Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine...Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.展开更多
AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.M...AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.展开更多
BACKGROUND Enteral nutrition(EN)is essential for critically ill patients.However,some patients will have enteral feeding intolerance(EFI)in the process of EN.AIM To develop a clinical prediction model to predict the r...BACKGROUND Enteral nutrition(EN)is essential for critically ill patients.However,some patients will have enteral feeding intolerance(EFI)in the process of EN.AIM To develop a clinical prediction model to predict the risk of EFI in patients receiving EN in the intensive care unit.METHODS A prospective cohort study was performed.The enrolled patients’basic information,medical status,nutritional support,and gastrointestinal(GI)symptoms were recorded.The baseline data and influencing factors were compared.Logistic regression analysis was used to establish the model,and the bootstrap resampling method was used to conduct internal validation.RESULTS The sample cohort included 203 patients,and 37.93%of the patients were diagnosed with EFI.After the final regression analysis,age,GI disease,early feeding,mechanical ventilation before EN started,and abnormal serum sodium were identified.In the internal validation,500 bootstrap resample samples were performed,and the area under the curve was 0.70(95%CI:0.63-0.77).CONCLUSION This clinical prediction model can be applied to predict the risk of EFI.展开更多
BACKGROUND:Swallowing disorder is a common clinical symptom that can lead to a series of complications,including aspiration,aspiration pneumonia,and malnutrition.This study aimed to investigate risk factors of post-ex...BACKGROUND:Swallowing disorder is a common clinical symptom that can lead to a series of complications,including aspiration,aspiration pneumonia,and malnutrition.This study aimed to investigate risk factors of post-extubation dysphagia(PED)in intensive care unit(ICU)patients with endotracheal intubation,and to develop a risk-predictive model for PED,which could serve as an assessment tool for the prevention and control of PED.METHODS:Patients retrospectively selected from June to December 2021 in a tertiary hospital served as the derivation cohort.Patients recruited from the same hospital from March to June 2022served as the external validation cohort for the predictive model.We used a combination of variable screening and least absolute shrinkage and selection operator(LASSO)regression to select the most useful candidate predictors and checked the multicollinearity of independent variables using the variance inflation factor method.Multivariate logistic regression analysis was performed to calculate the odds ratio(OR;95%confidence interval[95%CI])and P-value for each variable to predict diagnosis.The screened risk factors were introduced into R software to build a nomogram model.The performance of the model,including discrimination ability,calibration,and clinical benefit,was evaluated by plotting the receiver operating characteristic(ROC),calibration,and decision curves.RESULTS:A total of 305 patients were included in this study.Among them,235 patients(53PED vs.182 non-PED)were enrolled in the derivation cohort,while 70 patients(17 PED vs.53 nonPED)were enrolled in the validation cohort.The independent predictors included age,pause of sedatives,level of consciousness,activities of daily living(ADL)score,nasogastric tube,sore throat,and voice disorder.These predictors were used to establish the predictive nomogram model.The model demonstrated good discriminative ability,and the area under the ROC curve(AUC)was 0.945(95%CI 0.904-0.970).Applying the predictive model to the validation cohort demonstrated good discrimination with an AUC of 0.907(95%CI 0.831-0.983)and good calibration.The decision-curve analysis of this nomogram showed a net benefit of the model.CONCLUSION:A predictive model that incorporates age,pause of sedatives,level of consciousness,ADL score,nasogastric tube,sore throat,and voice disorder may have the potential to predict PED in ICU patients.展开更多
AIM: To assess the relationship between the P268S, JW1 and N852S polymorphisms and Crohn’s disease (CD) susceptibility in Zhuang patients in Guangxi, China.
