Protective effect of tert-butylhydroquinone on retinal morphology and function in early diabetic rats and its mechanism / 中华实验眼科杂志

Objective:To investigate the protective effects of an antioxidant tert-butylhydroquinone (tBHQ) on the morphology and function of retina in early-stage experimental diabetic rats, and to explore the mechanism of its protective effect.Methods:Forty-five healthy SD rats of clean degree were randomized into normal control group, diabetes model group and tBHQ intervention group, with 15 rats in each group according to a random number table.The diabetes model was established via a single intraperitoneal injection of streptozotocin (STZ) in diabetes model group and tBHQ intervention group.Normal control group was intraperitoneally administered with an equal-volume injection of sodium citrate buffer.Rats in the tBHQ intervention group maintained a diet with 1% tBHQ for 2 weeks before the STZ injection, and the other two groups were fed with normal rat food only.Blood from tail vein was collected to assay the blood glucose level at 72 hours, 2 weeks and 4 weeks following modeling.Rat electroretinogram (ERG) was detected at 4 weeks after modeling.Morphological changes of rat retina were observed by hematoxylin and eosin staining.The apoptosis of retinal cells in different layers was detected by TUNEL assay.The expression of protein kinase B (Akt), p-Akt, endothelial nitric oxide synthase (eNOS) and p-eNOS was detected by Western blot.Müller cell line rMC-1 cells cultured in vitro were divided into 5 groups, including normal control group (72-hour culturing in normal medium), mannitol control group (72-hour culturing in medium containing 5.5 mmol/L glucose and 24.5 mmol/L mannitol), high glucose group (72-hour culturing in high-glucose medium), tBHQ intervention group (24-hour culturing in normal-glucose medium containing 5 μmol/L tBHQ, 72-hour culturing in high-glucose medium containing 5 μmol/L tBHQ), and phosphoinositide 3-kinase (PI3K) inhibitor group (6-hour culturing in normal medium containing 5 μmol/L LY294002, 24-hour culturing in normal-glucose medium containing 5 μmol/L LY294002 and 5 μmol/L tBHQ, 72-hour culturing in high-glucose medium containing 5 μmol/L LY294002 and 5 μmol/L tBHQ). The expression of Akt, p-Akt, eNOS and p-eNOS in the cells was detected by western blot.The use and care of animals complied with Regulations for the Administration of Laboratory Animals in Southwest Medical University.The study protocol was approved by the Animal Ethics Committee of Southwest Medical University (No.201711189). Results:The blood glucose level at 72 hours, 2 weeks and 4 weeks after modeling was higher in diabetic model group than tBHQ intervention group and normal control group (all at P<0.01). Four weeks after modeling, the scotopic ERG a-wave and b-wave amplitudes of diabetic model group were lower than those of normal control group and tBHQ intervention group (all at P<0.05). With edema and thickening of inner plexiform layer, thinning of inner nuclear layer and outer nuclear layer, as well as loosely arrangement and disorder of retinal layers, the number of retinal ganglion cells was decreased in diabetic model group in comparison with normal control group, all of which were improved in tBHQ intervention group in comparison with diabetic model group.There were more apoptotic retinal cells in diabetic model group than normal control group and tBHQ intervention group (both at P<0.05), which mainly existed in the outer nuclear layer.The relative expressions of p-Akt/Akt and p-eNOS/eNOS in rat retina of normal control group, diabetic model group and tBHQ intervention group were 0.76±0.11 and 0.83±0.06, 0.52±0.10 and 0.52±0.08, 1.14±0.31 and 1.03±0.13, respectively.The relative expressions of p-Akt/Akt and p-eNOS/eNOS in diabetic model group were lower than those of normal control group and tBHQ intervention group (all at P<0.01). The relative expressions of p-Akt/Akt and p-eNOS/eNOS in normal glucose group, mannitol control group, high glucose group, tBHQ intervention group and PI3K inhibitor group were 0.95±0.38 and 0.86±0.11, 0.94±0.27 and 0.74±0.29, 0.33±0.25 and 0.45±0.29, 1.32±0.37 and 1.28±0.22, 0.24±0.09 and 0.73±0.29, respectively.The relative expressions of p-Akt/Akt and p-eNOS/eNOS were significantly lower in high glucose group than those in normal glucose group and tBHQ intervention group (all at P<0.05), which were significantly lower in PI3K inhibitor group compared with tBHQ intervention group (both at P<0.01). Conclusions:tBHQ has protective effects on the morphology and function of retina in early diabetic rats, and the mechanism may be related to the activation of Akt/eNOS signaling pathway.

