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Objective To explore whether ferulic acid can inhibit the progression of T-cell acute lymphoblastic leukemia in vivo and in vitro by regulating PTEN/PI3K/AKT signaling pathway.Methods The T-cell acute lymphoblastic leukemia Jurkat cells were divided into the control group,the ferulic acid treatment group and the LY294002 treatment group for in vitro experiment.The cells in the control group were given normal culture;cells in the ferulic acid treatment group were given different concentrations(1.25,2.5,5,10,20,40,80,160 μmol/L)of ferulic acid,respectively,and the cell proliferation was detected by CCK-8 method,to screen the experimental concentration;cells in the LY294002 treatment group were given 50 μmol/L PI3K/AKT inhibitor LY294002.The cells proliferation,apoptosis and invasion were detected by clone formation assay,flow cytometry and Transwell assay.The relative expression levels of nuclear protein Ki67,proliferating cell nuclear antigen(PCNA),cleaved caspase-3,cleaved caspase-9,E-cadherin,N-cadherin,Vimentin,PTEN,p-PI3K,PI3K,p-AKT and AKT proteins were detected by Western blot.The nude mice models of transplanted tumors were constructed by 30 male BALB/c nude mice,and they were averagely divided into the normal group and the ferulic acid treatment group for in vivo experiment.The normal group was given normal saline by gavage,while the ferulic acid treatment group was given 75 mg/kg ferulic acid by gavage after inoculating Jurkat cells.The weight and volume changes of transplanted tumors were compared,and the levels of Ki67,cleaved caspase-3/caspase-3,E-cadherin,N-cadherin,PTEN,p-PI3K,PI3K,p-AKT and AKT in tumor tissues were detected.Results In vitro experiment,compared with the control group,the clone formation rate of cells,number of invasion cells,Ki67,PCNA,N-cadherin,Vimentin,p-PI3K/PI3K and p-AKT/AKT in the 5,10,20 μmol/L ferulic acid treatment group and the LY294002 treatment group were significantly decreased(P<0.05),while the apoptosis rate,cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,E-cadherin and PTEN were significantly increased(P<0.05).In vivo experiment,compared with the normal group,the weight and volume of tumors were reduced in the ferulic acid treatment group,Ki67,N-cadherin,p-PI3K/PI3K and p-AKT/AKT in tumor tissues were significantly decreased,cleaved caspase-3/caspase-3,E-cadherin and PTEN were significantly increased,with statistically significant differences(P<0.05).Conclusion Ferulic acid can inhibit the proliferation and invasion of T-cell acute lymphoblastic leukemia Jurkat cells in vivo and in vitro,and induce apoptosis,its mechanism may be related to the regulation of PTEN/PI3K/AKT signaling pathway.
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Objective To analyze the relationship between MyD88L265P and CD79B mutations in tumor tissue and the prognosis of primary central nervous system lymphoma(PCNSL).Methods 18 PCNSL patients with normal immune function(no history of HIV infection and immunosuppressants administration)who were diagnosed by craniotomy or stereotaxic biopsy in the Second Hospital of Lanzhou University from August 2018 to November 2020 were retrospectively analyzed.Real-time quantitative PCR and first-generation sequencing techniques were respectively used to detect MyD88L265P and CD79B mutations in tumor tissues of 18 PCNSL patients.Univariate analysis and Cox regression multivariate analysis were performed for indicators that may be associated with first progression-free survival(PFS)and overall survival in PCNSL.Results The mutation rate of MyD88L265P was 38.9%,the mutation rate of CD79B was 33.3%,and the co-mutation rate of MyD88L265P/CD79B was 27.8%in PCNSL tissue of 18 patients.Univariate analysis showed that the PCNSL patients with multiple lesions,deep involvement of lesions,and tissue CD79B mutation had a statistically significant shorter time of PFS(P<0.05).Multivariate analysis showed that deep lesion involvement(HR=0.135,95%CI 0.023-0.799,P<0.05)and CD79B mutation(HR=0.149,95%CI 0.028-0.800,P<0.05)in PCNSL tissue were independent prognostic factors for PCNSL patients.Conclusion The frequency of MyD88L265P and CD79B mutations was high in tumor tissues of 18 PCNSL patients,and these two gene mutations may be associated with poor prognosis of PCNSL,especially CD79B mutation.
