Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Objective:To discuss the clinical efficacy and plausible mechanism of Tiao Yang Qu Xie(regulating Yang to eliminate pathogenic factors)needling method plus paroxetine in treating mild-to-moderate depression. Methods:Sixty-six patients with mild-to-moderate depression were divided into an observation group and a control group using the random number table method,each consisting of 33 cases.Another 25 healthy subjects were recruited as a healthy group.The control group took oral paroxetine tablets for treatment,and the observation group received additional acupuncture treatment 3 times weekly.Both groups underwent 4-week treatment.Before treatment,after 2-week and 4-week treatment,and 2 weeks after treatment(follow-up),the patients were assessed using the Hamilton depression scale-17-item(HAMD-17),self-rating depression scale(SDS),self-rating anxiety scale(SAS),and traditional Chinese medicine(TCM)pattern element identification scale for depression.The two groups each randomly contributed 25 cases to detect the protein content of brain-derived neurotrophic factor(BDNF)before treatment and after 4-week treatment,and compared with the healthy group. Results:After 2-week treatment,the markedly effective and total effective rates were significantly higher in the observation group than in the control group(P<0.05);after 4-week treatment,the observation group significantly surpassed the control group in comparing the markedly effective rate(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the HAMD-17 total score and sleep disorder factor score were lower in the observation group than in the control group(P<0.05);the anxiety-somatic score was lower in the observation group than in the control group after 2-week treatment(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the observation group was lower than the control group in comparing the scores of SDS,SAS,and TCM pattern element identification scale for depression(P<0.05).After 4-week treatment,the observation group had an increased serum BDNF protein content,higher than that in the control group(P<0.05)and had no significant difference compared to the healthy group(P>0.05). Conclusion:Compared to the use of oral paroxetine alone,acupuncture plus paroxetine can produce more significant efficacy in treating mild-to-moderate depression and act faster in improving sleep disorder and anxiety-somatic symptoms;increasing the serum BDNF protein content may be a part of the mechanism underlying its antidepressant actions.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Humans ; Asthma/drug therapy* ; Biological Therapy

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

OBJECTIVE：To analyze the metabolites of tetrahydroxystilbene glucoside （THSG）and speculate its metabolism pathway in rats. METHODS ：Male SD rats were randomly divided into plasma group （n＝3），urine group （n＝3），bile group （n＝3），and tissue group （n＝9）. Each group was given single dose of THSG 200 mg/kg intragastrically. Plasma samples 10，30 min and 1，1.5，2，4 h after medication ，the unrine 0-6 h after medication ，the bile 0-4 h after medication ，the tissue of heart ， liver，spleen，lung，kidney and stomach 30 min and 1，2 h after medication （3 at each time point ）were collected respectively.After precipitated with methanol ，the metabolites of samples were analyzed and identified by UHPLC-Q-Exactive Orbitrap MS and mass loss filtration （MDF）. Its metabolism pathway was speculated. RESULTS：In the blood ，urine，bile，heart，liver，spleen， lung，kidney，stomach samples ，6，7，11，1，5，1，3，4，4 metabolites were detected ，including two phase Ⅰ（hydrolysis， hydrogenation and hydroxylation ）metabolites，18 phase Ⅱ（glucuronic acid binding and sulfation ）metabolites. There were 12 glucuronic acid binding products. CONCLUSIONS：Most of the metabolites of THSG are found in bile ，mainly glucuronic acid binding products of phase Ⅱ metabolite THSG ； main metabolic pathways involve glucose hydrolysis ， hydrogenation， hydroxylation，glucuronic acid binding and sulfation.

OBJECTIVE：To establ ish the fingerprint of Sojae Semen Nigrum and content determination method of 5 kinds of isoflavones，so as to provide reference for controlling its quality better. METHODS ：HPLC method was adopted to establish the fingerprint and detect the contents of 5 kinds of isoflavones. The determination was performed on Phenomenex C 18 column with mobile phase consisted of acetonitrile- 0.12％ formic acid solution （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 260 nm；the column temperature was 30 ℃ and sample size was 10 μL. Using daidzin as reference，HPLC fingerprints of 12 batches of samples were determined. The similarity of 12 batches of samples was evaluated by TCM Chromatographic Fingerprint Similarity Evaluation System （2012A） to confirm common peak. Cluster analysis and principal component analysis were performed by using SPSS 20.0 software and SIMCA 13.0 software. RESULTS ：There were 19 common peaks in HPLC fingerprints of 12 batches of samples ，the similarity of which was higher than 0.94. Totally 5 components were identified，such as daidzin ，glycitin，genistin，daidzein，genistein. Cluster analysis showed that 12 batches of Sojae Semen Nigrum were clustered into 2 categories，i.e. S 1-S3 clustered into one category ，and S 4-S12 clustered into the other category. By principal component analysis ，the contribution rates of two principle components were 53.261％ and 40.715％；accumulative contribution rate was 93.976％. The linear range of above 5 components were 5.97-191.00 µg/mL（r＝0.999 9），1.05-33.46 µg/mL（r＝0.999 9）， 8.93-285.61 µg/mL（r＝0.999 5），0.82-26.33 µg/mL（r＝0.999 9），0.93-29.64 µg/mL（r＝0.999 7），respectively. The limits of quantitation were 0.881 1，0.611 6，0.078 6，0.243 3，0.511 6 μg/mL，respectively. The limits of detection were 0.264 3，0.244 7， 0.021 4，0.124 8，0.106 7 μg/mL，respectively. RSDs of precision ，stability，reproducibility and durability tests were all lower than 5％. Recoveries were 95.15％-96.56％（RSD＝0.51％，n＝6），98.52％-103.45％（RSD＝1.88％，n＝6），95.37％-97.91％ （RSD＝0.95％，n＝6），99.75％-102.00％（RSD＝0.78％，n＝6），100.26％-103.65％（RSD＝1.21％，n＝6）. Among 12 batches of Sojae Semen Nigrum ，the contents of above 5 components were 0.178 3-0.265 9，0.021 7-0.096 2，0.288 5-0.597 2，0.014 1- 0.058 8，0.012 9-0.082 9 mg/g. CONCLUSIONS ：Established HPLC fingerprint and content determination method of 5 kinds of isoflavones can be used for quality control of Sojea Semen Nigrum. The Isoflavone components are similar ，but the contents are different among Sojae Semen Nigrum from different producing areas.

