[Antidepressant mechanism of Shenling Kaixin Granules based on BDNF/TrkB/CREB pathway].

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1ß), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1ß and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1ß and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

[Neuroprotective effect of ginsenoside Re on drosophila model of Parkinson's disease].

This study aims to explore the neuroprotective mechanism of ginsenoside Re(GS-Re) on drosophila model of Parkinson's disease(PD) induced by rotenone(Rot). To be specific, Rot was used to induce PD in drosophilas. Then the drosophilas were grouped and respectively treated(GS-Re: 0.1, 0.4, 1.6 mmol·L~(-1); L-dopa: 80 µmol·L~(-1)). Life span and crawling ability of drosophilas were determined. The brain antioxidant activity [content of catalase(CAT), malondialdehyde(MDA), reactive oxygen species(ROS), superoxide dismutase(SOD)], dopamine(DA) content, and mitochondrial function [content of adenosine triphosphate(ATP), NADH:ubiquinone oxidoreductase subunit B8(NDUFB8) Ⅰ activity, succinate dehydrogenase complex, subunit B(SDHB) Ⅱ activity] were detected by enzyme-linked immunosorbent assay(ELISA). The number of DA neurons in the brains of drosophilas was measured with the immunofluorescence method. The levels of NDUFB8 Ⅰ, SDHB Ⅱ, cytochrome C(Cyt C), nuclear factor-E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), B-cell lymphoma/leukemia 2(Bcl-2)/Bcl-2-assaciated X protein(Bax), and cleaved caspase-3/caspase-3 in the brain were detected by Western blot. The results showed that model group [475 µmol·L~(-1) Rot(IC_(50))] demonstrated significantly low survival rate, obvious dyskinesia, small number of neurons and low DA content in the brain, high ROS level and MDA content, low content of SOD and CAT, significantly low ATP content, NDUFB8 Ⅰ activity, and SDHB Ⅱ activity, significantly low expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax, large amount of Cyt C released from mitochondria to cytoplasm, low nuclear transfer of Nrf2, and significantly high expression of cleaved caspase-3/caspase-3 compared with the control group. GS-Re(0.1, 0.4, and 1.6 mmol·L~(-1)) significantly improved the survival rate of PD drosophilas, alleviated the dyskinesia, increased DA content, reduced the loss of DA neurons, ROS level, and MDA content in brain, improved content of SOD and CAT and antioxidant activity in brain, maintained mitochondrial homeostasis(significantly increased ATP content and activity of NDUFB8 Ⅰ and SDHB Ⅱ, significantly up-regulated expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax), significantly reduced the expression of Cyt C, increased the nuclear transfer of Nrf2, and down-regulated the expression of cleaved caspase-3/caspase-3. In conclusion, GS-Re can significantly relieve the Rot-induced cerebral neurotoxicity in drosophilas. The mechanism may be that GS-Re activates Keap1-Nrf2-ARE signaling pathway by maintaining mitochondrial homeostasis, improves antioxidant capacity of brain neurons, then inhibits mitochondria-mediated caspase-3 signaling pathway, and the apoptosis of neuronal cells, thereby exerting the neuroprotective effect.

A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer.

Background: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems. Methods: According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021) and the Technical Guideline for the Clinical Comprehensive Evaluation of Antitumor Drugs (2022), a comprehensive clinical evaluation index system of first-line treatment drugs for ALK-positive advanced NSCLC was established by literature review and expert interviews. We conducted a systematic literature review, meta-analysis, and other relevant data analyses, combined with an indicator system, to establish a quantitative and qualitative integration analysis for each indicator and each dimension of crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib. Results: The comprehensive clinical evaluation results of all dimensions were as follows: in terms of safety, alectinib had a lower incidence of grade 3 and above adverse reactions; for effectiveness, alectinib, brigatinib, ensartinib, and lorlatinib showed better clinical efficacy, and alectinib and brigatinib have been recommended by several clinical guidelines; in terms of economy, second-generation ALK-TKIs have more cost-utility advantages, and both alectinib and ceritinib have been recommended by the UK and Canadian Health Technology Assessment (HTA) agencies; for suitability, accessibility, and innovation, alectinib has a higher degree of physician recommendations and patient compliance. Except for brigatinib and lorlatinib, all other ALK-TKIs have been admitted to the medical insurance directory; the accessibility of crizotinib, ceritinib, and alectinib is good, meeting the needs of patients. Second- and third-generation ALK-TKIs have higher blood-brain barrier permeability, stronger inhibition ability, and innovation than first-generation ALK-TKIs. Conclusions: Compared with other ALK-TKIs, alectinib performs better across six dimensions and has a higher comprehensive clinical value. The results provide better drug choice and rational use for patients with ALK-positive advanced NSCLC.

