Research progress in therapy drug monitoring of levetiracetam / 中国药房

Levetiracetam （LEV） is the second generation of broad-spectrum anti-epileptic drug. LEV has the advantages of rapid absorption， short half-life， precise efficacy， good tolerance and few drug interactions. In order to improve the clinical efficacy of LEV， and reduce the occurrence of adverse reactions， children， pregnant women， the elderly， and patients with renal insufficiency should receive therapeutic drug monitoring （TDM）. Clinically， the samples are usually plasma or serum， and the TDM methods are mostly immunoassay or chromatography. There is currently no consensus on the effective concentration range of LEV， and the correlation between plasma concentration and adverse reactions is also unclear. The main factors affecting LEV plasma concentration include age， pregnancy， and patient compliance. How to interpret TDM results and adjust dosage based on the results will be the focus of future work.

Molecular Mechanism and Structure-activity Relationship of the Inhibition Effect between Monoamine Oxidase and Selegiline Analogues.

INTRODUCTION: To investigate the inhibition properties and structure-activity relationship between monoamine oxidase (MAO) and selected monoamine oxidase inhibitors (MAOIs, including selegiline, rasagiline and clorgiline). METHODS: The inhibition effect and molecular mechanism between MAO and MAOIs were identified via the half maximal inhibitory concentration (IC50) and molecular docking technology. RESULTS: It was indicated that selegiline and rasagiline were MAO B inhibitors, but clorgiline was MAO-A inhibitor based on the selectivity index (SI) of MAOIs (0.000264, 0.0197 and 14607.143 for selegiline, rasagiline and clorgiline, respectively). The high-frequency amino acid residues of the MAOIs and MAO were Ser24, Arg51, Tyr69 and Tyr407 for MAO-A and Arg42 and Tyr435 for MAO B. The MAOIs and MAO A/B pharmacophores included the aromatic core, hydrogen bond acceptor, hydrogen bond donor-acceptor and hydrophobic core. CONCLUSION: This study shows the inhibition effect and molecular mechanism between MAO and MAOIs and provides valuable findings on the design and treatment of Alzheimer's and Parkinson's diseases.

Establishment of Specific Chromatogram and Thin-layer Identification Method for Kaixinsan / 中国实验方剂学杂志

ObjectiveTo establish the specific chromatogram and thin layer chromatography（TLC） identification method of Kaixinsan（KXS） samples， in order to clarify the key quality attributes and provide reference for the quality evaluation of KXS. MethodHigh performance liquid chromatography（HPLC） specific chromatogram of KXS was developed with YMC Hydrosphere C18 column（4.6 mm×250 mm， 5 μm）， the mobile phase was acetonitrile（A）-0.2% formic acid aqueous solution（B） for gradient elution（0-15 min， 2%-20%A； 15-25 min， 20%-25%A； 25-30 min， 25%-30%A； 30-45 min， 30%-31%A； 45-50 min， 31%-44%A； 50-65 min， 44%-45%A； 65-73 min， 45%-75%A； 73-95 min， 75%-100%A； 95-105 min， 100%A； 105-105.1 min， 100%-2%A； 105.1-120 min， 2%A）， the detection wavelength was 320 nm. Ultra high performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UHPLC-LTQ-Orbitrap MS） was used to identify the chemical components of KXS with electrospray ionization（ESI）， negative ion mode and scanning range of m/z 50-2 000. TLC identification methods for Poria and Ginseng Radix et Rhizoma in KXS were established. ResultThere were 11 common peaks in the specific chromatogram of KXS， attributed to Polygalae Radix， Poria and Acori Tatarinowii Rhizoma. Taking peak 9（α-asarone） as the reference peak， the relative standard deviations of the retention times of 15 batches of KXS samples were<0.2%. A total of 34 compounds were identified by UHPLC-LTQ-Orbitrap MS， including terpenoids， phenylpropanoids， oligosaccharides and ketones. The established TLC had good separation and was rapid， reliable， simple， feasible， suitable for the identification of Poria and Ginseng Radix et Rhizoma in KXS. ConclusionThe specific chromatogram and TLC of KXS are stable and reproducible. The material basis of KXS is basically clarified by MS， which can provide a reference for the development and quality control of KXS.

