AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.

Objective:To study the effect of a modified behavioral treatment(MBT)on functional anejaculation and analyze the factors influencing the therapeutic efficacy.Methods:We enrolled in this study 59 men aged 24-45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual inter-course but normally ejaculating during masturbation.Thirty-nine of the patients underwent conventional behavioral treatment(the CBT group)and the other 20 received MBT,namely,changing the masturbation method combined with audiovisual stimulation during sexual intercourse(the MBT group).We compared the therapeutic effects between the two groups of patients,and analyzed the correlation of the outcomes of MBT with age,abstinence duration,use of audiovisual stimulation,change of the sexual position,mean bilateral testis volume and sex hormone levels.Results:After treatment,22(37.29％)of the patients achieved successful ejaculation at least once in sexual intercourse,11(55.00％)in the MBT group,and the other 11(28.21)in the CBT group,with a significantly higher effec-tiveness rate in the former than in the latter(P＜0.05).The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treat-ment(P＜0.05).Conclusion:MBT has a certain effect on functional anejaculation,and targeting the previous events of the patient is the key to the therapeutic efficacy.Further exploration of more effective strategies of behavioral treatment will become the trend of de-velopment in the management of functional anejaculation.

AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective: Severe radiation-induced late rectal injury (sRLRI) directly affects the quality of life of patients with rectal cancer. Effective prediction of sRLRI before surgery may provide important information for the selection of surgical strategies and perioperative managements. The purpose of this study is to evaluate the feasibility of predicting sRLRI based on magnetic resonance imaging (MRI) features before and after radiotherapy for rectal cancer. Methods: This was a diagnostic study. Clinical and imaging data of 90 patients with rectal cancer receiving long-term radiotherapy from June 2013 to July 2018 in the Sixth Affiliated Hospital of Sun Yat-sen University were collected retrospectively. Case inclusion criteria: (1) rectal cancer was diagnosed by pathology and age of ≥ 18 years old; (2) patients received neoadjuvant chemoradiotherapy and anterior rectal resection; (3) follow up time ≥ 3 years; (4) patients had no history of other neoplasm. Exclusion criteria: (1) patients did not receive MRI examination in our hospital within 2 weeks before and/or 8 weeks after radiotherapy; (2) images were not good enough for evaluation; (3) medical records were incomplete; (4) patients had severe gastrointestinal diseases. According to the RTOG/EORTC classification criteria for radiation reactions, severe complications of grade 3-4 requiring surgical management were defined as sRLRI. T2WI and DWI images before and after radiotherapy were evaluated. The rectal wall thickness, bladder wall thickness, rectal sacral spacing and apparent diffusion coefficient (ADC) were measured. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above indicators for sRLRI. Results: Among the 90 patients with rectal cancer, 34 (37.8%) developed sRLRI. Before radiotherapy, the median rectal wall thickness of sRLRI and non-sRLRI patients was 4.530 mm and 4.355 mm, respectively; the median bladder wall thickness was 3.962 mm and 3.868 mm, respectively; the median rectal sacral spacing was 15.557 mm and 12.433 mm, respectively; the median ADC value of rectal wall was 1.620 ×10(-3) mm(2)/s and 1.653 ×10(-3) mm(2)/s, respectively. There were no significant differences in above indicators between sRLRI and non-sRLRI patients (all P>0.05). After radiotherapy, compared with non-sRLRI patients, sRLRI patients had increased rectal wall thickness (median: 8.239 mm vs. 6.223 mm, Z=-3.512, P=0.001), rectal sacral spacing (median: 17.728 mm vs. 13.885 mm, Z=-2.247, P=0.025), and change of rectal wall thickness after radiotherapy (median: 98.106% vs. 49.584%, Z=-4.169, P<0.001). After radiotherapy, there were no significant differences in the bladder wall thickness and its change value, the ADC value of rectal wall and its change rate before and after radiotherapy between the two groups (all P>0.05). The area under the curve (AUC) of the change rates of rectal wall thickness after radiotherapy, rectal wall thickness and rectal sacral spacing after radiotherapy for predicting sRLRI was 0.763, 0.722 and 0.642, respectively, while the sensitivity was 85.3%, 70.6% and 76.5%, respectively, and the specificity was 64.3%, 71.4% and 57.1%, respectively. Conclusion: Based on MRI examinations, assessments of rectal wall thickness after radiotherapy, the change rate of rectal wall thickness after radiotherapy, and rectal sacral spacing after radiotherapy are helpful for evaluating the risk of sRLRI after radiotherapy for patients with rectal cancer.
Adolescent ; Chemoradiotherapy ; Diffusion Magnetic Resonance Imaging ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; Quality of Life ; Rectal Neoplasms/radiotherapy* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To observe the therapeutic effect of horizontal penetration needling combined with rizatriptan monobenzoate tablets, simple horizontal penetration needling and simple rizatriptan monobenzoate tablets for migraine without aura in acute stage. METHODS: A total of 99 patients with migraine without aura in acute stage were randomized into an acupuncture plus medication group, an acupuncture group and a western medication group, 33 cases in each one. In the acupuncture group, horizontal penetration needling was applied once at Hanyan (GB 4) to Xuanli(GB 6), Shenting (GV 24) to Yintang (GV 29), Baihui (GV 20) to Qianding (GV 21), etc. for 2 h. In the western medication group, oral rizatriptan monobenzoate tablets for 10 mg were given once. In the acupuncture plus medication group, treatment of acupuncture combined with rizatriptan monobenzoate tablets were given, the application was the same as the acupuncture group and the western medication group. Before treatment and 0.5, 2, 24 h after treatment, the visual analogue scale (VAS) score was observed, the remission rate and the disappearance rate of migraine of 2, 24 h after treatment were compared in the 3 groups. RESULTS: Compared before treatment, the VAS scores of each time point after treatment were decreased in the 3 groups ( CONCLUSION Horizontal penetration needling combined with rizatriptan monobenzoate tablets have significant therapeutic effect on rapid analgesia and continuous analgesia for migraine without aura in acute stage, its effect is superior to simple horizontal penetration needling and simple rizatriptan monobenzoate tablets.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Migraine without Aura ; Tablets ; Treatment Outcome ; Triazoles ; Tryptamines

