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Purpose: The objective of the study is to explore the etiology, clinical manifestations, imaging features, diagnosis, treatment, and prognosis of cerebral air embolism complicated computed tomography (CT) scan-guided percutaneous liver biopsy.Materials and Methods: A case of air embolism was developed in the brain during a CT-guided percutaneous needle biopsy of the liver. In addition, retrospective analysis was performed on the previously reported typical cases of cerebral air embolism secondary to CT-guided percutaneous lung biopsy.Results: Cerebral air embolism has been recognized as a potentially fatal but extremely rare complication following CT-guided percutaneous liver or lung biopsy. It was usually caused by cough, positive pressure ventilation, incorrect puncture position, repeated punctures, cavity or cyst in the target sites, and vascular inflammatory lesions.Conclusions: Clinicians should focus on timely and correct diagnosis of this complication during their interventional procedures. The current main treatment for this complication has been hyperbaric oxygen therapy. [ABSTRACT FROM AUTHOR]

Purpose: Using MR imaging, nerve root sedimentation sign (SedSign) was demonstrated to have a high sensitivity and specificity for diagnosis of symptomatic lumbar spinal stenosis (LSS) in selected patients. This study was to evaluate the diagnostic value of SedSign in differential diagnosis of LSS and non-specific low back pain (LBP) in consecutive patients.Methods: A series of consecutive patients with lumbar spinal MRI examination for back/leg pain in orthopeadic clinic were included. These patients were followed up and divided into two groups, symptomatic LSS and non-specific LBP, according to symptoms and radiological findings. Using MR images, SedSign was assessed by two spine surgeons and one radiologist independently. Then sensitivity and specificity of SedSign was calculated.Result: A total of 320 patients (105 LSS and 215 non-specific LBP) were included. The SedSign had a sensitivity of 77.1 % and specificity of 47.0 % in the whole cohort. When these patients were stratified by dural sac cross-sectional areas (CSA), the SedSign had a sensitivity of 95.0 % and specificity of 4.7 % in patients with CSA ≤ 80 mm2 (severe radiologic stenosis), sensitivity of 74.2 % and specificity of 22.6 % in patients with CSA 80-100 mm2 (moderate radiologic stenosis), and sensitivity of 58.8 % and specificity of 61.0 % in patients with CSA 100-120 mm2 (mild radiologic stenosis). In selected cases composed by LSS patients with CSA ≤ 80 mm2 and non-specific LBP patients with CSA > 120 mm2, however, the SedSign had a sensitivity of 95.0 % and specificity of 80.0 %.Conclusion: The present data demonstrated that the SedSign was not able to discriminate symptomatic LSS from non-specific LBP after adjusting by dural sac CSA. The diagnostic value of the SedSign was still uncertain. [ABSTRACT FROM AUTHOR]

Microglia, the resident monocyte of the central nervous system, play a crucial role in the response to spinal cord injury. However, the precise mechanism remains unclear. To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury, we performed single-cell RNA sequencing dataset analysis, focusing on changes in microglial subpopulations. We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis, sphingomyelin metabolism, and neuroinflammation at high levels. Subsequently, we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury. Finally, we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells. Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis. Furthermore, ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway. Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function. Pla2g7 formed a "bridge" between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway. Collectively, these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3, thereby exerting neuroprotective effects. [ABSTRACT FROM AUTHOR]