Expression of CXC chemokine ligand 11 in gallbladder cancer and its effect on cell proliferation and invasion / 中华肝胆外科杂志

Objective:To investigate the expression of CXC chemokine ligand 11 (CXCL11) in gallbladder cancer (GBC) and its effect on cell proliferation and invasion.Methods:The surgically resected specimens of 47 GBC patients were collected in Lihuili Hospital Affiliated to Ningbo University from January 2017 to December 2020. There were 26 females and 21 males, with the age (62.0±8.2) years. The expression of CXCL11 protein in GBC tissues and corresponding paracancer tissues was detected by immunohistochemistry. Associations between CXCL11 expression and clinicopathological features were analyzed. After co-culturing of GBC-SD cells with exogenous CXCL11, cell counting kit-8 (CCK-8) and Transwell assays were performed to detect cell proliferation and invasion ability. The expression and phosphorylation level of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (Akt) were also detected by Western blot.Results:The positive expression rate of CXCL11 in GBC tissues was significantly higher than that in adjacent paracancerous tissues [63.8% (30/47) vs 31.9% (15/47), χ 2=9.59, P=0.002]. Furthermore, CXCL11 expression was significantly associated with tumor stage (χ 2=6.64, P=0.010) and lymph nodal metastasis (χ 2=7.86, P=0.005). CCK-8 assay revealed that the proliferation ability of GBC-SD cells in CXCL11-treated group significantly increased than that in the control group (absorbance value: 0.59±0.06 vs 0.32±0.04, t=9.64, P<0.001). Transwell assay showed that the cell invasion ability in CXCL11-treated group significantly increased than that in the control group [number of transmembrane cells: (133.4±12.3) cells vs (38.6±4.4) cells, t=16.21, P<0.001]. Western blot analysis showed that the relative expression levels of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) in CXCL11-treated group (0.88±0.06 and 0.83±0.04) were significantly higher than those in the control group (0.17±0.04 and 0.23±0.06), and the differences were statistically significant ( t=18.54, P<0.001 and t=15.21, P<0.001). Conclusion:CXCL11 is highly expressed in GBC and closely related to tumor progression. CXCL11 can promote the proliferation and invasion of GBC cells via PI3K/Akt signaling pathway.

Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population / 生物医学与环境科学（英文）

OBJECTIVE@#Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure.@*METHODS@#We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy.@*RESULTS@#No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed.@*CONCLUSIONS@#Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.

Application of a new plastic biliary stent modified based on pigtail nasal bile drainage tube to hilar biliary cholangiocarcinoma / 中华消化内镜杂志

