Comparative Investigation Between Raw and Stir-Frying Processed Cuscutae Semen Based on HPLC Fingerprints Coupled With Chemometric Methods.

BACKGROUND: The curative effect of Cuscutae Semen (CS) could be adjusted after stir-frying, and it is difficult to distinguish between the raw CS and stir-fried processed Cuscutae Semen (SFCS) in clinical practice. OBJECTIVE: The paper aims to establish the fingerprints of raw and fried Cuscutae Semen products by high-performance liquid chromatography (HPLC) so that the compounds in raw and stir-fried products could be analyzed qualitatively and quantitatively. At the same time, the chemometrics method was used to evaluate the difference between CS and SFCS to provide reference for the research of traditional Chinese medicine (TCM) CS. METHOD: The raw and SFCS products' related substances were separated on a C18 column (250 mm × 4.6 mm, 5 µm) maintained at 30 °C (column temperature). The mobile phase comprised 0.1% formic acid aqueous solution (A) and acetonitrile (B), and a detection wavelength of 328 nm. The data were imported into statistical software for chemometric analysis. RESULTS: The developed HPLC method exhibits good linearity and has good systematic applicability. The content of these 12 compounds in the samples was further determined and the data analyzed by chemometrics. The results showed that the composition of CS changed on heating, and HCA showed that CS and SFCS could be clearly distinguished. PCA showed that six components caused differences, namely neochlorogenic acid, cryptophyllogenic acid, caffeic acid, quercetin, isorhamnetin, and kaempferol. CONCLUSIONS: This study unequivocally establishes a chromatographic fingerprint method intended for the extensive analysis of raw and stir-fried processed CS, which could substantially enhance the quality control of CS and the rational development and utilization of TCM resources. HIGHLIGHTS: This method for the simultaneous quantification of multiple compounds in CS and SFCS revealed the components responsible for the differences between raw and processed products. This will provide support for quality control of this herbal medicine.

Percutaneous vertebral-disc plasty for very severe osteoporotic vertebral compression fractures / 中华创伤骨科杂志

Objective:To investigate the clinical efficacy of percutaneous vertebral-disc plasty (PVDP) in the treatment of very severe osteoporotic vertebral compression fractures (vsOVCF).Methods:A total of 26 patients with vsOVCF were treated by PVDP at Department of Spine Surgery, The Second Affiliated Hospital, Nantong University from November 2019 to August 2021. They were 8 males and 18 females with an age of (77.9±5.2) years. Fracture sites: T11 in 9 cases, T12 in 13 cases, L1 in 7 cases, and L2 in 2 cases. The loss of vertebral height exceeded 2/3 of its original height. The curative effects were evaluated by comparing the visual analogue scale (VAS), Oswestry disability index (ODI) and local kyphosis angle (LKA) at preoperation, 1 day postoperation and the last follow-up.Results:This cohort was followed up for 12(10, 15) months. No obvious neurological damage or other serious complications occurred. The VAS scores [(2.9±0.7) and (2.2±0.7) points] and ODIs [28.0%±4.8% and 16.9%±4.0%] at 1 day postoperation and the final follow-up were significantly lower than the preoperative values respectively [(6.7±0.8) points and 66.7%±6.0%], and the values at the last follow-up were significantly lower than those at 1 day postoperation ( P<0.05). The LKAs at 1 day postoperation and the last follow-up (18.1°±4.1° and 19.5°±4.4°) were significantly smaller than that before operation (32.0°±5.2°) ( P<0.05), but there was no significant difference between 1 day postoperation and the last follow-up in LKA ( P>0.05). Conclusion:PVDP is an effective surgical treatment of vsOVCF, because it can relieve pain and improve local kyphosis with satisfactory clinical outcomes.

