A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson's disease (PD). However, the mechanisms underlying these links remain to be defined. Here, we investigated the impact of deregulation of intestinal dopamine D2 receptor (DRD2) signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration. Dopamine/dopamine signaling in the mouse colon decreased with ageing. Selective ablation of Drd2, but not Drd4, in the intestinal epithelium, caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge, and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota. Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential. This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival. These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects* ; Animals ; Disease Models, Animal ; Dopamine ; Dopaminergic Neurons/metabolism* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Neuroprotection ; Parkinson Disease ; Pyrrolidines ; Receptors, Dopamine D2/metabolism* ; Substantia Nigra ; Succinates

Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.

Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.

Objective To study the application value of dynamic monitoring of blood pressure in the prevention and treatment of elderly hypertension. Methods 519 hypertensive patients from December 2017 to December 2018 were monitored with ambulatory blood pressure monitoring, and were divided into the elderly group (≥60 years old, 264 cases) and the control group (<60 years old, 255 cases). The results of ambulatory blood pressure monitoring in two groups were analyzed, which inclued the circadian rhythm of blood pressure, blood pressure, pulse pressure, coefficient of variation of blood pressure, blood pressure load value, average heart rate and morning blood pressure surge. Results The incidence of abnormal circadian rhythm of ambulatory blood pressure in the elderly group was 76.5%. Compared with the control group, there were differences in the indexes of diastolic blood pressure (DBP), diastolic blood pressure load value (DBPLV), pulse pressure (PP), 24 h average heart rate (24 hAHR), systolic blood pressure coefficient of variation (SBPCV), 24 h diastolic blood pressure coefficient of variation (24 h DBPCV) and morning diastolic blood pressure surge (MDBPS) between the two groups(all P<0.05). There were differences in 24 h systolic blood pressure (24hSBP), night systolic blood pressure (nSBP), night diastolic blood pressure (nDBP), night pulse pressure (nPP), day systolic blood pressure load value (dSBPLV), ninght systolic blood pressure load value (nSBPLV), 24 h SBPCV, 24 h dDBPCV and other indicators among different blood pressure types in the elderly group (all P<0.05). Conclusion Ambulatory blood pressure monitoring indicators have important guiding value for the prevention and treatment of elderly hypertension.

Objective To compare the genetic diversity of imported Plasmodium falciparum by Polyα and TAA87 microsatellite markers in Southeast Asian and African geographical isolates. Methods Ninety-two and 126 filter paper samples from patients infected with P. falciparum from Southeast Asia (Myanmar) and Africa (Ghana) were collected, respectively. Two neutral microsatellite loci, Polyα and TAA87 were amplified by PCR. The length of PCR fragments was detected by capillary electrophoresis. The allele frequency and expected heterozygosity (He) were calculated by Excel 2010 and GenALEx 6.0 software. Results A total of 146 P. falciparum samples were analyzed as single infection samples with a total of 26 alleles in locus Polyα and 12 alleles in locus TAA87. The mean He value of the two loci was 0.86 ± 0.02. Ten alleles in locus Polyα and 8 alleles in locus TAA87 were distributed in Myanmar isolates, with the He values of 0.86 and 0.81 respectively. Fifteen alleles in locus Polyα and 11 in locus TAA87 were detected in Ghana isolates, with the He values of 0.91 and 0.86 respectively. In addition, the haplotype of 174 bp (Polyα) and 113 bp (TAA87) were only detected in Myanmar isolates with more than 17% gene frequency, whereas they were absent in Ghana isolates. Conclusions The two different geographical sources of imported P. falciparum strains have different allele frequencies and haplotypes at the two neutral microsatellite markers, Polyα and TAA87. Therefore, these two microsatellite loci may be considered as the potential molecular marker candidates for identifying P. falciparum strains with different geographical sources.