Objective:To compare the efficacy and safety of a new type of plastic biliary stent modified based on the pigtail nasobiliary duct and the common plastic biliary stent for hilar cholangiocarcinoma.Methods:Data of a total of 38 patients with obstructive jaundice caused by hilar cholangiocarcinoma who received endoscopic retrograde cholangiopancreatography (ERCP) palliative treatment at the Endoscopy Center, General Hospital of Northern Theater Command from June 2018 to December 2020 were collected, including 20 cases using the new type of plastic biliary stent (the new stent group), and 18 cases using the common plastic stent (the common stent group). Patients were followed up to May 30, 2021. The procedure time, hospital stay, postoperative biliary infection incidence, the bilirubin decrease, and the patency time of the stents in the two groups were compared.Results:The procedure time was 19.85±1.07 minutes in the new stent group and 22.00±3.38 minutes in the common stent group, respectively, showing no significant difference between them ( t=1.26, P=0.607). The lengths of hospital stay of the two groups were 11.45±2.39 days and 11.33±3.51 days, respectively, showing no significant difference between them ( t=-0.52, P=0.938). The median margins of total bilirubin reduction in the two groups were 122.85 μmol/L and 96.25 μmol/L, respectively, with significant difference ( Z=-2.03, P=0.042). The incidence of long-term cholangitis of the new stent group was significantly lower than that of the common stent group [10.0% (2/20) VS 44.4% (8/18), P=0.027]. The patency time of the new stent group was significantly longer than that of the common stent group (109.45±32.67 days VS 82.11±20.95 days) with significant difference ( t=2.23, P=0.032). Conclusion:In the palliative treatment of hilar bile duct obstruction, the new plastic bile duct stent modified based on pigtail type can reduce the incidence of long-term cholangitis and prolong the patency of bile duct stent compared with the common stent group.

Research on the integrated development path of Guangxi Zhuang traditional medicine and health tourism industry / 国际中医中药杂志

With the development of social economy and the increase of leisure time for human beings, human beings are paying more and more attention to the health. The health tourism industry for the purpose of health preservation has also been brought out. In the health tourism industry, traditional medicine plays an important role in this. It is promoting mutual learning among human civilizations. It plays an important role in maintaining the physical and mental health of the people. China has abundant traditional medicine resources and a huge health tourism market. How to effectively integrate traditional medicine and health tourism industries, promote the long-term development of both is of research. This article takes the traditional medicine of the Zhuang nationality in Guangxi as the research object. We analyze the status quo of its integration with the health tourism industry, point out that the integration has not been done, such as the relatively backward infrastructure of traditional medicine and health tourism, urgent need to enrich experience products, lack of product structure, and lack of professional talents. We will deal with these problems to proposes a path to improve the effective integration. It is expected to provide theoretical guidance and practical reference for the integrated development of traditional medicine and health tourism.

The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients.@*METHODS@#Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared.@*RESULTS@#There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group.@*CONCLUSION@#The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.

Comparison ofhaploidentical donor versus HLA-matched sibling donor hematopoietic stem cell transplantation for severe aplastic anemia / 中华器官移植杂志

Objective:To compare the clinical outcomes and safety of haploidentical donor (HID)and HLA-matched sibling donor(MSD)hematopoietic stem cell transplantation(HSCT)for severe aplastic anemia(SAA).Methods:From January 1, 2012 to December 31, 2019, retrospective review of clinical data was performed for 75 SAA patients undergoing HSCT at Department of Hematology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.Based upon donor sources, they were divided into two groups of MSD(49 cases)and HID (26 cases). And two groups were compared with regards to hematopoietic recovery, graft-versus-host disease(GVHD)infection and overall survival(OS).Results:Time of platelet and neutrophil engraftment of two groups was comparable(11 d vs.11 d, P=0.84; 11 d vs.12 d, P=0.08). Compared with HID group, MSD group had a lower incidence of acute GVHD(46.2% vs.18.4%, P=0.01)with a comparable incidence of grade Ⅱ-Ⅳ acute GVHD(26.9% vs.14.3%, P=0.24), grade Ⅲ-Ⅳ acute GVHD(15.4% vs.4.1%, P=0.09)and chronic GVHD(23.9% vs.23.1 %, P=0.71). A reactivation of CMV occurred in 27(55.1%)MSD and 22(84.6%)HID recipients( P=0.01). And the incidence of EB viremia was 69.4% and 61.5% respectively.After a median follow-up period of 54.0 and 18.5 months, the estimated 3-year OS rate of MSD and HID groups were 94.0% and 88.0% respectively ( P=0.35). Conclusions:HID HSCT is an effective and relatively safe option for SAA patients, especially for those in urgent need of treatment without MSD or refractory/relapse to immunosuppressive therapy.