Melatonin promotes bone formation and prevents bone degradation via receptor-dependent or receptor-independent actions. The aim of this study is to encapsulate melatonin into poly (lactic-co-glycolic acid) (PLGA) microspheres (PLGA-MEL-MS) and create a melatonin sustained release system, then to evaluate its effect on the osteogenesis of human mesenchymal stem cells (hMSCs) in vitro. PLGA-MEL-MS were prepared by single emulsion solvent evaporation technique. Scanning electron microscopy demonstrated the incorporation of melatonin did not disturb the conventional generation of PLGA microspheres in size and morphology. In vitro drug release assay showed that PLGA-MEL-MS exhibited a biphasic drug release pattern: a low initial burst release effect with approximately 40% drug release at the first 3 days and a relatively retarded and continuous release with about 85% drug release over the 25 days. Cell proliferation assay demonstrated that PLGA-MEL-MS had no apparent effect on proliferation of human MSCs. In an osteogenesis assay, PLGAMEL- MS obviously enhanced alkaline phosphatase (ALP) mRNA expression and increased ALP activity compared to that in the control group. Meanwhile, several markers of osteoblast differentiation were also significantly upregulated, including runx2, osteopontin, and osteocalcin. Furthermore, quantificational alizarin red-based assay demonstrated that PLGA-MEL-MS significantly enhanced calcium deposit of hMSCs compared to the controls. Therefore, this simple melatonin sustained release system can control released melatonin to generate a microenvironment with a relatively stable concentration of melatonin for a period of time to support osteogenic differentiation of hMSCs in vitro. This suggests that this system may be used as bone growth stimulator in bone healing in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Degenerative lumbar spinal stenosis is a common cause of low back or leg pain and disability in the elderly population. Patients with spinal stenosis who fail to respond to conservative treatment often require surgical interventions. Minimally invasive transforaminal lumbar interbody fusion (TLIF) with microscopic tubular technique (MT-TLIF) is a well-established procedure for lumbar spinal stenosis. Recently, a novel MIS technique, unilateral biportal endoscopic TLIF (UBE-TLIF), has been frequently performed to treat spinal stenosis. However, the efficacy and safety of using UBE-TLIF in this population have not been well examined., Methods and Analysis: A total of 96 patients with lumbar spinal stenosis will be randomly assigned to the UBE-TLIF group or the MT-TLIF group at a 1:1 ratio to receive UBE-TLIF or MT-TLIF treatment respectively. The primary outcome is the Oswestry Disability Index (ODI) score at 1 year after receiving the surgery. Secondary outcomes include the ODI scores at additional time points, Visual Analogue Scale score, 36-Item Short Form Survey questionnaire, EuroQol 5 Dimensions questionnaire, radiological measurements (disc height, lumbar lordosis angles and vertebral fusion rate) and general condition during hospitalisation., Ethics and Dissemination: This protocol is approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. All participants of the study will be well informed and written informed consent will be requested. Findings from this trial will be published in peer-reviewed publications, specifically in orthopedic and spinal journals. The completion of this study will not only examine the use of UBE-TLIF in lumbar spinal stenosis but also provide helpful clinical references., Trial Registration Number: ChiCTR2300069333., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Type 2 Diabetes Mellitus (T2D) and Osteoarthritis (OA) are both prevalent diseases that significantly impact the health of patients. Increasing evidence suggests that there is a big correlation between T2D and OA, but the molecular mechanisms remain elusive. The aims of this study are to investigate the shared biomarkers and potential molecular mechanisms in T2D combined with OA., Methods: T2D and OA-related differentially expressed genes (DEGs) were identified via bioinformatic analysis on Gene Expression Omnibus (GEO) datasets GSE26168 and GSE114007 respectively. Subsequently, extensive target prediction and network analysis were finished with Gene Ontology (GO), protein-protein interaction (PPI), and pathway enrichment with DEGs. The transcription factors (TFs) and miRNAs coupled in co-expressed DEGs involved in T2D and OA were predicted as well. The key genes expressed both in the clinical tissues of T2D and OA were detected with western blot and qRT-PCR assay. Finally, the most promising candidate compounds were predicted with the Drug-Gene Interaction Database (DGIdb) and molecular docking., Results: In this study, 209 shared DEGs between T2D and OA were identified. Functional analysis disclosed that these DEGs are predominantly related to ossification, regulation of leukocyte migration, extracellular matrix (ECM) structural constituents, PI3K/AKT, and Wnt signaling pathways. Further analysis via Protein-Protein Interaction (PPI) analysis and validation with external datasets emphasized MMP9 and ANGPTL4 as crucial genes in both T2D and OA. Our findings were validated through qRT-PCR and Western blot analyses, which indicated high expression levels of these pivotal genes in T2D, OA, and T2D combined with OA cases. Additionally, the analysis of Transcription Factors (TFs)-miRNA interactions identified 7 TFs and one miRNA that jointly regulate these important genes. The Receiver Operating characteristic (ROC) analysis demonstrated the significant diagnostic potential of MMP9 and ANGPTL4.Moreover, we identified raloxifene, ezetimibe, and S-3304 as promising agents for patients with both T2D and OA., Conclusion: This study uncovers the shared signaling pathways, biomarkers, potential therapeutics, and diagnostic models for individuals suffering from both T2D and OA. These findings not only present novel perspectives on the complex interplay between T2D and OA but also hold significant promise for improving the clinical management and prognosis of patients with this concurrent condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mao, Xu, Wan, Wang, Xu, Zhang, Li, Zhang, Lai, Lan and Liu.)

