TNFSF14 mediates the impact of docosahexaenoic acid on atopic dermatitis: a Mendelian randomization study.

OBJECTIVE: While current research suggests potential value for docosahexaenoic acid (DHA) in the prevention and management of atopic dermatitis (AD), the causal relationship between DHA and AD remains unclear, and the underlying mechanisms are not well understood. MATERIALS AND METHODS: To investigate the potential causal relationship between DHA and AD, as well as to explore potential mediating mechanisms, we employed the Mendelian randomization (MR) methods. To study these potential relationships, we conducted MR analysis using publicly available Genome-Wide Association Studies (GWAS) data. Effect estimates were computed using the random-effects inverse-variance weighted method. RESULTS: Our study demonstrates a negative correlation between DHA levels and AD risk (OR: 0.915, 95% CI: 0.858-0.975, p=0.007). Furthermore, in MR analysis using tumor necrosis factor ligand superfamily member 14 (TNFSF14) levels as an outcome, DHA levels also show a negative association with TNFSF14 levels (OR: 0.933, 95% CI: 0.879-0.990, p=0.022). Subsequently, we performed further analysis to explore the relationship between TNFSF14 and AD risk, revealing a positive correlation (OR: 1.069, 95% CI: 1.005-1.137, p=0.033). This suggests a potential mediating role of TNFSF14 in the impact of DHA on AD risk. CONCLUSIONS: In summary, our study employs MR analysis to offer genetic evidence indicating a potential role of DHA in reducing the risk of AD, as well as opening avenues for further in-depth investigation into potential mechanisms. These findings emphasize the importance of ongoing research in this field.

[The companion diagnostics of targeted therapy and immunotherapy for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) has a high incidence and low five-year survival rate in China. There is a lack of effective therapeutic approaches available for unresectable patients with advanced HCC. Recently, the development of targeted and immunotherapy agents and their application in the therapy of various solid tumors have brought new options and benefits to patients with advanced HCC. Companion diagnostics (CDx) emerged with the development of targeted agents, and its roles in selecting eligible patients for specific targeted/immunotherapy agents and improving prognosis are getting more prominent. This article focuses on the CDx technologies and applications related to HCC targeting and immunotherapy, in order to provide inspiration for the precise diagnosis and treatment of HCC.

[CircRNA circTNPO1 promotes the proliferation and metastasis of osteosarcoma by sponging miR-338-3p].

Objective: To explore the effects of circTNPO1 on the proliferation and metastasis of osteosarcoma (OS) by sponging miR-338-3p. Methods: The expression of circTNPO1 on osteoblasts and multiple OS cell lines were detected by qRT-PCR. CircTNPO1 stable knockdown 143B cell line was constructed by sh-circTNPO1. Cell count kit 8 (CCK-8) assay and wound healing assay were applied to evaluate the proliferation and metastasis of this cell. Luciferase reporter assay was used to explore the binding between circTNPO1 and miR-338-3p. In xenograft tumor model, miR-338-3p inhibitor or its control was injected into the circTNPO1 knockdown tumors. The weight and size of the tumors were evaluated and Ki-67 expression was detected by immunohistochemistry. Results: The RNA expression of circTNPO1 in OS cell lines U2OS, HOS, MG63, 143B, ZOS and ZOSM were 2.73±0.27, 3.18±0.54, 4.33±0.52, 5.75±0.65, 4.50±0.49 and 3.96±0.35, respectively, higher than 1.00±0.09 in hFOB1.19 (P<0.001). CCK-8 assay revealed that after 48 h and 72 h, the absorbance of sh-circTNPO1 #1 was 0.81±0.05 and 1.09±0.06, while sh-circTNPO1 #2 143B cells was 0.84±0.04 and 1.2±0.04, which were sharply reduced compared with the control (1.00±0.06 and 1.49±0.06, P<0.001); after 48 h and 72 h, the absorbance of 143B cells transfected with circTNPO1 #1 and miR-338-3p (0.92±0.06 and 1.32±0.07) were higher than those of cells transfected with sh-circTNPO1 cells and miR NC (0.92±0.06 and 1.32±0.07, P<0.050). Wound healing assay demonstrated that the 24 hour-migration rates of sh-circTNPO1 #1 and sh-circTNPO1 #2 cells were (24.43±2.15)% and (39.70±4.20)% respectively, which were significantly lower than that of the control [(56.51±3.27)%, P<0.010]; the migration rates of sh-circTNPO1 #1+ miR NC and sh-circTNPO1 #1+ miR-338-3p inhibitor were (26.70±2.21)% and (46.10±5.71)%, with a significant difference (P<0.005). In xenograft tumor model, the weight and size of tumors in control, sh-circTNPO1 #1+ miR NC and sh-circTNPO1 #1+ miR-338-3p inhibitor mice were (458.80±158.10) mg, (262.50±82.09) mg, (395.40±137.60) mg and (593.00±228.40) mm(2,) (203.30±144.20) mm(2,) (488.60±208.60) mm(2,) respectively. Compared with control, sh-circTNPO1 tumors were significantly smaller (P<0.01). Injection with miR-338-3p inhibitor significantly reversed both the weight and size of tumors (P<0.05). Conclusion: CircTNPO1 promotes the proliferation and metastasis of OS by sponging miR-338-3p, which could be a new target for OS treatments.

