Nucleophilic aromatization of monoterpenes from isoprene under nickel/iodine cascade catalysis.

As a large number of organic compounds possessing two isoprene units, monoterpenes and monoterpenoids play important roles in pharmaceutical, cosmetic, agricultural, and food industries. In nature, monoterpenes are constructed from geranyl pyrophosphate (C10) via various transformations. Herein, the bulk C5 chemical-isoprene, is used for the creation of various monoterpenoids via a nucleophilic aromatization of monoterpenes under cascade catalysis of nickel and iodine. Drugs and oil mixtures from conifer and lemon can be convergently transformed to the desired monoterpenoid. Preliminary mechanistic studies are conducted to get insights about reaction pathway. Two types of cyclic monoterpenes can be respectively introduced onto two similar heterocycles via orthogonal C-H functionalization. And various hybrid terpenyl indoles are programmatically assembled from abundant C5 or C10 blocks. This work not only contributes a high chemo-, regio-, and redox-selective transformation of isoprene, but also provides a complementary approach for the creation of unnatural monoterpenoids.

[Acupuncture for prevention of moderate to severe seasonal allergic rhinitis: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of acupuncture for prevention of moderate to severe seasonal allergic rhinitis. METHODS: A total of 105 patients with moderate to severe seasonal allergic rhinitis were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). The patients in the observation group were treated with acupuncture at Yintang (GV 24+), Yingxiang (LI 20), Hegu (LI 4), Zusanli (ST 36), Fengchi (GB 20), Feishu (BL 13), etc. 4 weeks before the seizure period, once every other day, 3 times a week for 4 weeks. The patients in the control group were not given any intervention before the seizure period. Emergency drugs can be given appropriately during the seizure period in both groups. After seizure period, the seizure rate was recorded in the two groups; before treatment and on week 1, 2, 4, 6 of seizure period after treatment, the rhinoconjunctivitis quality of life questionnaire (RQLQ) score and total nasal symptom score (TNSS) were observed in the two groups; the rescue medication score (RMS) was recorded on week 1-6 of seizure period in the two groups. RESULTS: The seizure rate of the observation group was 84.0% (42/50), which was lower than 100.0% (48/48) in the control group (P<0.05). After treatment, the scores of RQLQ and TNSS at each time point of seizure period were decreased compared with before treatment in the observation group (P<0.01), which were lower than the control group (P<0.01). The RMS score at each time point of seizure period in the observation group was lower than the control group (P<0.05, P<0.01). CONCLUSION: Acupuncture can reduce the incidence of moderate to severe seasonal allergic rhinitis, relieve the symptoms, improve the quality of life and reduce the use of emergency drugs.

Effects of Ziyin Qianyang Formula on Renal Fibrosis through the TGF-ß1/Smads Signaling Pathway in Spontaneously Hypertensive Rats.

Objective: The aim of the study is to explore the effects and mechanisms of action of Ziyin Qianyang Formula (ZYQYF) on renal fibrosis in spontaneously hypertensive rats (SHRs). Methods: Forty SHRs were randomly divided into a model group, Ziyin Qianyang Formula regular-dose and high-dose groups (ZYQYF-R, 20 g/kg; ZYQYF-H, 40 g/kg), and a western medicine group (enalapril 10 mg/kg), and 10 Sprague-Dawley rats were selected as the normal group. The rats received continuous gavage administration for 6 weeks and systolic blood pressure (SBP) measurements were obtained every fortnight. The serum levels of urea, serum creatinine (sCr), and uric acid (UA) were measured; the pathological morphology and collagen content of the kidneys were observed by hematoxylin-eosin (HE) and Masson staining; and the serum Ang II level was measured by an enzyme-linked immunosorbent assay (ELISA). Transforming growth factor (TGF)-ß1, Smad-2, Smad-3, and Smad-7 protein and mRNA expressions in kidney tissues was evaluated by western blotting and reverse transcription-polymerase chain reaction. Results: The ZYQYF-H group showed significantly a lower renal weight and renal weight/body weight than the model group. The enalapril and ZYQYF-H groups showed significantly lower SBP than other groups after 6 weeks of administration. The ZYQYF-H group showed better improvement than the ZYQYF-R and enalapril groups in glomerular and tubular morphology and better reductions in inflammatory cell infiltration and collagen volumetric fraction. The ZYQYF-H group also showed better reductions in serum UA and Ang II levels; collagen-I, collagen-III, and p-Smad2/Smad-2 protein expression; and Smad-2 mRNA expression and a better increase in Smad-7 protein and mRNA expression than the enalapril group. Besides, the degree of renal function and fibrosis improvement was positively correlated with the dose of ZYQYF. Conclusion: ZYQYF can significantly reduce SHR blood pressure, protect renal function and structure, and improve renal fibrosis by regulating Smad proteins through TGF-ß1.

