Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population.

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.

Research progress in targeted therapies for gastric cancer.

Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.

[Effect of Jinlongshe Granule Drug-containing Serum on Tube Formation, Migration and Apoptosis of Human Lymphatic Endothelial Cells in vitro].

Objective To observe the inhibitory effect of Jinlongshe Granule drug-containing serum (JG-DS) on tube formation, migration, and apoptosis of human lymphatic endothelial cells ( HLECs) in vitro. Methods JG-DS was prepared. The 3rd-passage HLECs were divided into the control group (cultured with normal saline containing serum) and the experimental group (cultured with JG-DS). After cultured for 12 h, the tube formation ability was detected by Matrigel assay, and the migration ability was determined by Transwell assay in the two groups. Cell apoptosis rate was detected by flow cytometry and Annexin-V-FITC/Pl staining method. Results The total length of tube was (3 084. 49 ?326. 27) p.m after acted by 10% JG-DS for 12 h, significantly shorter than that of the control group (7 058.93 ?4 567. 39) pm (P <0.01). The migration number of HLECs was (99 ?26), obviously lower than that of the control group (160 ?32; P <0.05). The apoptosis rate of the two groups was not statistically significant (P >0.05). Conclusion JG could inhibit the tube formation and migration of HLECs in vitro, which might be one of mechanisms for inhibiting tumor micro-lymphatics.

Xiaotan Sanjie decoction normalizes tumor permissive microenvironment in gastric cancer (Review).

Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non­malignant stromal cell types within the TME are regarded as a clinical meaningful target with the lower risk of resistance and tumor relapse. Studies have revealed that the Xiaotan Sanjie decoction, which is formulated on the basis of the theory of phlegm syndrome, a Traditional Chinese Medicine concept, modulates released factors such as transforming growth factor­ß from tumor cells, immune cells, cancer­associated fibroblasts, extracellular matrix, as well as vascular endothelial growth factor involved in the process of angiogenesis within the TME. Clinical studies have also shown that the Xiaotan Sanjie decoction is associated with favorable survival and quality of life. The present review aimed to interpret the hypothesis that Xiaotan Sanjie decoction has the ability to normalize the GC tumor cells by influencing functions of stromal cells within the TME. The possible association between phlegm syndrome and the TME in GC was discussed in the present review. Overall, Xiaotan Sanjie decoction may be suitable to be added to tumor cell­directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.

A traditional Chinese herbal medicine compound preparation versus interventional therapy after resection of small hepatocellular carcinoma: 22-year follow-up.

OBJECTIVE: To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy (IT) in patients after resection of small hepatocellular carcinoma (HCC). in 399 patients after resection of small HCC who were admitted between January 1987 and December 2008 in the Department of Hepatobiliary Surgery and Center of Minimally Invasive Surgery, First Affiliated Hospital of Guangxi Medical University. Four groups were based on different therapy modes: a TCM-only (TCMO) group, a TCM combined with interventional therapy (TCM-IT) group, an interventional therapy-only (ITO) group, and a simple operation (SO) group. Prognostic factors were correlated with overall survival (OS) and OS rates were calculated with the Kaplan-Meier method, and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model. RESULTS: The median OS was 151.20 months in the TCM-IT group, 43.87 months in the ITO group, and 20.77 months in the SO group. All survival rates of the TCMO group were higher than those of the other three groups (>50%). The 5-, 10-, and 15-year OS in the TCMO and ITO patients were 83.94%, 45.50%, and 71.22% and 33.34%, 55.58%, and 9.26%, respectively (risk ratio, 0.209; 95% confidence interval, 0.126-0.347; P = 0.000). Multivariate analysis revealed that the independent risk factors were therapy mode (P = 0.000), sex (P = 0.005), family history (P = 0.011), TNM classification of malignant tumor staging (P = 0.000), medical care-seeking behavior (P = 0.021), and maximum diameter (P = 0.030). CONCLUSION: Long-term oral use of compound RJH tablets may improve OS for small HCC after resection compared with IT.

[Study of the syndromes of traditional Chinese medicine in terms of metabonomics technology: the current situation and considerations].

Syndromes constitute a core aspect in the study of Chinese medicine, and research on the concept of syndromes is important to the study of the process of modernization of traditional Chinese medicine. However, it is somewhat challenging to define a syndrome due to the complexity inherent in the subject, even with the assistance of the reductionism approach of modern medicine. Holistic and dynamic in nature and attaching much importance to functional changes, the newly emerging metabonomics is in many ways inline with the concepts of syndrome differentiation of pathological states in traditional Chinese medicine. Therefore, metabonomics has comparatively strong advantages in the very respect of revealing the natural laws of syndrome differentiation. By reviewing and analyzing the current research on the concept of syndromes and the application of metabonomic technology to exploring the essential core of syndrome differentiation, the authors illustrated the potential commonalities. This would also show the issues requiring attention between the study of syndromes and the metabonomic technology. In the meantime this study reflected the core problems in detail and put forward suggestions with regard to reaching solutions.