[Validation of the Pollard' s classification criteria (2010) for rheumatoid arthritis patients with fibromyalgia].

OBJECTIVE: To evaluate the sensitivity and specificity of Pollard' s classification criteria(2010) for the diagnosis of rheumatoid arthritis (RA) patients withfibromyalgia (FM) in Chinese patients, and to assess the clinical features and psychological status of RA-FM patients in a real-world observational setting. METHODS: Two hundred and two patients with rheumatoid arthritis were enrolled from the outpatients in Rheumatology and Immunology Department in Peking University People' s Hospital. All the patients were evaluated whether incorporating fibromyalgia translation occured using the 1990 American College of Rheumatolgy (ACR)-FM classification criteria. Forty two RA patients were concomitant with FM, while the other one hundred and sixty RA patients without FM were set as the control group. RESULTS: There was no significant difference in general demography between the two groups (P>0.05). In this study, the Pollard' s classification criteria (2010) for RA-FM in Chinese patients had a high sensitivity of 95.2% and relatively low specificity of 52.6%. Compared with those patients without FM, RA patients with FM (RA-FM patients) had higher Disease Activity Scale in 28 joints (DAS-28) score (5.95 vs. 4.38, P=0.011) and much more 28-tender joint counts (TJC) (16.5 vs.4.5, P < 0.001).RA-FM patients had worse Health Assessment Questionnaire (HAQ) score (1.24 vs. 0.66, P < 0.001) and lower SF-36 (28.63 vs. 58.22, P < 0.001). Fatigue was more common in RA-FM patients (88. 1% vs. 50.6%, P < 0.001) and the degree of fatigue was significantly increased in RA-FM patients (fatigue VAS 5.55 vs. 3.55, P < 0.001). RA-FM patients also had higher anxiety (10 vs.4, P < 0.001) and depression scores (12 vs.6, P < 0.001). erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), morning stiffness time and 28-swollen joint counts (SJC) showed no difference between these two groups. CONCLUSION: The Pollard' s classification criteria (2010) for RA-FM are feasible in Chinese rheumatoid arthritis patients. The Pollard' s classification criteria is highly sensitive in clinical application, while the relativelylow specificity indicates that various factors need to be considered in combination. RA patients with FM result in higher disease activity, worse function aland psychological status. RA patients with FM also have poorer quality of life. DAS-28 scores may be overestimated in RA patients with FM. In a RA patient thatdoes not reach remission, the possibility of fibromyalgia should be con-sidered.

[Study on the value of serum des-γ-carboxy prothrombin in predicting hepatocellular carcinoma recurrence after liver transplantation].

