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BACKGROUND@#Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.@*METHODS@#We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.@*RESULTS@#The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.@*CONCLUSION@#The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 .@*TRIAL REGISTRATION@#No. NCT00454519 ( https://clinicaltrials.gov/ ).
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Humans , Prognosis , Genotype , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci , Colorectal Neoplasms , Tumor Microenvironment , Aminopeptidases/metabolism , Minor Histocompatibility Antigens/geneticsABSTRACT
OBJECTIVE@#To compare the clinical efficacy on cervical spondylosis of nerve root type with qi stagnation and blood stasis treated with warming needle with different lengths of moxa stick.@*METHODS@#Six hundred patients with cervical spondylosis of nerve root type with qi stagnation and blood stasis were randomly divided into 4 groups: a 4 cm length group (150 cases, 5 cases dropped off, 2 cases suspended), a 3 cm length group (150 cases, 6 cases dropped off, 2 cases suspended), a 2 cm length group (150 cases, 6 cases dropped off), and a routine acupuncture group (150 cases, 6 cases dropped off). Warming needle with moxa stick in the length of 4 cm, 3 cm and 2 cm was delivered in the 4 cm length group, the 3 cm length group and the 2 cm length group, respectively. In the routine acupuncture group, simple acupuncture was applied. The acupoints selected in the above groups included Dazhui (GV 14) and bilateral Jiaji (EX-B 2) of C5 and C7, Fengchi (GB 20), Jianzhen (SI 9), Quchi (LI 11), Zhongzhu (TE 3), etc. In each group, the intervention was delivered once daily and 5 times a week. One course of intervention was composed of 2 weeks and 2 courses were required. The TCM syndrome score, the score of clinical assessment scale for cervical spondylosis (CASCS), the score of the brachial plexus traction test of the affected upper limb, F wave occurrence rate and conduction velocity of the ulnar nerve, the median nerve and the radial nerve of the affected upper limb were compared before and after treatment in the patients of each group. The levels of serum inflammatory factors, i.e. interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and hypersensitive C-reactive protein (hs-CRP), were measured before and after treatment in the patients of each group. The clinical cfficacy was evaluated in the 4 groups.@*RESULTS@#After treatment, the results of TCM syndrome evaluation, i.e. the scores of neck pain, activity limitation and upper limb numbness and pain, as well as the total scores; and the scores of brachial plexus traction test were reduced when compared with those before treatment in each group (P<0.01, P<0.05). The scores of subjective symptoms and adaptability, and the total scores of CASCS were elevated in comparison with those before treatment in each group (P<0.01, P<0.05). In the 4 cm length group, compared with the other 3 groups, the scores of neck pain and activity limitation for TCM syndrome evaluation, and its total score were lower (P<0.05, P<0.01); and the scores of subjective symptoms and adaptability, and the total score of CASCS were higher (P<0.05, P<0.01). The score of the brachial plexus traction test in the 4 cm length group was lower than that of the routine acupuncture group (P<0.05). After treatment, F wave occurrence rates and conduction velocity of median nerve and radial nerve were increased when compared with those before treatment in each group (P<0.05, P<0.01). F wave occurrence rate and conduction velocity of the radial nerve in the 4 cm length group were higher than those of the other 3 groups (P<0.05), and those of the median nerve were higher when compared with the routine acupuncture group (P<0.05). After treatment, the levels of serum IL-1β, IL-6 and TNF-α were all reduced when compared with those before treatment in each group (P<0.01, P<0.05); the level of serum IL-6 in the 4 cm length group was lower than those of the other 3 groups and serum level of TNF-α was lower compared with that in the routine acupuncture group (P<0.05). The total effective rate of the 4 cm length group was 78.3% (112/143), which was higher when compared with the 3 cm length group (67.6%, 96/142), the 2 cm length group (65.3%, 94/144) and the routine acupuncture group (53.5%, 77/144), respectively (P<0.05).@*CONCLUSION@#Warming needle with moxa stick of 4 cm in length effectively relieves the clinical symptoms of cervical spondylosis of nerve root type with qi stagnation and blood stasis, improves the nerve function of the upper limbs, and reduces the inflammatory responses caused by nerve compression. The clinical efficacy of this therapy with moxa stick of 4 cm in length is superior to the warming needle with moxa sticks of 3 cm and 2 cm, as well as the routine acupuncture.
Subject(s)
Humans , Interleukin-6 , Neck Pain , Qi , Tumor Necrosis Factor-alpha , Spondylosis/therapyABSTRACT
Lung cancer is one of the malignant tumors with the highest morbidity and mortality. Epidermal growth factor receptor is expressed in the majority of non-small cell lung cancer tumor cells, making it possible to give these patients more precise and targeted therapies. The mechanisms of abnormal EGFR regulation are closely related to the efficacy of targeted therapy and the occurrence of drug resistance. Therefore, this review will review the expression mechanism of EGFR in NSCLC and the acquired drug resistance of epidermal growth factor receptor tyrosine kinase inhibitor after treatment of NSCLC.