Ectopic invasive ACTH-secreting pituitary adenoma mimicking chordoma: a case report and literature review.

BACKGROUND: Ectopic pituitary adenoma (EPA) is defined as a special type of pituitary adenoma that originates outside of the sellar region, is extra- or intra-cranially located, and without connection to normal pituitary tissue. EPA is extremely rare, with most cases presented as case reports or small case series. Due to nonspecific symptoms and laboratory indicators, the preoperative diagnosis, treatment and management for EPA remain challenging. CASE PRESENTATION: Here, we report the imaging phenotype and pathological findings of a case of invasive EPA in a 47-year-old woman. A preoperative non-contrast CT scan revealed a 5.8 × 3.6 × 3.7 cm soft tissue mass located in the sphenoid sinus and clivus. MRI showed an ill-defined solid mass with heterogeneous signals on T1-weighted and T2-weighted images. The mass displayed infiltrative growth pattern, destroying bone of the skull base, invading adjacent muscles and encasing vessels. The patient underwent partial tumor resection via transsphenoidal endoscopic surgery. Pathological examination led to diagnosis of ectopic ACTH-secreting pituitary adenoma. Post-surgery, the patient received external beam radiotherapy. CONCLUSION: EPA with invasive growth pattern has rarely been reported. The imaging phenotype displays its relationship to the pituitary tissue and surrounding structures. Immunohistochemical examination acts as a crucial role in differentiating EPA from other skull base tumors. This case report adds to the literature on EPA by summarizing its characteristics alongside a review of the literature.

Laparoendoscopic single-site radical nephrectomy for localized renal cancer: a descriptive research study with at least a 10-year follow-up.

Background: Laparoendoscopic single-site (LESS) surgery is performed to further narrow the incisions and reduce tissue injury. It has been more than10 years since the surgery was first described. However, there is still no report on the results of 10-year follow-up. This study evaluated the use of long-term oncology and the renal outcomes of LESS radical nephrectomy (LESS-RN) in the treatment of localized renal cancer. Methods: We retrospectively analyzed the clinical data of patients treated with LESS-RN at Changhai Hospital from 2009 to 2012. Patients with localized kidney cancer who were followed-up for at least 10 years were included in the study. The baseline data and major perioperative outcome variables were analyzed. Overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method. Results: A total of 48 patients were included in the study, which had a median follow-up of 11 years (interquartile range, 10.7-11.8 years). The 10-year OS and CSS rates were 87.5% [42/48; 95% confidence interval (CI): 0.778-0.972] and 97.9% (47/48; 95% CI: 0.937-1.021), respectively. At the most recent follow-up, there were 5 patients with a chronic kidney disease stage ≥3. Among these 5 patients, 3 developed uremia and required continuous dialysis. Conclusions: For localized renal cancer, LESS-RN is safe and effective with excellent long-term oncology controllability and good functional outcomes. Prospective studies with large sample sizes need to be conducted to validate our results.

Differential expression of glucose metabolism-related genes and AMP-activated protein kinases in crop tissue of male and female pigeons (Columba livia domestica) during the incubation and chick-rearing periods.