Objective: To explore the clinical value of serum des-γ-carboxy prothrombin (DCP) in predicting hepatocellular carcinoma recurrence after liver transplantation. Methods: A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed. Receiver operating characteristic curve analysis, Mann-Whitney U test, Kaplan-Meier method, Log-Rank test, χ2 test, univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics. Results: The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population (P < 0.001). The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve. The sensitivity, specificity, Youden's index and the receiver operating characteristic curve was 87.90%, 57.30%, 0.452, and 0.726, respectively. Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP ≥200mAU/ml had a higher probability of recurrence (P < 0.001). Further, subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup, cumulative tumor diameter ≤ 9 cm subgroup and Milan criteria subgroup (P < 0.05). Cox regression analysis showed that preoperative DCP≥200 mAU/ ml (P = 0.017) and cumulative tumor diameter > 9 cm (P = 0.014) was an independent risk factor for recurrence after liver transplantation. χ (2) test results showed that preoperative serum DCP level was correlated with gender, serum gamma glutamyltransferase level, serum alpha fetoprotein level, cumulative tumor diameter, vascular invasion, tumor differentiation and liver cancer transplant criteria (P < 0.05). Conclusion: Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation. In addition, the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.

[Advances in the study of cellular immunotherapy for liver cancer].

Liver cancer is one of the most common malignant tumors and currently ranks the fourth in morbidity rate and the second in mortality rate in China. At present, the main clinical treatmentmethod is surgical treatment and other treatments, such as interventional therapy, local radiotherapy and chemotherapy, serve as supplementary treatment methods. However, due to the occult incidence of liver cancer, most patients have entered the advanced stage at the time of diagnosis and lack effective treatment methods, resulting in low overall survival rate, high mortality rate and poor prognosis. Immunotherapy, especially cellular immunotherapy, as an emerging cancer treatment method, can directly kill tumor cells or stimulate the anti-tumor immune response by isolating and activating immune effector cells. Common methods include chimeric antigen receptor T cells, tumor-infiltrating lymphocytes and cytokine-induced killer cells, etc. Recently, cellular immunotherapy has become a research hotspot because it can enhance the immune function, reduce the recurrence rate and prolong the survival time of patients. This article reviews the advances in the study of cellular immunotherapy in the clinical application of liver cancer.

Hsa_circ_001193 regulates proliferation and apoptosis of nasopharyngeal carcinoma cells through targeting mir-496.

OBJECTIVE: To explore the effects of hsa_circ_001193 on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: The messenger ribonucleic acid (mRNA) expression level of hsa_circ_001193 in three NPC cell lines (CNE-1, SUNE-1, and HONE-1) and human normal nasopharyngeal epithelial cell line (NP69) was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). The expression of hsa_circ_001193 was silenced through transient transfection with small-interfering RNA (siRNA). Regulatory effects of hsa_circ_001193 knockdown on the proliferation and apoptosis of HONE-1 cells were determined using cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry. Potential miRNAs binding hsa_circ_001193 were predicted in the StarBase, which was further verified via Dual-Luciferase reporter assay and qRT-PCR. Moreover, the involvement of the predicted target miRNA in the proliferation of HONE-1 cells regulated by hsa_circ_001193 was determined by CCK-8 assay. RESULTS: Compared with that in human normal nasopharyngeal epithelial cell line (NP69), the expression of hsa_circ_001193 was significantly upregulated in NPC cell lines (p<0.05). The results of CCK-8 assay and colony formation assay showed that knockdown of hsa_circ_001193 could significantly suppress the cell proliferation ability and colony formation ability compared with control group (p<0.05). The results of flow cytometry revealed that the apoptosis rate in hsa_circ_001193 knockdown group was remarkably higher than that in control group (p<0.05). Besides, according to the analysis of StarBase database, there were binding sites between hsa_circ_001193 and miR-496. The Dual-Luciferase reporter assay manifested that miR-496 bound hsa_circ_001193 (p<0.05). CONCLUSIONS: Hsa_circ_001193 can serve as the miR-496 sponge, which regulates proliferation and apoptosis of NPC cells through up-regulating miR-496. Our findings provide a new therapeutic target for NPC.

