[Esophageal dysmotility detection in patients with gastroesophageal reflux-related cough and its influence on the efficacy of anti-reflux therapy].

Objective: To investigate the characteristics of esophageal dysmotility in patients with an initial diagnosis of acid/non-acid gastroesophageal reflux-related cough (GERC), and its correlation with the therapeutic response to anti-reflux treatments to search for the useful indicators to screen patients with chronic cough suitable for anti-reflux therapy. Methods: A total of 173 patients with suspicious GERC who attended the Chronic Cough Specialist Clinic of Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University between June 2020 and December 2022 were retrospectively selected for the study. The age of the patients was (45.1±14.6) years old, including 87 males and 86 females. Their demographic characteristics, clinical manifestations, and the results of high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH) were collected. Information on the etiological identification process and final diagnosis was also recorded. The recruited cases were grouped according to therapeutic outcomes and divided into cases with a favourable response to conventional anti-reflux treatment, cases with a favourable response to intensified anti-reflux treatment, and cases with no response to anti-reflux treatment. Factors influencing the efficacy of anti-reflux treatment were investigated. Differences between groups were compared using the χ2 test, Student-Newman-Keuls test, and Kruskal-Wallis H(K) test, where applicable. Logistic regression analysis using forward stepwise regression based on maximum likelihood estimation was used to screen for influence factors. Results: The 175 patients with suspicious GERC included 45 (26.0%) patients who responded to conventional anti-reflux treatment, 54 (31.2%) who responded to intensified anti-reflux treatment and 74 (42.8%) who did not respond to anti-reflux therapies. Esophageal dysmotility was present in 52.0% of patients (90/173), but was less common in patients who responded to conventional anti-reflux treatment (χ2=8.09, P=0.018). Although the majority of reflux episodes were non-acid (136/173, 78.6%), the proportion of acid reflux (χ2=19.49, P<0.001) and acid exposure time (H=11.04, P=0.004) were significantly higher in patients who responded to conventional anti-reflux treatment. The patients with acid and non-acid GERC had comparable proportion of esophageal dysmotility (64.9% vs. 48.5%, χ2=3.11, P=0.078), with a shorter break [2.4 (0.7, 5.6) cm vs. 6.1 (1.4, 10.0) cm, Z=-2.39, P=0.017], longer upper esophageal sphincter [(4.1±0.9) cm vs. (3.7±1.3) cm, t=-2.09, P=0.038], higher percentage of normal esophageal contractions [60.0% (17.8%, 90.0%) vs. 30.0% (0, 80.0%), Z=-2.14, P=0.032], and lower percentage of large break [10.0% (0, 40.0%) vs. 50.0% (0, 100.0%), Z=-2.92, P=0.004] in the patients with non-acid GERC. The mean resting pressure of the lower esophageal sphincter was significantly lower (H=7.49, P=0.024), while the percentage of ineffective esophageal contractions was markedly higher (H=8.60, P=0.014) in the patients who responded to intensified anti-reflux treatment and in the patients who did not respond to the anti-reflux therapies. Multifactorial logistic regression analysis identified the percentage of ineffective contraction as an independent factor predicting the efficacy of conventional anti-reflux treatment, with a cut-off value of≤45% and a moderate predictive value (AUC=0.67, P=0.004). Conclusions: Esophageal dysmotility is common in GERC patients with different characteristics in acid and non-acid GERC. The percentage of ineffective esophageal contraction may be a useful indicator for selecting an anti-reflux strategy and predicting treatment outcomes.

[Analysis on monitoring results of occupational hazards in Yangzhou city from 2014 to 2018].

