Objective To study the impact of lung volume reduction surgery on inflammatory factors, pulmonary function and quality of life in patients with severe chronic obstructive pulmonary emphysema. Methods 57 cases patients with severe chronic obstructive pulmonary emphysema received lung volume reduction surgery from May 2009 to December 2013 were divided into observation group 32 cases and control group 25 cases, the control group were given open chest surgery, the observation group received video-assisted thoracoscopic surgery. Then compare the operation indicator, serum inflammatory factor content, pulmonary function and life quality score between the two groups. Results Operation indicators: Observation group: Intraoperative blood loss, thoracic drainage, hospital stay were significantly lower than that in control group (P< 0.05); Inflammatory factor: 3 d after surgery, observation group serum TNF-α, IL- 6, IL- 1 content were significantly lower than that in control group (P<0.05);Pulmonary function: 12 months after surgery, there were no statistical difference of FEV1, TLC, RV between two groups (P>0.05); SGRQ score: 12 weeks after the surgery, observation group respiratory symptoms, activity ability, disease im﹣pact, SGRQ total score were significantly lower than the control group (P< 0.05). Conclusion Video assisted tho﹣racic surgery helps to reduce surgical trauma, and alleviate inflammatory reaction, then improve the quality of life.

Objective To research the activated brain areas of decision making under uncertainty reward processing on healthy volunteers.Method The E-Prime programs were presented 3 kinds of tasks of the decision under uncertain reward processing.15 right-handed healthy volunteers made a response after receiving the task.At the same time,the GE 3.0T magnetic resonance scanner scanned the brains areas of subjects.Individual analysis and group analysis was done with SPM8 software,then the brain activating regions and the peak intensity were gotten.Results Orbitofrontal cortex was activated in certainty,peak intensity 2.4328 ± 0.1949 (P ＜ 0.05).Prefrontal cortex,occipital lobe,parietal lobe,posterior lobe of cerebellum,limbic lobe and midbrain were activated under the risk reward processing,peak intensity 2.4228 ± 1.3762 (P ＜ 0.05).When under ambiguity reward processing,prefrontal cortex,temporal lobe,occipital lobe,left inferior frontal gyrus and posterior lobe of cerebellum were activated,peak intensity 2.4056 ± 0.4222 (P ＜ 0.05).Compared with the task under certainty,posterior lobe of cerebellum,gyri subtemporalis and gyri fusiformis,inferior parietal lobule,anterior central convolution,orbitofrontal cortex,ventrolateral prefrontal cortex,both frontopolar and supramarginal gyrus were activated in task under risk (P ＜0.05) ;and both frontopolar were activated in task under ambiguity (P ＜ 0.05).Compared with the task under risk,dorsolateral prefrontal cortex and posterior lobe of cerebellum were activated in task under ambiguity (P ＜ 0.05).Conclusion There are differences in different types of reward processing of decision making.

Objective:To investigate the effects of GnRH agonist on the expressions of FSHR proteins in pituitary and ovaries in ewes,also to analyse the bioinformatics characteristics of ovine pituitary FSHR.Methods: Forty-two prepubertal ewes (Ovis aries) were randomly assigned to six groups (n=7).The ewes in experimental group EG-Ⅰ,EG-Ⅱand EG-Ⅲwere subcutaneously injected with 200μg,300μg and 400 μg alarelin antigens twice (at day 0 and 14),respectively.Ewes in EG-Ⅳand EG-Ⅴwere injected sub-cutaneously with 200μg and 300μg alarelin antigen four times (at day 0,7,14 and 21),respectively.Ewes in the control group (CG) were subcutaneously injected with 2.0 ml solvent twice (at day 0 and 14).Fluorescence quantitative RT-PCR was used to detect gene expression of FSHR in pituitary glands.The expression of FSHR protein in the ovaries was detected using Western blot.Results:The 2-ΔΔCt values of GnRHR,FSHR and LHR mRNAs in the pituitary gland of EG were lower than that in control group (CG).The 2-ΔΔCt values in EG-Ⅳ( P<0.05 ) and EG-Ⅴ( P<0.05 ) were lower than those in EG-Ⅰand EG-Ⅱ.Expressions of FSHR proteins in EG ovaries increased.Levels of FSHR proteins in EG-Ⅳand EG-Ⅴ( P<0.05 ) were higher than CG.The length of sheep FSHR sequence of nucleotides were 1 091 bp,the homology of FSHR sequences was 100% with that reported in NCBI.The theory isoelectric point , half-life,unstable index,fat index,hydrophobic average were respectively 1.2 h,5.05,47.75,0.836 and 30.61.Conclusion:Alarelin active immunization can inhibit the expression of FSHR mRNA in the pituitary gland ,but increase FSHR expression in ovarian of ewes.FSHR is an unstable hydrophobic protein.