Efficacy observation of auricular point sticking in combination with a healthy diet for simple obesity in children / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of combining auricular point sticking and a healthy diet to treat simple obesity in children aged 6-9 years old.Methods: A total of 190 eligible obese kids were divided into an observation group and a control group using the random number table method, with 95 cases in each group. The observation group was intervened by auricular point sticking plus guide on a healthy diet, while the control group was only provided with the guide on a healthy diet. The therapeutic efficacy was observed after intervention for three consecutive months, as well as the changes in body mass (BM), body mass index (BMI), waist circumference (WC), hip circumference (HC), and subcutaneous fat thickness. Results: After the 3-month intervention, the total effective rate was 91.6％ in the observation group, versus 74.7％ in the control group, and the between-group difference was statistically significant (P<0.01); in both groups, the BM, BMI, WC, HC, and subcutaneous fat thickness all decreased significantly (P<0.05), and were lower in the observation group than in the control group, showing statistical significance (P<0.05). Conclusion: Auricular point sticking plus a healthy diet is safe and effective in treating simple obesity in children, producing more significant efficacy than healthy diet intervention alone.

Epidemiological characteristics of traumatic spinal cord injury in China in 2018 / 中华创伤杂志

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Iodine nutrition and goiter among children aged 8 to 10 years in Linhai City, Zhejiang Province / 中华地方病学杂志

Objective:To investigate the urinary iodine and thyroid volume of children aged 8 to 10 years in Linhai City Zhejiang Province, and evaluate the iodine nutrition level of children so as to provide a basis for formulating intervention measures to eliminate iodine deficiency disorders.Methods:In 2019, a systematic sampling method was adopted to select 1 township (street) central primary school in each of the 5 areas in the east, west, south, north, and middle of Linhai City. At least 40 children aged 8 to 10 years were selected from each of the central primary schools in each township (street) to collect family edible salt samples and one-time urine samples during the day for salt iodine and urinary iodine testing, respectively, as well as thyroid B-ultrasound examination.Results:A total of 215 salt samples were collected. The median salt iodine was 21.0 mg/kg, the coverage rate of iodized salt was 57.2% (123/215), the qualified rate of iodized salt was 91.9% (113/123), and the consumption rate of qualified iodized salt was 52.6% (113/215). A total of 215 urine samples were collected. The median urinary iodine was 166.0 μg/L, and the proportion of urinary iodine < 50 μg/L accounted for 5.1% (11/215). A total of 215 children were examined, and the goiter rate was 4.7% (10/215).Conclusion:The overall iodine nutrition level of children aged 8 to 10 years in Linhai City is at an appropriate level (100-199 μg/L), and the goiter rate is within the standard limit for the elimination of iodine deficiency disorders (5%), but the coverage rate of iodized salt and the consumption rate of qualified iodized salt are seriously low.

Analysis of influencing factors for hepatic artery complications of liver transplantation from donation after citizen's death / 中华消化外科杂志

