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Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.
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This Synopsis covers recent reports of metal-catalyzed alkene functionalizations that likely involve iterative outer-sphere reactions in which the substrate reacts directly with a metal ligand instead of with the metal center itself. Traditional metal hydride-catalyzed alkene functionalizations involve this latter pathway whereby the alkene forms part of the metal ligand sphere (i.e. an inner-sphere reaction). In contrast, alkenes do not ligate the metal in so-called outer-sphere reactions and instead react with a metal ligand. These transformations have proved crucial for the synthesis of high fraction sp3 (Fsp3) targets, especially in hindered fragment couplings of relevance to natural product space.
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The synthesis of quaternary carbons often requires numerous steps and complex conditions or harsh reagents that act on heavily engineered substrates. This is largely a consequence of conventional polar-bond retrosynthetic disconnections that in turn require multiple functional group interconversions, redox manipulations, and protecting group chemistry. Here, we report a simple catalyst and reductant combination that converts two types of feedstock chemicals, carboxylic acids and olefins, into tetrasubstituted carbons through quaternization of radical intermediates. An iron porphyrin catalyst activates each substrate by electron transfer or hydrogen atom transfer, and then combines the fragments using a bimolecular homolytic substitution (SH2) reaction. This cross-coupling reduces the synthetic burden to procure numerous quaternary carbon---containing products from simple chemical feedstocks.
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Cross-coupling catalysts typically react and unite functionally distinct partners via sequential inner-sphere elementary steps: coordination, migratory insertion, reductive elimination, etc. Here, we report a single catalyst that cross-couples styrenes and benzyl bromides via iterative outer-sphere steps: metal-ligand-carbon interactions. Each partner forms a stabilized radical intermediate, yet heterocoupled products predominate. The system is redox-neutral and, thus, avoids exogenous oxidants, resulting in simple and scalable conditions. Numerous variations of alkene hydrobenzylation are made possible, including access to the privileged heterodibenzyl (1,2-diarylethane) motif and challenging quaternary carbon variants.
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Pilonidal sinus is a chronic condition characterized by inflammation, swelling, and pain in the sacrococcygeal region. In recent years, the rate of recurrence and wound complications in PSD remains high, and no treatment is universally accepted. This study aimed to compare the efficacy of phenol treatment with surgical excision treatment for PSD through a meta-analysis of controlled clinical trials. We searched three electronic databases, PubMed, Embase, and Cochrane library, to comprehensively search the literature comparing phenol treatment and surgical treatment of pilonidal sinus. Fourteen publications were included, including five RCTs and nine non-RCTs. The phenol group had a slightly higher rate of disease recurrence than the surgical group (RR = 1.12, 95% CI [0.77,1.63]), but the difference was not statistically significant (P = 0.55 > 0.05). As compared to the surgical group, wound complications were considerably less common (RR = 0.40, 95% CI [0.27,0.59]). Phenol treatment resulted in a significantly shorter operating time than surgery treatment (weighted mean difference -22.76, 95% CI [-31.13,-14.39]). The time to return to daily work was considerably shorter than in the surgical group (weighted mean difference -10.11, 95% CI [-14.58,-5.65]). Postoperative complete healing time was significantly shorter than surgical healing time (weighted mean difference -17.11, 95% CI [-32.18,-2.03]). Phenol treatment is effective for pilonidal sinus disease, and its recurrence rate is not significantly different from surgical treatment. The greatest advantage of phenol treatment is the low incidence of wound complications. Moreover, the time required for treatment and recovery are significantly lower than for surgical treatment.
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Fenol , Seio Pilonidal , Humanos , Fenol/uso terapêutico , Seio Pilonidal/cirurgia , Recidiva Local de Neoplasia , Cicatrização , Dor , Recidiva , Resultado do TratamentoRESUMO
Metal-hydride hydrogen atom transfer (MHAT) has emerged as a useful tool to form quaternary carbons from alkenes via hydrofunctionalization. Methods to date that cross-couple alkenes with sp3 partners rely on heterobimetallic catalysis to merge the two cycles. Here, we report an iron-only cross-coupling via putative MHAT/SH2 steps that solves a key stereochemical problem in the synthesis of meroterpenoid eugenial C and obviates the need for nickel. The concise synthesis benefits from a conformationally locked o,o'-disubstituted benzyl bromide and a locally sourced chiral pool terpene coupling partner.
