[Examining fermented mustard brine in terms of traditional Chinese medicine].

Fermented mustard brine was a unique liquid fermented with mustard long used in traditional Chinese medicine. It was previously known as Ji Shui, which refered to the yellow salty water after vegetables were fermented. Fermented mustard brine was not established in TCM until the Ming Dynasty. It was found that the original plant of ancient mustard was Brassica juncea (L.) Czern et Coss. var. juncea, and the origin of the mustard used in mustard brine mainly refereed to the cultivated species of Brassica (Brassica juncea var. multiceps Tsen et Lee) in the Brassica branch of the Cruciferae family, which belonged to the mustard leaf class in tillering mustard. Fermented mustard brine tasted spicy and salty and was considered as a feature of cold, and went to the lung meridian. Its effects were of clearing heat and reducing phlegm, calming coughing and expelling pus. It was mainly used for the treatment of lung carbuncle, and also for diseases such as lung impotence, laryngeal tinea, wheezing, coughing, vomiting pus and blood, and facial swelling. The ways to use it involved taking it directly (or taking it warm), taking it with hot soybean milk, having it with food, mixing it with decoction, and mixing it with houttuynia cordata juice. It was mainly produced in the Jiaxing area of Zhejiang province, especially famous for the collection by the Tianning Temple in Tianning in Jiashan, not the Tianning Temple in Changzhou.

Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database.

BACKGROUND: Since 2004, adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX or FLOX) have been the standard of care for patients with resected colon cancer. Herein we examine the change of outcomes over a 10-year period in patients with stage III colon cancer who received this regimen. PATIENTS AND METHODS: Individual patient data from the ACCENT database was used to compare the outcomes in older (1998-2003) and newer (2004-2009) treatment eras for patients with stage III colon cancer who received adjuvant FOLFOX or FLOX. The outcomes were compared between the two groups by the multivariate Cox proportional-hazards model adjusting for age, sex, performance score, T stage, N stage, tumor sidedness, and histological grade. RESULTS: A total of 6501 patients with stage III colon cancer who received adjuvant FOLFOX or FLOX in six randomized trials were included in the analysis. Patients enrolled in the new era group experienced statistically significant improvement in time to recurrence [3-year rate, 76.1% versus 73.0%; adjusted hazard ratio (HRadj) = 0.83 (95% CI, 0.74-0.92), P = 0.0008], disease-free survival (DFS) [3-year rate, 74.7% versus 72.3%; HRadj = 0.88 (0.79-0.98), P = 0.024], survival after recurrence (SAR) [median time, 27.0 versus 17.7 months; HRadj = 0.65 (0.57-0.74), P < 0.0001], and overall survival (OS) [5-year rate, 80.9% versus 75.7%; HRadj = 0.78 (0.69-0.88), P < 0.0001]. The improved outcomes remained in patients diagnosed at 45 years of age or older, low-risk patients (T1-3 and N1), left colon, mismatch repair proficient (pMMR), BRAF, and KRAS wild-type tumors. CONCLUSION: Improved outcomes were observed in patients with stage III colon cancer enrolled in clinical trials who received adjuvant FOLFOX/FLOX therapy in 2004 or later compared with patients in the older era. Prolonged SAR calls for revalidation of 3-year DFS as the surrogate endpoint of OS in adjuvant clinical trials and reevaluation of optimal follow-up of OS to confirm the trial findings based on the DFS endpoints. CLINICAL TRIALS NUMBERS: NCT00079274; NCT00096278; NCT00004931; NCT00275210; NCT00265811; NCT00112918.

Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies.

