Latest ArticlesObjective The study aimed to investigate the association between the genetic variant of neurofibromatosis 2 (NF2) gene and susceptibility to meningioma in Chinese population and analyze the correlation between NF2 gene polymorphism and meningioma. Methods 215 patients who had underwent neurosurgical treatment and been histologically diagnosed as meningioma were included as the case group in Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University between May 2010 to January 2011. The NF2 gene polymorphisms including rs2530673 and rs2530662 were analyzed by Multiplex SNaPshot methods. The correlation between NF2 gene polymorphism and prognosis of meningioma was analyzed. Results The NF2 gene polymorphisms rs2530673 and rs2530662 are not significant associated with the susceptibility to meningioma (P>0.05). According to the WHO grade I pathological subtypes, the result of stratification analysis showed that the patients carrying NF2 gene polymorphism loci rs2530673 CC genotype reduced the risk of transitional meningiomas in the dominant model distribution (OR=0.506, 95%CI 0.266-0.962, P=0.036). Besides, no significant association was found between NF2 gene polymorphism loci rs2530673 and rs2530662 and the recurrence of meningioma (P>0.05). For tumor location, the result of stratification analysis showed that the rs2530673 polymorphism of NF2 gene was associated with postoperative recurrence of meningiomas and patients carrying the rs2530673 CC genotype had shorter progression free survival time and higher recurrence risk in non-skull base meningiomas (all P<0.05). No significant correlation was found between rs2530673/rs2530662 polymorphisms and the prognosis of meningioma (P>0.05). Conclusions The C allele of rs2530673 may be a protective factor for the oneset of transitional meningioma. There may be no significant association between NF2 gene rs2530673/rs2530662 polymorphisms and the susceptibility in meningioma. However, the rs2530673 polymorphism of NF2 gene was associated with postoperative recurrence of meningiomas and patients carrying the rs2530673 CC genotype had higher recurrence risk in non-skull base meningiomas.
Objective To investigate the effect of lycopene (Lyc) on inflammatory factors and intestinal mucosal barrier function in mice with traumatic brain injury (TBI). Methods Forty-five SPF level of adult male BALB/c mice were randomly divided into sham group, TBI group and TBI+Lyc group, with 15 mice in each group. The TBI model was prepared by modified compression injury model, and the mice in sham group underwent an identical process without mechanical trauma. Each group was further divided into 5 subgroups at 1 d, 2 d, 3 d, 7 d and 14 d after modelling (n=3/subgroup). Mice in sham group and TBI group were treated with 10 mg/kg sunflower oil, and in TBI+Lyc group were treated with 10 mg/kg sunflower oil-dissolved Lyc (concentration 1 mg/ml), daily gavage at a fixed time for 14 d. The inferior vena cava blood and ileum tissue of mice in each subgroup were collected. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) were detected by ELISA, and the serum levels of D-lactic acid (D-LA) and endotoxin were detected by colorimetric method and endpoint chromogenic assay, respectively. Pearson correlation test was used to analyze the correlation between inflammatory factors and intestinal mucosal barrier function indicators. The pathological changes of ileum tissues were observed by HE staining, and the villus height and crypt depth of ileum were measured. Results The serum levels of TNF-α, IL-1β, I-FABP, D-LA, DAO and endotoxin of mice in TBI group and TBI+Lyc group gradually decreased with time, but were obviously higher than those in sham group at different time points (P<0.01 or P<0.001); the serum levels of TNF-α, IL-1β, I-FABP, D-LA, DAO and endotoxin of mice in TBI+Lyc group were significantly lower than those in TBI group at different time points (P<0.01 or P<0.001). Serum TNF-α and IL-1β were significantly positively correlated with I-FABP, D-LA, DAO and endotoxin, respectively (P<0.01). The sham group showed basically normal ileal villi, the structure of ileal villi in TBI group was obviously damaged, and the structure of ileal villi in TBI+Lyc group was basically neat. The ileal villus height and crypt depth of mice in TBI group were lower than those in sham group at each time points (P<0.05), and the ileal villus height and crypt depth of mice in TBI+Lyc group were significantly higher than those in TBI group at different time points (P<0.05). Conclusion Lyc can reduce the levels of inflammatory factors in various stages of TBI mice and may improve the intestinal mucosal barrier function by inhibiting inflammatory response.
The special environment of low oxygen in the plateau area will have a significant impact on human physiology and psychology, especially in a short period of time to reach the plateau, which can lead to the impairment of attention, memory, executive function, information processing and other types of cognitive functions, and directly affect health and working ability of people in the plateau. To correctly recognize and avoid the damage has become an urgent problem for researchers and clinicians. This paper summarizes the research status of the impact of acute high altitude hypoxia on human cognitive function in recent years, and summarizes the mechanism of high altitude hypoxia affecting brain physiological function, the damage characteristics of acute hypoxia on different types of cognitive function and hypoxia acclimatization strategies, in order to more clearly explain the relationship between high altitude hypoxia and cognitive changes, and better ensure the health and safety of people entering the plateau and Tibet.