Objective: To undersand the monitor of occupational hazards in the enterprises in the past 5 years, as well as the distribution of occupational disease hazards and their dynamic changes in their respective jurisdictions, for providing scientific basis for prevention and control of occupational diseases in relevant departments. Methods: Taking the method of cluster sampling, select the monitoring results of the occupational disease hazard factors commissioned by the Municipal Center for Disease Control and Prevention from 2014 to 2018 and the annual monitoring data of the network of the occupational hazard declaration system of the Safety Supervision Bureau, using chi-square test, trend Statistical analysis was performed by chi-square test or Fisher exact probability method. Results: There were 461 testing companies in the past 5 years, with a total of 15, 186 monitoring points and 43428 samples. The pass rate was 94.32% (14324/15186) . The pass rate was increasing year by year from 2014 to 2017 (P<0.05) ; The pass rate of various occupational disease hazards surveillance were greater than 90% except the rate of physical factors. In 2014, the qualified rate of physical factors was the lowest, which was 86.99% (1558/1791) ; the production rate of different production scale enterprises in 2018 was higher than that of 2014. From 2014 to 2018, the number of inspection enterprises and the number of inspection points of the joint-stock economy and state-owned economic enterprises are both high, 58 (10091 points) and 71 (1830 points) respectively; The qualified rate of state-owned economy and collective economy monitoring is high, 98.36% (1800/1830) and 100% (74/74) respectively. It had reached more than 95%; The enterprises tested mainly from the economic development zone and Guangling, respectively accounting for 34.27% (158/461) and 33.84% (156/461) of the total number of enterprises. Which followed by the Hanjiang, accounting for 23.21% of the total number of enterprises (107/461) ; The monitoring enterprises were mainly distributed in the manufacturing and power industries, which accounted for 85.25% (393/461) and 6.07% (28/461) of the total number of enterprises, respectively. Conclusion: The monitoring rate of enterprises had been increasing year by year from 2014 to 2018. Noise was the main disease prevention and controlling factor in the area.In addition, micro-enterprises, individual economy and foreign-invested economy were the key targets for occupational health.

Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-a [11C]MP4A PET study.

OBJECTIVE: To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed. RESULTS: Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p < 0.05, p < 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p < 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000). CONCLUSIONS: Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD.

[Current application and limitations of augmented reality in the stomatology].

Computer-assisted technology are gradually integrated into dental education and clinical treatment. As a cutting-edge technology in computer-aided medicine, augmented reality can not only be used as an aid to dental education by presenting three-dimensional scenes for teaching demonstration and experimental skills training, but also can superimpose virtual image information of patients onto real lesion areas for real-time feedback and intraoperative navigation. This review explores the current applications and limitations of augmented reality in dentistry to provide a reference for future research.

Invasive pulmonary fungal infections in children with severe human adenovirus type 7 pneumonia: A retrospective study.

BACKGROUND: There has been a rapid increase in the number of human adenovirus type 7 (HAdV-7) and invasive pulmonary fungal infections (IPFIs) co-infection. METHODS: In this study, we included patients with confirmed HAdV-7 infection during the period from 2018 to 2019 to explore clinical characteristics of severe HAdV-7 pneumonia combined with IPFIs. RESULTS: Among the 143 patients, 35 cases were co-infected with IPFIs. Others were assigned to the control group (n Z 108). Patients wereprone to be complicated with respiratory failure, heart failure and hemophagocytic syndromein IPFIs group. Thirty-one species of fungi were detected in the IPFIs group, among whichAspergillus was the most common species. Compared to control group, patients had lowerlevels of WBC, CD3þ T lymphocyte counts and CD19þ B lymphocyte counts in IPFIs group. CONCLUSION: Aspergillus is the most common species in IPFIs combined with severe HAdV-7 pneumonia. For children with severe HAdV-7 pneumonia who are younger, have a long course of disease, and have been admitted to the ICU, we should predict the occurrence of IPFIs when there is multi-system dysfunction and the reduction of CD3+ T lymphocyte counts and CD19+ B lymphocyte counts in course of their disease.

LncRNA PCAT6 aggravates the progression of bladder cancer cells by targeting miR-513a-5p.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been demonstrated to play critical roles in tumorigenesis of bladder cancer (BC). Our research aimed to explore the underlying mechanisms of lncRNA prostate cancer-associated transcript 6 (PCAT6) in BC. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain reaction (RT-qPCR) was used to measure the levels of PCAT6 and miR-513a in BC tissues and cells. The Kaplan-Meier analysis was utilized to evaluate the overall survival time of BC patients. Besides, cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion were evaluated by wound healing and transwell assays. Furthermore, starBase and Dual-Luciferase reporter assay were used to determine the interaction between PCAT6 and miR-513a in BC cells. RESULTS: PCAT6 expression was upregulated, while miR-513a was downregulated in BC tissues and cell lines. BC patients with high expression of PCAT6 exhibited a shorter overall survival time compared with those patients with low expression of PCAT6. Moreover, PCAT6 knockdown notably suppressed cell progression. In addition, PCAT6 inhibited miR-513a expression through direct interaction, and the silencing of PCAT6 remarkably increased the expression of miR-513a. Finally, the knockdown of miR-513a partly abolished PCAT6 silencing-induced inhibitory effects on BC progression. CONCLUSIONS: Our study illustrated that PCAT6 knockdown inhibited cell progression of BC by regulating miR-513a, suggesting that PCAT6 might act as a prognostic biomarker and therapeutic target for BC patients.

