Discussion on the Treatment of Malignant Tumors by the Method of Counteracting Toxin with Toxin / 中医杂志

Cancer toxin is the key pathogenesis of malignant tumors. The basic principle of cancer treatment is “dispelling pathogen and resolving toxins， reinforcing healthy qi and reinforcing the foundation”. As one of the “eight methods of anticancer and detoxification”， the counteracting toxin with toxin therapy is a commonly used clinical treatment of malignant tumors. This paper discussed the method of counteracting toxin with toxin and its application in the prevention and treatment of malignant tumors from the aspects of history tracing， academic connotation， application principles and clinical application. Toxic Chinese medicinals with anticancer function are required to eliminate cancer toxins based on the principles of excessive cancer toxicity and plentiful healthy qi， as well as in accordance with the various stages and classifications of tumors， thereby improving the theoretical connotation of the method of counteracting toxin with toxin， and promoting the popularization and application of the pathogenesis theory of cancer toxin in the prevention and treatment of malignant tumors.

Shenbai Jiedu Prescription Inhibits Proliferation of Colorectal Cancer Cells by Regulating PTEN/PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D1. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D1， β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD1 were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD1 were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.

Xiaoai Jiedu Prescription-containing Serum Enhances Lethal Effect of NK Cells on Colon Cancer Cells / 中国实验方剂学杂志

ObjectiveTo explore the influence of Xiaoai Jiedu prescription （XJP）-containing serum on natural killer （NK） cells′ lethal effect on colon cancer cells and the molecular mechanism. MethodXJP-containing serum （0.1%， 0.5%， 1%， 5%， 10%） was used to treat HCT-116 cells and NK-92MI cells respectively for 24 h， and methyl thiazolyl tetrazolium （MTT） assay was employed to detect cell proliferation. Then， low-concentration （0.1%， 0.5%， 1%） XJP-containing serum was selected to treat co-cultured HCT-116 cells and NK-92MI cells for 24 h and calcein acetoxymethyl ester/propidium iodide （Calcein-AM/PI） was applied to detect the killing effect of NK cells on colon cancer cells. Flow cytometry was used to detect apoptosis of colon cancer cells， Western blot the expression of apoptosis-related proteins and signal transducer and activator of transcription 4 （STAT4） pathway-related proteins， and enzyme-linked immunosorbent assay （ELISA） the secretion of interferon （IFN）-γ. ResultHigh-concentration （5%， 10%） XJP-containing serum inhibited the proliferation of HCT-116 and NK-92MI cells （P<0.01）， while low-concentration （0.1%， 0.5%， 1%） XJP-containing serum had no obvious influence on cell proliferation compared with the blank group. As compared with the blank group， low-concentration XJP-containing serum enhanced the killing activity of NK cells against colon cancer cells in a concentration-dependent manner （P<0.01）， and induced apoptosis of colon cancer cells （P<0.01）. Moreover， XJP-containing serum （0.1%， 0.5%， 1%） down-regulated the expression of B-cell lymphoma 2 （Bcl-2） and B-cell lymphoma-extra large （Bcl-xl）， and up-regulated the expression of Bcl-2-associated X （Bax） compared with the blank group （P<0.05， P<0.01）. Compared with the co-culture group， XJP-containing serum （0.1%， 0.5%， 1%） increased the expression of p-STAT4 and IFN-γ （P<0.05）. ELISA result showed that XJP-containing serum （0.1%， 0.5%， 1%） raised IFN-γ secretion （P<0.01）. ConclusionXJP-containing serum can enhance the activity of NK cells to kill colon cancer cells. The mechanism is the likelihood that it activates STAT4 pathway， increases IFN-γ secretion by NK cells， down-regulates the expression of Bcl-xl and Bcl-2， and up-regulates the expression of Bax， thereby promoting the apoptosis of colon cancer cells.

