-exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A ( 12 ) displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of D. brunonianum and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.

Objective: The objective of this study is to investigate the therapeutic effect of surfactant replacement therapy (SRT) on respiratory distress syndrome (RDS) in premature infants in the Qinghai-Tibet Plateau., Materials and Methods: This multi-center retrospective cohort study collected and screened reasonable clinical data of 337 premature infants with RDS from 10 hospitals in the Qinghai-Tibet Plateau from 2015 to 2017. We grouped the cases by rationally analyzing their baseline characteristics, using logistic analysis to evaluate each factor's effect on the prognosis of the infants, and comparing the short-term improvement in blood gas and mortality after SRT treatment at different altitudes, in high-altitude (1,500-3,500 m) and ultra-high-altitude (3,500-5,500 m) groups., Results: Independent of altitude, the mortality rate of children with RDS in the SRT group was significantly lower than that of children in the non-SRT group (both P < 0.05). The effect of SRT on preterm infants with RDS in the high-altitude group [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.22-0.87, P = 0.02] was better than that in the infants in the ultra-high-altitude group (OR = 0.26, 95% CI = 0.13-0.58, P < 0.01), with death rates of 34.34 and 49.71%, respectively. Similarly, after SRT, the improvement of PaO 2 /FiO 2 and pH of children at high altitude was significantly better than those of children at ultra-high altitude (all P < 0.01)., Conclusions: SRT plays a prominent role in curing infants with RDS in both high- and ultra-high-altitude regions, although with better effects at high rather than ultra-high altitude. This study provides a basis for further large-scale studies on SRT for RDS treatment at high altitudes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duan, Li, Chen, Shi, Chen, Xue, Liu, Wang, Qiu, Yu, Qiang, Wu, Wu, Zhang, Chen, Jigme, Xu, Mima, Da, Ren, Gesang, Pubu, Li, Lv, Zhou, Zhang, Dawa, Gongjue, Wang, Wu and Li.)

The study aimed to investigate the dynamic changes of percutaneous partial oxygen pressure during the development and evolution of a hypertrophic scar. Twenty cases of hypertrophic scar patients at different stages were selected. A percutaneous oxygen monitor was used to measure oxygen partial pressure in the scar and normal skin tissue at 14, 30, 60, and 90 days after surgery. The changes of oxygen partial pressure, tissue structure, HIF-1 α , and VEGF expression in the scar tissue were observed, and the correlation was analyzed. In the scar maturation process, with the prolongation of time, the partial oxygen pressure in the tissue increased gradually. The expression intensity of HIF-1 α and VEGF decreased gradually, HIF-1 α was positively correlated with VEGF ( r  = 0.98, P < 0.01), there was a negative correlation between oxygen partial pressure and HIF-1 α expression ( r  = -0.92, P < 0.01), and it was negatively correlated with VEGF ( r  = -0.88, P < 0.01). TcPO 2 measurement can be used to assess scar maturity; HIF-1 α and VEGF may play an essential role in regulating partial oxygen pressure in the scar tissue., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wanle Qi et al.)

We aimed to evaluate the association of altitudes with the prevalence of hypertension among residents aged 15 years and above in Tibet, China. Data for 11,407 Tibetan residents from the National Health Services Survey in 2013 were analyzed. Association between altitudes and prevalence of physician-diagnosed hypertension was assessed by two logistic regression models as follows: (i) a base model adjusted for age and gender, and (ii) a full model additionally adjusted for body mass index, education, marital status, area of residence, distance to the nearest medical institute, smoking, drinking, and exercise. Nonlinear relationship between altitudes and prevalence of hypertension was explored by restricted cubic spline analyses. Sensitivity analyses were conducted by restricting to residents of rural and/or nomadic areas. The prevalence of hypertension was estimated to be 37.6%. We found a U-shaped association between altitudes and prevalence of physician-diagnosed hypertension with a turning point at around 3800 m (12,467 ft). For residents living above 3800 m, a 1000 m increase in altitudes was associated with 2.05 (95% confidence interval [CI]: 1.62-2.61) times higher odds of having physician-diagnosed hypertension, after adjusting for age and gender. When further controlling for all covariates, the odds ratio (OR) dropped to 1.87 (95% CI: 1.46-2.41). For residents living below 3800 m, a 1000 m increase was associated with 0.29 (95% CI: 0.19-0.44) times less likelihood of having physician-diagnosed hypertension in the full model. Sensitivity analyses among residents in rural and/or nomadic areas showed similar associations. To conclude, altitudes were in a U-shaped association with prevalence of hypertension.