Experimental study on antibacterial properties and biocompatibility of Cu-Fe-Zn alloy microfilament dressings and their therapeutic effects on wound healing / 中国医师杂志

Objective:To study the antibacterial properties and in vivo and vitro biocompatibility of Cu-Fe-Zn alloy microfilament dressings, and to evaluate their wound healing promoting effect through clinical application.Methods:We evaluated the comprehensive antibacterial performance of dressings in vitro using plate counting method; After co culturing the extract of Cu-Fe-Zn alloy microfilament dressings with epidermal cells (HaCaT) and fibroblasts (NIH-3T3), their in-vitro biocompatibility was determined through the cell counting kit-8 (CCK-8) test; Further, Cu-Fe-Zn alloy microfilament dressing was applied to the wound surface of diabetes mice to test the biocompatibility of the material in vivo; Through a prospective randomized controlled trial, 50 burn and trauma patients admitted to the Burn and Plastic Surgery Department of the Third Xiangya Hospital of Central South University were selected and divided into an observation group of 25 patients and a control group of 25 patients. The observation group was treated with Cu-Fe-Zn alloy microfilament dressing, and the control group was treated with silver nanoparticle antibacterial dressing. The wound healing time and wound treatment effect of the two groups were compared.Results:The Cu 2+ release concentration of Cu-Fe-Zn alloy microfilament dressings detected by inductively coupled plasma-mass spectrometry (ICP-MS) was 1.3 μ g/ml, which had the effect of promoting the proliferation of HaCaT and NIH-3T3 cells (all P<0.05). The antibacterial rate of Cu-Fe-Zn alloy microfilament dressing against pseudomonas aeruginosa, escherichia coli and staphylococcus aureus reached 100%. The wound healing rate [(87.39±1.83)%] of diabetes mice treated with Cu-Fe-Zn alloy microfilament dressing was significantly higher than that of the control group [(58.66±3.54)%, P<0.05]. The inflammatory response of the wound tissue was relatively mild and the wound margin matrix was intact. The wound healing time of 25 patients treated with Cu-Fe-Zn alloy microfilament dressing [(23.52±10.02)d] was shorter than that of the control group [(40.84±21.22)d] ( t=17.159, P<0.001), and the overall treatment response rate of patients (96%) was significantly higher than that of the control group patients (64%) (χ 2=8.472, P=0.015). Conclusions:Cu-Fe-Zn alloy microfilament dressings have good antibacterial properties and biocompatibility, and have significant therapeutic effects on promoting wound healing. They not only effectively promote wound healing but also exert anti infection effects, and are expected to be a new type of wound repair dressing.

Network Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes.

INTRODUCTION: Insomnia is a novel pathogen for type 2 diabetes mellitus (T2DM). However, mechanisms linking insomnia and T2DM are poorly understood. In this study, we apply a network Mendelian randomization (MR) framework to determine the causal association between insomnia and T2DM and identify the potential mediators, including overweight (body mass index (BMI), waist-to-hip ratio, and body fat percentage) and glycometabolism (HbA1c, fasting blood glucose, and fasting blood insulin). RESEARCH DESIGN AND METHODS: We use the MR framework to detect effect estimates of the insomnia-T2DM, insomnia-mediator, and mediator-T2DM associations. A mediator between insomnia and T2DM is established if MR studies in all 3 steps prove causal associations. RESULTS: In the Inverse variance weighted method, the results show that insomnia will increase the T2DM risk (OR 1.142; 95% CI 1.072 to 1.216; p=0.000), without heterogeneity nor horizontal pleiotropy, strongly suggesting that genetically predicted insomnia has a causal association with T2DM. Besides, our MR analysis provides strong evidence that insomnia is causally associated with BMI and body fat percentage. There is also suggestive evidence of an association between insomnia and the waist-to-hip ratio. At the same time, our results indicate that insomnia is not causally associated with glycometabolism. Higher BMI, waist-to-hip ratio, and body fat percentage levels are strongly associated with increased risk of T2DM. CONCLUSIONS: Genetically predicted insomnia has a causal association with T2DM. Being overweight (especially BMI and body fat percentage) mediates the causal pathway from insomnia to T2DM.