Objective:To investigate the influencing factors for hepatic artery complica-tions of liver transplantation from donation after citizen's death.Methods:The retrospective cohort study was conducted. The clinicopathological data of 147 recipients who underwent liver transplan-tation from donation after citizen's death in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2020 were collected. There were 109 males and 38 females, aged (46±12)years. All recipients underwent liver transplantation from donation after citizen's death. Observation indicators: (1) surgical situations; (2) occurrence of hepatic artery complications after liver transplantation; (3) analysis of donor related influencing factors for hepatic artery complications after liver transplantation; (4) analysis of recipient related influencing factors for hepatic artery complications after liver transplantation; (5) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect survival of recipients up to June 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Univariate analysis was conducted using the Fisher exact probability, and multivariate analysis was conducted using the COX regression model. Kaplan-Meier method was used to calculate the cumulative survival rate and draw the survival curve. Results:(1) Surgical situations: of the 147 recipients, 108 cases underwent orthotopic liver transplantation, and 39 cases underwent piggyback liver transplantation. The operation time of 147 recipients was (458±101)minutes. (2) Occurrence of hepatic artery complications after liver transplantation: 4 of the 147 recipients had hepatic artery complications, including 3 cases with hepatic artery embolism and 1 case with hepatic artery stenosis. The time to occurrence of hepatic artery complications after liver transplantation was (5±2)days. (3) Analysis of donor related influencing factors for hepatic artery complications after liver transplantation: results of univariate analysis showed that age, atherosclerosis, fatty liver and arterial variation were not donor related factors influencing hepatic artery complications after liver transplantation ( P>0.05). (4) Analysis of recipient related influencing factors for hepatic artery complications after liver transplantation: results of multivariate analysis showed that insufficient hepatic artery blood flow in the recipient was an independent risk factor for hepatic artery complications after liver transplantation ( hazard ratio=10.13, 95% confidence interval as 1.05-97.42, P<0.05). (5) Follow-up: 146 of the 147 recipients were followed up for 1 to 77 months, with a median follow-up time of 34 months. The 1-year cumulative survival rate of the 146 recipients was 92.2%. Conclusion:Insufficient hepatic artery blood flow of the recipient is an independent risk factor for hepatic artery complications after liver transplantation from donation after citizen's death.

Network Meta-analysis on efficacy and safety of non-steroidal anti-inflammatory drugs for osteoarthritis in middle aged and old people / 药学实践杂志

Objective To systematically evaluate the efficacy and safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in middle-aged and old Chinese patients with osteoarthritis(OA). Methods A systematic literature search was conducted through PubMed, Cochrane Library, CNKI, Wan Fang Data and VIP databases to collect randomized controlled trials with non-steroidal anti-inflammatory drugs in middle-aged to old Chinese OA patients. The search time was from the establishment of the database to November 17, 2020. Two researchers independently carried out literature screening, data extraction and literature quality evaluation. Bayesian network meta-analysis was conducted with R3.6.0 software. Results 28 RCTs were included with 2531 patients. Based on the last follow-up pain visual analogue scale (VAS) score, the ranking chart showed that Etoricoxib had the highest probability of having the lowest pain VAS score (88.55%). In terms of total effective rate, the ranking chart showed that the probability of Etoricoxib as first choice was the highest (92.49%). As far as safety, diclofenac sodium patch had the lowest adverse effects rate (59.10%). Conclusion The results of this study indicated that Etoricoxib was the most effective treatment for middle-aged and old Chinese OA patients. It can significantly reduce the OA pain. Diclofenac sodium patch had the least adverse effects.

Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage / 神经科学通报·英文版

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy

An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an "all-in-one" vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared

Allogeneic Hematopoietic Stem Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation.@*METHODS@#Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed.@*RESULTS@#Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning.@*CONCLUSION@#Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.

Effects of Jiaotai Pills on CUMS-induced depression model in mice based on changes of SIRT1 expression in hippocampus / 中国中药杂志

The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1β, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1β, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.

Antioxidative effect and mechanism of tert-butyl hydroquinone on rat retinal Müller cells under high glucose condition / 中华实验眼科杂志