Recent evidence indicates that the voltage clock (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. However, the relative importance of the voltage clock and Ca2+ clock for pacemaking was not revealed in sick sinus syndrome. Previously, we mapped the intracellular calcium (Cai) and membrane potentials of the normal intact SAN simultaneously using optical mapping in Langendorff-perfused canine right atrium. We demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with robust late diastolic Cai elevation (LDCAE) during beta-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic sarcoplasmic reticulum (SR) Ca2+ release and was closely related to heart rate changes. In contrast, in pacing induced canine atrial fibrillation and SAN dysfunction models, Ca2+ clock of SAN was unresponsiveness to beta-adrenergic stimulation and caffeine. Ryanodine receptor 2 (RyR2) in SAN was down-regulated. Using the prolonged low dose isoproterenol together with funny current block, we produced a tachybradycardia model. In this model, chronically elevated sympathetic tone results in abnormal pacemaking hierarchy in the right atrium, including suppression of the superior SAN and enhanced pacemaking from ectopic sites. Finally, if the LDCAE was too small to trigger an action potential, then it induced only delayed afterdepolarization (DAD)-like diastolic depolarization (DD). The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis. We conclude that dysfunction of both the Ca2+ clock and the voltage clock are important in sick sinus syndrome.
Animals ; Arrhythmia, Sinus/physiopathology ; Atrial Fibrillation/physiopathology ; Bradycardia/physiopathology ; Calcium/*physiology ; Calcium Channels/*physiology ; Dogs ; Humans ; Sick Sinus Syndrome/physiopathology ; Sinoatrial Node/physiology/*physiopathology

Recent evidence indicates that the voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. Since the intact SAN is a heterogeneous structure that includes multiple different cell types interacting with each other, the relative importance of the voltage and Ca2+ clocks for pacemaking may be variable in different regions of the SAN. Recently, we performed optical mapping in isolated and Langendorff-perfused canine right atria. We mapped the intracellular calcium (Cai) and membrane potentials of the intact SAN simultaneously. Using previously described criteria of the timing of the late diastolic Cai elevation (LDCAE) relative to the action potential upstroke to detect Ca2+ clock activity, we demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with the robust LDCAE during beta-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic SR Ca2+ release and was closely related with heart rate changes. We conclude that the Ca2+ and voltage clocks work synergistically to generate SAN automaticity.
Action Potentials ; Calcium ; Heart Rate ; Membrane Potentials ; Membranes ; Sarcoplasmic Reticulum ; Sinoatrial Node ; Sympathetic Nervous System