MiR-548b-3p inhibits proliferation and migration of breast cancer cells by targeting MDM2.

OBJECTIVE: The aim of this study was to explore the expression and biological functions of micro ribonucleic acid (miR)-548b-3p in breast cancer (BC), and to investigate its potential molecular mechanism. PATIENTS AND METHODS: The expression level of miR-548b-3p in BC tissues and cells was detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Subsequently, the impacts of miR-548b-3p on the proliferation, apoptosis, and cycle, as well as migration and invasion of BC cells, were explored using colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and transwell assay, respectively. The possible downstream target genes of miR-548b-3p were predicted via bioinformatics and verified through qRT-PCR and Western blotting. Furthermore, Dual-Luciferase reporter gene assay was employed to confirm whether miR-548b-3p could directly bind to murine double minute 2 (MDM2). RESULTS: QRT-PCR results showed that miR-548b-3p expression was significantly downregulated in 37 out of 43 BC tissues. Subsequent in-vitro experiments indicated that the overexpression of miR-548b-3p significantly inhibited the proliferation and metastasis, whereas promoted the apoptosis of BC cells. Bioinformatics predicted that MDM2 was the downstream target gene of miR-548b-3p. After overexpression of miR-548b-3p, qRT-PCR, and Western blotting results revealed that the expression of MDM2 was remarkably downregulated. Dual-Luciferase reporter gene assay further confirmed that miR-548b-3p could directly bind to MDM2. CONCLUSIONS: MiR-548b-3p expression was significantly downregulated in BC. In addition, lowly expressed miR-548b-3p repressed the proliferation and metastasis of BC cells through targeted regulation of MDM2.

Retraction Note: Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Pathological features of immune-mediated hepatitis due to immune checkpoint inhibitors and anti-angiogenesis targeted therapy].

Objective: To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy. Methods: Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining. Results: Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. Conclusion: Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.

[Clinical efficacy of fixation bone fragments by screw though cortical bone tunnel combined with limited open reduction in treating 31A3 type irreducible femoral intertrochanteric fractures in elderly people].

Objective: To explore and analyze the clinical efficacy of fixation bone fragments by screw though cortical bone tunnel combined with limited open reductionin treating 31A3 type irreducible femoral intertrochanteric fractures in elderly people. Methods: Clinical data of 18 elderly patients with 31A3 type irreducible femoral intertrochanteric fractures treated from July 2017 to June 2018 in Orthopedics Department of Jiangsu Province Hospital were collected and analyzed retrospectively. There were 8 males and 10 females, aged from 65 to 88 years (mean age,(76±4) years). When confirmed as irreducible femoral intertrochanteric fractures by C-arm machine during operation, limited open reduction and fixation bone fragments by screw though cortical bone tunnel and intramedullary nail fixation were conducted. General surgical data,the quality of fracture reduction and functional recovery scale (FRS) score were collected.Data before and after operation were compared with paired t-test. Results: All patients were followed up for a mean of 13.6 months (10 to 22 months). The surgical time was (55±13) min (42 to 95 min), the intraoperative blood loss was (223±26) ml (180 to 320 ml), the number of intraoperative fluoroscopy was 23±4 (18-32 times), and the fracture healing time was (4.8±0.7) months. The quality of fracture reduction was rated as grade Ⅰ in 15 cases andgrade Ⅱ in 3 cases, with an excellent to good rate of 100% according to Kim classification. FRS score was 84±10 at the last follow-up and it was comparable with that before injury (84±11) (t=0.144, P=0.887). Conclusion: For elderly patients with 31A3 type irreducible femoral intertrochanteric fractures, fixation bone fragments by screw though cortical bone tunnel combined with limited open reduction is an efficient treating method with advantages of high quality of fracture reduction and fixation without increasing of surgical time and blood loss.

Arginase-2 protects myocardial ischemia-reperfusion injury via NF-κB/TNF-α pathway.

