Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.

Restless head syndrome:A retrospective study

BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.

CAD System for Cylinder Head Used in High-Speed and Heavy-Power Diesel Engine

A CAD system for the cylinder head is developed. As an integrated system, it can be used in 3 D modeling, 2 D drawing and finite element structural analysis and optimization. The key problems in system designing are introduced. Design flow, system structure and how to solve the key problems are focused on. All of those would form the base for more research on how to use the modern CAD technology to design complex engine parts. And it is also a good example of using the modern CAD technology.

Application of Predictive Algorithm in Head-Tracking System

The worldwide research status of head tracking is introduced and the works made in the research of the predictive algorithm and in the exploration of the rule of the head tracking are set forth. A time delay model for the telerobotic scout system is built. In respect of eliminating error caused by time delay and making reasonable prediction to the data stream, many methods are experimented in order to realize the aim of real time tracking. The application of extrapolation algorithm and auto recursive algorithm in the orientation tracking is described in detail. These two algorithms are realized in Matlab environment. Through analysis of the curves generated by using these two predictive algorithms, an appropriate method was applied in the telerobotic scout system. The effect is satisfying.

Flow patterns and boundary conditions for inlet and outlet conduits of large pump system with low head

The flow patterns in the inlet and outlet conduits have a decisive effect on the safe, stable, and highly efficient operation of the pump in a large pumping station with low head. The numerical simulation of three-dimensional （3D） turbulence flow in conduits is an important method to study the hydraulic performance and conduct an optimum hydraulic design for the conduits. With the analyses of the flow patterns in the inlet and outlet conduits, the boundary conditions of the numerical simulation for them can be determined. The main obtained conclusions are as follows： （i） Under normal operation conditions, there is essentially no pre-swirl flow at the impeller chamber inlet of an axial-flow pump system, based on which the boundary condition at the inlet conduit may be defined. （ii） The circulation at the guide vane outlet of an axial-flow pump system has a great effect on the hydraulic performance of the outlet conduit, and there is optimum circulation for the performance. Therefore, it is strongly suggested to design the guide vane according to the optimum circulation. （iii） The residual circulation at the guide vane outlet needs to be considered for the inlet boundary condition of the outlet conduit, and the value of the circulation may be measured in a specially designed test model.

Plant Ideotype at Heading for Super High-Yielding Rice in Double-Cropping System in South China

The newly released super high-yielding hybrid rice combinations, Yueza 122, Fengyou 428, Peiza 67, and the super high-yielding conventional cultivars, Guangchao 3 and Shengtai 1, were grown in both early and late seasons. The morphological characters of each population were investigated at the heading stage, and the data were analyzed by using ANOVY and other statistic methods. The plant ideal morphological characters at the heading stage were established as follows： 1 ） for the early-season cropping, 90-105 cm plant height; 11-12 tillers per plant; 35-40 em length and 2.1-2.2 cm width of flag leaf; 46-50 cm length and 1.8-2.1 cm width of the second leaf from the top （L2）; 59-64 cm length and 1.4-1.9 cm width of the third leaf from the top （L3）; 7°-14°, 18° and 200-33° for the ideal leaf angles of the flag leaf, L2 and L3, respectively; 2） for the late-season cropping, 90-100 cm plant height; 9-15 tillers per plant; 30-41 cm length and 1.8-2.0 cm width of flag leaf; 53-61 cm length and 1.3-1.8 cm width of L2; 52-58 cm length and 1.2-1.5 cm width of L3; 9°-19°, 15°-37° and 16°-49° for the ideal leaf angles of the flag leaf, L2 and L3, respectively. The main physiological characteristics of these varieties were also analyzed.