Evaluation of the chemical profile from four germplasms sources of Pruni Semen using UHPLC-LTQ-Orbitrap-MS and multivariate analyses / 药物分析学报

Pruni Semen,the seed of several unique Prunus plants,is a traditional purgative herbal material.To determine the authentic sources of Pruni Semen,46 samples from four species were collected and analyzed.Ten compounds including multiflorin A(Mul A),a notable purative compound,were isolated and identified by chemical separation and nuclear magnetic resonance spectroscopy.Seventy-six communal components were identified by ultra-high performance liquid chromatography with linear ion trap-quadrupole Orbitrap mass spectrometry,and acetyl flavonoid glycosides were recognized as characteristic constituents.The flavonoids were distributed in the seed coat and cyanogenic glycosides in the kernel.Based on this,methods for identifying Pruni Semen from different sources were established using chemical fingerprinting,quantitative analysis of the eight principal compounds,hierarchical cluster analysis,principal component analysis,and orthogonal partial least squares discriminant analysis.The results showed that the samples were divided into two categories:one is the small seeds from Prunus humilis(Ph)and Prunus japonica(Pj),and the other is the big seeds from Prunus pedunculata(Pp)and Prunus triloba(Pt).The average content of Mul A was 3.02.6.93,0.40,and 0.29 mg/g,while the average content of amygdalin was 18.5,17.7,31.5,and 30.9 mg/g in Ph,Pj,Pp,and Pt,respectively.All the above information suggests that small seeds might be superior sources of Pruni Semen.This is the first comprehensive report on the identification of chemical components in Pruni Semen from different species.

Research progress in endocrine clinical treatment of HR +/HER2 - metastatic breast cancer / 国际生物医学工程杂志

Breast cancer, as a heterogeneous disease, has different molecular subtypes. The most common molecular subtype is hormone receptor positive (HR +). Endocrine therapy is the predominant treatment for this subtype. The main treatment modality for HR +/human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (MBC) is novel targeted agents combined with endocrine therapy. In this review, researches in endocrine clinical treatment of HR +/HER2 - MBC was reviewed to provide a new targeted therapy, including CDK4/6 inhibitors combined with endocrine therapy, the debate between CDK4/6 inhibitors combined with endocrine therapy and chemotherapy, new directions of CDK4/6 inhibitor combination, exploration of multiple treatment strategies after CDK4/6 inhibitor therapy progresses, histone deacetylase inhibitor combined with endocrine therapy, PI3K/Akt/mTOR pathway targeting drugs in combination with endocrine therapy, polyadenosine diphosphate ribose polymerase (PARP) inhibitors for gBRCA1/2 mutated breast cancer, novel targeted drugs, and multi-target/multi-combination therapy model.

Research progress in therapeutic resistance mechanism and therapeutic strategy of cancer stem cells / 国际生物医学工程杂志

Cancer stem cells (CSCs) are a class of cells with self-renewal, differentiation, and tumorigenic potential in tumors. It is currently believed that the resistance of CSCs to chemotherapy and radiotherapy is an important cause of tumor recurrence and metastasis. Researchers have found that related factors in many signaling pathways endow CSCs with the ability to adapt to changes in the microenvironment, including inflammatory factors, hypoxia, low pH, and a lack of nutrients. In recent years, the mechanism of CSCs' resistance to therapy has been studied, mainly including the drug efflux mediated by the ATP-binding cassette transporter, the effect of aldehyde dehydrogenase 1 (ALDH1) activity on tumor stem cells, the enhancement of DNA damage repair and degradation of reactive oxygen species, autophagy, activation of development-related pathways, stimulation of the microenvironment, and EMT. The targeting strategies for CSCs include targeting signaling pathway inhibitors, targeting multidrug resistance, DNA damage repair, ALDH, targeting the tumor microenvironment, immunotherapy, etc. In this review, the research progress in CSCs treatment resistance and related treatment strategies was reviewed.

Effect and Mechanism of Steamed Allii Sativi Bulbus Polysaccharide Against Dysbiosis-induced Diarrhea in Young Rats / 中国实验方剂学杂志