BACKGROUND: Microsatellite instable/deficient mismatch repair (MSI/dMMR) metastatic colorectal cancers have been reported to have a poor prognosis. Frequent co-occurrence of MSI/dMMR and BRAFV600E complicates the association. PATIENTS AND METHODS: Patients with resected stage III colon cancer (CC) from seven adjuvant studies with available data for disease recurrence and MMR and BRAFV600E status were analyzed. The primary end point was survival after recurrence (SAR). Associations of markers with SAR were analyzed using Cox proportional hazards models adjusted for age, gender, performance status, T stage, N stage, primary tumor location, grade, KRAS status, and timing of recurrence. RESULTS: Among 2630 patients with cancer recurrence (1491 men [56.7%], mean age, 58.5 [19-85] years), multivariable analysis revealed that patients with MSI/dMMR tumors had significantly longer SAR than did patients with microsatellite stable/proficient MMR tumors (MSS/pMMR) (adjusted hazard ratio [aHR], 0.82; 95% CI [confidence interval], 0.69-0.98; P = 0.029). This finding remained when looking at patients treated with standard oxaliplatin-based adjuvant chemotherapy regimens only (aHR, 0.76; 95% CI, 0.58-1.00; P = 0.048). Same trends for SAR were observed when analyzing MSI/dMMR versus MSS/pMMR tumor subgroups lacking BRAFV600E (aHR, 0.84; P = 0.10) or those harboring BRAFV600E (aHR, 0.88; P = 0.43), without reaching statistical significance. Furthermore, SAR was significantly shorter in tumors with BRAFV600E versus those lacking this mutation (aHR, 2.06; 95% CI, 1.73-2.46; P < 0.0001), even in the subgroup of MSI/dMMR tumors (aHR, 2.65; 95% CI, 1.67-4.21; P < 0.0001). Other factors associated with a shorter SAR were as follows: older age, male gender, T4/N2, proximal primary tumor location, poorly differentiated adenocarcinoma, and early recurrence. CONCLUSIONS: In stage III CC patients recurring after adjuvant chemotherapy, and before the era of immunotherapy, the MSI/dMMR phenotype was associated with a better SAR compared with MSS/pMMR. BRAFV600E mutation was a poor prognostic factor for both MSI/dMMR and MSS/pMMR patients. TRIAL IDENTIFICATION NUMBERS: NCT00079274, NCT00265811, NCT00004931, NCT00004931, NCT00026273, NCT00096278, NCT00112918.

[Medical cultural communication between the Song Dynasty and Goryeo Dynasty].

Through the important roles of officials and businessmen as well as the role of bridge of Japan, the medical culture communication between Song Dynasty and Goryeo Dynasty involved many aspects. The Song Dynasty gave medical books to the Goryeo Dynasty which returned some medical books to the Song Dynasty after the inscribing and printing of the medical books. In addition, the phenomena of communication between the two countries are frequent and very common. By the invitation of Goryeo Dynasty, some people of Song dynasty left for Goryeo Dynasty to give medical treatment and to spread the medical knowledge for several times, at the same time, some people from Goryeo Dynasty came to Song Dynasty to study Traditional Chinese Medicine (TCM). Such medical culture communication facilitated and promoted the formation of the medical system and national medicine in Goryeo Dynasty, and enabled the return of some lost medical books in the Song Dynasty from Goryeo Dynasty. More importantly, the medical culture communications between the two countries promoted the influences of TCM in East Asia.

QTL verification of grain protein content and its correlation with oil content by using connected RIL populations of high-oil maize.

