Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

AIM To study the chemical constituents from flower buds of Magnolia biondii Pamp.and their in vitro acetylcholinesterase inhibitory activities.METHODS The 50% acetone extract from the flower buds of M.biondii was isolated and purified by Diaion HP-20,Toyopearl HW-40C,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro acetylcholinesterase inhibitory activities of these compounds were determined according to previous method established by research group.RESULTS Seventeen compounds were isolated and identified as crassifolioside(1),magnoloside B(2),rutin(3),isoquercitrin(4),quercetin(5),northalifoline(6),cordysinin B(7),thymidine(8),indazole(9),dihydrodehydrodiconiferyl alcohol(10),aesculetin(11),C-veratroylglycol(12),3,4-dihydroxyphenylethanol(13),3-methoxy-4-hydroxyphenylethanol(14),3,4-dihydroxybenzoic acid(15),2,4,6-trimethoxyphenol(16),syringic acid(17).CONCLUSION Compounds 1-17 are isolated from this plant for the first time,none of which show acetylcholinesterase inhibitory activities at the concentration of 20 μmol/L.

The 95% ethanol extract of Poria cocos was separated and purified by ODS, MCI gel CHP20 and silica gel column chromatography combined with the semi-preparative HPLC. The chemical structures of the isolated compounds were identified by NMR, MS, IR, and calculated NMR methods. Seven compounds were isolated from Poria cocos and identified as 20S-2β,3α,15α,19,20-hydroxy-pregnane-7-ene (1), dehydroeburicoic acid monoacetate (2), eburicoic acid acetate (3), dehydroeburicoic acid (4), eburicoic acid (5), dehydropachymic acid (6), pachymic acid (7). Compound 1 is a new pregnane steroid.

Abstract: Objective　To investigate the clustered regularly interspaced short palindromic repeats (CRISPR) genotypes and regional distribution of Yersinia pestis strains in the natural plague foci of Hainan Tibetan Autonomous Prefecture of Qinghai Province (referred to as "Hainan prefecture") and provide a scientific basis for plague prevention and control in this area. Methods　A total of 36 representative Yersinia pestis strains, which were isolated from different host animals and insect vectors from 1954 to 2009 in Hainan Prefecture, were selected as experimental subjects. The DNAs were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. Three pairs of CRISPR primers (YPa, Ypb, YPc) were used for PCR amplification, sequencing and analysis of the DNA of the tested strains, respectively, as a means to identify the CRISPR genotypes of Yersinia pestis in Hainan Prefecture. Results　A total of 17 spacers were observed among 36 strains of Yersinia pestis, including 9 of YPa, 5 of YPb and 3 of YPc. All strains were divided into 5 CRISPR gene clusters (Cb2, Cb4 ', Ca7, Ca7 ', Ca35 ') and 6 genotypes (G1, G9, G22, G22-A1 ', G26-A1 ', G26-A1 'A4 -). The G26-a1 ' was the main genotype, which was distributed in Gonghe, Guide and Xinghai County, and the G22 is the second type, which was distributed in Gonghe and Guide County. Conclusions　The genetic polymorphism of CRISPR loci of Yersinia pestis strains in Hainan was high, and the regional distribution characteristics of Yersinia pestis strains with different genotypes were significant.

Abstract: Objective To investigate the current status of streptomycin resistance of Yersinia pestis caused by point mutations of rpsL gene in Qinghai, so as to provide theoretical basis for precise clinical medication and prevention of drug resistance of human plague outbreak in South area of Qinghai Province in the future. Methods A total of 104 representative strains of Yersinia pestis collected from plague patients, vector insects and intermediate hosts in South area of Qinghai Province from 1957 to 2009 were screened, isolated and cultured by Hiss agar plates. The DNA of representative Yersinia pestis was extracted by sodium dodecyl sulfate lysis and phenol-chloroform method. The primers forward primer and reverse primer and TaqMan-MGB probes probe1 [FAM] and probe2 [VIC] were designed for the rpsL gene of streptomycin resistance gene in China. Real-time PCR with TaqMan-MGB fluorescent probe was used to detect the mutations of rpsL gene in streptomycin resistance locus of 104 strains of Yersinia pestis in South area of Qinghai Province. Results The FAM test results of 104 strains in South area of Qinghai Province were positive, corresponding to the detection of rpsL (128 : A ), RFU peak >1 000,negative <200. VIC test results of all tested strains were negative, corresponding to the detection of rpsL (128:G), RFU peak <200, positive >1 000. That is, no strains with rpsL gene mutation related to streptomycin resistance were found in the 104 strains of Yersinia pestis in Qingnan Province. Conclusion This study provides basic data on the distribution of streptomycin resistance of Yersinia pestis in South area of Qinghai Province, and lays a foundation for preventing the occurrence of drug resistance and clinical treatment of Yersinia pestis in South area of Qinghai Province.

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

Complicated chemical reactions occur in the decoction of traditional Chinese medicines(TCMs) which features complex components, influencing the safety, efficacy, and quality controllability of TCMs. Therefore, it is particularly important to clarify the chemical reaction mechanism of TCMs in the decoction. This study summarized eight typical chemical reactions in the decoction of TCMs, such as substitution reaction, redox reaction, isomerization/stereoselective reaction, complexation, and supramolecular reaction. With the "toxicity attenuation and efficiency enhancement" of aconitines and other examples, this study reviewed the reactions in decoction of TCMs, which was expected to clarify the variation mechanisms of key chemical components in this process and to help guide medicine preparation and safe and rational use of medicine in clinical settings. The current main research methods for chemical reaction mechanisms of decoction of TCMs were also summed up and compared. The novel real-time analysis device of decoction system for TCMs was found to be efficient and simple without the pre-treatment of samples. This device provides a promising solution, which has great potential in quantity evaluation and control of TCMs. Moreover, it is expected to become a foundational and exemplary research tool, which can advance the research in this field.
Medicine ; Medicine, Chinese Traditional ; Research Design