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The incidence and mortality rates of gastrointestinal (GI) cancer remain high. Despite constant improvements in diagnostic and therapeutic techniques, the early diagnosis, mid- and late-stage treatment, drug tolerance, and cancer recurrence and metastasis in GI cancer remain challenging. In this review article we summarize the recent research advance in the roles of keratins in GI cancer, with the hope that they will become efficient biomarkers for the prediction, diagnosis, or treatment of these malignancies.
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Humans , Biomarkers, Tumor , Gastrointestinal Neoplasms/therapy , KeratinsABSTRACT
As a new CRISPR/Cas-derived genome engineering technology, base editing combines the target specificity of CRISPR/Cas and the catalytic activity of nucleobase deaminase to install point mutations at target loci without generating DSBs, requiring exogenous template, or depending on homologous recombination. Recently, researchers have developed a variety of base editing tools in the important industrial strain Corynebacterium glutamicum, and achieved simultaneous editing of two and three genes. However, the multiplex base editing based on CRISPR/Cas9 is still limited by the complexity of multiple sgRNAs, interference of repeated sequence and difficulty of target loci replacement. In this study, multiplex base editing in C. glutamicum was optimized by the following strategies. Firstly, the multiple sgRNA expression cassettes based on individual promoters/terminators was optimized. The target loci can be introduced and replaced rapidly by using a template plasmid and Golden Gate method, which also avoids the interference of repeated sequence. Although the multiple sgRNAs structure is still complicated, the editing efficiency of this strategy is the highest. Then, the multiple gRNA expression cassettes based on Type Ⅱ CRISPR crRNA arrays and tRNA processing were developed. The two strategies only require one single promoter and terminator, and greatly simplify the structure of the expression cassette. Although the editing efficiency has decreased, both methods are still applicable. Taken together, this study provides a powerful addition to the genome editing toolbox of C. glutamicum and facilitates genetic modification of this strain.
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CRISPR-Cas Systems/genetics , Corynebacterium glutamicum/metabolism , Gene Editing , Plasmids , /metabolismABSTRACT
Objective: To analyze the clinical and genetic characteristics of clinical subtypes of non-obstructive hypertrophic cardiomyopathy (HCM). Methods: It was a cohort study. Patients with non-obstructive HCM admitted to Fuwai Hospital, Chinese Academy of Medical Sciences, from January 1999 to April 2019 were enrolled. According to the characteristics of cardiac morphology and function shown by echocardiography, the patients were divided into common type, dilated type, restricted type and reduced ejection fraction type. The clinical data of the patients were recorded, and 8 sarcomere pathogenic genes were screened by full exon sequencing or panel sequencing. Patienst were followed up and cardiovascular endpoint events were recorded. Results: A total of 815 patients with non-obstructive HCM were enrolled, including 27 (3.3%) restricted type, 51 (6.3%) dilated type, 30 (3.7%) reduced ejection fraction type and 707 (86.7%) common type. A total of 704 out of 815 patients underwent genetic testing. Among them, 299 (42.5%) patients carried at least 1 sarcomere gene mutation. MYBPC3 and MYH7 mutation accounted for 42.1% (126/299) and 35.8% (107/299) respectively. 66.7% (16/24) of the patients with restricted type carried sarcomere gene mutation, which was higher than that in patients with dilated type (36.4% (16/44)) and in common type (41.5% (250/602), P=0.015). Among the patients with reduced ejection fraction, 56.7% (17/30) patients carried sarcomere gene mutations, 23.3% (7/30) carried multiple sarcomere mutations, which was higher than that in restricted type (8.3% (2/24)), in dilated type (9.1% (4/44)) and in common type 4.2% ((24/577), P<0.001). MYH7 and MYBPC3 were the main mutation gene types of all clinical subtypes, and the genotypes were similar among groups (all P>0.05). Seven hundred and three out 815 patients were followed up for 2.9 (1.4, 4.0) years. There were 53(7.5%) cardiovascular death. Cardiovascular death occurred in 5.0% (29/578) patients with common type, 13.0% (3/23) patients with restricted type, 16.3% (7/43) patients with dilated type and 46.7% (14/30) patients with decreased ejection fraction. Univariate Cox proportional hazards model analysis showed that the risk of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type was higher than that in patients with common type (P<0.001). After adjusting for gender, age of onset, body mass index, history of hypertension, coronary heart disease and diabetes, multivariate Cox proportional hazards model analysis showed that the HR of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type were 5.454 (95%CI 1.137-26.157, P=0.034) and 6.597 (95%CI 1.632-26.667, P=0.008) and 9.028 (95%CI 2.201-37.039, P=0.002) respectively, as compared to patients with common type. Conclusions: Most of the patients with non-obstructive HCM are common type, featured by mild clinical manifestations and good prognosis. Although the proportion of restricted type and dilated type is relatively low, and cardiac systolic function is mostly preserved, the clinical phenotype and prognosis of these patients are similarly severe and poor as patients with reduced ejection fraction. The genotypes are similar in different clinical subtypes, but the proportion of patients with sarcomere gene mutation is higher in restricted type, and the proportion of patients with multiple sarcomere gene mutation is higher in decreased ejection fraction type.