Cross influence of discharge and circulation on head loss of conduit of pump system with low head

The relationship between the head loss and the discharge and circulation of the conduit of a pump system with low head is an important problem with an obvious influence on the improvement of its hydraulic performance. The velocity circulation from the pump guide vane makes the relationship more complicated, which has to be understood comprehensively. The results indicate that, under the condition of zero circulation, the head loss of the inlet and outlet conduits is in proportion to the square of discharge. Under the condition that the Reynolds number is satisfied with the resistant square area, the conduit loss is in proportion to the square of discharge for the similar working points with different speeds in a certain rotational speed range, indicating that the pump system efficiency is constant. The outlet conduit loss of design discharge for a pump system with low head depends on the velocity circulation from the guide vane exit, and the relationship between the loss and the circulation is an open curve with an upward direction, meaning that there is an optimal circulation for the loss. Under the condition of various working points for a pump system with low head, the head loss of the outlet conduit is under the cross influence of both the discharge and the circulation. As a result, the relationship between the head loss and the discharge is almost linear, and the mechanism needs to be further studied.

Safety and efficacy of surgical hip dislocation in managing femoral head fractures: A systematic review and meta-analysis

BACKGROUND Femoral head fractures(FHFs)are considered relatively uncommon injuries;however,open reduction and internal fixation is preferred for most displaced fractures.Several surgical approaches had been utilized with controversial results;surgical hip dislocation(SHD)is among these approaches,with the reputation of being demanding and leading to higher complication rates.AIM To determine the efficacy and safety of SHD in managing FHFs by reviewing the results reported in the literature.METHODS Major databases including PubMed,Embase,Web of Science,and Cochrane Central Register of Controlled Trials were searched to identify studies reporting on outcomes of SHD utilized as an approach in treating FHFs.We extracted basic studies data,surgery-related data,functional outcomes,radiological outcomes,and postoperative complications.We calculated the mean differences for continuous data with 95%confidence intervals for each outcome and the odds ratio with 95%confidence intervals for binary outcomes.P<0.05 was considered significant.RESULTS Our search retrieved nine studies meeting our inclusion criteria,with a total of 129 FHFs.The results of our analysis revealed that the average operation time was 123.74 min,while the average blood loss was 491.89 mL.After an average followup of 38.4 mo,a satisfactory clinical outcome was achieved in 85%of patients,ranged from 30%to 86%,with avascular necrosis,heterotopic ossification,and osteoarthritis being the most common complications occurring at an incidence of 12%,25%,and 16%,respectively.Trochanteric flip osteotomy nonunion and trochanteric bursitis as a unique complication of SHD occurred at an incidence of 3.4%and 3.8%,respectively.CONCLUSION The integration of SHD approach for dealing with FHFs offered acceptable functional and radiological outcomes with a wide range of safety in regards to the hip joint vascularity and the development of avascular necrosis,the formation of heterotopic ossification,and the development of posttraumatic osteoarthritis;however,it still carries its unique risk of trochanteric flip osteotomy nonunion and persistent lateral thigh pain.

Adaptive filter for a miniature MEMS based attitude and heading reference system

An extended Kalman filter with adaptive gain was used to build a miniature attitude and heading reference system based on a stochastie model. The adaptive filter has six states with a time variable transition matrix. When the system is in the non-acceleration mode, the accelerometer measurements of the gravity and the compass measurements of the heading have observability and yield good eslimates of the states. When the system is in the high dynamic mode and the bias has converged to an aceurate estimate, the attitude caleulation will be maintained for a long interval of time. The adaptive filter tunes its gain automatically based on the system dynamics sensed by the accelerometers to yield optimal performance,

Preoperative defining system for pancreatic head cancer considering surgical resection

AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing &#x0201c;resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly&#x0201d;. The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size &#x02265; 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 &#x02265; 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.