Establishment of Specific Chromatogram and TLC Identification for Qingxin Lianziyin / 中国实验方剂学杂志

ObjectiveTo establish the specific chromatogram and thin layer chromatography（TLC） of Qingxin Lianziyin（QXLZY） benchmark samples， in order to clarify the key quality attributes and provide a reference for the quality evaluation of QXLZY. MethodHigh performance liquid chromatography（HPLC） specific chromatogram of QXLZY benchmark samples was developed by using a YMC Hydrosphere C18 column（4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile（A）-0.2% formic acid aqueous solution（B） for gradient elution（0-10 min， 5%-20%A； 10-20 min， 20%A； 20-25 min， 20%-24%A； 25-40 min， 24%-30%A； 40-55 min， 30%-50%A； 55-65 min， 50%-100%A； 65-75 min， 100%A； 75-75.1 min， 100%-5%A； 75.1-90 min， 5%A）， and the detection wavelength was 360 nm. Ultra-high performance liquid chromatography-linear ion trap/orbitrap mass spectrometry（UHPLC-LTQ-Orbitrap MS） with electrospray ionization（ESI） was used to identify the components of QXLZY benchmark samples by accurate relative molecular weight and multilevel MS fragment ion information， the detection conditions were positive and negative ion modes and data dependency scanning mode. TLC identification methods for Ophiopogonis Radix， Lycii Cortex， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma in QXLZY were established. ResultA total of 15 characteristic peaks were identified from Glycyrrhizae Radix et Rhizoma， Plantaginis Semen and Scutellariae Radix， and the relative standard deviations of the retention times of 15 characteristic peaks in 15 batches of QXLZY benchmark samples were≤3% with peak 8（baicalin） as the reference peak. A total of 100 compounds， including flavonoids， organic acids， saponins， amino acids and others， were identified in the benchmark samples by UHPLC-LTQ-Orbitrap MS. The established TLC had good separation and was suitable for the identification of Ophiopogonis Radix， Lycii Cortex， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma in QXLZY. ConclusionThe material basis of QXLZY benchmark samples is basically determined by MS designation and source attribution. The established specific chromatogram and TLC of QXLZY are simple， stable and reproducible， which can provide a reference for the development and quality control of QXLZY.

Research Progress on Relation Between Shift Work and Ovarian Cancer / 肿瘤防治研究

The incidence rate of ovarian cancer ranks the third among female malignant tumors, the mortality rate ranks the first and the prognosis is poor. Ovarian cancer poses a serious threat to the health of women's lives. The incidence of ovarian cancer is related to heredity, endocrine disorders and adverse lifestyle factors. In recent years, some scholars have carried out the impact of lifestyle, especially shift work, on the occurrence and development of ovarian cancer. Shift work can lead to circadian disruption, which affects hormonal balance in the body and may be a risk factor for ovarian cancer. This review summarizes four cohort studies and two case-control studies on the relation between shift work and ovarian cancer. The conclusion of the studies is inconsistent, suggesting that further researches are needed.

Correlation of arterial blood lactic acid level in patients with septic shock and mortality 28 days after entering the intensive care unit / 中国医师杂志