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Humans , Cardiomyopathy, Hypertrophic/genetics , Cohort Studies , Mutation , Phenotype , Sarcomeres/geneticsABSTRACT
Objective To investigate the prevalence and risk factors of Blastocystis infections among primary school students in Jiangjin District, Chongqing City. Methods A cross-sectional questionnaire survey was conducted among students sampled from a primary school in Jiangjin District, Chongqing City on April, 2018, and their stool samples were collected for microscopic examinations, in vitro culture and PCR assays to analyze the prevalence of Blastocystis infections and subtype of the parasite. In addition, the risk factors of Blastocystis infections among primary school students were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 466 primary students were surveyed, and the subjects had a mean age of (9.81±1.66) years and included 236 males (50.64%) and 230 females (49.36%). The prevalence of Blastocystis infections was 15.24% (71/466) among the study students, and there was no significance difference in the prevalence between male and fe- male students (16.52% vs. 13.91%; χ2 = 0.616, P = 0.433). In addition, there was a significant difference in the prevalence of Blastocystis infections among grade 1 (6.35%, 4/63), grade 2 (5.17%, 3/58), grade 3 (21.74%, 15/69), grade 4 (25.30%, 21/83), grade 5 (10.19%, 11/108) and grade 6 students (20.00%, 17/85) (χ2 = 15.410, P = 0.009). There were four Blastocystis subtypes characterized (ST1, ST3, ST6 and ST7), in which ST6 was the most common subtype (45.07%, 32/71), followed by ST3 (25.35%, 18/71). Multivariate logistic regression analysis revealed that minority ethnicity [odds ratio (OR) = 4.259, 95% confidential inter- val (CI) : (1.161, 15.621)] and low maternal education level (primary school and below) [OR = 9.038, 95% CI: (1.125, 72.642)] were identified as risk factors of Blastocystis infection among primary school students in Jiangjin District, Chongqing City. Conclusions There is a high prevalence of Blastocystis infections detected among primary school students in Jiangjin District, Chongqing City, and ST6 and ST3 are predominant subtypes. Minority ethnicity and low maternal education level (primary school and below) are risk factors for Blastocystis infections in primary school students.
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Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.
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Objective To understand the prevalence and risk factors of Blastocystis hominis infection in inpatients in Jiangjin District, Chongqing City. Methods A cross-sectional study was conducted in a community hospital in Jiangjin District, Chongqing City, and the inpatients were surveyed by questionnaires. After obtaining the informed consent from the inpatients or legal guardians, the stool and blood samples were collected and examined by microscopy and PCR from April 17 to May 1, 2018. The univariate analysis and logistic regression analysis were used to analyze the risk factors of the B. hominis infection. Results A total of 198 hospitalized patients were investigated, and the infection rate of B. hominis was 10.61% (21/198), and the infection rate of the females (12.10%) was higher than that of the males (8.11%), but the difference was not statistically significant. The highest rate of infection was 19.23% in the age group of 10 to 20 years, followed by 17.74% in the age group of 60 years and above, and the lowest rate was 2.38% in the age group of 20 to 40 years. The difference in infection rates of B. hominis among the different age groups was statistically significant (P < 0.05). The infection rate of B. hominis in the people who used dry pail latrines was 33.30%, which was higher than that of the people who used water flush toilets (9.10%) (P < 0.05). The genotypes of B. hominis were ST1, ST3, ST6 and ST7, and ST6 and ST3 being the most predominant genotypes which accounted for 47.62% (10/21) and 38.10% (8/21) respectively, and among the infected males, the genotypes were only ST3 and ST6. The multiple logistic regression analysis showed that among the factors affecting B. hominis infection, only keeping pets was a risk factor [OR = 3.798, 95% CI (1.245, 11.581), P < 0.05]. Conclusion A high prevalence of B. hominis infection is found in the inpatients in Jiangjin District, Chongqing City, the predominant genotypes are ST6 and ST3, and keeping pets may be one of the main risk factors.
