[Different concentrations of adapalene induce differentiation and apoptosis of SH-SY5Y cells]. / 不同浓度阿达帕林诱导SH-SY5Y细胞的分化及凋亡.

OBJECTIVES: To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis. METHODS: SH-SY5Y cells were divided into control group, low concentration (0.1 µM and 1 µM) adapalene groups, and high concentration (10 µM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker ßIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit. RESULTS: Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of ßIII-tubulin and NFH increased in the 1 µM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (P<0.05). CONCLUSIONS: Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.

Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study.

OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: • The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. • Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. • The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.

The roles of phospholipase C-ß related signals in the proliferation, metastasis and angiogenesis of malignant tumors, and the corresponding protective measures.

PLC-ß is widely distributed in eukaryotic cells and is the key enzyme in phosphatidylinositol signal transduction pathway. The cellular functions regulated by its four subtypes (PLC-ß1, PLC-ß2, PLC-ß3, PLC-ß4) play an important role in maintaining homeostasis of organism. PLC-ß and its related signals can promote or inhibit the occurrence and development of cancer by affecting the growth, differentiation and metastasis of cells, while targeted intervention of PLC-ß1-PI3K-AKT, PLC-ß2/CD133, CXCR2-NHERF1-PLC-ß3, Gαq-PLC-ß4-PKC-MAPK and so on can provide new strategies for the precise prevention and treatment of malignant tumors. This paper reviews the mechanism of PLC-ß in various tumor cells from four aspects: proliferation and differentiation, invasion and metastasis, angiogenesis and protective measures.

Prevalence and risk factors of malnutrition in patients with pulmonary tuberculosis: a systematic review and meta-analysis.

Background: Malnutrition is prevalent in patients with pulmonary tuberculosis (PTB) and is associated with a poor prognosis. Objective: This study aims to assess the prevalence and risk factors of malnutrition in patients with PTB. Methods: Studies related to the prevalence and risk factors of malnutrition in patients with PTB were searched through PubMed, Embase, Web of Science, and Cochrane Library databases from January 1990 to August 2022, and two researchers screened the literature, evaluated the quality, and extracted data independently. A random-effects model was used to pool the effect sizes and 95% confidence intervals. Subgroup analysis, meta-regression analysis, and sensitivity analysis were further performed to identify sources of heterogeneity and evaluate the stability of the results. Publication bias was assessed by Doi plot, Luis Furuya-Kanamori (LFK) asymmetry index, funnel plot, and Egger's tests. Results: A total of 53 studies involving 48, 598 participants were identified in this study. The prevalence of malnutrition was 48.0% (95% CI, 40.9-55.2%). Subgroup analysis revealed that malnutrition was more common among male gender (52.3%), bacterial positivity (55.9%), family size over 4 (54.5%), drug resistance (44.1%), residing in rural areas (51.2%), HIV infection (51.5%), Asian (51.5%), and African (54.5%) background. The prevalence of mild, moderate, and severe malnutrition was 21.4%, 14.0%, and 29.4%, respectively. Bacterial positivity (OR = 2.08, 95% CI 1.26-3.41), low income (OR = 1.44, 95% CI 1.11-1.86), and residing in rural areas (OR = 1.51, 95% CI 1.20-1.89) were risk factors of malnutrition in patients with PTB. However, male (OR = 1.04, 95% CI 0.85-1.26) and drinking (OR = 1.17, 95% CI 0.81-1.69) were not risk factors for malnutrition in patients with PTB. Due to the instability of sensitivity analysis, HIV infection, age, family size, smoking, and pulmonary cavity need to be reevaluated. Meta-regression suggested that sample size was a source of heterogeneity of prevalence. The Doi plot and LFK asymmetry index (LFK = 3.87) indicated the presence of publication bias for prevalence, and the funnel plot and Egger's test showed no publication bias for risk factors. Conclusion: This meta-analysis indicated that malnutrition was prevalent in patients with PTB, and bacterial positivity, low income, and those residing in rural areas were risk factors for malnutrition. Therefore, clinical workers should pay attention to screening the nutritional status of patients with PTB and identifying the risk factors to reduce the incidence of malnutrition and provide nutritional interventions early to improve the prognosis in patients with PTB.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma.

OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Spautin-1 Protects Against Mild TBI-Induced Anxiety-Like Behavior in Mice via Immunologically Silent Apoptosis.

Anxiety is reportedly one of the most common mental changes after traumatic brain injury (TBI). Perineuronal nets (PNNs) produced by astrocytes in the lateral hypothalamus (LHA) that surround gamma-aminobutyric acid-ergic (GABAergic) neurons have been associated with anxiety. The potent anti-tumor effects of Spautin-1, a novel autophagy inhibitor, have been documented in malignant melanoma; moreover, the inhibition of autophagy is reported to mitigate anxiety disorders. However, little is known about the ability of spautin-1 to alleviate anxiety. In this study, we sought to investigate whether spautin-1 could alleviate anxiety-like behaviors post-TBI by reducing the loss of PNNs in the LHA. A mild TBI was established in mice through Feeney's weight-drop model. Then, Spautin-1 (20 mmol/2 µl) was immediately administered into the left lateral ventricle. Behavioral and pathological changes were assessed at 24 h, 7 days, 30 days, 31 days and 32 days after TBI by the neurological severity scores (NSS), open field test (OFT), elevated plus-maze (EPM) test, western blot, immunofluorescence assays and electron microscopy. Spautin-1 significantly reversed TBI-induced decreased time in the central zone during OFT and in the open-arm during the EPM test. Spautin-1 also increased PNNs around GABAergic neurons indicated by WFA- plus GAD2- positive A2-type astrocytes and attenuated M1-type microglia in the LHA 32 days after TBI compared to TBI alone. Moreover, compared to mice that only underwent TBI, spautin-1 downregulated autophagic vacuoles, abnormal organelles, the expression of Beclin 1, USP13, phospho-TBK1, and phospho-IRF3 and upregulated the levels of cleaved caspase-3, -7 and -9, but failed to increase TUNEL-positive cells in the LHA at 24 h. Spautin-1 alleviated anxiety-like behavior in mice exposed to mild TBI; this protective mechanism may be associated with decreased PNNs loss around GABAergic neurons via immunologically silent apoptosis induced by the caspase cascade.

Application of symptom-based mind mapping combined with PBL teaching method in emergency trauma standardized resident training in MDT model.

Explore the feasibility and effectiveness of accepting mind mapping combined with problem-based learning (PBL) teaching method in the standardized training of emergency surgery residents in the multi-disciplinary team (MDT) model of emergency trauma. Eighty-nine doctors under training who rotated in the Department of Emergency Surgery of the First Affiliated Hospital of Anhui Medical University from January 2021 to January 2022 were selected as the study subjects, and randomly divided into a group receiving mind mapping combined with PBL teaching and a group receiving traditional lecture-based learning teaching. Mini-clinical evaluation exercise (Mini-CEX), direct observation of procedural skills (DOPS), teaching adherence, and satisfaction assessments were completed at the time of discharge from the department. There were no significant differences between the observation and control group trainees in terms of gender, age, education, and entry grades. Both groups of doctors were better able to participate in their respective teaching modes and made significant progress. The participants in the observation group had significantly higher Mini-CEX, DOPS, and teaching satisfaction scores than the control group (P < .05). Under the MDT model of emergency trauma, the combination of mind mapping and PBL teaching can improve the comprehensive clinical ability of the trainees more than participating in the traditional lecture-based learning teaching, which is worth promoting and implementing in the clinical standardized training.

CT-Based Radiomics Analysis for Noninvasive Prediction of Perineural Invasion of Perihilar Cholangiocarcinoma.