BACKGROUND Joint,skin,oral cavity,and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset.The cases of ulcerative colitis with dermatomyositis(...BACKGROUND Joint,skin,oral cavity,and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset.The cases of ulcerative colitis with dermatomyositis(DM)are rare.In this study,we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab.CASE SUMMARY The patient was a 57-year-old female with a 2-year history of DM.The patient was admitted to hospital with abdominal pain,diarrhea,and blood in stool lasting for more than 2 mo.Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum.Pathological sections showed chronic inflammatory cell infiltration,especially neutrophil infiltration,in the colonic mucosa;therefore,the patient was diagnosed with ulcerative colitis.Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM,but its effect was unsatisfactory.The patient’s discomfort was relieved after infliximab treatment.CONCLUSION Infliximab can improve DM in the treatment of ulcerative colitis.Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.展开更多
The ears are air-filled structures that are directly impacted during blast exposure.In addition to hearing loss and tinnitus,blast victims often complain of vertigo,dizziness and unsteady posture,suggesting that blast...The ears are air-filled structures that are directly impacted during blast exposure.In addition to hearing loss and tinnitus,blast victims often complain of vertigo,dizziness and unsteady posture,suggesting that blast exposure induces damage to the vestibular end organs in the inner ear.However,the underlying mechanisms remain to be elucidated.In this report,single vestibular afferent activity and the vestibuloocular reflex(VOR)were investigated before and after exposure to blast shock waves(~20 PSI)delivered into the left external ear canals of anesthetized rats.Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure.Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents.Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5e2Hz.Blast exposure,however,resulted in few changes in the VOR responses to sinusoidal head rotation and translation.To the best of our knowledge,this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model.These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.展开更多
AIM: To study the polymorphisms of toll-like receptor 4 (TLR4) gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp and susceptibility to inflammatory bowel disease (IBD) in the Zhuang population from Guangxi,...AIM: To study the polymorphisms of toll-like receptor 4 (TLR4) gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp and susceptibility to inflammatory bowel disease (IBD) in the Zhuang population from Guangxi, China. METHODS: A case-control study was performed from February 2007 to October 2011 which included 146 Zhuang patients with IBD in the experimental group and 164 healthy Zhuang subjects who acted as the control group. All patients and healthy subjects were from the Guangxi Zhuang Autonomous Region of China. Genomic DNA was extracted from intestinal tissue by the phenol chloroform method. TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp were amplified by polymerase chain reaction (PCR), and then detected by PCR-restriction fragment length polymorphism (RFLP). RESULTS: The TLR4 gene Asp299Gly was digested using Nco Ⅰ restriction enzyme, and a single band of 249 bp was observed which showed that it was a wild type (AA). The TLR4 gene Thr399Ile was digested using Hinf Ⅰrestriction enzyme and only the wild type (CC) was detected. In addition, the TLR2 gene Arg-677Trp was digested using Aci Ⅰ restriction enzyme and only the wild type (CC) was detected. The TLR2 gene Arg753Gln was digested using Pst Ⅰ restriction enzyme. Only the wild type (GG) as a single band of 254 bp was observed during RFLP. Overall, no heterozygous or homozygous single nucleotide polymorphism mutations were found in patients with Crohn's disease and ulcerative colitis both in the TLR4 gene Asp299Gly, Thr399Ile and the TLR2 gene Arg677Trp, Arg753Gln in the Zhuang population from the Guangxi Zhuang Autonomous Region of China. CONCLUSION: The TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp polymorphisms may not be associated with IBD in the Zhuang population from the Guangxi Zhuang Autonomous Region of China.展开更多
Blast overpressure has become an increasing cause of brain injuries in both military and civilian populations. Though blast＇s direct effects on the cochlea and vestibular organs are active areas of study, little atte...Blast overpressure has become an increasing cause of brain injuries in both military and civilian populations. Though blast＇s direct effects on the cochlea and vestibular organs are active areas of study, little attention has been given to the ear＇s contribution to the overall spectrum of blast injury. Acute auto- nomic responses to blast exposure, including bradycardia and hypotension, can cause hypoxia and contribute to blast-induced neurotrauma. Existing literature suggests that these autonomic responses are elicited through blast impacting the thorax and lungs. We hypothesize that the unprotected ear also provides a vulnerable locus for blast to cause autonomic responses. We designed a blast generator that delivers controlled overpressure waves into the ear canal without impacting surrounding tissues in order to study the ear＇s specific contribution to blast injury. Anesthetized adult rats＇ left ears were exposed to a single blast wave ranging from 0 to 110 PSI （0-758 kPa）. Blast exposed rats exhibited decreased heart rates and blood pressures with increased blast intensity, similar to results gathered using shock tubes and whole-body exposure in the literature. While rats exposed to blasts below 50 PSI （345 kPa） exhibited increased respiratory rate with increased blast intensity, some rats exposed to blasts higher than 50 PSI （345 kPa） stopped breathing immediately and ultimately died. These autonomic responses were significantly reduced in vagally denervated rats, again similar to whole-body exposure literature. These results support the hypothesis that the unprotected ear contributes to the autonomic responses to blast.展开更多
基金supported by the Natural Science Foundation of Liaoning Province,China(Grant No.:2023-MS-172).
文摘Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.
