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Feasibility of Three-Dimensional Balanced Steady-State Free Precession Cine Magnetic Resonance Imaging Combined with an Image Denoising Technique to Evaluate Cardiac Function in Children with Repaired Tetralogy of Fallot

  • YaFeng Peng;XinYu Su;LiWei Hu;Qian Wang;RongZhen Ouyang;AiMin Sun;Chen Guo;XiaoFen Yao;Yong Zhang;LiJia Wang;YuMin Zhong
    • Korean Journal of Radiology
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    • v.22 no.9
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    • pp.1525-1536
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    • 2021
  • Objective: To investigate the feasibility of cine three-dimensional (3D) balanced steady-state free precession (b-SSFP) imaging combined with a non-local means (NLM) algorithm for image denoising in evaluating cardiac function in children with repaired tetralogy of Fallot (rTOF). Materials and Methods: Thirty-five patients with rTOF (mean age, 12 years; range, 7-18 years) were enrolled to undergo cardiac cine image acquisition, including two-dimensional (2D) b-SSFP, 3D b-SSFP, and 3D b-SSFP combined with NLM. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) of the two ventricles were measured and indexed by body surface index. Acquisition time and image quality were recorded and compared among the three imaging sequences. Results: 3D b-SSFP with denoising vs. 2D b-SSFP had high correlation coefficients for EDV, ESV, SV, and EF of the left (0.959-0.991; p < 0.001) as well as right (0.755-0.965; p < 0.001) ventricular metrics. The image acquisition time ± standard deviation (SD) was 25.1 ± 2.4 seconds for 3D b-SSFP compared with 277.6 ± 0.7 seconds for 2D b-SSFP, indicating a significantly shorter time with the 3D than the 2D sequence (p < 0.001). Image quality score was better with 3D b-SSFP combined with denoising than with 3D b-SSFP (mean ± SD, 3.8 ± 0.6 vs. 3.5 ± 0.6; p = 0.005). Signal-to-noise ratios for blood and myocardium as well as contrast between blood and myocardium were higher for 3D b-SSFP combined with denoising than for 3D b-SSFP (p < 0.05 for all but septal myocardium). Conclusion: The 3D b-SSFP sequence can significantly reduce acquisition time compared to the 2D b-SSFP sequence for cine imaging in the evaluation of ventricular function in children with rTOF, and its quality can be further improved by combining it with an NLM denoising method.

Genetic Diversity of Chinese Indigenous Pig Breeds in Shandong Province Using Microsatellite Markers

  • Wang, J.Y.;Guo, J.F.;Zhang, Q.;Hu, H.M.;Lin, H.C.;Wang, Cheng;Zhang, Yin;Wu, Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.1
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    • pp.28-36
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    • 2011
  • To investigate the genetic diversity of six Chinese indigenous pig breeds in Shandong province (Laiwu Black, Dapulian Black, Licha Black, Yantai Black, Yimeng Black and Wulian Black), explain their genetic relationship and assess their integrity and degree of admixture with three Western commercial breeds (Landrace, Yorkshire and Duroc), 303 individuals from these breeds were genotyped for 26 microsatellite markers. In general, high genetic diversity (observed heterozygosity ranging from 0.5495 to 0.7746) and large breed differentiation ($F_{ST}$ = 0.188) were observed. The indigenous pig breeds in Shandong exhibited consistently higher levels of genetic diversity than the three Western breeds. However, compared with the Western breeds, which have an $F_{ST}$ value of 0.252, the indigenous breeds in Shandong have smaller $F_{ST}$ value of 0.145. The analysis of breed relationship indicated that the six indigenous breeds are classified into two groups. One includes four breeds, Licha, Yantai, Yimeng and Wulian, which have experienced large gene introgression of the Western breeds through progressive crossbreeding as well as gene flow among themselves. The other includes Laiwu and Dapulian, which are less influenced by the Western breeds and other indigenous breeds in Shandong in the recent past. The results show that some measures must be taken to effectively protect these indigenous pig breeds in Shandong.

Overexpression of Cyclooxygenase-1 Correlates with Poor Prognosis in Renal Cell Carcinoma

  • Yu, Zu-Hu;Zhang, Qiang;Wang, Ya-Dong;Chen, Jing;Jiang, Zhi-Mao;Shi, Min;Guo, Xin;Qin, Jie;Cui, Guang-Hui;Cai, Zhi-Ming;Gui, Yao-Ting;Lai, Yong-Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3729-3734
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    • 2013
  • The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognostic value. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative realtime polymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and 91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1 expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 in RCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemical assays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated high expression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p = 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients with high expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. This is the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affected patients.