Efficacy and Mechanism of Shenbai Jiedu Prescription Against Proliferation of HCT116 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism by which Shenbai Jiedu prescription （SBJDF） inhibits the proliferation of colorectal cancer （CRC） HCT116 cells. MethodAfter 48 h treatment of HCT116 cells with SBJDF （0， 0.25， 0.5， 1， 2， 4 g·L-1）， the viability of HCT116 cells were determined by methyl thiazolyl tetrazolium （MTT） colorimetry. Following the classification of cells into blank control group and SBJDF （1， 2， 4 g·L-1） groups， the effect of SBJDF on HCT116 cell morphology was observed under an inverted microscope. The effects of SBJDF on the proliferation of HCT116 cells and mitochondrial membrane potential （Δψm） were detected by colony formation assay and JC-1 probe， respectively. The flow cytometry was then performed for determining cell cycle distribution and apoptosis. The effects of SBJDF on cell cycle-， apoptosis-， and nuclear factor kappa-B （NF-κB） signaling pathway-related proteins were determined by Western blot. ResultSBJDF effectively inhibited the vitality of HCT116 cells and changed their morphology in a concentration-dependent manner. Compared with the blank control group， SBJDF at 1， 2， 4 g·L-1 significantly reduced cell colony formation （P<0.05， P<0.01），and SBJDF at 2 and 4 g·L-1 arrested the HCT116 cell cycle at G0/G1 phase （P<0.05， P<0.01）. Compared with the blank control group， SBJDF at 1， 2， 4 g·L-1 remarkably down-regulated the protein expression of CyclinD1 （P<0.05， P<0.01）. SBJDF at 2 and 4 g·L-1 lowered the CyclinA2 and cyclin-dependent kinase 4 （CDK4） （P<0.05， P<0.01）. SBJDF at 4 g·L-1 reduced the cyclin-dependent kinase 1 （CDK1） （P<0.01）. Compared with the blank control group， SBJDF at 2 and 4 g·L-1 induced HCT116 cell apoptosis， down-regulated the protein expression of anti-apoptosis-related proteins Bcl-2 and Bcl-xl as well as the NF-κB signaling pathway-related proteins IκB kinase α （IKKα），inhibitor α of NF-κB （IκBα），and phospho-NF-κB p65 （p-p65） （P<0.05， P<0.01）， and diminished the mitochondrial membrane potential of HCT116 cells. ConclusionSBJDF inhibits the proliferation of HCT116 cells， which may be related to its inhibition of the activation of NF-κB signaling pathway and the induction of cell cycle arrest and apoptosis.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Advances in application of growth factors in stem cell cartilage tissue engineering / 中华骨科杂志

Natural degeneration or trauma of articular cartilage all can lead to its structural and functional damage.Without blood supply and nerve innervation,chondrocytes in the matrix lacunae obtain essential nutrients and excrete metabolites mainly through osmosis,finally leads to its low metabolic activity and difficulty in self-repair after injury.At present,drug conservative treatment and surgical operation are the main clinical treatment,but both of them can't meet the clinical needs well.The development of cartilage tissue engineering provides a new direction for the repair of articular cartilage injury,in which growth factors plays a very important role.Growth factors,together with seed cells and cell scaffolds,constitute the three elements for the construction of tissue-engineered cartilage.Among them,Growth factors can significantly promote cell proliferation and differentiation and induce their functions.Various growth factors synergistically mediate the differentiation of seed cells into chondrocytes.In recent years,stem cell cartilage tissue engineering developed rapidly,which has opened a new way for repair of articular cartilage damage due to its abundant cell resources,small damage to body itself,strong ability of proliferation and directional differentiation,biological repair and other prominent advantages.Different types of hydrogels and stem cells show different abilities to support chondrogenesis and require different growth factors to induce chondrocyte differentiation.Traditional growth factors for tissue engineering include transcription growth factor β,insulin-like growth factors,bone morphogenetic proteins,fibroblast growth factors and cartilage derived morphogenetic protein.Recently,some scholars found that platelet-rich plasma,platelet-rich fibrin,Kartogenin and Mechano-growth factor can also effectively induce chondrogenic differentiation of stem cells and maintain chondrocyte phenotype.In addition,some synthetic compounds such as dexamethasone and inorganic particles can also promote the differentiation of stem cells into cartilage.This article systematically summarized the new progress of the traditional growth factors,emphatically introduced the new discovered growth factors and some synthetic compounds and inorganic particles,which can induce stem cells into cartilage.Finally classified the different sources of stem cells and its suitable growth factors,and gave an outlook of the next research direction of growth factors.

Advances in application of growth factors in stem cell cartilage tissue engineering / 中华骨科杂志