基金Supported by National Natural Science Foundation of ChinaNo.81460114+5 种基金Natural Science Foundation of Guangxi Zhuang Autonomous RegionNo.1355005-3-2 and No.2012GXNSFAA053143Chinese Traditional Medicine Science Foundation of Guangxi Zhuang Autonomous RegionNo.GZPT1238Science Foundation of Guangxi Department of EducationNo.201203YB036 and No.2013LX031
文摘AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.
文摘BACKGROUND Enteral nutrition(EN)is essential for critically ill patients.However,some patients will have enteral feeding intolerance(EFI)in the process of EN.AIM To develop a clinical prediction model to predict the risk of EFI in patients receiving EN in the intensive care unit.METHODS A prospective cohort study was performed.The enrolled patients’basic information,medical status,nutritional support,and gastrointestinal(GI)symptoms were recorded.The baseline data and influencing factors were compared.Logistic regression analysis was used to establish the model,and the bootstrap resampling method was used to conduct internal validation.RESULTS The sample cohort included 203 patients,and 37.93%of the patients were diagnosed with EFI.After the final regression analysis,age,GI disease,early feeding,mechanical ventilation before EN started,and abnormal serum sodium were identified.In the internal validation,500 bootstrap resample samples were performed,and the area under the curve was 0.70(95%CI:0.63-0.77).CONCLUSION This clinical prediction model can be applied to predict the risk of EFI.
文摘BACKGROUND:Swallowing disorder is a common clinical symptom that can lead to a series of complications,including aspiration,aspiration pneumonia,and malnutrition.This study aimed to investigate risk factors of post-extubation dysphagia(PED)in intensive care unit(ICU)patients with endotracheal intubation,and to develop a risk-predictive model for PED,which could serve as an assessment tool for the prevention and control of PED.METHODS:Patients retrospectively selected from June to December 2021 in a tertiary hospital served as the derivation cohort.Patients recruited from the same hospital from March to June 2022served as the external validation cohort for the predictive model.We used a combination of variable screening and least absolute shrinkage and selection operator(LASSO)regression to select the most useful candidate predictors and checked the multicollinearity of independent variables using the variance inflation factor method.Multivariate logistic regression analysis was performed to calculate the odds ratio(OR;95%confidence interval[95%CI])and P-value for each variable to predict diagnosis.The screened risk factors were introduced into R software to build a nomogram model.The performance of the model,including discrimination ability,calibration,and clinical benefit,was evaluated by plotting the receiver operating characteristic(ROC),calibration,and decision curves.RESULTS:A total of 305 patients were included in this study.Among them,235 patients(53PED vs.182 non-PED)were enrolled in the derivation cohort,while 70 patients(17 PED vs.53 nonPED)were enrolled in the validation cohort.The independent predictors included age,pause of sedatives,level of consciousness,activities of daily living(ADL)score,nasogastric tube,sore throat,and voice disorder.These predictors were used to establish the predictive nomogram model.The model demonstrated good discriminative ability,and the area under the ROC curve(AUC)was 0.945(95%CI 0.904-0.970).Applying the predictive model to the validation cohort demonstrated good discrimination with an AUC of 0.907(95%CI 0.831-0.983)and good calibration.The decision-curve analysis of this nomogram showed a net benefit of the model.CONCLUSION:A predictive model that incorporates age,pause of sedatives,level of consciousness,ADL score,nasogastric tube,sore throat,and voice disorder may have the potential to predict PED in ICU patients.
基金Supported by Guangxi Graduate Education Innovation Project Fund,No.YCSZ2012035the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.0832009,No.2012GXNSFAA053143Traditional Chinese Medicine Science Fund of Guangxi Zhuang Autonomous Region,China,No.GZPT1238
文摘AIM: To assess the relationship between the P268S, JW1 and N852S polymorphisms and Crohn’s disease (CD) susceptibility in Zhuang patients in Guangxi, China.
基金the National Natural Science Foundation of China,No.81860104 and 81460114the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2017GXNSFAA198299+2 种基金the Development and Application of Medical and Health Appropriate Technology Project in Guangxi Zhuang Autonomous Region,No.S2018049the Youth Science Foundation of Guangxi Medical University,No.GXMUYSF201913 and GXMUYSF201908the Self-financing Project of Health Commission of Guangxi Zhuang Autonomous Region,No.Z20200398。
文摘BACKGROUND Joint,skin,oral cavity,and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset.The cases of ulcerative colitis with dermatomyositis(DM)are rare.In this study,we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab.CASE SUMMARY The patient was a 57-year-old female with a 2-year history of DM.The patient was admitted to hospital with abdominal pain,diarrhea,and blood in stool lasting for more than 2 mo.Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum.Pathological sections showed chronic inflammatory cell infiltration,especially neutrophil infiltration,in the colonic mucosa;therefore,the patient was diagnosed with ulcerative colitis.Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM,but its effect was unsatisfactory.The patient’s discomfort was relieved after infliximab treatment.CONCLUSION Infliximab can improve DM in the treatment of ulcerative colitis.Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.
