Research on signal mining of adverse events of tizanidine based on FAERS database / 药物流行病学杂志

Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

Pharmaceutical analysis for a patient with rebamipide-induced Stevens-Johnson syndrome by clinical pharmacists / 中国药房

OBJECTIVE To provide reference for the diagnosis and treatment of Stevens-Johnson syndrome caused by rebamipide， and to explore the predisposing factors of Stevens-Johnson syndrome. METHODS Clinical pharmacists analyzed the treatment process of a patient with gastrointestinal diseases and evaluated the correlation between the drug used and adverse reactions， in order to determine the suspected allergenic drug causing Stevens-Johnson syndrome. The predisposing factors of patients with Stevens-Johnson syndrome were explored. RESULTS & CONCLUSIONS The suspected allergenic drugs that caused the patient to develop Stevens-Johnson syndrome included Ilaprazole enteric-coated tablets， Rebamipide tablets and Kangfuxin liquid. In summary， the suspect drug was identified as Rebamipide tablets according to the causality evaluation method of the National Center for Adverse Drug Reaction Monitoring， Naranjo’s scoring method and the algorithm of drug causality for epidermal necrolysis scoring criteria. Hypoproteinemia， competitive binding of plasma proteins between drugs， advanced age， bacterial and viral infections were the predisposing factors of Stevens-Johnson syndrome. Therefore， before using rebamipide in clinical practice， it is necessary to inquire about the patient’s allergy history in detail. During the use process， it is necessary to strengthen the patient’s medication monitoring and be alert to the occurrence of serious adverse reactions. If any abnormalities are found， the medication should be stopped immediately and symptomatic treatment should be given as soon as possible to ensure the safety and effectiveness of the patient’s medication.

Related factors of three-vessel disease in patients with stable coronary artery disease / 中华全科医师杂志

Objective:To analyze the risk factors of three-vessel disease (TVD) in patients with stable coronary artery disease (SCAD).Methods:The clinical data of 447 patients with SCAD diagnosed in Zhongshan Hospital from May 2019 to April 2020 were retrospectively analyzed, including 108 cases with the single-vessel disease (SVD), 136 cases with the two-vessel disease, and 203 cases with three-vessel disease. The general data and hematological indexes were compared between patients with SVD and those with TVD; the related factors for TVD in SCAD patients were analyzed with univariate and multivariate logistic regression.Results:There were 244 males (78.5%) and 67 females (21.5%) with a median age of 57 years (64, 69). Univariate analysis showed that there were significant differences in diabetes history ( χ2=7.75, P=0.005), uric acid ( Z=-2.10, P=0.036), glycosylated hemoglobin ( Z=-2.77, P=0.006) and high density lipoprotein cholesterol (HDL-C) ( Z=-2.99, P=0.003) levels between SVD and TVD groups. Multivariate analysis showed that the high level of blood uric acid ( OR=1.01, 95% CI: 1.00-1.01, P<0.05) and the low level of HDL-C ( OR=3.29, 95% CI:1.23-8.85, P<0.05) were related risk factors of TVD. Conclusion:High blood uric acid level and low HDL-C level are related factors for TVD in patients with SCAD.

The association between the TyG index and the number of coronary artery lesions in patients with stable coronary artery disease / 中华全科医师杂志

Objective:To analyse the association between triglyceride glucose (TyG) index and the number of coronary artery lesions in patients with stable coronary artery disease.Methods:It was a cross-sectional study. Patients with stable coronary artery disease who were admitted to Zhongshan Hospital, Fudan University from 1st January 2019 to 30th April 2020 for percutaneous coronary intervention (PCI) were selected. We collected general clinical information and laboratory results from the enrolled patients, then calculated the TyG index. We evaluated coronary artery lesions by coronary angiography and analysed the factors associated with the number of coronary artery lesion branches by the logistic regression model.Results:A total of 832 patients were included in this study, 641 (77.0%) were male, the age was (64.6±11.5) years. The mean TyG index was 8.78. Patients with the TyG index≥8.78 were included in the high TyG index group (411 patients), and those with the TyG index<8.78 were included in the low TyG index group (421 patients). Compared with the low TyG index group, the high TyG index group had the higher body mass index and diastolic blood pressure, more smokers and diabetes mellitus, younger age of onset of coronary heart disease (all P<0.05), and a lower proportion of patients using statins ( P=0.027). Compared with the low TyG index group, the high TyG index group had the higher levels of erythrocyte count, hemoglobin, white blood cell count, albumin, urea nitrogen, uric acid, fasting blood glucose, HbA1c, triglyceride, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, apolipoprotein E, and C-reactive protein (all P<0.05). However, the levels of high density lipoprotein, apolipoprotein A1 and apolipoprotein A were lower in the high TyG index group than those in the low TyG index group (all P<0.05). The number of coronary artery lesions in patients in the high TyG index group was 2.35±0.91, more than the low TyG index group 2.10±0.95 ( P<0.001).After adjusting for the other factors, multivariate logistic regression analysis showed that male, smoking history (smoking cessation or smoking), TyG index and troponin T levels were independently positively associated with the number of coronary artery lesions (all OR>1, P<0.05), while ApoA1 was independently negatively associated with the number of coronary artery lesions ( OR=0.140, P=0.007). Conclusions:TyG index is positively associated with the number of coronary artery lesions in patients with stable coronary artery disease.

Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ / 부인종양

Objective@#To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. @*Methods@#Patients diagnosed with AIS after CC during 2007–2021 were identified by computerized databases at Women’s Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. @*Results@#Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. @*Conclusion@#CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

Ginsenoside Rk2,a dehydroprotopanaxadiol saponin,alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice / 药物分析学报

Heavy alcohol consumption results in alcoholic liver disease(ALD)with inadequate therapeutic options.Here,we first report the potential beneficial effects of ginsenoside Rk2(Rk2),a rare dehy-droprotopanaxadiol saponin isolated from streamed ginseng,against alcoholic liver injury in mice.Chronic-plus-single-binge ethanol feeding caused severe liver injury,as manifested by significantly elevated serum aminotransferase levels,hepatic histological changes,increased lipid accumulation,oxidative stress,and inflammation in the liver.These deleterious effects were alleviated by the treatment with Rk2(5 and 30 mg/kg).Acting as an nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inhibitor,Rk2 ameliorates alcohol-induced liver inflammation by inhibiting NLRP3 inflammasome signaling in the liver.Meanwhile,the treatment with Rk2 alleviated the alcohol-induced intestinal barrier dysfunction via enhancing NLRP6 inflammasome in the intestine.Our findings indicate that Rk2 is a promising agent for the prevention and treatment of ALD and other NLPR3-driven diseases.

Click chemistry-based enrichment strategy for tracing cellular fatty acid metabolism by LC-MS/MS / 药物分析学报

Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling molecules.Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events.Inspired by the advances in click chemistry for protein enrichment,we herein established a click chemistry-based enrichment(CCBE)strategy for tracing the cellular metabolism of eicosapentaenoic acid(EPA,20:5 n-3)in neural cells.Terminal alkyne-labeled EPA(EPAA)used as a surrogate was incubated with N2a,mouse neuroblastoma cells,and alkyne-labeled metabolites(ALMs)were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment.After removing unlabeled metabolites,ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry(LC-MS)analysis.The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices.In addition,this method can overcome current detection limits by enhancing MS sensitivity of targets,improving the chromatographic separation of sn-position glycerophospholipid regioisomers,facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature,and providing versatile fluorescence detection of ALMs for cellular distribution.This CCBE strategy might be expanded to trace the metabolism of other FAs,small molecules,or drugs.

Impact of low whole grain intake on the burden and trend of colorectal cancer among Chinese residents aged 70 and above from 1990 to 2019：Based on GBD data / 公共卫生与预防医学

Objective To analyze the impact of low whole grain intake on the burden and trend of colorectal cancer in China, and to explore health management strategies for high-risk populations. Methods Using the 2019 Global Burden of Disease Study (GBD 2019) data, the Joinpoint regression model was used to analyze the mortality rate and disability adjusted life years (DALYs) of colorectal cancer in China caused by low whole grain intake from 1990 to 2019. Results The number of colorectal cancer deaths, mortality and DALYs of residents over 70 years old caused by low whole grain intake in China increased from 4 615, 12.06/105 and 187.66/100 000 in 1990 to 21 094 , 19.54/100 000 and 291.02/100 000 in 2019. The trend analysis found that the total crude mortality rate of colorectal cancer in Chinese residents over 70 years old caused by low whole grain intake increased by 2.03% year by year, with men increasing by 2.61% year by year, and women increasing by 1.24% year by year (all P<0.001). From 1990 to 2019, the disease burden of colorectal cancer in China was higher than that of countries with middle, low-middle, and low SDI, but lower than the global average, and high and middle-high SDI countries or regions. The growth rate in China was higher than the above regions (China 1.86% vs. global -0.25%, high SDI -0.88%, middle-high SDI -0.09%, middle SDI 1.53%, low-middle SDI 1.12%, and low SDI 0.63%). Conclusion Based on the current situation and trend of colorectal cancer disease burden of residents over 70 years of age in the world and China, precise health management of unhealthy lifestyles of high-risk populations will help to achieve the goals of healthy aging and healthy China 2030.

Efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus in adolescents / 国际外科学杂志

Objective:To investigate the efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus (OLT) in adolescents.Methods:Retrospective case analysis was used. The clinical data and follow-up results of 13 adolescent patients (13 feet) with Hepple Ⅱ OLT were all treated with osteochondral fragment fixation using bioabsorbable pins admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were retrospectively analyzed. There were 7 males and 6 females, with 13 right feet. The age was (14.85±2.23) years old, ranged from 12 to 18 years old. According to the American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS) and SF-36 score before operation and at the last follow-up were used to evaluate the efficacy and function of the patients. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; The mearsurement data with skewness distribution were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. Results:Thirteen adolescent patients (13 feet) with Hepple Ⅱ OLT underwent surgery successfully and were followed up for (25.54±9.95) months. All wounds healed by first intention, and no complications such as wound infection and delayed healing occurred. Preoperative AOFAS ankle-posterior foot score, VAS and SF-36 score were 58.62±3.55, 7.00 (6.50, 8.00) and 68.38±4.81, respectively. At the last follow-up, the scores were 97.38±2.73, 1.00 (0.00, 1.00), 91.15±4.28, respectively, and the results were significantly improved at the last follow-up, with the difference between the two groups statistically significant( P<0.05). Conclusion:Osteochondral fragment fixation using bioabsorbable pins which can promote cartilage repair, significantly improve symptoms, and achieve better clinical satisfaction with fewer complications, is a safe and effective surgical treatment option for Hepple Ⅱ OLT in adolescents with satisfactory short-term clinical outcomes.

Mid-term effects of surgery for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture / 中华创伤骨科杂志

Objective:To evaluate the mid-term efficacy of surgery for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture.Methods:From July 2014 to October 2019, 14 patients were treated at Foot & Ankle Section, Department of Orthopaedics, Shanghai Sixth People’s Hospital for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture.There were 11 males and 3 females, aged from 17 to 61 years (mean, 35.9 years).According to Danis-Weber classification, 6 cases were type B and 8 type C; according to Lauge-Hansen classification, 7 cases belonged to supination-external rotation, one to pronation-abduction, and 6 to pronation-external rotation (Maisonneuve fracture in 4).The syndesmosis injury was treated by fixation with distal tibiofibular screws in 11 cases, by Tightrope elastic fixation in one, by hybrid fixation with distal tibiofibular screws and Tightrope in one, and by distal tibiofibular fusion in one.Postoperative complications were recorded.Their visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society ankle-hindfoot scores (AOFAS-AH) were compared between preoperation and the last follow-up.Results:The 14 patients were followed up for 24 to 85 months (mean, 46.8 months). Of the 9 patients whose distal tibiofibular screws had been removed (including one with hybrid fixation), wound infection occurred in one after removal of all the internal fixation, distal tibiofibular widening in 2, ankle degeneration in 5 and fibular nonunion in one. Of the other 3 patients whose distal tibiofibular screws had not been removed, screw breakage happened in 2, screw loosening in one and distal tibiofibular widening in one. The VAS scores were significantly improved from preoperative 6.8±0.9 to 1.4±1.3 at the last follow-up; the AOFAS-AH scores were increased significantly from preoperative 35.3±6.3 to 86.8±11.7 at the last follow-up (both P<0.001). According to AOFAS-AH scores, 8 cases were excellent, 4 good and 2 moderate. Conclusion:Surgery for sub-acute injury to distal tibiofibular syndesmosis associated with ankle fracture can restabilize the distal tibiofibular syndesmosis and ankle joint, reduce pain and improve ankle function, leading to fine mid-term efficacy.

