Sophoridine is a quinolizidine alkaloid extracted from Sophora in legumes, which is one of the main active ingredients of Sophora alopecuroides L, Sophora flavescentis Ait and Sophora davidii (Franch.) skeels. Its molecular formula is C

Objective To understand the distribution and changes in antimicrobial resistance of clinically isolated Pseudomonas aeruginosa(P.aeruginosa)in the member hospitals of Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods Antimicrobial susceptibility testing by disk diffusion or automa-ted instrument was performed on clinical isolates.Testing results were determined according to the standards of 2022 edition from American Clinical Laboratory Standards Institute(CLSI).Statistical analysis was performed by WHONET 5.6 software.Data were analyzed by trend test(Cochran-armitage)and Chi-square test with SPSS.Results A total of 176 441 strains of P.aeruginosa were surveilled by Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.99.4％of the strains were isolated from hospitalized patients,and about 70％of the strains were isolated from respiratory specimens.8.4％of P.aeruginosa were from children(0-17 years old),91.6％were from adults.Antimicrobial susceptibility testing results showed that P.aeruginosa was most sensitive to polymyxin B over 10 years,with a resis-tance rate of less than 6％.Resistance rates to piperacil-lin,piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,imipenem,amikacin,gentamicin,tobramycin,cip-rofloxacin,levofloxacin,and polymyxin B all showed downward trends.A total of 29 920 carbapenem-resistant P.aeruginosa(CRPA)strains were detected.The average isolation rate of CRPA in this province was 18.0％over 10 years.CRPA detection rate from adult was 18.5％,higher than that from children(12.3％),and both showing downward trends.Conclusion The resistance rate of clinically isolated P.aeruginosa in Hunan Province to most commonly used antimicrobial agents is decreasing.

OBJECTIVE: To investigate the effects of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on the pharmacokinetic behavior of rhodojaponin II and rhodojaponin III of Rhododendri Mollis Flos. METHODS LC-MS/MS of rhodojaponin II and rhodojaponin III in plasma of rats was developed. The method was then applied to study the blood concentrations of rhodojaponin II and rhodojaponin III in rats after oral compatibility administration of Gardeniae Fructus and Rhododendri Mollis Flos and single decoction administration of Rhododendri Mollis Flos, respectively, then their pharmacokinetic parameters were calculated and statistical analysed. RESULTS: The calibration curve was good linearity(r>0.999) in the range of 1-200 ng·mL-1 for rhodojaponin II and 1-100 ng·mL-1 for rhodojaponin III, the precision of quality control samples was less than 12% and the accuracy was less than 20%. After administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos and Rhododendri Mollis Flos alone, the AUC0-t of rhodojaponin II in vivo was(260.44±51.67) and (213.39±59.03)h·ng·mL-1, respectively, and the AUC0-t of rhodojaponin III was (60.97±22.78) and (22.38±5.55)h·ng·mL-1, respectively. Compared with single decoction of Rhododendri Mollis Flos administration group, the T1/2 and MRT(0-t)of the rhodojaponin II were significantly increased, the AUC0-t, T1/2, Tmax and CL of the rhodojaponin III were also significantly rised after administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos. CONCLUSION After the compatibility of Gardeniae Fructus and Rhododendri Mollis Flos, the rate of absorption and the distribution volume are increased of rhodojaponin III in rats, while the elimination rate has decreased, the T1/2 of rhodojaponin II and rhodojaponin III are extended, but don't affect the absorption rate of rhodojaponin II in rats.

Objective: To investigate the clinical manifestations and genetic features of 2 children with Smith-Kingsmore syndrome caused by MTOR gene variation and review the literature. Methods: The clinical data of 2 children carrying MTOR gene variant, diagnosed at Xi'an Children's Hospital from April 2018 to April 2021, were retrospectively summarized."MTOR"and"Smith-Kingsmore syndrome"were used as key words to search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and OMIM up to August 2021. The characteristics of MTOR gene variation and the clinical phenotype of children with Smith-Kingsmore syndrome were summarized. Results: Two children were both females, aged 1.5 years and 2 years respectively, the onset age were both in infancy. They both had developmental delay, megalencephaly and abnormal face. Both whole exome sequencing revealed a de novo heterozygous missense variant in MTOR gene. One case carried c.5395G>A (p.Glu1799Lys) and the other case carried c.7234G>C (p.Asp2412His). There was no literature of MTOR gene variation in Chinese. So far, a total of 45 cases were reported worldwide with detailed clinical information. Eleven variations in MTOR gene were involved, which were all heterozygous missense mutations. Among them, p.Glu1799Lys was the most common sites (28 cases,62%). Another case carried c.7234G>C (p.Asp2412His) was not reported before. Summarizing the 47 cases (including these 2 cases), 46 cases had developmental delay or intellectual disability, 9 cases had developmental regression,42 cases had megalencephaly, 30 cases had facial malformation,16 cases had hypotonia, 17 cases had autism spectrum disorders, 3 cases had hyperactivity, 3 cases had obsessive compulsive disorder, 13 cases had eye diseases, 11 cases had cutaneous vascular malformation, and 9 cases had hypoglycemia. Conclusions: The main clinical features of Smith-Kingsmore syndrome include megalencephaly, developmental delay or intellectual disability, and facial malformation, which can be combined with epilepsy, autism spectrum disorder, hypotonia, hypoglycemia and so on. The variation of MTOR gene is the cause of Smith-Kingsmore syndrome.
Autism Spectrum Disorder ; Female ; Humans ; Hypoglycemia ; Intellectual Disability/genetics* ; Megalencephaly/genetics* ; Muscle Hypotonia ; Mutation ; Retrospective Studies ; TOR Serine-Threonine Kinases/genetics*