Objective: To explore the predictive value of the nerve root sedimentation sign in the diagnosis of lumbar spinal stenosis (LSS)., Methods: Between January 2019 and July 2021, 201 patients with non-specific low back pain (NS-LBP) who met the selection criteria were retrospectively analyzed. There were 67 males and 134 females, with an age of 50-80 years (mean, 60.7 years). Four intervertebral spaces (L 1, 2 , L 2, 3 , L 3, 4 , L 4, 5 ) of each case were studied, with a total of 804. The nerve root sedimentation sign was positive in 126 intervertebral spaces, and central canal stenosis was found in 203 intervertebral spaces. Progression to symptomatic LSS was determined by follow-up for lower extremity symptoms similar to LSS, combined with central spinal stenosis. Univariate analysis was performed for gender, age, visual analogue scale (VAS) score for low back pain at initial diagnosis, treatment, dural sac cross-sectional area at each intervertebral space, number of spinal stenosis segments, lumbar spinal stenosis grade, positive nerve root sedimentation sign, and number of positive segments between patients in the progression group and non-progression group, and logistic regression analysis was further performed to screen the risk factors for progression to symptomatic LSS in patients with NS-LBP., Results: All patients were followed up 17-48 months, with an average of 32 months. Of 201 patients with NS-LBP, 35 progressed to symptomatic LSS. Among them, 33 cases also had central spinal stenosis, which was defined as NS-LBP progressing to symptomatic LSS (33 cases in progression group, 168 cases in non-progression group). Univariate analysis showed that CSA at each intervertebral space, the number of spinal stenosis segments, lumbar spinal stenosis grade, whether the nerve root sedimentation sign was positive, and the number of nerve root sedimentation sign positive segments were the influencing factors for the progression to symptomatic LSS ( P <0.05); and further logistic regression analysis showed that positive nerve root sedimentation sign increased the risk of progression of NS-LBP to symptomatic LSS ( OR =8.774, P< 0.001)., Conclusion: The nerve root sedimentation sign may be associated with the progression of NS-LBP to symptomatic LSS, and it has certain predictive value for the diagnosis of LSS.

Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy., Objective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100)., Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021., Interventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years., Main Outcomes and Measures: The primary end point was overall survival time from randomization., Results: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%)., Conclusions and Relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo., Trial Registration: ClinicalTrials.gov Identifier: NCT03745170.

Unilateral biportal endoscopic (UBE) spine surgery is an emerging minimally invasive surgical (MIS) technique that has gained popularity for treating lumbar spinal stenosis, particularly in Eastern Asia. The traditional UBE technique, with two portals on one side, can achieve successful unilateral laminotomy for bilateral decompression (ULBD) and, therefore, demonstrates favorable clinical outcomes. However, in the case of lumbar spinal stenosis combined with contralateral disc herniation, it is very difficult to remove the contralateral disc herniation, especially the loose disc fragment within the deep disc. Here, a third channel of the traditional UBE technique was developed to do the discectomy within the ipsilateral endoscopic vision, with which the instruments can go vertically into the contralateral disc, allowing easy discectomy. This technique can not only achieve adequate decompression of the bilateral spinal canal but also effectively remove contralateral herniated disc fragments. This technique avoids performing another UBE procedure on the opposite side, which can potentially shorten the duration of the operation, minimize blood loss and tissue damage, and ensure sufficient neural decompression. This paper will introduce the indications and surgical operation procedures, as well as present a classical case report and follow-up data, to facilitate the application of the third channel-assisted UBE (T-UBE) technique for spine surgeons.

