Prognostic model for identifying candidates for hepatectomy among patients with hepatocellular carcinoma and hepatic vein invasion.

BACKGROUND: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection. METHODS: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts. RESULTS: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus. CONCLUSION: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.

ANTECEDENTES: La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas. RESULTADOS: De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

Adhesion to pharyngeal epithelium and modulation of immune response: Lactobacillus salivarius AR809, a potential probiotic strain isolated from the human oral cavity.

Microbiome modulators such as probiotics are known to modulate oral diseases. Very few probiotics are commercially available for use in the oral cavity. In this context, we selected human-origin Lactobacillus salivarius AR809 as a promising oropharyngeal probiotic and characterized its functional and immunomodulatory properties. Results demonstrated that AR809 could efficiently adhere to pharyngeal epithelial FaDu cells, antagonize Staphylococcus aureus, adapt to the oral environment, and modulate host innate immunity by inducing potentially protective effects. Particularly, AR809 diminished proinflammatory activity by enhancing the production of IL10 and inhibiting the expression of tumor necrosis factor-α, IL1B, inducible nitric oxide synthase, and RELA. Finally, we observed that AR809 grew efficiently when cultured in milk, suggesting that the preparation of a fermented milk product containing AR809 could be a practical way to administer this probiotic to humans. In conclusion, AR809 has high potential to adhere to the pharyngeal mucosa and could be applied in novel milk-based probiotic fermented food products.

[Clinical study on topography-guided laser ablation combined with accelerated corneal collagen cross-linking for early keratoconus].

Objective: To study the safety and efficacy of topography-guided customized excimer laser subepithelial ablation combined with accelerated collagen cross-linking technique in treatment of early keratoconus. Methods: Ninteen patients(20 eyes) (13 males 14 eyes, and 6 females 6 eyes), aged 12 to 44 years (24.7±8.0) were diagnosed as keratoconus by three-dimensional corneal topography and tomography, clinical history and examinations, and classified as KC1~KC3. Based on the classical excimer laser subepithelial keratomileusis (LASEK) method, topography guided laser ablation was performed with an excimer laser system (WaveLight EX500). After laser ablation, the corneal stromal bed was immersed with 0.1% riboflavin for 10 minutes, and then was irradiated by ultraviolet light (Avedro KXL) at 30 mW/cm(2) for 4 minutes. All the patients were followed up for more than 12 months. The uncorrected visual acuity (UCVA), diopter, best corrected visual acuity (BSCVA), corneal topography, central corneal endothelial cell density (ECD), hexagonal cell percentage (HEX), coefficient of variation (CV) and other indicators were observed. For normal distribution variables, Dunnett-t test was used before and after operation, and Wilcoxon test was used for variables with abnormal distribution. And the complications were recorded. Results: There was no loss of BSCVA at 12 months postoperatively, 20% of the eyes had no change of BSCVA, and 15% of the eyes gained 1 line of BSCVA, 15% of the eyes gained 2 lines of BSCVA, 50% of the eyes gained 3 lines and more of BSCVA. There was no significant difference in UCVA, BSCVA, manifest refractive spherical equivalent (MRSE) and the cylinder at 3 months postoperatively (P>0.05). The BSCVA were significantly improved at 6 and 12 months postoperatively compared with those before operation (t=3.095, 3.079, <0.05). Although there was no significant difference in UCVA and MRSE, the cylinder was significantly reduced at 6 and 12 months postoperatively (t=-2.890, -2.435, P<0.05). Apex curvature (Kapex) and mean pupil power (MPP) within 4.5mm of central cornea decreased significantly (Z=-2.903, P<0.01; Z=-2.667, P<0.01). Even though the thinnest corneal thickness decreased from pre-operational (461.9±31.1) µm to post-operational (416.6±27.0) µm (Z=-3.059, P<0.01), the cornea became regular with keratometric asymmetry index of anterior corneal surface decreased (Z=-2.667, P<0.01). The corneal optical quality parameters were improved. There was no significant difference in ECD, HEX and CV at 12 months postoperatively (P>0.05). Twelve months after operation, grade 0, 0.5, 1 and 2 haze were seen on 20%, 55%, 20% and 5% corneas respectively. Conclusions: The topography guided excimer laser ablation combined with accelerated corneal collagen cross linking is safe and effective in treatment of early stage keratoconus. It can significantly improve corneal regularity while preventing keratoconus progression, so as to improve the best corrected visual acuity postoperatively. (Chin J Ophthalmol, 2019, 55: 904-910).