With the improvement of people's health awareness and the popularization of low-dose spiral CT (LDCT) screening, more and more pulmonary nodules have been found. Pulmonary nodules gradually become a common and frequently occurring disease. The diagnosis and treatment of pulmonary nodules has also become a clinical problem. The rise of transbronchial pulmonary nodule diagnosis and treatment technology guided by various navigation technologies provides possibility for more minimally invasive diagnosis and treatment of pulmonary nodules. Navigation guided bronchoscopy is in a rapid development stage both at home and abroad. In order to standardize and promote the development of navigation bronchoscopy technology in China, Committee for the Prevention and Treatment of Senile Tumors of the CSCO organized domestic experts with rich experience in this field to jointly agree and write the consensus.
Advances in the treatment of haematological malignancies have improved the long-term prognosis of patients to some extent, but have also highlighted the importance of tumour progression and cardiovascular events caused by anti-tumour therapy. A significant proportion of patients with haematological malignancies receiving existing and emerging oncological treatment regimens such as anthracyclines, proteasome inhibitors, targeted therapies and immunotherapy experience cardiovascular events at some point after disease remission, which seriously affects the survival and quality of life of the patients. This article reviews the mechanisms, clinical manifestations and interventions of cardiotoxicity induced by therapeutic agents for haematological malignancies, with the aim of providing a reference to protect patients with haematological malignancies from cardiovascular complications.
Objective To investigate the prevalence and risk factors of hypertension in young men first exposed to high altitude for half a year at 4500 m. Methods A total of 228 young men who firstly traveled from a plain area to an altitude of 4500 meters in northern Tibet and stayed there for six months were recruited in present study. They were divided into hypertension group (HTN, n=66) and non-hypertension group (NTN, n=162) based on their blood pressure status. A self-administered questionnaire, the Pittsburgh Sleep Quality Index (PSQI), physical examinations and laboratory tests were used to investigate the risk factors and clinical complications of hypertension. The general data and clinical complications of the two groups were compared, and multivariate logistic regression was used to analyze the risk factors of high-altitude hypertension and predisposition of clinical complications. Results Among the 228 individuals, 66 developed hypertension (incidence of 28.9%), including 52 cases of stage Ⅰ hypertension and 14 cases of stage Ⅱ hypertension. Fifty-eight individuals had isolated diastolic hypertension, and 8 individuals had combined systolic and diastolic hypertension. The proportions of obesity and overweight, central obesity, smoking over 10 cigarettes per day, family history of hypertension, dyslipidemia, and hyperuricemia were significantly higher in HTN group than those in NTN group (P<0.05). The PSQI score was also higher significantly in HTN group than that in NTN group (P<0.001). Multivariate logistic regression analysis showed that hyperuricemia (P=0.02), central obesity (P=0.04), family history of hypertension (P=0.03) and sleeping quality (P<0.001) were the independent risk factors for high-altitude hypertension. The proportion of clinical complications in the past month in HTN group was significantly higher than that in NTN group (P=0.001), and the proportion of three or more kinds of clinical complications was also higher in HTN group than that in NTN group (P=0.01). After adjusting for demographic differences, the risk of dizziness and headache in HTN group was higher than that in NTN group (P<0.05). Conclusions Young men firstly exposed to an altitude of 4500 meters still have a high incidence of hypertension after six months, mostly stage Ⅰ hypertension with diastolic pressure elevation; Hyperuricemia, central obesity, family history of hypertension, and poor sleep quality are the independent risk factors for high-altitude hypertension. High-altitude hypertension can cause various clinical complications, and the higher risk of accompanying dizziness and headache.
