Objective : To study the guidance effects of fibroblast growth factor 3 ( FGF3) on the prethalamic γ⁃aminobutyric acid (GABA) inhibitory axons, and to explore the effect of FGF3 on the formation of thalamic axonal network. Methods : Expression and localization of FGF3 and prethalamic GABA marker gene in chicken embryonic diencephalon were detected by immunofluorescence. Early orientation of GABA axons was tracked by DiI. Three⁃dimensional gel co⁃culture experiment was carried out to investigate guidance effects of FGF3 on early prethalamic GABA inhibitory axons. Results : Prethalamic GABA cells were adjacent to the FGF3 + hypothalamas, located above the hypothalamus. DiI tracing experiments revealed that prethalamic GABA inhibitory axons had already extended into the thalamus at E6. Compared with the blank control group, FGF3 not only significantly promoted the growth of prethalamic GABA inhibitory nerve fibers in the prethalamus, but also repelled the newborn prethalamic axons to the dorsal thalamus. The number of prethalamic axons was significantly less in proximal section (towards FGF3 beads) than that in distal section (away from FGF3 beads) (P < 0. 01) . Moreover, the guidance effects of FGF3 on prethalamic axons could be blocked by the FGF pathway inhibitor SU5402. Conclusion FGF3, an axon guidance molecule expressed in hypothalamus, exerts guidance effects on the pathway selection of adjacent prethalamic GABA inhibitory nerve fibers.

Objective:To systematically review the effects of limited fluid intake on the prognosis of patients with heart failure.Methods:RCTs about the effects of limited fluid intake on the prognosis of patients with heart failure published up to March 31, 2021 were retrieved from PubMed, The Cochrane Library, CINAHL, Embase, Web of Science, CNKI, Wanfang, VIP, and SinoMed. Two independent researchers were employed to extract data and evaluate the quality of included literature. Rev Man 5.3 was used for Meta-analysis, sequential analysis to evaluate the reliability and authenticity of the research results, and the Egger's test for publication bias.Results:A total of 7 articles were included, with a sample size of 867 cases. Meta-analysis showed that the body weight [ MD=-3.04, 95% CI (-4.70, -1.38) , P<0.001], B-type natriuretic peptide [ MD=-249.32, 95% CI (-305.00, -193.63) , P<0.001], blood creatinine [ MD=-22.03, 95% CI (-24.98, -19.09) , P<0.001], readmission rate [ OR=0.30, 95% CI (0.20, 0.45) , P<0.001] of the limited fluid intake group in the chronic phase of heart failure were lower than those in the control group; the body weight [ MD=1.41, 95% CI (-3.73, 6.55) , P=0.59], B-type natriuretic peptide [ MD=64.52, 95% CI (-50.01, 179.06) , P=0.27], serum creatinine [ MD=3.83, 95% CI (-9.69, 17.36) , P=0.58], readmission rate [ OR=1.21, 95% CI (0.65, 2.27) , P=0.55] of the acute fluid intake group were not statistically different from those in the control group. Conclusions:Limiting fluid intake in the chronic phase of heart failure can effectively improve the patients' heart and kidney function and the prognosis of the disease. In the acute phase of heart failure, it may be necessary to combine multiple treatments to keep the patients at the best volume state.

Objective To explore the relationship among depression,anxiety and social support in elderly patients in community outpatient clinic. Methods A total of 551 elderly outpatients from two com-munity health service centers of Hongkou District in Shanghai were evaluated with patient health question-naire-9 (PHQ-9),generalized anxiety disorder-7 (GAD-7),perceived social support scale( PSSS) for de-pression,anxiety,physical health and social support. Results The prevalence rates of depression and anxiety were 26. 1% and 17. 2%,respectively. The scores of PHQ-9 and GAD-7 were 2. 0(4. 0) and 1. 0(2. 0). There were statistically significant differences in the scores of family support,friend support,other support and social support among the elderly patients with different degrees of depression or anxiety (P<0. 01). Fam-ily support(B=-0. 196) and friend support(B=-0. 171) were protective factors of depression in elderly pa-tients in community outpatient clinic. Age,family support and friend support were protective factors of anxiety in elderly patients,while gender and fluctuation of physical diseases were protective factors of anxiety(P<0. 05). Con-clusions The depression and anxiety is intimately related to social support in elderly outpatients. Appropriate measures should be taken to optimize social support,mitigate bad mood negative improve their quality of life.

