Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021 / 中华预防医学杂志

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.@*METHODS@#The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP@*RESULTS@#Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP@*CONCLUSION@#Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.

Innovation of traditional Chinese medicine compounds and patent layout strategy with Lianhua Qingwen Formula as example / 中国中药杂志

The innovation and patent layout of traditional Chinese medicine compounds reflects the innovation level of the traditio-nal Chinese medicine industry to a certain extent. Lianhua Qingwen Formula was taken as an example to analyze the innovation and patent layout of traditional Chinese medicine compounds. The study first proposed an innovative technology system for traditional Chinese medicine compounds, and then analyzed the advantages and disadvantages of Lianhua Qingwen Formula in innovation and patent layout based on 56 patents and other relevant patents. The analysis results showed that Lianhua Qingwen Formula had the following characte-ristics in terms of patent layout. In terms of innovation technical route, the patented technical route of Lianhua Qingwen Formula was mainly based on the composition and preparation of granules as the first choice, followed by corresponding process improvements, new uses, and detection methods as the main improvement routes. In terms of the corresponding patent layout, the basic patent protection scope of Lianhua Qingwen Formula completely covered marketed drugs, and then took new functions as the main layout strategy for subsequent patent applications. With the advancement of modern technical means, the preparation process and testing methods have been optimized continuously. At the same time, the international patent layout was given the priority in domestic patent application. Based on the above characteristics, the study gave suggestions for follow-up innovation and patent work for Lianhua Qingwen Formula, so as to provide enlightenment for other traditional Chinese medicine companies in exploring original innovation of traditional Chinese medicine compounds, improving innovative methods, and enhancing the ability of patent layout of innovative achievements.

Finite element analysis of the comprehensive impact of scar and maxillary expansion combined with protraction on the development of maxilla with cleft lip and palate after repair operation / 华西口腔医学杂志

OBJECTIVE@#To study the comprehensive impact of scar and maxillary expansion combined with protraction on the development of maxilla with cleft lip and palate after repair operation.@*METHODS@#In the original finite element model of the maxilla with cleft palate, a finite element model of the maxilla with cleft lip and palate was established by using Boolean operation in ANSYS. Scar force after cleft lip and palate repair and maxillary expansion force combined with protraction were added simultaneously to process the stress analysis.@*RESULTS@#Maxillary deformation occurred in the three-dimensional direction. The comparison of displacements was as follows: X-axis>Z-axis>Y-axis.@*CONCLUSIONS@#Maxillary growth is significantly inhibited in the three-dimensional direction under the comprehensive impact of scar and maxillary expansion combined with protraction after repair operation, especially transverse and sagittal growth.

Screening and Verification of Antioxidant Small Molecular Compounds for Expansion of Human Hematopoietic Stem Cells Ex Vitro / 中国实验血液学杂志

OBJECTIVE@#To screen the antioxidant small molecular compounds with optimal efficiency of expansing the human hematopoietic stem cells (hHSC) In vitro based on antioxidant small molecular compound database of LKT laboratory, and to verify the effects of these compounds on the biological functions of hHSC.@*METHODS@#The umbilial cord blood CD34 cells were enriched by using the MACS beads; the absolute number and percentage of CD34 cells and CD34 CD49f cells were detected by high throughput flow cytometry after culture of hHSC with compounds in vitro for 1 week, the SR1 (1 μmol/L) was used as positive control, the candidate compounds were screened out; then 4 compounds were selected for follow-up experiments by comprehensive evaluation of concentration, safety and expansion efficacy, the optimal used concentrations of selected compounds were determined through the concentration gradient analysis, and CFC short-term colony-forming cell test was performed by using the determined concentration so as to verify the effect of compounds on the self-renewal, multilineage differentiation.@*RESULTS@#Out of 85 antioxidant small molecular compounds, 4 compounds (C2968, D3331, B1753 and B3358) with obvious expansion efficacy for CD34 cells and CD34 CD49f cells were screened out by high throughput flow cytometry; their optimal concentrations of 4 compounds were 0.5 μmol/L for C2968, 1.5 μmol/L for D3331 and 1.5 μmol/L for B1753 and 15 μmol/L for B3358. The CFC assay showed the colony formation number in compound-treated group significantly increased as compared with control group, moreover the self-renewal and multilineage differentiation were maintained.@*CONCLUSION@#The antioxidant small molecular compounds C2968 (0.5 μmol/L), D3331 (1.5 μmol/L), B1753 (1.5 μmol/L) and B3358 (1.5 μmol/L) possess good expansion efficacy for hHSC, they can maintain hHSC self-renewal, at the same time ensure the multilineage differentiation potentiality of hHSC.