Morphology of dorsal medial talar neck osteophyte and its clinical significance: based on three-dimensional computed tomography / 中华创伤骨科杂志

Objective:To study the morphology of dorsal medial talar neck osteophyte (DMTNO) and its association with anteromedial ankle impingement syndrome (AAIS) using CT 3D reconstruction images.Methods:The present retrospective study included 23 patients with AAIS due to DMTNO (case group) and 23 patients with DMTNO but without AAIS (control group) who had been admitted from February 2019 to June 2021. Multi-slice CT data (DICOM) of DMTNO in both groups were collected and imported into Arigin 3D Pro 3D reconstruction software to reconstruct and observe the 3D morphology of DMTNO. The dorsal convex distance, medial convex distance and anterior convex distance of DMTNO were measured to find their association with AAIS.Results:In the case group, DMTNO clearly showed a flat polyhedral shape with a large base and a small top; in the control group, DMTNO showed various shapes that were different mainly in an irregular top but similar in a large, long and narrow base. The dorsal convex distance [(8.07±2.30) mm] and medial convex distance [(6.70±2.62) mm] in the case group were significantly larger than those in the control group [(3.59±1.10) mm and (1.98±0.93) mm] ( P<0.05), but there was no significant difference between the 2 groups in the anterior convex distance ( P>0.05). Conclusions:The DMTNO leading to AAIS shows a flat polyhedral shape with a large base and a small top. No correlation is found between the anterior convex and AAIS whereas the dorsal convex and medial convex of DMTNO may be closely associated with AAIS.

Arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy for the treatment of chronic lateral ankle instability combined with subtle cavus foot / 中华创伤杂志

Objective:To evaluate the short-term outcome of arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy for the treatment of chronic lateral ankle instability combined with subtle cavus foot.Methods:A retrospective cohort study was conducted to analyze the clinical data of 12 patients suffering chronic lateral ankle instability combined with subtle cavus foot admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from November 2016 to November 2020, including 5 males and 7 females, aged 16-62 years [(40.3±15.1)years]. All patients were treated with arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy. The calcaneal pitch angle, Meary′s angle and medial cuneiform height on the foot weight-bearing lateral view plus calcaneus valgus angle on the hindfoot long axial view were compared to evaluate the improvement of bony structure and foot alignment preoperatively and at 3 months and 1 year postoperatively. At the same time, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to evaluate the improvement of ankle function and pain. Postoperative complications were also observed and recorded.Results:All patients were followed up for 1-3 years [(1.6±0.6)years]. The calcaneal pitch angle was decreased from (24.6±5.3)° preoperatively to (22.5±4.9)° at postoperative 3 months and (22.3±5.0)° at postoperative 1 year; the Meary′s angle was decreased from 6.6°(5.2°,7.6°) preoperatively to 2.5°(0.5°,3.8°) at postoperative 3 months and 2.1°(0.5°,3.2°) at postoperative 1 year; the medial cuneiform height was decreased from (24.3±5.3)mm preoperatively to (22.3±4.8)mm at postoperative 3 months and (22.3±4.6)mm at postoperative 1 year; the calcaneus valgus angle was increased from -7.1°(-10.3°,-5.9°) preoperatively to 2.3°(-2.5°,4.5°) at postoperative 3 months and 2.4°(-1.6°,3.8°) at postoperative 1 year (all P<0.01). However, there were no significant differences in the calcaneal pitch angle, Meary′s angle, medial cuneiform height, and calcaneus valgus angle at postoperative 3 months and 1 year (all P>0.05). AOFAS ankle-hindfoot score was increased from (66.8±8.7)points preoperatively to (81.0±5.9)points at postoperative 3 months and (88.6±3.6)points at postoperative 1 year (all P<0.01). According to AOFAS ankle-hindfoot score, the results were excellent in four patients and good in eight patients at postoperative 1 year, with the excellent and good rate of 100%. VAS was decreased from 2.5(2.0,4.0)points preoperatively to 2.0(1.3,2.8)points at postoperative 3 months and 1.0(0,2.0)points at postoperative 1 year (all P<0.01). There were significant differences in the AOFAS ankle-hindfoot score and VAS at postoperative 3 months and 1 year (all P<0.05). Wound malunion was seen in one patient, and healed with a dress changing. All patients had no complications such as vascular or nerve injury. There was no recurrence of malformation or joint instability during 1-year follow-up. Conclusion:For chronic lateral ankle instability combined with subtle cavus foot, arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy can stabilize ankle joint, correct hindfoot alignment, improve function and relieve pain.