The objective of this study was to explore the carbohydrate contents of crop milk, insulin and glucose concentrations in serum and the expression patterns of AMP-activated protein kinases (AMPKs) and genes related to glucose metabolism in pigeon crops during the breeding period. Crop milk was collected from squabs of rearing Day 1 (R1) to R6. Contents of total sugar and reducing sugar increased to the maximum levels at R6 (p < 0.05). Forty-two pairs of adult pigeons were allotted to seven groups by different breeding stages, and their crops and serum were sampled. No significant differences were found in either insulin or glucose levels in serum. The glucose transporter 2 gene level was the greatest at R15 in females, whereas it was at R7 in males. However, sodium-dependent glucose transporters 1 expression in both sexes decreased from incubation Day 17 (I17) to R7. In females, glucokinase expression peaked at R1, and at R1 and R7 in males. Pyruvate kinase mRNA levels peaked at R7 in females and at R15 males. The mRNA abundance of fructose-1,6-bisphosphatase 1 in both sexes and glucose-6-phosphatase in females decreased after I10. While phosphoenolpyruvate carboxykinase 1 expression decreased after I17 (p < 0.05). Protein levels of AMPKα in crops were minimized at R1 (p < 0.05). In females, expression of AMPKα1 and AMPKα2 was inhibited at I17 and R1 (p < 0.05). In males, AMPKα1 expression was decreased at R7 (p < 0.05) and AMPKα2 was reduced at I10 and R1. pAMPK expression was the lowest at I17 in females, and it was at R7 and R25 in males. Conclusively, glycolysis in pigeon crops was enhanced during chick-rearing, while gluconeogenesis was significantly inhibited. The stability of the insulin level suggests that it was probably not involved in the regulation of glucose metabolism in crop tissues.

A model based on machine learning for the prediction of cyclosporin A trough concentration in Chinese allo-HSCT patients.

BACKGROUND: Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients. METHODS: A total of 7874 cases of CsA therapeutic drug monitoring data from 2069 allo-HSCT patients were retrospectively included. Sequential forward selection was used to select variable subsets, and eight different algorithms were applied to establish the prediction model. RESULTS: XGBoost exhibited the highest prediction ability. Except for the variables that were identified by previous studies, some rarely reported variables were found, such as norethindrone, WBC, PAB, and hCRP. The prediction accuracy within ±30% of the actual trough concentration was above 0.80, and the predictive ability of the models was demonstrated to be effective in external validation. CONCLUSION: In this study, models based on machine learning technology were established to predict CsA levels 3-4 days in advance during the early inpatient phase after HSCT. A new perspective for CsA clinical application is provided.

Differentiating benign from malignant gallbladder wall thickening in non-contrast MRI imaging: Preliminary study of a combined diagnostic indicator.

To synthetically evaluate the diagnostic accuracy of image features for differentiating benign from malignant gallbladder wall thickening disease with non-contrast MRI and establish the optimal diagnostic indicator. A total of 23 patients with wall thickening type gallbladder carcinoma and 61 patients with benign wall thickening disease were included. The diagnostic performance of six image features including the layered pattern on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) images, T2WI signal intensity, papillary growth, the apparent diffusion coefficient (ADC) value, and the lesion to liver parenchyma ratio (LLR) of gallbladder were evaluated and compared. The receiver operating characteristic (ROC) curve and binary logistic regression analysis were used to construct the optimally combined indicator. All six indicators showed high diagnostic accuracy. The layered pattern on DWI and LLR had the highest area under the curve (AUC) value (0.904), followed by the layered pattern on T2WI (0.883), T2WI signal intensity (0.859), ADC value (0.836), and papillary growth (0.796). There was no statistically significant difference in the AUC among indicators for pairwise comparisons. A combination of layered patterns on DWI and papillary growth was shown to be the optimal indicator by binary logistic regression analysis. The AUC value of the combination (0.972) was higher than the layered pattern on DWI (0.904) and papillary growth (0.796) (P < .001). Non-contrast MRI provides several reliable indicators for differentiating benign from malignant gallbladder thickening disease. The combination of layered patterns on DWI and papillary growth is the optimal indicator.

Cost-effectiveness analysis of rhTPO and rhIL-11 in the treatment of chemotherapy-induced thrombocytopenia in hematological tumors based on real-world data.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system. METHODS: We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed. RESULTS: A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO. CONCLUSIONS: In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.

Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism.

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro, and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.

Drug-related problems identified by clinical pharmacists in nephrology department of a tertiary hospital in China-a single center study.

BACKGROUND: There is a lack of data on drug-related problems (DRPs) occurring in nephrology department in China. The objective of this study was to identify and categorize the types and causes of DRPs and to assess their severity. DRPs were examined by clinical pharmacists and the results of their interventions were rated. METHODS: Clinical pharmacists reviewed all medication orders for patients and documented clinical pharmacy services within a nine-month study period. The Pharmaceutical Care Network Europe (PCNE) classification (Version 9.00) was used to identify DRPs. Our Primary outcomes measured the number, causes, types, potential hazards of DRPs and the types and success rate of intervention. RESULTS: Admission medication reconciliation data of 113 patients with chronic kidney disease (CKD) were collected and all of the medications were reviewed retrospectively. Exclude 26 patients who did not occurred DRPs, 87 patients (77%) identified 101 DRPs. The average DRP number per patient was 1.16. The most common type of problem was "treatment effectiveness P1" (84.16%; 85/101). The most common causes were "drug selection C1" (36.00%; 45/125), "dose selection C3" (29.60%; 37/125), and "patient related C7" (26.40%; 33/125). Clinical pharmacists totally proposed 249 interventions, of which 190 (76.31%) were fully accepted and implemented. CONCLUSIONS: DRPs are common among CKD patients in the nephrology department. Hence the necessity for pharmaceutical care to be improved to ensure the ongoing safety of patients.

Prevalence and determinants of potentially inappropriate medications prescribing in elderly patients in Chinese communities.

BACKGROUND: To assess the prevalence and associated risk of potentially inappropriate medications (PIMs) prescribing in community-dwelling elderly patients in China and to examine the most frequently used PIMs. This will provide a reference for the formulation of medication manuals for the community-dwelling elderly and further standardize the use of medications in elderly patients. METHODS: We conducted a cross-sectional retrospective study from April 1, 2020 to April 30, 2020. Data from elderly patients aged ≥65 years were collected from the Hengjie (N=2,294), Loujiang (N=3,972), and Tongxing communities (N=1,969) in Suzhou. The frequency of PIMs was detected using the 2019 Beers criteria and the 2017 Chinese criteria. Chi-square (for categorical variables), ANOVA (for continuous variables as applicable), and logistic regression were used to describe and identify potential predictors of PIMs. RESULTS: A total of 8,235 elderly patients were examined. Using the Chinese criteria, the prevalence of PIMs was 37.07%, which was slightly higher than that found using the 2019 Beers criteria (32.16%). The most prescribed PIMs were estazolam (21.53%) and insulin (4.60%) based on the Chinese criteria. Logistic regression analysis showed that advanced age, polypharmacy, and comorbid disease of patients were associated with a high risk of PIMs. Furthermore, the educational background and professional title of physicians were also associated with PIMs. CONCLUSIONS: Given the high prevalence of PIMs in the Chinese community-dwelling elderly population, the implementation of evidence-based interventions to promote rational clinical drug use could improve their quality of life.

Functional classification of prostate cancer­associated miRNAs through CRISPR/Cas9­mediated gene knockout.

The aim of the present study was to use the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR­associated (Cas) 9­mediated gene knockout technology for the rapid classification of the differential function of micro (mi)RNAs screened using miRNA expression profiling by microarray. The rational design of single guide RNAs for the CRISPR/Cas9 system was verified to function in human LNCaP cells with rapid and efficient target gene editing. miRNA (miR)­205, miR­221, miR­222, miR­30c, miR­224, miR­455­3p, miR­23b and miR­505 were downregulated in patients with prostate cancer (PCa) and were experimentally validated to function as tumor suppressors in prostate cancer cells, affecting tumor proliferation, invasion and aerobic glycolysis. In addition, the data of the present study suggested that miR­663a and mfiR­1225­5p were upregulated in prostate cancer tissues and cell proliferation of miR­663a and miR­1225­5p knockout PCa cells was significantly lower compared with miR­NC cells. Furthermore, knockout of miR­1225­5p and miR­663a significantly decreased the lactate production in LNCaP cells in vitro. In conclusion, the present study offered a simple and efficient method for rapidly classifying miRNA function by applying CRISPR/Cas9 in LNCaP cells. The present study suggested, for the first time to the best of the authors' knowledge, that the aberrant expression of miR­663a and miR­1225­5p may be involved with the progression of prostate cancer, implying their potential as candidate markers for this type of cancer. However, the precise role of miR­663a and miR­1225­5p in accelerating the development of prostate cancer and promoting tumor progression remains to be elucidated.