Objective:To investigate the relationship between the arterial blood lactic acid level after entering the intensive care unit (ICU) and the 28-day mortality of patients with septic shock.Methods:The clinical data of 303 patients with septic shock hospitalized in the department of critical medicine of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were analyzed retrospectively. According to the blood lactate (Lac) level, the patients were divided into <4 mmol/L group ( n=203), 4-10 mmol/L group ( n=69) and >10 mmol/L group ( n=31). The baseline characteristics of the patients were analyzed. Multiple logistic regression analysis was used to analyze the independent influencing factors of the 28-day mortality of patients with septic shock. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the Lac level after entering the ICU for 28-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. Results:A total of 303 patients with septic shock were included, with 179 died in 28 days, and the total mortality was 59.08%. There were 203, 69, 31 patients in Lac<4 mmol/L, 4-10 mmol/L and >10 mmol/L group, respectively. There were significant differences in Acute Physiology and Chronic Health Evalution Ⅱ (APACHE Ⅱ), Sequential Organ Failure Assessment (SOFA), oxygenation index (PaO 2/FiO 2), abdominal infection, the proportion of vasoactive drugs use among the three groups ( P<0.05). Multiple logistic regression analysis showed that the independent influencing factor of the 28-day mortality of septic shock were age, SOFA, use of mechanical ventilation, lactic acid (Lac). ROC curve analysis showed that the area under the ROC curve (AUC) for predicting 28-day mortality of patients with septic shock was 0.604 5 (95% CI: 0.540 8-0.668 2). When the optimal cut-off value was 3.55 mmol/L, the sensitivity was 0.508 4, the specificity was 0.733 9, the positive likelihood ratio was 1.910 3 and the negative likelihood ratio was 0.669 9. According to the best cut-off value of entrance Lac, patients were divided into high Lac group (≥3.55 mmol/L) and low Lac group (<3.55 mmol/L), and their 28-day mortality rates were 73.39%(91/124) and 49.16%(88/179). Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of the high Lac group was significantly lower than that of the low Lac group ( P<0.001). Multiple logistic regression analysis showed that after adjusting for confounding factors, the 28 d mortality increased to 1.22 times for each increase of 1 mmol/L of Lac [odds ratio ( OR)=1.22, 95% confidence interval (95% CI) was 1.08-1.37, P=0.001 4]. The 28 d mortality in high Lac group was 3.53 times higher than that in low Lac group ( OR=3.53, 95% CI was 1.36-7.09, P=0.000 4). Conclusions:In patients with ICU septic shock, the arterial blood Lac level after admission was associated with 28-day mortality. Patients with septic shock whose arterial blood Lac level exceeded 3.55 mmol/L within 1 hour of entering the room had a significantly increased risk of death.

Current status of chronic respiratory disease management capacity in community health centers in Beijing Miyun district / 中华全科医师杂志

Objective:To investigate the current status of chronic respiratory disease (chronic obstructive pulmary disease, bronchial asthma and obstructive sleep apnea) management capacity in community health centers in Beijing Miyun district.Methods:From November 21 to 22,2018,nineteen community health centers and 65 general practitioners in Miyun district of Beijing were selected to participate in a questionnaire survey. The self-designed questionnaire was divided into two parts: the questionnaire for medical institutions(institution questionnaire)and questionnaire for general practitioners(doctor questionnaire). The institution questionnaires were distributed by the Miyun District Health Commission,and filled in by the person in charge of the institution; the knowledge questionnaires were sent to all general practitioners of 4 community health service centers. The two independent sample t test was used to compare the measurement data in accordance with normal distribution between the two groups, and analysis of variance was used for multi group comparison. Results:Nineteen institution questionnaires were sent to all centers in the district and all 19 valid questionnaires were recovered. Among them, 18 centers thought that chronic respiratory diseases should be included in the management of chronic non-communicable diseases, and health records should be established to achieve regular follow-up monitoring, but only one center had put asthma in the record. Nine centers purchased pulmonary function instrument; 8 centers were equipped with inhaled glucocorticoid, and 1 center was equipped with β 2-receptor agonists. The effective recovery rate of knowledge questionnaire was 100.0% (65/65). There was no significant difference in the knowledge scores of three kinds of chronic respiratory diseases (chronic obstructive pulmary disease, bronchial asthma, obstructive sleep apnea) among general practitioners [(63±19), (64±23), (62±21), F=0.087, P>0.05]. The scores of general practitioners with different ages and professional titles were (57±15), (66±13), (42±16) and (54±19), (67±12), (68±11) respectively. There were significant differences in the knowledge scores of general practitioners with different ages and professional titles ( F= 8.582 and 6.079, all P<0.05). The average scores of general practitioners with age>50 years or junior professional title were lower than others. Conclusions:The leaders of each center in Miyun district have a clear understanding of the necessity of diagnosis and treatment of chronic respiratory diseases, but there are still some problems, such as insufficient attention to chronic respiratory system, insufficient investment in disease management infrastructure, and lack of professional knowledge of chronic respiratory diseases among general practitioners. It is hoped that in the future, chronic respiratory diseases can be introduced into public health service projects, investment in related disease infrastructure will be strengthened, and comprehensive respiratory knowledge and ability training courses suitable for grass-roots general practitioners can be popularized as soon as possible.

