Clinical Observation of Xiaotan Tongluo Gel Combined with Mecobalamin Tablets in Ttreating Peripheral Neurotoxicity Induced by Chemotherapy / 中国中医药信息杂志

Objective To investigate clinical efficacy of Xiaotan Tongluo Gel combined with mecobalamin tablets in treating chemotherapy-induced peripheral neuropathy (CIPN). Methods Totally 67 cases of CIPN were divided into the treatment group (36 cases) and the control group (31 cases). Both groups were given mecobalamin tablets, 0.5 mg each time, three times a day, orally. Patients in the treatment group were treated with Xiaotan Tongluo Gel for external use at the same time. The patients in control group were treated with placebo gel for external use, 1 mL/cm2, rubbed on the skin 1 cm more than sensory obstruction in diameter. The treatment for both groups lasted for 14 d as a treatment course, and the treatment lasted for 2 courses. The changes of peripheral nerve toxicity, TCM syndrome scores and the nerve conduction velocity were observed in the two groups. Results On the 14th and 28th days of treatment, the total effective rates of peripheral nerve toxicity were 75.00% and 91.67% in the treatment group, and 38.71% and 67.74% in the control group, and the treatment group was significantly better than those of the control group (P=0.002, P=0.005); On the 14th and 28th days of treatment, the total effective rate of TCM efficacy in the treatment group was 75.00% and 94.44% respectively, and that in the control group was 45.16% and 64.52% respectively, and the treatment group was significantly better than the control group (P=0.018, P=0.005). Compared with before treatment, the TCM syndrome scores in both groups were significantly reduced on the 14th and 28th days (P＜0.01); The TCM syndrome scores in the treatment group were significantly lower than those in the control group at the same time points after treatment (P＜0.01). Compared with before treatment, the sensory and motor nerve conduction speeds of the peroneal and median nerves in the two groups at 14th and 28th days were significantly increased (P＜0.01); Comparing the two groups at the same time point after treatment, the sensory and motor nerve conduction velocity of the peroneal and median nerves in the treatment group was significantly better than that in the control group (P＜0.05, P＜0.01). Conclusion Xiaotan Tongluo Gel combined with mecobalamin tablets can effectively improve the peripheral neurotoxicity induced by chemotherapy, TCM syndrome scores, and the nerve conduction velocity.

Therapeutic effect of Jinlongshe Granule () on quality of life of stage IV gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled clinical trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients.</p><p><b>METHODS</b>This randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores.</p><p><b>RESULTS</b>Using time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Additional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.</p>

Inhibitory effect of Xiaotan Sanjie Recipe on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.</p><p><b>METHODS</b>The 3rd passage subcutaneous transplantation tumor was taken as the origin of the model by using MKN-45 human gastric cancer cell lines. MKN-45 human gastric cancer nude mouse model was established using OB glue adhesive method. Then 30 nude mice were divided into the model group, the XSR group, and the chemotherapy group. Mice in the XSR group were intragastrically given XSR at the daily dose of 0.4 mL. Mice in the chemotherapy group were intragastrically given Fluorouracil at the daily dose of 0.4 mL. No intervention was given to mice in the model group. After 6 weeks of medication, the tumor weight was measured, and the tumor inhibition rate calculated. The size, the peak height, and the peak area of 5 microsatellite instability sites were detected.</p><p><b>RESULTS</b>The tumor inhibition rate was 40. 84% in the XSR group. The tumor weight was significantly lower in the XSR group than in the model group (P < 0.01), showing no statistical difference when compared with the chemotherapy group (P >0.05). The incidence of high microsatellite instability (MSI-H) in the model group was 70%, and the incidence of low microsatellite instability (MSI-L) was 30%. Microsatellite stable site tended be stable after 6 weeks of XSR treatment.</p><p><b>CONCLUSION</b>XSR showed inhibition on microsatellite instable orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.</p>

Tumor interstitial fluid and gastric cancer metastasis: an experimental study to verify the hypothesis of "tumor-phlegm microenvironment" / 中国结合医学杂志

<p><b>OBJECTIVE</b>To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.</p><p><b>METHODS</b>An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.</p><p><b>RESULTS</b>There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.</p><p><b>CONCLUSIONS</b>TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".</p>