Maize with high grain protein and oil contents offers great advantages for human food and animal feed. In this study, grain protein contents of 282 and 263 F7:8 recombinant inbred lines (RILs) of 2 crosses were evaluated in 4 environments within and between populations. The RILs were developed from crosses between an inbred high-oil maize line and 2 normal dent inbred maize lines. A total of 16 single-population QTLs and 19 joint-population QTLs were identified for protein content, and 21 QTLs were detected for protein-oil in each of the 4 environments tested and in combination. Most of the QTLs for protein content were greatly influenced by variation among populations and environments. Seven QTLs showed generational consistency compared with QTLs detected in the 2 F2:3 populations. However, 7 and 6 QTLs were detected in only the RIL and F2:3 populations, respectively. Protein and protein-oil QTLs with the same parental effects were detected at bins 3.03-3.05, 5.04-5.06, 6.03-6.05, 8.03-8.04, and 8.04-8.06, demonstrating that tightly linked and/or pleiotropic QTLs are controlling both traits at these bins. Four single-population QTLs and 11 joint-population QTLs identified at bins 3.02-3.03, 3.05, 7.01, 8.02, 8.03, 8.04-8.05, 8.05, 9.03, and 9.05 with intervals <5 cM could be used in marker-assisted selection. Along with the previously detected QTLs qPRO1-8-1 and qPRO1-5-1 at bins 8.03-8.04 and 5.02-5.04, the QTLs detected herein could be used to develop near isogenic lines and chromosome segment substitution lines in future studies.

In vitro activity of isoimperatorin, alone and in combination, against Mycobacterium tuberculosis.

UNLABELLED: Previous studies have shown that isoimperatorin (IO), a furanocoumarin isolated from several medicinal plants, has antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294). This study demonstrated that IO has antimycobacterial activity against 2 drug-sensitive and 6 drug-resistant isolates, with minimum inhibitory concentrations (MICs) of 50-100 µg ml(-1) and 100-200 µg ml(-1), respectively. IO exhibited synergistic antimycobacterial effects with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) against 6 drug-resistant strains, with fractional inhibitory concentration index (FICI) values of 0·133-0·472, 0·123-0·475 and 0·124-0·25, respectively. The IO/RMP, IO/INH and IO/EMB combination treatments had synergistic effects or no interaction in the 2 drug-sensitive strains and the standard strain ATCC 27294. The synergism of combined drugs against drug-resistant strains was better than drug-sensitive strains. No antagonism was observed in with the aforementioned combinations against all strains tested. IO exhibited relatively low cytotoxicity to Vero cells. Our results indicate that IO may serve as promising a template for future antimycobacterial drug development. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the in vitro synergistic antimycobacterial effects of isoimperatorin (IO) in combination with three first-line drugs: rifampin (RMP), isoniazid (INH) and ethambutol (EMB). The results indicated that the antimycobacterial activity of IO was modest; however, IO was a useful and effective agent against Myco. tuberculosis when it was combined with first-line antimycobacterial drugs and is worthy of further development as a lead compound for the development of novel antimycobacterial therapeutic agents.

A novel monoclonal antibody against human CD80 and its immune protection in a mouse lupus-like disease.

Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), is an attractive means to induce antigen-specific peripheral tolerance in autoimmune disease and organ transplantation. In this study, we generated and characterized a monoclonal antibody (Clone 4E5) against human CD80. 4E5 could recognize both human and mouse CD80 and suppress mixed lymphocyte reaction in vitro. To investigate their potency for clinical use, we further administrated 4E5 to a mouse lupus-like disease model (C57BL/J6) induced by Pristane. 4E5 could inhibit the immune response and attenuate the severity of lupus-like disease. The data showed 4E5 function and suggested that blockade of CD80/CD28 co-stimulatory signal pathway with 4E5 is a promising strategy to decelerate the progression of lupus-like disease and other autoimmune diseases.

Novel anti-prostate cancer curcumin analogues that enhance androgen receptor degradation activity.

The androgen receptor (AR) plays a crucial role in the physiological and pathological functions of androgen. As a transcription factor, the AR modulates androgen activity by regulating the transcription of target genes that are involved in numerous physiological functions and pathological disorders, such as acne vulgaris, androgenetic alopecia, benign prostate hyperplasia (BPH), and prostate cancers. Although many natural and synthetic curcumin analogues have been reported to possess anticancer activity through a common cytotoxic property against proliferating tumor cells, none has been reported to inhibit cancer cell growth through a more specific mechanism or target in the cancer cells. Recently, new curcumin analogues were studied extensively regarding their synthesis, structure-activity (i.e., anticancer activity) relationships, and mechanism of action. These compounds, such as ASC-J9 and its analogues (3 and 4), have now been shown to inhibit prostate cancer proliferation through a novel mechanism of enhancing AR degradation.

