Objective:To develop multiplex cytokine detection reagents to analyze expression levels of cytokines,angiogene-sis and bone remodeling proteins in relapse/refractory multiple myeloma(RRMM).Methods:Multiplex bead-based immunoassay by flow cytometry was used to develop quantitative detection reagents of multiplex cytokines,which were applied to detect serum samples from 55 RRMM patients and 22 healthy controls.Expression levels of cytokines,angiogenesis,and bone remodeling proteins in pa-tients,and their correlation with clinical characteristics were analyzed.Results:Detection reagents of 10-plex cytokine immunoassay were successfully developed in this study,with average sensitivity of 7.1 pg/ml,average recovery rate of 97.4%,average intra-assay CV of 4.8%,and average inter-assay CV of 9.0%.In addition,results of RRMM samples found that levels of IL-2,IL-17,DKK1,RANKL and OPG were positively correlated with the level of IgG monoclonal protein,and TIMP1 was positively correlated with levels of IgG and IgA monoclonal protein.Conclusion:In this study,ten kinds of cytokine detection reagents with high sensitivity and speci-ficity are developed,and we found that IL-2,IL-17,DKK1,RANKL,OPG and TIMP1 have potential value in tracking disease pro-gression in RRMM.The established development process of multiplex cytokine reagents has important reference significance for ex-panding the development and application of multiplex detection reagents for protein markers in the future.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

OBJECTIVE To establish the HPLC fingerprint and content determination of five components in Ranunculus sceleratus L.. METHODS The separation was developed on an Agilent ZORBAX SB C18 chromatographic (4.6 mm×250 mm, 5 μm)column by gradient elution with methanol(A)-0.1 % phosphoric acid aqueous solution(B) as mobile phase to establish HPLC fingerprint of Ranunculus sceleratus L.. Combined with similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis, the quality of 13 batches of Ranunculus sceleratus L. was evaluated. RESULTS Thirteen batches of Ranunculus sceleratus L. samples were calibrated with 20 common peaks, of which 5 common peaks were identified, and the similarity ranged from 0.874 to 0.984. The results of cluster analysis and principal component analysis were basically the same, indicating that there might be differences in the content of chemical components of Ranunculus sceleratus L. in different regions. Protocatechuic aldehyde, caffeic acid, ferulic acid, hyperoside and isoquercitrin were determined in thirteen batches of Ranunculus sceleratus L., and their contents were 0.016−0.035, 0.010−0.070, 0.010−0.029, 0.016−0.051, 0.028−0.086 mg·g–1, respectively. CONCLUSION The established HPLC fingerprint and content determination method is simple, stable, and reliable, which can be used for qualitative analysis and provide reference to quality evaluation and resource utilization of Ranunculus sceleratus L..

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.

Objective To explore the characteristics of social behaviors in toddlers with high-risk of autism spectrum disorder (HR-ASD),and the correlation to the severity of ASD symptoms.Method 32 high-risk ASD toddlers,aged from 12 months to 24 months,and 34 typical developmental (TD) infants/toddlers,aged from 6 months to 24 months,were recruited.Behavioral video of the Still-Face Paradigm (SFP) was used to measure the frequencies and duration of social behaviors,including non-social smiling,protest,eye contact,social smiling and social positive engagement,during the mother-infant interaction and the still face.Autism Diagnostic Observation Scale was used to evaluate severity of clinical symptoms in high-risk ASD toddler.Gesell Development Scale was used to assess the developmental level of the two groups.Independent-sample t test was used to compare the differences of social behaviors between two groups.Pearson correlation analysis was used to analyze the correlation between the social behaviors of high-risk ASD and the age,the developmental level and the severity of ASD symptoms.Binary logistic regression was used to analyze the power of discrimination of social behaviors between HR-ASD and TD.Results During mother-infant interaction,compared with TD group,HR-ASD had significantly shorter duration ((19.8±23.4) s vs.(61.5±34.0) s,t=-5.75,P＜0.01;(6.5±9.3) s vs.(29.0±25.2) s,t=-4.73,P＜0.01;(3.0±8.8) s vs.(13.2±23.1) s,t=-2.34,P=0.02) and lower frequencies (t=-6.62、-3.03、-2.74,all P＜0.01) of eye contact,social smiling and social positive engagement.During the still face,compared with TD group,HR-ASD had significantly shorter duration (t=-3.32,P＜0.01;t=-2.59,P=0.01) and lower frequencies (t=-6.13、-3.48,all P＜0.01) of eye contact and social positive engagement.According to Pearson correlation analysis,during the still face,in HR-ASD group,the duration of eye contact and social positive engagement had significantly negative influence on the score of the language and communication in ADOS (r=-0.49、-0.52,all P＜0.01);The duration and frequencies of eye contact and social positive engagement had significantly negative influence on the score of mutually social interaction in ADOS (r=-0.57,P＜0.01;r=-0.49,P＜0.01;r=-0.74,P＜0.01;r=-0.44,P=0.01);The duration of eye contact and social positive engagement had significantly negative influence on the score of the playing in ADOS (r=-0.43,P=0.01;r=-0.45,P=0.01).According to binary logistic regression,the duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction could distinguish between HR-ASD and TD (OR=1.36,95％CI:1.08-1.71,P=0.01;OR=5.99,95％CI:1.15-31.14,P=0.03).Conclusion HR-ASD hasthe lower levels of eye contact,social smiling and social positive engagement,which may suggestthe severity of ASD core symptoms.The duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction may possiblyfigure out theHR-ASD and could be further developed as a predictablebehavioral maker.