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression.

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.

[Towards better understanding the definition of cancerous toxin].

The author explained the definition and its scientific value of "cancerous toxin" proposed by Professor Chang-quan Ling, pointing out that it is helpful for better understanding the pathogenic factor and guiding the diagnosis and treatment of cancer. In regard to the new definition of "cancerous toxin", the author put forward three key issues which should be solved in the field of integrated Chinese and Western medicine. First, the pathological property of cancerous toxin should be uncovered. Second, the relationship between cancerous toxin and syndrome differentiation or dosage of herbs need be further explored. Last, the cause of cancerous toxin is still unknown.

[Preventive effects of a sachet of Chinese herbs on influenza and its immune regulation].

OBJECTIVE: To study the clinical efficacy of Pihui Fanggan Sachet (PHFGS), a sachet of traditional Chinese herbs, in preventing influenza and its immune regulation on mice. METHODS: In clinical study, 239 children from Shanghai Baoshan Xubeihong Art Kindergarten were randomly divided into two groups according to different class; 118 children were treated with PHFGS for 45 days as treatment group and 121 children were as blank control. During the observation period, the incidence rate of influenza, the course of disease and the severity of symptoms were recorded. In experimental study, 40 Kunming mice were randomly divided into normal control group (normal mice treated or not treated with PHFGS), and immunocompromised group (immunocompromised mice treated or not treated with PHFGS). Immunocompromise was induced by intraperitoneal injection of 80 mg/kg cyclophosphamide for 3 days. Some mice in the normal control and immunocompromised groups were then treated with extracted solution of PHFGS through nasal cavity for one week. Spleen index, content of CD(3)(+) T cells and CD(4)(+) T cells, CD(4)(+)/CD(8)(+) ratio, activity of natural killer (NK) cells, serum level of interferon γ (INF-γ) and respiratory level of secretory immunoglobulin A (SIgA) were evaluated. RESULTS: The incidence rate of influenza in the treatment group was much lower than that in the blank control group (P<0.01), and the average course was shortened as compared with the control group (P<0.01). The fever, rhinocleisis, runny nose, and throat congestion in the treatment group were improved as compared with the blank control group (P<0.05, P<0.01). After injection of cyclophosphamide, the spleen index, content of CD(3)(+) T cells and CD(4)(+) T cells, CD(4)(+)/CD(8)(+) ratio, activity of NK cells, serum level of INF-γand respiratory level of SIgA in the immunocompromised group were significantly lower than those in the normal control group (P<0.05 or P<0.01), which indicated the immunosuppression. After treated with PHFGS for one week, the spleen index and the respiratory level of SIgA in the immunocompromised group were improved significantly. Although the content of CD(3)(+) T cells and CD(4)(+) T cells, CD(4)(+)/CD(8)(+) ratio and the serum level of INF-γ were improved, the differences did not reach the significant level. No significant effects on immune function of normal mice were observed. CONCLUSION: PHFGS can prevent influenza effectively by improving the immunity, especially the respiratory mucosal immune function.

Xiaotan Jieyu Prescription Alleviates Breast Precancerous Lesions through PI3K/Akt Signaling Pathway.

METHODS: The successfully established breast precancerous lesion rat model and normal healthy rats were randomly assigned into the blank (BLA), model (MOD), XTJY-low (LD), XTJY-medium (MD), XTJY-high (HD), and tamoxifen (TAM) groups. Different concentrations of XTJY and saline were supplied by intragastric administration for 4 consecutive weeks to assess the protective effect of XTJY on the progress of the breast precancerous lesion in rats involving the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. RESULTS: In this study, it determined that 10 mg/each rat DMBA-combined estrogen and progesterone induction for 10 weeks was the optimal condition for the establishment of the breast precancerous lesion rat model. In vivo administration of XTJY or TAM was found to inhibit the development of the breast precancerous lesion, and the occurrence rate of breast invasive carcinomas was decreased by about 50%. Furthermore, XTJY or TAM markedly reduced protein expressions of PI3K and p-Akt and increased protein expressions of PTEN. CONCLUSION: These data indicated that XTJY can significantly alleviate the development of breast precancerous lesions by inhibiting the activation of the PI3K/Akt signaling pathway. XTJY may be a promising drug for the treatment of precancerous lesions in breast cancer.

[Syndrome differentiation and treatment of Taiyang disease in Shanghan Lun].