ObjectiveTo verify the efficacy of steamed Allii Sativi Bulbus polysaccharide in regulating the intestinal flora of young dysbiosis-induced diarrhea rats based on 16S rRNA gene sequencing. MethodThe young SD rats were randomly divided into blank group，model group，positive drug group （bifid triple viable capsules），and high-dose and low-dose steamed Allii Sativi Bulbus polysaccharide groups，six in each group. The dysbiosis-induced diarrhea rat model was established，and the blank group and the model group were given normal saline by gavage （each 10 mL·kg-1），and the high-dose and low-dose steamed Allii Sativi Bulbus polysaccharide groups were administered with corresponding drugs （500 mg·kg-1 and 250 mg·kg-1， respectively） ，once a day for seven consecutive days. The loose stool rate，loose stool grade，diarrhea index，small intestine propulsion rate and hematoxylin-eosin （HE） staining were used as indexes to investigate the effect of steamed Allii Sativi Bulbus polysaccharide on improving diarrhea symptoms in young rats. The feces of rats were collected for 16S rRNA gene high-throughput sequencing. ResultCompared with the model group， the positive drug group and the high-dose and low-dose steamed Allii Sativi Bulbus polysaccharide groups had alleviated symptoms， down-regulated loose stool rate and diarrhea index （P<0.01） and decreased small intestine advancement rate （P<0.05）. HE staining showed that after the treatment with steamed Allii Sativi Bulbus polysaccharide，the inflammatory cell infiltration of the colon tissue was improved and the intestinal gland recovered to the normal condition，which indicated that steamed Allii Sativi Bulbus polysaccharide could significantly ameliorate the diarrhea in young rats. The sequencing results revealed that steamed Allii Sativi Bulbus polysaccharide had a moderating effect on the abundance of the intestinal flora of young dysbiosis-induced diarrhea rats，elevating the flora richness and diversity indexes. Specifically， the abundance of Bacteroidota was increased while that of Firmicutes and Proteobacteria was decreased. ConclusionSteamed Allii Sativi Bulbus polysaccharide can be used to treat dysbiosis-induced diarrhea in young rats by regulating the abundance of intestinal microbiota.

Determination of arsenic in urine by hydride generation atomic fluorescence spectrometry with ammonium persulfate digestion / 中华地方病学杂志

Objective:To establish a hydride generation atomic fluorescence method using ammonium persulfate as the digestion reagent for determination of arsenic in urine (hereinafter referred to as this method).Methods:The collected urine samples with ammonium persulfate were heated and digested on the tubular electric heating automatic control constant temperature digester (60 holes), with 5% hydrochloric acid solution as reaction medium and current carrier and 1.5% potassium borohydride solution as reducing agent. Arsenic content was determined with a four-channel atomic fluorescence spectrometer. The arsenic standard solution of 0 - 10 μg/L was prepared to determine the standard curve of this method, and the method was evaluated from the detection limit, linear range, correlation coefficient, precision, standard addition recovery experiment, and urine arsenic quality control sample detection. The standard method "Determination of Arsenic in Urine by Hydride Generation Atomic Fluorescence Spectrometry" (WS/T 474-2015, referred to as the standard method) was used for comparison experiments.Results:When the sampling volume was 1 ml, the detection limit of this method (digest with 1 ml 1.5 mol/L ammonium persulfate) was 0.03 μg/L. In the range of arsenic content from 0 - 10 μg/L, the linear relationship between arsenic content and fluorescence intensity was good, and the correlation coefficients ( r) were all 0.999 9. The relative standard deviations( RSD) of the three replicates of urine samples with different concentrations were 1.00%, 0.89% and 0.49%, respectively. Urine arsenic quality control samples were tested, and the test results were all within the range of public values; the overall average recovery was 102.29%, and the recovery range was 92.10% - 108.15%. Compared with the standard method in the determination results of 20 urine samples, the difference was not statistically significant ( t = - 0.40, P > 0.05). Conclusions:The hydride generation atomic fluorescence spectrometry using ammonium persulfate as digestion reagent for the determination of arsenic in urine has the advantages of low detection limit, good precision, high accuracy, small amount of sampling and digestion reagent, simple operation, and less harmful gas generation in sample pretreatment. It is suitable for rapid determination of arsenic in urine in large quantities.