Posterior ankle arthroscopic microfracture with platelet-rich plasma injection for the treatment of osteochondral lesions of the talus / 中华创伤杂志

Objective:To investigate the efficacy of posterior ankle arthroscopic microfracture with platelet-rich plasma (PRP) injection for the treatment of posterior osteochondral lesions of the talus (OLT).Methods:A retrospective case series study was conducted on clinical data of 13 patients with posterior OLT admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from September 2019 to October 2020. There were 10 males and 3 females, aged 10-65 years [(38.2±15.9)years]. According to Hepple′s classification, four patients were with type II, three with type IV, and six with type V. According to Elias′ grid scheme, nine patients were in zone 7 and four patients in zone 9. The disease duration was 13-51 months [(26.2±11.4)months]. All patients underwent posterior ankle arthroscopic microfracture with PRP injection. The operation time was recorded. The visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle range of motion (ROM) were compared before operation and at 3 months and 1 year after operation. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used to evaluate the repair of cartilage injury at 1 year after operation. Complications were recorded.Results:All patients were followed up for 12-25 months [(15.7±3.7)months]. The operation time ranged from 50 to 90 minutes [(63.8±13.3)minutes]. The VAS improved from 3.0(3.0, 4.0)points before operation to 1.0(0, 2.0)points at 3 months after operation and 1.0(0,1.5)points at 1 year after operation; the AOFAS ankle-hindfoot score was improved from (66.1±11.8)points before operation to (84.8±9.5)points at 3 months after operation and (92.9±8.6)points at 1 year after operation; the ankle ROM was improved from (48.5±7.5)° before operation to (61.9±10.3)° at 3 months after operation and (65.4±11.8)° at 1 year after operation (all P<0.05). There was no significant difference in VAS at 3 months and 1 year after operation ( P>0.05). There were significant differences in AOFAS ankle-hindfoot score and ankle ROM at 3 months and 1 year after operation (all P<0.05). According to AOFAS ankle-hindfoot score, the results were excellent in 11 patients, good in one, and fair in one, with the excellent and good rate of 92%. The MOCART score was 40-85 points [(70.4±14.2)points] at 1 year after operation. There was no postoperative necrosis, infection or neurovascular injury. Two patients had slight transient pain during rehabilitation training and were improved after non-surgical treatment. Conclusion:For posterior OLT, posterior ankle arthroscopic microfracture with PRP injection can effectively alleviate pain, improve ankle function and repair cartilage damage, with satisfactory short-term efficacy.

Exploration and prospects of fat mass and obesity-associated in glioblastoma / 国际外科学杂志

Glioblastoma (GBM) is a common malignant neuroepithelial tumor of the central nervous system with rapid progression and high drug resistance. Fat mass and obesity associated (FTO), as the main demethylase in the modification process of N6-methyladenosine, is widely involved in GBM regulation, including tumor occurrence and development. It is also associated with the mutation of isocitrate dehydrogenase. The role of FTO in the aspects of biological function, glioblastoma stem cell sustaining and selfrenewing and chemotherapy resistance remained contentious. In this paper, FTO is preliminarily described through bioinformatics and current research, and the future research is prospected from the perspectives of energy metabolism, small molecule RNA regulation and post-translational modification.

Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome / 中国骨伤

OBJECTIVE@#To investigate the surgical skills and clinical curative results of arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome.@*METHODS@#From February 2019 to August 2020, 13 patients with ankle instability combined with anteromedial impingement were retrospectively analyzed. There were 10 males and 3 females with age of (40.0±15.1) years old. The course of disease was(44.1±33.2) months. All patients had history of ankle sprain. MRI showed the injury of anterior talofibular ligament. All patients had anteromedial pain and pressing pain when ankle dorsiflexion. All patients were treated with ankle debridement and Brostr?m-Gould surgery under ankle arthroscopic. Postoperative results were evaluated by VAS(visual analogue scale) and AOFAS-AH(American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, AOFAS-AH).@*RESULTS@#All 13 patients completed the surgery successfully with an operative time of 60 to 90 minutes. All the surgical incisions healed by first intention, and no complications such as incision infection, skin necrosis and neurovascular injury. Follow-up time was (18.1±4.7) months. At the latest follow-up, the VAS score was 1.2±1.1, which was significantly lower than the preoperative score 4.8±1.5 (P<0.05);the AOFAS-AH score 94.2±5.1 was significantly higher than the preoperative score 65.5±11.5 (P<0.05). The AOFAS-AH score at the final follow-up ranged from 84 to 100. All patients walked with normal gait without ankle instability or impingement recurrence.@*CONCLUSION@#Ankle anteromedial impingement syndrome combined with ankle instability is easy to be ignored clinically. Such kind of anteromedial impingement syndrome is mostly related to osteophyte at dorsal medial talar neck. Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome has satisfactory curative effect with safety and minimal injury.

