中医药防治胃癌研究进展

胃癌(gastric cancer, GC)是我国常见的上消化道恶性肿瘤之一,其早期缺乏特异性的症状和体征,发现时往往处于疾病终末期,严重威胁我国人民的生命健康.中医药(traditional chinese medicine, TCM)对GC的防治具有良好疗效,本文主要从GC的病因病机,辨证分型和TCM在GC癌前病变、术前新辅助化疗、术后化疗、延长患者生存期等方面的应用做一综述.

Present and future of hydrology

The complexities of hydrological phenomena, the causes that lead to these complexities, and the essences and defects of reductionism are analyzed. The driving forces for the development of hydrology and the formation of branch subjects of hydrology are discussed. The theoretical basis and limitations of existing hydrology are summarized. Existing misunderstandings in the development of the watershed hydrological model are put forward. Finally, the necessity of the expansion of hydrology from linear to nonlinear is discussed.

PI3K/AKT/mTOR signaling pathway inhibitors in proliferation of retinal pigment epithelial cells

AIM: To determine whether the PI3K/AKT/mTOR pathway is activated in proliferative vitreoretinopathy (PVR) in homo-sapiens. METHODS: The retina of controls and patients with PVR were collected and their levels of PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6k and phospho-4EBP-1 were determined by Western blot. The cultured human retinal pigment epithelial cell line D407 was treated with a specific mTOR inhibitor, rapamycin (RAPA) or a PI3K inhibitor, LY294002, of various concentrations and durations. Cell morphology was observed by phase contrast microscopy and the proliferation and apoptosis of treated cells were determined by MTT assay and flow cytometry. RESULTS: Levels of PI3K, phospho-AKT, phospho-mTOR, phospho-P70S6K and phospho-4EBP1 was increased in the retina in PVR (P <0.05). In D407 cells, both RAPA and LY294002 significantly inhibited cell proliferation and cell cycle progression, and promoted apoptosis (P <0.05); morphologically, the cells became smaller. Both RAPA and LY294002 reduced levels of phospho-AKT, phospho-mTOR, phospho-p70S6k and phospho-4EBP1 expression (P <0.05). RAPA, but not LY294002, had no significant effect on PI3K expression. CONCLUSION: PI3K/AKT/mTOR signaling pathway is highly activated in the retinal pigment epithelial cells of PVR. The inhibitors of PI3K/AKT/mTOR signaling pathway, RAPA and LY294002, could inhibited the PI3K/AKT/mTOR signaling pathway by reducing the levels of phosphorylation of mTOR pathway components.

Effect of Jianpi Jiedu Recipe on angiogenesis and the PTEN/PI3K/AKT signaling pathway in the course of Helicobacter pylori-induced gastric cancer in C57BL/6 mice

目的：观察健脾解毒方对幽门螺杆菌（H.pylori）感染C57BL/6小鼠诱发胃癌过程中的胃粘膜血管新生和PTEN（Phosphatase and tensin homolog deleted on chromosometen）/PI3K/AKT信号通路的影响.方法：建立H.pylori标准株NCTC11637感染C57BL/6小鼠诱发胃癌的动物模型,将200只C57BL/6小鼠随机分成5组,即对照组、模型组、健脾解毒方低中高剂量组,每组40只.健脾解毒方低、中、高剂量每只小鼠分别灌服健脾解毒方250、500、1000mg·kg-1·d-1.72周后,尿素酶实验检测小鼠胃粘膜H.pylori感染情况,组织病理学检查小鼠胃粘膜癌变率,免疫组化法检测H.pylori感染对小鼠胃粘膜微血管密度（Microvessel density,MVD）、血管内皮生长因子（vascular endothelial growth factor,VEGF）和PTEN/PI3K/AKT信号通路的影响.结果：72周后,对照组、模型组、健脾解毒方低中高剂量组H.pylori感染率分别为0%,100%,3%,0%,0%,中药组感染率明显下降;各组小鼠胃癌发生率分别为为0%、26.3%、13.2%、10%、7.5%,中药组较模型组发生率明显减低（P=0.020,P=0.023,P=0.007）.模型组MVD和VEGF表达量较对照组明显升高（P=0.002,P〈0.001）,中药组可降低MVD和VEGF表达.模型组p-PTEN和p-AKT的表达较对照组明显升高（均P〈0.001）,中药组可不同程度的降低p-PTEN和p-AKT的表达.结论：H.pylori长期感染C57BL/6小鼠可诱发胃粘膜癌变,增加胃粘膜MVD,促进VEGF表达,抑制PTEN活性,从而激活PI3K/AKT信号通路.健脾解毒方可降低小鼠胃粘膜H.pylori感染率,降低癌变率,抑制MVD和VEGF表达,减少PTEN失活,从而阻断PI3K/AKT信号通路可能是其预防胃癌的重要靶点.