Natural degeneration or trauma of articular cartilage all can lead to its structural and functional damage. Without blood supply and nerve innervation, chondrocytes in the matrix lacunae obtain essential nutrients and excrete metabolites mainly through osmosis, finally leads to its low metabolic activity and difficulty in self-repair after injury. At present, drug conservative treatment and surgical operation are the main clinical treatment, but both of them can't meet the clinical needs well. The development of cartilage tissue engineering provides a new direction for the repair of articular cartilage injury, in which growth factors plays a very important role. Growth factors, together with seed cells and cell scaffolds, constitute the three elements for the construction of tissue-engineered cartilage. Among them, Growth factors can significantly promote cell proliferation and differentiation and induce their functions. Various growth factors synergistically mediate the differentiation of seed cells into chondrocytes. In recent years, stem cell cartilage tissue engineering developed rapidly, which has opened a new way for repair of articular cartilage damage due to its abundant cell resources, small damage to body itself, strong ability of proliferation and directional differentiation, biological repair and other prominent advantages. Different types of hydrogels and stem cells show different abilities to support chondrogenesis and require different growth factors to induce chondrocyte differentiation. Traditional growth factors for tissue engineering include transcription growth factor β, insulin-like growth factors, bone morphogenetic proteins, fibroblast growth factors and cartilage derived morphogenetic protein. Recently, some scholars found that platelet-rich plasma, platelet-rich fibrin, Kartogenin and Mechano-growth factor can also effectively induce chondrogenic differentiation of stem cells and maintain chondrocyte phenotype. In addition, some synthetic compounds such as dexamethasone and inorganic particles can also promote the differentiation of stem cells into cartilage. This article systematically summarized the new progress of the traditional growth factors, emphatically introduced the new discovered growth factors and some synthetic compounds and inorganic particles, which can induce stem cells into cartilage. Finally classified the different sources of stem cells and its suitable growth factors, and gave an outlook of the next research direction of growth factors.

Kirschner wire combined with external fixator for open comminuted distal tibiofibular fractures according to the concept of damage control orthopaedics / 中华创伤骨科杂志

Objective To report the clinical efficacy of Kirschner wire combined with external fixator in the treatment of open comminuted distal tibiofibular fractures according to the concept of damage control orthopaedics.Methods A case series study was done on the clinical data of 15 open comminuted distal tibiofibular fractures which had been treated with kirschner wire combined with external fixation from January 2015 to August 2018 at Department of Orthopedics,Affiliated Hospital to Logistics College of Chinese People's Armed Police.They were 12 men and 3 women,aged from 27 to 62 years (mean,46.5 years).By the Gustilo classification,there were one case of type Ⅰ,4 cases of type Ⅱ,7 cases of type Ⅲ A,2 cases of type ⅢB and one case of type ⅢC.All the patients were treated with emergency debridement,tibial fixation using external fixator and fibular fixation using kirschner wire,followed by vacuum sealing drainage(VSD).Effective anti-inflammatory and other comprehensive treatments were given postoperatively.Regular follow-up was conducted to observe fracture healing and complications like osteomyelitis and bone disconnection.At the final follow-up,the American Orthopaedic Foot Ankle Society (AOFAS) ankle-hindfoot scale was used to evaluate the ankle function.Results All the patients were followed up for 12 to 18 months (mean,12.8 months).Primary bone union was achieved in 13 cases (86.7％),delayed healing observed in one case (6.7％) and bone nonunion in one case (6.7％).No osteomyelitis occurred.By the AOFAS ankle-hindfoot scale,the ankle function was rated as excellent in 9 cases,as good in 4,as fair in one and as poor in one.Conclusions For patients with open comminuted distal tibiofibular fracture,treatment should be conducted according to the concept of damage control orthopaedics.After early thorough debridement,the tibia should be fixated using external fixator and the fibula using kirschner wire,followed by VSD,leading to economical cost and satisfactory clinical efficacy.

Effects of atorvastatin on the microglia activation after traumatic brain injury / 天津医药

Objective To observe the effects of atorvastatin on the microglia activation after traumatic brain injury (TBI). Methods Sixty adult male C57/BL6 mice were randomly divided into sham group, atorvastatin group and saline group, 20 mice for each group. The atorvastatin group and saline group were given hydraulic combat to establish TBI mouse model. The shame group underwent the same surgical procedure without being exposed to percussion injury. The atorvastatin group was treated with atorvastatin (orally, 1 mg/kg)1 h after TBI and for 7 consecutive days. The saline group was given sa?line orally. The expression of microglia (Iba-1+) at the 1st, 3rd, and 7th day after TBI and matrix metalloproteinase-9 (MMP-9) around the lesion at the 3rd day after TBI were detected by immunohistochemical staining. Tumor necrosis factor (TNF)-αwas detected by Western blot assay at the 3rd day after TBI. Results The positive expression of Iba-1+microglia was signifi?cantly decreased in atorvastatin group than that of saline group at the 1st, 3rd, and 7th day after TBI (80.00±7.44 vs. 118.40± 6.65,85.60±10.87 vs. 189.00±7.51,69.40±5.54 vs. 102.40±10.89, P<0.05). The positive expression of MMP-9 was signifi?cantly decreased in atorvastatin group compared with that of saline group at the 3rd day after TBI (86.80 ± 8.40 vs. 133.80 ± 8.46, P<0.05). Results of Western blot assay showed that the positive expression of TNF-αwas significantly decreased in astorvastatin group than that of saline group at the 3rd day after TBI (0.64±0.01 vs. 0.97±0.02,P<0.05). Conclusion Ator?vastatin can reduce inflammation factor by influencing the microglia activation after TBI in mice.