Production cross sections of radioisotopes from 3He-particle induced nuclear reactions on natural titanium.

Excitation functions were measured using the stacked-foil method for the natTi(3He,x)44mSc, 46m+gSc, 47Sc, 48Sc, 48V and 48Cr nuclear processes up to 68MeV. Our new cross-section data were compared with the earlier reported values as well as the evaluated theoretical predictions by means of the TALYS 1.6 code as compiled in the TENDL-2015 library. The new data show acceptable agreement with the previous experimental values in the overlapping energy regions, however only a partial agreement was found in the case of the results of the nuclear reaction model code. The present work not only strengthens the experimental datasets of the above processes but also provides new cross-section values above 36MeV where only one dataset is available for each reaction.

Interleukin-10 does not modulate clopidogrel platelet response in mice.

UNLABELLED: ESSENTIALS: It is unclear whether interleukin-10 (IL-10) could affect clopidogrel metabolism and response. The bioactivation of and response to clopidogrel were determined between mice with or without IL-10. Maximum clopidogrel active metabolite levels were the major driver of platelet response to clopidogrel. IL-10 did not modulate maximum levels of clopidogrel active metabolite and its antiplatelet effects. BACKGROUND: Elevated plasma interleukin-10 (IL-10) levels were observed in patients who responded less to clopidogrel (a prodrug that is required for further metabolic bioactivation in the liver). However, no data are currently available suggesting whether there is such an association. OBJECTIVE: To systematically explore possible differences in the formation of and response to clopidogrel active metabolite (CAM) in mice with or without IL-10 gene expression. METHODS: A single oral dose of clopidogrel (10 mg kg(-1)) was given to IL-10 knockout (KO) mice and wild-type (WT) control mice, respectively, and pharmacokinetic parameters of clopidogrel and CAM were calculated. Moreover, adenosine diphosphate-induced whole-blood platelet aggregation was measured in mice receiving 0, 5, 10, or 20 mg kg(-1) of clopidogrel, respectively. RESULTS: Compared with IL-10 KO mice, WT mice had significantly lower area under the plasma concentration-time curve (AUC) of CAM as a result of a shorter mean elimination half-life but had significantly higher AUC of clopidogrel due to slower systemic clearance and smaller volume of distribution. Although AUC of CAM was significantly lower in WT mice than in KO mice, antiplatelet effects of clopidogrel did not differ significantly between the two mouse groups, as their maximum plasma concentrations (Cmax ) of CAM were not significantly different. CONCLUSIONS: IL-10 expression level affects AUC rather than Cmax of CAM, but the Cmax of CAM is the major driver of antiplatelet effects of clopidogrel in mice.

Cigarette smoke mediates epigenetic repression of miR-217 during esophageal adenocarcinogenesis.

Although microRNAs (miRs) have been implicated in the pathogenesis of various human malignancies, limited information is available regarding mechanisms by which these noncoding RNAs contribute to initiation and progression of tobacco-induced esophageal cancers. In this study, array and quantitative reverse transcriptase-PCR techniques were used to examine miR expression in immortalized esophageal epithelia (IEE) and esophageal adenocarcinoma (EAC) cells cultured in normal media with or without cigarette smoke condensate (CSC). Under relevant exposure conditions, CSC significantly decreased miR-217 expression in these cells. Endogenous levels of miR-217 expression in cultured EAC cells (EACC)/primary EACs were significantly lower than those observed in IEE/ paired normal esophageal tissues. RNA crosslink immunoprecipitation, quantitative reverse transcriptase-PCR (qRT-PCR) and immunoblot experiments demonstrated direct interaction of miR-217 with kallikrein 7 (KLK7), encoding a putative oncogene not previously implicated in EAC. Repression of miR-217 correlated with increased levels of KLK7 in primary EACs, particularly those from smokers. Chromatin and methylated DNA immunoprecipitation experiments demonstrated that CSC-mediated repression of miR-217 coincided with DNMT3b-dependent hypermethylation and decreased occupancy of nuclear factor 1 within the miR-217 genomic locus. Deoxyazacytidine induced miR-217 expression and downregulated KLK7 in EACC; deoxyazacytidine also attenuated CSC-mediated miR-217 repression and upregulation of KLK7 in IEE and EACC. Overexpression of miR-217 significantly decreased, whereas overexpression of KLK7 increased proliferation, invasion and tumorigenicity of EACC. Collectively, these data demonstrate that epigenetic repression of miR-217 contributes to the pathogenesis of EAC via upregulation of KLK7 and suggest that restoration of miR-217 expression may be a novel treatment strategy for these malignancies.

Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans.

We performed in vitro and in vivo assays of the metabolism of [(11)C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [(11)C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [(11)C]Ro15-4513 in the blood was metabolized to hydrolysate [(11)C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [(11)C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [(11)C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats.

[Scanning electron microscopical observations on Pagumogonimus skrjabini metacercaria and juveniles].

The present paper reports on the results of scanning electron microscopical observations on seven excysted metacercariae and twelve juveniles of Pagumogonimus skrjabini. The former were from the naturally excysted metacercariae in fresh water in Ningquang District of Shaanxi Province and the latter were collected from the dogs and rats experimentally infected with metacercariae from the District mentioned above. Both excysted metacercariae and juveniles have tegumental ridges or folds on the surface of the body. The anterior two-thirds of the body surface are covered with many dome-shaped sensory papillae. There are rings of this kind of papillae on the rim of oral and ventral suckers. The papillae being obviously in decreasing number in the 30-40-day-old juveniles and adult worms. Except for the suckers and excretory pores, the whole body surface of the metacercariae and the juveniles are covered with posteriorly pointing tegumental spines which are relatively denser in the forebody than in the hindbody. Spines around the oral sucker are bayonet-shaped, and those on the rest part of the body surface are basically chisel-shaped. The authors considered it important that spines of P. skrjabini can be arranged singly or in groups.

[Some problems concerning the population thought in the Ming and Quing dynasties].

PIP: After the middle of the Ming dynasty, the Chinese feudal system began to show some influence of capitalism in its production models. Changes began to take place in its political and economic systems. In 1723, a new method of household taxation was adopted to replace the traditional taxation system, which had been based upon the population of each household. Under the new system, taxation was based upon the size of the land each household owned. As a result of this change, the population showed rapid growth. Intellectuals began to form the concept of curbing excessive population growth. They also began to pay attention to the problems of adequate material supplies, overpopulation, and possible solutions. Chinese intellectuals and scholars of the late Ming and Qing dynasties, including Xu Guangqi, Hong Liangji, Wang Shifeng, and Xue Fucheng realized the serious nature of population growth. In fact, the population figure doubledever 30 years on a regular basis. The rapid population growth caused a decline in the living standard, higher prices for consumer goods, unemployment, a decline in the population quality, and social disorders. Hong Liangji suggested that natural disasters such as floods and droughts could help reduce the population, and that improvement in agriculture, emigration, and tax reductions could promote production. Wang Shifeng was in favor of using severe laws and restrictions on marriage to control population. Xue Fucheng proposed the idea of imitating Western countries to develop capitalism and industries and increase employment opportunities to reduce the pressure of the rapid population growth.^ieng

In vivo binding properties of [carbonyl-11C]WAY-100635: effect of endogenous serotonin.

[Carbonyl-(11)C]WAY-100635 has been reported to be a useful ligand for the investigation of 5-HT(1A) receptor imaging in vivo. However, the cellular distribution and the influence of endogenous serotonin (5-HT) on in vivo binding have not been fully examined. In this study, we investigated the effect of 5,7-dihydroxytryptamine-produced destruction of 5-HT neurons, reserpine-induced 5-HT depletion, and fenfluramine-induced 5-HT increase on [carbonyl-(11)C]WAY-100635 binding in vivo. There was no significant change in the uptake of [carbonyl-(11)C]WAY-100635 in the slice of 5-HT denervated rat brain except in the raphe nucleus, where 5-HT cell bodies exist. There was no obvious effect of enhanced 5-HT release by fenfluramine or decreased release by reserpine on [carbonyl-(11)C]WAY-100635 binding in the dissected brain region. No significant effect was observed in the time course of [carbonyl-(11)C]WAY-100635 in the hippocampus and frontal cortex measured by PET. These results indicated that the in vivo binding of [carbonyl-(11)C]WAY-100635 in the hippocampus and cerebral cortex mainly reflects postsynaptic 5-HT(1A) receptor binding, and that this binding is not sensitive to endogenous 5-HT.

A prodrug of NMDA/glycine site antagonist, L-703,717, with improved BBB permeability: 4-acetoxy derivative and its positron-emitter labeled analog.

4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.