Objective To observe the influence of exosomal miR-155 derived from monocytes stimulated by heat stress on the inflammatory response of hepatocytes. Methods According to different treatments, we termed THP-1 monocytes into the control group, the heat stress group, and the ulinasatin group. We then extracted the exosomes from each group. To study the function of exsome on hepatocytes, we incubated hepatocytes with these exosomes. We then tested the alanine aminotransferase and lactate dehydrogenase levels in the supernatant, measured cell viability, and detected the relative mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the hepatocytes. Then, the expression changes of exosomal miR-155 derived from monocytes were detected using RT-qPCR. Furthermore, the potential target of miR-155 was analyzed using database retrieval, dual-luciferase report, and Western blotting assay. Finally, the effect of monocyte exosomes on hepatocyte miR-155 and the treatment with ulinastatin or miR-155 inhibitor on hepatocyte injury were observed. Results When incubating hepatocytes with the exosomes derived from monocytes stimulated by heat stress, the levels of alanine aminotransferase and lactate dehydrogenase in the supernatant and the mRNA levels of TNF-α and IL-6 in hepatocytes were all significantly increased (P<0.01) with decreased cell survival rate (P<0.05). Heat stress increased the level of miR-155 contained in monocytes and their release of exosomes. Database retrieval, dual-luciferase reports, and Western blotting assay showed that miR-155 might target SOCS1. The exosomes from monocytes stimulated by heat stress increased miR-155 in liver cells. Ulinastatin or miR-155 inhibitor could reduce the exosomal miR-155 level and decrease TNF-α and IL-6 mRNA expression in liver cells. The difference was statistically significant (P<0.05). Conclusion The monocytes stimulated by heat stress increase the inflammatory response of hepatocytes, which may be associated with increased exosomal miR-155 using SOCS1 as a potential target. Ulinastatin may relieve the hepatocytic mRNA expression of inflammatory cytokines in this setting.
Objective To investigate the risk factors for concomitant pulmonary thromboembolism (PTE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to construct a line graph prediction model accordingly and validate it. Methods 426 patients with AECOPD who attended the Affiliated hospital of North Sichuan Medical College from January 2019 to December 2021 were selected for retrospective analysis. The patients were divided into 256 cases in model group and 170 cases in validation group in a ratio of 6∶4. Indicators that may affect AECOPD patients with concurrent PTE were collected, and patients in model group were divided into PTE subgroup and non-PTE subgroup according to the presence or absence of concurrent PTE, and the above-mentioned indicators in the 2 subgroups were compared, and the independent influencing factors of AECOPD patients with concurrent PTE were screened by multifactorial logistic regression analysis, which was used to construct a column line graph prediction model. The prediction model was internally validated by Bootstrap method, and then externally validated by using the validation group data. Results A total of 39 (15.2%) of 256 AECOPD patients in model group were complicated by PTE. Multifactorial logistic regression analysis showed that Barthel index score, bed rest time, deep vein thrombosis of lower extremity, right heart insufficiency, PaO2, fibrinogen, and C-reactive protein were independent influencing factors for complicated PTE in AECOPD patients (P<0.05). According to the results of multi-factor regression analysis, the column line graph prediction model was constructed using R4.1.3 software, and the internal validation area under ROC curve (AUC) of the model was 0.863, 95%CI was 0.798-0.927, sensitivity was 82.94%, and specificity was 74.36%; the internal validation results of the column line graph model by Bootstrap method showed that the mean absolute error was 0.02, and the prediction model was basically fitted with the ideal model; the external validation results showed that the AUC of the column line graph model constructed by the validation group was 0.892 with 95%CI of 0.803-0.942. Conclusions The major risk factors for concomitant PTE in patients with AECOPD include Barthel index score, bed rest time, deep vein thrombosis of lower extremity, right heart insufficiency, PaO2, fibrinogen, and C-reactive protein, and the column line graph prediction model constructed from this has a high sensitivity and specificity.
Objective To investigate the molecular mechanism of histone demethylase 5C (KDM5C) regulating human cervical carcinogenesis through Hippo-YAP1 pathway. Methods Using CaSki cell lines stably overexpressing KDM5C protein, whole transcriptome sequencing was performed by RNA-Seq technique, and differentially expressed genes were analyzed, and then GO analysis, KEGG analysis and protein interaction network analysis were performed on these differential genes. After that, siRNA knocked down KDM5C and reversely verified the expression changes of key regulated gene Yes associate protein 1 (YAP1) by RT-qPCR and Western blotting. Meanwhile, in CaSki cell lines, the effect of KDM5C protein overexpression on the methylation status of YAP1 gene promoter region was analyzed by chromatin immunoprecipitation sequencing (ChIP-Seq) and ChIP-qPCR methods. Results RNA-Seq analysis showed that overexpression of KDM5C significantly up-regulated expressions of 356 mRNAs and down-regulated 335 mRNAs expressions (P<0.05). GO enrichment analysis showed that KDM5C protein was mainly involved in various biological development processes of the body. KEGG enrichment analysis showed that KDM5C protein was mainly involved in focal adhesion, steroid hormone biosynthesis, Hippo-YAP1 pathway, FoxO pathway, apoptosis and infection. Further RT-qPCR analysis showed that knockdown of KDM5C with gene specific siRNAs could up-regulate the expression of YAP1, and Western blotting results also confirmed that reduction the expression of KDM5C protein could up-regulate the levels of YAP1 and phosphorylated YAP1 simultaneously (P<0.05). ChIP-Seq analysis showed that KDM5C overexpression cell line could significantly increase the H3K4me1 level and decrease the H3K4me3 level in the promoter interval of YAP1 gene compared with the control cell line, and this expression change was also verified by subsequent ChIP-qPCR (P<0.05). Conclusions The KDM5C protein regulates the methylation level of the histone H3K4me1/me3 in the YAP1 gene promoter of cervical cancer cells, thereby affecting the transcription of the YAP1 gene. As a core factor in Hippo-YAP1 pathway, the expression of YAP1 protein directly affects cell adhesion, proliferation, and apoptosis, thereby participating in the occurrence and development of cervical cancer.