Aim: This study was designed to evaluate the clinical characteristics and prognosis of elderly small cell lung cancer (SCLC) patients complicated with hyponatremia, thus providing increased attention for appropriate intervention and improving outcomes in symptomatic subjects., Patients and Methods: The clinical data of 320 patients with SCLC in the Yuhuangding Hospital from March 1st, 2006, to March 1st, 2012, were studied retrospectively. The prognosis and possible association with hyponatremia was investigated., Results: The incidence rate of hyponatremia in SCLC was 46.56% (149/320). The mean survival time was 1.10±0.42 years in patients with normal values and 0.83±0.35 years in patients with subnormal serum sodium. In the hyponatremia group, the mean survival time of corrected hyponatremia patients was 0.91±0.42 years, which was significantly longer than uncorrected hyponatremia patients whose mean survival time was 0.68±0.26 years (t=2.75, p<0.05) after symptomatic treatment. The mean survival time of the normal group and the hyponatremia group in elderly patients had a tendency to decrease when compared to another group of patients younger than 60 years old. Hyponatremia at 1- and 3-year follow-up was associated with worse survival rates (p<0.05)., Conclusion: The severity of hyponatremia has unfavorable prognostic impacts. Elderly SCLC patients with hyponatremia are difficult to cure and associated with significantly shorter survival, especially in the uncorrected group. It is important that the cause of the hyponatremia is diagnosed at an early stage and precise medical treatment is provided., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To analyze the relative position between lumbar plexus and access corridor of minimally invasive lateral transpsoas approach based on magnetic resonance imaging distribution of lumbar plexus by three dimensional reconstruction technique, so as to evaluate approach safety., Methods: Three-dimensional fast imaging employing steady-state acquisition sequences of lumbar spine were performed on 71 patients with lumbar degenerative diseases between July 2012 and January 2015. The axial image distance between the anterior edge of lumbar plexus and sagittal central perpendicular line (SCPL) of disc was determined using the distance formula at the mid-disc space from L 1, 2 to L 4, 5 level. SCPL was drawn perpendicularly to the sagittal plane of intervertebral disc and it passed through its central point, which is initial dilator trajectory for transpsoas approach. With respect to the SCPL of disc, the distance with a positive value indicated neural tissue posterior to it whereas anterior to it represented by a negative value., Results: Various branches of lumbar plexus which passed through the psoas major anterior to the SCPL of disc were identified in 42 (59.2%), 58 (81.7%), and 70 (98.6%) patients at L 2, 3 , L 3, 4 , and L 4, 5 levels, respectively. It is possible to infer the presence of genitofemoral nerve in accordance with relevant anatomic research. A ventral migration of intrapsoas nerves is identified from L 1, 2 to L 4, 5 level. All differences between levels were statistically significant ( P <0.05)., Conclusions: With respect to the SCPL of disc, a pass way of guide wire or a radiographic reference landmark to place working channel, lumbar plexus lie posterior to it from L 1, 2 to L 3, 4 level and shift anteriorly to it at L 4, 5 level, while genitofemoral nerve locate anterior to the SCPL from L 2, 3 to L 4, 5 level. Neural retraction may take place during sequential dilation of working channel especially at L 4, 5 level.