Comparison of the clinical efficacy of different fixation systems for the treatment of transverse patellar fractures / 中华创伤杂志(英文版)

PURPOSE@#This study was designed to compare the clinical efficacy of "8" and "0" wire fixation systems combined with double-head cannulated compression screws or Kirschner wires for the treatment of transverse patellar fractures.@*METHODS@#From September 2011 to September 2018, patients with closed transverse patellar fractures treated with a double-head compression screw or Kirschner wire were included and analyzed retrospectively. Patients with patellar fractures combined with distal femoral fractures, tibial plateau fracture or preoperative lower limb dysfunction were excluded. The patients treated with the "8" tension band wire fixation system and Kirschner wire were taken as Group A; those treated with the "0" fixation system and Kirschner wire were taken as Group B; those treated with the "8" fixation system and double-head cannulated compression screw were taken as group C; and those treated with the "0" fixation system and double-head cannulated compression screw were taken as group D. Six weeks and one year after the operation and every month from the third month after the operation until the fractures healed, an X-ray examination was performed to identify fracture healing. The time of fracture healing and postoperative complications of the four groups were compared. One year after the operation, knee function was evaluated by Bostman's score.@*RESULTS@#During the study period, 168 patients with patellar fractures were treated by operations, and 88 patients were excluded because the fracture type did not meet the requirements or because there were combined fractures of the distal femur or tibial plateau. As a result, 80 patients were included in this study, 20 in each group. All the patients were followed up for an average period of 12.2 months. Compared with Group A, patients in Group D presented less postoperative discomfort in the prepatellar region, quicker fracture healing, less fixation failure and better postoperative knee function scores (all p 0.05).@*CONCLUSION@#The "0" wire fixation system combined with a double-head cannulated compression screw seems to be more beneficial than the other three fixation systems for the treatment of transverse patellar fractures.

No Clear Benefit to the Use of Corticosteroid as Treatment in Adult Patients with Coronavirus Disease 2019 : A Retrospective Cohort Study

BackgroundCoronavirus disease 2019 (COVID-19) is becoming an increasing global health issue which has spread across the globe. We aimed to study the effect of corticosteroids in the treatment of adult inpatients with COVID-19. MethodsA retrospective cohort of 115 consecutive adult COVID-19 patients admitted to The Third Peoples Hospital of Hubei Province between Jan 18, 2020, and Feb 28, 2020 was analysed to study the effectiveness of corticosteroid. They were categorized according to whether or not corticosteroid therapy was given, and compared in terms of demographic characteristics, clinical features, laboratory indicators and clinical outcomes. The primary endpoint was defined as either mortality or intensive care unit (ICU) admission. Known adverse prognostic factors were used as covariates in multiple logistic regressions to adjust for their confounding effects on outcomes. ResultsAmong 115 patients, 73 patients (63.5%) received corticosteroid. The levels of age, C-reactive protein, D-dimer and albumin were similar in both groups. The corticosteroid group had more adverse outcomes (32.9% vs. 11.9%) and statistically significant differences were observed (p=0.013). In multivariate analysis, corticosteroid treatment was associated with a 2.155-fold increase in risk of either mortality or ICU admission, although not statistically significant. ConclusionNo evidence suggests that adult patients with COVID-19 will benefit from corticosteroids, and they might be more likely to be harmed with such treatment.

Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells.