[Analysis on the role of Sirius combined topography and tomography system in screening for suspect keratoconus].

Objective: To evaluate the role of Sirius combined topography and tomography system in screening for suspect keratoconus among the corneal refractive surgery candidates. Methods: Retrospective case series study. Eight hundred and sixteen consecutive ametropic patients (1 632 eyes) who underwent routine examinations before corneal refractive surgery at Peking University Third Hospital from January 2016 to September 2016 were reviewed. All the cases were analyzed with Sirius combined topography and tomography system. Fifty-nine eyes of 37 patients, aged (28.9±7.4) years, classified as suspect keratoconus by the system were enrolled in the suspect group, including 25 females (40 eyes) and 12 males (19 eyes). A random eye of the first 59 patients, aged (27.1±6.4)years, whose both eyes were classified as normal by Sirius system were enrolled in the control group, including 38 females and 21 males. The corneal anterior surface, posterior surface and minimum thickness data of the suspect group were analyzed and then compared with the control group. The classified results were further verified by Pentacam system. Independent-samples t test and Mann-Whitney U test were applied to analyze the normal distribution and non-normal distribution data respectively. Results: The medians of anterior surface and posterior surface symmetry index and Baiocchi Calossi Versaci index of anterior surface and posterior surface of the suspect group were 0.84, 0.22, 0.58 and 0.51 D, and that of the control group were 0.05, 0.04, 0.09 and 0.06 D, and the differences were of statistical significance (Z=-18.764, -8.351, -12.248, -10.709, P<0.01). Mean corneal minimum thickness data of the suspect group were (504.4±30.0)µm, and that of the control group were (541.2±32.1)µm, the differences were of statistical significance (t=-6.408, P<0.01). In the suspect group, the eyes related with suspect or abnormal corneal anterior indices accounted for 47.5% (28/59), the eyes related with suspect or abnormal corneal posterior indices accounted for 55.9% (33/59), and the eyes related with suspect or abnormal corneal minimum thickness accounted for 40.7% (24/59). In the suspect group, 45 eyes (76.3%) were classified as suspect or abnormal according to the overall variance index "D" by Belin-Ambrósio Display (BAD) of the Pentacam system, and the other 14 eyes exhibited at least one abnormal index related with keratoconus. Conclusions: Sirius 3D combined topography and tomography and its integral automatic classification system is capable to screen out the suspect keratoconus simply and effectively. These indices maybe arranged in descending order in terms of the sensitivity as corneal posterior surface, followed by corneal anterior surface and then corneal thinnest point thickness. (Chin J Ophthalmol, 2018, 54: 33-38).

[Research progress of the mechanisms underlying cadmium-induced carcinogenesis].

Since cadmium is an indirect genotoxic carcinogen, epigenetic modifications could be one of the major mechanisms underlying cadmium-induced carcinogenesis. It has been proposed that epigenetic alterations might be associated with cadmium-induced carcinogenesis, such as disruptions of DNA methylation, histone modifications, and microRNA expression profile, which would result in abnormal expression of carcinogenesis-related genes and/or imbalance of signal transduction pathways. Other mechanisms of cadmium-induced carcinogenesis consist of disruption of gene regulation and signaling pathways, repression of DNA repair, suppression of apoptosis, induction of oxidative stress and autophagy. Here, we reviewed the research of both epigenetic and non-epigenetic mechanisms underlying cadmium-induced carcinogenesis.