Background: Community-acquired pneumonia (CAP) is the most important cause of hospitalisation in Malaysia and the 6th most important cause of mortality in patients aged 65 years and above. CAP is a lower respiratory tract infection that includes signs and symptoms like cough, fever, dyspnoea, the presence of new focal chest signs and new radiographic shadowing with no prior cause. To assist clinical judgement in deciding whether to admit the patient for in-ward treatment or otherwise, the severity of CAP is most commonly graded using the CURB-65 score as the components are more readily accessible in the Accidents and Emergency Department. We believe that cardiopulmonary diseases, immunosuppressive diseases like HIV infection or diabetes mellitus and other co-morbidities may affect the severity of CAP and are thus aspects of a patients’ history that should play a more significant role in influencing a clinician’s judgement of CAP severity. The general objective of the study is therefore to identify the relationship between co-morbidities and initial severity assessment of a patient admitted for community acquired pneumonia. The 3 specific objectives are i) to determine if presence of co-morbidities affects initial severity assessment in a patient admitted with CAP ii) To identify which co-morbidities affects initial severity assessment and iii) to determine whether having multiple co-morbidities increases initial severity assessment. Methodology: A retrospective study was carried out from the month of February 2013 to July 2013 at Hospital Tuanku Ja’afar, Seremban (HTJS). Patients admitted to the four Medical wards – 6A, 6B, 7A, and 7B – from July 2012 to December 2012 and have been diagnosed with CAP were chosen. A checklist was used as a survey instrument. Using statistical analysis, the severity of CAP in patients was compared in patients with different factors like gender, different co-morbidities and the number of co-morbidities. Results: A total of 63 patients in the control group had no co-morbidities and 54 patients were of low risk, 7 patients had moderate risk, and 2 patients had high risk CAP. Of the remaining 337 patients in the sample population, 124 patients had one co-morbidity, while 213 patients had multiple co-morbidities. Among those with a single co-morbidity, 100 patients had low risk, 19 patients had moderate risk, and 5 patients had high risk CAP. For the group with multiple co-morbidities, 135 patients had low risk, 58 patients had moderate risk, and 20 patients had high risk CAP. This study found that the presence and number of co-morbidities present in a patient affected the severity of CAP. Co-morbidities like diabetes mellitus, hypertension and asthma had significant correlation to the severity of CAP in patients. The gender of the patient had no significant correlation to the severity of CAP. Conclusion: The presence and number of co-morbidities present in a patient increases the severity of CAP. Hypertension, diabetes mellitus, and asthma are comorbidities that are prerequisites for increased caution and alert when judging the severity of CAP in patients. Comparison of patients with single and multiple comorbidities showed that patients in the latter group present with higher severity scores (p-value = 0.004).
Morbidity

BACKGROUND AND OBJECTIVES: Recent studies showed that, in addition to parasympathetic nerves, cervical vagal nerves contained significant sympathetic nerves. We hypothesized that cervical vagal nerve stimulation (VNS) may capture the sympathetic nerves within the vagal nerve and activate the stellate ganglion. MATERIALS AND METHODS: We recorded left stellate ganglion nerve activity (SGNA), left thoracic vagal nerve activity (VNA), and subcutaneous electrocardiogram in seven dogs during left cervical VNS with 30 seconds on-time and 30 seconds off time. We then compared the SGNA between VNS on and off times. RESULTS: Cervical VNS at moderate (0.75 mA) output induced large SGNA, elevated heart rate (HR), and reduced HR variability, suggesting sympathetic activation. Further increase of the VNS output to >1.5 mA increased SGNA but did not significantly increase the HR, suggesting simultaneous sympathetic and parasympathetic activation. The differences of integrated SGNA and integrated VNA between VNS on and off times (DeltaSGNA) increased progressively from 5.2 mV-s {95% confidence interval (CI): 1.25-9.06, p=0.018, n=7} at 1.0 mA to 13.7 mV-s (CI: 5.97-21.43, p=0.005, n=7) at 1.5 mA. The difference in HR (DeltaHR, bpm) between on and off times was 5.8 bpm (CI: 0.28-11.29, p=0.042, n=7) at 1.0 mA and 5.3 bpm (CI 1.92 to 12.61, p=0.122, n=7) at 1.5 mA. CONCLUSION: Intermittent cervical VNS may selectively capture the sympathetic components of the vagal nerve and excite the stellate ganglion at moderate output. Increasing the output may result in simultaneously sympathetic and parasympathetic capture.
Animals ; Autonomic Nervous System ; Dogs* ; Electrocardiography ; Heart Rate ; Stellate Ganglion* ; Vagus Nerve Stimulation*

BACKGROUNDMuch is known about the cytogenetic lesions that characterize multiple myeloma (MM) patients from the USA, Europe, and East Asia. However, little has been published about the disease among Southeast Asians. The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population.

