Effect of YU Ying-ao's Tongzhifang in Treatment of Epilepsy Based on Clinical Diagnosis and Treatment Data / 中国实验方剂学杂志

Objective:Analyze the composition of Tongzhifang，regularity of modified prescriptions based on outpatient medical records of national famous Chinese medicine practitioner Professor YU Ying-ao for the treatment of epilepsy as well as data mining， and summarize the clinical experience of Professor YU in diagnosis and treatment of epilepsy， in order to provide the reference basis for the traditional Chinese medicine treatment epilepsy. Method:Based on the data of outpatient medical records of Professor YU for epilepsy diagnosis and treatment，this study conducted standard patient follow-up，clinical data collection，pretreatment and mining analysis，and was confirmed through expert interviews. Liquorice 2.3 data mining platform and SPSS 17.0 were used for data management and statistical analysis. Result:A total of 1 219 medical records of 243 cases were completely collected. As a result， Professor YU Ying-ao's Tongzhifang for epilepsy was based on ancient prescription Baijinwan，in which Shenglongchi and Ostreae Concha enhance tranquilizing and hyperactivity-subduing effects，Citri Reticulatae Pericarpium，Armeniacae Semen Amarum，Arisaema Cum Bile and Bambusae Caulis in Taenias eliminate phlegm and free channels， Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen promote blood circulation to remove blood stasis， and the 10 herbs were meticulously composed and well compatible. According to the small sample data，the total effective rate of patients with tetany type epilepsy taking this prescription for 3 months and 6 months was 80% （P<0.01）， with no adverse reactions. As for the dosage of Tongzhifang，the dosage for adult pills is generally 3-6 times that of decoction prescriptions，and the dosage for children's pills is generally 5-10 times that of decoction prescriptions. Under the guidance of the combination of disease differentiation and syndrome differentiation，epilepsy at the acute phase was treated with additionally Hupomo 1.5-3 g，the ratio of Curcumae Radix to Alumen is usually 4∶1， severe convulsion was treated with additionally Uncariae Ramulus Cum Uncis， Bombyx Batryticatus and Pheretima， epilepsy due to trauma was treated with additionally Typhae Pollen， Eupolyphaga Steleophaga， Carthami Flos and Radix Paeoniae Rubra； constipation was treated with additionally Cannabis Fructus； fatigue was treated with additionally Astragali Radix； dyspepsia was treated with additionally Galli Gigerii Endothelium Corneum； and irritability treated with additionally Gentiana scabra Bunge. Conclusion:The composition of Professor YU's Tongzhifang for treating epilepsy with Qianzhen Zhixian Huatan Tongluo method is relatively stable. Modified prescriptions are based on syndrome differentiation. Clinical experience and dosage range of decoction prescription and pill prescription for adults and children are available.

A machine learning model based on initial gut microbiome data for predicting changes of Bifidobacterium after prebiotics consumption / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake.</p><p><b>METHODS</b>With a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model.</p><p><b>RESULTS</b>Fecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in β diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01).</p><p><b>CONCLUSION</b>Short-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.</p>

Protective effects and possible mechanism of 12-O-tetradecanoylophorbol-13-decano-ate against acute intestinal radiation injury of mice / 军事医学

Objective To investigate the effect of 12-O-tetradecanoylophorbol-13-decanoate(TPD)on protection against acute intestinal radiation injury of mice and the possible mechanism.Methods Twenty female BALB/c mice aged 6-8 weeks were divided by random number table method into the control group and TPD groups(25,50,and 100 μg/kg). A radiation-damaged model of mice was irradiated by 10 Gy 60Co γ-rays,while the TPD groups were pretreated for 3 d with caudal vein injection before irradiation.The survival time of 20 days and the number of crypts at 3.5 days after irradiation were detected.Rat intestinal epithelial cells(IEC-6)were treated with 1 nmol/L TPD for 12 h before irradiation with 10 Gy 60Co γ-rays,and CCK-8 was used to detect the capability of cell proliferation at 0,1,2,3 and 4 d after irradiation. Results The mice in the control group survived for an average of 4.2 days,compared to 10 days in the optimal TPD group (100 μg/kg).The average number of crypts in the control group and the best TPD group was 11.0 ±1.3 and 35.1 ±1.9 respectively.The proliferation activity of IEC-6 was measured for four consecutive days.The average D value of the TPD groups was significantly higher than that of control.Conclusion TPD has a protective effect against acute intestinal radiation injury, and its protective mechanism may be achieved by promoting intestinal crypt cell proliferation and increasing the number of crypts in the intestine.

Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients.</p><p><b>METHODS</b>Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/mper day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated.</p><p><b>RESULTS</b>Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 10/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%).</p><p><b>CONCLUSION</b>Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.</p>

A machine learning model using gut microbiome data for predicting changes of trimethylamine-N-oxide in healthy volunteers after choline consumption / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease.</p><p><b>METHODS</b>We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge. Fresh fecal samples were collected before taking fasting blood samples for amplifying 16S rRNA V4 tags, and the PCR products were sequenced using the platform of Illumina HiSeq 2000. The differences in gut microbiata between subjects with increased and decreased plasma TMAO were analyzed using QIIME. Based on the gut microbiota data and TMAO levels in the two groups, the prediction model was established using the machine learning random forest algorithm, and the validity of the model was tested using a verified dataset.</p><p><b>RESULTS</b>An obvious difference was found in beta diversity of the gut microbota between the subjects with increased and decreased plasma TMAO level following choline challenge. The area under the curve (AUC) of the model was 86.39% (95% CI: 72.7%-100%). Using the verified dataset, the model showed a much higher probability for correctly predicting TMAO variation following choline challenge.</p><p><b>CONCLUSION</b>The model is feasible and reliable for predicting the level of TMAO metabolism in vivo based on gut microbiota.</p>

Effects of Cataract Surgery on Endothelium in Transplanted Corneal Grafts: Comparison of Extracapsular Cataract Extraction and Phacoemulsification for Complicated Cataract after Penetrating Keratoplasty / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The endothelium should be carefully evaluated when choosing a surgical technique for cataract removal. Therefore, we aimed to study the effects of different cataract surgery techniques on endothelial cell loss in transplanted corneal grafts.</p><p><b>METHODS</b>A total of 54 patients who received complicated cataract surgery in post-penetrating keratoplasty (PKP) eyes at the Shandong Eye Institute between February 2001 and June 2014 were included, and clinical records were reviewed. Baseline demographic details, clinical characteristics, endothelial cell density (ECD), and best-corrected visual acuity (BCVA) were recorded. Wilcoxon rank-sum test and Wilcoxon signed-rank test were used to test the equality of medians. A regression model was constructed to compare the reduced rate of ECD.</p><p><b>RESULTS</b>Of the 54 eyes included in this study, extracapsular cataract extraction (ECCE) was performed in 34 eyes of 33 patients (ECCE group) whereas phacoemulsification was performed in 20 eyes of 20 patients (phacoemulsification group). There was no significant difference in the median age (P = 0.081) or preoperative ECD (P = 0.585) between the two groups. At 6 months after cataract surgery, ECD in ECCE group was significantly higher than that in phacoemulsification group (P = 0.043). In addition, the endothelial cell loss rate in ECCE group was significantly lower than that in phacoemulsification group at 2 months (P = 0.018), 4 months (P < 0.001), and 6 months (P < 0.001) after cataract surgery. Endothelial cell loss rate after cataract surgery increased over the 6-month study duration in both ECCE group (P < 0.001) and phacoemulsification group (P < 0.001), but phacoemulsification resulted in a greater reduction in ECD than that of ECCE in transplanted corneal grafts (P < 0.001). There was no significant difference in postoperative BCVA between the two groups (P = 0.065).</p><p><b>CONCLUSION</b>ECCE is more suitable than phacoemulsification in cataract surgery in complicated cataract after PKP.</p>

Effect of intermittent fasting on physiology and gut microbiota in presenium rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of intermittent fasting on metabolize and gut microbiota in obese presenium rats fed with high-fat-sugar-diet.</p><p><b>METHODS</b>We fed the Wistar rats with high-fat and high-sugar diet to induce adiposity, and the rats for intermittent fasting were selected base on their body weight. The rats were subjected to fasting for 72 h every 2 weeks for 18 weeks. OGTT test was performed and fasting blood samples and fecal samples were collected for measurement of TC, TG, HDL-C and LDL-C and sequence analysis of fecal 16S rRNA V4 tags using Illumina. Gut microbial community structure was analyzed with QIIME and LEfSe.</p><p><b>RESULTS</b>After the intervention, the body weight of the fasting rats was significantly lower than that in high-fat diet group (P<0.01). OGTT results suggested impairment of sugar tolerance in the fasting group, which showed a significantly larger AUC than compared with the high-fat diet group (P<0.05). Intermittent fasting significantly reduced blood HDL-C and LDL-C levels (P<0.05) and partially restored liver steatosis, and improved the gut microbiota by increasing the abundance of YS2, RF32 and Helicobacteraceae and reducing Lactobacillus, Roseburia, Erysipelotrichaceae and Ralstonia. Bradyrhizobiaceae was found to be positively correlated with CHOL and HDL-C, and RF39 was inversely correlated with the weight of the rats.</p><p><b>CONCLUSION</b>Intermittent fasting can decrease the body weight and blood lipid levels and restore normal gut microbiota but can cause impairment of glucose metabolism in obese presenium rats.</p>