[Relationship of blood aryl hydrocarbon receptor mRNA and cytochrome P450 1A1 mRNA expression with corrected QT interval among residents exposed to arsenic via drinking water].

OBJECTIVE: To investigate the relationship between blood aryl hydrocarbon receptor(AhR)mRNA and cytochrome P450(CYP)1A1 mRNA expression and corrected QT interval among residents exposed to arsenic via drinking water. METHODS: Arsenic exposure area in Bayannao'er city of Nei Monggol Autonomous Region was selected as the survey point, and the residents living more than 10 years in this area were investigated from December 2012 to January 2015.A total of 233 residents were divided into four groups according to drinking water arsenic concentration (ranged from 0.8 to 824.7 µg/L): control group (drinking water arsenic concentration <10.0 µg/L, n=55), low exposure group (drinking water arsenic concentration 10.0-99.9 µg/L, n=47), middle exposure group (drinking water arsenic concentration 100.0-199.9 µg/L, n=45), high exposure group (drinking water arsenic concentration ≥200.0 µg/L, n=86). Epidemiological investigation was performed.Real-time PCR technology was used to detect the expression levels of blood AhR mRNA and CYP1A1 mRNA, and the relationship between expression levels of blood AhR mRNA and CYP1A1 mRNA and corrected QT interval was analyzed. RESULTS: (1) Blood AhR mRNA and CYP1A1 mRNA expression levels were similar among control group, low exposure group and middle exposure group (all P>0.05) while blood AhR mRNA (3.18×10(-3)(2.42×10(-3), 4.45×10(-3)) vs.2.30×10(-3)(1.53×10(-3), 3.20×10(-3)), P<0.05) and CYP1A1 mRNA (1.58×10(-3)(0.80×10(-3), 2.73×10(-3))vs.1.00×10(-3)(0.59×10(-3), 2.09×10(-3)), P<0.05) expression levels were significantly higher in high dose group than in control group.(2) AhR mRNA expression level was similar between residents with longer corrected QT interval and residents with normal corrected QT interval (2.89×10(-3)(1.90×10(-3), 3.71×10(-3)) vs.2.58×10(-3)(1.85×10(-3), 3.57×10(-3)), P>0.05). CYP1A1 mRNA expression level was significantly higher in residents with longer corrected QT interval than in residents with normal corrected QT interval (1.50×10(-3)(0.78×10(-3), 2.63×10(-3)) vs.1.16×10(-3)(0.64×10(-3), 2.36×10(-3)), P<0.05). (3) AhR mRNA expression level was similar between residents with sinus tachycardia or bradycardia or normal heart rate(2.89×10(-3)(1.71×10(-3), 4.45×10(-3)) vs.2.64×10(-3)(1.86×10(-3), 3.52×10(-3)), P>0.05). CYP1A1 mRNA expression level was significantly higher in residents with sinus tachycardia or bradycardia than in residents with normal heart rate (1.47×10(-3)(0.87×10(-3), 2.77×10(-3)) vs.1.24×10(-3)(0.64×10(-3), 2.31×10(-3)), P<0.05). CONCLUSIONS: Long-term exposure to arsenic is associated with upregulated blood AhRmRNA and CYP1A1 mRNA expression.Blood CYP1A1 mRNA expression, but not AhRmRNA expression, is associated with prolonged corrected QT interval.

The (TTTA)n polymorphism in intron 4 of CYP19 and the polycystic ovary syndrome risk in a Chinese population.