Study on mechanism difference of baicalein and wogonin inhibiting energy metabolism of hepatoma cells / 中国药房

OBJECTIVE To explore the difference in th e mechanis m of baicalein and wogonin inhibiting the energy metabolism of hepatoma cells. METHODS Human hepatoma HepG 2 cells were divided into blank control group （without medicine），different dose groups of baicalein and wogonin （1.25，2.5，5，10 and 20 μmol/L）. The effects of baicalein and wogonin on the viability of HepG 2 cells were detected by MTT assay. HepG 2 cells were divided into blank control group （without medicine），baicalein group and wogonin group. After administration ，the concentration of ATP in cell was detected by enhanced ATP kit. The levels of cell glycolysis and mitochondrial energy metabolism were evaluated by glycolysis and mitochondrial pressure test kit ；the affinity of baicalein and wogonin with key enzymes of energy metabolism was predicted by molecular docking ，and the key enzymes of energy metabolism with high affinity were screened ；the expression of key enzymes of energy metabolism was detected by Western blot. RESULTS Within the dose range of 2.5-20 μmol/L，the half inhibitory concentrations of baicalein and wogonin were 12.84 and 24.09 μmol/L；baicalein 1.25 μmol/L and wogonin 2.5 μmol/L had no effect on cell viability ，so it was selected as the dosage for subsequent experiments. Compared with blank control group ，the concentration of ATP in HepG 2 cells decreased significantly in baicalein group and wogonin group （P＜0.05）；the inhibitory effects on basic acidification rate of HepG 2 cells in wogonin group were significantly stronger than those of baicalein group （P＜0.05），but there was no significant difference between them on the basic oxygen consumption rate （P＞0.05）；baicalein had strong binding to pyruvate kinase M 2 and mitochondrial enzyme complexes Ⅰ（CⅠ），C Ⅱ and C Ⅳ，while wogonin only had strong binding to pyruvate kinase M 2； wogonin could significantly down-regulate the protein expressions of hexokinase ，phosphofructokinase，pyruvate kinase M 2，CⅠ， C Ⅱ and C Ⅳ（P＜0.05），but there was no statistical significance in the effect of baicalein on the regulation of these enzymes （P＞ 0.05）. CONCLUSIONS Both baicalein and wogonin can inhibit the energy metabolism of hepatoma HepG 2 cells，but the mechanism is different ：the effect of baicalein is related to the activity of key enzymes ，while the effect of wogonin is related to the inhibition of the expression of key enzymes of energy metabolism.

Study on quality grade standard of premature Forsythia suspensa / 中国药房

OBJECTIVE To study the quality grade stand ard of the premature Forsythia suspensa . METHODS A total of 138 batches of premature F. suspensa were collected from the main producing areas of F. suspensa in China. According to 2020 edition of Chinese Pharmacopoeia ，the contents of impurities ，moisture，ethanol-soluble extract ，volatile oil ，forsythin and forsythoside A in the premature F. suspense were determined ，and the qualified samples were screened. AHP-PCA mixed weighting method was used to give comprehensive weight to the indicators （except for the limit of impurity ）. The comprehensive score of the samples was calculated. The suggestions on the quality grade division of premature F. suspensa were put forward according to cluster analysis of K-mean value. RESULTS & CONCLUSIONS The contents of impurities ，moisture，ethanol-soluble extract ，volatile oil ，forsythin and forsythoside A in the premature F. suspense were 0-7.80％，1.60％-8.18％，13.13％-61.60％，0.21％-3.47％，0.02％-2.15％ and 0.79％-14.04％，respectively；average contents of them were 1.24％，4.97％，34.88％，2.01％，0.42％，6.86％，respectively. Totally 47 batches of 138 batches were qualified in all indexes. It is suggested that the quality grade of the premature F. suspense can be divided into three grades ：in first grade of F. suspense ，the contents of volatile oil ，forsythin，forsythoside A ， ethanol-soluble extract and moisture were ≥2.40％，≥0.59％，≥8.34％，≥38.66％ and ≤4.99％，respectively；in second grade of F. suspense ，the contents of above indicators were ≥2.26％，≥0.41％，≥7.47％，≥32.58％ and ≤5.33％，respectively；in third grade of F. suspense ，the contents of above indicators were ≥2.15％，≥0.32％，≥4.60％，≥31.52％ and≤7.23％，respectively.

Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

Investigation and analysis of knowledge and behavior of iodine deficiency disorders prevention and treatment among pregnant women in iodine deficiency areas in Anhui Province / 中华地方病学杂志

Objective:To understand the knowledge and behavior changes of pregnant women on iodine deficiency disorders (IDD) prevention and treatment in iodine deficiency areas in Anhui Province before and after the implementation of the intervention measures, and to provide a scientific basis for pregnant women's iodine nutrition improvement.Methods:From March to December 2018, from Lujiang County, an iodine deficiency area in Anhui Province, Lucheng and Nihe towns were selected as the survey sites. Relying on the township health centers, pregnant women in early pregnancy (≤12 weeks) were selected as the survey subjects, and long-term follow-up was conducted. The edible salt samples of pregnant women in early pregnancy were collected and salt iodine content was detected by direct titration method. The urine samples of pregnant women in the morning in early, middle (13 - 28 weeks) and late pregnancies (≥29 weeks) were collected, urinary iodine content was determined by arsenic-cerium catalytic spectrophotometry. Baseline questionnaire survey was conducted for pregnant women in early pregnancy, mainly including basic information, IDD prevention and treatment knowledge (pregnant women prone to iodine deficiency, the harm of iodine deficiency in pregnant women, suitable iodine supplement methods for pregnant women and foods with high iodine content), and the consumption frequency of iodine-rich foods. After the baseline survey, the knowledge publicity on IDD prevention and treatment was carried out in townships, and iodine-rich foods such as kelp and laver were recommended to supplement iodine. The intervention activities lasted for 6 months, and retrospective questionnaire survey was conducted on pregnant women in late pregnancy.Results:A total of 128 edible salt samples were collected from the families of pregnant women in early pregnancy, and the median salt iodine was 21.5 mg/kg. The iodized salt coverage rate was 99.2% (127/128), the qualified rate of iodized salt was 98.4% (125/127), and the consumption rate of qualified iodized salt was 97.7% (125/128). A total of 129, 95 and 70 urine samples were collected from pregnant women in early, middle and late pregnancies, the medians urinary iodine were 179.0, 185.5 and 189.7 μg/L, respectively, all of which were at the appropriate iodine level. The total awareness rates of IDD prevention and treatment before and after intervention were 22.4% (28/125) and 64.6% (82/127), respectively, and the difference was statistically significant (χ 2 = 45.538, P < 0.01). Compared with the awareness rates before the intervention, the awareness rates of the harm of iodine deficiency in pregnant women, suitable iodine supplement methods for pregnant women and foods with high iodine content were all higher after the intervention ( P < 0.01). There were statistically significant differences in the frequency of eating kelp, laver and other iodine-rich foods among pregnant women in early, middle and late pregnancies (χ 2 = 163.170, 102.373, P < 0.01). Before the intervention, 57 (45.2%) pregnant women had not eaten kelp, which decreased to 1 (0.8%) pregnant woman after the intervention. Before the intervention, 72 (57.1%) pregnant women had not eaten laver and other iodine-rich foods, which decreased to 7 (5.5%) pregnant women after the intervention. Conclusions:After the intervention, the awareness rate of IDD prevention and treatment knowledge and the frequency and proportion of iodine-rich foods consumption among pregnant women in iodine deficiency areas in Anhui Province have increased significantly. It is recommended to carry out publicity and education on IDD prevention and treatment knowledge in early pregnancy.

Preparation and pharmacokinetics of polydopamine-loaded bavachinin nanoparticles coated with erythrocyte membrane / 中国药科大学学报

@#Polydopamine (PDA) nanoparticles were prepared as a carrier, and bavachinin (BVA) was efficiently loaded by physical adsorption.The erythrocyte membrane was further utilized to modify and construct the erythrocyte membrane biomimetic nanoparticles (RBC-BP), the residence time in the body was extended and the in vivo analytical method was established to investigate their pharmacokinetics in mice.Polydopamine nanoparticles loaded with BVA (BP) were prepared by solvent replacement method, and the influencing factors of PDA loaded with BVA were investigated with the adsorption rate as the evaluation index.The erythrocyte membrane was extracted and separated, and RBC-BP was prepared by incubation coextrusion method. The effects of pH value on membrane coating and the extrusion times on the particle size and uniformity of RBC-BP were investigated.The particle size, potential, morphology, and cumulative release rate of RBC-BP were systematically characterized, and their pharmacokinetics in mice were preliminarily explored.The results showed that the adsorption rate of BP was as high as (92.08 ± 0.17) % and the drug loading rate was (42.05 ± 2.95) % at the PDA to BVA ratio of 1∶0.5, the solution pH value of 7, the incubation time of 6 h, and the incubation temperature of 20 °C, and that the erythrocyte membrane could be successfully oriented and coated on the surface of BP by the action of electric charge at the pH value of 4. The in vitro studies showed that RBC-BP has the apparent core-shell structure with the particle size of (308.63 ± 6.56) nm and good stability, and in vivo pharmacokinetic studies showed that RBC-BP can significantly extend the circulation time of nanoparticles in vivo.