[Talking about the key factors to improve the therapeutic effect of acupuncture from "the arrival of qi ensures curative effect"].

"The arrival of qi ensures curative effect" reminds us that the key to acupuncture is "the arrival of qi ". And "arrival of qi " has the dual meanings of "qi arriving at the needles" (getting qi ) and "qi arriving at the pathogenic locations". "Qi arriving at the needles" is the starting point, the nature and strength of the arrival of qi is closely related to the efficacy; "qi arriving at the pathogenic locations" is the end point, so the speed of the qi is an important part of the final effect. This paper mainly discusses the meaning of the above two aspects and its value in improving the efficacy of acupuncture.

[Cohort Study of EGFR-TKIs Combined with Traditional Chinese Medicine and Single EGFR-TKIs for Advanced NSCLC (Non₋small Cell Lung Cancer)].

OBJECTIVE: To explore the curative effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) combined with Traditional Chinese Medicine (TCM) versus single EGFR-TKIs for Advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 59 NSCLC patients with EGFR mutation were divided (2:1) into treatment group and control group. Patients in treatment group (39 cases) take EGFR-TKIs plus TCM and control group (20 cases) take EGFR-TKIs. Analysis the progression-free survival (PFS), disease control rate (DCR) and treatment-related adverse events of two groups. RESULTS: The DCR of the treatment group and control group was 94.1% and 84.2% respectively (P=0.24). In the total population, PFS was 12.1 months in treatment group and 9.1 months in control group [hazard ratio (HR) 0.46; 95%CI 0.23-0.9; P=0.025]. Among patients with exon 19 deletion (19-del), PFS between treatment group and control group was 10.5 months and 9.5 months respectively (P=0.17). For patients with exon Leu858Arg point mutation (L858R), PFS was significantly longer with treatment group than withcontrol group (median 13.2 months vs. 7.8 months; HR 0.32, 95%CI 0.10-0.97; P=0.046). Grade 3-4 treatment-related adverse events were less common withtreatment-group (8.33 %) than control group (15.00%) (P=0.65). CONCLUSION: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM has a certain effect to prolong PFS, especially for the patients with L858R.

[Effects of ShenFu Injection on Peripheral Neurotoxicity of Paclitaxel].

OBJECTIVE: To investigate the effects and the underlying mechanisms of ShenFu Injection on paclitaxel-induced peripheral neuropathy. METHODS: Twenty-eight adult male Wister rats were randomized into 4 groups (n=7) : control group, paclitaxel group, paclitaxel combined with low or high dose of ShenFu Injection groups. Rats were intraperitoneally injected with paclitaxel 8 mg/kg every 4 d for a total of 4 doses except control group. From Day 1 of the experiment (injection),low dose (4 mL/kg) and high dose (8 mL/kg) of Shenfu Injection were intraperitoneally injected daily in the combination groups for a total of 21 d respectively,while normal saline (NS) was injected in control group in the same way instead. Mechanical withdraw threshold (MWT) and thermal withdraw latency (TWL) of rats' hind paw were measured before (0 d) and after the first injection (6 d,14 d). The level of nerve growth factor (NGF) in the serum was measured at 22 d before the euthanasia,and the ultrastructure of the sciatic nerve was observed with transmission electron microscope. RESULTS: The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group ( P<0.05). The combination of paclitaxel with ShenFu Injection,especially the high dose ( P<0.05),significantly reduced the MWT and TWL when compared to paclitaxel group at 14 d. Compared with simultaneous control group,there was no remarkably increased MWT and TWL in the low and high dose of ShenFu Injection (P>0.05) . Compared with control group,the serum NGF level significantly decreased ( P<0.05) in paclitaxel group,while the serum NGF level in low and high dose of ShenFu Injection groups were higher than paclitaxel group,particularly in the high dose group ( P<0.05). When compared to control group,the sciatic nerve fiber structure in the paclitaxel group was generally damaged,including myelin sheath swelling,fragmentation and vacuolization,endoplasmic reticulum swelling and matrix structure disorder in Schwann cells. The structural damages were mitigated in the low dose and high dose groups,especially the latter one,when compared to the paclitaxel group. CONCLUSION: Shenfu Injection can reduce the peripheral neurotoxicity of paclitaxel by promoting the expression of NGF in serum.