The soil bacterial communities have been widely investigated. However, there has been little study of the bacteria in Qinghai-Tibet Plateau, especially about the culturable bacteria in highland barley cultivation soil. Here, a total of 830 individual strains were obtained at 4°C and 25°C from a highland barley cultivation soil in Qamdo, Tibet Autonomous Region, using fifteen kinds of media. Seventy-seven species were obtained, which belonged to 42 genera and four phyla; the predominant phylum was Actinobacteria (68.82%), followed by Proteobacteria (15.59%), Firmicutes (14.29%), and Bacteroidetes (1.30%). The predominant genus was Streptomyces (22.08%, 17 species), followed by Bacillus (6.49%, five species), Micromonospora (5.19%, four species), Microbacterium (5.19%, four species), and Kribbella (3.90%, three species). The most diverse isolates belonged to a high G+C Gram-positive group; in particular, the Streptomyces genus is a dominant genus in the high G+C Gram-positive group. There were 62 species and 33 genera bacteria isolated at 25°C (80.52%), 23 species, and 18 genera bacteria isolated at 4°C (29.87%). Meanwhile, only eight species and six genera bacteria could be isolated at 25°C and 4°C. Of the 77 species, six isolates related to six genera might be novel taxa. The results showed abundant bacterial species diversity in the soil sample from the Qamdo, Tibet Autonomous Region., Competing Interests: Conflict of interest The authors do not report any financial or personal connections with other persons or organizations, which might negatively affect the contents of this publication and/or claim authorship rights to this publication, (© 2021 Hu Pan et al.)

Five new amide alkaloids, named delamide A-E (1-5), along with five known ones, methyl-N-(3-carboxy-2-methylpropanoyl) anthranilate (6), benzoic acid, 2-[(1-oxodecyl) amino]-methylester (7), puberline (8), benzoic acid, 2-[(4-methoxy-2-methyl-1, 4-dioxobutyl) amino]-methylester (9) and benzoic acid, 2-[(4-methoxy-3-methyl-1, 4-dioxobutyl) amino]-methylester (10) were isolated from the extract of Delphinium brunonianum. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). 1-10 were also evaluated for their acetylcholinesterase (AChE) inhibiting activity by the Ellman's method. Delamide A (1) showed highly selective AChE inhibition activity. The kinetic analysis revealed that 1 was a mixed-type reversible inhibitor of AChE., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Previous small sample studies suggested that elevated altitudes might be associated with the incidence of cardiovascular diseases. However, it remains uncertain whether high altitudes (over 3000 m above sea level) are related to congenital heart disease. We therefore explored the prevalence of congenital heart disease in a large cohort of students in the world's largest prefecture-level city with the highest altitude., Methods: This cross-sectional study included 84,302 student participants (boys 52.12%, girls 47.88%, with an average age of 10.62 ± 3.33 years). Data were extracted from the screening results among different altitude area schools in Nagqu from June 2016 to August 2017. Students were first screened by performing a physical examination consisting of cardiac auscultations and clinical manifestation screenings. An echocardiography was performed to confirm and identify the subtype of congenital heart disease., Results: The prevalence of congenital heart disease among students in Nagqu, Tibet, was 5.21‰ (439 cases). The most common congenital heart disease type was patent ductus arteriosus, representing 66.3% of congenital heart diseases diagnosed in this study, followed by atrial septal defect and ventricular septal defect, representing 20.3% and 9.1% of congenital heart diseases, respectively. Students living in higher altitudes were significantly more prone to have congenital heart disease than students in locations with lower altitudes. The prevalence of congenital heart disease in girls was found to be higher than that of boys., Conclusions: The correlation between congenital heart disease and increased altitude is noteworthy. This study's results are the first big data epidemiological investigation to confirm that high altitude is a significant environmental risk factor for congenital heart disease, especially patent ductus arteriosus. Furthermore, the results provide additional support to make a diagnostic and treatment plan to prevent congenital heart disease in high altitude areas.