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OBJECTIVE To provide reference for improving the classification management of prescription drugs and non- prescription drugs in China by learning from the classification management system of prescription drugs and non-prescription drugs in Canada. METHODS The content and experience of classification management system of prescription drugs and non-prescription drugs in Canada were analyzed, and the thinking of the classification management of prescription drugs and non-prescription drugs in China was proposed. RESULTS &&CONCLUSIONS According to the classification of prescription drugs and non-prescription drugs, drugs can be divided into class Ⅰ drugs, class Ⅱ drugs, class Ⅲ drugs, unclassified drugs in Canada. Specific evaluation factors and management requirements have been established for drug classification. Canada has established a set of systematic management systems and technical standards, which has reference value for improving the classification management system in China. It is suggested to further improve the drug classification management system and supporting policies, strengthen fine classification management of prescription drugs and non-prescription drugs and improve classification registration and transformation review standards in China, by learning from Canadian prescription drug and non-prescription drug system and management model.
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OBJECTIVE To predict the development trends of licensed pharmacist staffing in retail pharmacies within the western China and provide reference for the formulation of policies related to licensed pharmacists. METHODS Based on the data of retail pharmacies and licensed pharmacists in the western China from 2016 to 2022, a grey model was constructed to analyze and predict the number development trends of retail pharmacies and licensed pharmacists in the western China from 2023 to 2026. RESULTS Currently, the 1∶1 staffing requirement for licensed pharmacists and retail pharmacies had been met in Shaanxi, Guangxi and Gansu. Based on current trends, Inner Mongolia, Chongqing, Yunnan, and Qinghai were expected to meet the 1∶1 staffing requirement for licensed pharmacists and retail pharmacies between 2023 and 2026. Sichuan and Xinjiang were also expected to meet this requirement in the future. However, there was still a significant gap in Guizhou, Xizang, and Ningxia towards achieving the above goals. CONCLUSIONS There is still a discrepancy between the deployment of licensed pharmacists and the national requirements in certain western provinces. Local authorities should formulate relevant policies according to local circumstances. Regions that have already met or will soon achieve the staffing requirement for licensed pharmacists should continue to enhance the quantity and quality of their licensed pharmacist workforce. In areas where meet this criterion in the short term is not feasible, it is necessary to strengthen the development of the licensed pharmacist workforce, and control the number of new retail pharmacies.
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Objective: The present study aims to evaluate the relationship of thyroid function during the first trimester of pregnancy with lipid levels and pregnancy outcomes. Methods: Women who delivered babies at the Shanghai General Hospital between March 2019 and December 2019 with a known pregnancy outcome and complete data were included in the present study (n = 1779). A retrospective cohort study of all subjects with available first-trimester thyroid function testing and lipid levels data was conducted, and the relationship of thyroid function with lipid levels and pregnancy outcomes was evaluated. The data were analyzed using the SPSS software for statistical correlation. Results: The proportion of caesarean sections was higher in women with hypothyroxinemia (HIA) and hypothyroidism than in women with euthyroidism. Hypothyroidism was shown to be related with polyhydramnios, preterm labor and hypertriglyceridemia. HIA was correlated with increased rates of gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension and hypertriglyceridemia. Compared with the euthyroidism group, the hypothyroidism group had a higher apolipoprotein A1 (Apo A1) level and apolipoprotein B level; the subclinical hypothyroidism group had a higher total cholesterol (TC) level and low-density lipoprotein cholesterol level; the HIA group had higher triglyceride, high-density lipoprotein cholesterol levels and lower TC, Apo A1 levels. TC levels were positively correlated with the thyroid-stimulating hormone level and negatively correlated with free thyroxine (FT4) level, and free triiodothyronine and FT4 levels were positively correlated with GDM occurrence. Conclusion: Thyroid function in early pregnancy is associated with dyslipidemia and pregnancy outcomes; conventional screening of thyroid diseases in early pregnancy may help improve lipid levels and decrease adverse pregnancy outcomes.