Objective: To record the efficacy and toxicity of combining bevacizumab with cisplatin in treating malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion., Patients and Methods: Forty-three patients were admitted to the Oncology Department of Yantai Yuhuangding Hospital with confirmed malignant effusion since January, 2011. Twenty of them received intrapleural and intraperitoneal perfusion of 200 mg bevacizumab plus 60 mg cisplatin every three weeks, and 23 patients received 60 mg cisplatin alone after draining effusion as much as possible. Reduction of effusion was determined by type-B ultrasonography., Results: The complete remission rate and effective rate of bevacizumab group was superior to that of the cisplatin group. The quality of life recovery rate of bevacizumab group was superior to that of the cisplatin group. The anhelation and abdominal distention of bevacizumab group was significantly improved. There was no significant difference in level III/IV toxicities and adverse effects between two groups., Conclusion: Bevacizumab significantly improved the objective response rate and quality of life of patients with malignant pleural effusion and ascites, while not causing notable adverse events., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To evaluate the effectiveness of modified "eggshell" osteotomy for the treatment of thoracolumbar kyphoscoliosis. METHODS Between April 2009 and June 2014, 19 patients with spinal deformity underwent modified "eggshell" osteotomy consisting of preserving posterior bony structures initially and enlarging surgical field for cancellous bone removal. There were 14 males and 5 females with an average age of 37.8 years (range, 18-76 years) and with a median disease duration of 7 years (range, 1-40 years). The disease causes included ankylosing spondylitis in 13 cases, spinal tuberculosis in 3 cases, and chronic vertebral compression fracture in 3 cases. Eleven patients showed single kyphosis and 8 patients had kyphoscoliosis. Preoperative Cobb angle of kyphosis was (64.2 ±30.1)degrees, while Cobb angle of scoliosis was (19.9 ± 12.8)degrees. Apical vertebraes were T10 in 1 case, L1 in 3 cases, L2 in 7 cases, T10, 11 in 2 cases, T12, L1 in 4 cases, T12-L2 in 1 case, and T10-L1 in 1 case. Preoperative visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score were 6.1 ± 1.9 and 15.2 ± 5.6, respectively. According to Frankel criteria for spinal cord function, 16 cases were rated as grade E and 3 cases as grade D before operation. Cobb angle, VAS, and JOA scors were used to assess relief of symptom., Results: The operation time was 215-610 minutes (mean, 343 minutes); intraoperative blood loss ranged from 900 to 3 000 mL (mean, 1 573 mL). All incisions healed primarily. Delayed onset ischemia-reperfusion injury of spinal cord occurred in 1 case at 6 days after operation, and symptoms alleviated after conservative treatments. All 19 cases were followed up 14-76 months (mean, 46 months). No loosening or breakage of internal fixation was observed during follow-up. Cobb angle of kyphosis, Cobb angle of scoliosis, VAS and JOA scores at 1 week after operation and last follow-up were significantly improved when compared with preoperative ones (P < 0.05). VAS and JOA scores at last follow-up were significantly improved when compared with scores at 1 week after operation (P < 0.05), but no significant difference was found in Cobb angle of both kyphosis and scoliosis between at 1 week after operation and at last follow-up (P > 0.05). At 1 week after operation, the correction rate for kyphosis was 34.1%-93.4% (mean, 62.2%), and the correction rate for scoliosis was 42.4%-100% (mean, 68.9%). At 48 months after operation, 3 patients with preoperative impaired spinal cord function achieved full recovery., Conclusion: Modified "eggshell" osteotomy owns the advantages of shorter operation time and less intraoperative blood loss, thus it is able to correct thoracolumbar kyphoscoliosis safely and effectively.

Objective: To conduct a meta-analysis of all association studies on two of the collagen 1 alpha 1 (COL1A1) gene polymorphisms, the -1997G/T (rs1107946) and the -1663indelT (rs2412298) polymorphisms and osteoporosis/BMD and fracture., Methods: PubMed/Medline and Web of Knowledge were searched for relevant association studies published in English. Pooled OR and its corresponding 95% CI or pooled MD and its corresponding 95% CI was calculated with the Cochrane Review Manager (Revman, version 5.2) using a random-effect or a fixed effect model., Results: No significant association between the -1997G/T polymorphism and Lumbar Spine (LS) and Femoral Neck (FN) BMD except for the Caucasian subpopulation wherein subjects with the T allele of the -1997G/T polymorphism was associated with significantly higher LS BMD. Our analysis did reveal that women, especially postmenopausal or perimenopausal women with the GG genotype, had significantly higher Total Hip (TH) BMD than those with the GT. Additionally, our meta-analysis did not show significant association between the -1997G/T polymorphism and risk of fracture, between the -1663indelT polymorphism and LS BMD in postmenopausal or perimenopausal women, or between the -1663indelT polymorphism and the risk of fracture., Conclusions: Our results suggested the possibility of the COL1A1 -1997G/T and the -1663indelT polymorphisms individually playing very little role in osteoporosis and fracture, although more studies are needed especially for the analysis of association between these two polymorphisms and fracture. Haplotype studies may become one important future direction of study to further elucidate whether and how various COL1A1 polymorphisms affect bone health, osteoporosis and fracture.