Protection strategies of typical herbal medicine patent in German and their enlighten on domestic pharmaceutical enterprises / 中草药

Herbal medicine and Chinese materia medica (CMM), Kampo, traditional medicine in Australia, and other traditional medicines have been an important part of the world medicine, and the patent protection strategies of herbal medicine and Kampo at the international level have been already quite mature. However, China have less experience in patent protection strategies of CMM, and apparently fall behind the herbal medicine patent protection strategies of European countries, especially Germany. In this paper, based on the perspective of research and development, the patent application and protection strategies of Tebonin® from Germany are analyzed in depth. Considering patent conservation status of CMM, some workable references for the domestic pharmaceutical enterprises of CMM in the field of research and development of new drugs are provided.

Antioxidant effects of celastrol against hydrogen peroxide-induced oxidative stress in the cell model of amyotrophic lateral sclerosis / 生理学报

To investigate the anti-oxidative effect of celastrol on HO-induced oxidative stress in the cell model of amyotrophic lateral sclerosis (ALS) and its molecular mechanism, NSC34 motor neuron-like cells were transfected with EGFP-G93A-SOD1 plasmid and used as in vitro ALS cell model. SOD1transfected NSC34 cells were treated with different doses of HOand celastrol. The survival rate of the cells was detected by CCK-8 assay, and malondialdehyde (MDA) content was detected by corresponding kit. The mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione S-transferases (GST) were detected by real-time PCR. The activation of intracellular MEK/ERK and PI3K/Akt signal pathways was detected by Western blot. The results showed that pre-incubation of celastrol (50 nmol/L) for 4 h prior to HO(10 μmol/L) co-treatment for another 24 h significantly attenuated HO-induced cell death and MDA level in SOD1transfected NSC34 cells. Real-time PCR showed that the mRNA expressions of GCLC and GST were enhanced with pre-incubation of celastrol. Celastrol quickly induced phosphorylation of ERK1/2 and Akt within 30 min and 1 h respectively in SOD1transfected NSC34 cells. Pharmacological inhibitors of MEK (PD98059, 10 μmol/L) or Akt (MK2206, 10 μmol/L) could reverse the phosphorylation of ERK1/2 and Akt, and abolish up-regulation of GCLC and GST induced by celastrol at mRNA levels. Taken together, we conclude that celastrol exerts a beneficial antioxidant effect in SOD1NSC34 cells, which might be dependent on MEK/ERK and PI3K/Akt signaling pathway activation.

Bone protection effects of a novel Chinese herbal formula, taikong yangxin prescription, in hindlimb unloaded rats against bone deterioration / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of a Chinese herbal formula, taikong yangxin prescription (TKYXP) against bone deterioration in a hindlimb unloaded (tail-suspension) rat model.</p><p><b>METHODS</b>Thirty-two male Sprague-Dawley rats were divided into 4 groups: tail-suspension group fed with 2.5 g•kg(-1)•day(-1) of TKYXP extract (high dose), tail-suspension group fed with 1.25 g•kg(-1)•day(-1) (low dose), tail-suspended group treated with water placebo (placebo control group) and non tail-suspended group. The effects of TKYXP on bone were assessed using peripheral quantitative computed tomography (pQCT), microcomputerized tomography (micro-CT) and three-point bending biomechanical test on the femur in vivo.</p><p><b>RESULTS</b>TKYXP had a significant protective effect against bone loss induced by tail-suspension on day 28, as shown in the reduction in bone mineral density (BMD) loss, preservation of bone micro-architecture and biomechanical strength. The administration ofhigh dose TKYXP could significantly reduce the total BMD loss by 4.8% and 8.0% at the femur and tibia regions, respectively, compared with the placebo control group (P<0.01) on day 28. Its bone protective effect on the femur was further substantiated by the increases of the trabecular BMD (by 6.6%), bone volume fraction (by 20.9%), trabecular number (by 9.5%) and thickness (by 11.9%) as compared with the placebo control group.</p><p><b>CONCLUSION</b>TKYXP may protect the bone under weightless influence from gradual structural deterioration in the tail-suspension model.</p>