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Using microdata from the Chinese General Social Survey (CGSS 2010), this paper investigates whether there are green returns to education in China, where educational attainment promotes pro-environmental attitudes and behaviors. We establish causality by exploiting the exogenous variation induced by the implementation of the Compulsory Schooling Law (CSL) in China. We find evidence that educational attainment is associated with higher levels of pro-environmental attitudes and behaviors, and these estimates are robust to various robustness checks. Further analysis reveals that the acquisition of environmental knowledge is the channel that drives the effect of education on pro-environmental attitudes and behaviors. Finally, the effects of education are heterogeneous across individuals.
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Educação , Meio Ambiente , Atitude , China , Mudança Climática , Escolaridade , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Nível de Saúde , Humanos , Conhecimento , Análise de Regressão , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
OBJECTIV E To in vestigate the situation ,achievements and proble ms of consistency evaluation policy of generic medicines in China. METHODS The descriptive analysis was performed after collecting and sorting out the information of generic medicine passing consistency evaluation (GMPCE) published on the official website of the National Medical Products Administration. The basic information ,the distribution and changes of GMPCE were analyzed statistically in National Essential Medicine List (hereinafter refer to as “essential medicine list ”),Medicine List for National Basic Medical Insurance ,Industrial Injury Insurance and Maternity Insurance (hereinafter refer to as “medical insurance list ”)and the result of the successful selection of centralized medicine procurement organized by the state (hereinafter refer to as “centralized procurement list ”). RESULTS From 2017 to 2021,415 chemical generic drugs had passed consistency evaluation in China ,including 309 varieties,1 822 specifications, 6 dosage forms ,and 17 pharmacological mechanisms ,basically belonging to 30 provinces,and 492 drug manufacturers (except 12 products had not been found the manufacturers );the proportion of GMPCE in essential medicine list increased from 0.96% in 2012 edition to 25.40% in 2018 edition;that of GMPCE in medical insurance list increased f rom 2.13% in 2017 edition to 11.68% in 2021 edition;in the first 5 batches of centralized procurement list,GMPCE accounted for 81.65%,and the maximum price drop after entering the list was 97.52%. CONCLUSIONS The policy linkage has been achieved with the continual increase of the number of GMPCE and their total amount in three lists in China. The accessibility and affordability of related medicines have been improved with the apparent decrease of the price of those medicines. H owever,total number of GMPCE is a little small,with the higher repetition rate of variety and the low proportion in the three lists ;the guarantee measures of those medicine supply need to be strengthened.
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OB JECTIVE To explore the construction of system of pharmacoeconomic evaluation fo r Chinese patent medicine in preventing and treating major chronic diseases. METHODS The problems in pharmacoeconomic evaluation of Chinese patent medicine for preventing and treating major chronic diseases were analyzed. Based on the problem ,the pharmacoeconomic theory , tools and methods that can be used to systematically evaluate the prevention and treatment of major chronic diseases by Chinese patent medicine were explored to build the relevant pharmacoeconomic evaluation system. RESULTS & CONCLUSIONS Traditional Chinese medicine shows the advantages in the prevention and treatment of major chronic diseases. This unique advantage needed to be explored ,reflected and proved in the pharmacoeconomic evaluation. The pharmacoeconomic evaluation of Chinese patent medicine had made some progress in recent years. However ,there were still deficiencies of theory and methodology in the pharmacoeconomic evaluation for the advantages of Chinese patent medicine in preventing and treating major chronic diseases. It was difficult to truly and comprehensively reflect the value of Chinese patent medicine by simply applying the economic evaluation indicators and technologies of chemical medicine. It is necessary to focus on the unique pharmacoeconomic attributes of Chinese patent medicine ,excavate the economic value indicators of Chinese patent medicine for “preventive treatment of disease ” and playing the self-regulation role of human body ,comprehensively consider the pharmacoeconomic particularity of Chinese patent medicine in respects of research design ,research angle ,target population ,intervention measures and control selection ,research time limit and evaluation method ,etc. Through the use of system modeling ,real-world research and the establishment of Chinese medicinal quality of life scale that reflects the characteristics of TCM ,the economic value of Chinese patent medicine in the prevention and treatmen t of major chronic diseases is reflected comprehensively,so as to reflect the advantage of Chinese patent medicine in preventing and treating major chronic diseases.
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BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.
