Migraine is a common chronic neurological disease，faces still certain limitations in the design of some clinical trials of migraine in China. Based on the principle of “PICO” in clinical research， this article summarizes the core contents of Guidelines for controlled trials of preventive treatment of episodic migraine in adults published by International Headache Society and its Clinical Trials Standing Committee， including subject selection， key points of trial design， and endpoint evaluation indicators. This article also discusses the deficiencies in current clinical trial design， so as to provide a basis for the design of clinical trials for migraine.

The American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and the American Society of Regional Anesthesia and Pain Medicine collaborated to develop an evidence-based study about the safe and effective use of Ketamine in total joint arthroplasty(TJA). Based on the systematic review and Meta-analysis of several studies, the following conclusions are drawn: Ketamine can effectively relieve the postoperative pain of patients; Ketamine can effectively reduce the occurrence of postoperative nausea and vomiting; Ketamine can reduce the use of postoperative opioids; intraoperative use of Ketamine does not increase the incidence of postoperative adverse reactions. The above conclusions are graded according to the strength of evidence support. This article interprets the guidelines to provide reference for addressing the effectiveness and safety of Ketamine use in TJA.

ObjectiveTo explore the effect of Anmeidan on the sleep quality and serum levels of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and irisin in the patients with chronic insomnia. MethodA multicenter， randomized， double-blind， placebo-controlled clinical study was carried out， including 480 patients with chronic insomnia （deficiency syndrome） in Wuhan （Hubei）， Guangzhou （Guangdong）， and Lanzhou （Gansu）. They were randomized into an observation group and a control group at a ratio of 1∶1. The observation group was orally administered with Anmeidan granules at a dose of 11 g， 3 times per day， and the control group with Anmeidan simulant at a dose of 11 g， 3 times per day， Both groups of patients received sleep education after enrollment. After 4 weeks of medication， the Athens insomnia scale （AIS） scores， Spiegel scale scores， and serum levels of BDNF， GFAP， and irisin were compared between the two groups as well as between before and after treatment. ResultA total of 480 adult patients with chronic insomnia were enrolled in this study， with 64 patients falled off. Finally， the 415 patients were included in the analysis， including 213 patients in the observation group and 202 patients in the control group. There was no difference in age or sex between the two groups of patients. Compared with before treatment， the treatment in both groups decreased the AIS and Spiegel scores （P<0.01）. After treatment， the observation group had lower AIS and Spiegel scores than the control group （P<0.01）. The treatment in the observation group slightly lowered the level of BDNF， elevated the level of irisin （P<0.05）， and lowered the level of GFAP （P<0.05） in the serum. After treatment， the observation group showed higher level of irisin （P<0.05） and lower levels of BDNF and GFAP in the serum than the control group. ConclusionAnmeidan may improve the sleep quality of patients with chronic insomnia by elevating the irisin level and lowering the GFAP level in the serum.

OBJECTIVE: To validate the effectiveness of a novel comprehensive classification for intertrochanteric fracture (ITF). METHODS: The study included 616 patients with ITF, including 279 males (45.29%) and 337 females (54.71%); the age ranged from 23 to 100 years, with an average of 72.5 years. Two orthopaedic residents (observers Ⅰ and Ⅱ) and two senior orthopaedic surgeons (observers Ⅲ and Ⅳ) were selected to classify the CT imaging data of 616 patients in a random order by using the AO/Orthopaedic Trauma Association (AO/OTA) classification of 1996/2007 edition, the AO/OTA classification of 2018 edition, and the novel comprehensive classification method at an interval of 1 month. Kappa consistency test was used to evaluate the intra-observer and inter-observer consistency of the three ITF classification systems. RESULTS: The inter-observer consistency of the three classification systems evaluated by 4 observers twice showed that the 3 classification systems had strong inter-observer consistency. Among them, the κ value of the novel comprehensive classification was higher than that of the AO/OTA classification of 1996/2007 edition and 2018 edition, and the experience of observers had a certain impact on the classification results, and the inter-observer consistency of orthopaedic residents was slightly better than that of senior orthopaedic surgeons. The intra-observer consistency of two evaluations of three classification systems by 4 observers showed that the consistency of the novel comprehensive classification was better for the other 3 observers, except that the consistency of observer Ⅳ in the AO/OTA classification of 2018 version was slightly higher than that of the novel comprehensive classification. The results showed that the novel comprehensive classification has higher repeatability, and the intra-observer consistency of senior orthopaedic surgeons was better than that of orthopaedic residents. CONCLUSION The novel comprehensive classification system has good intra- and inter-observer consistency, and has high validity in the classification of CT images of ITF patients; the experience of observers has a certain impact on the results of the three classification systems, and those with more experiences have higher intra-observer consistency.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Observer Variation ; Reproducibility of Results ; Hip Fractures/surgery* ; Tomography, X-Ray Computed/methods* ; Radiography

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed with α-,β-,y-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm iso-mers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-CD+Ca-H]+with Rp-p of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R2＞0.99)was ob-tained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

