Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Circular RNA circRSF1 binds to HuR to promote radiation-induced inflammatory phenotype in hepatic stellate cells / 南方医科大学学报

OBJECTIVE@#To investigate whether circular RNA circRSF1 regulates radiation-induced inflammatory phenotype of hepatic stellate cells (HSCs) by binding to HuR protein and repressing its function.@*METHODS@#Human HSC cell line LX2 with HuR overexpression or knockdown was exposed to 8 Gy X-ray irradiation, and the changes in the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) were detected by qRT-PCR. The expressions of IκBα and phosphorylation of NF-κB were detected with Western blotting. The binding of circRSF1 to HuR was verified by RNA pull-down assay and RNA-binding protein immunoprecipitation (RIP). The expressions of inflammatory factors, IκBα and the phosphorylation of NF-κB were detected after modifying the interaction between circRSF1 and HuR.@*RESULTS@#Knockdown of HuR significantly up- regulated the expressions of IL-1β, IL-6 and TNF-α, decreased IκBα expression and promoted NF-κB phosphorylation in irradiated LX2 cells, whereas overexpression of HuR produced the opposite changes (P < 0.05). Overexpression or knockdown of circRSF1 did not significantly affect the expression of HuR. RNA pull-down and RIP experiments confirmed the binding between circRSF1 and HuR. Overexpression of circRSF1 significantly reduced the binding of HuR to IκBα and down-regulated the expression of IκBα (P < 0.05). Overexpression of circRSF1 combined with HuR overexpression partially reversed the up-regulation of the inflammatory factors, down-regulated IκBα expression and increased phosphorylation of NFκB in LX2 cells, while the opposite effects were observed in cells with knockdown of both circRSF1 and HuR (P < 0.05).@*CONCLUSION@#circRSF1 reduces IκBα expression by binding to HuR to promote the activation of NF-κB pathway, thereby enhancing radiation- induced inflammatory phenotype of HSCs.

Spatial epidemiological characteristics of the mortality and probability of premature death caused by chronic obstructive pulmonary disease among residents in Pudong New Area of Shanghai in 2010-2020 / 公共卫生与预防医学

Objective To explore the spatial epidemiological characteristics of mortality and probability of premature death caused by chronic obstructive pulmonary disease (COPD) among residents in Pudong New Area of Shanghai from 2010 to 2020, and to provide reference for the formulation of chronic obstructive pulmonary disease prevention and control strategies according to local conditions. Methods The death data of chronic obstructive pulmonary disease were obtained from the local death surveillance system of Pudong New Area. Crude mortality, age-standardized mortality, and probability of premature death caused by COPD in each subdistricts and towns of Pudong New Area were calculated. The geographical information system (GIS) was used to plot the spatial distribution maps of chronic obstructive pulmonary disease death. The trend surface analysis and the spatial autocorrelation analysis were performed to analyze the spatial distribution of chronic obstructive pulmonary disease death. Results The crude mortality, age-standardized mortality and probability of premature death caused by COPD among residents in Pudong New Area between 2010 and 2020 were 58.40/100,000, 22.35/100,000, and 0.26%, respectively. The results of trend surface analysis showed that the crude mortality, age-standardized mortality and probability of premature death caused by COPD gradually increased from north to south. In the east-west direction, the crude mortality, age-standardized mortality, and probability of premature death showed an upward trend from west to east. The global autocorrelation analysis suggested that there existed a positive spatial autocorrelation for the crude mortality, age-standardized mortality, and probability of premature death. The local spatial autocorrelation analysis showed that the high-high clustering areas of COPD crude mortality, standardized mortality and premature mortality were all located in the rural areas of the southeast of Pudong New Area. Conclusion There are urban and rural differences in the mortality of chronic obstructive pulmonary disease among residents in Pudong New Area from 2010 to 2020. The residents living in rural southeast coast of Pudong New Area are more seriously affected by chronic obstructive pulmonary disease and should be paid more attention.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Progress in research of long-term protective efficacy of human papillomavirus vaccine / 中华流行病学杂志

The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.