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Demência , População Rural , Criança , China/epidemiologia , Estudos Transversais , Demência/epidemiologia , Humanos , Prevalência , Fatores de Risco , População UrbanaRESUMO
BACKGROUND: Despite the improved access to health services in China, inadequate diagnosis and management of dementia are common issues, especially in rural regions. OBJECTIVE: The Hubei Memory & Aging Cohort Study was designed as a prospective study in Central China to determine the prevalence, incidence, and risk factors for dementia and mild cognitive impairment (MCI) among urban and rural older adults. METHODS: From 2018-2020, participants aged ≥65 years were screened, and data regarding their life behaviors, families, socio-economic status, physical and mental health, social and psychological factors, and cognition were collected. Diagnoses of MCI and dementia were made via consensus diagnosis using the Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria. RESULTS: Of 8,221 individuals who completed their baseline clinical evaluation, 4,449 (54.1%) were women and 3,164 (38.4%) were from remote rural areas (average age: 71.96 years; mean education period: 7.58 years). At baseline, 25.98%(95%confidence interval [CI]: 24.99-26.96) and 7.24%(95%CI: 6.68-7.80) of the participants were diagnosed with MCI and dementia, respectively. Prevalence showed a strong relationship with age. The substantial disparities between rural and urban regions in MCI and dementia prevalence and multiple dementia-related risk factors were revealed. Especially for dementia, the prevalence rate in rural areas was 2.65 times higher than that in urban regions. CONCLUSION: Our results suggested that public health interventions are urgently needed to achieve equitable diagnosis and management for people living with dementia in the communities across urban and rural areas.
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Disfunção Cognitiva/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Testes Neuropsicológicos , Prevalência , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , População Rural , População UrbanaRESUMO
INTRODUCTION: Exposure to antibiotics (ABX) during pregnancy can have a systematic effect on both fetal and maternal health. Although previous biomonitoring studies have indicated the effects on children of extensive exposure to ABX, studies on pregnant women remain scarce. To explore the effect on pregnant women of environmental exposure to ABX through accidental ingestion and identify potential health risks, the present study investigated 122 pregnant women in East China between 2019 and 2020. RESEARCH DESIGN AND METHODS: The presence of six categories of ABX (quinolones, sulfonamides, lincosamides, tetracyclines, amide alcohol ABX, and ß-lactams) in plasma samples taken from the pregnant women was investigated using an ABX kit and a time-resolved fluorescence immunoassay. RESULTS: All six ABX were detected in the plasma, with a detection rate of 17.2%. It was discovered that the composition of intestinal flora in pregnant women exposed to ABX was different from that of pregnant women who had not been exposed to ABX. The intestinal flora of pregnant women exposed to ABX also changed at both the phylum and genus levels, and several genera almost disappeared. Furthermore, the metabolic levels of glucose and insulin and the alpha diversity of pregnant women exposed to ABX were higher than those of pregnant women not exposed to ABX. CONCLUSION: Pregnant women are potentially at higher risk of adverse microbial effects. Glucose metabolism and insulin levels were generally higher in pregnant women exposed to ABX than in unexposed women. Also, the composition and color of the gut microbiome changed.
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Microbioma Gastrointestinal , Antibacterianos/efeitos adversos , Criança , Feminino , Glucose , Humanos , Insulina , Gravidez , GestantesRESUMO
OBJECTIVE: To investigate the characteristics of intestinal flora in overweight pregnant women and the correlation with gestational diabetes mellitus (GDM). METHODS: A total of 122 women were enrolled and divided into four groups according to their pre-pregnancy BMI and the presence of GDM: group 1 (n = 71) with a BMI <24 kg/m2, without GDM; group 2 (n = 27) with a BMI <24 kg/m2, with GDM; group 3 (n = 17) with a BMI ≥24 kg/m2, without GDM; and group 4 (n = 7) with a BMI ≥24 kg/m2 with GDM. Feces were collected on the day that the oral glucose tolerance test was conducted. The V3-V4 variable region of 16S rRNA was sequenced using the Illumina Hiseq 2500 platform, and a bioinformatics analysis was conducted. RESULTS: There were differences between the four groups in the composition of intestinal flora, and it was significantly different in group 4 than in the other three groups. Firmicutes accounted for 36.4% of the intestinal flora in this group, the lowest among the four groups, while Bacteroidetes accounted for 50.1%, the highest among the four groups, making ratio of these two bacteria approximately 3:5, while in the other three groups, this ratio was reversed. In women with a BMI <24 kg/m2, the insulin resistance index (homeostatic model assessment for insulin resistance (HOMA-IR)) in pregnant women with GDM was higher than in those without (P3 = 0.026). CONCLUSION: The composition of the intestinal flora of pregnant women who were overweight or obese before pregnancy and suffered from GDM was significantly different than women who were not overweight or did not suffer from GDM.