Panaxadiol is a triterpenoid sapogenin monomeric compound found in the roots of Panax ginseng and has a variety of biological activities such as neuroprotective and anti-tumour functions. However, the mechanisms how panaxadiol exerts the anticancer effects remain unknown. The current study aimed to investigate the potential activity of panaxadiol on programmed cell death-ligand 1 (PD-L1) expression and tumour proliferation in human colon cancer cells and to identify the underlying mechanism. Results showed that panaxadiol showed little cytotoxicity as assessed by a cytotoxicity assay and significantly inhibited PD-L1 expression at the protein and mRNA level in a dose-dependent manner. Furthermore, panaxadiol supressed the hypoxia-induced synthesis of hypoxia-inducible factor (HIF)-1α via the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways without affecting HIF-1α degradation. Simultaneously, panaxadiol inhibited STAT3 activation through the JAK1, JAK2, and Src pathways. Moreover, pre-treatment with panaxadiol enhanced the activity of cytotoxic T lymphocytes (CTL) and regained their capacity of tumour cell killing in a T cell and tumour cell co-culture system. Immunoprecipitation showed that panaxadiol inhibited PD-L1 expression by blocking the interaction between HIF-1α and STAT3. The inhibitory effect of panaxadiol on tumour proliferation was further demonstrated by colony formation and EdU labelling assays. The anti-proliferative effect of panaxadiol was also proved by a xenograft assay in vivo. Taken together, the current work highlights the anti-tumour effect of panaxadiol, providing insights into development of cancer therapeutic through PD-L1 inhibition.

Patent analysis of Bruton's tyrosine kinase inhibitor ibrutinib / 国际药学研究杂志

The aim of this paper is to analyze the global patent layout of ibrutinib, the patent layout of key themes, and the original research company's patent layout of ibrutinib, so as to provide a reference for the related domestic drug companies to be acquainted with the patent status of the drug, and to select and decide their breakthrough points and market competition strategies. In this study, the drug name and drug structure were used as keywords for search in the patent databases CNABS and DWPI, and the results were combined with the search results from the International Online Search System STN. Then, the patent with ibrutinib as the invention point was selected and used for further analysis. Pharmacyclics has applied for 26 patents on ibrutinib in China, and the subject matter relates to compounds, compositions, new uses, dosage forms, preparation methods and so on. Among them, 4 patents have been granted, 8 patents have been rejected or overdue, and 14 patent applications are still pending. In order to break through the patent barriers of ibrutinib, Chinese pharmaceutical companies should always pay much attention to the patent approval process and the expiration status of patents from the original research company, and make full use of the intellectual property system to effectively protect their own innovations.

Infectious disease rotation for general practice residency training / 中华全科医师杂志

The ability of prevention, treatment and management of infectious diseases is a basic requirement for general practitioners. This article introduces our experience in the infectious disease rotation for general practice residency training, focusing on the rotation management at different stages of training to explore how to improve teaching quality and the ability of trainers in a short period of the rotation.

Infectious disease rotation for general practice residency training / 中华全科医师杂志

The ability of prevention, treatment and management of infectious diseases is a basic requirement for general practitioners. This article introduces our experience in the infectious disease rotation for general practice residency training, focusing on the rotation management at different stages of training to explore how to improve teaching quality and the ability of trainers in a short period of the rotation.

Construction and clinical preliminary validation of an automaticbone age assessment model based on deep learning / 中华放射学杂志

Objective@#To build an automatic bone age assessment system based on China 05 Bone Age Standard and the latest deep learning technology, and preliminary clinical verification was carried out.@*Methods@#The left-hand radiographs of 5 000 children with suspected metabolic disorders were acquired from Wuxi Children′s Hospital. Among these cases, 2 351 patients were randomly chosen as training set, and 101 patients were randomly used as validation set. Four professional pediatric radiologists annotated the development stage according to the China 05 RUS-CHN standard with double-blind method. The mean value of the bone age assessed by experts was the reference standard which was used to train and validate the deep learning mothods based artificial intelligence (AI) model. Accuracy, mean absolute error (MAE), root mean squared error (RMSE) and time efficiency of bone age assessment were compared by using Chi-square test and t test and F test between resident doctors and AI model in the validation set.@*Results@#The MAE and RMSE was (0.37±0.35) years and 0.50 years between AI model and reference standard, respeactively. When the error range was within ±1.0, ±0.7 and ±0.5 years, the accuracy of model on the validation set was 94.1% (95/101), 89.1% (90/101), 74.3% (75/101) respectively. The accuracy between two resident doctors and AI prediction wasn′t statistical significant (P>0.05).@*Conclusion@#The AI model of bone age assessment based on deep learning is feasible and has the characteristics of high accuracy and efficiency.