Exposure to microplastics impairs digestive performance, stimulates immune response and induces microbiota dysbiosis in the gut of juvenile guppy (Poecilia reticulata).

Microplastics (MPs) are widely distributing in aquatic environment. They are easily ingested by aquatic organisms and accumulate in digestive tract especially of intestine. To explore the potential effects of MPs on intestine, here we, using juvenile guppy (Poecilia reticulata) as experimental animal, investigated the response characteristics of digestion, immunity and gut microbiota. After exposure to 100 and 1000 µg/L concentrations of MPs (polystyrene; 32-40 µm diameters) for 28 days, we observed that MPs could exist in guppy gut and induce enlargement of goblet cells. Activities of digestive enzymes (trypsin, chymotrypsin, amylase and lipase) in guppy gut generally reduced. MPs stimulated the expression of immune cytokines (TNF-α, IFN-γ, TLR4 and IL-6). Through high throughput sequencing of 16S rRNA gene, decreases in diversity and evenness and changed composition of microbiota were found in guppy gut. PICRUSt analysis revealed that MPs might have effects on intestinal microbiota functions, such as inhibition of metabolism and repair pathway. Our findings suggested that MPs could retain in the gut of juvenile guppy, impair digestive performance, stimulate immune response and induce microbiota dysbiosis in guppy gut. The results obtained here provide new insights into the potential risks of MPs to aquatic animals.

[Xiao's "xingnaofusu" needling for regaining consciousness and the influence on width of the third ventricle in patients with persistent vegetative state].

OBJECTIVE: To observe the influence of Xiao's "xingnaofusu" needling (the technique for resuscitation) on regaining consciousness in the patients with persistent vegetative state (PVS). METHODS: A total of 50 patients of PVS were randomized into an observation group and a control group, 25 cases in each. The patients in the control group were treated by the routine western medicine, and those in the observation group treated by Xiao's "xingnaofusu" needling and routine western medicine. Baihui (GV20), Dingshen (Extra) to Shangen (Extra) (penetrating technique), Fengchi (GB20) to GB20 (penetrating technique), Neiguan (PC6) to Waiguan (TE5) (penetrating technique), Hegu (LI4) to Laogong (HT8) (penetrating technique) and Taichong (LR3) to Yongquan (KI1) (penetrating technique) were selected. The treatment was given once a day, 10 days as one treatment course, 3 courses in total. The coma recovery scale-revised (CRS-R) score, the modified Ashworth scale (MAS) score and the Glasgow coma scale (GCS) were separately compared before and after the treatment. Additionally, CT scanning was adopted to measure the width of the third ventricle before and after treatment so as to evaluate the clinical therapeutic effect. RESULTS: After the treatment, the CRS-R and GCS scores in the two groups increased remarkably, and MAS score reduced obviously as compared with that before the treatment(P<0.05); and the CRS-R and GCS scores were higher, and MAS score lower in the observation group than those in the control group(P<0.05). Compared with the control group, the width of the third ventricle reduced obviously in the observation group after the treatment(P<0.05). At the end of the treatment courses, the effective rate was 79.2%(19/24)in the observation group and was 47.8%(11/23) in the control group. The effective rate of the observation group was obviously higher than that of the control group (P<0.05). CONCLUSION: Xiao's "xingnaofusu" needling can remarkably improve the central nerve function, promote the recovery of brain function and the motor function of limbs, reduce the width of the third ventricle and improve the clinical therapeutic effect of regaining consciousness in the patients with PVS.