Hepatoprotective activity of cis-(trans)-emodin-emodin dianthrone from Polygonum multiflorum Thunb / 药学学报

The cis-emodin-emodin dianthrone (compound 1) and trans-emodin-emodin dianthrone (compound 2) were extracted from Polygonum multiflorum Thunb. The protective effect and mechanism of compound 1 and compound 2 (emodin-emodin dianthrones) on acute liver injury induced by concanavalin A (ConA) in ICR mice was first investigated. The results indicated that emodin-emodin dianthrones at 1 mg·kg-1 significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level (P < 0.05). Emodin-emodin dianthrones also improved liver histopathological damage in liver-injured mice. The level of Bcl-2-associated X protein (Bax) mRNA in liver was significantly reduced by 1 mg·kg-1 of emodin-emodin dianthrones, while the level of B-cell lymphoma-2 (Bcl-2) mRNA expression was significantly increased (P < 0.05). The protective activity of compounds 1 and 2 against hepatocyte injury was further evaluated by hydrogen peroxide (H2O2)-induced hepatocyte injury. Compounds 1 and 2 significantly inhibited H2O2-induced hepatocyte injury and reduced the levels of ALT, AST, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in cell culture. Compounds 1 and 2 also significantly improved the cell survival rate and decreased H2O2-induced oxidative stress in hepatocytes. Compound 1 (0.5 µmol·L-1) significantly increased the enzymatic activity of superoxide dismutase (SOD) in hepatocytes (P < 0.01), and 0.5 µmol·L-1 of compound 2 significantly decreased the intracellular reactive oxygen species (ROS), increased SOD enzyme activity, and glutathione (GSH) content (P < 0.01). Compounds 1 and 2 at 0.5 µmol·L-1 also inhibited hepatocyte apoptosis by increasing the protein expression ratio of Bcl-2/Bax (P < 0.05) and decreasing the protein expression ratio of cleaved caspase-3 and pro caspase-3 (P < 0.05). This study indicates that the emodin-emodin dianthrones from Polygonum multiflorum Thunb. have liver-protective activity. Compounds 1 and 2 exerted hepatoprotective effects by inhibiting apoptosis and oxidative stress. The study provides an important material basis for the hepatoprotective effect of commonly used amounts of Polygonum multiflorum Thunb.

Predictive value of postoperative serum procalcitonin concentration for moderate to severe acute respiratory distress syndrome in patients undergoing cardiopulmonary bypass surgery / 中华危重病急救医学

OBJECTIVE@#To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS.@*METHODS@#Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS.@*RESULTS@#108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (μg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 μg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001].@*CONCLUSIONS@#Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 μg/L.

Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM).@*METHODS@#From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed.@*RESULTS@#Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy.@*CONCLUSION@#The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.

Ethical Management Experience and Enlightenment of Finnish Red Cross Blood Center Biobank / 中国医学伦理学

To strengthen the ethical management of blood samples for scientific research in blood collection and supply institutions, promote the effective use of blood sample resources, and protect the rights and interests of blood donors. Drawing on the experience of the Finnish Red Cross Blood Center biobank which has rich experience in management and recruitment, this paper summarized from the aspects of extensive informed consent, management of sample data, application of biological samples and data, and ethical management of research projects, and put forward the enlightenment to improve the ethical management of blood samples in blood collection and supply institutions, including further improving the construction of ethical laws and regulations, strengthening the ethical review norms of the ethics committee, standardizing the use of informed consent, and enhancing the privacy protection of blood donors.

Status analysis of informed consent of blood donors based on content analysis / 中国输血杂志

【Objective】 To understand the current status and shortcomings of the informed consent of blood donors, and to ensure that the informed consent of blood donors complies with ethical norms and management requirements. 【Methods】 From January 1 to 31, 2022, the " Informed Consent Form for Blood Donor" and " Health Status Consultation Form", issued by 6 blood services in Beijing, Shanghai, Tianjin, Chongqing, Guangzhou and Zhejiang, were collected. The contents regarding individual informed consent were set as an analysis unit; 7 first-level codes such as the form of information disclosure, 19 second-level codes such as the title of the content to be informed, and 56 items such as the content to be informed before blood donation were established to make frequency statistics. 【Results】 The informed consent, issued by six blood centers, included such elements as the form of information disclosure, blood donation process and risks, authenticity of information, donor shielding requirements, screening for transfusion-transmitted infections, other uses of blood, and consent decisions. The second-level coding with frequency≥ 4 included 12 items(63.16%), such as the title of informed consent, truthful provision of health consultation information, and blood donation under real-name, of which precautions after blood donation, privacy statement, and withdrawal were " unexplained" frequency codes. The proportion of 56 items with frequency 1~6 was 55.36%, 12.50%, 10.71%, 17.86%, 1.79% and 1.79%, respectively. 【Conclusion】 The informed consent forms and health status consultation forms play a certain role in explaining and conducting informed consent in different places, but some contents are scattered and lack of specifications, information notification weights in shielding requirements while lacks post-donation care and privacy protection, and the decision-making process is inadequate. A standardized content framework for informed consent of blood donors should be established, the caring for blood donors should be promoted, and the full process of consent decision-making should be valued seriously.