Effect of Corticosterone Administration on Small Intestinal Weight and Expression of Small Intestinal Nutrient Transporter mRNA of Broiler Chickens

  • Hu, X.F.;Guo, Yuming;Huang, B.Y.;Zhang, L.B.;Bun, S.;Liu, D.;Long, F.Y.;Li, J.H.;Yang, X.;Jiao, P.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.2
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    • pp.175-181
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    • 2010
  • The effects of corticosterone (CORT) administration on the weight of small intestine and the expression of nutrient transporter mRNA in the small intestine of broiler chickens (Gallus gallus domesticus) were investigated. One hundred and eight sevenday-old birds were randomly divided into two equal groups comprising a control group (CTRL) and an experimental group (CORT). CTRL birds were fed a basal diet and the CORT birds were fed a basal diet containing 30 mg corticosterone/kg from d 8 to 21. At 21 d of age, average daily feed intake (ADFI), serum corticosterone level, small intestinal absolute wet weight and relative weight, and relative abundance of SGLT1, CaBP-D28k, PepT1 mRNA in the duodenum and L-FABP mRNA in the jejunum were determined. The results showed that serum corticosterone level, liver weight and small intestinal relative weight (small intestinal wet weight/body weight) of CORT chickens were about 30.15%, 26.72% and 42.20% higher, respectively, than in the CTRL group (p<0.05). CORT birds had relative mRNA abundance of CaBP-D28k and PepT1 in the duodenum, and L-FABP in the jejunum which was 1.77, 1.37 and 1.94 fold higher, respectively, than in the CTRL group (p<0.05); the relative abundance of SGLT1 was 1.67 fold higher than in the CTRL group (p = 0.097). ADFI, small intestinal wet weight and length in CORT-treated broiler chickens was about 29.11%, 31.12% and 12.35% lower, respectively, than in the CTRL group (p<0.05). In conclusion, corticosterone administration lowered the wet weight but increased the relative weight of the small intestine and the expression of intestinal nutrient transporter mRNA of broiler chickens.

Prognostic Values of Various Clinical Factors and Genetic Subtypes for Diffuse Large B-cell lymphoma Patients: A Retrospective Analysis of 227 Cases

  • Zhou, De;Xie, Wan-Zhuo;Hu, Ke-Yue;Huang, Wei-Jia;Wei, Guo-Qing;He, Jing-Song;Shi, Ji-Min;Luo, Yi;Li, Li;Zhu, Jing-Jing;Zhang, Jie;Lin, Mao-Fang;Ye, Xiu-Jin;Cai, Zhen;Huang, He
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.929-934
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    • 2013
  • Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-cell lymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectively reviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH), ${\beta}2$-microglobulin (${\beta}2$-M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predicting the prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-cell-like (GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOP management, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%, P=0.288). Conclusion: Elevated LDH and ${\beta}2$-M levels, positive B symptoms, Ann Arbor stage III/IV, and primary nodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have a better prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment with the addition of rituximab can improve the prognosis of patients with DLBCL.

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

  • Tang, Yan-Hui;Hu, Min;He, Xiao-Peng;Fahnbulleh, Sando;Li, Cui;Gao, Li-Xin;Sheng, Li;Tang, Yun;Li, Jia;Chen, Guo-Rong
    • Bulletin of the Korean Chemical Society
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    • v.32 no.3
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    • pp.1000-1006
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    • 2011
  • The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

Growth Inhibitory and Pro-Apoptotic Effects of Hirsuteine in Chronic Myeloid Leukemia Cells through Targeting Sphingosine Kinase 1

  • Gao, Shan;Guo, Tingting;Luo, Shuyu;Zhang, Yan;Ren, Zehao;Lang, Xiaona;Hu, Gaoyong;Zuo, Duo;Jia, Wenqing;Kong, Dexin;Yu, Haiyang;Qiu, Yuling
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.553-561
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    • 2022
  • Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete Resection

  • Zhou, Hang;Li, Xiong;Zhang, Yuan;Jia, Yao;Hu, Ting;Yang, Ru;Huang, Ke-Cheng;Chen, Zhi-Lan;Wang, Shao-Shuai;Tang, Fang-Xu;Zhou, Jin;Chen, Yi-Le;Wu, Li;Han, Xiao-Bing;Lin, Zhong-Qiu;Lu, Xiao-Mei;Xing, Hui;Qu, Peng-Peng;Cai, Hong-Bing;Song, Xiao-Jie;Tian, Xiao-Yu;Zhang, Qing-Hua;Shen, Jian;Liu, Dan;Wang, Ze-Hua;Xu, Hong-Bing;Wang, Chang-Yu;Xi, Ling;Deng, Dong-Rui;Wang, Hui;Lv, Wei-Guo;Shen, Keng;Wang, Shi-Xuan;Xie, Xing;Cheng, Xiao-Dong;Ma, Ding;Li, Shuang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3773-3777
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    • 2015
  • Background: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. Materials and Methods: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. Results: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. Conclusions: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

