Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial.

BACKGROUND: Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. METHODS/DESIGN: This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. DISCUSSION: This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT03607656 . Registered on 1 July 2018. The final protocol version is V1.1.

A Glutathione Activatable Photosensitizer for Combined Photodynamic and Gas Therapy under Red Light Irradiation.

Although photodynamic therapy (PDT) is a promising approach for cancer therapy, most existing photosensitizers lack selectivity for tumor cells and the overexpressed glutathione (GSH) in tumor cells reduces the PDT efficiency. Therefore, designing photosensitizers that can be selectively activated within tumor cells and combine PDT with other therapeutic modalities represents a route for precise and efficient anticancer treatment. Herein, an organic activatable photosensitizer, CyI-DNBS, bearing 2,4-dinitrobenzenesulfonate (DNBS) as the cage group is reported. CyI-DNBS can be uptaken by cancer cells after which the cage group is selectively removed by the intracellular GSH, resulting in the generation of SO2 for gas therapy. The reaction also releases the activated photosensitizer, CyI-OH, that can produce singlet oxygen (1 O2 ) under red light irradiation. Therefore, CyI-DNBS targets cancer cells for both photodynamic and SO2 gas therapy treatments. The activatable photosensitizer provides a new approach for PDT and SO2 gas synergistic therapy and demonstrates excellent anticancer effect in vivo.

Near-Infrared Light Triggered H2 Generation for Enhanced Photothermal/Photodynamic Therapy against Hypoxic Tumor.

The principle of photochemical transformation has shown significant inspiration on phototherapy of solid tumors. However, both photodynamic therapy (PDT) and photothermal therapy (PTT) can induce stress response of tumor cells, which draw the attention in recent. Herein, an asymmetric and lollipop like nanostructure consisting of gold nanorod/titanium dioxide (l-TiO2 -GNR) is developed by controlling single head growth of titanium dioxide (TiO2 ) on gold nanorods (GNR). Through the reasonable utilization of hot electrons of GNR by 808 nm light irradiation, l-TiO2 -GNR perform type I-PDT, mild PTT (48 °C), and H2 therapy which is efficient for hypoxic tumors. In particular, H2 can downregulate both triphosadenine and heat shock protein which are found to be main source of tumor stress response. l-TiO2 -GNR opens a new window for treatment of hypoxic tumor by the perfect synergy of type I-PDT, mild PTT, and H2 therapy.

Sublethal hyperthermia enhances anticancer activity of doxorubicin in chronically hypoxic HepG2 cells through ROS-dependent mechanism.

Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful antitumor effect than thermal ablation alone in hepatocellular carcinoma patients. However, the underlying mechanisms remain unclear. The purpose of the present study was to evaluate whether sublethal hyperthermia encountered in the periablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms. In the present study, HepG2 cells precultured under chronic hypoxic conditions (1% oxygen) were treated in a 42°C water bath for 15 or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity. The results confirmed that sublethal hyperthermia enhanced the intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells as compared with hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of MMP. Pretreatment with the ROS scavenger N-acetyl cysteine significantly inhibited the apoptotic response, suggesting that cell death is ROS-dependent. These findings suggested that sublethal hyperthermia enhances the anticancer activity of doxorubicin in hypoxic HepG2 cells via a ROS-dependent mechanism.

Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits.

OBJECTIVES: To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. METHODS: BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 µm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 µm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. RESULTS: The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). CONCLUSIONS: The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.

Author Correction: Diversity and bioactive potential of culturable fungal endophytes of Dysosma versipellis; a rare medicinal plant endemic to China.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Diversity and bioactive potential of culturable fungal endophytes of Dysosma versipellis; a rare medicinal plant endemic to China.

The plant Dysosma versipellis is known for its antimicrobial and anticancer properties but is a rare and vulnerable perennial herb that is endemic to China. In this study, 224 isolates were isolated from various tissues of D. versipellis, and were classified into 53 different morphotypes according to culture characteristics and were identified by sequence analyses of the internal transcribed spacer (ITS) region of the rRNA gene. Although nine strains were not assignable at the phylum level, 44 belonged to at least 29 genera of 15 orders of Ascomycota (93%), Basidiomycota (6%), and Zygomycota (1%). Subsequent assays revealed antimicrobial activities of 19% of endophytic extracts against at least one pathogenic bacterium or fungus. Antimicrobial activity was also determined using the agar diffusion method and was most prominent in extracts from four isolates. Moreover, high performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry analyses (UPLC-QTOF MS) showed the presence of podophyllotoxin in two Fusarium strains, with the highest yield of 277 µg/g in Fusarium sp. (WB5121). Taken together, the present data suggest that various endophytic fungi of D. versipellis could be exploited as sources of novel natural antimicrobial or anticancer agents.

[Effect of Buyang Huanwu decoction and its simple prescription (Naojian tablet) on CDK4/Cyclin D1 expression of rats with cerebral ischemia].