文摘The ears are air-filled structures that are directly impacted during blast exposure.In addition to hearing loss and tinnitus,blast victims often complain of vertigo,dizziness and unsteady posture,suggesting that blast exposure induces damage to the vestibular end organs in the inner ear.However,the underlying mechanisms remain to be elucidated.In this report,single vestibular afferent activity and the vestibuloocular reflex(VOR)were investigated before and after exposure to blast shock waves(~20 PSI)delivered into the left external ear canals of anesthetized rats.Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure.Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents.Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5e2Hz.Blast exposure,however,resulted in few changes in the VOR responses to sinusoidal head rotation and translation.To the best of our knowledge,this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model.These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.
基金Supported by The Natural Science Foundation of Guangxi Zhuang Autonomous Region, China, No. 0832009the Chinese Traditional Medicine Science Foundation of Guangxi Zhuang Autonomous Region, China, No. GZKZ10-108
文摘AIM: To study the polymorphisms of toll-like receptor 4 (TLR4) gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp and susceptibility to inflammatory bowel disease (IBD) in the Zhuang population from Guangxi, China. METHODS: A case-control study was performed from February 2007 to October 2011 which included 146 Zhuang patients with IBD in the experimental group and 164 healthy Zhuang subjects who acted as the control group. All patients and healthy subjects were from the Guangxi Zhuang Autonomous Region of China. Genomic DNA was extracted from intestinal tissue by the phenol chloroform method. TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp were amplified by polymerase chain reaction (PCR), and then detected by PCR-restriction fragment length polymorphism (RFLP). RESULTS: The TLR4 gene Asp299Gly was digested using Nco Ⅰ restriction enzyme, and a single band of 249 bp was observed which showed that it was a wild type (AA). The TLR4 gene Thr399Ile was digested using Hinf Ⅰrestriction enzyme and only the wild type (CC) was detected. In addition, the TLR2 gene Arg-677Trp was digested using Aci Ⅰ restriction enzyme and only the wild type (CC) was detected. The TLR2 gene Arg753Gln was digested using Pst Ⅰ restriction enzyme. Only the wild type (GG) as a single band of 254 bp was observed during RFLP. Overall, no heterozygous or homozygous single nucleotide polymorphism mutations were found in patients with Crohn's disease and ulcerative colitis both in the TLR4 gene Asp299Gly, Thr399Ile and the TLR2 gene Arg677Trp, Arg753Gln in the Zhuang population from the Guangxi Zhuang Autonomous Region of China. CONCLUSION: The TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp polymorphisms may not be associated with IBD in the Zhuang population from the Guangxi Zhuang Autonomous Region of China.
基金supported by the United States National Institutes of Health[grant numbers:NIDCD R01DC014930(WZ),NIDCD R01DC012060(HZ)]
文摘Blast overpressure has become an increasing cause of brain injuries in both military and civilian populations. Though blast＇s direct effects on the cochlea and vestibular organs are active areas of study, little attention has been given to the ear＇s contribution to the overall spectrum of blast injury. Acute auto- nomic responses to blast exposure, including bradycardia and hypotension, can cause hypoxia and contribute to blast-induced neurotrauma. Existing literature suggests that these autonomic responses are elicited through blast impacting the thorax and lungs. We hypothesize that the unprotected ear also provides a vulnerable locus for blast to cause autonomic responses. We designed a blast generator that delivers controlled overpressure waves into the ear canal without impacting surrounding tissues in order to study the ear＇s specific contribution to blast injury. Anesthetized adult rats＇ left ears were exposed to a single blast wave ranging from 0 to 110 PSI （0-758 kPa）. Blast exposed rats exhibited decreased heart rates and blood pressures with increased blast intensity, similar to results gathered using shock tubes and whole-body exposure in the literature. While rats exposed to blasts below 50 PSI （345 kPa） exhibited increased respiratory rate with increased blast intensity, some rats exposed to blasts higher than 50 PSI （345 kPa） stopped breathing immediately and ultimately died. These autonomic responses were significantly reduced in vagally denervated rats, again similar to whole-body exposure literature. These results support the hypothesis that the unprotected ear contributes to the autonomic responses to blast.