A Study on the ' Zhe Zhong Pai'(折衷派) of the Traditional Medicine of Japan (일본(日本) 의학(醫學)의 '절충파(折衷派)'에 관(關)한 연구(硏究))

  • Park, Hyun-Kuk;Kim, Ki-Wook
    • The Journal of Dong Guk Oriental Medicine
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    • v.10
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    • pp.41-61
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    • 2008
  • The outline and characteristics of the important doctors of the 'Zhe Zhong Pai'(折衷派) are as follows. Part 1. In the late Edo(江戶) period The 'Zhe Zhong Pai', which tried to take the theory and clinical treatment of the 'Hou Shi Pai (後世派)' and the 'Gu Fang Pai(古方派)' and get their strong points to make treatments perfect, appeared. Their point was 'The main part is the art of the ancients, The latter prescriptions are to be used'(以古法爲主, 後世方爲用) and the "Shang Han Lun(傷寒論)" was revered for its treatments but in actual use it was not kept at that. As mentioned above The 'Zhe Zhong Pai' viewed treatments as the base, which was the view of most doctors in the Edo period. However, the reason the 'Zhe Zhong Pai' is not valued as much as the 'Gu Fang Pai' by medical history books in Japan is because the 'Zhe Zhong Pai' does not have the substantiation or uniqueness of the 'Gu Fang Pai', and also because the view of 'gather as well as store up'(兼收並蓄) was the same as the 'Kao Zheng Pai'. Moreover, the 'compromise'(折衷) point of view was from taking in both Chinese and western medical knowledge systems(漢蘭折衷). Generally the pioneer of the 'Zhe Zhong Pai' is seen as Mochizuki Rokumon(望月鹿門) and after that was Fukui Futei(福井楓亭), Wadato Kaku(和田東郭), Yamada Seichin(山田正珍) and Taki Motohiro(多紀元簡). Part 2. The lives of Wada Tokaku(和田東郭), Nakagame Kinkei(中神琴溪), Nei Teng Xi Zhe(內藤希哲), the important doctors of the 'Zhe Zhong Pai', are as follows. First Wada Tokaku(和田東郭, 1743-1803) was born when the 'Hou Shi Pai' was already declining and the 'Gu Fang Pai' was flourishing and learned medicine from a 'Hou Shi Pai' doctor, Hu Tian Xu Shan(戶田旭山) and a 'Gu Fang Pai' doctor, Yoshimasu Todo(吉益東洞). He was not hindered by 'the old ways(古方)' and did not lean towards 'the new ways(後世方)' and formed a way of compromise that 'looked at hardness and softness as the same'(剛柔相摩) by setting 'the cure of the disease' as the base, and said that to cure diseases 'the old way' must be used, but 'the new way' was necessary to supplement its shortcomings. His works include "Dao Shui Suo Yan(導水瑣言)", "Jiao Chiang Fang Yi Je(蕉窗方意解)" and "Yi Xue Sho(醫學說)". Second. Nakagame Kinkei(中神琴溪, 1744-1833) was famous for leaving Yoshimasu Todo(吉益東洞) and changing to the 'Zhe Zhong Pai', and in his early years used qing fen(輕粉) to cure geisha(妓女) of syphilis. His argument