Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective:To investigate the relationship between the methylation of apelin receptor early endogenous ligand ( APELA) gene promoter and preeclampsia. Methods:A systematic review was conducted to evaluate the cg02779075 locus methylation in APELA gene associated with preeclampsia in six previous studies on placenta genome-wide methylation based on the GEO gene expression database from 2007 to 2017. After testing the heterogeneity, the random-effects model was applied for meta-analysis. Placenta samples of 17 preeclamptic patients and 24 healthy gravidas were retrospectively collected in Obstetrics and Gynecology Hospital of Fudan University from 2008 to 2010. MassARRAY was used to quantify the methylation level of CpGs, and the expression of APELA gene was determined by qRT-PCR. All data were analyzed by t test or Mann-Whitney U test. Results:(1) Analysis of the six genome-wide methylation studies showed significant heterogeneity ( I2=0.64, P=0.016) and the meta-analysis using random-effects model showed that the methylation of cg02779075 locus in the placenta samples of preeclamptic women was down-regulated significantly ( Pmeta=6.7×10 -6). (2) Placenta tissue analysis revealed that the methylation of CpG1 [0.12 (0.00-0.25) vs 0.21 (0.09-0.33), U=-2.569] and CpG2 [0.07 (0.01-0.14) vs 0.17 (0.09-0.34), U=-4.160] in patients with preeclampsia was significantly reduced compared with those in healthy control (both P<0.05). The expression of APELA gene in the placenta was up-regulated in patients with preeclampsia, but no significant difference was observed between the two groups ( U=0.891, P=0.384). Conclusions:Aberrant methylation of APELA gene promoter was detected in the placentas of patients with preeclampsia.

Objective:To investigate the risk factors of birth weight discordance in dichorionic diamniotic (DCDA) twins.Methods:This study retrospectively analyzed 1 757 cases of DCDA twin pregnancies from 11 Chinese hospitals from January 1, 2014, to December 31, 2017. Birth weight discordance was defined as ≥ 20% difference between the twins. All cases were divided into two groups: the concordant group ( n=1 520) and discordant group ( n=237). General information was compared and the high-risk factors of birth weight discordance were analyzed. Mann-Whitney U test, Chi-square test or Fisher's exact test, and logistic regression analysis were used as statistical methods. Results:Compared with the concordant group, the discordant group showed a higher incidence of hypertensive disorders of pregnancy [24.5% (58/237) vs 12.8% (194/1 520), χ2=22.882, P<0.05], fetal structural malformations [4.2% (10/237) vs 1.0% (15/1 520), χ2=15.160, P<0.05], fetal distress [6.3% (15/237) vs 1.4% (21/1 520), χ2=22.602, P<0.05], umbilical cord abnormalities [3.8% (9/237) vs 1.2% (18/1 520), χ2=7.607, P<0.05] and abnormal placental cord insertion [3.8% (9/237) vs 1.4% (21/1 520), χ2=34.904, P<0.05], but lower incidence of premature rupture of membranes [11.0% (26/237) vs 16.5% (250/1 520), χ2=4.645, P=0.034]. Logistic regression analysis showed that the independent risk factors of birth weight discordance in DCDA twins were hypertensive disorders of pregnancy ( OR=2.258, 95% CI: 1.620-3.184, P<0.001), fetal structural malformations ( OR=4.268, 95% CI: 1.892-9.631, P<0.001), umbilical cord abnormalities ( OR=2.889, 95% CI: 1.245-6.705, P=0.014) and abnormal placental cord insertion ( OR=2.318, 95% CI: 1.012-5.311, P=0.047). Conclusions:Hypertensive disorders of pregnancy, fetal structural malformations, umbilical cord abnormalities and abnormal placental cord insertion may be the risk factors of birth weight discordance in DCDA twins.

Objective To understand the distribution of water iodine in the external environment of Shanxi Province, and to provide a basis for redefining and implementation of scientific iodine supplementation in iodine deficiency, iodine adequate or iodine high areas. Methods In 2012 - 2016, administrative villages (neighborhood committees)in 119 counties(cities,districts)in 11 cities of Shanxi Province were selected as the investigation units, and 1 to 5 drinking water samples were collected. Water iodine content was detected using arsenic-cerium catalytic spectrophotometry. Areas standard was designated: water iodine content < 10 μg/L as iodine deficiency areas, > 100 μg/L as iodine high areas. Results A total of 26 213 administrative villages (neighborhood committees) of 1 362 townships (towns) of 119 counties (cities, districts) were surveyed, covering 2 850.94 ten thousand people. A total of 32 766 water samples were collected and the median iodine was 5.2 μg/L. There were 18 199 villages with water iodine < 10 μg/L, accounting for 69.4% (covering 1 812.17 ten thousand people, accounting for 63.6%), 6 471 villages with water iodine 10-<50 μg/L,accounting for 24.7%(covering 787.44 ten thousand people,accounting for 27.6 %),1 166 villages with water iodine 50 - < 100 μg/L,accounting for 4.4% (covering 181.46 ten thousand people, accounting for 6.4%), 377 villages with water iodine ≥100 μg/L, accounting for 1.4%(covering 69.87 ten thousand people, accounting for 2.5%).In 1 362 townships (towns), 71.1% (969)water iodine median was<10 μg/L,24.2%(330)water iodine median was in 10-<50 μg/L,3.4%(46)water iodine median was in 50-<100 μg/L,and 1.2%(17) water iodine median was ≥100 μg/L. In 119 counties(cities,districts),there were 90 counties(accounting for 75.6%) with the water median < 10 μg/L, there were 26 counties (accounting for 21.8%) with the water median 10 - < 50 μg/L. Conclusions Most parts of Shanxi Province(or the resident population) are iodine deficiency areas, the external environment water iodine contents in the rest of the regions are different, we should adopt different iodine supplement or iodine reduction measures in regions with different water iodine levels.

