Research on genetic model of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of genetic factors on the pathogenesis of keratoconus and its genetic model.METHODS: Genetic epidemiological methods were used to investigate the prevalence of keratoconus in 280 first-degree relatives of 100 patients with keratoconus who attended Henan Eye Hospital between July 2020 and April 2023. The heritability was estimated by Falconer regression method. The general genetic model was calculated using Penrose method, and the genetic model was confirmed by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory.RESULTS: The results showed that there were 16(5.714%)first-degree relatives of keratoconus probands suffering from keratoconus, and the heritability of keratoconus was(86.100±7.400)%. The S/q score calculated by the Penrose method was 35.348, which was near to 1/(q)1/2, suggesting that the genetic model of keratoconus might be polygenic inheritance. The expected prevalence in first-degree relatives of keratoconus patients by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory were 5.900%, 7.714% and 5.700%, respectively, which showed no significant differences from the actual prevalence(5.714%), suggesting that keratoconus was a polygenetic disease.CONCLUSION:Genetic factors might play an important role in the pathogenesis of keratoconus, and keratoconus is a polygenetic disease.

Progress in genetic research on keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

@#Keratoconus is a corneal disease characterized by corneal ectasia, progressive corneal thinning, conical protrusion and irregular astigmatism. Several studies have indicated that keratoconus is a complex disease with genetic heterogeneity. Genetic studies on keratoconus involving nuclear genome, mitochondrial genome and epigenetics were increasing. This article reviews the recent progress in genetic research on keratoconus.

Biomechanical properties of trabecular bones in femoral head under loads with different angles / 医用生物力学

Objective To investigate the effects from loads with different angles on morphological and biomechanical properties of trabecular bones in femoral head, so as to provide theoretical basis for studying biomechanical mechanism of necrosis and collapse of femoral head. Methods Ninety-four specimens of 12-month-old ovine trabecular bones in femoral head and forty-three specimens of human cadaver trabecular bones in femoral head were prepared. According to different angles between loading direction and principle compression direction, all the trabecular bones were divided into five groups by 10° interval (i.e. varus 10° and 0°, valgus 10°, 20° and 30°) to simulate the reduction condition under different Garden index after internal fixation of femoral neck fractures. Micro-CT scanning and calculation, compression failure test on ovine trabecular bones in femoral head and cyclic compression test on human cadaver trabecular bones in femoral head were performed to investigate morphological and mechanical indices, including BV/TV (bone volume vs. total volume), BS/BV (bone surface vs. bone volume), Tb.Th (thickness of trabecular bone), Tb.N (number of trabecular bone), Tb.Sp (trabecular separation), elastic modulus, ultimate strength, yield strength, initial secant modulus and number of cycles. Results When the angle between loading direction and principle compression direction of trabecular bones was 0°, BV/TV, Tb.Th, elastic modulus, ultimate strength, yield strength, initial secant modulus and number of cycles for trabecular bones were the maximum while BS/BV and Tb.N were the minimum, and all the formers presented decreasing tendency while BS/BV and Tb.N showed increasing tendency along with the angle increasing. ConclusionsAlong with the angle changes, the tendency of BV/TV and ultimate strength for 12-month-old ovine trabecular bones in femoral head displayed as the same as human trabecular bones in femoral head. Both the morphological and biomechanical properties of trabecular bones in femoral head will decrease when the angle between loading direction and principle compression direction of trabecular bones increases. The more the Garden index deviating from 160°, the more likely trabecular bones in femoral head to be damaged.

Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the intervention effect of thalidomide on paraquat-induced acute lung injury in mice and its mechanism.</p><p><b>METHODS</b>Male ICR mice were randomly allocated to negative control group (n = 30), thalidomide control group (n = 30), paraquat poisoning group (n = 30), 50 mg/kg thalidomide treatment group (n = 30), 100 mg/kg thalidomide treatment group (n = 30), and 150 mg/kg thalidomide treatment group (n = 30). The negative control group was intraperitoneally injected with the same volume of saline; the thalidomide control group was intraperitoneally injected with thalidomide (150 mg/kg); the paraquat poisoning group was intraperitoneally injected with diluted paraquat solution (22 mg/kg); each thalidomide treatment group was intraperitoneally injected with the same volume of paraquat solution (22 mg/kg) and was injected with thalidomide (50, 100, or 150 mg/kg) 1 h later. All mice were anesthetized and sacrificed at 1, 3, or 7 d after paraquat poisoning, and their lung tissue was collected. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in lung tissue were measured by double-antibody sandwich ELISA; the mRNA expression of nuclear factor-kappa B (NF-κB) was measured by RT-PCR; the protein expression of nuclear NF-kgr;B p65 was measured by Western blot. The pathological changes of lung tissue were observed under light microscope; the wet/dry ratio of the lung was calculated.</p><p><b>RESULTS</b>Compared with the negative control group, the paraquat poisoning group had significantly increased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratio of the lung (P < 0.05). Compared with the paraquat poisoning group, the thalidomide treatment groups had significantly decreased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratios of the lung (P < 0.05), and the 150 mg/kg thalidomide treatment group showed the most significant decrease in the levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65. The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning, and the lung tissue damage was lessened in the thalidomide treatment groups.</p><p><b>CONCLUSION</b>Thalidomide can reduce paraquat-induced acute lung injury and lung edema. The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-α, IL-1β, and IL-6.</p>