Efficacy of intravitreal conbercept combined with panretinal photocoagulation for severe nonproliferative diabetic retinopathy without macular edema

AIM: To assess efficacy of intravitreal conbercept(IVC) injection in combination with panretinal photocoagulation(PRP) vs PRP alone in patients with severe nonproliferative diabetic retinopathy(SNPDR) without macular edema(ME).METHODS: Forty-eight patients with SNPDR without ME(56 eyes) were divided into the PRP group and IVC+PRP group(the pulse group) in this retrospective clinical study. Conbercept was intravitreally administered to patients in the pulse group 1 wk before treatment with PRP and followed up for 1, 3, and 6 mo. The best-corrected visual acuity(BCVA, log MAR), center foveal thickness(CFT), visual acuity(VA) improvement, and adverse reactions were compared between groups.RESULTS: In the PRP group, the BCVA reduced at 1 and 3 mo before improving at 6 mo. In the pulse group, baseline BCVA decreased continuously at 1 mo, increased at 3 and 6 mo. BCVA in the pulse group was better than that in the PRP group at 1, 3, and 6 mo. There was an increase in CFT in the PRP group during follow-up compared with baseline. In the pulse group, CFT was increased at 1 mo relative to baseline, steadily decreased to the baseline level at 3 and 6 mo. There was a more significant reduction in CFT in the pulse group during follow-up compared with the PRP group. The effective rates of VA in the PRP and the pulse groups were 81.48% and 100%, respectively. CONCLUSION: As PRP pretreatment, a single dose of IVC administration has beneficial effects for preventing PRPinduced foveal thickening and increasing VA in patients with SNPDR without ME.

Effect of adenovirus-mediated brain derived neurotrophic factor in early retinal neuropathy of diabetes in rats

AIMTo observe effect of adenovirus-mediated brain derived neurotrophic factor in early retinal neuropathy of diabetes in rats.

Concomitant adenosquamous carcinoma and cystadenocarcinoma of the extrahepatic bile duct: A case report

BACKGROUND Infiltrative adenosquamous carcinoma(ASC) of the extrahepatic bile duct is reported infrequently, which is an unusual variant of the ordinary adenocarcinoma. The simultaneous development of ASC and cystadenocarcinoma in the extrahepatic biliary tree is rare. In addition, the accurate preoperative diagnosis of concomitant carcinoma in the multiple biliary trees at an early stage is often difficult. Thus, awareness of the risk of the multiplicity of biliary tumors is perhaps the most important factor in identifying these cases.CASE SUMMARY Here, we report a case of a 63-year-old female with jaundice, who was referred to Shuguang Hospital because of abdominal pain for 1 mo. An abdominal contrastenhanced computed tomography revealed a type I choledochal cyst and intraluminal masses suggestive of adenoma of the common bile duct. In addition,a preoperative diagnosis of a concomitant Klatskin tumor and type I choledochal cyst was made. The patient underwent anti-inflammatory therapy, followed by radical surgery due to hilar cholangiocarcinoma and resection of the choledochal cyst. Examination of the surgical specimen revealed a papillary tumor of the common bile duct, which arose from the malignant transformation of a preexisting cystadenoma. Histologic examination confirmed a special type of cholangiocarcinoma; the tumor in the hilar bile duct was an ASC, whereas the tumor in the common bile duct was a moderately differentiated cystadenocarcinoma. The patient showed rapid deterioration 8 mo after surgery.CONCLUSION Although concomitant ASC and cystadenocarcinoma of the extrahepatic bile duct is difficult to diagnose before surgery, and the prognosis is poor after surgery,surgical resection is still the preferred treatment.

What are the challenges facing cancer therapy base on the dissipative structure theory

Cancer therapy is facing challenges.Since current theory could not have a breakthrough,we ought to find a new way to conquer cancer by exploring the emerging theory in cancer therapy.The complexity science,emerging in the 1980s,is the new stage of the system science development.It raises a series of transformation from humanities to natural science.Dissipative structure theory as a major science of complexity science,when applied to medical field,probable provide opportunity and inspiration referring to treatment.Dissipative structure theory,in brief,claims that a dissipative structure transform chaos to relatively stable non-equilibrium state through non-equilibrium phase transition.From the microscopic order,cancer composed by tumor cells is a dissipative structure,whose external environment is the human body.From the macroscopic order,the human body is a dissipative structure,whose external environment is the natural and social environment.The reason for tumor occurrence and progression is relatively non-equilibrium disrupted and negative entropy is not enough to correct high positive entropy.Survival with the tumor is to enhance negative entropy to resist highly positive entropy and then build a new relative non-equilibrium state.Innovative angle from the theory may enlighten us make the better use of dissipative structure theory in clinical cancer therapy.