Objective To observe the impacts of acupuncture and moxibustion on kelch like epichlorohydrin related protein 1(Keap1)and nuclear factor E2 related factor 2(Nrf2)signal pathway in kidney tissue of cisplatin(DDP)-induced kidney injury model mice,and to explain the protective mechanism of acupuncture and moxibustion on improving kidney injury caused by DDP.Methods Forty SPF male KM rats were randomly divided into 4 groups,with 10 rats in each group.One day before the start of treatment,the three groups of mice outside the blank group were intraperitoneally injected with cisplatin 10 mg·kg-1 according to their body weight,and the blank group was injected with the same dose of 0.9%NaCl solution.The model was established 24 hours later.Both acupuncture group and moxibustion group selected"Dazhui"(GV14),"Ganshu"(BL18),"Shenshu"(BL23)and"Zusanli(Housanli)"(ST36)for acupuncture and moxibustion respectively,once a day for 5 days.The other two groups were fixed every day without treatment.After fasting for 1 day,the contents of BUN,Scr,CysC and NGAL in serum and Keap1 and Nrf2 in renal tissue were detected by ELISA;Western blot and Real-time PCR were used to detect the protein expression and gene transcription of Keap1 and Nrf2 in the kidney tissue of mice in each group.Results Compared with the blank group,the content of Keap1 protein,protein expression and relative expression of mRNA in the model group increased(P<0.05),the content of Nrf2 protein,protein expression decreased(P<0.05),Nrf2 relative expression of mRNA increased(P<0.05);Compared with the model group,the content of Keap1 protein,the expression of Keap1 protein and the relative expression of Keap1 mRNA in the kidney of mice in the acupuncture and moxibustion groups decreased(P<0.05);Nrf2 protein content,protein expression and relative mRNA expression increased(P<0.05).Conclusion Acupuncture and moxibustion can improve the renal function of DDP renal injury model mice and enhance their antioxidant stress ability,so as to improve the renal injury caused by DDP chemotherapy.Its mechanism may be related to Keap1/Nrf2 signal pathway.

Objective : To investigate the correlation between co-signaling molecule B7-H3 and epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) target therapy in acquired drug resistance of lung adenocarcinoma. Methods : Immunohistochemical method was used to detect B7-H3 expression in 56 lung adenocarcinoma patients, and the cohort was divided into low and high B7-H3 expression groups.The proportion and occurrence time of acquired drug resistance after EGFR-TKI targeted therapy were compared between the two groups.Gefitinib-resistant EGFR mutant lung adenocarcinoma cell lines H3255 and HCC827 were induced and cultured in vitro.The wild-type cell lines were used as control, and the expression level of B7-H3 on resistant cell lines B7-H3 was analyzed by flow cytometry. Results: In 56 lung adenocarcinoma patients, 31 cases and 25 cases had low and high B7-H3 expression, respectively.By the end of this study, the cases of acquired drug resistance in patients with low and high B7-H3 expression were 12 cases(38.7%) and 14 cases(56.0%)(P=0.19,χ2=1.663),and the median drug resistance time was 13.2 months and 5.1 months(P=0.004,t=3.193),respectively.Compared with wild-type H3255 and HCC827 cell lines, the expression level of drug-resistant strain B7-H3 further increased. Conclusion B7-H3 expression level is correlated with acquired drug resistance of EGFR-TKI targeted therapy in lung adenocarcinoma.

Objective : To investigate the diagnostic endoplasmic reticulum aminopeptidase-1 (ERAP1) in patients with hepatocellular carcinomae (HCC) ． Methods : Enzyme-linked immunosorbent assay (ELISA) was used to de- tect the serum levels of ERAP1 in HCCpatients，cirrhosis patients and healthy controls (HC) ．Multivariate logistic regression was used to analyze the independent risk factors of the severity and prognosis ，and receiver operating characteristic curve (ROC) was used to evaluatesensitivity and specificity of ERAP1 in the diagnosis of different degree of disease and prognosis. Results : The serum ERAP1 level of HCC was related to tumor stage，tumor size and number of cancer focal (P ＜0. 05 ) ． ERAP1 level of HCC patients was positivecorrelated with ALT ，AST， TBIL and AFP，while negative correlated with ALB(P＜0. 05) ．ERAP1 was found to be an independent predictor of different severity and prognosis．When joint diagnosing HCC with AFP，the area under the curve ( AUC) was 0. 932．For the diagnosis of poor prognosis，the AUC was 0. 742． Conclusion Serum ERAP1 level has important clinical significance and potential application value in evaluating the severity and prognosis of HCC patients.

Objective: To investigate the mechanism of down-regulation of the phosphatase and tensin homolog deleted on chromosome ten(PTEN) caused by hepatitis B virus(HBV) infection and the antiviral activity of interferon α(IFN-α). Methods: HepG2 cells and HepG2.2.15 cells were cultured under suitable conditions. HepG2 cells were transfected with empty vector(pcDNA3.1) and HBV1.3 plasmid respectively, and the protein expression of PTEN was detected by Western blot; pcDNA3.1 and PTEN over-expression(PTEN-OE) plasmid were transfected into HepG2.2.15 cells respectively. Chemiluminescence was used to analyze the expression of HBV-related antigens in the cell culture supernatant, and real-time quantitative PCR(qRT-PCR) was used to analyze the expression of HBV pregenomic RNA(HBV pgRNA); the synthetic RNA duplex [poly(I∶C)]was used to stimulate PTEN-OE cells, qRT-PCR was used to analyze IFN-α mRNA expression and Western blot was used to analyze the expression of interferon regulatory factor 9(IRF9) protein as well as myxovirus resistance protein 1(MxA) protein in the JAK/STAT signaling pathway. Results: In HepG2 cells expressing HBV transiently and HepG2.2.15 cells stably expressing HBV, the expression of PTEN protein both decreased; the expression of HBV-related antigens and HBV pgRNA decreased in PTEN-OE HepG2.2.15 cells compared with the control group. After the treatment by poly(I∶C), the level of IFN-α mRNA was significantly higher than that of the control group, and the expression of IRF9 and MxA ptotein related to the JAK/STAT signaling pathway both increased. Conclusion HBV may play a role in antagonizing the antiviral activity of IFN-α by down-regulating the expression of PTEN.

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*