Efficacy and safety of erlotinib as monotherapy for advanced non-small cell lung cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the efficacy and safety of erlotinib monotherapy for advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Totally 50 patients with advanced NSCLC received oral erlotinib 150 mg/d treatment, and tumor specimen in 19 patients were collected for epidermal growth factor receptor (EGFR) gene mutation tests. Median survival (MS) was calculated using the Kaplan-Meier method.</p><p><b>RESULTS</b>The most common adverse events (AEs) were skin rash (96%) and diarrhea (32%). The overall survival (OS) of all patients was 21.8 months 95% confidential interval (CI): 17.1-26.4 months and the median progression-free survival (PFS) of all patients was 7.0 months (95% CI: 3.9-10.1 months). EGFR mutation analysis showed gene mutation in 8 cases and wild type in 11 cases. The objective response rate in patients with or without EGFR gene mutations were 62.5% and 9.1%, respectively (chi(2)=6.631, P=0.036). PFS in patients with or without EGFR gene mutations were 16.330 (95% CI: 2.803-29.857 months) and 5.570 months (95% CI: 2.441-8.699 months), respectively (chi(2)=8.799, P=0.003).</p><p><b>CONCLUSION</b>Erlotinib monotherapy is safe and effective for some Chinese NSCLC patients after failure of prior chemotherapy.</p>

Expression and significance of heat shock proteins in esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression and significance of HSP27, HSP60, HSP70 and HSP90 alpha in esophageal squamous cell carcinoma (ESCC) and tissues along the incision margin (TIM).</p><p><b>METHODS</b>The presence and the level of expression of HSP27, HSP60, HSP70 and HSP90 alpha were determined in 168 specimens from ESCC and 42 from tissues along TIM by EnVision immunohistochemistry and Western blotting, to compare their positive staining rates and explore the correlation between their expressions and clinicopathologic features in ESCC.</p><p><b>RESULTS</b>The positive staining rates of HSP27, HSP60, HSP70 and HSP90 alpha in ESCC and TIM were 62.0% and 42.1%, 92.7% and 63.2%, 57.9% and 22.2%, and 33.7% and 18.5%, respectively. There was very significant difference between the expression of HSP60 and HSP70 in ESCC and TIM (P < 0.01), but not significant about HSP27 and HSP90 alpha (P > 0.05). The positive staining rate of HSP27 declined with the lower grade of differentiation of ESCC (P < 0.05).</p><p><b>CONCLUSION</b>The present findings suggest that the expression of HSPs of different molecular weight in ESCC and TIM is a common event. The level of expressions of HSP60 and HSP70 are higher than those in TIM. HSP60 and HSP70 expression correlated with the biological behavior of ESCC. The expression of HSP27 was positively correlated to the grade of differentiation of ESCC. Overexpression of HSP27 may be associated to the differentiation of squamous cell carcinoma.</p>

Circulating endothelial cells in the peripheral blood of advanced NSCLC patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the changes and clinical value of circulating endothelial cells (CEC) in the peripheral blood of advanced NSCLC patient.</p><p><b>METHODS</b>Sixty-seven advanced NSCLC patients were randomly divided into either the treatment group with NP plus endostatin or control group with NP alone. Level of CEC and cytokeratin (CK) in the peripheral blood were measured by flow cytometry.</p><p><b>RESULTS</b>The response rate and benefit rate was 44.4%, 80.0% in the treatment group, and 27.3%, 50.0% in the control group, respectively (P = 0.176 and P = 0.012). Time to tumor progression (TTP) was 146.7 days in the treatment group and 91.1 days in the control group (P = 0.061). However, when the cut-off of TTP was defined as > 170 days, there was a significant difference between two groups (cut-off = 170, P = 0.034; cut-off = 180, P = 0.009). The number of CEC decreased by 0.29 +/- 0.47 in the treatment group and by 0.01 +/- 0.43 in the control group (P = 0.033). The correlation between CEC and CK was found to be positive either before (r = 0.381, P = 0.013) or after the treatment (r = 0.450, P = 0.004).</p><p><b>CONCLUSION</b>Chemotherapy combined with endostatin is superior to chemotherapy alone in the treatment of NSCLC. CEC, as a biomarker, may be useful in predicting the efficacy of the combined treatment.</p>