An approach based on antioxidant fingerprint-efficacy relationship and TLC bioautography assay to quality evaluation of Rubia cordifolia from various sources.

In this work, an approach based on antioxidant fingerprint-efficacy relationships and TLC bioautography assay was developed for quality evaluation of traditional Chinese medicine (TCM). First, chemical fingerprints of 20 batches of different sources of Rubia cordifolia were established by HPLC. The antioxidant activities of these samples were evaluated by 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Then, five active components from fingerprint peaks were determined by both multiple correlation analysis and TLC bioautography assay. Similarity analysis and hierarchical clustering analysis (HCA) based on these active peaks were chosen to evaluate the quality of R. cordifolia from different sources. The samples with similarities below 0.9 had poorer antioxidant activities and those having stronger activities fell into the same cluster in HCA. Finally, five batches of commercial samples were processed in the same way to verify the feasibility of this method. The results suggested that chemical fingerprinting combined with similarity analysis based on fingerprint-efficacy relationship and TLC bioautography could evaluate the antioxidant activity of R. cordifolia from various sources. The established technique would also provide an easy method of evaluating the quality of other TCMs.

Clinical observation on chemical damage of nephron and the preventive and therapeutic effects of Baoshen Mixture on it.

OBJECTIVE: To observe the change of nephron damaged by chemotherapy and to evaluate the effect of Baoshen Mixture (, BSM) in protecting and treating damaged nephrons. METHODS: Four hundred tumor patients with normal renal function and ready to receive chemotherapy were randomly assigned to two groups. Both groups received one cycle of chemotherapy program of 28-30 days with conventional hydratization, alkalization and chloridization. To the 200 cases in the treated group BSM was given orally thrice a day, 150 mL every time for 15 successive days and the other 200 cases in the control group were treated by chemotherapy alone. The clinical efficacy was compared after treatment, and the changed condition of damaged nephrons were monitored dynamically and compared at different time points (the 3rd, 7th, 14th and 21st day after chemotherapy) by measuring the micro-globulin beta(2) (beta(2)-MG), albumin (Alb) and immunoglobulin G (IgG) levels in urine with radioimmunoassay (RIA). RESULTS: (1) The effective rates in the treated group at the 4 time points of observation were all higher than those in the control group respectively (P<0.05 or P<0.01); (2) Less occurrence of abnormal beta(2)-M, Alb and IgG levels on the 14th and 21st day in the treated group took place compared to that in the control group (P<0.01); (3) Urinary levels of beta(2)-MG, Alb and IgG reached the peak on the 7th day in both groups, and then, they came down gradually and returned to the normal level on the 21st day. However, comparison between the two groups showed that all the three parameters in the treated group on day 3, 14 and 21 were lower than the respective one at the corresponding time points in the control group (P<0.05 or P<0.01). CONCLUSION: The chemotherapy damage on nephron is regular in time, and reversible when treated suitably. TCM shows a marked effect in protecting and treating the damage on nephron caused by chemotherapy.

[Mechanism of hypothalamic effect in small intestine electro-activity of rats regulated by fructus aurantii immaturus].

OBJECTIVE: To observe the effect of Fructus Aurantii Immaturus (FAI) on the electro-activity of small intestines in rats, and evaluate the interrelations between the FAI regulating effect and choecystokinin (CCK) and somatostatin (SS). METHODS: Migrating myoelectric complex (MMC) cyclic period, the ratio of the active time to the cyclic period, and the number of the fast wave within the active time per minute were observed between FAI and the normal saline group by external alimentary canal electrodes; the CCK contents in dorsomedial hypothalamic nucleus (DMH), ventromedia hypothalamic nucleus (VMH), lateral hypothalamus area (LHA) and SS in VMH, LHA, paraventricular nucleus (PVN) by using immuno-chemistry technique and micro-image pattern quantitative analysis and scanning system. RESULTS: The MMC cyclic period shortened, the ratio of the active time to the cyclic period increased and the number of the fast wave within the active time per minute increased in the FAI group, which showed significant difference from the normal saline group; CCK positive neurons were reduced in the areas of DMH, VMH and LHA, SS positive neurons were increased in the areas of VMH, LHA and PVN in the FAI gioup,which showed significant difference compared with the normal saline and the blank control group. CONCLUSION: FAI can stimulate the electro-reactivity of small intestines. The stimulative effect of FAI might be related to CCK and SS in hypothamus.