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Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
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Polymyxin antibiotics,particularly polymyxin B and polymyxin E(colistin),are often considered a last line of defense against penicillin carbapenem-resistant Enterobacteriaceae(CRE),because of their favorable clinical antibacterial effects.However,the emergence and spread of plasmid-mediated colistin resistance genes(mcr),and their multiple isoforms,have posed a substantial threat to public health in recent years.The mcr-1 genes exhibit complexity in both host and transmis-sion routes,and diversity in both the genetic environment and ecological locus distribution.Herein,we discuss the prevalence,transmission routes,drug resistance and transmission mechanisms of mcr-1 positive isolates,on the basis of epidemiological studies of Enterobacteriaceae carrying mcr-1 worldwide.to provide a theoretical reference for researchers.
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Objective:colorectal cancer is one of the common malignant tumors in the gas-trointestinal tract.Oxaliplatin is the first-line drug for the treatment of advanced colorectal cancer,but drug resistance often occurs.The mechanism of CXCR4 in oxaliplatin resistance of colon cancer is not clear.This study intends to explore the mechanism of CXCR4 mediated oxaliplatin resistance and the potential therapeutic value of CXCR4 inhibitor AMD3100.Methods:oxaliplatin resistant strains HCT116 were constructed.The expression of CXCR4 and the phosphorylation level of PI3K-Akt signal pathway were detected by Q-PCR and Western blot.The phosphorylation level of PI3K-Akt signal pathway was detected by Q-PCR and Western blot.The effect of AMD3100 an-tagonizing CXCR4 or combined application of Akt inhibitor LY294002 on oxaliplatin resistance of drug-resistant cells was detected by CCK8.Results:CCK-8 was used to detect the proliferation activity of Oxaliplatin in HCT116 drug resistant group compared with control cells in the absence of drugs and at different concentrations.The results showed that there was no significant change in the activity of the resistant strains,while the control cells showed a significant decrease.Q-PCR and Western blot showed that the expression of CXCR4 and the phosphorylation level of PI3K-Akt increased significantly in the drug-resistant group(P<0.05).After administration of CXCR4 inhibitor AMD3100,CXCR4 expression and PI3K-Akt phosphorylation decreased significantly(P<0.05).AMD3100 enhanced the sensitivity of drug-resistant cell lines to oxaliplatin.The combination of AMD3100 and Akt inhibitor LY294002 can further enhance the sensitivity of drug-resistant cell lines to oxaliplatin.Conclusion:CXCR4 mediated activation of PI3K-Akt signaling pathway plays an important role in the resistance of colon cancer to oxaliplatin.AMD3100 may become a potential therapeutic drug against chemoresistance of colon cancer.
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Objective To investigate the effect of inhaled corticosteroids(ICS)on adverse outcomes in chronic obstructive pulmonary disease(COPD)(COPD-CAP)patients with community-acquired pneumonia(CAP).Methods The clinical data of COPD-CAP patients who visited the respiratory department of respiratory of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2021 to January 2023 was retrosspective collected.They were divided into an ICS group and a non ICS group based on whether they were eligible for ICS treatment.A univariate analysis was used to compare the differences in general data,imaging outcomes(multilobed infiltration and pleural effusion),and clinical outcomes(non-invasive mechanical ventilation,invasive mechanical ventilation,ICU admission,and 30-day mortality)between two groups.The Logistic regression was used to explore the relationship between ICS and imaging and clinical outcomes.Result A total of 120 COPD patients were included in this study,including 38 in the ICS group,62 in the non ICS group.The univariate results showed that COPD-CAP patients in the ICS group had lower GOLD scores,PSI scores,and CURB-65 scores(P<0.05).The multivariate Logistic regression showed that the use of ICS reduces the risk of multi leaf infiltration[OR=0.291,95%CI(0.123,0.687),P=0.005],pleural effusion[OR=0.309,95%CI(0.105,0.908),P=0.033],non-invasive mechanical ventilation[OR=0.040,95%CI(0.012,0.129),P<0.001],invasive mechanical ventilation[OR=0.099,95%CI(0.013,0.783),P=0.028],ICU occupancy[OR=0.207,95%CI(0.056,0.762),P=0.018],and 30-day mortality[OR=0.179,95%CI(0.039,0.822),P=0.027].Conclusion ICS reduces the risk of multilobed infiltration,pleural effusion,mechanical ventilation usage,ICU occupancy,and 30-day mortality in COPD patients admitted to CAP.