[Effects of elevated CO2 concentration on grain filling capacity and quality of rice grains located at different positions on a panicle.] / 高浓度CO2对稻穗不同位置籽粒结实和米质性状的影响.

The rising atmospheric CO2 concentration affects spikelets development, grain filling process, and rice quality. However, it is unclear that whether such effects are related to grain positions on rice panicle. By using a rice FACE (Free-Air CO2 Enrichment) platform, we grew a japoni-ca rice cultivar Wuyunjing 23, characterized with high yield and good quality, under ambient (Ambient) and elevated CO2 concentrations (+200 µmol·mol-1, FACE). The effects of increased CO2 concentration on spikelet density, grain filling capacity, the appearance and eating quality of rice grains were examined and the association of such effects with grain positions on rice panicle were investigated. The results showed that CO2 enrichment increased grain yield of Wuyunjing 23 by 18.3%. The panicle number per unit land area and filled-grain weight increased by 21.4% and 9.4%, respectively; whereas the number of spikelets per panicle and filled-grain percentage decreased by 9.0% and 2.2%, respectively. The decreased filled-grain percentage of rice grown under FACE treatment was mainly related to the increases of empty-grain percentage in all parts of rice panicle. The decrease of rice spikelets number per panicle by FACE treatment was mainly due to the substantial decrease of surviving spikelets of secondary branches in upper and middle parts of rice panicles instead of other positions. The CO2-induced changes of filled-grain weight and filled-grain percentage were similar among grains located at different positions on rice panicle. FACE treatment reduced the green grain rate and increased the grain length and width, with the grains at different positions on rice papnicle showing similar responses. FACE significantly increased chalky grain percentage by 59% and chalkiness degree by 55%, with the increases for both parameters following the order of primary branches＞secondary branches and upper part＞middle part＞lower part. FACE treatment slightly increased amylose content while decreased peak viscosity, hot viscosity, breakdown, final viscosity and setback, but most of these effects were nonsignificant. The gelatinization temperature of rice also reduced by 5% under FACE, and the decrease of inferior spikelets was greater than that of superior spikelets. In summary, the yield increase of Wuyunjing 23 under high CO2 concentration was mainly related to the increases of panicle number and individual grain weight, while the panicle size was reduced. Elevated CO2 concentration reduced green grain percentage but increased grain chalkiness, and had little effect on cooking and eating quality. The grain positions on rice panicle affected the responses of spikelets development, grain filling capacity and grain quality of rice to elevated CO2 concentration, but the effects varied across different indices.

Transcriptome Reveals the Rice Response to Elevated Free Air CO2 Concentration and TiO2 Nanoparticles.

Increasing CO2 levels are speculated to change the effects of engineered nanomaterials in soil and on plant growth. How plants will respond to a combination of elevated CO2 and nanomaterials stress has rarely been investigated, and the underlying mechanism remains largely unknown. Here, we conducted a field experiment to investigate the rice (Oryza sativa L. cv. IIyou) response to TiO2 nanoparticles (nano-TiO2, 0 and 200 mg kg-1) using a free-air CO2 enrichment system with different CO2 levels (ambient ∼370 µmol mol-1 and elevated ∼570 µmol mol-1). The results showed that elevated CO2 or nano-TiO2 alone did not significantly affect rice chlorophyll content and antioxidant enzyme activities. However, in the presence of nano-TiO2, elevated CO2 significantly enhanced the rice height, shoot biomass, and panicle biomass (by 9.4%, 12.8%, and 15.8%, respectively). Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that genes involved in photosynthesis were up-regulated while most genes associated with secondary metabolite biosynthesis were down-regulated in combination-treated rice. This indicated that elevated CO2 and nano-TiO2 might stimulate rice growth by adjusting resource allocation between photosynthesis and metabolism. This study provides novel insights into rice responses to increasing contamination under climate change.

CXCL12/CXCR4 signaling contributes to neuropathic pain via central sensitization mechanisms in a rat spinal nerve ligation model.