Expressions of survivin and vascular endothelial growth factor in a Murine model of proliferative retinopathy

AIM: To examine the expression of survivin and vascular endothelial growth factor (VEGF) during the development of retinal neovascularization (NV) in a mouse model. METHODS: A well-characterized murine model of retinal NV was used to study the expression of survivin and VEGF. NV of the retina was induced in mice by exposure to 75% O-2 from postnatal day P7 to P12, followed by return to room air from P12 to P17. Expression of survivin and VEGF protein was analyzed by Immunohistochemistry. In addition, mouse model of proliferative retinopathy was analyzed by retinal fluorescein angiography and quantification analysis. RESULTS: The normal mice had both superfiekal and deep vascular layers that extended from the optic nerve to the periphery. In intraocular pressure (IOP) mice were characterized by represent a typical pattern of pathological retinal NV. There are less or little nuclei of new vessels vascular endothelial cell breaking through the inner retinal than in retinopathy of prematurity (ROP) mice, large clusters of blood vessels were adherent to the internal limiting membrane(ILM) (0.27 +/- 0.20 vs23.38 +/- 1.027, t=9.454, P <0.001). During the angiogenic period from P13 to P17, survivin and VEGF protein expression increased in experimental retinas compared with control samples (2.56 +/- 0.46 vs 3.34 +/- 0.40, t=17.43, P <0.01: 2.18 +/- 0.75 vs 4.34 +/- 0.25, t=19.61, P<0.01). Protein levels of VEGF and survivn has significantly positive correlation(P<0.05, r=0.411). CONCLUSION: Correlation was made at the protein levels of survivin expression compared with that of VEGF in a murine model of retinal NV, which suggests a temporal role for survivin and VEGF in new vessel formation in response to hypoxic stimulation.

Oral Microbiota:A New Insight into Cancer Progression,Diagnosis and Treatment

The polymorphic microbiome has been defined as one of the“Hallmarks of Cancer”.Extensive studies have now uncovered the role of oral microbiota in cancer development and progression.Bacteria,fungi,archaea,and viruses in the oral cavity interact dynamically with the oral microenvironment to maintain the oral micro-ecological homeostasis.This complex interaction is influenced by many factors,such as maternal transmission,personal factors and environmental factors.Dysbiosis of oral microbiota can disturbed this host-microbiota interaction,leading to systemic diseases.Numerous studies have shown the potential associations between oral microbiota and a variety of cancers.However,the underlying mechanisms and therapeutic insights are still poorly understood.In this review,we mainly focus on the following aspects:(1)the factors affect oral microbiota composition and function;(2)the interaction between microenvironment and oral microbiota;(3)the role of multi-kingdom oral microbiota in human health;(4)the potential underlying mechanisms and therapeutic benefits of oral microbiota against cancer.Finally,we aim to describe the impact of oral microbiota on cancer progression and provide novel therapeutic insights into cancer prevention and treatment by targeting oral microbiota.

Phase-and epidemic region-adjusted estimation of the number of coronavirus disease 2019 cases in China

The outbreak of the coronavirus disease 2019 in China was first reported in Wuhan in December 2019 and gradually spread to other areas in China.After implementation of prevention and control measures,the estimation of the epidemic trend is needed.A phase-and region-adjusted SEIR model was applied for modeling and predicting the number of cases in Wuhan,Hubei Province and regions outside Hubei Province in China.The estimated number of infections could reach its peak in late February 2020 in Wuhan and Hubei Province,which is 55303–84520 and 83944–129312,respectively,while the epidemic peaks in regions outside Hubei Province in China could appear on February 13,2020 with the estimated 13035–19108 cases.According to the estimation,the outbreak would abate in March and April all over China.Current estimation provided evidence for planned work resumption under stringent prevention and control in China to further support the fight against the epidemic.Nevertheless,there is still possibility of the second outbreak brought by the work resumption and population migration,especially from Hubei Province and high intensity cities outside Hubei Province.Strict prevention and control measures still need to be considered in the regions with high intensity of epidemic and densely-populated cities.