Objective: To analyze the characteristics of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM who frequently using the Internet in Guangzhou. Methods: An online survey was conducted among MSM who were recruited through gay-website portals between August and September, 2018 in Guangzhou, to collect information regarding the use of and attitudes on the "Interner Plus-based AIDS Comprehensive Prevention Service System" . Logistic regression was used to explore the association between the use of Internet intervention tools and related behavioral characteristics. Information on the awareness of AIDS, HIV testing, and condomless anal sex behavior were compared between the core or non-core services users. Results: A total of 777 Internet-based MSM were recruited as participants including 638 men (82.1%) as core service users. MSM were satisfied in using the the "Interner Plus-based AIDS Comprehensive Prevention Service System" while more than 80.0% of the users felt that the tools were helpful in: increasing the HIV awareness, promoting test uptake, and reducing those related risk behavior. Comparing with those who did not use the tools, the users showed higher rates in practising condomless anal intercourse (1.50-1.86 times), commercial sex with men (11.60-21.21 times), and unprotected vaginal intercourse (13.62-20.67 times), in the last 6 months. Proportions of core service users appeared as: [96.6% vs. 74.8%, aOR (95%CI): 8.80 (4.85-15.97)] on HIV testing, [56.4% vs. 22.3%, aOR (95%CI): 4.54 (2.94-7.02)] on regular HIV testing and [86.2% vs. 80.6%, aOR (95%CI): 1.75 (1.06-2.89)] on awareness of HIV knowledge respectively, which were all significantly higher than the non-core service users. Conclusions The frequent Internet using MSM in Guangzhou claimed to have had high acceptance and satisfaction on the local Internet HIV intervention service tools. The "Internet Plus-based AIDS Comprehensive Prevention Service System" had effectively reached the high-risk subgroups of MSM, increasing the awareness on related risk and promoting testing on HIV.

OBJECTIVE： To optimize and improve the quality standard for Citrus reticulata formula granules. METHODS： Totally 13 batches of C. Reticulata formula granules from 4 different manufacturers were used as trial samples， and qualitative identification of hesperidin and nobiletin in the samples were carried out by TLC according to the method of 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. The quantitative analysis of naringin， hesperidin， hesperetin， nobiletin and tangeretin in C. reticulatae formula granules were conducted by UPLC[The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile-0.2％ phosphoric acid aqueous solution （gradient elution）. The detection wavelength was set at 283 nm， and sample size was 3 μL]. RESULTS： The results of TLC showed that in the chromatograms of samples， same color spots were shown in the corresponding positions of the chromatogram of reference substance. The results of UPLC showed， that the linear range of naringin， hesperidin， hesperetin， nobiletin and tangeretin were 0.64-6.44， 15.78-157.80， 0.17-1.66， 2.08-20.85 and 2.04-20.43 μg/mL， respectively （all r≥0.999 2）； the limits of detection were 0.03， 0.33， 0.10， 0.20 and 0.06       μg/mL； the limits of quantitation were 0.07， 1.34， 0.20， 0.60 and 0.22 μg/mL. The average recoveries were 99.4％， 99.6％， 99.7％， 99.7％ and 99.7％ （n＝9）； RSDs of precision （n＝6）， stability （n＝7） and reproducibility （n＝6） tests were all≤2.03％； naringin was detected in only 3 batches of samples from one manufacturer （the content ranged from 0.067 3 to 0.069.6    mg/g）， while the other 4 components were detected in 13 batches of samples （the contents of them ranged 0.646 5-1.728 0，   0.102 6-0.290 5， 0.023 1-0.689 8， 0.018 2-0.270 7 mg/g）. CONCLUSIONS： In this study， the quality standard of C. reticulata formula granules was improved by qualitative and quantitative methods， and the contents of hesperidin， hesperetin， nobiletin and tangeretin were not less than 0.60， 0.10， 0.02 and 0.01 mg/g， respectively.

OBJECTIVE:To establish UPLC fingerprint of Glycyrrhiza uralensis. METHODS:UPLC method was adopted. The determination was performed on Waters CORTECS UPLC C18column with mobile phase consisted of acetonitrile-0.1% formic acid(gradient elution)at the flow rate of 0.3 mL/min. The detection wavelength was set at 254 nm,and column temperature was 30 ℃. The sample size was 1 μ L. Using glycyrrhizic acid as control,UPLC chromatograms of 27 batches of sample were determined. Similarity evaluation was conducted by using TCM Chromatogram Fingerprint Similarity Evaluation System(2004 A edition)to determine common peak and conduct cluster analysis of 27 batches of samples. RESULTS:There were 20 common peaks in UPLC chromatograms of 27 batches of samples. The similarity degree of S2,S4,S19,S21,S22,S24 were less than 0.90, the others samples were more than 0.90.After validation,UPLC chromatograms of 21 batches of batches of samples were in good agreement with control fingerprint. 27 batches of samples were clustered into 3 categories,in which S24 was categoryⅠ;S2,S4, S12,S19,S21,S22 were categoryⅡ;other were categoryⅢ. CONCLUSIONS:Established fingerprint can provide reference for quality evaluation of G.uralensis.