New taxanes from the seeds of Taxus mairei.

Two new taxoid metabolites were isolated from the methanol extract of the Taxus mairei seeds. Their structures were established as 2alpha-hydroxy-9alpha,10beta,13alpha-triacetoxy-5alpha-cinnamoyloxytaxa-11-en-4beta,20-epoxide (1) and 2'-acetyl taxol (2) on the basis of spectral analysis.

Chemical analysis of Radix Astragali (Huangqi) in China: a comparison with its adulterants and seasonal variations.

Radix Astragali (root of Astragalus; Huangqi) is a popular traditional Chinese medicine, and Astragalus membranaceus and A. membranaceus var. mongolicus are two commonly used species; however, there are many Astragalus species that could act as adulterants of Radix Astragali. To find the chemical composition of Radix Astragali, the main constituents including flavonoids, saponins, polysaccharides, amino acids, and trace elements were determined in two Radices Astragali, A. membranaceus and A. membranaceus var. mongolicus, and its eight adulterants, Astragalus propinquus, Astragalus lepsensis, Astragalus aksuensis, Astragalus hoantchy, Astragalus hoantchy subsp. dshimensis, Astragalus lehmannianus, Astragalus sieversianus, and Astragalus austrosibiricus. The results showed that the amounts of main constituents such as isoflavonoids and astragalosides varied in different species. In distinction, A. membranaceus and A. membranaceus var. mongolicus contained a higher amount of astragaloside I and IV. In addition, the main constituents of A. membranaceus var.mongholicus changed according to seasonal variation and age of the plant. The chemical composition of different species of Astragalus would provide useful information for the quality control of Radix Astragali.

Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction.

In order to make new analogs of the dopamine (DA) uptake inhibitor methylphenidate, a synthetic methodology based on the Blaise reaction was developed. The reaction between alpha-bromophenylacetic acid esters, zinc and alpha-cyano-omega-mesylates gave stable primary enamines. After reduction of the enamines with cyanoborohydride, the amines could be cyclized to methylphenidate analogs in which the amine ring size and aromatic ring were varied. These compounds were tested for inhibitory potency against [(3)H]WIN 35,428 binding to the cocaine recognition site and [(3)H]DA uptake using rat striatal tissue. When the heterocyclic ring size was varied, the six-membered ring of methylphenidate appeared to be the optimum ring size. When the aryl ring was varied the 4-trifluoromethylphenyl analog was less potent than methylphenidate, the beta-naphthyl congener was considerably more potent, whereas the alpha-naphthyl congener was less potent. Most of the compounds tested had ratios of uptake to binding inhibition (discrimination ratio) that were similar to cocaine and were therefore not lead compounds for the development of cocaine antagonists.

Four polyoxygenated cyclohexenes from the Chinese tree, Uvaria purpurea.

Two novel polyoxygenated cyclohexenes, 6-methoxyzeylenol (3) and 2-acetoxyzeylenone (4), together with two known compounds, zeylenol (1) and zeylenone (2), were isolated from the heartwood of the Chinese tree, Uvaria purpurea. Zeylenol (1) and zeylenone (2) both showed inhibitory activity toward the root growth of Lactuca sativa. Their structures were established by spectroscopic and chemical methods.

[Studies on the supercritical-CO2 fluid extraction of complex prescription Danshen-Jiangxiang].

This paper first reported the supercritical-CO2 fluid extraction of complex prescription Danshen-Jiangxiang. With the active constituents and yield of extracts as index, the each other effect of each drug and effect on total complex prescription in extraction were studied. And the effects of pressure and temperature were also studied. The results showed the effects were different in complex prescription extraction and single prescription. Active constituents can be extracted, but a obvious effect exist each other and effects together the yield of extract, extraction rate and content of active constituents of complex prescription extraction, which are concerned in extraction conditions. These study results have important reference on the modernization of traditional Chinese medicines.

