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Purpose@#Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. @*Materials and Methods@#TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. @*Results@#The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. @*Conclusion@#Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.
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Abstract@#Long-term use of levodopa in the treatment of Parkinson's disease can cause motor complications, which seriously impair the patients'motor function, reduce the quality of life, and aggravate the functional disability. Since there has been no effective treatment for motor complications, clarifying the influencing factors and prevention methods are conducive to reducing the risk of incidence and improving the quality of life of the patients. This paper summarizes the types and mechanism of motor complications of Parkinson's disease, the influencing factors ( levodopa dose, onset age, Helicobacter pylori infection and high protein diet ) and preventive measures ( psychological intervention, low protein diet, rehabilitation exercise and drugs ), so as to provide reference for the prevention and control of the disease.
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Pain post spinal cord injury (SCI) is treated clinically with drug and non-drug treatments, commonly including opioid analgesics, antiepileptics, antidepressants, acupuncture and moxibustion, stimulation therapy, surgical treatment, and so on. The effect of the drug treatment is obvious but following serious side effect; the non-drug treatment has small side effect and is safe and controllable, which has shown great development potential with the development of science and technology although the treatment effect is not certain.
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Objective:To investigate the effect of electroacupuncture at Jiaji (EX-B2) points and Stomach Meridian Foot-Yang Ming points on the neurological function and the expression of local Synapsin I in rats after spinal cord injury, and to explore its molecular mechanism. Methods:A total of 60 Sprague-Dawley rats were established spinal cord injury model and they were randomly divided into normal control group, Jiaji group and Yang Ming group, with 20 rats in each group. On the third day after operation, Jiaji group and Yang Ming group were treated with electroacupuncture while the normal control group was not. Their neurological function was assessed with BBB every day. Four rats in each group were sacrificed at the end of the 1st, 2nd, 3rd, 4th and 5th week during the intervention period. HE staining was used to observe the morphology of spinal cord. Immumohistochemical staining was used to detect the expression of Synapsin I protein. Reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting was used to detect the content of of Synapsin I mRNA and protein. Results:The BBB scores were higher in Jiaji group and Yang Ming group than in the normal control group at all the time points (P < 0.05), and were higher in Yang Ming group than in Jiaji group from one to three weeks (P < 0.05). The immunohistochemical scores of Synapsin I protein were higher in Jiaji group than in the normal control group in the first week (P < 0.05), and were higher in Yang Ming group than in the normal control group from one to four weeks (P < 0.05). The immunohistochemical scores of Synapsin I protein were higher in Yang Ming group than in Jiaji group from three to four weeks (P < 0.05). The expression of Synapsin I mRNA and protein first increased and then decreased in the normal control group; which was higher in Jiaji group than in the normal control group in the first week (P < 0.05) and was higher in Yang Ming group than in the normal control group from one to four weeks (P < 0.05). The Synapsin I mRNA expression in the third week and the Synapsin I protein expression from two to three weeks was higher in Yang Ming group than in Jiaji group (P < 0.05). Conclusion:Electroacupuncture at both Jiaji points and Stomach Meridian Foot-Yang Ming points promote the recovery of nerve function in rats with spinal cord injury. It may be related to the elevated level of Synapsin I in the damaged parts of the spinal cord.
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Iron-doped titanium dioxide nanosheets was prepared by hydrothermal method using tetrabutyl titanate (C16H36O4Ti) and iron trifluoride (FeF3) and modified on ITO electrode.ITO/Fe : TiO2/CdS photoelectrochemical sensor was fabricated by successive ionic layer absorption and reaction(SILAR) method for determination of copper ion.The band gap of electode material was narrowed by iron doped TiO2 nanosheets,which made its absorption red-shifted and its response range of light was magnified.Based on the sensitization effect of CdS,the absorption and utilization of visible light of sensor was significantly enhanced and the photoelectric signal was amplified via reducing the recombination of electrons and holes.The sensor displayed excellent analytical performance for detection of copper ion with linear range of 0.2-4.0 μmol/L and 4.0-80.0 μmol/L and with the detection limit of 85 nmol/L.The sensor was used to detect copper ion in tap water,drinking water and Yongjiang river water with recoveries ranging from 94% to 111%.