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Objective To investigate the clinical features of patients with allergic reactions induced by hepatic arterial perfusion chemotherapy,and to discuss its nursing strategy.Methods The clinical manifestations,severity grading,time of onset,high-risk drugs,and the initial symptom of anaphylactic shock in 82 patients with allergic reactions were analyzed.Results Of the 82 patients,57(69.5%)had liver metastases from colorectal cancer,aged 42-82 years.Most patients(98.8%)were allergic to oxaliplatin.Degree I allergic reaction was most commonly seen(80.5%),and the clinical manifestations were mainly skin symptoms.Multiple symptoms could occur at the same time.The allergic reactions could occur in various time periods of medication,and anaphylactic shock usually occurred within 30 min after medication,and the initial symptom was atypical.Conclusion Oxaliplatin is a common drug that may cause allergic reactions in patients receiving hepatic artery infusion chemotherapy.Nursing staff should be familiar with the relevant drug allergic reactions,especially the clinical symptoms,features,and nursing measures of anaphylactic shock,so as to ensure the safety of patients.(J Intervent Radiol,2023,32:1242-1245)
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It has become a common consensus that resource conservation and intensive recycling for improving resource utilization efficiency is an important way to achieve carbon peak and carbon neutrality(dual carbon). Traditonal Chinese medicine(TCM)resources as national strategic resources are the material basis and fundamental guarantee for the development of TCM industry and health services. However, the rapid growth of China's TCM industry and the continuous expansion and extension of the industrial chain have exposed the low efficiency of TCM resources. Resource waste and environmental pollution caused by the treatment and discharge of TCM waste have emerged as major problems faced by the development of the industry, which has aroused wide concern. Considering the dual carbon goals, this paper expounds the role and potential of TCM resource recycling and circular economy industry development. Taking the typical model of TCM resource recycling as the case of circular economy industry in reducing carbon source and increasing carbon sink, this paper puts forward the suggestions for the TCM circular economy industry serving the double carbon goals. The suggestions mainly include strengthening the policy and strategic leading role of the double carbon goals, building an objective evaluation system of low-carbon emission reduction in the whole industrial chain of TCM resources, building an industrial demonstration park for the recycling of TCM resources, and promoting the establishment of a circular economy system of the whole industrial chain of TCM resources. These measures are expected to guide the green transformation of TCM resource industry from linear economic model to circular economy model, provide support for improving the utilization efficiency and sustainable development of TCM resources, and facilitate the low-carbon and efficient development of TCM resource industry and the achievement of the double carbon goals.
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Medicine, Chinese Traditional , Equipment Reuse , Goals , Environmental Pollution , Economic Development , Carbon , ChinaABSTRACT
This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Subject(s)
Animals , Rats , Caspase 1/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Interleukin-18 , Blood Glucose , Pyroptosis , Tumor Necrosis Factor-alpha , Diabetes Complications , Vascular Diseases , Inflammasomes , Cholesterol , Lipids , Diabetes MellitusABSTRACT
Human bocavirus is a novel pathogen first detected in respiratory tract samples in 2005. People of different ages can be infected by human bocavirus. Children are the susceptible population, especially the infants aged from 6-24 months old. The epidemic season varies in different regions due to the differences in climate and geographical location, and it mainly occurs in autumn and winter. It's demonstrated that human bocavirus-1 is closely related to respiratory system diseases and even causes life-threatening critical illness. Also, the severity of symptom is positively correlated with viral load. Co-infections between human bocavirus-1 and other viruses often present high frequency occurrence. Human bocavirus-1 interferes immune function of host by inhibiting interferon secrete pathway. Currently, it remains limited knowledge and understanding of the roles of human bocavirus 2-4 in diseases, but the gastrointestinal diseases should be paid more attention. Detection of human bocavirus DNA by traditional polymerase chain reaction (PCR) assay shouldn't be regarded as conclusive diagnostic basis. Instead, combined with mRNA and specific antigen detection, it is beneficial to improve the accuracy of diagnosis. Till now, the knowledge of human bocavirus remains poorly studied, which is deserved to further progress.
