BACKGROUND:Liuwei Dihuang Wan takes"three tonifying and three reducing effects"as its compatibility feature to nourish yin and tonify the kidneys,while Zuogui Wan takes"seeking yin in yang"as its compatibility feature to nourish yin and tonify the kidneys by promoting yang.Both of them belong to the same method of nourishing yin and tonifying the kidneys,and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE:To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism,and to explore their mechanism of action in the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)osteoblastic pathway. METHODS:Thirty-two Sprague-Dawley rats were randomized into model,Liuwei Dihuang Wan,Zuogui Wan,and sham operation group,with eight rats in each group.Osteoporosis models were prepared using removal of both ovaries in the first three groups.Starting at 30 days postoperatively,rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d;rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d;and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d.After 12 weeks of gavage,the rat tibia was taken to measure bone mineral density.The serum levels of estrogen,bone alkaline phosphatase,and cAMP/cGMP were measured using ELISA,and the expression of OPG/RANKL in the femur was detected using western blot. RESULTS AND CONCLUSION:Compared with the sham operation group,the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase(P＜0.05)and an increase in cAMP/cGMP level(P＜0.05).Compared with the model group,the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density(P＜0.05)and bone alkaline phosphatase levels(P＜0.05);the Zuogui Wan group significantly decreased cAMP/cGMP levels(P＜0.05)and upregulated OPG expression(P＜0.05);the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression(P＜0.05);and both groups were unable to significantly increase estrogen levels(P＞0.05).To conclude,Zuogui Wan,which seeks yin from yang,can effectively increase the expression of OPG but cannot downregulate the expression of RANKL.However,Liuwei Dihuang Wan,which has three tonifying and three reducing effects,can bidirectionally regulate the expression of OPG and RANKL.This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan,and further research is needed to verify this conclusion.

BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

BACKGROUND:The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE:To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS:Female Sprague-Dawley rats were randomly divided into three groups(n=12 per group):model group,alendronate group and sham-operated group.Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups.At 4 weeks after modeling,rats in the alendronate group were gavaged with alendronate;the other two groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology,Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION:There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group.Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions,such as binding and catalytic activity,and in biological processes,such as cellular process and metabolic process.Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A.Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group,Hspa1l,Enpp3,Unc45a,Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism.Overall,these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A.

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

In this study, insulin (insulin, INS)/Ca₃PO₄ complex and glucose oxidase (glucose oxidase, GOx)/Cu₃(PO₄)₂ complex were prepared by coprecipitation method. The mineralized insulin (mineralized insulin, m-INS) showed irregular crystalline clusters, and the mineralized glucose oxidase (m-GOx) showed flower spherical morphology, with a diameter of about 1-2 μm. In vitro simulated release experiment showed that m-INS released INS as the pH value of the medium decreased. When the pH value was 4.5, the release amount reached 96.68%. The enzyme activity detection experiment showed that the enzyme activity stability of m-GOx was higher than that of free GOx. It still maintained high activity after 10 days at room temperature, while the activity of GOx was less than 60%. The glucose solution was prepared to simulate the state of normal blood glucose (5.6 mmol/L) and hyperglycemia (22.2 mmol/L). When m-INS and m-GOx were added to the glucose solution, the release amount of INS showed a significant glucose concentration dependence. The higher the glucose concentration, the greater the release amount and release rate of INS. Finally, m-INS, m-GOx and hyaluronic acid (HA) solution were mixed to prepare HA microneedle arrays loaded with m-INS and m-GOx. Type 1 diabetes mice were constructed to evaluate the effect of drug-loaded HA microarray on blood glucose control in diabetic rats. The results show that the HA microneedles loaded with m-INS/m-GOx could deliver drugs effectively. The average blood glucose concentration in diabetic rats dropped to about 7 mmol/L within 1 h, normal blood glucose concentration could be maintained for 10 h, and the overall blood glucose concentration was lower than the level before administration for 36 hours. Compared with HA microneedles loaded with INS only, m-ins microneedles showed better glucose tolerance, longer-lasting glucose control effect and less risk of hypoglycemia. Compared with other sustained-release systems, the preparation process of the core components in this study is simple, efficient, safe and effective, and has great commercial potential.
Animals ; Blood Glucose ; Delayed-Action Preparations/therapeutic use* ; Diabetes Mellitus, Experimental/drug therapy* ; Drug Delivery Systems/methods* ; Glucose Oxidase/chemistry* ; Hyaluronic Acid ; I Blood-Group System ; Insulin/therapeutic use* ; Mice ; P Blood-Group System ; Rats