Professor Wei Pin-kang's experience in treating chemotherapy induced nausea and vomiting: an analysis of herbal medication / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To summarize the herbal medication by Professor WEI Pin-kang's prescriptions in treating chemotherapy induced nausea and vomiting (CINV).</p><p><b>METHODS</b>On the basis of outpatient and inpatients' medical records concerning CINV from case-database (keywords: chemotherapy and vomiting), data of 143 patients and 143 effective prescriptions were collected. The herbs and those category, nature, flavor and meridian distribution were summarized by frequency method using SPSS 13.0 Software. The couple herbs were analyzed by hierarchical cluster analysis.</p><p><b>RESULTS</b>A total of 144 herbs were used (2 353 frequencies). Six groups of herbs [ frequency >5%, cumulative relative frequency (CRF) 58.89%] were used frequently as follow: the herbs for regulating qi (17.81%), resolving phlegm (13.51%), invigorating qi (8.07%), relieving food retention (7.44%), calming Gan to stop endogenous wind (7.05%), and warming the interior (5.01%). The most frequently used herbs ( >20 frequencies, CRF 77.31%) had 31 species as follow: the herbs for regulating qi (6 species), calming Gan to stop endogenous wind (4 species), resolving phlegm (3 species), external application (2 species), invigorating qi (2 species), warming the interior (2 species), activating blood and removing blood stasis (2 species), promoting diuresis and resolving dampness (1 species), purgation (1 species), invigorating blood (1 species), relieving exterior syndrome with pungent-warm property (1 species), relieving exterior syndrome with pungent-cool property (1 species), astringent (1 species), resolving dampness with aromatic property (1 species), calming the mind (1 species), eliminating heat and dampness (1 species), relieving food retention (1 species). Frequency of Rhizoma Pinelliae was 127 including Rhizoma Pinelliae (processed with ginger) 83 (65.35%). Frequency of prepared Radix et Rhizoma Rhei was 85 (95.51% of Prea- praed Rhizoma Rhei). These herbs were mostly of warm nature (43.99%). The total frequency of herb-nature was 3 677 and the pungent (34.76%), bitter (32.06%) and sweet herbs (18.22%) were most frequently used (CRF 85.04%). The total frequency of meridian distribution was 6 627 and these herbs were mostly attributed to Pi, Wei, Gan, and Fei meridians (CRF 71.34%). The most frequently used couple-herbs included Rhizoma Pinelliae and Rhizoma Atisaematis, Fructus Aurantii Immaturus and Submature Bitter Orange, Flos Caryophylli and Calyx Kaki, Rhizoma Coptidis and Os Sepiae, Rumulus Ginnamomi and Radix Paeoniae, Fructus Citri Sarcodactylis and Fructus Citri, aloeswood and toad skin, scorpion and centipede, earth worm and Gekko Swinhoana, bupleurum root and curcumae, fossilia ossis mastodi and oyster, large head atractylodes and poria, and so on.</p><p><b>CONCLUSIONS</b>Professor WEI Pin-kang regarded the therapy of dissolving phlegm and regulating Wei as the fundamental treatment of CINV. He emphasized gastrointestinal metabolic disorders induced by phlegm and stagnation related to chemotherapeutics. He laid equal emphasis on regulating qi, dissolving phlegm, and removing stagnation.</p>

Effect of xiaotan sanjie recipe on expressions of VEGF-C and VEGFR-3 in nude mice with transplanted human gastric adenocarcinoma cell MKN-45 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the mechanism of Xiaotan Sanjie Recipe (XSR) in inhibiting lymphatic metastasis of gastric carcinoma by observing its effects on the expressions of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 in nude mice with transplanted human gastric adenocarcinoma cell MKN-45.</p><p><b>METHODS</b>Thirty mice were made into MKN-45 tumor model and randomly divided into three groups treated with saline, 5-Fu, and XSR, respectively. Gene and protein expressions of VEGF-C and VEGFR-3 in the tumor tissue were detected by RT-PCR, and the lymphatic microvessel density (LMVD) in tumor was measured with immunohistochemistry.</p><p><b>RESULTS</b>Compared with the group treated with saline, the mRNA and protein expressions of VEGF-C and VEGFR-3 as well as LMVD level were significantly lower (P < 0.05 or P < 0.01) in the group treated with XSR. There was no significantly statistic difference between the group of XSR and 5-Fu on the indices mentioned above (P > 0.05).</p><p><b>CONCLUSION</b>By down-regulating the mRNA and protein expressions of VEGF-C and VEGFR-3 might be one of possible mechanisms for XSR in preventing and curing the lymphatic metastasis of gastric carcinoma.</p>

Effects of xiaotan sanjie recipe on vasculogenic mimicry of human gastric cancer xenografts in nude mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Xiaotan Sanjie Recipe (XTSJD) and its mechanism on vasculogenic mimicry (VM) of human gastric cancer xenografts in nude mice.</p><p><b>METHODS</b>The tumor-bearing mice model was established by subcutaneous inoculating with xenografts of human gastric cancer into the right armpit of 30 BALB/c nude mice. After modeling, the tumor-bearing mice were randomly divided into the normal saline group, the XTSJD group, and the doxycycline hyclate (DH) group, 10 in each. And the mice were administered with corresponding medicine by gastrogavage for 4 weeks. Then all mice were killed by cervical dislocation. The tumor mass were weighed and the tumor inhibition rate calculated. The amount of VM in tumor was counted. Expressions of matrix metalloproteinase (MMP) -2 and MMP-9 were tested using immunohistochemical method.</p><p><b>RESULTS</b>Tumor weight in the XTSJD group and the OH group decreased significantly when compared with the NS group (P<0.01). The amount of VM in the XTSJD group (24.50+/-3.03) and the OH group (14.70+/-1.34) was significantly less than that in the NS group (33.10+/-2.64) (P<0.01). The positive expressions of MMP-2 and MMP-9 in the XTSJD group and the OH group was significantly lower than that in the NS group (P <0.01).</p><p><b>CONCLUSION</b>XTSJD could inhibit the formation of VM in xenografted tumor of nude mice. The mechanism might be correlated with the down-regulation of MMP-2 and MMP-9 expressions.</p>