Objective To evaluate the hemostatic efficacy and safety of a new type of pushable compressed cellulose hemostatic device in emergency treatment of deep tissue massive hemorrhage. Methods The internal compressed cellulose hemostatic granules were placed in excess normal saline to test their saline absorption and volume expansion properties. Femoral artery blood was taken from 3 big-eared white rabbits for measuring the in vitro clotting time of the compressed cellulose hemostatic granules, and equal quality CELOX-A® hemostatic powder was set as the positive control group, and the blank plasma as negative control group. Ten rats were divided into the compressed cellulose hemostatic granule dressing group, CELOX-A® hemostatic powder group and negative control group, and plasma was taken to test the coagulation activity by using a thromboelastometer. The swine models of massive hemorrhage were established by complete transection of the femoral artery and vein, and divided into the model group of medical defatted gauze block, the pushable compressed cellulose hemostatic device group, and the positive control group of CELOX-A®. The three groups used parallel operation for hemostasis. The number of pushable compressed cellulose hemostatic device used in the hemostasis process, the number of presses, the hemostasis time, the total blood loss during the hemostasis process were recorded, the routine blood tests before and after hemostasis, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured and HE staining was used to observe the pathological changes of the tissue vessels. After DMEM medium was used to extract the pushable compressed cellulose hemostatic device, and the extract was added to L929 cells with vigorous growth to test the cytotoxicity. At the same time, the complete DMEM medium with phenol was set as the positive control group and the complete DMEM medium as the negative control group. After pushable compressed cellulose hemostatic device was extracted with normal saline, the normal saline extract was injected into the mice to test its acute toxicity, and equal volume of the normal saline into the mice in the same way as the negative control group. The normal saline was set as the negative control group and the deionized water was set as the positive control group, the hemolysis test was used to detect the hemolysis rate of pushable compressed cellulose hemostatic device. Results The compressed cellulose hemostatic granules inside the device rapidly absorbed and expanded in normal saline buffer, the maximum absorption ratio was more than 7.3 times, and the swelling rate reached about (9.0±0.3) times after 3 s in normal saline buffer. The in vitro clotting time of the compressed cellulose hemostatic granules was (451.7±26.6) s, significantly shorter than that of the negative control group (703.7±32.1) s (P<0.01), and was also shorter than that of the CELOX-A® hemostatic powder about (521.7±18.1) s (P<0.05). The result of thromboelastography showed that compared with negative control group, both the compressed cellulose hemostatic granules and CELOX-A® hemostatic powder significantly shortened the clot formation time (P<0.01), and the compressed cellulose hemostatic granules had shorter coagulation time than CELOX-A® hemostatic powder (P<0.05). The evaluation results of hemostatic efficacy study on the model of massive groin hemorrhage by complete transaction of the femoral artery and vein in the swine showed the pushable compressed cellulose hemostatic device group used (1.2±0.4) devices to achieve hemostasis, while CELOX-A® group needed (2.2±0.4) devices (P<0.05), and the total hemostatic time needed for the pushable compressed cellulose hemostatic device and CELOX-A® was (185.5±2.4) s and (268.5±83.4) s, respectively, and the difference between them was statistically significant (P<0.05). The APTT, PT and pathological changes of tissue and blood vessels were not obvious after the experiment in the pushable compressed cellulose hemostatic device group. The results of in vitro cytotoxicity test, acute toxicity test and hemolysis test were all within the standard range. Conclusions Pushable compressed cellulose hemostatic device has favourable hemostatic efficacy and biological safety. The compressed cellulose hemostatic granule can rapidly block the injured vessel and effectively fill the wound cavity based on its strong absorption and swelling property. To summarize, the pushable compressed cellulose hemostatic device is a promising candidate to be used for controlling junctional hemorrhage and evacuation of the wounded, especially for the hemorrhage caused by gunshot or penetrating injuries in battlefield, thus saving valuable time for the further evacuation and treatment.