BACKGROUND: Previous studies have demonstrated that the CXCL12/CXCR4 signaling axis is involved in the regulation of neuropathic pain (NP). Here, we performed experiments to test whether the CXCL12/CXCR4 signaling pathway contributes to the pathogenesis of neuropathic pain after spinal nerve ligation (SNL) via central sensitization mechanisms. METHODS: Neuropathic pain was induced and assessed in a SNL rat model. The expression and distribution of CXCL12 or CXCR4 were examined by immunofluorescence staining and western blot. The effects of CXCL12 rat peptide, CXCL12 neutralizing antibody, CXCR4 antagonist, and astrocyte metabolic inhibitor on pain hypersensitivity were explored by behavioral tests in naive or SNL rats. We measured the expression level of c-Fos and CGRP to evaluate the sensitization of neurons by RT-PCR. The activation of astrocyte and microglia was analyzed by measuring the level of GFAP and iba-1. The mRNA levels of the pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 and Connexin 30, Connexin 43, EAAT 1, EAAT 2 were also detected by RT-PCR. RESULTS: First, we found that the expression of CXCL12 and CXCR4 was upregulated after SNL. CXCL12 was mainly expressed in the neurons while CXCR4 was expressed both in astrocytes and neurons in the spinal dorsal horn after SNL. Moreover, intrathecal administration of rat peptide, CXCL12, induced hypersensitivity in naive rats, which was partly reversed by fluorocitrate. In addition, the CXCL12 rat peptide increased mRNA levels of c-Fos, GFAP, and iba-1. A single intrathecal injection of CXCL12 neutralizing antibody transiently reversed neuropathic pain in the SNL rat model. Consecutive use of CXCL12 neutralizing antibody led to significant delay in the induction of neuropathic pain, and reduced the expression of GFAP and iba-1 in the spinal dorsal horn. Finally, repeated intrathecal administration of the CXCR4 antagonist, AMD3100, significantly suppressed the initiation and duration of neuropathic pain. The mRNA levels of c-Fos, CGRP, GFAP, iba-1, and pro-inflammatory cytokines, also including Connexin 30 and Connexin 43 were decreased after injection of AMD3100, while EAAT 1 and EAAT 2 mRNAs were increased. CONCLUSION: We demonstrate that the CXCL12/CXCR4 signaling pathway contributes to the development and maintenance of neuropathic pain via central sensitization mechanisms. Importantly, intervening with CXCL12/CXCR4 presents an effective therapeutic approach to treat the neuropathic pain.

Assessment of cerebral infarction after transient cerebral ischemic attack by ABCD2 score combined with the position of intracranial vascular stenosis.

This study aims to investigate the value of the ABCD score combined with the position of the offending vessel stenosis in predicting the risk of transient ischemic attack (TIA) to develop into cerebral infarction.The ABCD score and head magnetic resonance imaging + magnetic resonance angiography (MRA) results of 192 patients with TIA were retrospectively analyzed. With the 7th day as the endpoint time, these patients were divided into 3 groups, according to ABCD scores: low-risk group (n = 105), moderate-risk group (n = 60), and high-risk group (n = 27). Blood vessels were screened using head MRA results, and patients were accordingly divided into 2 groups: proximal vascular stenosis group (n = 71) and nonproximal vascular stenosis group (n = 171). Then, the association of the position of the intracranial vascular stenosis and ABCD score with short-term prognosis was analyzed.Based on the ABCD score, the incidence of cerebral infarction after 1 week was significantly higher in the high-risk group (85.7%) than in the moderate-risk group (16.7%) and low-risk group (1.9%), and the differences were statistically significant (P < .05). When the ABCD score was ≥4 points, the incidence of cerebral infarction after 1 week was significantly higher in the proximal vascular stenosis group (59.1%) than in the nonproximal vascular stenosis group (30.8%), and the difference was statistically significant (P < .05). When the ABCD score was <4 points, the incidence of cerebral infarction after 1 week in the proximal stenosis group (2%) was not significantly different from that in the nonproximal stenosis group (1.9%, P > .05).The ABCD score combined with proximal offending vessel stenosis can improve the short-term prediction of cerebral infarction in patients with TIA.