Impact of 60 days of 6° head down bed rest on cardiopulmonary function, and the effects of Taikong Yangxin Prescription as a countermeasure / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the changes in cardiopulmonary function induced by mid/long-term simulated microgravity with 6° head down bed rest (HDBR), and the effects of Taikong Yangxin Prescription (, TYP) as a countermeasure.</p><p><b>METHODS</b>Fourteen healthy male volunteers were randomly divided into a control group and a Chinese medicine (CM) group (7 in each group) by a random digital table based on their body weight. Both groups underwent 6° HDBR for 60 days. Subjects in the CM group received daily TYP pills and subjects in the control group received daily placebo pills. Cardiac systolic and pumping functions were measured by echocardiography before HDBR; on days 20, 42, and 57 of HDBR; and on day 3 of recovery after HDBR (R+3). Cardiopulmonary functional reserve and exercise capacity were evaluated before HDBR, on day 29, and on day R+3 by exercise testing.</p><p><b>RESULTS</b>The heart rate (HR) increased gradually during HDBR. The HR was significantly higher on day 57 than before HDBR in the control group (P<0.05), but did not increase significantly in the CM group. The stroke volume/stroke volume index, ejection fraction, and left ventricular fractional shortening tended to decrease over time in the control group, but not in the CM group. These parameters were significantly higher in the CM group than in the control group on day 42 (P<0.05 or <0.01). Exercise testing showed that maximum O2 consumption (VO2max), metabolic equivalents, relative O2 consumption (VO2), O2 pulse, and exercise duration were significantly lower on day 29 than before HDBR in the control group, but not in the CM group.</p><p><b>CONCLUSIONS</b>Sixty days of 6° HDBR induced a reduction in cardiac systolic and pumping functions, and reduced cardiopulmonary functional reserve and exercise capacity. Administration of TYP significantly improved cardiac systolic and pumping functions, and maintained cardiopulmonary functional reserve and exercise capacity.</p>

Determination of metformin, pioglitazone and active metabolites of pioglitazone in human plasma by HPLC-MS/MS / 中国药学杂志

OBJECTIVE: To establish an LC-MS method to determine the concentrations of metformin, pioglitazone and the active metabolites of pioglitazone(ketopioglitazone M-III and hydroxylpioglitazone M-IV) in plasma after administration of compound metformin and pioglitazone tablets. METHODS: Pioglitazone and the internal standard carbamazepine were extracted from plasma with acetonitrile. The concentrations of pioglitazone and its active metabolites were analyzed on Ultimate C18 column(2.1 mm×150 mm, 5 μm) with mobile phase consisting of acetonitrile-5 mmol·L-1 ammonium acetate(55:45) at a flow rate of 0.3 mL·min-1. The column temperature was 35°C. Metformin and the internal standard memantine were extracted from plasma with acetonitrile and analyzed on Ultimate XB-CN column(2.1 mm×150 mm, 5 μm) with mobile phase consisting of acetonitrile-0.1% formic acid(containing 10 mmol·L-1 ammonium acetate)(73:27) at a flow rate of 0.3 mL·min-1. RESULTS: The liner ranges were 5.08-1016.0 μg·L-1, 2.45-490.0 μg·L-1, and 4.20-840.0 μg·L-1 for metformin, pioglitazone, ketopioglitazone(M-III)and hydroxylpioglitazone(M-IV)respectively. The limits of quantitation were 6.0, 5.08, 2.45, and 4.2 μg·L-1, respectively. The extraction recoveries were more that 89.67%, while the intra- and inter-day precisions(RSD) were less that 15%. CONCLUSION: This assay is accurate, reliable and suitable for pharmacokinetic studies of metformin, pioglitazone and its active metabolites in human plasma.