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Objective To understand the prevalence and risk factors of Blastocystis hominis infection in inpatients in Jiangjin District, Chongqing City. Methods A cross-sectional study was conducted in a community hospital in Jiangjin District, Chongqing City, and the inpatients were surveyed by questionnaires. After obtaining the informed consent from the inpatients or legal guardians, the stool and blood samples were collected and examined by microscopy and PCR from April 17 to May 1, 2018. The univariate analysis and logistic regression analysis were used to analyze the risk factors of the B. hominis infection. Results A total of 198 hospitalized patients were investigated, and the infection rate of B. hominis was 10.61% (21/198), and the infection rate of the females (12.10%) was higher than that of the males (8.11%), but the difference was not statistically significant. The highest rate of infection was 19.23% in the age group of 10 to 20 years, followed by 17.74% in the age group of 60 years and above, and the lowest rate was 2.38% in the age group of 20 to 40 years. The difference in infection rates of B. hominis among the different age groups was statistically significant (P < 0.05). The infection rate of B. hominis in the people who used dry pail latrines was 33.30%, which was higher than that of the people who used water flush toilets (9.10%) (P < 0.05). The genotypes of B. hominis were ST1, ST3, ST6 and ST7, and ST6 and ST3 being the most predominant genotypes which accounted for 47.62% (10/21) and 38.10% (8/21) respectively, and among the infected males, the genotypes were only ST3 and ST6. The multiple logistic regression analysis showed that among the factors affecting B. hominis infection, only keeping pets was a risk factor [OR = 3.798, 95% CI (1.245, 11.581), P < 0.05]. Conclusion A high prevalence of B. hominis infection is found in the inpatients in Jiangjin District, Chongqing City, the predominant genotypes are ST6 and ST3, and keeping pets may be one of the main risk factors.
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Objective To explore the clinical factors that can be used to predict the early weight loss after laparoscopic sleeve gastrectomy(LSG).Methods The clinical data of 64 obese patients undergoing LSG in Peking Union Medical College Hospital from August 2015 to January 2018 were retrospectively analyzed.We analyzed the relationship between different clinical factors and early weight loss,determined the independent predictors based on models,and estimated their test power by using the receiver operating characteristic(ROC)curves.Results Correlation analysis indicated that preoperative body mass index(=0.000,=0.000,=0.000),waist circumference(WC)(=0.000,=0.000,=0.000),whole body fat volume(=0.000,=0.006,=0.003),homeostatic model assessment for insulin resistance(HOMA-IR)(=0.000,=0.000,=0.002),and hypersensitive C-reactive protein(hsCRP)(=0.004,=0.002,=0.025)were negatively correlated with excess weight loss percentage(EWL %) after 3,6 and 12 months.Also,hsCRP after 6 months showed negative correlation with EWL % after 1 year(=0.029).Binary Logistic regression analysis showed that WC was an independent predictor of early weight loss(=0.018).ROC analysis showed that when the optimal cutoff value is 142.5 cm for WC, index was highest,with a sensitivity of 80% and a specificity of 87%.Patients were further divided into low WC group and high WC group based on this optimal cutoff value.The low WC group had significantly higher EWL% than the high WC group 3 months(=6.677,=0.000),6 months(=6.157,=0.000),and 1 year(=4.006,=0.000)after surgery.The low WC group also had significantly lower hsCRP than high WC group 6 months after surgery(=-3.510,=0.000).HOMA-IR showed no significant difference between these two groups(=-0.821,=0.412).Conclusions WC is an independent predictor of weight loss early after LSG.The patients with low WC have better weight loss effectiveness.