Novel mutations of PKD genes in Chinese patients suffering from autosomal dominant polycystic kidney disease and seeking assisted reproduction.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), the commonest inherited kidney disease, is generally caused by heterozygous mutations in PKD1, PKD2, or GANAB (PKD3). METHODS: We performed mutational analyses of PKD genes to identify causative mutations. A set of 90 unrelated families with ADPKD were subjected to mutational analyses of PKD genes. Genes were analysed using long-range PCR (LR-PCR), direct PCR sequencing, followed by multiplex ligation-dependent probe amplification (MLPA) or screening of GANAB for some patients. Semen quality was assessed for 46 male patients, and the correlation between mutations and male infertility was analysed. RESULTS: A total of 76 mutations, including 38 novel mutations, were identified in 77 families, comprising 72 mutations in PKD1 and 4 in PKD2, with a positive detection rate of 85.6%. No pathogenic mutations of GANAB were detected. Thirty-seven patients had low semen quality and were likely to be infertile. No association was detected between PKD1 mutation type and semen quality. However, male patients carrying a pathogenic mutation in the Ig-like repeat domain of PKD1 had a high risk of infertility. CONCLUSION: Our study identified a group of novel mutations in PKD genes, which enrich the PKD mutation spectrum and might help clinicians to make precise diagnoses, thereby allowing better family planning and genetic counselling. Men with ADPKD accompanied by infertility should consider intracytoplasmic sperm injection combined with preimplantation genetic diagnosis to achieve paternity and obtain healthy progeny.

Novel FOXL2 mutations cause blepharophimosis-ptosis-epicanthus inversus syndrome with premature ovarian insufficiency.

BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a malformation of the eyelids. Forkhead Box L2 (FOXL2) is the only gene known to be associated with BPES. METHODS: We identified two Han Chinese BPES families with premature ovarian insufficiency (POI). Sanger sequencing and in vitro functional analysis were performed to identify the genetic cause. RESULTS: Sanger sequencing identified two novel mutations (c.462_468del, c.988_989insG) in FOXL2, one in each family. The in vitro functional analysis confirmed that both novel mutations were associated with impaired transactivation of downstream genes. Specifically, the single-base insertion, c.988_989insG, led to subcellular mislocalization and aggregation of the encoded protein, which validated the hypothesis that the two novel FOXL2 mutations are deleterious and associated with POI in the two BPES families. CONCLUSION: The novel mutations identified in the present study will enhance the present knowledge of the mutation spectrum of FOXL2. The in vitro experiments provide further insights into the molecular mechanism by which the two new variants mediate disease pathogenesis and may contribute to elucidating the genotype-phenotype correlation between the two novel FOXL2 mutations and POI.

DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing.

BACKGROUND: The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. OBJECTIVE: To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. METHODS: We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. RESULTS: We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient's seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. CONCLUSIONS: To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.

The experimental research of Qingzao-Jiufei decoction and its composition under the influence of immune inflammation of mice infected with mycoplasma pneumoniae / 国际中医中药杂志

Objective To observe the effect of Qingzao-Jiufei decoction and its composition on the levels of IL-10,TNF-α, CD4+cells, CD8+T cells and the change of CD4+/CD8+ratio in the serum to explore the mechanism of anti-MP infection. Methods The 144 SPF grade BALB/c mice were randomly divided into the normal group, the model, the whole decoction group, the composition Ⅰ group, the composition Ⅱgroup with the method of random digital table, and the azithromycin group and every group had 24 mice. The following five groups were treated with infection of MP model. After successful modeling, the rats in the whole decoction group were treated by gavage with 1 g/ml Qingzao-Jiufei decoction. The rats in the composition Ⅰ group were treated by gavage with 0.61 g/ml composition Ⅰ decoction. The rats in the composition Ⅱ group were treated by gavage with 0.39 g/ml composition Ⅱ decoction. And the three groups were administered for 14 days. The rats in the azithromycin group were treated by gavage with azithromycin suspension once a day. After three days, the drug was stopped. Each group was infected on 3,7,10,14 day. Then mice were sacrificed, with the method of taking the eye of the mice to take blood. The level of IL-10, TNF-α in the mice blood with the method of ELISA were detected. The level of CD4+, CD8+T in the rinsing solution of mice spleen with the method of FCM and the CD4+/CD8+ ratio were detected. Results Compared with the model group, the expressions of CD4+T cells (24.50 ± 1.41 vs. 22.08 ± 1.99) and IL-10 (18.15 ± 0.36 vs. 8.75 ± 0.16) in the whole decoction group significantly increased. The expressions of CD8+T cells (7.29 ± 1.23 vs. 9.13 ± 1.14) and TNF-α (28.32 ± 1.90 vs. 37.97 ± 1.71) significantly decreased (P<0.05), and the level of CD4+/CD8+ratio increased. In the composition Ⅰ group, the expressions of CD8+T cells (7.50 ± 1.45 vs. 9.13 ± 1.14) and TNF-α(33.48 ± 1.08 vs. 37.97 ± 1.71) significantly decreased (P<0.05). In the composition Ⅱ group, the expressions of CD4+T cells (23.63 ± 1.10 vs. 22.08 ± 1.99) and IL-10 (17.82 ± 0.63 vs. 8.75 ± 0.16) significantly increased (P<0.05). Conclusions The mechanism of Qingzao-Jiufei decoction on anti-MP infection may be related to the regulation of the cellular immune.