Based on the latest results of international researches, combining with the experiences of our team in the simulation of acute dyspnea, Xiangya Hospital Central South University has summarized 7 characteristics, procedures and methods of debriefing, including that immediate feedback happens after simulation; feedback is provided by a trained instructor with clinical experience; feedback time is at least longer than the simulation time; various international methods of feedback can be used; the content of feedback is the learning objective; oral feedback is preferred; video can be used to review the details. The study aims to provide a theoretical basis for debriefing in domestic scenario stimulation teaching, and finally improve the effectiveness of the scenario stimulation teaching.

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboo-feeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda populations.Here,we present a 293-megabase chromosome-level genome assembly of B.schroederi to infer its biology,including host adaptations.Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new hosts.Genomic and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that B.schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism.Additionally,we characterized the secretome of B.schroederi and predicted potential drug and vaccine targets for new control strategies.Overall,this genome resource provides new insights into the host adaptation of B.schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages.Our findings on the unique biology of B.schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

【Objective】 To evaluate the effect of Arntl on T cell development and T cell-mediated anti-viral immunity. 【Methods】 Arntl^F/FCD4cre⁺(KO) in mice was constructed to delete Arntl gene specifically in T cells. We examined the percentage and number of T cell subsets in the thymus and spleen by flow cytometry (FCM). At day 8 after lymphocytic choriomeningitis virus (LCMV) infection, the proportions of T cell subsets, virus-specific CD8⁺ T cells and IFN-γ secreting T cells were analyzed. The viral load in the spleen was measured using qPCR. Naive CD4⁺ T cells (CD4⁺CD25^-CD44^-CD62L⁺) were sorted by flow cytometry to perform T helper cell differentiation in vitro. 【Results】 The percentage and number of T cells in the thymus and spleen of KO mice showed no significant change compared with those in the control group (Arntl^F/FCD4cre^- mice, WT) (P>0.05). Acute LCMV infection did not cause observable changes in effector T cell proportion in the spleen of KO mice compared to that in WT mice (P>0.05), but KO mice showed a higher proportion of IFN-γ secreting T cells (P<0.05) and better virus clearance (P<0.05). In addition, naive CD4⁺ T cells from KO mice were more prone to differentiate into Th1 cells in vitro (P<0.05). 【Conclusion】 Arntl deletion in T cells does not affect T cell development, but enhances their ability to defend against viral infection by promoting Th1 cell differentiation and response.

Objective:To analyze the influencing factors of HIV-testing awareness of Myanmar people in Dehong, and provide references for early discovery of HIV infection among Myanmar people.Methods:A cross-sectional study was conducted among 400 Myanmar people in Dehong through convenient sampling method in a form of face-to-face questionnaire interview. HIV-testing awareness and influencing factors were described and analyzed with χ2 and logistic regression method . Results:A total of 393 participants were included in the study, in whom 241 (61.3%) were males, 256(65.1%) were Myanmar people, 233(59.3%) received 1-7 years of education in Myanmar, 348 do not speak Chinese (88.5%), 226(57.5%) were married, 378(96.2%) were non-solitary, 257(65.4%) were workers, the main purpose of etering into China in 273(69.5%) was working in China, 273(69.5%) had stayed in China for more than 2 years, 573(95.4%) had a clear plan on whether to stay in China for a long time in the future. In these Myanmar people, the rate of AIDS-related knowledge awareness was 75.6%; 165(42.0%) had sexual behavior in the last 6 months. 221(56.2%) knew that they had been tested for HIV. Ninety (22.9%) were more likely to actively seek HIV-testing after they had unprotected behaviors such as homosexual sex, injecting drug use, and sex without using condom. Multivariate logistic regression analysis showed that the influencing factors of HIV-testing awareness included being women (compared with men, OR=2.155, 95% CI: 1.088-4.270), educational level of 8-10 years or more than 10 years (compared with education level 1-4 years, OR=5.207, 95% CI: 2.094-12.950; OR=19.780, 95% CI: 5.800-67.457), having sexual behavior in the last 6 months (compared with those who had not, OR=2.534, 95% CI: 1.343-4.779), having received AIDS-related education in the last 6 months (compared with those who had not, OR=2.462, 95% CI: 1.303-4.654), AIDS-related knowledge awareness (compared with those who had no awareness, OR=8.126, 95% CI: 2.936-22.491). Conclusions:Myanmar people have low awareness of HIV-testing in Dehong. Those who were women and high literacy levels, having received AIDS-related knowledge education in the past 6 months, and having AIDS-related knowledge have an active HIV-testing awareness, after they have high-risk behaviors. AIDS-related knowledge should be publicized to promote early discovery of high-risk behaviors.