Objective To study the nutritional status of pregnant women in Shanxi Province before and after the implementation of the new standards of iodized salt content,provide the basis for scientific supplementation of iodine for pregnant women.Methods According to the method of population proportion sampling,30 county-level monitoring sites were selected,a primary school was selected from each county (city,district) by the method of simple random sampling and 40 students in 2011 or 50 students in 2014 aged 8-10 years were selected in each school,direct titration was used to detect salt iodine;at the same time,20 pregnant women were selected from each town where the primary school was located and urinary iodine was determined using arsenic cerium catalytic spectrophotometry (WS/T 107-2006).Results A total of 1 182 and 1 437 salt samples was detected in Shanxi Province in 2011 and 2014,the median of salt iodine was 30.5 and 24.1 mg/kg,respectively,and the difference was statistically significant (H =567.45,P ＜ 0.01);it was 95.41％,80.31％,76.62％ of the coverage rate of iodized salt,qualified rate of iodized salt,qualified iodized salt consumption rate in 2014,respectively;which were compared with those in 2011 (97.63％,97.49％,95.18％),the differences were statistically significant (x2 =9.27,232.40,166.25,P ＜ 0.01).A total of 440 and 630 urinary samples of pregnant women were tested in 2011 and 2014,the median of urinary iodine was 279.6 and 177.1 μg/L,respectively,iodine nutrition of pregnant women was more than adequate in 2011,and iodine nutrition was suitable in 2014.The difference was statistically significant (H =153.89,P ＜ 0.01).The proportion of pregnant women's median of urinary iodine less than 150 μg/L in 2014 [41.11％ (259/ 630)] was significantly higher than that in 2011 [8.18％ (36/440),x2 =140.68,P ＜ 0.01].The constituent ratio of 250 to 500 μg/L was significantly decreased [23.65％ (149/630) vs 54.77％ (241/440),x2 =108.33,P ＜ 0.01).Conclusion It is at a reasonable level of iodine nutrition level of pregnant women in Shanxi after the adjustment of iodized salt content,but the ratio of ＜ 150 μg/L is increasing,which needs to be paid attention to.

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9 basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9 BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9 BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient's lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9 BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.
Bronchiectasis ; genetics ; metabolism ; Humans ; Pulmonary Alveoli ; cytology ; metabolism ; SOX9 Transcription Factor ; genetics ; metabolism ; Stem Cell Transplantation ; methods ; Stem Cells ; cytology ; metabolism

Objective KV-CBCT was utilized to evaluate the setup errors in lung SBRT with R624-SCF immobilization equipment,quantitatively analyze the percentage of all types of errors in the cumulative errors and unravel the main sources of setup errors.Methods The CBCT data weekly and QA data monthly from 32 patients diagnosed with lung neoplasms were collected to quantitatively analyze the setup errors.The cumulative errors were calculated by statistical model.The proportion and source of each type of setup error was analyzed.Results All 32 patients received a total of 420 times of CBCT.The setup errors of immobilization equipment in the lateral,supine-inferior,anterior-posterior directions were (0.03±0.72) mm,(0.73± 1.16) mm and (0.21±0.95) mm,respectively.The errors of tumor motion in three directions were (0.71±2.61) mm,(-0.80±2.60) mm and (0.075± 1.77) mm,respectively.According to the calculation formula proposed by Vance Keeling,the proportion of the cumulative error was 54.55％,9.21％ for immobilization equipment,12.97％ for tumor motion,2.55％ for couch sagging,5.70％ for Gantry radiation isocenter,4.73％ for Collimator radiation isocenter,4.61％ for couch radiation isocenter and 5.70％ for Xray field isocenter,respectively.Conclusions The main factors of setup errors during SBRT treatment for lung cancer are setup random,tumor motion,immobilization equipment,couch sagging and machine isocenter.During radiotherapy,targeted control of tumor motion is of significance for minimizing the cumulative errors.