OBJECTIVE: To evaluate the clinical effect of haploid allogeneic hematopoietic stem cell transplantation(haplo-HSCT) in the treatment of severe aplastic anemia (SAA), and to explore the efficacy different between post-transplant cyclophosphamide (PT/Cy) and standard-dose ATG. METHODS: The clinical data of 38 patients with SAA in our hospital from January 2012 to December 2019 were collected and retrospectively analyzed. The efficacy was evaluated. The patients with haplo-HSCT were divided into low-dose ATG combined with PT/Cy group and standard-dose ATG group, and the blood cell hematopoietic reconstruction time, GVHD incidence, mortality and survival time of the patients in the two groups was compared. RESULTS: Among the 32 patients, hematopoietic reconstitution were detected in 9375%(30/32) recipients. The median time of neutrophil and platelet engraftment was 15(10-22) days and 13(7-30) days, respectively. The incidence of GVHD was 21.89%, the incidence of infection was 93.75%, and the 2-year overall survival rate was 84.38%. The hematopoietic reconstitution time, incidence of GVHD, mortality rate and survival time were no statistical differences between the patients in the two groups(all P>0.05). CONCLUSION Haplo-HSCT is an effective method for the treatment of SAA，low-dose ATG combined with PT/Cy can lighten the economic burden on patients, it would be a feasible treatment plan for SAA with light side effect.
Anemia, Aplastic/therapy* ; Cyclophosphamide ; Graft vs Host Disease ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Transplantation Conditioning

Background::As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.Methods::Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.Results::Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera ( Enterobacter and Enterococcus) are unaffected by rifaximin therapy. Conclusions::IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.Registration::Chinese Clinical Trial Registry, ChiCTR1800017911.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
Animals ; Inflammation ; Mice ; NF-kappa B/metabolism* ; Particulate Matter/toxicity* ; Signal Transduction ; Sirtuin 2/metabolism* ; Transcription Factor RelA/metabolism*

OBJECTIVE: To study the relationship between serum microRNA-122 (miR-122) and insulin resistance in obese children. METHODS: Forty-seven children with severely obesity aged 7-14 years and 45 age- and gender matched healthy children with normal weight (control group) were enrolled. The levels of height, weight, waistline, hip circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), interleukin-6 (IL-6) and miR-122 in the two groups were measured. Body mass index (BMI), waist-hip ratio (WHR) and insulin resistance index (HOMA-IR) were calculated. RESULTS: Compared with the control group, the height, weight, BMI, WHR, FINS, HOMA-IR, TG, FFA, IL-6, and miR-122 levels in the obese group were significantly increased (P<0.05). MiR-122 levels in the obese group were positively correlated with FINS, HOMA-IR and IL-6 levels (r=0.408, 0.442, and 0.464 respectively, P<0.05). The changes of miR-122 have a linear regression relationship with IL-6 (b'=0.318, P<0.05). CONCLUSIONS The elevated serum miR-122 levels may be correlated with insulin resistance in obese children. The mechanism needs to be further studied.
Adolescent ; Blood Glucose ; Body Mass Index ; Child ; Humans ; Insulin ; Insulin Resistance ; MicroRNAs ; genetics ; Obesity ; Waist-Hip Ratio

Objective To evaluate the efficiency of REPLI-g® Single Cell Kit for sample DNA amplification, and explore its application value in forensic trace DNA amplification. Methods Three DNA extraction kits were selected to extract DNA from peripheral blood of 10 unrelated individuals. The DNA yield and purity of the three DNA extraction kits were compared. According to the results of comparison, one DNA sample was selected to concentrate and dilute, then used as the initial sample of whole genome amplification （WGA）. REPLI-g® Single Cell Kit was used to amplify the initial sample at the whole genome level. The amplification yield and amplification times were calculated, and the distribution of DNA fragments was detected by agarose gel electrophoresis. Goldeneye® DNA ID System 20A Kit was used to perform the STR typing of the initial sample and DNA samples amplified at the whole genome level to evaluate the performance of REPLI-g® Single Cell Kit in trace DNA amplication in terms of purity and yield as well as the success rate of STR typing. Results After comparison, one DNA sample was selected from QIAsymphony® DNA Investigator® Kit extracts to concentrate and dilute as the initial sample of WGA. After amplifying the whole genome of a series of initial samples by REPLI-g® Single Cell Kit, the lowest average of amplification yield reached 8.77×103 ng, while the average of the corresponding amplification times reached 1.40×106. DNA fragments were large and concentrated. The STR typing success rate of WGA samples became lower with the decrease of initial samples used, but when the amount of samples was lower than 0.5 ng, the STR typing success rate of samples after DNA WGA was higher than that of samples without DNA WGA. Conclusion REPLI-g® Single Cell Kit can increase the yield of template DNA. Especially for trace DNA, the STR typing success rate can be improved to a certain extent.
DNA ; DNA Fingerprinting ; Humans ; Microsatellite Repeats ; Nucleic Acid Amplification Techniques/standards* ; Sequence Analysis, DNA/methods*