Polycystic ovary syndrome (PCOS) is a heterogeneous disease with a strong genetic origin, but the specific determinants are still unknown. The aim of this study was to investigate the association between the (TTTA) n polymorphism in intron 4 of CYP19 and the PCOS risk in a Chinese population. We performed a case-control study which involved 222 PCOS patients and 281 controls. The fluorescent-labeled target DNA fragments containing the (TTTA)n short tandem repeats were obtained by PCR, thereafter genotyped via capillary electrophoresis. Representative alleles were directly sequenced to confirm their repeat numbers. Genotype analysis revealed seven different alleles including 7-3(∆)-, 7-, 8-, 10-, 11-, 12- and 13-TTTA-repeats. The most common allele in a Chinese population is (TTTA) 11 in our study (0.354 for PCOS and 0.390 for controls). PCOS patients showed a higher frequency of short alleles compared with controls (0.47 vs. 0.41, OR=1.245, 95% CI 0.97-1.60). The overall allelic distributions of this polymorphism did not show any significant differences between PCOS patients and the control group. No statistical differences were found in the clinical parameters or serum steroid hormone levels among PCOS patients with different genotypes. In conclusion, PCOS patients had a higher frequency of short alleles, albeit this might not strongly affect the risk of PCOS.

Role of monokine induced by interferon-γ in liver injury induced by hepatitis B virus in mice.

The chemokine monokine induced by interferon-γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)-κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome-containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad-HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF-κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo-jetPEI-Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF-κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3-kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.

Evaluation of the effects of right ventricular pressure load on left ventricular myocardial mechanics in patients with chronic obstructive pulmonary disease by ultrasound speckle tracking imaging.

OBJECTIVE: This paper aims to evaluate the effects of right ventricular pressure load on left ventricular myocardial mechanics in patients with chronic obstructive pulmonary disease (COPD) by ultrasound speckle tracking imaging. PATIENTS AND METHODS: 119 patients with COPD and pulmonary hypertension (PH) were selected from December 2016 to March 2018 in Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University. 42 healthy subjects were selected as control group. According to the pulmonary arterial systolic pressure (PASP), 41 patients were classified into mild group, 47 in moderate group, and 31 cases in severe group. Echocardiography and STI were used to measure the indexes. RESULTS: Compared with those in control group, EI and E/e of moderate group and severe group increased significantly (p<0.001). Compared with those in control group, parameters in moderate and severe groups significantly decreased (p<0.001), including early diastolic mitral annular velocity/late peak blood flow velocity (E/A), left ventricular end diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), PASP and left ventricular end-diastolic diameter (LVEDD), stroke volume (SV), left ventricular end-systolic diameter (LVESD), cardiac output (CO), peak rotation angle and peak time of in the basal and apical segments. Compared with those in control group, parameters in moderate group significantly decreased (p<0.001), including left ventricular strain parameters segmental systolic peak longitudinal strain (LS), circumferential strain (CS), and radial strain (RS). Compared with those in control group, parameters in mild group significantly decreased (p<0.001), including peak rotation angle of basal segment and apical segment of the left ventricle. Compared with those in moderate group, peak rotation angle and peak time of the whole basal segment and apical segment of severe group gradually decreased (p<0.001). CONCLUSIONS: Left ventricular whole peak rotation angle can be used to sensitively evaluate the change of left ventricular myocardial mechanics function in PH patients, and can reflect changes of left ventricular myocardial mechanics function in patients with COPD when mild PH occurs.

[Research progress in titanium dental implant biological modification].

During the past three decades, the technology of implant surface modification has already formed well-developed methods including physical and chemical means. However, titanium is a kind of bioinert material, which will directly result in slowly bone-bond with bone tissue after implantation and ultimately reduce the success rate of dental implant surgery. Therefore, the introduction of bioactive substances which can effectively regulate and promote the proliferation of bone cells to modify the titanium implant surface has received tremendous attention in the research of oral implant field. The research of biological modification starts relatively late and it has not formed well-established system yet. The research progress is given in this paper concerning the bioactivators and methods used in biological modification. Furthermore, the current situation as well as the recent developments involving the biological modification of dental implant are also discussed in this review.

Microlaryngoscopic surgery. An analysis of 300 cases.

Microlaryngoscopic operations were performed on 300 cases of very small lesions of the vocal cord from October 1985 to December 1987 under high frequency ventilation (HFV) and compound venous anaesthesia. 233 cases were followed up for at least 1 month after operation. Among them, 91% recovered completely or improved significantly. The indications, contraindications, anaesthesia, surgical procedures, complications, results, merits and disadvantages of the microlaryngoscopic surgery were discussed in detail.