PURPOSE: Accumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: miR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191. RESULTS: miR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion. CONCLUSION: Our findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.
3' Untranslated Regions ; Blotting, Western ; Bromodeoxyuridine ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Proliferation ; Epithelial Cells* ; In Vitro Techniques ; Luciferases ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis* ; Real-Time Polymerase Chain Reaction ; RNA, Small Interfering

Objective To establish a method for determination of arsenic in urine,using hydrogen peroxide as the main digestion reagent to digest urine,and using hydride generation atomic fluorescence spectrometry (HG-AFS) to determine arsenic (this method was referred to below),the feasibility of the application in the monitoring of endemic arsenic poisoning was discussed.Methods Temperature control instrument (60 holes) and supporting special calibration tube were used to digest urine.Digestion reagents was mainly hydrogen peroxide plus a small amount of nitric acid and sulfuric acid,HG-AFS was used to determinate.Based on standard curve to calculate linear relationship.Using this method to determinate detection limit,precision,accuracy and stability of samples,this method was compared with the national hygienic standard method (DDCAg method,WS/T 28-1996).Results The detection limit was 0.8 μg/L (1 ml of urine was tested),the correlation coefficient was larger than 0.999 5.Precision:3 samples were determined,the arsenic contents were (11.0 ± 0.6),(39.2 ± 1.0),(174.4 ± 3.8) μg/L and the relative standard deviations were 5.03％,2.59％ and 2.17％,respectively.Recovery rate:3 samples were determined for standard addition recovery test,the average recovery rate was 99.4％ and the recovery rate ranged between 94.0％-104.3％.Methods contrast:this method [(125.9 ± 61.6) μg/L] and DDCAg method [(121.3 ± 52.5) μg/L] were used to determinate 20 samples from endemic arsenic poisoning areas,respectively,the determination results of the two methods were not significantly different (t =1.22,P ＞ 0.05).Conclusions This method is built successfully,it has good precision and accuracy,it needs small amount of sample and reagent,the amount of harmful gases generated is greatly reduced,and it is easy to operate and beneficial to operator's health.Therefore,it is a good method to determine arsenic in urine,and it can be applied in prevention of endemic arsenism.

Objective To establish a arsenic cerium catalytic rate method for determination of urinary iodine,and increase the linear range of urinary iodine determination.Methods Standard series and urine samples after digestion treatment,were tested using dynamics function of spectrophotometer to record the curve of absorbance value (A) change with time (t) during arsenic cerium catalytic reaction for each measurement system,choice (A1,t1) and (A 2,t2) on this curve and calculating the reaction rate (v),v =(lgA1-lgA2)/(t2-t1).Through the determination of the standard series it could calculate regression equation of iodine concentration (C) with X:C =a ± bX,X =1 000 (v-v0),and the v0 is the reaction rate of reagent blank.Results (① C and X were positively correlated.The standard series linear range was 0-1 200 pμg/L and correlation coefficient r was higher than 0.999 1.The minimum detection limit was 3.9 μg/L (0.25 ml urine).②)Precision:5 urine samples (A,B,C,D,E) were selected within the range of 0-1 200 μg/L and the measured value were (72.3 ± 2.7),(148.2 ± 5.2),(210.5 ± 4.4),(562.7 ± 6.8),and (899.3 ± 8.0) μg/L.The relative standard deviation (RSD) was between 0.9％-3.8％.(③)Accuracy:4 samples (A,B,C,D) were measured for standard addition recovery test,recovery was between 94.2％-107.2％;urinary iodine standard material [the given values were (67.9 ± 9.0),(142.0 ± 10.0),(195.0 ± 10.0),(558.0 ± 17.0),(885.0 ± 28.0) μg/L] were determined and the results were in the range of uncertainty of the standard material.④Method contrast:with the national health standard method (method for determination of iodine in urine by arsenic cerium catalytic spectrophotometry) to determinate 120 urine samples,the results showed that there were 60 urine samples within 0-300 μg/L,60 urine samples were more than 300 μg/L.Then rate method was used to test the 120 urine samples.For the 60 samples within the scope of 0-300 μg/L,the determination results of the two methods were positively correlated (r =0.994,P ＜ 0.01);the results of the rate method were lower than those of the standard method and the difference was statistically significant (t =2.047,P ＜ 0.05).But the average deviation was only 2.1 μg/L,for the determination of urine iodine there was no practical significance;for the 60 samples higher than 300 μg/L,the determination results of the two methods were positively correlated (r =0.993,P ＜ 0.01) and the difference was not statistically significant (t =-1.092,P ＞ 0.05).Conclusions Arsenic cerium catalytic rate method has increased the linear range of urinary iodine determination.Using this method,the vast majority samples can be tested directly without dilution,thereby reducing the workload for determination of urine iodine.