Objective To expore the impact of teniary butyl hydroquinone (tBHQ) on Müller cells in SD rats retina under high glucose condition,and discuss the mechanism of tBHQ.Methods The Müller cells of SD rats were cultured in vitro and the experiment was divided into normal control group,high glucose group and tBHQ intervention group.Western blot and quantitative real time PCR were used to determine the expression of nuclear factor erythroid 2-related factor 2 (Nrf2),hemeoxygenase-1 (HO-1),hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein and mRNA in each group.Results Müller cells cultured in vitro were flat with irregularly sharp.The nucleus was oval,while the cytoplasm was abundant.Adjacent cells were interwoven to a network.Western blot assay showed the overall expression of Nrf2,HO-1,HIF-1α,and VEGF in Müller cells of normal control group,high glucose group,and tBHQ intervention group were significantly different (F =73.831,148.618,152.269,91.217,all at P＜0.001);Among them,the relative expressions of Nrf2,HO-1,HIF-1α and VEGF proteins in the high glucose group were 0.17±0.02,0.47±0.02,0.67±0.07,and 0.6±0.05,which were increased in comparion with 0.06±0.01,0.19±0.03,0.06±0.00 and 0.07±0.02 in the normal control group,with statistically significant differences (t =4.114,9.275,16.479,13.353,all at P ＜ 0.001);the relative expressions of Nrf2 and HO-1 proteins in the tBHQ intervention group were 0.40±0.06 and 0.72±0.05,which were increased by comparion with those in the higher glucose group,with statistically significant differences (t =7.847,7.947,both at P＜0.001);the relative expressions of HIF-1α and VEGF proteins in the tBHQ intervention group were 0.18±0.04,0.26±0.07,which were decreased in comparion with those in the higher glucose group,but were increased in comparion with those in normal control group,with statistically significant differences (t =13.215,8.444,both at P＜ 0.001).Quantitative real time PCR showed that the relative mRNA expressions of Nrf2,HO-1,HIF-1α,and VEGF in Müller cells of normal control group,high glucose group,and tBHQ intervention group were significantly different (F =340.317,1 582.911,488.852,185.699,all at P＜0.001);the relative mRNA expressions of Nrf2,HO-1,HIF-1α,and VEGF proteins in the high-glucose group were 1.53 ± 0.06,1.50 ± 0.04,2.56 ± 0.09,and 3.04 ± 0.19,which were increased in comparion with 1.07±0.07,0.95±0.05,0.99±0.02,and 1.09±0.08 in the normal control group,with statistically significant differences (t =7.292,15.014,30.550,18.573,all at P ＜ 0.001);The relative mRNA expressions of Nrf2 and HO-1 proteins in the tBHQ intervention group were 2.68±0.09 and 2.94±0.05,which were increased in comparion with those in the high-glucose group,with statistically significant differences (t =18.046,39.458,both at P＜0.001);The relative mRNA expression of HIF-1α and VEGF protein in the tBHQ intervention group were 1.48±0.05 and 1.6±0.08,which were decreased by comparion with those in the higher glucose group were increased in comparion with those in normal control group,with statistically significant differences (t =21.036,13.739,both at P＜0.001).Conclusions tBHQ protects Müller cells from damage in high glucose condition by activating anti-oxidative stress signaling pathway of Nrf2/ARE.

The clinical significance of globus pallidus MRI signal intensity in the early identification of neonatal bilirubin encephalopathy / 中国新生儿科杂志