OBJECTIVE: Arginase-2 exerts an anti-inflammatory potential. However, whether nuclear factor-κB (NF-κB)/TNF-α (tumor necrosis factor-α) pathway is involved in the anti-inflammation effect of arginase-2 has not been fully elucidated. Our study aims to explore the regulatory role of arginase-2 on ischemia-reperfusion injury (IRI) in rats and its underlying mechanism. MATERIALS AND METHODS: 24 male Sprague Dawley (SD) rats were randomly assigned into sham group, IRI group and arginase-2 group, with 8 rats in each group. Electrocardiogram was performed in each rat before and after animal procedures. Serum samples and heart samples of each rat were collected 10 days after animal procedures. Serum levels of CK-MB (creatine kinase-MB) and LDH (lactate dehydrogenase) in each rat were detected using the relative commercial kits. Pathological lesions in rat myocardium were observed by hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis in rat heart was accessed by TUNEL (Terminal Deoxynucleotidyl Transferase dUTP Nick-end Labeling) staining. Expression levels of NF-κB, TNF-α, VCAM-1, ICAM-1 and MCP-1 in rat myocardium were detected by Western blot and immunohistochemistry. RESULTS: Electrocardiogram showed slower heart rate, lower voltage of QRS wave and longer Q-T interval in rats of IRI group than those of sham group (p < 0.05). A few rats in IRI group even presented arrhythmia. On the contrary, rats in arginase-2 group presented higher heart rate and voltage of QRS wave, as well as shorter Q-T interval compared with those of IRI group (p < 0.05). Rats in arginase-2 group presented lower plasma levels of CK-MB and LDH than those of IRI group. Pathological lesions in rat myocardium and cardiomyocyte apoptosis were alleviated in arginase-2 group in comparison with those of IRI group. Western blot and immunohistochemistry indicated that arginase-2 pretreatment remarkably downregulated expressions of NF-κB, TNF-α, VCAM-1, ICAM-1 and MCP-1 in rat myocardium. CONCLUSIONS: Arginase-2 protects myocardial ischemia-reperfusion injury in rats through inhibiting the inflammatory response via suppression of NF-κB/TNF-α pathway.

[Comparison of efficacy of first-line administration of generic dasatinib or imatinib in patients with Philadelphia chromosome positive acute lymphoblastic leukemia treated by hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+) ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph(+) ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph(+) ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ(2)=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ(2)=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ(2)=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ(2)=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions: First-line administration of generic dasatinib could improve EFS for Ph(+)ALL patients treated by HSCT when compered with imatinib.

[Review and prospect of clinical study on liver transplantation of hepatocellular carcinoma].

The focus of clinical research on liver transplantation of hepatocellular carcinoma over past decade is as follows: (1) the appropriate indications, so that the limited liver resources can be used more fairly and reasonably. A number of new indications standards have been proposed and validated. Our country scholar puts forward the standard norms, which could benefit more liver cancer patients from liver transplant. (2) To explore the appropriate immunosuppressive regimen in the control of rejection while preventing and reducing tumor recurrence rate after transplantation. At present, there is not enough clinical trial data to conclude, but for patients with high recurrence risk, it is recommended to minimize the dosage of calmodulin inhibitors and convert them to mTOR inhibitors after liver transplantation. In recent years, the rapid development of cancer precision medicine and immunotherapy technology has provided new opportunities for the study of liver transplantation in liver cancer.

The role of angiogenesis inhibitors re-challenge in colorectal cancer previously treated with bevacizumab: a meta-analysis of randomized controlled trials.