Purpose: The study aimed to construct and evaluate a CT-Based radiomics model for noninvasive detecting perineural invasion (PNI) of perihilar cholangiocarcinoma (pCCA) preoperatively. Materials and Methods: From February 2012 to October 2021, a total of 161 patients with pCCA who underwent resection were retrospectively enrolled in this study. Patients were allocated into the training cohort and the validation cohort according to the diagnostic time. Venous phase images of contrast-enhanced CT were used for radiomics analysis. The intraclass correlation efficient (ICC), the correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression were applied to select radiomics features and built radiomics signature. Logistic regression analyses were performed to establish a clinical model, a radiomics model, and a combined model. The performance of the predictive models was measured by area under the receiver operating characteristic curve (AUC), and pairwise ROC comparisons between models were tested using the Delong method. Finally, the model with the best performance was presented as a nomogram, and its calibration and clinical usefulness were assessed. Results: Finally, 15 radiomics features were selected to build a radiomics signature, and three models were developed through logistic regression. In the training cohort, the combined model showed a higher predictive capability (AUC = 0.950) than the radiomics model and the clinical model (AUC: radiomics = 0.914, clinical = 0.756). However, in the validation cohort, the AUC of the radiomics model (AUC = 0.885) was significantly higher than the other two models (AUC: combined = 0.791, clinical = 0.567). After comprehensive consideration, the radiomics model was chosen to develop the nomogram. The calibration curve and decision curve analysis (DCA) suggested that the nomogram had a good consistency and clinical utility. Conclusion: We developed a CT-based radiomics model with good performance to noninvasively predict PNI of pCCA preoperatively.

[Effects of Low-dose Antibiotic Exposure on Fetal Growth and Development].

Objective To analyze maternal blood exposure to non-therapeutic antibiotics in late pregnancy and explore the effects of low-dose antibiotics on fetal growth and development.Methods A total of 104 pregnant women in late pregnancy (28-32 weeks) without serious pregnancy complications were enrolled,who had regular antenatal examination and delivery in Peking Union Medical College Hospital and did not use therapeutic antibiotics 2 months before pregnancy and in the whole pregnant process.The levels of antibiotics in the maternal blood were detected by liquid chromatography-tandem mass spectrometry,and the pregnant women were assigned into an antibiotic exposure group (antibiotic positive) and a non-exposure group (antibiotic negative).The length,weight,placental weight,and placental volume of the newborns in the two groups were measured,and the data were statistically analyzed by t test or χ2 test.Results The maternal blood antibiotic test showed 7 positive cases (6.73%,antibiotic exposure group) and 97 negative cases (93.27%,non-exposure group). The average length of newborns in the antibiotic exposure group and the non-exposure group was (49.57±1.40) cm and (48.85±1.77) cm,respectively,with no significant difference (t=1.060,P=0.363).The average weight of newborns in the antibiotic exposure group and the non-exposure group was (3558.57±382.95) g and (3275.36±356.41) g,respectively,with significant difference (t=2.021,P=0.046).The mean placental weight in the antibiotic exposure group and the non-exposure group was (676.43±124.59) g and (631.96±129.25) g,respectively,with no significant difference (t=0.881,P=0.380).The mean placental volume in the antibiotic exposure group and the non-exposure group was (724.67±174.91) cm3 and (676.82±220.86) cm3,respectively,with no significant difference (t=0.560,P=0.388).Compared with those in the non-exposure group,the neonatal length,neonatal weight,placental weight,and placental volume in the antibiotic exposure group increased by 1.47%,8.65%,7.04%,and 7.07%,respectively.Conclusion There are antibiotics in the environment,and maternal blood exposure to non-therapeutic antibiotics can promote the growth and development of the fetus and placenta,especially increasing the fetal weight.

S-ketamine administration in pregnant mice induces ADHD- and depression-like behaviors in offspring mice.

BACKGROUND: Anesthesia and psychotropic drugs in pregnant women may cause long-term effects on the brain development of unborn babies. The authors set out to investigate the neurotoxicity of S-ketamine, which possesses anesthetic and antidepressant effects and may cause attention deficit hyperactivity disorder (ADHD)- and depression-like behaviors in offspring mice. METHODS: Pregnant mice were administered with low-, medium-, and high-dose S-ketamine (15, 30, and 60 mg/kg) by intraperitoneal injection for 5 days from gestational day 14-18. At 21 days after birth, an elevated plus-maze test, fear conditioning, open field test, and forced swimming test were used to assess ADHD- and depression-like behaviors. Neuronal amount, glial activation, synaptic function indicated by ki67, and inhibitory presynaptic proteins revealed by GAD2 in the hippocampus, amygdala, habenula nucleus, and lateral hypothalamus (LHA) were determined by immunofluorescence assay. RESULTS: All the pregnant mice exposed to high-dose S-ketamine administration had miscarriage after the first injection. Both low-dose and medium-dose S-ketamine administration significantly increased the open-arm time and attenuated frozen time in the fear conditioning, which indicates impulsivity and memory dysfunction-like behaviors. Medium-dose S-ketamine administration reduced locomotor activity in the open field and increased immobility time in the forced swimming test, indicating depression-like behaviors. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were found in the hippocampus, amygdala, and habenula nucleus. CONCLUSIONS: These results demonstrate that S-ketamine may lead to detrimental effects, including ADHD-and depression-like behaviors in offspring mice. More studies should be promoted to determine the neurotoxicity of S-ketamine in the developing brain.