New 11(15-->1)abeotaxane, 11(15-->1),11(10-->9)bisabeotaxane and 3,11-cyclotaxanes from Taxus yunnanensis.

Chemical examination of the seeds of Chinese yew, Taxus yunnanensis Cheng et L. K. Fu resulted in the isolation of an 11(15-->1)abeotaxane, an 11(15-->1), 11(10-->9)bisabeotaxane and two 3,11-cyclotaxanes. The structures of these new taxoids were established as 13alpha-acetoxy-5alpha-cinnamoyloxy-11(15-->1)abeotaxa-4(20),11-diene-9alpha,10beta,15-triol (1), 20-acetoxy-2alpha-benzoyloxy-4alpha, 5alpha, 7beta, 9alpha, 13alpha-pentahydroxy-11(15-->1), 11(10-->9) bisabeotax-11-eno-10,15-lactone (2), 2alpha,10beta-diacetoxy-5alpha-cinnamoyloxy-9alpha-hydroxy-3,11 -cyclotax-4(20)-en-13-one (3) and 10beta-acetoxy-2alpha,5alpha,9alpha-trihydroxy-3,11-cyclotax-4(20)-en-13-one (4) on the basis of spectral analyses.

[Bo tuo, a study on the reasons of its denomination].

Research is made on the reasons of Bo tuo's denomination by studying its got - up method and the evolution of these two characters' font, in order to get a more rational commentary. Discussion is made on each variant forms of Bo tu, so as to explain the reasons of the variation.

[Dynamic observation on imbalance of dynamic and static forces and degenerated cervical intervertebral disc in rats].

OBJECTIVE: To study the relation between biomechanical imbalance and the degree and course of degeneration of cervical intervertebral disc in rats. METHODS: Sixty SD rats, 8 months old, were randomly divided into 6 groups, the control and model groups of 3, 5, 7 months, 10 in each group. The cervical disc dynamic and static forces imbalance of degeneration model was established to assess the degree of degeneration as well as the content some inflammatory mediators (prostaglandin E2, 6-keto-prostaglandin F1 alpha) and collagenase (MMP-1) activity. RESULTS: (1) In 3 months model group and 5 months control group, fibrous ring of intervertebral disc showed some fissure and slight irregular arrangement, nucleus pulposus shrunken or became smaller, mild herniation of nucleus pulposus was seen in some disc. The nucleus pulposus of intervertebral disc in 5 months model group was fibrosed completely and the disc in 7 months model group herniated or became osteophytosis. (2) Compared with the control group of same time period, MMP-1 was increased significantly in the 5 months and 7 months model groups (P < 0.05), and prostaglandin E2 and 6-keto-prostaglandin F1 alpha elevated in the model groups (P < 0.05, P < 0.01). (3) Comparison between model groups, MMP-1 activity in 5 months and 7 months groups was higher than that in the 3 months group (P < 0.05), and 6-keto-prostaglandin F1 alpha was higher in 7 months group than that in 3 months group (P < 0.05). CONCLUSION: Cervical intervertebral disc undergoes a progressive degenerating process. By breaking the dynamic-static balance of neck in rats could accelerate the progression of degeneration. The fact could be used to elucidate the theory of pathogenesis of cervical spondylopathy, dynamic force imbalance in priority and static force imbalance in predominance.

New taxane diterpenoid from seed of the Chinese yew, Taxus yunnanensis.

A novel taxane diterpenoid with a rearranged 5/7/6-membered ring system was isolated from seeds of the Chinese yew, Taxus yunnanensis. Its structure was established as 9alpha,13alpha-diacetoxy-10beta-benzoxy-5alpha- cinnamoyl-11(1 5-->1)-abeotaxa-4(20),11-dien-15-ol on the basis of a spectroscopic analysis. Its relative stereochemistry is proposed from the results of NOESY experiments.