METHODSForty-five newly-diagnosed, morphologically confirmed patients comprising 18 males and 27 females, aged 46 - 84 years (median 65 years) were investigated by karyotyping and fluorescence in situ hybridization (FISH). FISH employing standard panel probes and 1p36/1q21 and 6q21/15q22 probes was performed on diagnostic bone marrow samples.

RESULTSThirty-four cases (75.6%) had karyotypic abnormalities. Including FISH, a total detection rate of 91.1% was attained. Numerical and complex structural aberrations were common to both hyperdiploid and non-hyperdiploid patients. Numerical gains of several recurring chromosomes were frequent among hyperdiploid patients while structural rearrangements of several chromosomes including 8q24.1 and 14q32 characterized non-hyperdiploid patients. With FISH, immunoglobulin heavy chain (IGH) gene rearrangements, especially fibroblast growth factor receptor 3 (FGFR3)/IGH and RB1 deletion/monosomy 13 were the most common abnormalities (43.4%). Amplification 1q21 was 10 times more frequent (42.5%) than del(1p36) and del(6q21).

CONCLUSIONSWe have successfully reported the comprehensive cytogenetic profiling of a cohort of newly-diagnosed myeloma patients in our population. This study indicates that the genetic and cytogenetic abnormalities, and their frequencies, in our study group are generally similar to other populations.

Aged ; Aged, 80 and over ; Chromosome Aberrations ; Cytogenetics ; Female ; Humans ; Immunoglobulin Heavy Chains ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Monosomy ; genetics ; Multiple Myeloma ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 3 ; genetics ; Retinoblastoma Protein ; genetics ; Singapore

Objective:To examine the expression of core clock genes in the peripheral blood mononuclear cells (PBMCs) and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis (CP) patients with pancreatic exocrine insufficiency (PEI), and explore their potential diagnostic value in clinical practice.Methods:The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected. Peripheral blood samples from 30 healthy individuals were used for control. The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP. The mRNA expression of the core clock genes, including Clock, Bmal1, Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR, and the expression of circadian disturbance-related proteins like TrkB, CD 36 and Rbp in serum was measured with ELISA. The receiver operating characteristic curve(ROC) and the area under curve (AUC) was used to test the efficiency for diagnozing PEI. Results:The mRNA expression of Per1 in CP patients was significantly decreased (0.76 vs 1, P<0.05), and the AUC for diagnozing PEI was 0.744 (95% CI 0.628-0.860), with a cut-off value of 0.72; and the sensitivity and specificity was 84.8% and 57.1%, respectively. The protein abundance of serum CD 36 was significantly increased in CP patients (33.85±19.74ng/ml vs 24.71±11.53 ng/ml, P<0.05); the AUC for diagnozing PEI was 0.834 (95% CI 0.735-0.932), with a cut-off value of 29.75 pg/ml; and the sensitivity and specificity was 74.3% and 84.8%, respectively. The expression of CD 36 was increased with the increase of CP clinical stage, and there were statistically significant differences between either two stages (all P value <0.05). The mRNA expression of Per1 in patients with CP in Stage Ⅰ was significantly higher than that in patients with CP in Stage Ⅱ or Ⅲ, and the differences were statistically significant ( P<0.05), but no statistical difference was found between Stage Ⅱ and Stage Ⅲ. Conclusions:The decreased expression of Per1 mRNA in PBMCs and increased level of CD 36 in serum are significantly related to the occurrence of PEI in CP, suggesting that they may have potential value for diagnozing PEI and guiding the clinical practice.

INTRODUCTION: The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome. METHODS: Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses. RESULTS: The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively. CONCLUSION The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.