OBJECTIVE: To explore the laws in syndrome differentiation of Taiyang disease and the prescriptions and herbs used in its treatment in Shanghan Lun (Treatise on Febrile Diseases). METHODS: The occurrence rates of main syndromes of Taiyang disease, and the usage frequency of the prescriptions and herbs in its treatment were calculated, and the laws in syndrome differentiation and herbal medication were analyzed by hierarchical clustering analysis. RESULTS: Fever and aversion to cold were found to be the main symptoms of Taiyang disease and usually accompanied with headache, absent sweating, neck stiff, floating and tight pulse, and body ache. The accompanying or aggravated symptoms could be classified into lung system syndrome with the manifestations of sweating and asthma, spleen-deficiency syndrome with the manifestations of gastric fullness and diarrhea, stomach syndrome with vomit and constipation. Guizhi decoction was the main prescription used in the treatment of Taiyang disease. Mahuang (Herba Ephedrae) matching Xingren (Semen Armeniacae), Dahuang (Radix et Rhizoma Rhei) matching Mangxiao (Natrii Sulfas), Baizhu (Rhizoma Atractylodes Macrocephalae) matching Fuling (Poria), Fuzi (Radix Aconiti Lateralis) matching Ganjiang (Rhizoma Zingiberis), Chaihu (Radix Bupleuri) matching Huangqin (Radix Scutellariae), Banxia (Rhizoma Pinelliae), and Renshen (Radix Ginseng) as the main compatibilities were used in treating lung diseases, stomach diseases, spleen-deficiency diseases, kidney-deficiency diseases and Shaoyang diseases respectively. CONCLUSION: Exterior syndrome, as a common syndrome in Taiyang disease, is usually treated with Guizhi decoction. The change in syndromes from upper-energizer to lower-energizer in exterior disease can be found from the change of symptoms and the use of herbs. And the development from defending stage to qi stage in exterior disease can be found in the use of prescriptions in Shanghan Lun.

[Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun].

In order to explore the dose-response patterns of Gancao (Radix Glycyrrhizae) in Shanghan Lun (Treatise on Febrile Diseases), all prescriptions containing Gancao in Shanghan Lun were analyzed by frequency and hierarchical clustering analysis. The doses of Gancao used in Shanghan Lun ranged from six zhu (Chinese unit, and one zhu is equal to 0.65 g) to four liang (Chinese unit, and one liang is equal to 15.625 g). Doses of one, two, three or four liang were commonly used. One liang Gancao as juvantia was usually matched with Mahuang (Herba Ephedrae), Xingren (Semen Armeniacae) and Guizhi (Ramulus Cinnamomi) for restricting the excessive diaphoresis of Mahuang. Two liang Gancao was often matched with some couple drugs, such as Guizhi and Shaoyao (Radix Paeoniae), Shigao (Gypsum Fibrosum) and Zhimu (Rhizoma Anemarrhenae), Fuzi (Radix Aconiti Lateralis) and Ganjiang (Rhizoma Zingiberis), for warming yang to supplement qi, nourishing yin, detoxifying Fuzi, and preventing qi impairment from heat evil. Three liang Gancao was mainly matched with Banxia (Rhizoma Pinelliae) or Renshen (Radix Ginseng) for treating middle energizer emesis. Four liang Gancao was matched with Ganjiang or tonifying herbs for invigorating vital qi and relieving spasm in deficiency syndromes with contraction, palpitation or diarrhea. Gancao is used for treating many syndromes in Shanghan Lun. It is frequently used to treat excess or heat syndromes with one or two liang in a dose and deficiency or cold syndromes with three or four liang in a dose.

[Effects of a formula of components from Shengmai Powder on glucocorticoid receptor in rats after thermal injury].

OBJECTIVE: To investigate the effects of a formula of components from Shengmai Powder, a compound traditional Chinese herbal medicine, on glucocorticoid receptor (GR) in rats after thermal injury. METHODS: A total of 32 male SD rats were randomly assigned into normal control group, untreated group, ginsenosides group and components group, with 8 rats in each group. Rats in the normal control group were intragastrically administered with normal saline (NS) at room temperature once daily. Rats in the untreated group were treated with NS before thermal injury, and rats in the components group and ginsenosides group were once daily treated with a mixture of aqueous extracts of Ophiopogonis Japoni, Fructus schizandrae Chinensis and ginsenosides and ginsenosides respectively. Rats were administered for one week. After the last administration, rats in the untreated group and treated groups underwent thermal injury for one hour, and then were sacrificed immediately by decapitation. Blood serum was collected, and the serum corticosterone (CS) and adrenocorticotropic hormone (ACTH) levels were determined with enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) respectively. The liver, lung and kidney homogenates were used to determine the GR binding capacity by radioligand receptor binding assay. The results were analyzed by one point analysis. RESULTS: GR binding capacities in liver, lung and kidney cytosols in the untreated group were obviously lower than those in the normal control group (P<0.01). The GR binding capacities in the liver and lung cytosols in the components group and the ginsenosides group were significantly higher than those in the untreated group (P<0.01), but no significant difference was found in kidney cytosol. Compared with the ginsenosides group, GR binding capacity in liver cytosol in the components group was increased (P<0.01), but there were no noticeable differences when compared with the GR binding capacities in lung and kidney cytosols. Serum CS and ACTH levels of the normal rats were (66+/-16)microg/L and (59+/-18) ng/L respectively. There were significant differences in CS and ACTH levels between the normal control group and the other groups (P<0.01), in which the serum CS and ACTH levels were (113+/-33)microg/L and (125+/-20) ng/L, (123+/-26) microg/L and (110+/-30) ng/L and (118+/-17) microg/L and (115+/-35) ng/L respectively. But there was no significant difference between the untreated group and the other treated groups. CONCLUSION: The formula of components from Shengmai Powder can enhance the effect of ginsenosides in up-regulating GR in rats after thermal injury.

[Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

OBJECTIVE: To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. METHODS: Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. RESULTS: The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. CONCLUSION: Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

[To explore "the relief time" of diseases involving the six meridians in Shang Han Lun in light of the sequence of three yin and three yang].

The time of six meridians diseases tending to be cured in Shang Han Lun (Treatise on Cold Diseases) is always one of the key points for study, but up till now no satisfied explanations are made. The authors try to study it on the basis of the theory of "three-yin and three-yang" according to the relationship between human body and the environment.

["Opening-closing-pivoting" theory on six meridians in Shang Han Lun and the space and time differentiation of three-yin and three-yang].

The "opening-closing-pivoting" theory on the six meridians is one of the difficult points in the study of Shang Han Lun (Treatise on Cold Diseases). The authors give an explanation on the space and time differentiation of three-yin and three-yang as well as the "opening-closing-pivoting" theory based on the predecessor's experience, and then analyze the physiological and pathological characteristics of the six-meridian disorders.

[Professor Ling Changquan's experience in treating primary liver cancer: an analysis of herbal medication].

On the basis of outpatients' medical records concerning primary liver cancer (PLC), data of 552 patients (with 2020 effective prescriptions) from the Outpatient Department of Changhai Hospital treated by Professor Ling Changquan were collected. The nature, flavor and meridian distribution of the herbs used in the prescriptions were summarized by frequency method, and the features of the herbs used according to syndrome differentiation were analyzed by logistic regression. The couple herbs used were analyzed by cluster analysis. All the data were analyzed in combination with the experience of the specialist. It showed that most of the frequently used herbs were herbs for invigorating the spleen to promote appetite, removing toxic materials to inhibit tumor growth, and activating blood circulation to dissipate blood stasis. These herbs are mostly of plain or cool nature, and mainly of sweet, bitter, or acrid taste. It also showed that the most frequently used herbs for qi deficiency were Astragalus membranaceus, Atractylodes macrocephala, and Pseudostellariae; Caulis Spatholobi and Chinese jujube for blood asthenia; Fructus Corni and Ophiopogon japonicus for yin deficiency; Agastache rugosa, Semen Plantaginis and Poria for water-dampness; cape jasmine fruit and baikal skullcap root for heat excess; peach seed and Radix Paeoniae Rubra for blood stasis; Curcuma wenyujin, Akebia trifoliata and Bupleurum chinese for qi stagnation. A total of 19 pairs of couple herbs were summarized by the cluster analysis.

FAM46C is critical for the anti-proliferation and pro-apoptotic effects of norcantharidin in hepatocellular carcinoma cells.

Norcantharidin (NCTD), a demethylated analog of cantharidin derived from Chinese traditional medicine blister beetle, has been currently used as an anticancer drug for various cancers including hepatocellular carcinoma (HCC). In this study, for a more comprehensive understanding of the targets of NCTD in HCC, next-generation RNA-Seq was utilized. We revealed that the expression of FAM46C, which has been reported as a tumor suppressor for multiple myeloma, was enhanced after NCTD treatment. Re-analysis of TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) dataset demonstrated that FAM46C expression was significantly lower in HCC tissues than in normal liver tissues. NCTD injection or FAM46C overexpression could mitigate diethylnitrosamine (DEN)-initiated HCC in mice. Ectopic expression of FAM46C in two HCC cell lines, SMCC-7721 and SK-Hep-1, significantly repressed cell proliferation, and increased cells population in G2/M phase and cell apoptotic rate. We also found that FAM46C overexpression caused a notable decrease in Ras expression, MEK1/2 phosphorylation and ERK1/2 phosphorylation. More importantly, FAM46C knockdown significantly weakened the biological effects of NCTD on HCC cells, which suggested NCTD exerted the anticancer functions partially through up-regulating FAM46C. In conclusion, FAM46C, a tumor suppressor for HCC, is important for the anti-proliferation and proapoptotic effects of NCTD.