Therapeutic evaluation of galangin on cartilage protection and analgesic activity in a rat model of osteoarthritis

BACKGROUND Osteoarthritis (OA) is a form of arthritis due to degradation of articular cartilage. OA is asso ciated with stiffness, joint pain, and dysfunction, affecting adults worldwide. Galangin is a bioactive fla vonoid that exerts several therapeutic and biological activities. Anti-hyperglycemic, anti-inflammatory, anti-cancer, and anti-apoptotic activities of galangin have been reported in several studies. In the present study, rats were divided into normal control, OA (control), galangin 10 mg/kg (low-dose), galangin 100 mg/kg (high-dose), and celecoxib 30 mg/kg (positive control) groups. All doses were administered orally for 14 consecutive days. The urinary type II collagen (mCTX-II) level as well as reactive oxygen spe cies, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, superoxide dismutase, catalase, lipid peroxidation, reduced glutathione, and glutathione peroxidase levels were measured. In addition, the CTX-II mRNA and protein expression levels were measured. RESULTS Galangin supplementation significantly reduced the mCTX-II level compared with controls. Galangin treatment significantly reduced reactive oxygen species, lipid peroxidation, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha levels, but increased catalase, superoxide dismutase, glu tathione peroxidase, and reduced glutathione levels. Galangin treatment significantly reduced the CTX-II mRNA and protein expression levels. The low CTX-II level in tissue indicated the inhibition of cartilage degradation. CONCLUSIONS In summary, supplementation with galangin was effective against OA. The identification of potential therapeutic agents that inhibit inflammation may be useful for the management and prevention of OA

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 / 中国天然药物

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aβ

Effects of prostaglandin E2 receptor on the activation of inflammasomes and cell damage in human retinal microvascular endothelial cells in a high-glucose environment / 中华眼底病杂志