Path analysis of mediating effect of perceived stress affecting impact of event in rehabilitation patients with traumatic injury / 中国康复理论与实践

ObjectiveTo explore the effect of perceived stress on the impact of event in rehabilitation patients with traumatic injury, and the mediating role of difficulties in emotion regulation, rumination and sleep. MethodsFrom March, 2022 to March, 2023, using the convenient sampling method, a questionnaire survey was conducted on 192 rehabilitation patients with traumatic injury from Southwest Hospital, Xinqiao Hospital and Daping Hospital. Assessment tools included Perceived Stress Scale, Difficulties in Emotion Regulation Scale, Brief Ruminative Response Scale, Self-Rating Scale of Sleep, and Impact of Event Scale-revised. ResultsPerceived stress, difficulties in emotion regulation, rumination, sleep and the impact of event were correlated with each other in rehabilitation patients with traumatic injury (r = 0.447~0.684, P < 0.01). Perceived stress significant positively predicted the impact of event (β = 0.49, P < 0.001), as well as difficulties in emotion (β = 0.70, P < 0.001), rumination (β = 0.21, P < 0.05) and sleep (β = 0.29, P < 0.001). The direct effect of perceived stress on the impact of event was not significant, but it affected the impact of event through seven mediation paths, among which the independent mediation effect size of difficulties in emotion regulation, rumination and sleep accounted for 24.41%, 11.91% and 24.82%, respectively; the chain mediation effect size of difficulties in emotion regulation and rumination accounted for 13.88%, the chain mediation effect size of difficulties in emotion regulation and sleep accounted for 18.08%, the chain mediation effect size of rumination and sleep accounted for 3.17%, and the chain mediation effect size of difficulties in emotion regulation, meditation and sleep accounted for 3.70%. ConclusionPerceived stress affected the impact of event in rehabilitation patients with traumatic injury through the independent mediation and chain mediation of difficulties in emotion regulation, rumination and sleep.

Polysaccharide Krestin Prevents Alzheimer's Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-β Processing / 神经科学通报·英文版

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.

Intravenous Immunoglobulin to Suppress Progression in a Patient With Advanced Breast Cancer / 한국유방암학회지

Intravenous immunoglobulin (IVIG) is used to treat various diseases and has anticancer effects that suppress metastases in animal models of sarcoma and melanoma. However, these effects have been observed in a limited number of clinical cases. We report the case of a patient with metastatic breast cancer in which long-term IVIG treatment stopped disease progression in the absence of salvage chemotherapy. The patient was treated with IVIG for the treatment of immune thrombocytopenia. Surprisingly, the lung and brain metastases were stabilized, and the patient achieved a progression-free interval of 29 months. More cases are needed to investigate and confirm the efficacy of IVIG in solid tumors in the future.

Visual analysis of research hotspots and frontiers on randomized controlled trials of acupuncture and moxibustion in the past 10 years / 中国针灸

Retrieved the literature on randomized controlled trials (RCT) of acupuncture and moxibustion from 2011 to 2020 in the Web of Science (WOS) database, and explored research hotspots and frontiers in the field of acupuncture and moxibustion by visually analyze to countries, institutions, authors, keywords, cited literature, etc. using CiteSpace V5.6.R2. A total of 1147 articles were included. China has the largest number of publications, and the top 3 publications are Beijing University of Chinese Medicine, Capital Medical University and Kyung Hee University. The hot research interventions in acupuncture and moxibustion include acupuncture, electroacupuncture, and bee acupuncture. The hot research topics include nerve regeneration, spasms, nausea, pain, obesity, cancer, etc. The research frontiers include acupuncture analgesia, diversification of acupuncture and its clinical effects, brain effects of acupuncture and acupuncture clinical mechanisms. It is believed that the cooperation between countries and institutions should be strengthened in the future, and deeper research should be carried out on the research content that is both hot spot and frontier.