"Three-in-One" Structural-Building-Mode-Based Ti16-Type Titanium Oxo Cluster Entirely Protected by the Ligands Benzoate and Salicylhydroxamate.

Titanium oxo clusters (TOCs) with accurate molecular structures have potential applications in photocatalysis, such as photocatalytic degradation, hydrogen production, and water oxidation. The hydrolytic stability and light absorption ability of TOCs have important impacts on photocatalysis, where the selection of peripheral organic ligands plays a significant role. In this regard, salicylhydroxamic acid (abbreviated as H3L) attracts our attention, acting as a ligand for its multidentate and dye-functional features, which can increase the hydrolytic stability and broaden light absorption for TOCs. Herein, two TOCs were solvothermally synthesized and structurally characterized using H3L, formulated as [Ti8(µ2-O)2(µ3-O)2(OiPr)12(L)4]·2CH3CN (1) and [Ti16(µ2-O)10(µ3-O)4(PhCOO)14(L)6(HL)2]·4CH3CN·2iPrOH (2). Complex 2 was obtained by adding excessive benzoic acid over the reaction system of 1, resulting in enhanced hydrolytic stability via the replacement of all alkoxy ligands by multidentate ligands for protection. Interestingly, for the first time, the "three-in-one" structural building mode with {Ti6} + {Ti4} + {Ti6} by the common subunits in 2 was observed among all reported TOCs. Moreover, complex 2 can strongly absorb visible light reaching up to 700 nm and exhibit obvious activity for the photodegradation of methyl orange.

Effect of PLC-ß1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma.

OBJECTIVE: To study the roles of AT1R, PLC-ß1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation. METHODS: ELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver tissue of HCC patients, and the correlation between AT1R, PLC-ß1 and CaM and postoperative survival status of patients was followed up and determined. CCK-8 method was used to screen the doses of Ang II and candesartan sensitive to HepG2 and HCCLM3 cells. Transwell experiment was used to observe the effects of different drugs on the migration and invasion activity of HCC cells. Meanwhile, flow cytometry and Western blot were used to detect the expression levels of AT1R, PLC-ß1 and CaM in the cells. Then PLC-ß1 siRNA was selected to transfect HCC cells, so as to further clarify the mechanism of the above signal proteins. HepG2 cells were inoculated under the hepatic capsule of mice to induce the formation of HCC in situ. Ang II and candesartan were used to stimulate HCC mice to observe the difference in liver appearance and measure the liver index. Finally, ELISA and immunofluorescence experiments were selected to analyze the levels of target proteins in mouse serum and liver tissue. RESULTS: The expression levels of target proteins in serum and liver tissue of HCC patients were significantly increased, and the postoperative survival time of patients with high expression of AT1R, PLC-ß1 or CaM was obviously shortened. Ang II and candesartan could significantly promote and inhibit the motility of HCC cells, and had different effects on the levels of AT1R, PLC-ß1 and CaM in cells. However, in hepatocellular carcinoma cells transfected with PLC-ß1 siRNA, the intervention ability of drugs was obviously weakened. Ang II could significantly promote the formation and progression of mouse HCC, while candesartan had the opposite effect. Meanwhile, medications could affect the expressions of target proteins in mouse serum and liver tissue. CONCLUSION: AT1R, PLC-ß1 and CaM may be risk factors affecting the formation and prognosis of HCC, and the PLC-ß1/CaM signaling pathway mediated by AT1R is an important way to regulate the migration and invasion activity of HCC cells.