Objective:To observe the effects of four prostaglandin E2 (PGE2) receptors (EP 1-4R) on the activation of inflammasomes and cell damage in human retinal microvascular endothelial cells (hRMEC) in a high glucose environment. Methods:The hRMEC were divided into normal group and high glucose group, and they were cultured in Dulbecco modified Eagle medium containing 5.5 and 30.0 mmol/L glucose, respectively. Flow cytometry was used to observe the apoptosis rate of the high glucose group and the normal group; enzyme chain immunosorbent assay (ELISA) was used to detect the level of PGE2 in the culture supernatant of hRMEC cells. Western blot was used to detect the protein expression of cyclooxyganese (COX2) and EP 1-4R in hRMEC. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of EP 1-4R mRNA in hRMEC. After 72 h of culture, the cells in the high glucose group were divided into control group, PGE2 group, EP 1-4R agonist group, PGE2+EP 1-4R inhibitor group, and dimethylsulfoxide group. According to the group, each group was given the corresponding agonist or inhibitor to continue the culture for 24 h. QRT-PCR was used to detect the expression of nucleotide-binding oligomerization structure-like receptor protein (NLRP3) and pro-interleukin (IL)-1β mRNA in each group of cells. ELISA was used to detect the content of IL-1β and lactic dehydrogenase (LDH) in the cell culture supernatant. Western blot was used to detect the expression of cleaved Caspase-1 in each group of cells. At the same time, hRMEC in a high glucose environment was given IL-1β stimulation for 24 h, and the activity of LDH in the supernatant of the cell culture medium was detected. Results:The apoptotic rate, COX2 protein expression, and PGE2 protein content in hRMEC in the high glucose group were significantly higher than those in the normal group, and they were time-dependent. Compared with the normal group, the expression levels of EP 1R, EP 2R, EP 4R protein and mRNA in hRMEC in the high glucose group were higher than those in the normal group ( P<0.05). Compared with the control group, PGE2 group ( t=4.627, P<0.01), EP 1-4R agonist group ( t=3.889, 3.583, 2.445, 3.216; P<0.05) hRMEC NLRP3 mRNA expression level was significantly increased; the expression level of pro-IL-1β mRNA increased, however the difference was not statistically significant (PGE2 group: t=1.807, P>0.05; EP 1-4R agonist group: t=1.807, 1.477, 0.302, 1.926, P>0.05). Compared with the PGE2 group, the expression of NLRP3 mRNA in hRMEC in the PGE2+EP 2R inhibitor group was significantly reduced ( t=2.812, P<0.05); the expression of pro-IL-1β mRNA in hRMEC in the PGE2+EP 3R inhibitor group was significantly increased ( t=4.113, P<0.01). The protein content of IL-1β in the cell culture supernatant of the PGE2 group, EP 1R agonist group and EP 2R agonist group was significantly higher than that of the control group ( t=5.155, 4.136, 4.817; P<0.01). Compared with PGE2 group, the protein content of IL-1β in the cell culture supernatant of the PGE2+EP 2R inhibitor group and the PGE2+EP 4R inhibitor group were significantly lower than that of the PGE2 group ( t=1.964, 4.765; P<0.05). The expression of cleaved Caspase-1 in hRMEC in the PGE2 group and EP 2R agonist group was significantly higher than that in the control group ( t=5.332, 4.889; P<0.05). The expression of cleaved Caspase-1 in hRMEC in the PGE2+EP 2R inhibitor group was significantly lower than that of the PGE2 group ( t=6.699, P<0.01). The LDH activity in the cell culture supernatant of the PGE2 group and the EP 2R agonist group was significantly higher than that of the control group ( t=4.908, 4.225; P<0.05). The activity of LDH in the cell culture supernatant of the PGE2+EP 2R inhibitor group was significantly lower than that of the PGE2 group ( t=5.301, P<0.01). Compared with the control group, the LDH activity in the culture supernatant of hRMEC cells in the high glucose environment was significantly increased ( t=3.499, P<0.05). Conclusions:The four receptors of PGE2 can activate NLRP3 and its effector molecules to varying degrees. EP 2R mainly mediates hRMEC damage under high glucose environment.

Transfibular osteotomy with open reduction and fixation for treatment of old ankle fractures involving the posterior malleolus in middle-aged and elderly patients / 中华创伤杂志

Objective:To evaluate the clinical results of reduction and fixation via fibular osteotomy for treatment of old ankle fractures involving the posterior malleolus in middle-aged and elderly patients.Methods:A retrospective case series study was made for 13 middle-aged and elderly patients with old ankle fractures involving the posterior malleolus treated from July 2013 to March 2018 in Sixth People's Hospital Affiliated to Shanghai Jiao Tong University. There were 2 males and 11 females, with age of 48-63 years (mean, 54.8 years). The mean surgical period was 8-18 weeks from injury (mean, 9.6 weeks). According to Haraguchi classification, all posterior malleolar fractures were type I. According to Lauge-Hansen classification, there were 2 patients with pronation-external rotation type and 11 with supination-external rotation type. All patients underwent open reduction and fixation via fibular osteotomy. Bone healing time and postoperative complications were recorded. Clinical results were assessed by visual analogue scale (VAS) score and American orthopedic foot and ankle society (AOFAS) ankle-hind score.Results:All patients were followed up for average 20.3 months (range, 9-36 months). All patients had bone union, with the mean healing period of 12-15 weeks (average 14.8 weeks). No infection, implant loosening or breakage occurred after operation. X-ray film of one patient suggested mild traumatic arthritis. At the latest follow-up, VAS was improved to (1.0±0.2)points compared to pre-operative (5.3±0.6)points ( P<0.05), and the AOFAS ankle-hind score was improved to (85.2±7.4)points compared to pre-operative (42.4±6.7)points ( P<0.05). According to the AOFAS ankle-hind score, the results were excellent in 4 patients, good in 8, moderate in 1, with the excellent and good rate of 92%. Conclusion:For old ankle fractures involving the posterior malleolus in the middle-aged and elderly patients, reduction and fixation via fibular can reduce postoperative complications, facilitate bone healing, relieve ankle pain and improve function recovery.

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs.@*METHODS@#We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model.@*RESULTS@#Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE.@*CONCLUSIONS@#The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.