Objective To explore the characteristics of social behaviors in toddlers with high-risk of autism spectrum disorder (HR-ASD),and the correlation to the severity of ASD symptoms.Method 32 high-risk ASD toddlers,aged from 12 months to 24 months,and 34 typical developmental (TD) infants/toddlers,aged from 6 months to 24 months,were recruited.Behavioral video of the Still-Face Paradigm (SFP) was used to measure the frequencies and duration of social behaviors,including non-social smiling,protest,eye contact,social smiling and social positive engagement,during the mother-infant interaction and the still face.Autism Diagnostic Observation Scale was used to evaluate severity of clinical symptoms in high-risk ASD toddler.Gesell Development Scale was used to assess the developmental level of the two groups.Independent-sample t test was used to compare the differences of social behaviors between two groups.Pearson correlation analysis was used to analyze the correlation between the social behaviors of high-risk ASD and the age,the developmental level and the severity of ASD symptoms.Binary logistic regression was used to analyze the power of discrimination of social behaviors between HR-ASD and TD.Results During mother-infant interaction,compared with TD group,HR-ASD had significantly shorter duration ((19.8±23.4) s vs.(61.5±34.0) s,t=-5.75,P＜0.01;(6.5±9.3) s vs.(29.0±25.2) s,t=-4.73,P＜0.01;(3.0±8.8) s vs.(13.2±23.1) s,t=-2.34,P=0.02) and lower frequencies (t=-6.62、-3.03、-2.74,all P＜0.01) of eye contact,social smiling and social positive engagement.During the still face,compared with TD group,HR-ASD had significantly shorter duration (t=-3.32,P＜0.01;t=-2.59,P=0.01) and lower frequencies (t=-6.13、-3.48,all P＜0.01) of eye contact and social positive engagement.According to Pearson correlation analysis,during the still face,in HR-ASD group,the duration of eye contact and social positive engagement had significantly negative influence on the score of the language and communication in ADOS (r=-0.49、-0.52,all P＜0.01);The duration and frequencies of eye contact and social positive engagement had significantly negative influence on the score of mutually social interaction in ADOS (r=-0.57,P＜0.01;r=-0.49,P＜0.01;r=-0.74,P＜0.01;r=-0.44,P=0.01);The duration of eye contact and social positive engagement had significantly negative influence on the score of the playing in ADOS (r=-0.43,P=0.01;r=-0.45,P=0.01).According to binary logistic regression,the duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction could distinguish between HR-ASD and TD (OR=1.36,95％CI:1.08-1.71,P=0.01;OR=5.99,95％CI:1.15-31.14,P=0.03).Conclusion HR-ASD hasthe lower levels of eye contact,social smiling and social positive engagement,which may suggestthe severity of ASD core symptoms.The duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction may possiblyfigure out theHR-ASD and could be further developed as a predictablebehavioral maker.

OBJECTIVETo explore the role of eukaryotic translation elongation factor 1A1 (eEF1A1) in regulating the invasion and metastasis of hepatocellular carcinoma (HCC) cells and the possible mechanism.

METHODSqRT-PCR and Western blotting were used to detect the mRNA and protein expression of eEF1A1 and NOB1 in different HCC cell lines and normal liver cells. The invasion and migration abilities of HCC cells with eEF1A1 knockdown or overexpression were examined using Transwell chamber assay and RTCA assay, and the changes in NOB1 mRNA and protein expressions in the cells were detected. The effects of increasing NOB1 expression in HCCLM3-sheEF1A1 cells and decreasing NOB1 expression in eEF1A1-overexpressing MHCC97h cells on eEF1A1 expression and cell invasion and migration abilities were analyzed using Western blotting, Transwell chamber assay and RTCA assay.

