The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Background/Aims: This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniforms were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B.vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Although immune checkpoint inhibitors (ICIs) have great breakthrough in cancer treatment in recent years, most patients have not benefited from it on account of immune microenvironment. Studies have shown that tryptophan metabolism is not only involved in the formation of tumor immunosuppressive microenvironment but also plays an important role in the therapeutic application of ICIs. At present, inhibiting the kynurenine pathway of tryptophan metabolism is now in various stages of clinical trials, while the other two metabolic pathways, 5-HT and the indole pathway, also have aroused wide concern. This article reviews the latest developments in this field.

The role of 5-hydroxytryptamine (5-HT) has attracted more and more attention in the development of tumor. In addition to the synthesis of 5-HT by enterochromaffin cells, some tumor cells and immune cells can also secrete 5-HT, and there are different 5-HT receptors on the surface of these cells. 5-HT plays multiple biological effects through activating different receptors. 5-HT promotes the proliferation and invasion of tumor and induces the angiogenesis of tumor tissues through activating its corresponding receptors, such as 5-HT1D, and so on. Furthermore, various 5-HT receptors are expressed on the surface of immune cells. On the one hand, physiological doses of 5-HT promote the proliferation and secretion of immune cells. On the other hand, pathologic 5-HT has an effect on inducing the differentiation of immune cells in the direction of immunosuppression, thus participating in the occurrence and development of tumor.

Objective: To access the influence of voice disorders on children′s voice-related quality of life through the parental version of pediatric voice handicap index (pVHI). Methods: From April 2017 to March 2018, a total of 192 children with voice disorders (dysphonic group) and 111 children without voice disorders (control group) were enrolled in this work. Parents of children in both groups were asked for fill out the questionnaire containing the parental version of pVHI and the data of non-normal distribution were analyzed by Mann-Whitney U test. Spearman test was used for correlation analysis. Results: (1)Vocal cord nodule was the most common voice disorder in children, and boys were more susceptible to voice disorder than girls in this study (70.3%(135/192) vs 29.7%(57/192)). (2)The most common voice abuse or misuse habit was "Shouting loudly". (3)In dysphonic group, the scores of function, physiology, emotion and total were higher than those in control group (all P<0.05). (4)In dysphonic group, there was a weak correlation between the parents′ overall evaluation of the children′s voice status and the three dimensions of the parental version of pVHI (function: r=0.339, physiology: r=0.334, emotion: r=0.208, all P<0.001). Conclusions Voice disorders can cause a negative impact on children′s quality of life. Parental version of pVHI can be used to assess the voice-related quality of life in children with voice disorders.

Vocal cord leukoplakia is a clinical diagnosis defined as a whitish patch or a plaque on a mucosal surface. Because of the diversity of histopathological types, the complexity and unpredictability risks for malignant transformation, there are still many controversies about its histopathological classification, diagnosis and treatment. The aim of this article is to review the epidemiology, etiology, pathological classification, diagnosis, treatment and prognosis of vocal cord leukoplakia.

Objective: To investigate the clinical and pathological features and prognosis of white lesion of vocal cord. Methods: One hundred and fifty-four cases of white lesion of vocal cord from January 2009 to February 2016 were retrospectively analysed. All the patients had undergone the resection of white lesion of vocal cord resection through retaining laryngoscope under general anesthesia with the specimens pathologically examined. Results: There were 148 males and 6 females in this study. The ages ranged from 36 to 83 years, and the median age was 54.5.There were 103(66.88%) long-term smokers, and 64(41.56%) long-term drinkers. Postoperative pathology showed that chronic mucosal inflammation in 19 cases (12.34%), squamous epithelial hyperplasia in 56 cases(36.36%), mild dysplasia in 25 cases(16.23%), moderate dysplasia in 34 cases(22.08%), severe dysplasia in 12 cases(7.79%), carcinoma in situ in 6 cases(3.90%), and invasive carcinoma in 2 cases(1.30%). The recurrence rate and canceration rate of chronic mucosal inflammation were 0. The recurrence rate of squamous epithelial hyperplasia was 10.71%, the canceration rate was 0.The recurrence rate of mild dysplasia was 8.00%, the canceration rate was 0. The recurrence rate of moderate dysplasia was 20.59%, the canceration rate was 8.82%. The recurrence rate of severe dysplasia was 25.00%, the canceration rate was 16.67%. Conclusions White lesion of vocal cord is a predominantly male disease. Long-term smokering and drinking are one of common causes. The final diagnosis of white lesion of vocal cord relies on the pathology. Closed observation is necessary for theses dysplasia cases. The majority of which are benign, the operation effect is good.

ObjectiveTo explore the value of immuomagnetic beads(IMB) technique for detection of intraperitoneal free cancer cells from colorectal cancer.MethodsPeritoneal lavage fluid was obtained from 80 patients with colorectal cancer during laparotomy.Peritoneal lavage cytology (PLC) and IMB were used to detect free cancer cells in peritoneal lavage fluid.10 patients with hysteromyoma during laparotomy were enrolled into the control group.ResultsThe positive rate of PLC was 8.8％ (7/80),the positive rate of IMB was 28.8％ (23/80).The positive case after useing PLC detect,IMB detect also was positive.The detected samples of control group were negative by these two methods.IMB was superior to PLC ( x2 =10.503,P =0.001 ).ConclusionIMB was more sensitive and specific than PLC,which could provide a effective method for finding intraperitoneal free cancer cells.

Objective To investigate the effect of small interfering RNA (siRNA) suppressing discoidin domain receptor 1 (DDR1) gene on biological behaviour of Kupffer cells (KC) in acute hepatic injury. Methods Male BALB/c mice were randomly divided into control, hepatic injury model, non-silencing siRNA and DDRlsiRNA groups. Hepatic injury model induced by intravenous injection of Con-canavalinA (ConA) 15 mg/kg, with or without hydrodynamic tail intravenous injection of naked siRNA (50 μg,2.0-2.5 mg/kg)/mouse or 1.5 ml normal saline. The expression of DDRI was assayed by West-ern blot and pro-inflammatory cytokine expression analyzed by ELISA. In the meantime, alanine amin-otransferase (ALT) and Kupffer cells'clearance to carbon granules was detected. Results The expres-sion of DDR1 obviously increasod at 6 h after hepatic injury, roached peak at 24 h and began to decrease at 48 h. Pretreatment with DDRisiRNA could obviously inhibit the expression of DDR1 and abrogate the high levels of ALT, expressions of TNF-α and IL-1β as well as phagocytosis of Kupffer cells. Conclu-sions Inhibition of discoidin domain receptor 1 by in vivo delivery of siRNA attenuates ConA-induced hepatic injury. Possible mechanism is that the inhibition of activity of KC inhibits the expression of pro-in-flammatory cytokines and thus alleviates hepatic injury.

OBJECTIVETo investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism.

METHODSBy establishing D-galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology.

RESULTSThere was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved.

CONCLUSIONSOxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.

Alkaloids ; therapeutic use ; Animals ; Anti-Arrhythmia Agents ; therapeutic use ; Calcium Hydroxide ; metabolism ; Chemoprevention ; Disease Models, Animal ; Galactosamine ; Liver Cirrhosis ; chemically induced ; drug therapy ; metabolism ; pathology ; prevention & control ; Liver Function Tests ; Male ; Quinolizines ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta ; genetics ; metabolism