Improved Urothelial Cell Proliferation, Cytoskeleton and Barrier Function Protein Expression in the Patients With Interstitial Cystitis/Bladder Pain Syndrome After Intravesical Platelet-Rich Plasma Injection / 대한배뇨장애요실금학회지

Purpose@#To investigate urothelial cell proliferation, cytoskeleton, inflammation, and barrier function protein expressions in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) after intravesical platelet-rich plasma (PRP) injections @*Methods@#A total of 19 patients with IC/BPS underwent 4 monthly intravesical PRP injections. Bladder biopsies were taken at the first and fourth PRP treatment. The bladder specimens were analyzed using the Western blot and immunochemical staining for progenitor cell markers for sonic hedgehog (Shh), CD34, and cytoskeleton proteins cytokeratin 5 (CK5), CK14, CK20; barrier function markers for zonula occludens-1 (ZO-1), E-cadherin, and intercellular adhesive molecule-1, tryptase and transforming growth factor-β (TGF-β). Global response assessment (GRA) was used to evaluate treatment outcomes. @*Results@#The mean age of patients was 55.6 years. After PRP injections, the functional bladder capacity and maximum flow rate increased, and the visual analogue scale (VAS) of pain, interstitial cystitis (IC) symptom index, IC problem index, O’Leary-Sant symptom score, and GRA improved in all patients. Urothelium Shh, CK5, ZO-1, E-cadherin, and TGF-β expressions increased significantly after repeated PRP injections. By subgrouping, according to PRP treatment outcomes, significant increases in Shh, E-cadherin, and ZO-1 expressions were noted only in patients with GRA ≥1 or improved VAS, but not in patients with GRA=0 and no improvement in VAS. @*Conclusions@#The level of urothelial barrier function protein and cell proliferation protein expression in the patients with IC/BPS was increased after repeat intravesical PRP injections. Intravesical repeat PRP injections may have potential to improve urothelial health and result in symptoms improvement in the patients with IC/BPS.

Investigation of acupuncture in improving sleep, cognitive and emotion based on attenuation of oxidative stress in prefrontal cortex in sleep-deprived rats / 针灸推拿医学（英文版）

Objective: To explore whether acupuncture can improve sleep disturbance, cognitive impairment and emotional disorders caused by sleep deprivation, and its association with the attenuation of oxidative stress injury in prefrontal cortex. Methods: Fifty-two male Sprague-Dawley rats were randomly divided into a control group (n=10), a model group (n=14), a manual acupuncture (MA) group (n=14), and a sham-MA group (n=14). All the groups were established as sleep deprivation models via the modified multiple platform method, except for the control group. Rats in both the MA group and the sham-MA group received corresponding intervention, respectively. After modeling and intervention, the four groups received three behavioral tests, namely sleep monitoring, by comprehensive lab animal monitoring system (CLAMS), Morris water maze (MWM) test and open-field test (OFT), followed by oxygen free radical level test and Western blot (WB) detection for the expression levels of Bax and Bcl-2. Results: The MA group derived more sleep time within 24 h than either the model group or the sham-MA group (both P<0.05). On MWM orientation navigation test day 1, there were no significant differences in escape latency among the control, MA and sham-MA groups (P>0.05), and the escape latency was significantly shorter in these three groups than that in the model group (all P<0.05). On test day 4, the escape latency was markedly shorter in the MA group than that in either the model group or the sham-MA group (both P<0.05); meanwhile, the MA group showed significantly better performance compared with these two groups in space probe test (both P<0.05). In OFT, compared with the control group, there was a significant decline in the horizontal movement score in the other three groups (all P<0.05), and the decrease was more significant in the model group and the sham-MA group than that in the MA group (both P<0.05). The superoxide dismutase (SOD) content was markedly higher and the malondialdehyde (MDA) content was markedly lower in the MA group than those in the model group and the sham-MA group (all P<0.05). Compared with the model group and the sham-MA group, the expression of Bax was significantly lower and the expression of Bcl-2 was significantly higher in the MA group (all P<0.05). Conclusion: MA therapy can lengthen the sleep time in sleep-deprived rats and improve learning and memory impairments induced by sleep deprivation, and the underlying mechanism may be associated with the enhancement of antioxidant capacity in the prefrontal cortex and the inhibition of hippocampal neuronal apoptosis.