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Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.
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Humans , Female , Breast Neoplasms/genetics , Clinical Relevance , In Situ Hybridization, FluorescenceABSTRACT
Glucagon-like peptide-1 (GLP-1) is a major hormone of incretin hormone and gut-brain axis, which is related to the control of energy homeostasis and the occurrence of obesity. In addition to suppressing appetite, GLP-1 has neuroprotective effects by acting on areas of the brain involved in stress response and mood regulation. Depression is a common mental disease, and GLP-1 is closely related to depression. This article reviews the role and mechanism of GLP-1 in depression.
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Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H
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Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.
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Male , Female , Humans , Adult , Middle Aged , Aged , Blast Crisis/drug therapy , Primary Myelofibrosis/genetics , Prognosis , Splenomegaly , Retrospective Studies , Myeloproliferative Disorders/genetics , Mutation , Leukemia, Myeloid, Acute , Janus Kinase 2/geneticsABSTRACT
Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.
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Humans , Hepatitis B virus , Hepatic Encephalopathy/complications , Acute-On-Chronic Liver Failure/diagnosis , End Stage Liver Disease/complications , Severity of Illness Index , Risk Factors , ROC Curve , Prognosis , Retrospective StudiesABSTRACT
Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.
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Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.
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Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Subject(s)
Humans , Aged , Treatment Outcome , Retrospective Studies , Combined Modality Therapy , Chemoradiotherapy/methods , Urinary Bladder Neoplasms/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm StagingABSTRACT
Objective:To compare the lymph node tracing of indocyanine green (ICG) and nanocarbon in laparoscopic right hemicolectomy.Methods:Fifty-two patients with right colon cancer were randomly divided into two groups: ICG group and nanocarbon group at Peking University International Hospital between Oct 2020 and Jul 2022. Sentinel lymph node (SLN) mapping and standard oncologic resection was performed. The micrometastasis was to detect when the routine SLN pathological test was negative.Results:In ICG group, the detection rate of SLN was 100%, the sensitivity was 93%, the false negative rate was 7%, and the accuracy was 96%,which were better than nanocarbon group (92%,57%,43%,77%). The number of SLN and positive SLN detected in ICG group were significantly higher than nanocarbon group [(3.2±0.7) vs. (2.6±1.1), t=4.424, P=0.020; (1.2±1.2) vs.(0.5±0.8), t=15.176, P=0.013]. The SLN biopsy accuracy of patients with BMI ≥24 kg/m 2 and tumor diameter ≥3 cm in ICG group was significantly higher than nanocarbon group (90% vs. 44%, χ 2=7.935, P=0.005; 90% vs.57%, χ 2=4.309, P=0.038). The detection rate of micrometastasis in SLN of ICG group was significantly different from nanocarbon group (35% vs. 15%, χ 2=5.853, P=0.016). Conclusion:ICG fluorescence imaging is superior to nanocarbon in SLN biopsy during laparoscopic radical right hemicolectomy, especially when patients' BMI ≥24 kg/m 2 and tumor diameter ≥3 cm.
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Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.
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Hie high altitude hypoxic environment affects the pharmacokinetic process of rlnjgs by changing the body's gastrointestinal emptying rate, organ blood flow, drug plasma protein binding rate, dnjg metabolizing enzymes and transporter expression.Epilepsy is a brain disease that requires long-term medication.Most anti-epileptic drugs have a low therapeutic index and a narrow range of effective blood drug concentrations.'Ilierapeu- tic dnjg monitoring (TDM) is commonly used clinically to find the best individualized medication method for antiepileptic dnjgs.rI1iis article summarizes the commonly used anti-epileptic dnjgs and their treatment windows in clinical practice, and analyzes the influence of the pharmacokinetics of anti-epileptic dnjgs in the high altitude hypoxic environment, so as to provide reference for the clinical use of anti-epileptic drugs at high altitude.