OBJECTIVE: The potential usefulness of angiogenesis inhibitors (AIs) re-challenge in the treatment of metastatic colorectal cancer (CRC) who previously treated with bevacizumab has not been established yet. MATERIALS AND METHODS: We identified relevant clinical studies through searching databases up to October 2016. Prospective clinical trials investigating AIs re-challenge in metastatic CRC were included for analysis. The primary endpoint was overall survival with secondary endpoint progression-free survival. Estimates of treatment effect from individual trials were combined using standard techniques. RESULTS: A total of 2.686 patients with metastatic CRC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI re-challenge significantly improved progression-free survival (hazard ratio: 0.63, 95% confidence interval: 0.52-0.76, p < 0.001) and overall survival (hazard ratio: 0.82, 95% confidence interval: 0.76-0.89, p < 0.001) when compared to non-AI containing regimens. No publication bias was detected by Begg's and Egger's tests for PFS (p = 0.09 and p = 0.32) and OS (p = 0.85 and p = 0.50). CONCLUSIONS: Our pooled analysis shows that AIs re-challenge offers an improved PFS and OS in the treatment of metastatic CRC patients who relapsed after a first-line bevacizumab-containing therapy. Further prospective clinical trials are still needed to confirm our findings.

[Clinical, biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency by neonatal screening].

Objective: To investigate the incidence, clinical, biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency (SCADD). Method: From January, 2009 to October, 2015, a retrospective analysis of the urine organic acids and acyl-coenzyme A dehydrogenase (ACADS) gene mutation characteristics of patients diagnosed as SCADD by newborn screening using tandem mass spectrometry in Department of Genetics and Metabolism (Newborn screening Center of Zhejiang Province), Children's Hospital, Zhejiang University School of Medicine. Dietary guidance, life management and supplementation of L-carnitine were conducted, and growth and intelligence development were observed during follow-up among the SCADD patients. Result: A total of 1 430 024 neonates, seventeen cases were diagnosed with SCADD with an incidence of 1/84 117. All patients had no clinical symptoms, and intelligence and physical development were normal. Blood butylacyl-carnitine (C4) levels and the ratios increased, C4 0.713.14 µmol/L(reference value 0.03-0.48 µmol/L), C4/C2 0.07-0.23(reference value 0.01-0.04), C4/C3 0.65-2.04(reference value 0.05-0.39). Thirteen with increased urinary ethyl malonic acid (9.30-90.99 mg/g creatinine (reference value 0-6.20 mg/g creatinine )), one patient was accompanied by increased methyl succinic acid (12.33 mg/g creatinine(reference value 0-6.40 mg/g creatinine)), one subject with increased acetylglycine (3.52 mg/g creatinine(reference value 0-0.70 mg/g creatinine)). A total of 13 known mutations were detected in the ACADS gene, 1 homozygous mutation (c.1031A>G), the others are compound heterozygous mutations. One frameshift mutation (c.508_509delGC) and 12 missense mutations were detected. Common mutation were c. 1031A>G(35.3%), c. 164C>T(20.6%) and c. 991G>A(11.8%). SCADD in newborn screening program had no clinical symptoms and normal growth development after 8-42 months follow-up. Conclusion: Cases with SCADD had no clinical symptoms with an incidence of 1/84117. The c. 164C>T and c. 1031A>G may be the common mutations.

Bioactive Natural Protein-Hydroxyapatite Nanocarriers for Optimizing Osteogenic Differentiation of Mesenchymal Stem Cells.

Improving the controlled release of bioactive growth factors to regulate cell behavior and tissue regeneration remains a need in tissue engineering and regenerative medicine. Inorganic and polymeric nanoparticles have been extensively fabricated as bioactive biomaterials with enhanced biocompatibility and effective carriers of therapeutic agents, however, challenges remain such as the achievement of high loading capacity and sustained release, and the bioactivity preservation of growth factors. Here, a multilayered, silk coated hydroxyapatite (HA) nanocarrier with drug loading-release capacity superior to pure silk or HA nanoparticles was developed. Bone morphogenetic protein-2 (BMP-2) was bound to the silk coatings with a high binding efficiency of 99.6%, significantly higher than that in silk or the HA nanoparticles alone. The release of BMP-2 was sustained in vitro over a period of 21 days without burst release. Compared with BMP-2 loaded silk or HA particles, bone mesenchymal stem cells (BMSCs) showed improved proliferation and osteogenesis when cultured with the BMP-2 loaded composite nanocarriers. Therefore, these silk-HA composite nanoparticles present a useful approach to designing bioactive nanocarrier systems with enhanced functions for bone tissue regeneration needs.