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<p><b>OBJECTIVE</b>To detect RAS mutations in the circulating cell-free DNA (cfDNA) in the plasma and explore the their correlation with the clinicopathological features in patients with colorectal cancer.</p><p><b>METHODS</b>Real-time PCR was used to detect RAS mutations in plasma cfDNA and matched tumor tissue DNA samples from 71 colorectal cancer patients. The correlation of RAS mutations with the clinicopathological features of the patients were analyzed.</p><p><b>RESULTS</b>Of the 71 patients with colorectal cancer, 23 (32.39%) showed RAS mutations in the cfDNA and 36 (50.7%) showed RAS mutations in tumor tissue DNA, with a concordance rate of 76.06% in the results between the two samples (Kappa=0.523). RAS mutations in the cfDNA were not related to the patients' age (P=0.072), gender (P=0.320), tumor stage (IVa and IVb, P=0.450), primary tumor position (P=0.324), lung metastasis (P=0.237), CEA level (P=0.284) or CA199 level (P=0.427). The positivity rate of RAS mutations in plasma cfDNA was significantly higher in patients with liver metastasis than those without liver metastasis (P=0.045).</p><p><b>CONCLUSION</b>Plasma cfDNA can be a reliable source of diagnostic DNA to replace the tumor tissue DNA for diagnosis of RAS mutations. RAS mutations in plasma cfDNA occur more frequently in colorectal cancer patients with liver metastasis.</p>
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Objective:The clinical features, risk factors, and outcomes of coma were analyzed in patients treated with bevacizum-ab combined with chemotherapy This study also aims to increase the awareness on the toxicity of this regimen. Methods:Two cases of coma induced by bevacizumab combined with chemotherapy were reported. Diagnosis, treatment, and relevant literature were reviewed and discussed. Results:Inadequate blood pressure (BP) control was one of the risk factors leading to coma in patients treated with this therapy. The clinical feature of these patients was reversible posterior leukoencephalopathy syndrome (RLPS). Imaging results showed no typical finding. Reinforced supportive treatment including intensive BP control showed satisfactory outcomes. Conclusion:Coma is common in patients treated with bevacizumab combined with chemotherapy. This regimen should be used cautiously in patients with a history of hypertension. BP should be monitored closely and managed promptly during the combination therapy to prevent coma. RLPS-related coma is reversible after appropriate treatment.
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Objective To evaluate the tolerance and efficacy of nasogastric enteral nutrition (NGEN) in the treatment of severe acute pancreatitis (SAP). Methods PUBMED, Web of Science and The Cochrane Central Register of Controlled Trials from 1966 to 2011 (up to October) and Chinese Journals Full-text Database (CNKI), Database for Chinese Technical Periodicals (VIP) and Wanfang Digital Journal Full-text Database from 1978 to 2011 (up to October) were retrieved to collect clinical randomized controlled trials of NGEN to compare with nasojejunal enteral nutrition (NJEN) in the treatment of SAP. Two reviewers independently screened the literature for eligibility and evaluated the quality with confirmation of cross-check. Different opinions would be decided by the third party. Statistical analysis was performed by meta-analysis using Review Manager 4.2. Results Three randomized controlled trails including 159 patients with SAP met the inclusion criteria, involving 82 patients in NGEN group and 77 in NJEN group. There was no significant difference between NGEN and NJEN group in the risk of mortality of SAP (RR=0.69, 95%CI: 0.37-1.29, P=0.25), conversion to surgery (RR=2.09, 95% CI: 0.55-7.92, P=0.28), diarrhea subsequent to enteral nutrition (RR=1.43, 95% CI: 0.59-3.45, P=0.43), rate of tube displacement (RR=0.42, 95%CI: 0.08-2.17, P=0.30) and pain related with enteral nutrition (RR=0.94, 95%CI: 0.32-2.70, P=0.90). While compared with NJEN, the risk of infectious complications was lower than NGEN (RR=0.64, 95%CI: 0.42-0.99, P=0.04). Conclusion In enteral nutrition support of SAP, NGEN is comparable to NJEN in efficacy and tolerance, but the former has the lower rate of infectious complications and easier to operate, and there is a tendency of NEGN to replace the latter.
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Objective: To explore independent risk factors of coronary artery calcification (CAC) and analyze correlation among risk factors of CAC and serum osteopontin (OPN) level. Methods: According to results of 64-slice spiral computed tomography (MSCT) coronary angiography, a total of 65 patients were continuously enrolled and divided into CAC group (n=37) and non-CAC control group (n=28). Enzyme linked immunosorbent assay (ELISA) was used to measure serum level of OPN. Single factor and multiple factor Logistic regression analysis’s were used to analyze risk factors of CAC. Spearman’s straight line analysis was used to analyze correlation between risk factors of CAC and serum OPN. Results: 1、 The age, hypertension, diabetes, poor eating habits，lack of exercise, overweight, etc., which were independent risk factors of CAC （OR=3.47～12.96, P=0.018～0.003）by single factor Logistic regression analysis, were inducted to multiple factor Logistic regression analysis, its result showed that age, overweight, poor sleep quality, poor eating habits were independent risk factors of CAC, OR=35.31～5.17, P＜0.01～0.05; 2、Serum level of OPN in CAC group was significant higher than that of non-CAC control group ［(39.919±11.879) μg /L vs. (24.000±6.000) μg /L，P<0.01］; 3、The Spearman straight line correlation analysis indicated that serum level of OPN was correlated with risk factors of CAC : positively correlated with LDL-C, overweight, age, TC（r=0.487～0.286,P＜0.001～＜0.05）, and positively correlated with poor sleep quality, diabetes, poor eating habits, lack of exercise（r=4.10～2.24， P<0.01～0.05）; negatively correlated with HDL-C（r=-0.250,P＜0.05）. Conclusion: Correlation analysis indicates that age, overweight, poor sleep quality, poor eating habits etc. are independent risk factors of CAC；Serum OPN level is correlated with LDL-C, overweight，age, diabetes, lack of exercise etc., so these indicate that must decrease OPN level and risk factors of CAC to relieve CAC and slow down its development.