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BACKGROUND: Some studies have demonstrated an association between low and high body mass index (BMI) and an increased risk of dementia. However, only a few of these studies were performed in rural areas. OBJECTIVE: This cross-sectional study investigated the associations between BMI and cognitive impairment among community-dwelling older adults from rural and urban areas. METHODS: 8,221 older persons enrolled in the Hubei Memory & Ageing Cohort Study (HMACS) were recruited. Sociodemographic and lifestyle data, comorbidities, physical measurements, and clinical diagnoses of cognitive impairment were analyzed. Logistic regression was performed to assess the associations of BMI categories with cognitive impairment. A series of sensitivity analyses were conducted to test whether reverse causality could influence our results. RESULTS: Being underweight in the rural-dwelling participants increased the risk of cognitive impairment. Being overweight was a protective factor in rural-dwelling participants aged 65-69 years and 75-79 years, whereas being underweight was significantly associated with cognitive impairment (OR, 1.37; 95% CI: 1.03-1.83; pâ<â0.05). Sensitivity analyses support that underweight had an additive effect on the odds of cognitive impairment and was related to risk of dementia. Interaction test revealed that the differences between urban/rural in the relationship between BMI and cognitive impairment are statistically significant. CONCLUSION: Associations between BMI and cognitive impairment differ among urban/rural groups. Older people with low BMI living in rural China are at a higher risk for dementia than those living in urban areas.
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Índice de Massa Corporal , Disfunção Cognitiva/epidemiologia , População Rural , População Urbana , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Vida Independente , MasculinoRESUMO
BACKGROUND: The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. METHODS: Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. RESULTS: Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. CONCLUSION: Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.
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Diabetes Gestacional , Microbioma Gastrointestinal , Glicemia , China , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , RNA Ribossômico 16S/genéticaRESUMO
With the publication of Registration and Classification of Traditional Chinese Medicine (TCM) and Application Data Requirements, the related management and technical documents of TCM with the same name and prescription need to be further studied and formulated. In this paper, the management mode and technical evaluation of TCM with the same name and prescription are discussed to provide reference for the formulation of management and technical documents of TCM with the same name and prescription. The issues to be discussed include which management mode to adopt, how to select the control drugs with the same name and prescription, whether the indication risk level should be divided, whether the indication should be limited to medium and low risk, and how to carry out the technical evaluation of similarity/consistency. From the perspective of technical document research and formulation, this paper mainly focuses on the technical level. However, there are still other theoretical possibilities in the management mode and technical evaluation of TCM with the same name and prescription. Therefore, this paper, as a preliminary summary of the management and technical evaluation of TCM with the same name and prescription, needs more scholars and industry experts to pay attention to and participate in this work.
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In this paper, a comparative analysis is carried out on the policy of listed drugs in Australia, the policy of over-the-counter drugs in Japan, the policy related to the conversion of Chinese patent medicines to over-the-counter drugs, and the policy related to health food. The focus is on one of the possible situations for the registration of over-the-counter traditional Chinese medicines (TCMs), namely new prescription-composed over-the-counter TCMs. This paper discussed separately from the three parts of the scope of Chinese medicinal materials in the prescription medicines, the scope of indications, and the technical requirements, in order to provide references for the technical requirements related to the registration of over-the-counter TCMs. Recommendations on the marketing and registration of new prescription-composed over-the-counter TCMs:①It is recommended to formulate a list of medicinal materials for the use of Chinese herbal medicines, and consider including raw materials of health food. On this basis, a batch of safe Chinese medicinal materials/decoction pieces was added. And consider dynamic supervision, such as allowing the addition or recall of Chinese medicinal materials/decoction pieces in the list of medicinal materials. ②The scope of indications is recommended to consider the scope of indications for the conversion of Chinese patent medicines to over-the-counter TCMs in China, and the selection of medium-risk indications can reflect the characteristics and advantages of TCM treatment. ③Efficacy evaluation needs to provide high-quality scientific evidence, including clinical research data, and consider relaxing the requirements for non-clinical pharmacodynamic trials.