was "the "Shang Han Lun" must be revered but needs to be adapted", "Zhong Jing can be made into a follower but I cannot become his follower", "the later medical texts such as "Ru Men Shi Qin(儒門事親)" should only be used for its prescriptions and not its theories". His works include "Shang Han Lun Yue Yan(傷寒論約言)". Third, Nei Teng Xi Zhe(內藤希哲, 1701-1735) learned medicine from Qing Shui Xian Sheng(淸水先生) and went out to Edo. In his book "Yi Jing Jie Huo Lun(醫經解惑論)" he tells of how he went from 'learning'(學) to 'skepticism'(惑) and how skepticism made him learn in 'the six skepticisms'(六惑). In the latter years Xi Zhe(希哲) combines the "Shen Nong Ben Cao Jing(神農本草經)", the main text for herbal medicine, "Ming Tang Jing(明堂經)" of accupuncture, basic theory texts "Huang Dui Nei Jing(皇帝內經)" and "Nan Jing(難經)" with the "Shang Han Za Bing Lun", a book that the 'Gu Fang Pai' saw as opposing to the rest, and became 'an expert of five scriptures'(五經一貫). Part 3. Asada Showhaku(淺田宗伯, 1815-1894) started medicine at Zhong Cun Zhong Zong(中村中倧) and learned 'the old way'(古方) from Yoshimasu Todo and got experience through Ouan Yue(川越) and Fu Jing(福井) and received teachings in texts, history and Wang Yangmin's principles(陽明學) fmm famous teachers. Showhaku(倧伯) meets a medical official of the makufu(幕府), Ben Kang Zong Yuan(本康宗圓), and receives help from the 3 great doctors of the Edo period, Taki Motokato(多紀元堅), Xiao Dao Xue Gu(小島學古) and Xi Duo Cun Kao(喜多村栲窻) and further develops his arts. At 47 he diagnoses the general Jia Mao(家茂) with 'heart failure from beriberi'(脚氣衡心) and becomes a Zheng Shi(徵土), at 51 he cures a minister from France and received a present from Napoleon, at 65 he becomes the court physician and saves Ming Gong(明宮) Jia Ren Qn Wang(嘉仁親王, later the 大正天皇) from bodily convulsions and becomes 'the vassal of merit who saved the national polity(國體)' At the 7th year of the Meiji(明治) he becomes the 2nd owner of Wen Zhi She(溫知社) and takes part in the 'kampo continuation movement'. In his latter years he saw 14000 patients a year, so we can estimate the qualjty and quantity of his clinical skills. Showhaku(宗伯) wrote over 80 books including the "Ju Chuang Shu Ying(橘窻書影)", "Wu Wu Yao Shi Fang Han(勿誤藥室方函)", "Shang Han Biang Shu(傷寒辨術)", "Jing Qi Shen Lun(精氣神論)", "Hunag Guo Ming Yi Chuan(皇國名醫傳)" and the "Xian Jhe Yi Hua(先哲醫話)". Especially in the "Ju Chuang Shu Ying(橘窻書影) he says "the old theories are the main, and the new prescriptions are to be used"(以古法爲主, 後世方爲用), stating the 'Zhe Zhong Pai' way of thinking, In the first volume of "Shang Han Biang Shu(傷寒辨術)" and "Za Bing Lun Shi(雜病論識)", 'Zong Ping'(總評), He discerns the parts that are not Zhang Zhong Jing's writings and emphasizes his theories and practical uses.