Tumor interstitial fluid and postoperative recurrence of tumors: An experimental study for verifying hypothesis of "tumor-phlegm microenvironment" / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore a method of extracting tumor interstitial fluid (TIF) which is similar to muddy phlegm in Chinese medicine (CM), interleukin-8 (IL-8) in concentration was taken as the representative of the content of TIF, analyzed in the extracted TIF and the original tumor tissue, and examined to see whether TIF has an interfering effect on tumor recurrence.</p><p><b>METHODS</b>Tumor tissue was ground, centrifuged, and filtered for intercellular substances. Tumor-bearing Kunming S180 mice were raised for 21 days and then the tumors were removed to observe the influence of intervention with TIF, normal saline (NS) and a blank control on tumor recurrence.</p><p><b>RESULTS</b>The content of IL-8 in the filtered and unfiltered tumor tissue was not significantly different (P>0.05). Postoperative tumor recurrence in TIF intervention group was significantly higher than that in the NS intervention and control groups (60%, 12/20 vs. 20%, 4/20. vs. 15%, 3/20, χ(2) =11.058, P<0.01). Tumor cells grew vigorously and infiltrated to muscular tissue in TIF intervention group. Large numbers of tumor cells were seen necrotic in the NS intervention group, and small numbers of tumor cells were seen necrotic in the blank control group.</p><p><b>CONCLUSIONS</b>TIF can be effectively extracted by the means described. It does not contain tumor cells, but its contents such as IL-8 may stimulate tumor cell growth and promote postoperative tumor recurrence, which provided preliminary experimental basis for hypothesis of "tumor-phlegm microenvironment".</p>

Mechanisms of treatment of cancer pain with a topical Chinese herbal formula in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pain has a substantial impact on patients' activities and overall quality of life, but current conventional drugs have debilitating side effects, including gastrointestinal disorders. Thus there is a pressing need for new therapies with fewer side effects to alleviate cancer pain. We recently developed a topical herbal formula Xiaotan Tongluo analgesic gel (XTTL gel) based on the principles of traditional Chinese herbalism, and we have received positive feedback from bone cancer pain patients. The aim of this study was to determine the analgesic effects and explore the mechanisms of XTTL gel in a rat model of bone cancer pain.</p><p><b>METHODS</b>The rat model of bone cancer pain was established by inoculating Walker-256 rat carcinoma cells directly into the right tibial medullary cavity of Wistar rats. The rats were randomly assigned to three groups (n = 10 per group): (1) sham bone cancer control (sham group): vehicle (PBS) inoculation without carcinoma cells plus topical administration of blank gel; (2) Sham treatment control (vehicle group): Walker-256 cell inoculation plus topical administration of blank gel; (3) XTTL gel treatment (treatment group): Walker-256 cell inoculation plus topical administration of XTTL gel. XTTL gel treatments were applied daily for 7 days starting on day 14 following inoculation. Outcomes were assessed 21 days after inoculation by mechanical allodynia, histological staining, and by measuring concentrations of type I collagen carboxy-terminal telopeptide (ICTP) and bone-specific alkaline phosphatase (BAP) in serum.</p><p><b>RESULTS</b>Fourteen days after cancer cell incubation, significant mechanical allodynia in the ipsilateral hind paw and tumor growth in proximal end of the tibia were observed in the vehicle and treatment groups but not in the sham group. At day 21, mechanical withdrawal thresholds in treatment group rats were significantly higher ((4.8557 +/- 0.8336) g) compared with those of the vehicle group ((1.8630 +/- 1.4369) g, P < 0.05). ICTP and BAP levels increased significantly in vehicle group rats ((101.5176+/- 11.0694) U/L and (370.7838 +/- 12.8273) U/L, respectively) compared with those of the sham group ((11.7553 +/- 1.1885) U/L and (185.7338 +/- 3.6761) U/L, respectively; P < 0.05). XTTL gel decreased the level of blood serum ICTP ((41.8998 +/- 6.4970) U/L, P < 0.05) but had little effect on blood serum BAP ((365.5338 +/- 18.5361) U/L, P > 0.05).</p><p><b>CONCLUSION</b>Topical use of XTTL gel may have an analgesic effect on bone cancer pain, an effect mediated by lowering of ICTP levels and inhibiting bone resorption.</p>

Study on analgesic effect of traditional Chinese medicine / 中国结合医学杂志

Chinese medicine has been used in treating pain for a long time. Much progress has been made in studies on the mechanism of the analgesic effect of Chinese medicine in animal experiments. It is found that the analgesic action may be related to the following actions: (1) Reducing the secretion of peripheral algogenic substances and inducing the secretion of pain-sensitive substances; (2) Alleviating the accumulation of local algogenic substances; (3) Increasing the release of endogenous analgesic substances; (4) Regulating c-fos gene and increasing the secretion of such substances in the central nervous system, etc. In this paper, the experimental methods and analgesic effect of Chinese medicines are reviewed.