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Risk Assessment ; Severity of Illness Index

Objective:Study on the mechanism of Tongfengning in promoting uric acid excretion from the perspective of urate transporter and mRNA in renal of hyperuricemia （HUA） model rats. Method:The 80 sprague-dawley rats were randomly divided into two groups， the blank group with 20 rats and the model group with 60 rats. Rats in model group were established as hyperuricemia （HUA） models by intraperitoneal injection of oxonic acid potassium salt （OAPS） and intragastric administration ethambutol hydrochloride （EMB） once a day for 21 days. After successful modeling， rats in the model group were divided into the model group， Tongfengning group and benzbromarone group， with 20 rats per group. Tongfengning solution （15.3 g·kg^-1·d^-1） was administered to the Tongfengning group by gavage feeding. Rats in benzbromarone group were administered 5.2 mg·kg^-1·d^-1 benzbromarone suspension， whereas those in the blank group and the model group were administered the equivalent amount of normal saline for 21 days. On days 14^th and 21^st following intervention， urine， blood， and kidney were collected from rats， serum uric acid （SUA） and urinary uric acid （UUA） levels， blood urea nitrogenand（BUN） and creatinine（CRE） levels and the expression of urate transporter proteins and their mRNAs of all rats were detected by enzyme-colorimetric method， urease method， sarcosine oxidase method， Western blot and Real-time quantitative PCR（Real-time PCR）， respectively. Result:On days 14^th and 21^th following intervention， compared with blank group， SUA， CRE and BUN levels， and urate transporter 1（URAT1），glucose transporter 9（GLUT9） expression increased（P<0.05，P<0.01）， whereas UUA level， and adenosine triphosphate-binding cassette transporter protein G2（ABCG2）， organic anion 1（OAT1）， organic anion 3（OAT3） expression decreased in the model group（P<0.05，P<0.01）. Compared with model group， SUA， CRE and BUN levels， and URAT1， GLUT9 expression decreased in Tongfengning group and the benzbromarone group（P<0.05）， whereas UUA level， and ABCG2， OAT1， OAT3 expression increased（P<0.05）. Creatinine and BUN levels decreased in the Tongfengning group（P<0.05，P<0.01）， with the trend much better than the benzbromarone group（P<0.05）. On day 21^st， except for the BUN level did not change much compared with day 14^th， all the rest indicators got improved obviously. Conclusion:Intraperitoneal injection of OAPS and intragastric administration of EMB can cause HUA models with renal dysfunction. Tongfengning reduced URAT1， GLUT9 mRNA and protein expression， and upregulated ABCG2， OAT1， OAT3 mRNA and protein expression in the rat kidney， which may be one of the mechanisms of promoting uric acid excretion. Tongfengning has a certain protective effect on renal function.