Content Determination of 17 Quality Markers in Dahuang Zhechong Pills / 中国药房

OBJECTIVE：To establish the method for the content de termination of 17 quality markers in Dahuang zhechong pills（DHZCP）. METHODS ：HPLC method was adopted to determine the contents of 17 quality markers in 10 batches of DHZCP ， such as allantoin ，hypoxanthine，salidroside，hydroxypaeoniflorin，glycyrrhizin，isoglycyrrhizin，baicalin，p-methoxyphenylacetic acid，wogonin，cinnamic acid ，apigenin，naringin，norwogonin，aloe emodin ，rhein，chrysin，emodin. The determination was performed on Kromasil 100-5-C18（250 mm × 4.6 mm，5 μm）column with mobile phase consisted of 0.1％ phosphoric acid solution-acetonitrile （gradient elution ） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃ ，the detection wavelength was 210 nm and the sample size was 20 μ L. RESULTS：The linear range of above 17 quality markers were 5.74-183.53，6.51-208.24，4.30-137.65，4.60-147.06，4.12-131.76，4.25-135.88，6.31-201.76，4.60-147.06，1.94-62.06，4.47- 142.94，0.69-22.06，2.29-73.24，2.33-74.41，1.42-45.29，6.65-212.94，1.11-35.44 and 1.47-47.06 μg/mL，respectively（all R2≥ 0.999 0）. RSDs of precision ，repeatability，stability and durability tests were all less than 2％（n＝6）；average recovery of 17 quality markers ranged from 96.31％ to 101.73％，and the RSDs were less than 3％（n＝6）. CONCLUSIONS ：The method is simple， rapid，speific，specise，reproducible，stable，accurate and durable ，and can be used for improving the quality standard of DHZCP.

The effects of clostridium butyricum and butyrate on acute necrotizing pancreatitis with acute liver injury in rats and the mechanism / 中华胰腺病杂志

Objective:To observe the protective effects of Clostridium butyricum and butyrate on pancreas, liver and intestinal mucosa in rats with acute necrotizing pancreatitis (ANP), and to explore the possible mechanism.Methods:Forty Sprage-dawley rats were randomly divided into control group, ANP group，Clostridium butyricum treated group(CB group) and butyrate treated group(SB group), with 10 rats in each group by random number method. The ANP rat models were prepared by retrograde injection of sodium taurocholate into the biliopancreatic duct. Rats in CB and SB group were given intragastic administration of Clostridium butyricum 1×10 9 CFU or sodium butyrate (100 mg/kg) in 10 days once a day before modeling. Serum amylase (SAMY), lypase, ALT, AST, TBil, tumor necrosis factor alpha(TNF-α), IL-6 and HMGB1were measured after 24 h. Protein from intestinal mucosa was extracted and Western Blotting was used to measure expression of tight-junction proteins ZO-1, claudin-1 and occludin. Pancreas and liver tissues were stained with hematoxylin-eosin and scored by pathology. Results:The levels of amylase [(9365.1±716.5), (5947.3±512.0), (6517.7±269.6)U/L], lipase[(8343.7±1041.4), (6600.4±899.7), (6754.4±1046.4)U/L], AST[(560.5±72.7), (432.0±76.2), (429.8±40.5)U/L], ALT[(499.9±65.2), (385.7±46.0), (395.8±45.8)U/L], TBil[(134.2±56.2), (74.3±65.2), (81.3±35.3)U/L], TNF-α[(162.0±14.4), (100.4±6.3), (119.2±12.5)ng/L], IL-6[(161.4±26.0), (104.8±15.2), (105.5±12.7)ng/L], HMGB1[(100.1±6.7), (58.0±7.7), (63.4±7.2)ng/L] in ANP group, CB group and SB group were detected; and the pathological scores of pancreas[(11.2±1.08)，(9.45±1.06), (9.04±0.89)] and liver[(2.89±0.73), (2.09±0.49), (2.12±0.52)] in ANP group，CB group and SB group were higher than those in control group[(100.6±5.20)U/L, (966.5±301.9)U/L，(30.2±6.3)U/L, (27.6±5.9)U/L, (2.4±0.6)U/L, (29.5±4.8)ng/L，(36.9±7.6)ng/L，(35.5±5.7)ng/L，(1.18±0.05)，(0.56±0.09)]. However, those indexes in CB group and SB group were lower than those in ANP group, and the difference was statistically significant (all P<0.05). The expression of ZO-1 in control group, ANP group, CB group and SB group was 1.83, 0.79, 1.25 and 1.16. The expression of claudin-1 in control group, ANP group, CB group and SB group was 0.58, 0.13, 0.43 and 0.37. The expression of occludin in control group, ANP group, CB group and SB group was 1.06, 0.38, 0.82 and 0.79. The expression of TJ proteins in ANP group was significantly lower than that in other groups and the difference was statistically significant (all P<0.05). Conclusions:Clostridium butyricum and metabolites butyrate can alleviate the inflammatory response in ANP rats with liver injury, maintain the function of intestinal mucosal barrier and prevent the liver injury.