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Humans , Body Mass Index , C-Reactive Protein , Gastrectomy , Insulin Resistance , Laparoscopy , Obesity, Morbid , General Surgery , Retrospective Studies , Treatment Outcome , Waist Circumference , Weight LossABSTRACT
Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract and respond poorly to conventional radiochemotherapy.Complete excision is the only possible way to cure GISTs.Although targeted therapy is effective for GISTs,multiple and/or secondary mutations of KIT or PDGFRA gene have lead to increased drug resistance and disease relapse.A variety of tumor infiltrating immune cells and complex immune microenvironments have been found in GISTs.Many immune cells participate in the occurrence and development of GISTs and play key roles in targeted therapy.The feasibility and effectiveness of immunotherapy for GISTs have been well demonstrated in preclinical and clinical studies.
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Humans , Gastrointestinal Stromal Tumors , Allergy and Immunology , Therapeutics , Immunotherapy , Mutation , Proto-Oncogene Proteins c-kit , Genetics , Receptor, Platelet-Derived Growth Factor alpha , Genetics , Tumor MicroenvironmentABSTRACT
Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
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Animals , Male , Angiotensin I , Metabolism , Antioxidants , Pharmacology , Blood Pressure , Hypertension , Drug Therapy , Oxidative Stress , Paraventricular Hypothalamic Nucleus , Peptide Fragments , Metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species , Metabolism , Sodium Chloride, Dietary , PharmacologyABSTRACT
Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.
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Animals , Male , Rats , Antioxidants , Therapeutic Uses , Arterial Pressure , Hypertension , Drug Therapy , Infusions, Intraventricular , Metformin , Pharmacology , Neurotransmitter Agents , Metabolism , Oxidative Stress , Paraventricular Hypothalamic Nucleus , Reactive Oxygen Species , Metabolism , Sodium Chloride, Dietary , PharmacologyABSTRACT
This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bilirubin , Blood , Coronary Disease , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacokinetics , Metabolic Clearance Rate , Models, Biological , Phenanthrenes , Blood , PharmacokineticsABSTRACT
OBJECTIVE@#To compare the correlation between musculoskeletal ultrasound features, dysfunction and X-ray findings in patients with knee osteoarthritis, and to analyze the pathological mechanism of soft tissue inflammation in knee osteoarthritis.@*METHODS@#Cross-sectional method was performed in this research (Evidence level: III). The patients with knee osteoarthritis were collected according to the screening criteria from September 2016 to January 2017 in Orthopedic clinic in our hospital. Musculoskeletal ultrasound and X-ray images were obtained and measured, knee function was measured by Lysholm scale. Pearson coefficient, t test and Wilcoxon were applied to analyze the correlation between soft tissue inflammation, knee dysfunction and X-ray features.@*RESULTS@#Total 123 patients with knee osteoarthritis were recruited in this research. Soft tissue inflammation around knee had a high incidence in patients with knee osteoarthritis (infrapatellar fat pad inflammation 81%), and the synovial membrane thickness, joint effusion depth and meniscus bulging were beyond the normal range. Correlation analysis showed that the about Lysholm score and joint effusion depth had negative correlations with "Squat" score(=-0.21, =0.02). and Medial meniscus bulging had negative correlations with "Sustain" score(=-0.26, <0.01) and Lysholm total score (=-0.19, =0.04). Lateral meniscus bulging had a negative correlation with "Unstable" score (=-0.22, =0.02). The X-ray features, and medial joint space narrow had negative correlations with joint effusion depth(=-0.27, <0.01) and synovial membrane thickness(=-0.17, =0.007), and had a positive correlation with medial meniscus bulging. Medial joint space narrow was significantly correlated with patellar ligament inflammation and fat pad inflammation(<0.05). Lateral joint space narrow was significantly correlated with patellar ligament inflammation(=0.02).@*CONCLUSIONS@#Soft tissue inflammation around the knee-a major pathological manifestation of knee osteoarthritis, has significant correlations with knee dysfunction and bony structure lesions, and affects the progression of knee osteoarthritis by damaging knee joint function and promoting the destruction of articular cartilage.