Background: Mutations in the epidermal growth factor receptor gene (EGFR) are found in around half of Asian patients with non-small cell lung cancer (NSCLC). For this reason, EGFR tyrosine kinase inhibitors (TKI) are often prescribed depending on the EGFR status. Two common EGFR mutations, a deletion in exon 19 and L858R in exon 21, demonstrate a positive response to gefitinib, the first approved EGFR TKI. However, T790M and an insertion in EGFR exon 21 are resistant to EGFR TKI treatment. The relationships between the EGFR mutation type and response to the target drug have not been fully investigated., Case Presentation: We describe a 66-year-old Chinese male diagnosed with stage IV lung adenocarcinoma based on evidence from a computed tomography (CT) scan and histological features of a biopsy taken during fiberoptic bronchoscopy surgery. Molecular analysis of EGFR exons 19 and 21 revealed the presence of only one mutation in exon 19: L747P (2239-2240 TT>CC). The patient requested gefitinib treatment for 2 weeks but his response was poor. A CT scan revealed that the number and relative volume of the liver metastases had increased after treatment., Conclusion: L747P (2239-2240 TT>CC) in exon 19 is a rare EGFR mutation that appears to lead to gefitinib resistance and might accelerate liver metastases.

The aim of this study was to provide an effective procedure for immunohistochemistry (IHC) investigations of bone specimens. Samples from rat femoral and human vertebral bone were processed with a detailed and effective IHC protocol summarized here. First, a novel antigen retrieval (AR) method of hyaluronidase combined pepsin predigestion (H+P) was established and the optimal concentration and pH value for AR of bone specimens were determined. Second, the newly developed method was compared with existing AR methods (boiling in sodium citrate, hyaluronidase predigestion (H) and pepsin predigestion (P), with PBS only as the negative control) using two chromogenic detection systems (horseradish peroxidase (HRP) and alkaline phosphatase (AP)) to evaluate their efficacy in obtaining the best IHC results for bone samples. Considering the drawbacks of significant shrinking and detachment from slide for heat retrieval methods and the only moderate immunolabeling for H and P, H+P was the optimal AR method for IHC of bone specimens with the advantages of both good morphological preservation and strong immunoreactivity. Moreover, AP-mediated chromogenic detection was superior to HRP-labeled chromogenic detection due to significantly less non-specific staining. In conclusion, we presented an effective and practical IHC protocol for bone specimens characterized by H+P predigestion combined with AP-mediated chromogenic detection. Finally, a detailed troubleshooting guide was provided for common mistakes that occur during IHC processing of the bone tissue samples.

Prostate cancer, the most commonly diagnosed male cancer in North America, has a high incidence of bone metastasis. Our previous study showed collapsin response mediator protein 4 (CRMP4) gene inhibited prostate cancer migration and invasion. In this study, we investigated whether overexpression of CRMP4 gene in prostate cancer cells inhibit tumor bone metastasis. The stable prostate cancer cells overexpressing the CRMP4 gene were constructed using lentivirus infection. Prostate cancer bone metastasis nude mouse model was built though orthotopic prostate implantation, intracardiac injection and intratibial injection with CRMP4 overexpress and control cancer cells. Small animal PET/CT scanning results showed no difference of bone metastatic capacity in orthotopic and intracardiac injection models between CRMP4 overexpression and control group, while CRMP4 overexpression inhibited tumor growth in the intratibial injection model. Moreover, our in vitro study showed CRMP4 overexpression downregulates the Neuropilin1 (NRP1) expression and upregulate the Noggin expression. Immunohistochemical staining of the hind limbs of intratibial injection model was confirmed with cytological experiments. Taken together, our research indicated CRMP4 inhibits prostate cancer cells growth in the nude mouse bone microenvironment and this effect may relate with regulation of NRP1 and Noggin expression.