Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Chemokines are small cytokines with chemotactic activity, they are involved in regulating immune responses and inflammatory responses. In the development of tumors, chemokines are multi-functional mediators that not only affect the infiltration of immune cells into the tumor, but also have an important impact on tumor growth, angiogenesis, invasion, and metastasis. Besides, they are important targets of tumor therapy. Here we review chemokines involved in the regulation of signaling pathways, analyze the mechanism of chemokines in the development of breast cancer, summarize the chemokines targeted drugs for breast cancer in recent years and make a prospect about the role of chemokines in anti-breast cancer therapy.

The aim of this study was to determine whether the anti-fibrotic effects of pirfenidone (Pirf) and nintedanib (Nint) associated with the regulation of the alveolar epithelial type 2 cell (AEC II)-mediated lung alveolar regeneration in single- and multiple-dosage animal models of bleomycin-induced pulmonary fibrosis. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We found that the Pirf and Nint treatment of mice decreased the lung weight index, inflammation level, and the content of hydroxyproline compared with nontreated fibrotic mice in the single dosage model. Also, Pirf and Nint increased the oxygen saturation level and improved the lung functions in fibrotic mice, indicating that both drugs have anti-fibrotic effects in this model. However, the anti-fibrotic effects of Pirf and Nint were not observed in the multiple-dosage model. Further studies showed that Pirf and Nint decreased the expression of β-catenin, Axin2, c-Myc, Cyclin D1, and inhibited the Wnt/β-catenin signaling pathway, suggesting that Pirf and Nint did not produce anti-fibrotic effects in the multiple-dosage model due to their inhibiting the Wnt/β-catenin pathway and suppressing the stemness of AEC II, namely, suppressing AEC II-mediated lung alveolar regeneration.

Although noninvasive trachea cannula is a common technique in clinic, this technique is hard to be applied in mice. It is even more difficult to perform the repeated noninvasive trachea cannula on the same mouse due to the throat injury. Here we report an effective, rapid and easy method to perform the noninvasive intubation on mice. This method can effectively be applied to many pharmacological and other related studies. In addition, this strategy can protect the mouse from physical injury caused by operative procedure. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. In alliance with lung function measurement system, we detected the normal lung function values and presented the lung function development curves of mice of different age. We found that the lung function of mice was matured at 8 weeks old or at the body weight of 18-20 g. In addition, we constructed the mouse model of multiple bleomycin induced pulmonary fibrosis by using this method and illustrated that the trachea cannula is more efficiency than nasal inhalation. Using this method, we have confirmed that the immune microenvironment in lung tissue of multiple bleomycin model is distinct from that of single bleomycin induced pulmonary fibrosis model. Thus, this method is a reliable and safe strategy for the pharmacology study.

This study was to determine the expression of the cell cycle inhibitor p21 in alveolar macrophages (AMs) and the role of p21 in activation of AMs in bleomycin (BLM) injury-induced lung fibrosis. The expression of CD206 in AMs was measured by immunofluorescence staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of macrophage activation markers. The coculture assay for macrophage and fibroblast was employed to explore the effect of macrophage on fibroblast activation. Immunofluorescence staining and western blotting assay were adopted to detect the expression of p21 in fibrotic tissues. AMs were treated with p21 knockdown or overexpression virus, RT-PCR and the co-culture system were used to explore the effect of p21 expression on macrophage activation. The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. Our results showed that the expression of CD206 and macrophage activation markers was increased in AMs from fibrotic mice, indicating that AMs from fibrotic mice were associated with a profibrotic phenotype. Moreover, the expression of p21 was upregulated in AMs after BLM treatment. Depletion of p21 suppressed macrophage activation, while overexpression of p21 promoted the profibrotic phenotype of AMs from healthy mice. In summary, BLM injury causes the progressive accumulation of p21 in AMs, which induces the production of a number of profibrotic factors promoting the development of pulmonary fibrosis.

Objective To establish a method for determination of escitalopram in biological samples by ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with gas chromatography-tandem mass spectrometry （GC-MS/MS） and provide evidences for forensic determination of cases related to escitalopram. Methods The 1-hexyl-3-methylimidazolium hexafluorophosphate （[C₆MIM][PF₆]） was selected as an extract solvent to process biological samples. Ultrasound-assisted extraction was used on the samples. Then the samples were detected by GC-MS/MS. Results The linear range of escitalopram in blood and liver were 5.56-1 111.10 ng/mL and 0.025-5.00 mg/g, respectively. The correlation coefficient （r） were greater than 0.999, limit of detection （LOD） were 4.00 ng/mL and 2.00 μg/g, limit of quantitation （LOQ） were 14.00 ng/mL and 6.00 μg/g, respectively. The extraction recovery rates were all greater than 50%, the interday and intraday precision were less than 20%. Escitalopram was detected in blood and liver samples from the actual poisoning case by this method with a content of 1.26 μg/mL and 0.44 mg/g, respectively. Conclusion The ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with GC-MS/MS is environment friendly, rapid, has good enriching effect and consumes less organic solvent and can be used for forensic determination of escitalopram related cases.
Citalopram ; Gas Chromatography-Mass Spectrometry ; Limit of Detection ; Liquid Phase Microextraction ; Tandem Mass Spectrometry