Objective: To provide a reference for the standardization of Tibetan medicine., Method: Investigating the hospital preparations , Tibetan formulated products, and the literature recorded preparations in the Tibetan, Qinghai, Gansu, Sichuan and Yunnan Provinces. Moreover, the varieties, original bases and standard conditions of these preparations were analyzed. According to Chinese Pharmacopoeia, Tibetan medicine part of ministerial standard, Tibetan medicine standards and related monographs and literatures of Tibetan medicine., Result: About 502 various of herbs were used in 711 hospital preparations from 40 medical institutions, Tibetan formulated products from Tibetan pharmaceutical factories, and 439 literature recorded preparations. About 154 herbs were used in more than 10 preparations, while most of them were Tibetan endemic species. About 416 medicinal varieties have the original documented basis, including 287 botanicals, 78 animal medicines, 51 mineral medicines, involving a total of 94 families, 261 genus and 643 species of botanical origin (including species of the next grade), 35 families, 52 genera and 61 species of the animal origin (including species of the next grade). About 122 varieties of herbs were cross-used in the traditional Chinese medicine and Tibetan medicine, about 80% of Tibetan medicinal varieties are produced in the Tibetan Areas of Tibet Plateau. About 293 medicinal varieties were contained in the above standards. Most of the herb's standards only contains character, indentification, and examination, except for 8 varieties which were recorded in the Chinese Pharmacopoeia (2010) as Tibetan medicine., Conclusion: This study of quality standard of Tibetan medicine should have an emphasis on the general varieties, especially the study on the arrangement research and the efficacious material basis of the varieties and the original, as well as term standardization of the National Medicine.

Objective: To study the chemical constituents of Incarvillea younghusbandii., Method: The chemical constituents were isolated by various column chromatographic methods and structurally identified by NMR and MS evidence., Result: Fifteen compounds were obtained and identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), boschniakinic acid (11), tert-O-beta-D-glucopyranosyl-(R)-heraclenol (12), 5-methoxy-8-O-beta-D-glucopyranosyloxypsoralen (13), 1'-O-beta-D-glucopyranosyl-3-hydroxynodakenetin (14) and phenylethyl-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (15)., Conclusion: All of these compounds were isolated from this plant for the first time and most of them are furocoumarins.

The chemical constituents of the traditional Tibetan medicine of Saussurea medusa Maxim. (Compositae) were investigated and a new flavonoid glucoside, together with 14 known compounds, was isolated. The structure of the new compound was established as 6''-O-crotonoylhomoplantaginin by using one- and two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry analyses.

An improved HPLC-DAD-ESI-MS(n) method has been developed to simultaneously quantify eight major compounds in Saussurea tridactyla Sch.-Bip. ex Hook. f. which has long been used as a traditional Tibetan medicine. This method was validated to be sensitive, precise and accurate with the LODs of 0.11-5.01 microg/ml, the overall intra-day and inter-day variations less than 2.70%, and the overall recovery over 98.0%, respectively. The correlation coefficients (r(2)) of the calibration curves were higher than 0.991. This newly established method was successfully applied to reveal the difference in the chemical profiles and contents of these analyses in S. tridactyla from different localities. In addition, by comparison UV and MS spectra with those of authentic compounds and literatures, a total of fourteen peaks were identified. It can be concluded that this method was effective to ensure the safety and efficacy consistency of S. tridactyla, and can be applied to other traditional Tibetan medicinal plants from different resources in Tibet.

After the digestion of cigarettes and its ash are digested with concentrated nitric acid and perchloric acid, the change in mineral elements (Ca, Mg, Cu, Fe, Zn, Mn, Ni, Co, Cr, Pb and Cd) content in the cigarette and its ash were determined by flame atomic absorptionspectrophotometry. The experimental results showed that there were differences between the cigarette (tobacco) and its ash, especially, the contents of Pb and Cd harmful to human health in the ash are lowed 26.4% and 44.2%, respectively. It is concluded that a part of Pb and Cd in the cigarette passes through the human lung respiration and air environment.