objective:To observe the effect of high-flow nasal cannula (HFNC) oxygen therapy on patients with acute respiratory failure after gastrointestinal operation under general anesthesia and its efficacy on prognosis.Methods:Totally 107 patients with acute respiratory failure after gastrointestinal operation under general anesthesia in ICU of our hospital were selected from January 2017 to June 2019. Patients were randomly divided into the HFNC group ( n=57) and non-invasive ventilation (NIV) group ( n=50). The changes of pH, PaO 2, PaCO 2, PaO 2/FiO 2, SpO 2, heart rate (HR), respiration rate (RR), and intra-abdominal pressure (IAP) before and after oxygen treatment were compared. The differences of comfort level, duration of oxygen treatment, re-intubation rate, 48-h pulmonary infection rate, incidence of anastomotic fistula, length of stay in ICU, length of hospital stay, hospitalization cost, and 28-day mortality were compared between the two groups. The t test of two independent samples was used for the comparison of normal measurement data. Non-normal data were expressed by median (quartile), fractional count data by case number (percentage), and comparison between the two groups by Chi-square test. Results:PaO 2, PaCO 2, PaO 2/FiO 2 and SpO 2 were not significantly different after 2-h oxygen therapy. PH of the HFNC group was lower than that of the NIV group (7.39 ± 0.04 vs. 7.42 ± 0.03), PaO 2, PaCO 2, PaO 2/FiO 2 and SpO 2 were higher than that of the NIV group [ (89.22 ± 8.70) vs. (84.99± 9.76) mmHg, (41.3 ± 3.43) vs. (39.34 ± 4.21) mmHg, (250.07 ± 18.34) vs. (237.89±19.38) mmHg, (96.14 ± 2.19) vs. (94.78 ± 2.76)%, P <0.05]; pH, PaO 2, PaCO 2, PaO 2 /FiO 2 and SpO 2 were significantly higher in the HFNC group than those in the NIV group [ (7.39 ± 0.04) vs. (7.36 ± 0.04) ; (97.2 ± 12.45) vs. (93.82 ± 12.54) mmHg; (40.84 ± 5.22) vs. (45.10 ± 6.40) mmHg; (277.16 ± 13.98) vs. (248.86 ± 12.81) mmHg, (98.14 ± 1.64)% vs. (95.48 ± 2.71) %] after 12 h oxygen treatment. The HR, RR and IAP of the HFNC group were lower than those of the NIV group, and the differences were statistically significant ( P <0.05). The duration of oxygen therapy in the HFNC group was shorter than that in the NIV group [(32.01 ± 7.57) vs. (40.88 ± 8.89) h], the reintubation rate was lower than that in the NIV group (1.75% vs. 12%), the pulmonary infection rate within 48 h oxygen therapy was lower than that in the NIV group (8.78% vs.30%), and the length of stay in ICU was shorter than that in the NIV group [(5.61 ± 1.73) vs. (7.60 ± 2.31) d], and the hospitalization cost was lower than that in the NIV group ( t = 4.822, P <0. 05). Conclusions:HFNC can improve the oxygenation index of patients with hypoxemia after gastrointestinal operation under general anesthesia, reduce oxygen treatment time, reduced reintubation rate, reduce pulmonary infection rate within 48 h, and improve the prognosis.