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Humans , Cartilage, Articular , Cross-Sectional Studies , Knee Joint , Menisci, Tibial , Osteoarthritis, KneeABSTRACT
Objective: To investigate the mechanical properties of the novel compound calcium phosphate cement (CPC) biological material as well as the biological activity and osteogenesis effects of induced pluripotent stem cells (iPS) seeding on scaffold and compare their bone regeneration efficacy in cranial defects in rats. Methods: Ac- cording to the different scaffold materials, the experiment was divided into 4 groups: pure CPC scaffold group (group A), CPC∶10% wt chitosan as 2∶1 ratio mixed scaffold group (group B), CPC∶10% wt chitosan∶whisker as 2∶1∶1 ratio mixed scaffold group (group C), and CPC∶10% wt chitosan∶whisker as 2∶1∶2 ratio mixed scaffold group (group D). Mechanical properties (bending strength, work-of-fracture, hardness, and modulus of elasticity) of each scaffold were detected. The scaffolds were cultured with fifth generation iPS-mesenchymal stem cells (MSCs), and the absorbance ( A) values of each group were detected at 1, 3, 7, and 14 days by cell counting kit 8 (CCK-8) method; the alkaline phosphatase (ALP) activity, Live/Dead fluorescence staining and quantitative detection, ALP, Runx2, collagen typeⅠ, osteocalcin (OC), and bone morphogenetic protein 2 (BMP-2) gene expressions by RT-PCR were detected at 1, 7, and 14 days; and the alizarin red staining were detected at 1, 7, 14, and 21 days. Twenty-four 3-month-old male Sprague Dawley rats were used to establish the 8 mm-long skull bone defect model, and were randomly divided into 4 groups ( n=6); 4 kinds of scaffold materials were implanted respectively. After 8 weeks, HE staining was used to observe the repair of bone defects and to detect the percentage of new bone volume and the density of neovascularization. Results: The bending strength, work-of-fracture, hardness, and modulus of elasticity in groups B, C, and D were significantly higher than those in group A, and in groups C, D than in group B, and in group D than in group C ( P0.05). Live/Dead fluorescence staining showed that the proportion of living cells in groups B, C, and D at 7 and 14 days was significantly higher than that in group A ( P0.05). RT-PCR showed that the relative expressions of genes in groups B, C, and D at 7 and 14 days were significantly higher than those in group A, and in groups C, D than in group B ( P0.05). Alizarin red staining showed that the red calcium deposition on the surface of scaffolds gradually deepened and thickened with the prolongation of culture time; the A values in groups B, C, and D at 14 and 21 days were significantly higher than those in group A ( P0.05). In vivo repair experiments in animals showed that the new bone in each group was mainly filled with the space of scaffold material. Osteoblasts and neovascularization were surrounded by new bone tissue in the matrix, and osteoblasts were arranged on the new bone boundary. The new bone in groups B, C, and D increased significantly when compared with group A, and the new bone in groups C and D was significantly higher than that in group B. The percentage of new bone volume and the density of neovascularization in groups B, C, and D were significantly higher than those in group A, and in groups C and D than in group B ( P0.05). Conclusion: The mechanical properties of the new reinforced composite scaffold made from composite chitosan, whisker, and CPC are obviously better than that of pure CPC scaffold material, which can meet the mechanical properties of cortical bone and cancellous bone. iPS-MSCs is attaching and proliferating on the new reinforced composite scaffold material, and the repair effect of bone tissue is good. It can meet the biological and osteogenic activity requirements of the implant materials in the bone defect repair.