Effects of Celastrol on Accelerated Healing of Skin Wounds of Diabetic Ulceration in Rats and Mechanism Revealed by Nuclear Magnetic Resonance-based Metabonomics / 分析化学

The experimental SD rats were randomly divided into normal control group (Con group),diabetic ulcer model group (DM group) and Celastrol group (Cel group).Except the control group,diabetic ulceration rat models were established by intraperitoneal injection of streptozotocin along with skin scald.And then,each group was treated by spraying the saline solution on the affected skin with (Cel group) or without (Con group and DM group) Cel (q.d.×14 d).Nuclear magnetic resonance (NMR)-based metabonomic analysis was applied to detect metabolic characteristics,accompanied by healing rate calculation and HE and Masson staining to study therapeutic effect of celastrol on accelerated healing of skin wounds of diabetic ulceration rats,which could be used to elucidate therapeutic effects of celastrol on the rat diabetic ulceration and its mechanism.The results showed that celastrol could induce epithelial regeneration of the rat ulcer wound,regulate the infiltration of inflammatory cells and the distribution of collagen fibers,and promote the healing of the ulcer wound.About 20 endogenous potential differential metabolites were screened and identified by partial least square analysis.Metabolic pathway analysis was carried out to show that celastrol can significantly recovery the level of the tricarboxylic acid cycle,promote its energy supply,accelerate the protein synthesis,improve mitochondrial dysfunction and oxidative stress,and accelerate the self-repair ability of skin tissue.Celastrol can promote the healing of ulcers skins of the diabetic rats,which contribute to experimental basis of the drugs for the treatment of diabetic ulcers.

[Chemical constituents from petroleum ether fraction of Swertia chirayita and their activities in vitro].

The present work is to study the chemical constituents from petroleum ether fraction of Tibetan medicine Swertia chirayita by column chromatography and recrystallization. The structures were identified by physical and chemical properties and spectral data as swerchirin (1), decussatin (2), 1,8-dihydroxy-3,5,7-trimethoxyxanthone (3), 1-hydroxy-3,5,7,8-tetramethoxyxanthone (4), bellidifolin (5), 1-hydroxy-3, 7-dimethoxyxanthone (6), methylswertianin (7), 1-hydroxy-3,5-dimethoxyxanthone (8), erythrodiol (9), oleanolic acid (10), gnetiolactone (11), scopoletin (12), sinapaldehyde (13), syringaldehyde (14), and ß-sitosterol (15). Compounds 3, 4, 9, 11-14 were isolated from S. chirayita for the first time. Compounds 9 and 12 were firstly isolated from the genus Swertia. The cytotoxic activities of compounds 1, 2, 5, 7 and 8 against human pancreatic cancer cell lines SW1990 and BxPC-3,and the protective effects of these compounds against hydrogen peroxide (H2O2)-induced oxidative stress in human endothelium-derived EA.hy926 were investigated in vitro. The results showed no obvious effect at the high concentration of 50 µmol•L⁻¹.