Clinical significance of endothelin-1 and transforming growth factor-β in the newborns with respiratory distress / 中国综合临床

Objective To measure the serum levels of endothelin-1 (ET-1) and transforming growth factor-β(TGF-β) in the newborns with respiratory distress and investigate its clinical significance. Methods Newborns with respiratory distress hospitalized into the Newborn Intensive Care Unit were included. The serum levels of ET-1 and TGF-β were all detected with ELISA in the first six hours,3,7,14 and 28 days after birth. Results The highest levels of ln ( 1 + ET-1 ) and ln ( 1 + TGF-β) were obtained from newborns with diagnosis as meconium aspiration syndrome ( 1.95 ± 1.02) ng/L and ( 1.51 ±0.99) ng/L,respectively) in the samples obtained in the first six hours after birth, and these were statistically different from those of the control group ( P ＜ 0. 05 ). Following were obtained for newborns with respiratory distress syndrome ( ( 1.52 ± 0.74 ) ng/L and ( 1.13 ± 0. 48 ) ng/L, t = 2.28,2. 13,respectively). After oxygen treatment, ET-1 levels obtained in the first six hours of life decreased gradually in the following days (P ＜0.05 ). Conclusions The measurements of ET-1 and TGF-β levels will help in differentiating diagnosis of the respiratory distress of newborns. The ET-1 levels will help to assess the therapy effectiveness and prognosis.

Screening of the Antiviral Active Parts from Isatis indigotica / 中国药房

OBJECTIVE:To study the activity of 10 chemical parts extracted from Isatis indigotica against herpes simplex virus(HSV)in vitro and to determine the antiviral active parts.METHODS:10 crude fractions and refined portions were extracted from Isatis indigotica using solvent isolation and absorption chromatography.Their inhibitory effects against HSV-Ⅰ and HSV-Ⅱ were determined by MTT using virus inhibition ratio and therapeutic index(TI)as appraisal targets to compare the antiviral effects among all the chemical parts.RESULTS:The parts(Ⅷ,Ⅹ)with EtOH(10% and 50% in concentration)elution via macroporous resin absorption showed the most potent activities,whose inhibitory rates against HSV-Ⅰ were 53.21% and 56.28% respectively,similar the action of its positive control acyclovir(62.55%),and their TI were 4.61 and 18.62 respectively.CONCLUSION:There were significant differences in the antiviral activity among all the chemical parts extracted from Isatis indigotica,

Study on Chemical Constituents Extracted with Ethanol from Radix Isatidis / 中国药房

OBJECTIVE:To isolate the chemical constituents from Radix isatidis.METHODS:The 95% ethanol extract of Radix Isatidis underwent adsorption by silica gel,and the portion eluted by different solvents was isolated and purified on silica gel column repeatedly.The physico-chemical constants and spectral data of the obtained compounds were determined and their chemical structure was identified.RESULTS:6 compounds were separated from chloroform and n-Butanol parts of Radix Isatidis and identified as:cholesterol(Ⅰ),indigotin(Ⅱ),indirubin(Ⅲ),p-Hydroxybenzaldehyde(Ⅳ),salicylic acid(Ⅴ),lariciresinol-4,4'-2-O-?-D-glucopyranoside(Ⅵ),respectively.CONCLUSION:For the first time,compound(Ⅰ)and compound(Ⅳ)were isolated from Radix Isatidis,this finding serves as reference.

Studies on Water-soluble Chemical Constitutions in Radix Isatidis / 中国药房

OBJECTIVE:To extract and separate the water-soluble chemical constitutions from Radix Isatidis.METH ODS:The Radix Isatidis water extract underwent adsorption by D 101 macroporous resin,the portion eluted by ethanol of different concentrations was isolated and purified on silica gel column repeatedly,the physicochemical constants and the spectra data of the compound obtained were determined and its chemical constitutions were identified.RESULTS:3compounds temporarily separated from Radix Isatidis water extract,were identified as:syringin(Ⅰ),indole—3—acetonitrile—6—O—?—D—glucopyranoside(Ⅱ)and(+)—isolariciresinol(Ⅲ),respectively.CONCLUSION:For the first time,compound(Ⅰ)and compound(Ⅱ)were isolated from Radix Isatidis.