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<p><b>BACKGROUND AND OBJECTIVE</b>Oxaliplatin is one of the effective drugs for the treatment of advanced colorectal cancer (CRC). Oxaliplatin-induced allergic reactions in European and American patients have been reported, but in China there are only a few case reports. This study investigated the incidence rate and characteristics of oxaliplatin-induced allergic reactions in Chinese patients with CRC.</p><p><b>METHODS</b>Clinical data of 109 patients with advanced CRC receiving oxaliplatin plus capecitabine (the XELOX regimen) as first-line therapy were collected and analyzed retrospectively.</p><p><b>RESULTS</b>Of 109 patients, 13 (11.9%) patients had hypersensitivity. In 546 cycles, 23 (4.2%) cycles involved hypersensitivity. Grade-I,-II, and -III reactions were seen in 13 cycles, 8 cycles, and 2 cycles, respectively, and no grade-IV reaction was observed. Allergic reactions usually occurred at the median time during the fifth cycle (range, the 1st-8th cycle) of oxaliplatin-containing therapy, and the cumulative oxaliplatin dose was 1200 mg (range, 400-1600 mg). Symptoms associated with anaphylaxis appeared 5-360 min (median, 180 min) after oxaliplatin infusion, and were relieved after withdrawing the oxaliplatin infusion and treating with antiallergic drugs. A total of 8 patients continued to receive oxaliplatin therapy after prophylactic administration of antiallergic drugs, such as steroids, and 4 patients did not report persistent allergic reactions. Compared with men, oxaliplatin-induced allergic reactions were more commonly seen in women patients (P<0.05), while age, body surface area, performance status, tumor location, and pathologic type showed no significant difference.</p><p><b>CONCLUSION</b>Oxaliplatin-induced allergic reactions occurred in Chinese patients with CRC, and the incidence rate, occurrence time, degree of severity, and clinical outcome were consistent with literature published abroad.</p>
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Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Drug Therapy , Pathology , Adenocarcinoma, Mucinous , Drug Therapy , Pathology , Anaphylaxis , Drug Therapy , Anti-Allergic Agents , Therapeutic Uses , Antineoplastic Agents , Antineoplastic Combined Chemotherapy Protocols , Asian People , Capecitabine , Colorectal Neoplasms , Drug Therapy , Pathology , Deoxycytidine , Drug Hypersensitivity , Drug Therapy , Fluorouracil , Liver Neoplasms , Lung Neoplasms , Neoplasm Staging , Organoplatinum Compounds , Retrospective Studies , Sex FactorsABSTRACT
<p><b>OBJECTIVE</b>To elucidate the efficacy and probable prognostic factors of surgical resection of pulmonary metastasis from colorectal cancer.</p><p><b>METHODS</b>Clinical data and outcomes of 35 colorectal patients with pulmonary metastasis undergone pulmonary metastasectomy were analyzed retrospectively.</p><p><b>RESULTS</b>Median follow-up time was 48.0 months. The median overall survival time was 36.0 months. Five-year survival rate was 33.0%. Nineteen patients died of tumor progression. Sixteen patients were survival including survival with tumor (10 cases) and without tumor (6 cases). One patient was still alive without tumor for 164 months. Univariate analysis revealed that disease free interval (DFI) was a prognostic risk factor, while gender, age, primary tumor site, pulmonary metastasis size and location, surgical procedure, pre-surgical CEA level, re-metastasectomy did not show influence on the survival time after pulmonary metastasectomy.</p><p><b>CONCLUSIONS</b>For some selected patients with indication, pulmonary metastasectomy may be a potential curative method. DFI may be associated with the prognosis after pulmonary metastasectomy.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Colorectal Neoplasms , Mortality , Pathology , General Surgery , Lung Neoplasms , Mortality , General Surgery , Pneumonectomy , Prognosis , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
By using whole blood selenium, 24 hr urinary selenium and hair selenium contents as the indices of assessing human selenium status, it was found that the populations in the endemic areas of Keshan disease were practically in a selenium poor status. The selenium contents in locally grown staple grains and daily diets in the endemic areas were also lower than those in the non-endemic areas. In an area covering a cross section of Keshan disease geographic belt in our country, the hair selenium contents of agricultural populations were measured. The results indicated that all the hair selenium contents in the endemic sites were always at a lower level, whereas those in the non-endemic sites distant from the endemic areas were generally at a higher level; they decreased gradually until the endemic areas were reached; and finally, along the contiguous region of the endemic and non-endemic areas they were insignificantly different.The hair selenium contents among the agricultural populations were significantly lower than those among the non-agricultural ones in the same endemic areas. However, no regular correlation had been observed between the seasonal prevalence of Keshan disease and the variation of hair selenium contents in the same populations living in the same endemic sites.It is considered that the endemic areas of the disease seem to be a Se-deficiency belt, and Se-deficiency probably might be a pathogenic geo-gen in the prevalence of Keshan disease.