[Risk factors and visual prognosis of 407 patients with retinal vein occlusion].

Among 407 patients (416 eyes) with retinal vein occlusion (RVO), 196 eyes had branch RVO, 185 eyes central RVO, and 26 eyes hemi-central RVO. The ischemic type accounted for 39.7%, and the non-ischemic type 60.3%. The risk factors were vascular hypertension (59.8%), retinal arteriosclerosis (58.0%), increased blood beta-lipoprotein (49.0%) and fibrinogen (21.7%), and high blood viscosity. The mean levels of whole blood and plasma viscosity were significantly higher in the patients than in the controls. The therapeutic effective rate was 63.2% for branch RVO, 52.4% for central RVO, and 69.2% for hemicentral RVO. The resultant rate of blindness was 15.9%, and that of low vision 23.1%, due to cystoid macular edema (44.4%) and vitreous hemorrhage (15.4%). The incidence of neovascular glaucoma was 9.5% in central RVO.

AKR1B10, a good prognostic indicator in gastric cancer.

BACKGROUND AND OBJECTIVES: The aim of the study was to investigate the correlation between AKR1B10 expression and clinicopathological features of gastric cancer (GC). METHODS: Real-time polymerase chain reaction (RT-PCR) was performed to determine AKR1B10 mRNA expression. AKR1B10 protein levels were measured by immunohistochemistry. RESULTS: RT-PCR analysis confirmed that AKR1B10 was significantly down-regulated in gastric cancer compared with paired, normal mucosa. Immunohistochemistry revealed that the percentage of AKR1B10-positive specimens was lower in gastric carcinoma compared with normal specimens. The frequency of AKR1B10-positive GC specimens was higher in patients with tumor size <5 cm, no lymph node metastasis, no distant metastasis and lower tumor stages The mean survival time for patients in the AKR1B10-positive group was significantly higher compared with the AKR1B1-negative group. The 5-year survival rate for the AKR1B10-positive group was also significantly higher than for the AKR1B1-negative group. Cox regression analysis revealed that AKR1B10 expression is an independent prognostic factor of GC. CONCLUSIONS: Expression of AKR1B10 in gastric cancer was significantly associated with tumor size, lymph node metastasis, distance metastasis and TNM stage, and AKR1B10 may be a good prognostic indicator in gastric cancer.

Study on the effect of different oxygen therapies on rats with acute carbon dioxide poisoning.

OBJECTIVE: To study the effect of different oxygen therapies on the rats with carbon dioxide poisoning for screening out the best on-the-spot oxygen-therapy technology for treating acute carbon dioxide poisoning. METHODS: The 60 healthy male Sprague Dawley rats were randomly divided into normal control group (A group), carbon dioxide poisoning group (B group), low-concentration oxygen inhalation treatment group (C group), high-concentration oxygen inhalation treatment group (D group) and hyperbaric oxygen-therapy group (E group). Various kinds of oxygen therapies were given after the contamination. The pH, partial pressure of oxygen (PO(2)) and partial pressure of carbon dioxide (PCO(2)) of arterial blood, serum troponin I (CTNI), creatine kinase (CK), glutamic-oxaloacetic transaminase (AST), γ-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), potassium (K), sodium (Na) and chlorine (Cl) for the rats of each group were inspected. The lung and the brain tissues were taken for observing the pathological changes. RESULTS: There is no significant difference in pH, PO(2) and PCO(2) among all oxygen-therapy groups (p > 0.05). The levels of CTNI, CK and AST in E group are obviously lower than that in B, C and D groups (p < 0.05). The level of serum K in E group is obviously lower than that in B, C and D groups (p < 0.05). The levels of serum Na and Cl in E group are obviously higher than that in B, C and D groups (p < 0.05). The pathological change of lungs in E group is significantly better than that in C and D groups. CONCLUSIONS: We recommend that the medical units with related conditions can give the hyperbaric oxygen therapy to patients as soon as possible.