Development of a Three-Dimensional Measuring System for Neonates' Head and Facial Morphology

A web camera based multi-camera convergent close-range photogrammetric system is developed to obtain the neonates＇ head and facial morphology. The data will then be used to develop a secure and good-fitting eye-patch protector for neonates, particularly whoa they are exposed to bright lights such as phototherapy light. Measurements obtained by the system are evaluated and validated against data obtained from optical scanning. Results show that the photogrammetric system meets the requirements of measuring accuracy and safety for neonate in the neonatal units.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears:A systematic review and meta-analysis

BACKGROUND Superior capsular reconstruction(SCR)with long head of biceps tendon(LHBT)transposition was developed to massive and irreparable rotator cuff tears(MIRCTs);however,the outcomes of this technique remain unclear.AIM To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs.METHODS We performed a systematic electronic database search on PubMed,EMBASE,and Cochrane Library.Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria.Biomechanical studies were assessed for main results and conclusions.Included clinical studies were evaluated for quality of methodology.Data including study characteristics,cohort demographics,and outcomes were extracted.A meta-analysis was conducted of the clinical outcomes.RESULTS According to our inclusion and exclusion criteria,a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion(ROM)after LHBT transposition for MIRCTs.A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes,consisting of 253 patients.The results indicated that compared to other surgical methods for MIRCTs,LHBT transposition had advantages of more significant improvement in ROM(forward flexion mean difference[MD]=6.54,95%confidence interval[CI]:3.07-10.01;external rotation[MD=5.15,95%CI:1.59-8.17];the acromiohumeral distance[AHD][MD=0.90,95%CI:0.21-1.59])and reducing retear rate(odds ratio=0.27,95%CI:0.15-0.48).No significant difference in American Shoulder and Elbow Surgeons score,visual analogue scale score,and University of California at Los Angles score was demonstrated between these two groups for MIRCTs.CONCLUSION In general,SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs,both in terms of biomechanical and clinical outcomes,with comparable clinical outcomes,improved ROM,AHD,and reduced the retear rates compared to conventional SCR and other established techniques.More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

融合MacBERT和Talking⁃Heads Attention实体关系联合抽取模型

针对现有的医学文本关系抽取任务模型在训练过程中存在语义理解能力不足,可能导致关系抽取的效果不尽人意的问题,文中提出一种融合MacBERT和Talking⁃Heads Attention的实体关系联合抽取模型。该模型首先利用MacBERT语言模型来获取动态字向量表达,MacBERT作为改进的BERT模型,能够减少预训练和微调阶段之间的差异,从而提高模型的泛化能力;然后,将这些动态字向量表达输入到双向门控循环单元(BiGRU)中,以便提取文本的上下文特征。BiGRU是一种改进的循环神经网络(RNN),具有更好的长期依赖捕获能力。在获取文本上下文特征之后,使用Talking⁃Heads Attention来获取全局特征。Talking⁃Heads Attention是一种自注意力机制,可以捕获文本中不同位置之间的关系,从而提高关系抽取的准确性。实验结果表明,与实体关系联合抽取模型GRTE相比,该模型F1值提升1%,precision值提升0.4%,recall值提升1.5%。

Immune checkpoint inhibitors in head and neck squamous cell carcinoma:A systematic review of phase-3 clinical trials

BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.

Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model,cellular platform,and clinical human data

Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics.It originates from the squamous epithelium of the oral cavity,oropharynx,nasopharynx,larynx,and hypopharynx.The most frequently impacted regions are the tongue and larynx.Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC.Despite the advances in our knowledge,the improved survival rate of HNSCC patients over the last 40 years has been limited.Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods.These results indicate a need to identify more genetic factors underlying this complex disease,which can be better used in early detection and prevention strategies.The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors.In this report,we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes(e.g.Smad 4 and P53 genes)to identify genetic factors affecting the development of this complex disease using genome-wide association studies,epigenetics,micro RNA,long noncoding RNA,lnc RNA,histone modifications,methylation,phosphorylation,and proteomics.