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OBJECTIVE@#To observe the effect of electroacupuncture (EA) on the proliferation of endogenous neural stem cells in the hippocampus of young mice with Alzheimer's disease (AD), so as to explore its mechanisms underlying improvement of AD.@*METHODS@#Forty 1.5-month-old APP/PS1 transgenic male mice were randomly divided into an EA group and a model group, 20 mice in each group, and other 20 C57BL/6J male mice of the same age were used as the normal control group. EA (intermittment wave 10 Hz, 2 mA) was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23) for 20 min, once a day, 6 days a week for 16 weeks. H.E. staining was used to assess histopathological changes of neurons of the hippocampal dentate gyrus. Immunohistochemical stain was used to detect the expression of 5-bromodeoxyuridine (BrdU)-positive in the hippocampus, and immunofluorescence double-labeled technique was used to detect the number of proliferated positive neurons of hippocampal neural stem cells. The expression levels of brain derived neurotrophic factor (BDNF) and Nestin mRNA and protein were detected by using real-time PCR and Western blot, separately.@*RESULTS@#The immunoactivity of BrdU, and the expression levels of BDNF and Nestin mRNA and protein in the hippocampus in the model group were significantly lower than in the normal control group (P<0.01, P<0.05), and considerably higher in the EA group than in the model group (P<0.01, P<0.05). The number of BrdU/NeuN dual labeled neurons was slightly increased in the model group than in the normal control group (P>0.05), and evidently increased in the EA group relevant to the model group (P<0.05), suggesting a proliferation of hippocampal neural stem cells. After modeling, the neurons of hippocampal dentate gyrus were arranged loosely and irregularly and their structure was fuzzy, with an appearance of different degrees of nuclear pyknosis, whereas in the EA group, the neuronal contour was clear and the nuclear structure was relatively distinct.@*CONCLUSION@#EA can activate the proliferation of neural stem cells in the hippocampus in AD mice, which may contribute to its function in improving the neuronal structure by upregulating the expression of BDNF.
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Animals , Male , Mice , Alzheimer Disease/therapy , Cell Proliferation , Electroacupuncture , Hippocampus , Mice, Inbred C57BL , Neural Stem CellsABSTRACT
@#Esophageal carcinoma is a malignant tumor with high morbidity and mortality worldwide, and surgery is the main treatment currently. With the development of patient-centered care, the effect of surgery should not be limited to the improvement of the incidence of postoperative complications, mortality and other indicators. It is also important to provide experience related to disease and surgery from the perspective of patients. Therefore, more and more attention is paid to patient-reported outcomes by scholars. This paper will provide an overview of the international widely used, reliable and effective scales and researches about patient-reported outcomes in esophageal carcinoma.
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Objective:To investigate the correlation and predictive value of thromboelastography (TEG) in the severity and prognosis of patients with sepsis.Methods:Clinical data of 147 patients with sepsis admitted to Intensive Care Unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019 were retrospectively analyzed. Inflammation indicators and TEGt were performed within 24 h after admission, and APACHE Ⅱ score was evaluated. According to APACHE Ⅱ score, the patients were divided into the mild group and severe group. TEG indicators were compared between the two groups. Patients with sepsis were divided into the death group and survival group to assess the value of TEG for prognosis of patients with sepsis.Results:Compared with patients with mild sepsis, patients with severe sepsis had lower α angle ( P=0.015), longer K time ( P=0.015), and higher maximum amplitude ( P=0.045). The K time of the death group was significantly longer than that of the survival group. When K time ≥2.2 min (sensitivity 77.27% and specificity 95.2%), the risk of sepsis death was the highest ( P<0.001). Conclusions:Patients with severe sepsis show marked hypocoagulability, and K time has predictive value for the prognosis of patients with sepsis.