ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Hypoxia is one of the factors restricting the survival of people at high altitudes, which can cause various symptoms such as vomiting, diarrhea, palpitations, shortness of breath and acute coma. About 80% of patients with acute mountain sickness have at least one symptom of a gastrointestinal distress (e. g., anorexia, nausea, diarrhea, vomiting, etc.). The pathological characteristics, pathogenesis and drug treatment of intestinal injury caused by high-altitude hypoxia were studied, which is conducive to the diagnosis and treatment of plateau gastrointestinal diseases. Therefore, by summarized relevant literature and systematically expounds the related researches on intestinal damage caused by high altitude hypoxia. We summarized the changes of intestinal morphology, intestinal cells, intestinal flora and other intestinal homeostasis caused by high altitude hypoxia, the mechanism of intestinal inflammation and oxidative damage, and the treatment of traditional Chinese medicine, which provide reference and information for reference for scientific research workers and clinicians.

Danggui Buxuetang， derived from Clarifying Doubts about Damage from Internal and External Causes （Volume 2）： Treatise on Heat Injury to Stomach Qi（《内外伤辨惑论卷中·暑伤胃气论》） by LI Dongyuan in the Jin and Yuan dynasties， is a classic and famous formula for tonifying qi and generating blood that has been inherited and promoted by successive generations of medical practitioners and has been included in the "Catalogue of Ancient Classical Prescriptions （First Batch）" published by the National Administration of Traditional Chinese Medicine in 2018. The paper analyzed the historical origin， composition， dosage， processing， preparation， decocting， and taking methods， efficacy， and application of the classic formula Danggui Buxuetang by consulting ancient and modern literature and combining the key information examination principles of ancient classic prescriptions. A total of 604 pieces of information on relevant ancient literature were collected， including 186 ancient Chinese medical books， of which 40 （five in the Jin and Yuan dynasties， 19 in the Ming Dynasty， and 16 in the Qing Dynasty） had detailed records of composition， processing， and dosage. Danggui Buxuetang is mainly comprised of Astragali Radix and Angelicae Sinensis Radix. According to the ancient and modern dose conversion， there are 37.3-38.1 g of Astragali Radix and 7.5-7.6 g of Angelicae Sinensis Radix in the formula. Astragali Radix is preferably fried with honey and Angelicae Sinensis Radix with wine. Astragali Radix and Angelicae Sinensis Radix are decocted with 600 mL of water to 300 mL， and taken warm before meals. The main effect of this formula are described in ancient books as blood deficiency and fever， with symptoms of muscle fever， dryness and heat， irritability and thirst， red eyes and face， sleeplessness in daytime and night， and surging and feeble pulse which is weak under hard pressing， and it is a famous formula for replenishing qi and generating blood. Modern research shows that Danggui Buxuetang is commonly used in the treatment of various kinds of anemia， diabetic nephropathy， tumors， and cardiovascular and cerebrovascular diseases. The above research results can provide a reference for the subsequent development and research on the classic formula Danggui Buxuetang.

Neurons in the primary auditory area (AUDp) innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions. However, the brain-wide connections of these neurons have not been comprehensively investigated. Here, we simultaneously applied virus-based anterograde and retrograde tracing, labeled the connections of excitatory and inhibitory neurons in the mouse AUDp, and acquired whole-brain information using a dual-channel fluorescence micro-optical sectioning tomography system. Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions. In the isocortex, functionally different areas consistently sent feedback-dominated projections to these neurons, with concomitant laterally-dominated projections from the sensory and limbic cortices to inhibitory neurons. In subcortical regions, the dorsal and medial parts of the non-lemniscal auditory thalamus (AT) were reciprocally connected to the AUDp, while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back, indicating the regional heterogeneity of the AUDp-AT circuit. Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.

The zona incerta (ZI) is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation. However, the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped. Here, we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing. The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized. The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors, while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus. Clustering results show that the medial and lateral ZI are two different major functional compartments, and they can be further divided into more subdomains based on projection and input connectivity. This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information, conveying motivational states, and modulating global behaviors.
Animals ; Mice ; Zona Incerta ; GABAergic Neurons ; Connectome

Objective:To explore the clinical significance of different metabolic parameters measured by 18F-fluorodeoxyglucose (FDG) PET/CT in predicting the effectiveness of chemotherapy in advanced lung adenocarcinoma patients. Methods:A set of metabolic parameters of PET/CT and clinical characteristics which were detected from 127 patients (70 males, 57 females, age (56.8±10.1) years) with advanced lung adenocarcinoma treated with at least two cycles of chemotherapy in Hainan Cancer Hospital between August 2017 and June 2019 were retrospectively analyzed. The effects of those parameters on patients′ survival were analyzed by receiver operating characteristic (ROC) curve, Kaplan-Meier method (log-rank test) and Cox proportional hazards model.Results:Maximum standardized uptake value (SUV max), metabolic tumor volume 30% (MTV 30), and total lesion glycolysis 30% (TLG 30) had larger areas under the curve (0.581, 0.606 and 0.693 respectively) compared with other imaging parameters, and the optimal cut-off values were 10.12, 20.21 cm 3 and 81.25 g respectively. Kaplan-Meier univariate and Cox analyses synergistically showed that clinical stage (hazard ratio ( HR)=0.293(95% CI: 0.190-0.451), P<0.001), smoking ( HR=0.732(95% CI: 0.605-0.885), P=0.001), and MTV 30 ( HR=1.555(95% CI: 1.078-2.242), P=0.018) had significant predictive value for progression-free survival (PFS). Stratified analysis showed that smoking and MTV 30>20.21 cm 3 were independent prognostic factors for poor PFS in patients with advanced lung adenocarcinoma receiving chemotherapy ( HR=0.738(95% CI: 0.611-0.893), P=0.002; HR=1.502(95% CI: 1.037-2.177), P=0.032). Conclusions:Clinical stage, smoking and MTV 30 are independent prognostic factors of PFS in patients with advanced lung adenocarcinoma receiving chemotherapy. MTV 30≤20.21 cm 3 is expected to be an image biomarker for predicting survival and selecting patients with advanced lung adenocarcinoma who are more likely to benefit from chemotherapy.