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AIM:To observe the effect of central prostaglandin E2(PGE2) on sympathetic activation in chronic heart failure (CHF) and to explore the underlying mechanism. METHODS:Male SD rats were subjected to coronary ar-tery ligation to induce heart failure (HF), and the intracerebroventricular infusion was performed by osmotic pump continu-ously. The rats in sham group and HF group were given artificial cerebrospinal fluid (0. 25 μL/h). The rats in HF plus treatment group was given celecoxib (CLB; 20 mg/h). After 4 weeks, the levels of PGE2 in cerebrospinal fluid ( CSF), the sympathetic nerve excitability and cardiac function were measured, and the changes of corticotropin-hormone releasing hormone ( CRH)-containing neurons activation and neurotransmitter contents in the hypothalamic paraventricular nucleus ( PVN) were also determined. RESULTS:Compared with the sham-operated rats, the HF rats had raised level of PGE2 in CSF, up-regulated renal sympathetic nerve activity and plasma norepinephrine, increased left ventricular end diastolic pres-sure, lung-to-body weight and right ventricular-to-body weight ratios, and decreased maximal increase and decreased rate of left ventricular pressure (P<0.05). In addition, the number of CRH positive neurons in PVN and the level of plasma ad-renocorticotropic hormone were higher in HF rats than those in sham-operated rats (P<0.05). After administration of CLB into the lateral ventricle of HF rats, the contents of PGE2 in CSF were significantly reduced, the number of activation CRH neurons in PVN was decreased, the excitability of sympathetic nerves was down-regulated and cardiac function was im-proved (P<0.05). Compared with the sham-operated rats, the content of glutamic acid in PVN of HF rats was increased, the content of γ-aminobutyric acid and the number of glutamate decarboxylase 67-positive neurons were decreased ( P<0.05). After the CLB was given, the above indexes were reversed (P<0.05). CONCLUSION:These findings indicate that in CHF, the increased central PGE2 may activate CRH-containing PVN neurons and contribute to the augmented sym-pathetic drive possibly by modulating the neurotransmitters within the PVN.
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Objective To develop a new algorithm to reconstruct the distribution of acoustic sources of magnetoacoustic tomography with magnetic induction(MAT-MI)in the acoustic inhomogeneous media,which is developed on the basis of generalized finite element method (GFEM) and modified time inversion algorithm. Methods The acoustic and acoustic coupling theory and the basic equations of acoustics were used to study the forward and inverse problems of the acoustic inhomogeneous concentric sphere magneticacoustic coupling model. The solution of acoustic non-uniform media wave equation based on GFEM was proposed.The method solved the problem of acoustically inhomogeneous media sound source reconstruction and conductivity reconstruction.At the same time,the distribution of velocity was reconstructed by rotating the pairs of transducers and the time reversal algorithm. Results The proposed algorithm could accurately reconstruct the acoustic source distribution in acoustic inhomogeneous media,and could obtain the distribution of sound velocity during the reconstruction of sound source and recover the image well. Conclusion The proposed algorithm had its feasibility and effectiveness verified,and gains advantages in MAT-MI reconstruction of acoustic inhomogeneous media.
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<p><b>OBJECTIVE</b>To investigate the relationship between living habit and cervical instability in adolescent patients with neck pain.</p><p><b>METHODS</b>Fifty-nine adolescent patients with neck pain(neck pain group) and seventeen healthy teenagers (control group) were recruited and divided into two groups, and clinical information, living habit were collected. In addition, all people were taken lateral, hyperextension and hyperflexion radiography to analyze relationship between living habit and cervical instability.</p><p><b>RESULTS</b>There was no obvious difference in age, height, weight and body mass index between two groups. The neck pain group using cellphone time per day is longer than control group, while control group had more exercise time than neck pain group(<0.01). The incidence of instability in neck pain group was significantly higher than that in control group(<0.01). In hyperflexion, angular displacement(AD) of neck pain group in vertebral body between C₃-C₄, C₄-C₅ and C₅-C₆ was significantly higher than that of control group. In neck pain group, AD of hyperflexion was higher than that of hyperextension on C₄-C₅(<0.01), and AD of hyperextension is higher than that of hyperflexion on C₆-C₇(<0.05). In neck pain group, AD of hyperextension on C₄-C₅ was positively correlated with time of using cellphone every day(=0.275, =0.035). And AD of hyperflexion was significantly positive correlated with time of using cellphone(=0.577, <0.001), but was negatively correlated with exercise time(=-0.279, =0.032). The AD of hyperflexion on C₅-C₆ was negatively correlated with exercise time every day(=-0.292, =0.025), AD of hyperextension was negatively correlated with time of using computer every day(=-0.262, =0.045).</p><p><b>CONCLUSIONS</b>Adolescent neck pain patients had more time to use cellphone than normal teens every day, and exercise time is less than healthy teenagers, and occurrence rate of cervical instability is higher on C₃-C₄, C₄-C₅, C₅-C₆ segment. The longer daily exercise time, the smaller C₄-C₅ and C₅-C₆ AD values; the longer cellphone usage every day, the greater C4-C5 AD values.</p>
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Bariatric/metabolic surgery is the most effective method to treat morbid obesity and its complications. Tracing its origin back to jejunoileal bypass in 1950s, bariatric/metabolic surgery has been continuously improved after more than 60 years of development. At present, the mainstream surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion/duodenal switch, and mini gastric bypass. In addition, new procedures such as single-anastomosis duodenal switch, duodenal-jejunal bypass with sleeve gastrectomy, laparoscopic greater curvature plication and endoscopic surgeries have been developed. This article reviews the history, status quo, and prospects of bariatric/metabolic surgery.