ObjectiveTo determine the impact of lupus flares on maternal and fetal outcomes in pregnant patients with systemic lupus erythematosus(SLE).MethodsData was obtained from 46 pregnancies of 44 pregnant women with SLE.The relationship between lupus flares and pregnant outcomes,and the risk factors for adverse maternal and fetal prognosis were analyzed.T-test,X2 test or Fisher's exact test and Logistic regression were used for statistical analysis.Results① Lupus flares occurred in19(41％)pregnancies(group A) and stable lupus disease was observed in 27(59％) pregnancies(group B) during pregnancy.Compared to pregnancies in patients with stable lupus disease at the conception(n=32),pregnancies in patients with unstable lupus disease at the conception(n=8) had higher lupus flare during pregnancy( 100％ vs 16％,P＜0.05).(②) The common manifestations of lupus flares during pregnancy were lupus nephritis (LN) (11 cases),skin rashes (10 cases),arthritis (7 cases),and the common complication was infection ( 11 cases).(③) The incidence of premature labor,fetal growth retardation (FGR) and fetal loss in group A was 42％,47％ and 26％ respectively,which was significantly higher than that of the group B (7％,15％ and 0 respectively)(P＜0.05).There was no difference in the incidence of preeclampsia,fetal distress and neonatal asphyxia between the two groups ( 16％ vs 7％,16％ vs 19％,5％ vs O,respectively,P＞0.05).The incidence of premature labor and FGR in patients with active LN was higher than that of patients without active LN (55％ vs 11％,64％ vs 17％,respectively,P＜0.05).(④)The binary Logistic regression analysis showed that renal impairment,hypocomplementemia,aPL and serum urea nitrogen level were independent risk factors for premature delivery,FGR,fetal loss and fetal distress.Conclusion(①) Lupus flares during pregnancy increase the incidence of premature labor,FGR and fetal loss.Active LN during pregnancy can increase the incidence of premature labor and FGR.② Renal impairment,hypocomplementemia,aPL and serum urea nitrogen level are associated with adverse fetal outcomes in pregnant patients with SLE.

A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.1 mm, 3.5 microm, Waters). An isocratic program was used at a flow rate of 0.4 m x min(-1) with mobile phase consisting of acetonitrile and ammonium buffer (pH 8). The protonated ions of analytes were detected in positive ionization by multiple reactions monitoring (MRM) mode. The plasma method, with a lower limit of quantification (LLOQ) of 0.1 ng x mL(-1), demonstrated good linearity over a range of 0.1 - 30 ng x mL(-1) of olanzapine. Specificity, linearity, accuracy, precision, recovery, matrix effect and stability were evaluated during method validation. The validated method was successfully applied to analyzing human plasma samples in bioavailability study.
Antipsychotic Agents ; blood ; pharmacokinetics ; Benzodiazepines ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, Liquid ; methods ; Humans ; Indicator Dilution Techniques ; Isotope Labeling ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; methods

OBJECTIVETo develop a chitosan (CH)/polyethylene glycols succinate acid (PEG-SA)-mediated mitomycin C (MMC) delivery system and investigate its drug release characteristics in vitro and its effect against scar tissue adhesion in vivo.

METHODSMitomycin C loading in the composite CH/PEG-SA/MMC films was determined using ultraviolet. The freeze-dried films were dispersed in 1 ml PBS (pH7.4) and mitomycin C release in vitro was determined according to the mitomycin C concentration-UV value standard curve. The influence of the film structure on the drug release was evaluated. The drug delivery system was then implanted in SD rats, and 4 weeks later, immunohistochemical and histological examinations were carried out to assess the therapeutic effect on epidural scar tissue.