[Effects of Different Exogenous Selenium Species Application on Growth and Cadmium Uptake of Pak Choi in Cadmium Contaminated Soil].

This study explored the discrepancy in the detoxification effects of different exogenous selenium (Se) species in cadmium (Cd)-contaminated soil to provide a scientific basis for the control of Cd pollution in the soil and the safe production of crops. A pot experiment was conducted to compare the effects of different concentrations (0, 0.5, 1.0, and 2.5 mg·kg-1) of selenite and selenate on the growth (root length, shoot height, biomass, and photosynthetic parameters), uptake, and translocation of Cd on pak choi in Cd-contaminated soil. The results indicated that the detoxification effect of a low Se concentration (≤1.0 mg·kg-1) treatment on Cd was better than that with a high Se concentration (2.5 mg·kg-1) treatment, and the selenite treatment demonstrated a greater detoxification effect on Cd than the corresponding selenate treatment. Meanwhile, the application of low-concentration selenite and selenate both increased the SPAD value, Pn, Gs, Ci, biomass, and shoot length of the pak choi, and the 1.0 mg·kg-1 selenite treatment had the most significant (P<0.05) effect (except Ci). Nevertheless, the photosynthetic parameters of the pak choi under the high-concentration Se were significantly lower than those under the low Se concentration treatment (except Tr, P<0.05). Compared with the treatment without Se (control), the uptake of Cd in the pak choi was reduced under different Se treatments. Compared with the control, the Cd concentration in the shoots of the pak choi treated with 1.0 mg·kg-1 of selenite and selenate decreased by 40.0% and 20.5% (P<0.05), respectively. In addition, the translocation of Cd from the root to the shoot was significantly reduced under the 0.5 mg·kg-1 selenate treatment, while the high-concentration treatments of either exogenous Se promoted the translocation of Cd. Overall, applying the appropriate amount of exogenous Se could promote the photosynthesis and biomass of pak choi, and reduce the accumulation of Cd in pak choi. Therefore, the 1.0 mg·kg-1 selenite treatment is recommended for the control and safe utilization of Cd in Cd-contaminated soil.

[Killing Effect of A CD7 Chimeric Antigen Receptor-Modified NK-92MI Cell Line on CD7-Positive Hematological Malignant Cells].

OBJECTIVE: To investigate the killing effect of NK-92MI cells modified by chimeric antigen receptor (CD7-CAR) and specifically targeting CD7 to CD7+ hematological malignant cells. METHODS: Three types of hematological malignant tumor cells, including 5 cases of CD7+ acute T-lymphoblastic leukemia (T-ALL), 10 cases of acute myeloid leukemia (AML) and 6 cases of T-cell lymphoma were collected, centrifuged, cultured and used to detect the expression levels of tumor cell surface targets; 7-AAD, CD56-APC, CD3-FITC, IgG Fc-PE flow cytometry were used to detected the transfection efficiency of NK-92MI and CD7-CAR-NK-92MI cells, killing efficiencies of CD7-CAR-NK-92MI cells to CD7+ hematological tumor cells in vitro were determined by flow cytometry using PE Annexin V Apoptosis Detection Kit. Secretion differences of NK-92MI and CD7-CAR-NK-92MI cytokines interleukin (IL)-2, interferon (IFN)-γ, and granzyme B detection were estimated by using CBA kit. RESULTS: The killing efficiencies of CD7-CAR-modified NK-92MI cells to CD7+ T-ALL, AML, T-cell lymphoma tumor cells were significantly higher than those of NK-92MI cells without genetical modification. The difference showed statistically significant (P＜0.05). The level of IFN-γ and granzyme B were significantly increased among cytokines secreted by CD7-CAR-modified NK-92MI cells as compared with those of NK-92MI cells without genetical modification (P＜0.05) . CONCLUSION: CD7-CAR-modified NK-92MI cells have significantly improved killing efficiency against CD7+ T-ALL, AML and T lymphoma cells, and shows specific targeting effects, which provides a clinical basis for the treatment of CD7+ hematological malignancies.