Effect of Joint Cavity Injection of Dioscoreae Rhizoma Polysaccharides on Inflammatory Factors and Articular Cartilage Metabolism in Rabbit Knee Osteoarthritis / 中国实验方剂学杂志

Objective:To investigate the mechanism of joint cavity injection of Dioscoreae Rhizoma polysaccharides （DRP） in protecting against cartilage degeneration and inhibiting the expression of inflammatory factors in the rabbit model of knee osteoarthritis to provide relevant references for the development and further research on DRP. Method:Fifty-five New Zealand white rabbits were selected for the induction of knee osteoarthritis model by the modified Hulth's modeling method. The model rabbits were randomly divided into a model group， a sodium hyaluronate group （1.00 mg·kg^-1）， and low- （0.7 mg·kg^-1）， medium- （1.43 mg·kg^-1）， and high-dose （2.15 mg·kg^-1） DRP group according to a random number table. One week after modeling， the rabbits in the groups with drug intervention were treated correspondingly for five weeks， once per week， and no intervention was performed in the model group. Five weeks later， the joint specimens were observed by visual observation. The articular cartilage tissues were observed under the light microscope for pathological sections and scores by hematoxylin-eosin （HE） staining and toluidine blue （TB） staining. The expression levels of interleukin-6 （IL-6）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， and tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） in the synovial fluid were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of matrix metalloproteinase-13 （MMP-13）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， and type Ⅱ collagen （Col-Ⅱ） in the articular cartilage were measured by immunohistochemistry. Result:After five weeks of DRP intervention， compared with the model group， the DRP groups exhibited lowered levels of IL-6， IL-1<italic>β</italic>， and TNF-<italic>α</italic> in the synovial fluid （<italic>P</italic><0.05）， reduced expression of MMP-13 in the articular cartilage （<italic>P</italic><0.05）， and increased levels of TGF-<italic>β</italic>₁and Col-Ⅱ （<italic>P</italic><0.05）. Compared with the low-dose and high-dose DRP groups， the medium-dose DRP group showed reduced levels of IL-6， IL-1<italic>β</italic>， and TNF-<italic>α</italic> in the knee joint （<italic>P</italic><0.05）， increased levels of TGF-<italic>β</italic>₁ and Col-Ⅱ in cartilage tissues （<italic>P</italic><0.05）， and dwindled level of MMP-13 （<italic>P</italic><0.05）. Compared with the sodium hyaluronate group， the medium-dose DRP group showed no significant differences in IL-6， IL-1<italic>β</italic>， and TNF-<italic>α</italic> in rabbit knee joints， and TGF-<italic>β</italic>₁， Col-Ⅱ， and MMP-13 in cartilage tissues. Conclusion:Joint cavity injection of DRP can significantly reduce the expression of IL-6， IL-1<italic>β</italic>， and TNF-<italic>α</italic> in rabbit synovial fluid， effectively inhibit the expression of MMP-13 in the articular cartilage to suppress the degradation of articular cartilage collagen and promote the synthesis of TGF-<italic>β</italic>₁ and Col-Ⅱ. Therefore， DRP can protect and repair articular cartilage to delay the degeneration of articular cartilage.

Evaluation of Accessibility of Road Traffic Sidewalks Using the Codes for Accessibility Design in the Mega-city: a Case of Shanghai / 中国康复理论与实践

Objective:To evaluate the accessibility construction status of road traffic sidewalks in Shanghai. Methods:From July to September, 2019, 46 road traffic sidewalks in Shanghai were selected using a convenience sampling, and evaluation tools were designed based on the Codes for Accessibility Design (GB 50763-2012) and Standards for Design on Accessibility of Buildings and Facilities (DGJ08-103-2003). After field check and experience for the sidewalks, the compliance rates of evaluation dimensions and evaluation contents of sidewalks were analyzed using the descriptive analysis. The weights of each dimension were calculated using the principal component analysis to construct the sidewalk comprehensive barrier score model, and to compare the sidewalk comprehensive barrier scores in different areas of Shanghai. From September to November 2019, in-depth interviews were conducted with eleven persons with disabilities to understand the sidewalk barriers for them. Results:The overall compliance rate of sidewalk accessibility was 4.35%. Among the evaluated contents, 93.5% sidewalks had a curb ramp, 91.3% had a height difference between the ramp and the carriageway, 26.1% were not paved with tactile ground surface indicators; 71.7% tactile ground surface indicators were blocked by poles, etc., and 84.8% were occupied by obstacles. The warning indicator was the greatest weight among the evaluated dimensions. The barrier of sidewalks was high (36.7%) and medium (20.0%) in the central area, which was higher than that in the sub-central area (both 6.3%) (P < 0.05). There were many obstacles during the experience of sidewalks using, resulting in less using of the barrier-free facilities. Conclusion:Most of the sidewalks in Shanghai do not meet the standards of the Codes for Accessibility Design. It is urgent to construct and maintain the barrier-free facilities.

Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca

Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali / 中国结合医学杂志

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.