RESULTSThe linear regression equation of the mitomycin C concentration-UV value standard curve was y=0.593x(3)-2.563x(2)+25.944x-0.236 (R(2)=1.000). The film demonstrated good drug delivery capability, and 20 mg of the samples in PBS showed a peak mitomycin C release after 12 days of 14.9616 microg/ml, which was higher than the ID(50) of mitomycin C (10.4713 microg/l) to the fibroblasts. On days 18 and 32, another two drug release peaks occurred (14.4824 microg/ml and 11.4092 microg/ml, respectively), followed by maintenance of slow release. Till day 60, the accumulative mitomycin release reached 0.1793 microg/ml, and the loaded drug was ultimately completely released. Significant differences were noted in the hydroxyproline content in the scar tissues of different groups (F=12.085, P=0.000), and the CH/PEG-SA/MMC DDS reduced the amount of scar tissue and promoted its orderly alignment to control potential scar hyperplasia that may compress the spinal cord and nerve roots.

CONCLUSIONThe composite film for drug delivery possesses good flexibility and mechanical properties and allows sustained drug release of mitomycin C to prevent epidural scar tissue adhesion following lumbar laminectomy.

Animals ; Chitosan ; chemistry ; Drug Delivery Systems ; Intervertebral Disc ; drug effects ; physiopathology ; surgery ; Mitomycin ; administration & dosage ; chemistry ; Polyethylene Glycols ; chemistry ; Polyethylenes ; chemistry ; Rats ; Rats, Sprague-Dawley ; Succinates ; chemistry ; Tissue Adhesions ; prevention & control

OBJECTIVETo investigate the expressions of VEGF in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), their clinical significance and their relationship with that of ET-1.

METHODSA total of 44 specimens of PCa and 36 of BPH tissues were examined by the immunohistochemical Elivision plus method for the expressions of VEGF and ET-1. The intensity of staining for VEGF and ET-1 was assessed by light microscopy on a scale from "-" to "+ + +".

RESULTSThe rates of positive expression of VEGF were 69.4% in BPH and 80.9% in PCa, positive staining mostly in the cytoplasm of glandular epithelia and cancer cells, and strongly positive in all the stroma vascular endothelial cells. The staining intensity of VEGF was significantly higher in the PCa than in the BPH group (P < 0.05) , in the bone metastasis (BM) than in the non-BM group (P < 0.01), and in the lowly than in the highly and moderately differentiated PCa tissues (P < 0.01). The expression of VEGF was positively correlated with that of ET-1 ( r(s) = 0.780, P < 0.01).

CONCLUSIONVEGF is involved in the development, progression and metastasis of PCa. VEGF and ET-1 may play a joint role in its development and progression.

Aged ; Aged, 80 and over ; Endothelin-1 ; biosynthesis ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prostatic Hyperplasia ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor Receptor-1 ; biosynthesis

Objective In order to compare the iodine deficiency disorders(IDD)prevalent slatus in Chun'an County between 2006 and 2007,and to provide the science information for iodine supplementation in different regions.Methods Three schools of Wangzhai,Pingmen and Wenchang which the goiter prevalenee was the most severe were selected in Chun'an County;and from each school,90 pupils aged 8-10 years were randomly selected.B-ultrasound examination of thyroids,urine iodine and salt iodine were measured.Results The goiter rate in B-ultrasound were 7.5%(20/267),median of urine iodine was 247.5 μg/L,mean of salt iodine was 32.7 ms/ks in 2006;and the goiter rate in B-uhrasound were 3.7%(10/271),median of urine iodine was 383.4 μg/L,mean of salt iodine was 33.5 mg/kg in 2007.The goiter prevalence in Wangzhai,Pingrnen and Wenehang township were 15.2%(14/92),6.0%(5/83)and 2.2%(2/92),respectively,and median of urine iodine were 360.1.211.3,189.3μg/L,respectively,in 2006;The goiter prevalence were 6.6%(6/91),3.3%(3/90)and 1.1%(1/90),respectively.and median of urine iodine were 388.6,41 1.5,327.8μg/L,respectively,in 2007.Family ineome of Wangzhai,Pingmen and Wenchang township were 1000,2000,3000 yuan,respectively.Conclusions Goiter prevalence was correlated with urinary iodine,nutritional state and economic condition,high urinary iodine contents and poor nutritional status lcad to a high goiter rate.