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A Study on the 'Zhe Zhong Pai'(折衷派) of the Traditional Medicine of Japan (일본(日本) 의학醫學의 '절충파(折衷派)'에 관(關)한 연구(硏究))

  • Park, Hyun-Kuk;Kim, Ki-Wook
    • Journal of Korean Medical classics
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    • v.20 no.3
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    • pp.121-141
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    • 2007
  • The outline and characteristics of the important doctors of the 'Zhe Zhong Pai'(折衷派) are as follows. Part 1. In the late Edo(江戶) period The 'Zhe Zhong Pai', which tried to take the theory and clinical treatment of the 'Hou Shi Pai (後世派)' and the 'Gu Fang Pai (古方派)' and get their strong points to make treatments perfect, appeared. Their point was 'The main part is the art of the ancients, The latter prescriptions are to be used'(以古法爲主, 後世方爲用) and the "Shang Han Lun(傷寒論)" was revered for its treatments but in actual use it was not kept at that. As mentioned above The 'Zhe Zhong Pai ' viewed treatments as the base, which was the view of most doctors in the Edo period, However, the reason the 'Zhe Zhong Pai' is not valued as much as the 'Gu Fang Pai' by medical history books in Japan is because the 'Zhe Zhong Pai' does not have the substantiation or uniqueness of the 'Gu Fang Pai', and also because the view of 'gather as well as store up' was the same as the 'Kao Zheng Pai', Moreover, the 'compromise'(折衷) point of view was from taking in both Chinese and western medical knowledge systems(漢蘭折衷), Generally the pioneer of the 'Zhe Zhong Pai' is seen as Mochizuki Rokumon(望月鹿門) and after that was Fukui Futei(福井楓亭), Wadato Kaku(和田東郭), Yamada Seichin(山田正珍) and Taki Motohiro(多紀元簡), Part 2. The lives of Wada Tokaku(和田東郭), Nakagame Kinkei(中神琴溪), Nei Teng Xi Zhe(內藤希哲), the important doctors of the 'Zhe Zhong Pai', are as follows First. Wada Tokaku(和田東郭, 1743-1803) was born when the 'Hou Shi Pai' was already declining and the 'Gu Fang Pai' was flourishing and learned medicine from a 'Hou Shi Pai' doctor, Hu Tian Xu Shan(戶田旭山) and a 'Gu Fang Pai' doctor, Yoshimasu Todo(吉益東洞). He was not hindered by 'the old ways(古方), and did not lean towards 'the new ways(後世方)' and formed a way of compromise that 'looked at hardness and softness as the same'(剛柔相摩) by setting 'the cure of the disease' as the base, and said that to cure diseases 'the old way' must be used, but 'the new way' was necessary to supplement its shortcomings. His works include "Dao Shui Suo Yan", "Jiao Chiang Fang Yi Je" and "Yi Xue Sho(醫學說)" Second. Nakagame Kinkei(中神琴溪, 1744-1833) was famous for leaving Yoshirnasu Todo(吉益東洞) and changing to the 'Zhe Zhong Pai', and in his early years used qing fen(輕粉) to cure geisha(妓女) of syphilis. His argument was "the "Shang Han Lun" must be revered but needs to be adapted", "Zhong jing can be made into a follower but I cannot become his follower", "the later medical texts such as "Ru Men Shi Qin(儒門事親)" should only be used for its prescriptions and not its theories". His works include "Shang Han Lun Yue Yan(傷寒論約言) Third. Nei Teng Xi Zhe(內藤希哲, 1701-1735) learned medicine from Qing Shui Xian Sheng(淸水先生) and went out to Edo. In his book "Yi Jing Jie Huo Lun(醫經解惑論)" he tells of how he went from 'learning'(學) to 'skepticism'(惑) and how skepticism made him learn in 'the six skepticisms'(六惑). In the latter years Xi Zhe(希哲) combines the "Shen Nong Ben Cao jing(神農本草經)", the main text for herbal medicine, "Ming Tang jing(明堂經)" of accupuncture, basic theory texts "Huang Dui Nei jing(黃帝內徑)" and "Nan jing(難經)" with the "Shang Han Za Bing Lun", a book that the 'Gu Fang Pai' saw as opposing to the rest, and became 'an expert of five scriptures'(五經一貫). Part 3. Asada Showhaku(淺田宗伯, 1815-1894) started medicine at Zhong Cun Zhong(中村中倧) and learned 'the old way'(古方) from Yoshirnasu Todo and got experience through Chuan Yue(川越) and Fu jing(福井) and received teachings in texts, history and Wang Yangmin's principles(陽明學) from famous teachers. Showhaku(宗伯) meets a medical official of the makufu(幕府), Ben Kang Zong Yuan(本康宗圓), and recieves help from the 3 great doctors of the Edo period, Taki Motokato(多紀元堅), Xiao Dao Xue GU(小島學古) and Xi Duo Cun Kao Chuang and further develops his arts. At 47 he diagnoses the general Jia Mao(家茂) with 'heart failure from beriberi'(脚氣衝心) and becomes a Zheng Shi(徵I), at 51 he cures a minister from France and received a present from Napoleon, at 65 he becomes the court physician and saves Ming Gong(明宮) jia Ren Qn Wang(嘉仁親王, later the 大正犬皇) from bodily convulsions and becomes 'the vassal of merit who saved the national polity(國體)' At the 7th year of the Meiji(明治) he becomes the 2nd owner of Wen Zhi She(溫知社) and takes part in the 'kampo continuation movement'. In his latter years he saw 14000 patients a year, so we can estimate the quality and quantity of his clinical skills Showhaku(宗伯) wrote over 80 books including the "Ju Chuang Shu Ying(橘窓書影)", "WU Wu Yao Shi Fang Han(勿誤藥室方函)", "Shang Han Biang Shu(傷寒辨術)", "jing Qi Shen Lun(精氣神論)", "Hunag Guo Ming Yi Chuan(皇國名醫傳)" and the "Xian Jhe Yi Hua(先哲醫話)". Especially in the "Ju Chuang Shu Ying(橘窓書影)" he says "the old theories are the main, and the new prescriptions are to be used"(以古法爲主, 後世方爲用), stating the 'Zhe Zhong Pai' way of thinking. In the first volume of "Shung Han Biang Shu(傷寒辨術) and "Za Bing Lun Shi(雜病論識)", 'Zong Ping'(總評), He discerns the parts that are not Zhang Zhong Jing's writings and emphasizes his theories and practical uses.

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