To evaluate the regulating effect of Buyang Huanwu decoction and its simple prescription (Naojian tablet) on CDK4/Cyclin D1 expression in hippocampus tissues of rats with cerebral ischemia, SD rats were divided into the sham-operation group, the model group, the Buyang Huanwu decoction group (ig, 3.15 g · kg⁻¹) and the simple prescription group (ig, 2.41 g · kg⁻¹). Each group was further divided into five subgroups based on time points after the administration, i. e. 1 d, 3 d, 7 d, 14 d and 28 d, respectively. CDK4/Cyclin D1 expressions of the group at different time points were examined by using immunohistochemistry and real-time qPCR. According to the results, the cerebral ischemia model group showed higher CDK4/Cyclin D1 expression than the sham-operation groups (P < 0.05), suggesting that the cell cycle signal pathway would be activated by the cerebral ischemic injury. Both Buyang Huanwu decoction and simple prescription groups showed significantly lower cyclin expression than the model group at 3 d, 7 d, 14 d, 28 d (P < 0.05), indicating both Buyang Huanwu decoction and its simple prescription could play the neuroprotective effect through the cell cycle signal pathway.

[Topsoil phosphorus forms and availability of different soil and water conservation plantations in typical black soil region, northeast China].

Aiming to understand soil phosphorus status of plantations in typical black soil region of Northeast China, the topsoil (0-10 cm) phosphorus fractionations and its availability were examined in four soil and water conservation plantations dominantly composed of Larix gmelini, Fraxinus mandshurica, Pinus sylvestris var. mongolica and Populus nigra var. italica x P. cathayan, respectively. The results showed that total P, Olsen-P and the concentration of different P fractionations in F. mandshurica and P. nigra var. italica x P. cathayan plantations were significantly higher than that of the other two coniferous plantations. Organic P was the major fractionation in the four plantations' topsoil, and sodium hydroxide extractable organic P (NaOH-Po ) representing moderately labile organic phosphorus was predominant, which accounted for 58.9% of total P. The contents of H2O-Pi and NaHCO3-P which were more labile to plant were lower, only accounting for 1.2% and 6.6% of total P, respectively. Except for NaHCO3-Po, all the other P fractions of four plantations correlated with each other, and they also had significant correlations with soil organic matter, total P, Olsen-P. Compared with the coniferous plantations, the broadleaf plantations presented higher availability of phosphorus.

[Effect of Baisuifang Granule on cognitive malfunction after cerebral infarction].

OBJECTIVE: To explore the mechanism of Baisuifang Granule in treating cognitive malfunction after cerebral infarction. METHODS: One hundred and sixty patients with cerebral infarction were divided randomly into two groups. Eighty patients were treated with Baisuifang Granule and 80 with nimodipine for two months. Clinical observation and laboratory examinations were performed for Mini-Mental State Examination (MMSE), clinical symptoms, Chinese Stroke Scale (CSS), hemorrheological indexes and fibrinogen before and after the treatment. RESULTS: Baisuifang Granule could improve MMSE, reduce the scores of clinical symptoms and CSS, and meliorate the blood rheology. The total effective rate for clinical symptoms in the Baisuifang treated group accounted to 76.25%, with statistical difference comparing to 58.75% of nimodipine treated group (P<0.05). There was significant difference in symptom integral, CSS and whole blood viscosity at the high shear rate, respectively (P<0.01). CONCLUSION: Baisuifang Granule is an effective Chinese medicine for treating cognitive malfunction after cerebral infarction.

A ten-year study on non-surgical treatment of postoperative bile leakage.

AIM: To summarize systematically our ten-year experience in non-surgical treatment of postoperative bile leakage, and explore its methods and indications. METHODS: The clinical data of 57 patients with postoperative bile leakage treated non-surgically from January 1991 to December 2000 were reviewed retrospectively. RESULTS: The site of the leakage was mainly the disrupted or damaged fistulous tracts of T tube in 25 patients (43.9 %), the fossae of gallbladder in 14 cases (24.6 %), the cut surface of liver in 7 cases(12.3 %), and it was undetectable in the other 2 cases. Besides bile leakage, the wrong ligation of bile ducts was found in 3 patients, residual stones of the distal bile duct in 5 patients, benign papillary strictures in 3, and biloma resulting from bile collections in 2. The diagnoses were made according to the history of surgery, clinical situation, abdominal paracentesis, ultrasonography, ERCP, PTC, MRI/MRCP, gastroscopy and percutaneous fistulography. All 57 patients were treated non-surgically at the beginning of bile leakage. The non-surgical methods included keeping original drainage unobstructed, percutaneous abdominal paracentesis or drainage, percutaneous transhepatic cholangial/biliary drainage (PTCD/PTBD),endoscopic management, traditional Chinese medicine and so on. Of the 57 patients,2 patients died,5 were converted to reoperation later, the other 50 were directly cured by non-surgical methods without any complication. The cure rate of the non-surgery was 82.5 %(50/57). CONCLUSION: Many nonoperative methods are available to treat postoperative bile leakage. Non-surgical treatment may serve as the first choice for the treatment of bile leakage for its advantages in higher cure rate, convenience and safety in practice. It is important to choose the specific non-surgical method according to the volume, site of bile leakage and patient's condition.