Objective To investigate the clinical value and surgical methods of pancreaticoduodenectomy (PD) combined with portal vein (PV)/superior mesenteric vein (SMV) resection and reconstruction in the treatment of pancreatic cancer with PV/SMV invaded by tumor.Methods The clinical data of 21 patients of pancreatic cancer with PV/SMV invaded by tumor (group A) and 62 patients of pancreatic head cancer without PV/SMV invaded by tumor (group B) in the same period were collected and analyzed retrospectively from Jan 2014 to Apr 2017.There were no distinct invasion of celiac artery (CA),hepatic common artery (HCA) and superior mesenteric artery (SMA) in two groups of pancreatic cancer patients.The patients of group A underwent PD combined with PV/SMV resection and reconstruction,and the patients of group B were only treated with PD surgery.The complication rate and overall survival time after PD was compared between the 21 patients of pancreatic cancer with PV/SMV invaded by tumor and the 62 patients of pancreatichead cancer without PV/SMV invaded by tumor.'Results The average overall survival time of 21 patients of pancreatic cancer with PV/SMV invaded by tumor (group A) was 19.2 months,specifically with 1-year survival rate of 57.1％ (12/21),2-year survival rate of 28.6％ (6/21),and 3-year survival rate of 14.3％ (3/21).Meanwhile,the average overall survival time of group B was 19.4 months,specifically with 1-year survival rate of 58.1％ (36/62),2-year survival rate of 30.6％ (19/62),and 3-year survival rate of 14.5％ (9/62).The results indicated that no differences for overall survival time of patients treated with PD including 1,2,3-year survival rate between two groups were found (P ＞ 0.05).Conclusions For pancreatic cancer accompanied by PV/SMV invasion without invasion of SMA,CA and HCA,PD combined with PV/SMV resection and reconstruction are safe and feasible surgical procedures.The surgical reconstruction method was determined according to the location and length of the invaded vessels,and also there were no significant differences on the complication rate and overall survival time after PD between the pancreatic cancer patients with invasion of PV/SMV and the pancreatic head cancer patients without invasion of PV/SMV.

This study aimed at comparing the precise powder decoction pieces and market raw TCM slices of P.cacumen over the decocting quality.ITS2 sequence was adopted as a DNA barcode to identify P.cacumen.The chemical composition of the medicinal materials was characterized by HPLC fingerprints for the evaluation of the similarity of precise powder decoction pieces and market TCM slices.The concentrations of quercitrin were determined using UPLC,and the characteristic common peaks were identified.In addition,the extraction efficiency between the market TCM slices and the precise powder decoction pieces was also compared by standard decoction method.It was found that P.cacumen was accurately identified by ITS2 sequences.HPLC fingerprints showed that the extraction efficiency and similarity of the precise powder decoction pieces increased compared with the market TCM slices.However,the extraction yield rate of the precise powder decoction pieces was improved by 20％ increased in accordance with the standard decoction method,while the contents of the index component,quercitrin,presented rare increase and the decocting rates of the other chemical components little change in the study.In conclusion,it was indicated that precise powder decoction pieces improved the extraction efficiency and uniformity in comparison with TCM slices.

This study aimed at evaluating the quality of the precise powder decoction pieces (PPDP) of L.japonicae Flos (LJF) compared with the traditional commercial slices with chemical fingerprint methods and DNA molecular identification technology.Different specifications of PPDP were prepared,their dry extract contents were in contrast with that of commercial slices.The three batches of commercial slices were collected,and the content uniformity,fingerprint and similarity evaluation before and after the mixing and pulverization were studied by HPLC-DAD and DNA sequence alignment.As a result,the paste rate of PPDP was slightly higher than that of the traditional commercial slices.The dissolution of chlorogenic acid of PPDP was higher than that of the traditional commercial slices.RSD of inter-assay dissolutions of chlorogenic acid of commercial slices was 11.93％,which was reduced to 8.29％ after mixing and preparing into PPDP.The fingerprint showed that the slimilarity of the fringerprint of the mixed and powdered LJF was elevated with 7 common peaks.All the common peaks were increased at different levels.In conclusion,compared with traditional commercial slices of LJF,PPDP apparently improved the dissolution rate and the quality uniformity,indicating that the boiled powder of CRP obviously presented vantages in clinic.