Fetal growth restriction mice are more likely to exhibit depression-like behaviors due to stress-induced loss of dopaminergic neurons in the VTA.

Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.

Assessment of proliferation, migration and differentiation potentials of bone marrow mesenchymal stem cells labeling with silica-coated and amine-modified superparamagnetic iron oxide nanoparticles.

Superparamagnetic iron oxide nanoparticles have been widely used for cell labeling in preclinical and clinical studies, to improve labeling efficiency, particle conjugation and surface modifications are developed, but some modified SPIONs exert side-effect on physiological activity of cells, which cannot be served as ideal cell tracker. In this study, amine-modified silica-coated SPIO (SPIO@SiO2-NH2, SPIO@S-N) nanoparticles were used to label bone marrow derived mesenchymal stem cells (BM-MSCs), then the stem cell potentials were evaluated. It was found BM-MSCs could be efficiently labeled by SPIO@S-N nanoparticles. After labeling, the BM-MSCs viability kept well and the migration ability increased, but the osteogenesis and adipogenesis potentials were not impaired. In steroid associated osteonecrosis (SAON) bone defect model, stem cell implantation was performed by injection of SPIO@S-N labeled BM-MSCs into marrow cavity locally, it was found the SPIO positive cells homed to the periphery of defect region in control group, but were recruited to the defect region in poly lactic-coglycolic acid/tricalcium phosphate (PLGA/TCP) scaffold implantation group. In conclusion, SPIO@S-N nanoparticles promoted migration while retained proliferation and differentiation ability of BM-MSCs, implying this kind of nanoparticles could be served not only an ideal tracking marker but also an accelerator for stem cell homing during tissue repair.

The absence of NIPA2 enhances neural excitability through BK (big potassium) channels.

AIM: To reveal the pathogenesis and find the precision treatment for the childhood absence epilepsy (CAE) patients with NIPA2 mutations. METHODS: We performed whole-cell patch-clamp recordings to measure the electrophysiological properties of layer V neocortical somatosensory pyramidal neurons in wild-type (WT) and NIPA2-knockout mice. RESULTS: We identified that layer V neocortical somatosensory pyramidal neurons isolated from the NIPA2-knockout mice displayed higher frequency of spontaneous and evoked action potential, broader half-width of evoked action potential, and smaller currents of BK channels than those from the WT mice. NS11021, a specific BK channel opener, reduced neuronal excitability in the NIPA2-knockout mice. Paxilline, a selective BK channel blocker, treated WT neurons and could simulate the situation of NIPA2-knockout group, thereby suggesting that the absence of NIPA2 enhanced the excitability of neocortical somatosensory pyramidal neurons by decreasing the currents of BK channels. Zonisamide, an anti-epilepsy drug, reduced action potential firing in NIPA2-knockout mice through increasing BK channel currents. CONCLUSION: The results indicate that the absence of NIPA2 enhances neural excitability through BK channels. Zonisamide is probably a potential treatment for NIPA2 mutation-induced epilepsy, which may provide a basis for the development of new treatment strategies for epilepsy.

[Moxibustion improves cardiac function by up-regulating autophagy-related proteins of cardiomyocytes in rats with chronic heart failure].