Voltage-gated sodium (Na) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na channels, with Na1.1 and Na1.5 each harboring more than 400 mutations. Na channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca) channel Ca1.1 provides a template for homology-based structural modeling of the evolutionarily related Na channels. In this Resource article, we summarized all the reported disease-related mutations in human Na channels, generated a homologous model of human Na1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na channels, the analysis presented here serves as the base framework for mechanistic investigation of Na channelopathies and for potential structure-based drug discovery.
Animals ; Calcium Channels, L-Type ; chemistry ; genetics ; metabolism ; Channelopathies ; genetics ; metabolism ; Humans ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel ; chemistry ; genetics ; metabolism ; NAV1.5 Voltage-Gated Sodium Channel ; chemistry ; genetics ; metabolism ; NAV1.7 Voltage-Gated Sodium Channel ; chemistry ; genetics ; metabolism ; Protein Domains ; Rabbits ; Structure-Activity Relationship

Equilibrative nucleoside transporters (ENTs), which facilitate cross-membrane transport of nucleosides and nucleoside-derived drugs, play an important role in the salvage pathways of nucleotide synthesis, cancer chemotherapy, and treatment for virus infections. Functional characterization of ENTs at the molecular level remains technically challenging and hence scant. In this study, we report successful purification and biochemical characterization of human equilibrative nucleoside transporter 1 (hENT1) in vitro. The HEK293F-derived, recombinant hENT1 is homogenous and functionally active in proteoliposome-based counter flow assays. hENT1 transports the substrate adenosine with a K of 215 ± 34 µmol/L and a V of 578 ± 23.4 nmol mg min. Adenosine uptake by hENT1 is competitively inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), nucleosides, deoxynucleosides, and nucleoside-derived anti-cancer and anti-viral drugs. Binding of hENT1 to adenosine, deoxyadenosine, and adenine by isothermal titration calorimetry is in general agreement with results of the competitive inhibition assays. These results validate hENT1 as a bona fide target for potential drug target and serve as a useful basis for future biophysical and structural studies.
Adenine Nucleotides ; chemistry ; metabolism ; Equilibrative Nucleoside Transporter 1 ; chemistry ; genetics ; metabolism ; HEK293 Cells ; Humans ; Protein Domains ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Structure-Activity Relationship

Objective To investigate the anesthesia and perioperative blood management of patients with Marfan syndrome (MS) undergoing scoliosis surgery.Methods The clinical data of MS patients underwent scoliosis surgery from January 2013 to December 2015 in Peking Union Medical College Hospital were collected and compared with patients received the same surgery but without MS.Perioperative information and data on anesthesia and blood management were analyzed.Results Compared with control group,MS patients were found with more preoperative comorbidities with statistical significance,including eye disease,echocardiographic abnormalities,and ventilatory defects.MS patients had significantly more blood loss,more intraoperative and postoperative allogeneic and autologous blood transfusion.The operation time,anesthesia time,and length of postoperative hospital stay were all significantly longer in MS patients.Conclusions MS patients are common with multi-system involvement and comorbidities.Considering the high risk of perioperative bleeding,the anesthesia and blood management for MS patients undergoing scoliosis surgery should be with extra caution.Blood management should be applied and appropriate invasive monitoring methods should be considered when necessary.

Objective A rat model of chronic post-thoracotomy pain is used to study whether acute pain and pre-operative diffused noxious inhibitory controls(DNIC) can predict chronic pain and how DNIC changes when pain maintains.Methods Rats were randomly divided into three groups:naive group,sham group and model group.DNIC was constantly assessed in individual rats,along with each animal's mechanical hyperalgesia and cold allodynia after thoracotomy.Results In model group,the incidence of chronic post-thoracotomy pain was 55%(11 of 20),which was named CPTP group,and the other 9 rats without chronic pain was defined as non-CPTP group.The pre-operative DNIC was significantly weaker in CPTP group with lower mechanical threshold on 6 days after surgery and higher cold sensitivity on 6 days after surgery comparing with non-CPTP group.In the acute pain phase (day 3),DNIC was decreased in both CPTP group and non-CPTP group as compared with pre-operative period.Besides,DNIC was recovered in non-CPTP group while kept impaired in CPTP group on 21 days after surgery.Conclusions Pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP.DNIC was decreased both in acute pain and chronic state,while returned to normal when pain sense was normal.