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice / 神经科学通报·英文版

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice / 神经科学通报·英文版

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Education and stroke: evidence from epidemiology and Mendelian randomization study.

We aim to characterize the association between education and incident stroke (including total stroke, ischemic stroke, and hemorrhagic stroke) and assess whether there is a causal relationship between them. The final sample size was 11,509 in this study from the Atherosclerosis Risk in Communities (ARIC) study. Cox hazard regression models were used to explore the association between education level and incident stroke. Two-sample Mendelian randomization (MR) was used to estimate the causality. During a median follow-up of 25.3 years, 915 cases (8.0%) of stroke occurred. Participants with advanced education level were associated with 25% (HR 0.75; 95% CI 0.62, 0.91) decreased the rate of incident total stroke. Hazard ratio of intermediate and advanced education level for ischemic stroke were 0.82 (0.69, 0.98) and 0.73 (0.60, 0.90) separately. In the MR analysis, we observed evidence that education was likely a negetive causal risk factor for ischemic stroke (OR 0.764, 95% CI 0.585-0.998, P = 0.048). Higher education level was associated with a decreased rate of total stroke and ischemic stroke incident, but not hemorrhagic stroke incident. There might be a protective causal association between education and ischemic stroke (but not total stroke nor hemorrhagic stroke).

Death of a neonate born to a critically ill mother with COVID-19: a case report / 中华围产医学杂志

We report a critically ill pregnant woman in the third trimester with severe pneumonia due to COVID-19 who presented to Xiaolan People's Hospital of Zhongshan in February 2020. The 32-year-old patient was admitted at 35 +2 gestational weeks with a 4-day history of a sore throat and a fever for three hours. The patient had been to Xiaogan City, Hubei Province, and the symptoms occurred during a period of self-isolation after back home. The condition of the patient deteriorated rapidly, with left-sided chest and back pain, shortness of breath, dizziness, progressing to respiratory failure and septic shock 7 hours after her admission. In view of her critical condition and a history of two previous cesarean sections, an emergency cesarean section was performed. Blood gas analysis of the mother before the operation suggested respiratory failure, respiratory acidosis, and metabolic acidosis. During the operation, a baby boy was born. The Apgar score of the boy, birth weight of 2 700 g, was one at 1, 5 and 10 minutes despite the resuscitation efforts. The neonate died after withdrawing treatment. The patient was treated with tracheal intubation ventilator and other supportive treatments after the operation. The result of the new coronavirus nucleic acid test, taken on admission, but which was reported after delivery, was positive. The patient was transferred to the designated hospital for further treatment and was recovering with the withdrawal of extracorporeal membrane oxygenation and ventilation support at 26 and 36 days after surgery, respectively.