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Infant , Humans , Child , Child, Preschool , Human bocavirus , Climate , Coinfection , Epidemics , InterferonsABSTRACT
Objective:To investigate the application value of the Nottingham Hip Fracture Score (NHFS) in China and establish a formula specifically designed to assess the risk for 30-day mortality after surgery for hip fracture patients in China.Methods:A retrospective study was conducted to analyze the clinical data of 824 hip fracture patients who had been treated at Department of Orthopaedics, The First Hospital Affiliated to Zhengzhou University from August 2019 to May 2022. There were 312 males and 512 females with a median age of 73 (63, 82) years. The clinical data were compared between patients with different survival outcomes. The 30-day mortality was calculated by the formula according to the patients' NHFS, and compared with the actual one to validate the effectiveness of the original prediction model. The patients were divided into a training group ( n=577) and a validation group ( n=247). Binary logistic regression analysis was performed to establish a new prediction model for the patients in the training group. The discrimination, calibration, and clinical effectiveness of the predictive model were assessed in both the training and validation groups. Results:Multivariate logistic regression analysis showed that advanced age (≥86 years old) ( OR=3.775, 95% CI: 1.099 to 12.972, P=0.035), male ( OR=3.151, 95% CI: 1.574 to 6.306, P=0.001), admission hemoglobin concentration ≤100 g/L ( OR=2.402, 95% CI: 1.189 to 4.850, P=0.015), dependence on others for care before admission ( OR=2.673, 95% CI: 1.298 to 5.505, P=0.008), and comorbidities ≥2 ( OR=4.988, 95% CI: 1.874 to 13.274, P=0.001) were identified as risk factors for postoperative 30-day mortality (all P<0.05). In validation of the original prediction model, the C-index was found to be 0.764, indicating good discrimination. However, there was a significant discrepancy between the mortality forecast by the original prediction model and the actual mortality ( P<0.05), indicating poor calibration. After the prediction model was recalibrated, 30-day mortality (%) = 100/[1 + e (5.818-NHFS×0.599)]. After the new prediction model was validated in both the training and validation groups, the C-indexes were 0.762 and 0.780, indicating a good level of discrimination. The predicted 30-day mortality by the prediction model was closely aligned with the actual mortality ( P>0.05), demonstrating good calibration. When the threshold probabilities of the training and the validation groups were 0 to 26% and 0 to 35%, respectively, the patients might benefit from clinical intervention, showing clinical effectiveness of the model. Conclusions:The NHFS can predict the risk for 30-day mortality after hip fracture surgery. The new NHFS prediction model after calibration has a good predictive value for 30-day mortality after hip fracture surgery in Chinese population.
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Objective:To assess the long-term follow-up results of intensity-modulated radiotherapy (IMRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitor (TKI) in patients with hepatocellular carcinoma (HCC) showing macrovascular invasion (MVI).Methods:A retrospective analysis was conducted for 63 patients with HCC showing MVI without distant metastasis treated in Peking University Cancer Hospital from October 2015 to October 2018. Among them 28 patients were treated with IMRT combined with TACE and sorafenib (Group A) and 35 patients were treated with IMRT combined with TACE (Group B). Propensity score matching (PSM) was applied to assess the progression-free survival (PFS) and the overall survival (OS) of both groups.Results:The median follow-up time was 62 months. Before PSM, the median OS of group A and B were 19.0 months and 15.2 months ( χ2=3.15, P=0.076), respectively, and the median PFS of groups A (10.7 months) was longer than that of group B (8.6 months; χ2=3.99, P=0.046). After PSM, the median OS of group A (30.6 months) was significantly longer than that of group B (15.2 months; χ2=5.34, P=0.023), and the PFS of groups A (12.5 months) was still longer than that of group B (8.3 months; χ2=4.79, P=0.026). In the whole group, 10 patients (15.9%) suffered from grade-3 hematologic toxicity, and seven patients (11.1%) experienced grade-3 hepatic toxicity. The incidence of skin reactions, hand-foot syndrome, and diarrhea in group A was higher than that in group B, but all these adverse events were grade 1-2. Moreover, no grade-4 adverse events, radiation-induced liver disease, and treatment-related mortality occurred in both groups. Conclusions:As demonstrated by the long-term follow-up result, IMRT combined with TACE and TKI could improve both the PFS and the OS of patients with HCC showing MVI after PSM.
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In China, patients with hepatocellular carcinoma (HCC) are usually with late stage and long medical history when diagnosed, resulting in a lower 5-year survival rate. For advanced HCC, guidelines from different countries have different indications for local treatment. The applica-tion of hepatic artery chemoembolization has brought new treatment opportunities to patients with advanced HCC. Due to tumor heterogeneity, the response to immunotherapy is different in patients with intrahepatic recurrent lesions and extrahepatic metastatic lesions of primary hepatic carcinoma. Therefore, hepatic artery chemoembolization combined with systemic treatment is beneficial to prolong the survival of patients. The authors introduce the clinical experience of a patient with recurrent advanced HCC combined with abdominal lymph node metastasis who was treated with hepatic artery chemoembolization combined with atezolizumab plus bevacizumab. The results show that tumor is controlled in a short period with a good clinical effect.