OBJECTIVE: To observe the effect of moxibustion on cardiac function and the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) and selective autophagy receptor signaling adaptor sequestosome 1 (SQSTM1/p62) in rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in preventing and treating CHF. METHODS: Sixty male SD rats were randomly divided into normal, model, moxibustion, autophagy inhibitor 3-methyladenine (3-MA) and autophagy agonist rapamycin (RAPA) groups (n＝12 rats/group). The CHF model was established by intrape-ritoneal injection of adriamycin (ADR, 2 mg/kg, once every week for 12 weeks). Mild moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min every time. Rats of the 3-MA group were treated by intraperitoneal injection of 3-MA suspension (15 mg/kg), and those of the RAPA group treated by gavage of RAPA suspension (2 mg/kg). All the treatments were given once a day for 3 weeks. The heart rate (HR), cardiac output (CO), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rising and lowering rates of left ventricular pressure (±dp/dtmax) were measured for assessing the cardiac performance. Histopathological changes of the left ventricular myocardium were observed by HE staining. The expression levels of LC3-Ⅰ， LC3-Ⅱ and p62 proteins of the left ventricle myocardium tissue were detected by Western blot. RESULTS: After modeling, the pathological changes of myocardium (as myocardial cell swelling with vacuoles, myocardial fibre breakage, etc.) were obvious, and the HR, LVEDP, LC3-Ⅱ and LC3-Ⅱ/Ⅰ protein expression levels were significantly increased in the model group compared with the normal group (P<0.01), while the CO, LVSP, ±dp/dtmax, and the expression of p62 protein were significantly down-regulated (P<0.01). Following the interventions, the myocardial injury was reduced, the HR, LVEDP, LC3-Ⅱ and LC3-Ⅱ/Ⅰ levels in both moxibustion and 3-MA groups were significantly decreased (P<0.05, P<0.01), while the CO, LVSP, ±dp/dtmax and p62 expression level were significantly increased relevant to the model group (P<0.05, P<0.01). In addition, the ratio of LC3-Ⅱ/Ⅰ was significantly increased, and the expression level of p62 significantly down-regulated in the RAPA group compared with the model group (P<0.01). CONCLUSION: Moxibustion can improve cardiac function in CHF rats, which may be related to its effects in down-regulating the ratio of LC3-Ⅱ/Ⅰ and up-regulating the expression of p62 protein to inhibit cardiomyocyte autophagy.

Comparison of Vaginal Gel and Intramuscular Progesterone for In vitro Fertilization and Embryo Transfer with Gonadotropin-Releasing Hormone Antagonist Protocol.

BACKGROUND: Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer (IVF-ET) with gonadotropin-releasing hormone (GnRH)-antagonist protocol. This study aimed to compare the effect between vaginal progesterone (VP) and intramuscular progesterone (IMP) with GnRH-antagonist protocol after IVF-ET. METHODS: A total of 1760 patients (18 years ≤ age ≤35 years) undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital. In the patients, 1341 patients received VP (VP group) and 419 patients received IMP (IMP group) as luteal support. We compared clinical outcomes between these two groups. The primary objective of the study was the live birth rate. Measurement data between the two groups were conducted using independent samples t-test. The variables in line with non-normal distribution were expressed as median (p25 and p75) and were compared using nonparametric Mann-Whitney U-test. RESULTS: Live birth rate in VP group was 38.55%, significantly higher than that in the IMP group, which was 30.79% (χ2 = 8.287, P = 0.004). The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group (clinical intrauterine pregnancy rate 47.35% vs. 41.29%, χ2 = 4.727, P = 0.030; implantation rate 30.99% vs. 25.26%, χ2 = 14.546, P < 0.001). Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed. CONCLUSION: : Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol.

[Development and application of polymorphic microsatellite markers in Saxifraga genus].

In order to develop genomic-SSR markers for species of Saxifraga genus, a mixed plant genomic DNA sample was sequenced based on high-throughput Illumina MiSeq platform. According to genomic sequencing data, SSR loci were identified with MISA software, and then primers were designed with Primer 3 software. A total of 120 pairs of primers were randomly synthesized and amplified in genomic DNA of a few plant samples. Those primers who have yielded polymorphic bands and were considered easy to amplify were identified. After that, transferability of these primers was evaluated, and phylogenetic relationship of 25 species of Saxifraga genus was analyzed with UPGMA (unweighted pair group method analysis). In our results, 587 256 sequences containing SSRs were identified from a total of 1 881 979 combined read pairs obtained in genomic sequencing. Primers were designated to amplify SSRs containing two to six nucleotide repeat units, screened in a small portion of species. Finally, 17 pairs of primers which have produced abundant of polymorphic bands with little problem were amplified in 25 species of Saxifraga genus. A total of 2 687 polymorphic bands were obtained, the average polymorphic rate was 158 bands per pairs of primers. The transferability rate was ranging from 88.0% to 100% across 25 species of Saxifraga. In phylogenetic analysis, the clustering of 25 species based on 17 pairs of SSR primers was different from morphological classification. Our analysis has provided molecular data for genetic relationship of Saxifraga genus, and the transferable and polymorphic SSRs have provided information for genetic diversity research.