Objective:To investigate the effect of plasma exosome miR-18a-3p on of apoptosis and cell cycle cumulus cells (CCs) in polycystic ovary syndrome (PCOS) via targeting CITED2.Methods:qRT-PCR assay was used to detect the expression of miR-18a-3p in plasma, plasma-derived exosome and CCs of patients no matter with PCOS and non PCOS. After being transfected with miR-18a-3p mimic, the exosome was co-cultured with CCs, the cell cycle distribution and apoptosis of CCs were detected by flow cytometry assays. Gene ontology (GO) analysis was performed and CITED2 was included in follow up experiments. pcDNA3.1-CITED was transfected into CCs and then co-cultured with exosome to explore the co-effect of miR-18a-3p and CITED2 on the cell cycle and apoptosis of CCs.Results:The plasma-derived exosome isolated from CCs with PCOS were identified successfully, and the expression of miR-18a-3p was significantly decreased in plasma, exosome and CCs in PCOS, compared with that in non-PCOS (all P<0.05) . CITED2 could be regulated as a target of miR-18a-3p in CCs. Compared with NC group, overexpression of miR-18a-3p could significantly decrease proportion of CCs cells in G0/G1 phase and inhibit their apoptosis in PCOS patients (all P<0.05) . The effect of over-expressing miR-18a-3p could be partially reversed by up-regulating CITED2 (all P<0.05) . Conclusions:Plasma exosomal miR-18a-3p has the effect to induce the S phase of CCs cells, subsequently inhibit apoptosis, then restrain the progression of PCOS. Plasma exosomal miR-18a-3p is expected to play a paramount role in the target therapy of PCOS.

Objective:To investigate the role of WWC2-AS1/miR-382-5p/FZD3 in granulosa cell (GCs) of polycystic ovary syndrome (polycystic ovarian syndrome, PCOS) patients and its molecular mechanism.Methods:Bioinformatics tools were used to predict the molecular mechanism of PCOS. The expressions of WWC2-AS1, miR-382-5p and FZD3 in serum and GCs of patients with PCOS and healthy controls were detected by qRT-PCR. The effects of WWC2-AS1/miR-382-5p/FZD3 on the proliferation and apoptosis of GCs were observed by CCK-8 and flow cytometry. The interaction between WWC2-AS1 and miR-382-5p, miR-382-5p and FZD3 was verified by double luciferase report experiment.Results:Compared with the control group, the expression of WWC2-AS1 and FZD3 in serum and GCs of PCOS patients was significantly up-regulated, while the expression of miR-382-5p was down-regulated. Silencing WWC2-AS1 could significantly promote the proliferation of GCs in PCOS and inhibit the apoptosis of GCs (all P<0.05) . There is a WWC2-AS1/miR-382-5p/FZD3 interaction network in PCOS, and miR-382-5p inhibitor or overexpressed FZD3 can partially reverse the regulatory effect of silent WWC2-AS1 on GCs in PCOS. Conclusion:This study shows that WWC2-AS1 regulates miR-382-5p and up-regulates FZD3, which promotes the proliferation of GCs and inhibits apoptosis in the progression of PCOS. WWC2-AS1/miR-382-5p/FZD3 may be an effective molecular target for the treatment of PCOS.

Objective To learn the effects of family supportive supervisors on medical staff turnover intention. Methods The scales of family supportive supervisor behavior scales, work-family conflict scale and turnover intention scale were used in the study. The data were collected from a questionnaire survey of 214 army tertiary hospitals′ medical staff during October to December 2017. Hierarchical regression analysis was used to establish a model to understand the influence of family supportive supervisor behavior, two-way conflict between work and family, using the independent variables, on turnover intention of medical staff. Results The and family supportive supervisor behaviors had a negative explanation to medical staff turnover intention ( β = - 0. 211, P < 0. 01), work interference with family had a positive explanation to it (β = 0. 358, P < 0. 01), family interference with work had an obscure explanation to medical staff turnover intention (β = 0. 104, P > 0. 05). Work interference with family had a partially mediating effect which influenced family supportive supervisor behaviors on medical staff turnover intention. Conclusions Family supportive supervisor behavior, as an organizational support, can effectively alleviate the work interference on family for medical staff and thus minimize their turnover intention.

Research team shows virtual and distributed characteristics in the big science era.It is common and frequent that researcher often communicates with each other informally for knowledge sharing regularly or non-regularly.Thus raised the attention paid by research administrators to such informal communication in the research team.From the aspect of community practice,we tried to propose helpful suggestions and considerations to improve the effectiveness of informal communication from following four perspectives:focusing on the informal social network in research team,create conditions for informal communication,train communication coordinators and measure the values of informal communication scientifically.