Objective To study the clinical significance of globus pallidus signal intensity and the intensity ratio of globus pallidus and putamen (G/P ratio) on magnetic resonance T1WI for the early recognition of neonatal bilirubin encephalopathy.Method From January to December 2017,full-term neonates with hyperbilirubinemia admitted to the neonatology department of our hospital were enrolled in the case group,and full-term neonates without hyperbilirubinemia in the control group.The clinical data,globus pallidus T1WI signal intensity,G/P ratio and the follow-up data were collected.According to the level of hyperbilirubinemia,the neonates in the case group were further assigned into mild hyperbilirubinemia group (serum bilirubin:222 to ＜256 μmol/L),moderate hyperbilirubinemia group (serum bilirubin:256 to ＜342 μmol/L),and severe hyperbilirubinemia group (serum bilirubin:≥ 342 μmol/L).According to the injury score of ABE,the neonates with ABE were assigned into mild ABE group,moderate ABE group and severe ABE group.The correlation of globus pallidus T1WI and T2WI signal values,G/P ratio and the serum bilirubin level and ABE degree were analyzed;receiver operating characteristic (ROC) curve was drawn to explore the predictive value of the T1WI signal value and G/P ratio for the diagnosis of ABE;the changes of globus pallidus T1WI and T2WI signal values during the first 6 months after birth and the results of follow-up to 1 year after discharge were also analyzed.Result A total of 175 neonates were included in the case group (65 in the mild hyperbilirubinemia group,71 in the moderate hyperbilirubinemia group and 39 in the severe hyperbilirubinemia group) and 43 neonates in the control group.39 neonates were diagnosed as ABE (21 mild ABE,12 moderate ABE,and 6 severe ABE).The first T1WI signal value and G/P ratio of neonates in the severe hyperbilirubinemia group was higher than the moderate hyperbilirubinemia group,the mild hyperbilirubinemia group and the control group;the T1WI signal value and G/P ratio in the moderate hyperbilirubinemia group was higher than the mild hyperbilirubinemia group and the control group (P ＜ 0.05).No significant difference existed between the mild group and the control group(P ＞ 0.05).T2WI values showed no differences among neonates with different bilirubin levels (P ＞ 0.05).The first T1WI signal value and G/P ratio in the severe ABE group were significantly higher than the moderate and mild ABE group,and the moderate ABE group higher than the mild ABE group (P ＜ 0.05).The ROC curve indicated the optimal cut-off value of T1WI signal and G/P ratio were 628 and 1.38,respectively.Among all the 175 neonates,9 had a decrease in T1WI signal value and an increase in T2WI signal value at 6 months after birth.After 1 year of follow-up visits,7 children were finally diagnosed as chronic bilirubin encephalopathy.All these children had increased signal intensity on T1WI in the acute phase,plus a decreased T1WI signal and an increased T2WI signal in 1 ～ 6 months after birth.Conclusion The globus pallidus T1WI signal and G/P ratio are closely related to the serum bilirubin level and ABE severity.If T1WI signal value ＞ 628 or G/P value ＞ 1.38,ABE should be considered.The T1WI signal value and G/P ratio play important roles as indicators for the early recognition of neonatal bilirubin encephalopathy.

miR-133b inhibits myocardial ischemia-reperfusion-induced cardiomyocyte apoptosis and accumulation of reactive oxygen species in rats by targeting YES1 / 南方医科大学学报

OBJECTIVE@#To investigate the effect of miR-133b on cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion (I/R) and explore the mechanism.@*METHODS@#Thirty-six adult SD rats were randomized into sham-operated group, I/R group, AdmiR-NC group and AdmiR-133b group, and rat models of myocardial I/R were established in the latter 3 groups with myocardial injections of saline or recombinant adenoviruses in the left ventricle. The expression of MiR-133b was detected using RT-qPCR, and cardiac function of the rats was determined using FDP 1 HRV and BRS analysis system. Serum CK-MB and cTnI levels were determined by ELISA, myocardial injury was evaluated with HE staining, cardiomocyte apoptosis was detected by flow cytometry, and ROS content was determined using a DCFH-DA probe. In the in vitro experiment, H9C2 myocardial cells with hypoxia/reoxygenation (H/R) treatment were transfected with Mir-NC or MiR-133b mimic, and the cellular expression of MiR-133b, cell apoptosis, and ROS content were determined. Dual luciferase reporter assay was performed to verify the targeting relationship between miR-133b and YES1. The effects of pc-YES1 or miR-133b mimic transfection on YES1 expression, apoptosis, and ROS content in H9C2 cells were evaluated.@*RESULTS@#Compared with those in I/R group, miR-133b expression was obviously up-regulated, LVEDP, cTnI and CK-MB levels were significantly decreased, and LVSP, +dp/dt, -dp/dt, HR and CF levels were increased in admiR-133b group (@*CONCLUSIONS@#miR-133b can inhibit I/R-induced myocardial cell apoptosis and ROS accumulation by targeting YES1 to reduce myocardial I/R injury in rats.

Fatigue correlates with sleep disturbances in Parkinson disease / 中华医学杂志(英文版)

BACKGROUND@#Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.@*METHODS@#Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.@*RESULTS@#Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.@*CONCLUSION@#Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.