RESULTSThe expressions of eEF1A1 and NOB1 were significantly increased in positive correlation in HCC cells as compared with normal hepatocytes. Knockdown of eEF1A1 significantly decreased the invasion and migration of HCC cells and reduced the mRNA and protein expression of NOB1 ( < 0.01). Overexpression of eEF1A1 significantly enhanced invasion and migration of HCC cells and increased NOB1 mRNA and protein expressions ( < 0.01). Increasing NOB1 expression in HCCLM3-sheEF1A1 cells led to the restoration of NOB1 expression and cell invasion and migration abilities ( < 0.01), whereas decreasing NOB1 in MHCC97h-eEF1A1 cells resulted in inhibition of NOB1 expression and cell invasion and migration ( < 0.01).

CONCLUSIONSeEF1A1 positively regulates the expression of NOB1 to promote the invasion and migration of HCC cells .

Objective: To investigate the methods and short-time clinical results of reconstruction of Paprosky type Ⅲ acetabulum bone defects by using tantalum augments. Methods: A total of 17 patients (17 hips) with Paprosky type Ⅲ acetabulum bone defects, treated with tantalum augments in revision of total hip arthroplasty at Department of Orthopedics Surgery in General Hospital of Chinese People′s Liberation Army were retrospectively analyzed from March 2014 to May 2016.There were 6 males and 11 females aged from 23 to 74 years with an average of (50.2±16.3) years. Tantalum augments or TM-Cup augment (the cup-on-cup technique) were used to reconstruct the defects.The TM-Cup augment was the tantalum revision cup which was removed titanium ring. The cup-on-cup technique combined TM-Cup augment and biological acetabulum cup. Augments were served as the nonresorptive structural allograft in revision of total hip arthroplasty. Harris hip score was used to evaluate clinical effects. The vertical position of the rotation center was measured and analyzed. Radiographic assessments of the acetabular components were performed by DeLee-Charnley and the Anderson criteria and recorded postoperative complications. Results: All the patients were followed up from 3 to 29 months with an average of (16.2±5.4) months, tantalum augments and biological acetabulum cup were used in 13 patients, the TM-Cup augment and biological acetabulum cup were used in 4 patients. At the time of the latest follow-up, the mean Harris hip score increased compared to preoperatively (86.8±8.3 vs. 30.0±12.0) (t=12.78, P<0.01), the average vertical location of the center of rotation was decreased ((25.3±9.8) mm vs.(47.6±10.5)) mm (t=4.95, P<0.01). All the tantalum augments and biological acetabulum cups were stable, there were no infection, dislocation and other complications. Conclusions The use of tantalum augments could be considered as an effective management of Paprosky type Ⅲ defects providing good clinical and radiographic outcomes in the short term.The cup-on-cup technique which was used in reconstruction of severe superior-invagination acetabular bone defects and restoration relatively normal center of rotation had special application value.

Objective To investigate the efficiency of 16S rRNA Real-time reverse transcription PCR technique in the diagnosis of periprosthetic joint infection,and compare its sensitivity and specificity with conventional culture.Methods There were 43 revision cases from July 2013 to December 2015.Synovial fluid collected by puncture preoperatively,tissues from five different parts around the prosthesis collected intra-operatively were cultured by blood plate and BacT/Alert FN respectively.The 16S rRNA in interface membrane was detected by real-time reverse transcription PCR as a marker to diagnose PJI.At the same time,the synovial fluid was routinely bacterial cultured.We compared the sensitivity and specificity of two methods.Results There are 22 THAs and 21 TKAs respectively in 43 cases,23 cases diagnosed prosthetic joint infection and 20 cases diagnosed non prosthetic joint infection.The sensitivity of 16S rRNA Real-time reverse transcription PCR is higher than the conventional bacterial culture (78.2％ vs.47.8％).There was no difference in the specificity and PPV and NPV.For PCR in prosthetic joint infection group,Staphylococcus epidermidis in 5 cases,Staphylococcus aureus in 3 cases,streptococcus in 4 cases,E.coli in 2 cases,Staphylococcus lugdunensis,Pseudomonas aeruginosa,Staphylococcus haemolyticus and Mycoplasma in 1 case respectively.For culture in prosthetic joint infection group,Staphylococcus epidermidis in 5 cases,Staphylococcus aureus in 2 cases,Staphylococcus lugdunensis,Pseudomonas aeruginosa,Staphylococcus haemolyticus and E.coli in 1 case respectively.For non prosthetic joint infection group,PCR and culture are all negative.Conclusion The sensitivity of 16S rRNA Real-time reverse transcription PCR is higher than the conventional bacterial culture.