Longitudinal analysis of vaginal microbiota in women with recurrent vulvovaginal candidiasis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the vaginal flora in patients with recurrent vulvovaginal candidiasis (RVVC).</p><p><b>METHODS</b>Vaginal swabs were collected at different time points from 6 RVVC patients and 5 healthy women of child-bearing age. The dynamic changes, microbiota composition, alpha diversity and beta diversity in the two groups were assessed by analyzing the 16S rRNA V4 hypervariable region amplified from the total genomic DNA from the swabs.</p><p><b>RESULTS</b>Lactobacillus was the predominant species in healthy women with similar proportions of L.iners and L.crispatus; small proportions of Gardnerella, Prevotella and other genus were also detected. In some healthy women, the vaginal flora showed a high relative abundance of anaerobic bacteria such as Gardnerella, Prevotella, Atopobium, Sneathia. Compared with the healthy women, patients with RVVC showed a significantly reduced diversity of vaginal flora, where L.iners was the predominant species and the content of L.crispatus decreased significantly. In healthy women, the vaginal flora fluctuated with the menstrual cycle, and the fluctuation was the most prominent during menstruation; the dominant species either alternated regularly or maintain an absolute superiority in the menstrual cycle. The vaginal flora showed attenuated fluctuation in women with RVVC, were highly conserved within the menstrual cycle, and maintained a similar composition in the episodes and intermittent periods.</p><p><b>CONCLUSION</b>The vaginal flora of RVVC patients do not undergo regular variations with the menstrual cycle and shows a similar composition between the episodes and intermittent periods. Promoting the production of L.iners or inhibiting the colonization of L.crispatus to restore the composition of the vaginal flora may help in the treatment of RVVC.</p>

Distribution characteristics of trimethylamine N-oxide and its association with gut microbiota / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the distribution of trimethylamine N-oxide (TMAO) in healthy adults with different risk factors and explore its association with gut microbiota.</p><p><b>METHODS</b>We collected fasting blood samples and fresh fecal samples from 181 subjects without atherogenesis in the carotid arteries. Plasma TMAO levels of the subjects were determined using stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). The fecal DNA was extracted, and the 16S rRNA V4 tags were amplified and sequenced by Illumina HiSeq 2000. The association between TMAO and classical cardiovascular risk factors were analyzed. Gut microbial community structure was analyzed with QIIME, and LEfSe was used to identify the biomarkers.</p><p><b>RESULTS</b>The median (IQR) TMAO level was 2.66 (1.96-4.91) µmol/L in the subjects. TMAO level was significantly correlated with body mass index and operational taxonomic units (OTU). Individuals with high TMAO levels were found to have abundant Clostridiales, Phascolarctobacterium, Oscillibacter, and Alistipes but less abundant Anaerosprobacter.</p><p><b>CONCLUSION</b>Chinese subjects have in general low levels of TMAO. TMAO levels are not significantly correlated with the classical cardiovascular risk factors or the gut microbial structures.</p>

Methods, challenges and opportunities for big data analyses of microbiome / 南方医科大学学报

Microbiome is a novel research field related with a variety of chronic inflamatory diseases. Technically, there are two major approaches to analysis of microbiome: metataxonome by sequencing the 16S rRNA variable tags, and metagenome by shot-gun sequencing of the total microbial (mainly bacterial) genome mixture. The 16S rRNA sequencing analyses pipeline includes sequence quality control, diversity analyses, taxonomy and statistics; metagenome analyses further includes gene annotation and functional analyses. With the development of the sequencing techniques, the cost of sequencing will decrease, and big data analyses will become the central task. Data standardization, accumulation, modeling and disease prediction are crucial for future exploit of these data. Meanwhile, the information property in these data, and the functional verification with culture-dependent and culture-independent experiments remain the focus in future research. Studies of human microbiome will bring a better understanding of the relations between the human body and the microbiome, especially in the context of disease diagnosis and therapy, which promise rich research opportunities.