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Objective To analyze the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) in treating obesity and its co-morbidities.Methods The clinical data of obese patients undergoing LSG in Peking Union Medical College Hospital from August 2012 to August 2017 were retrospectively analyzed. Medium-term outcome measures included excess weight loss (%EWL),co-morbidity improvement,and complications.Results Seventy-five obese patients comprising 28 men[ body mass index(BMI):(47.3±7.5)kg/m ) ] and 47 women [BMI (41.1±7.0) kg/m ] were enrolled in this analysis. The common co-morbidities were liver dysfunction (53.3%),dyslipidemia (52.0%),obstructive sleep apnea (45.3%),type 2 diabetes mellitus (38.7%),and arterial hypertension (37.3%),which were improved by 75.0%,58.3%,83.3%,75.0% and 58.3% three years after surgery. The mean %EWL at 1,2,and 3 years after surgery was 81.6±34.7,80.9±30.2 and 79.7±30.8,respectively. The proportions of patients achieving successful weight loss were 81.7% (n=49),81.0% (n=34),and 79.3% (n=23) at 1,2,and 3 years (%EWL>50%). Early severe complications (Clavien-Dindo classification>2) occurred in 2.6% of patients,and the most common late complications was gastroesophageal reflux disease,which could be relieved by acid suppressants.Conclusion LSG is effective and safe in treating obesity and its co-morbidities.
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Objective To investigate the depression status and quality of life (QoL) of patients with severe obesity who have undergone bariatric surgery and to evaluate their potential correlation.Methods A total of 50 patients with severe obesity who had undergone elective bariatric surgery in the general surgical ward of Peking Union Medical College from January 2013 to December 2017 were enrolled in this study. The general data were collected. The patient's depression status and QoL were assessed by the Zung's Depression Self-Assessment Scale and the SF-36 Quality of Life Scale,respectively.Results The depression score was (44.85±9.07) scores in these 50 patients,including 38 patients (76%) without depression and 12 (24%) with mild depression. The scores of the mental-emotional,physical,psychomotor,and psychological barrier dimensions of patients with severe obesity were (3.70±1.25),(18.65±4.10),(4.25±1.35),and (18.75±5.46)scores,respectively. The physiological function score of patients with mild depression was (95.83±10.21)scores,which was significantly higher than those without depression (68.42±38.95) scores(F=6.209,P=0.011). The vitality and mental health scores were (46.67±14.72) and (57.33±14.68) scores in patients with mild depression,which were significantly lower than those [(65.79±21.94) (F=4.867,P=0.030) and (75.16±17.21) scores (F=0.212,P=0.032)] in patients without depression. Correlation analysis showed that the mental-emotional score was positively correlated with physical score in patients with severe obesity (r=0.503,P=0.015),whereas the depression score was negatively correlated with the general health status (r=-0.430,P=0.032),vitality (r=-0.594,P=0.002),social functioning (r=-0.455,P=0.022),mental health (r=-0.562,P=0.003),and QoL score (r=-0.439,P=0.028).Conclusions The QoL is remarkably affected by depression in patients with severe obesity before surgery. Assessment of the mental status of patients with severe obesity may help to identify this problem and thus improve the QoL.