Objective The locus coeruleus noradrenergic system regulates the recovery process of general anesthesia, but its mechanism remains unclear. The locus coeruleus has a large amount of projection to the paraventricular nucleus of the thalamus (PVT). This study was to investigate the effect of the α-noradrenergic receptor in PVT neurons in propofol anesthesia. Methods The immunofluorescence technique was used for comparison of the c-fos expression in the PVT neurons collected from male SD rats under propofol anesthesia (the PA group, n = 4) or no anesthesia (the non-PA group, n = 4) and observation of the activity of PVT neurons. PVT microinjection models were established in 40 rats and randomized into four groups of equal number: noradrenaline, phentolamine, propranolol, and isotonic saline. Under propofol anesthesia, the animals received microinjection of noradrenaline, phentolamine, propranolol, and isotonic saline at 1 μL into the PVT, respectively, and were observed for the time of recovery of righting reflex (RORR) and the δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), β (12-25 Hz) and γ waves (25-60 Hz) on EEG before and after microinjection. Results The expression of c-fos was significantly reduced in the PA group compared with that in the non-PA control. The Ca2+ signals in the PVT were significantly increased during the propofol induction of the loss of righting reflex (LORR), but decreased in the early stage of and during propofol anesthesia (P < 0.05), and remarkably increased at the emergence of and during RORR (P < 0.05). In comparison with the isotonic saline control, the noradrenaline group showed markedly shortened time of RORR (837.8 s vs 647.7 s, P < 0.05), reduced rate of δ waves (P < 0.05) and elevated rate of β waves (P < 0.05), while the phentolamine group exhibited prolonged time of RORR (837.8 s vs 1045.1 s, P < 0.05) and increased rate of δ waves after microinjection (P < 0.05). Conclusion The α-noradrenergic receptors in PVT neurons play a critical role in promoting recovery from propofol anesthesia.

Objective To analyze the surveillance data after schistosomiasis transmission interruption from 1985 to 2018, so as to provide scientific basis for the future prevention and control of schistosomiasis. Methods The data pertaining to snail survey, surveillance of schistosomiasis in humans and livestock, and health education were collected and analyzed in Songjiang District after schistosomiasis transmission interruption from 1985 to 2018. Results From 1985 to 2018, there were 8 townships, 68 villages and 1 462 settings with snails in Songjiang District, covering an area of 96.399 hm². There were 4 townships and 59 villages with snails newly identified in previously schistosomiasis non-endemic areas, with emerging snail habitats of 60.161 hm². A total of 26 148 snails were captured, and no infections were detected. The snail habitats were mainly distributed in the river course, ditches and farmlands, which accounted for 45.28%, 33.17% and 21.55% of total snail habitats, respectively. A total of 245 955 humans were subjected to the serological test, with a positive rate of 0.03%, and 37 humans were subjected to the parasitological test, with 3 positives detected. These three egg-positives were all imported chronic cases with schistosomiasis. A total of 9 109 livestock were detected using the serological test, and no infection was found. Most of the awareness rate of schistosomiasis control knowledge and the rate of correct behavior formation were over 80% in residents and students. Conclusions The achievements of schistosomiasis control are consolidated in Songjiang District; however, there are still risk factors of schistosomiasis transmission, including residual snails, snail diffusion and importation of external source of infection. The future surveillance of schistosomiasis should focus on snails and sources of infection.

Objective · To investigate the effect of modified electroconvulsive therapy (MECT) on oxidative stress parameters in patients with bipolar disorder. Methods · Forty-three patients with bipolar disorder (case group) were enrolled that received MECT intervention for 6 weeks, and 49 healthy volunteers (control group) were recruited. Chinese versions of the 17 items Hamilton Depression Rating Scale (HAMD-17), Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) were used to assess the efficacy and side effects at baseline and after 6 weeks of treatment. The plasma levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured at baseline and after 6 weeks of treatment to assess the level of oxidative stress. Results · The serum MDA and GSH-Px levels of the case group were higher while the serum SOD levels of the case group was lower than that of the control group, and there was no significant difference in the serum CAT levels between two groups at baseline. MDA levels were higher in manic states than in depressed states, and they were positively correlated with the CGI-S scores. After MECT treatment, the CGI-S scores of patients decreased significantly, and the plasma MDA levels decreased significantly in manic and depressive states, but there was no change in other oxidative stress parameters. Conclusion · There was oxidative stress damage in patients with bipolar disorder, and the severity of the disease varied with the degree of damage. MECT improved the symptoms of the disease and decreased the level of plasma MDA, while there was no effect on the anti-oxidation index.

Objective·To explore the association between neuropeptide Y (NPY) gene polymorphism and schizophrenia in Chinese Han population. Methods·Four single nucleotide polymorphism (SNP) loci (rs16148, rs1859290, rs16147, and rs16478 in NPY gene) were selected and genotyped by TaqMan genotyping assay in a case-control study with 678 schizophrenia cases (case group) and 685 healthy controls (control group). The allele, genotype and haplotype frequencies distribution of the SNPs between the groups were compared with SHEsis online software. Results·The distribution of genotype frequency of locus rs16478 showed a nominal statistically difference between the adult-onset schizophrenia (AOS group) and control group (χ2=6.66, P=0.036, P correction=0.144). Under recessive inherited model, the distribution of CC genotype frequency of locus rs1859290 showed statistically difference between the male schizophrenia cases and control group (P=0.012, OR=0.97, 95％CI 0.94-0.99, P correction=0.048). The distribution of haplotype CCTA (consisted of rs16148, rs1859290, rs16147, and rs16478) frequency showed statistically difference between the male AOS group and control group (8.1％ vs 13.2％, OR=0.57, P=0.010, P correction=0.040). Conclusion·The polymorphisms in NPY gene may be associated with schizophrenia in Chinese Han population.