Initial alignment for low-cost attitude and heading reference systems

MEMS （micro electro mechanical systems） inertial navigation system ~, Mll＇~3） nas Been WllUly used in robots for its low-cost. The MINS and magnetometers are commonly the component parts of the attitude and heading reference systems （AHRS）, which provide pitch and roll angles relative to the earth gravity vector, and heading angle relative to the north. However, the performance of sen- sors with low cost AHRS is not so good. The gyros are not sensitive enough to observe the earth an- gular velocity, so the traditional technique like alignment algorithm is invalid. The measurements of gyros become useless to determine the initial attitude matrix from navigation frame to body frame. The alignment algorithm is computed by the accelerometers and magnetometers. The process is es- tablished as an optimization problem of finding the maximum eigenvector. Meanwhile the sensitive analysis with respect to the biases of accelerometers is proposed. Then the recursive least squares al- gorithm （RLSA） is introduced. The comparison between the proposed method and RLSA is provid- ed. The results demonstrate its accuracy favorably and verify the feasibility of the proposed algo- rithm.

An Experimental System Development for Head Posture Estimation Based on 3-D Images Measurement

Although automobile is an indispensable vehicle to modern life, it also serves as a social problem with a big traffic accident. Among the reasons of traffic accidents, careless driving accounts for the largest part. So in order to avoid the careless driving, a system which can measure the posture of a driver and warns driver to drive carefully in the case of looking aside is necessary. Although the image measurement method is used broadly, there is a problem on which measurement accuracy is influenced by environment light, makeup of the driver, etc. in the general method based on the two-dimensional image. Therefore, in this study, we propose an image measurement method to obtain the head posture of driver. First we use three-dimensional measurement method which based on the infrared pattern projection to get 3-D information of head, and then we calculate the angle for faces. In this paper, we explain the composition method of an experiment system, and the results of head posture measurement experiment.

Fuzzy Sliding Mode Observer for Vehicular Attitude Heading Reference System

In low-cost Attitude Heading Reference Systems (AHRS), the measurements made by Micro Electro-Mechanical Systems (MEMS) type sensors are affected by uncertainties, noises and unknown disturbances. In this paper, considering the robustness of sliding mode observers against structured and unstructured uncertainties, and also exogenous inputs, the process of design and implementation of a sliding mode observer (SMO) is proposed based on a linearized model of the AHRS. To decrease the chattering phenomenon is the main difficulty of the SMO. Through smoothing the discontinuity term, the tracking performance of the observer is attenuated. Boundary layer technique, for example, using a saturation term, is the common smoother to remove the chattering drawbacks. However, through poor tracking performance, the high range chattering could not be removed by this method. Therefore, a knowledge-based Mamdani-type fuzzy SMO (FSMO) is proposed to decrease the chattering effects intelligently, which in turn could obtain the high accuracy tracking performance of the SMO. Following proving the stability of the proposed SMOs based on direct Lyapunov’s method, the performance of the proposed observers is compared with that of the extended Kalman filter through simulation and real experiments of an AHRS.

Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing:A pilot study

BACKGROUND Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head(ONFH)in systemic lupus erythematosus(SLE).Some gene loci such as complement C3d receptor 2(CR2),nitric oxide synthase 3(NOS3),collagen type II alpha 1 chain(COL2A1),protein tyrosine phosphatase non-receptor type 22(PTPN22),and transient receptor potential cation channel subfamily V member 4(TRPV4)were reported to be involved in this process.AIM To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations(SNVs)in these five genes.METHODS SNVs in the CR2,NOS3,COL2A1,PTPN22,and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH.Burrows–wheeler aligner was used to align the sequencing reads to hg19,and GATK and Varscan programs were used to perform SNV calling.PolyPhen-2,SIFT,and MutationTaster were used to assess the functional effects of non-synonymous SNVs.RESULTS Six of the 49 patients were confirmed to have low frequency SNVs,including one patient with SNVs in NOS3(exon 6:c.814G>A:p.E272K and exon 7:c.814G>A:p.E272K.),four in COL2A1(rs41263847:exon 29:c.1913C>T:p.T638I,exon 28:c.1706C>T:p.T569I,and rs371445823:exon 8:c.580G>A:p.A194T,exon 7:c.373G>A:p.A125T),and one in CR2(rs45573035:exon 2:c.200C>G:p.T67S).CONCLUSION The onset of ONFH in SLE might be associated with the identified SNVs in NOS3,COL2A1,and CR2.