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Abstract Background Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce. Methods CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J). Different doses (10 mg/kg, 20 mg/kg, and 30 mg/kg) and injection methods (subcutaneous/intraperitoneal/gavage injection) of tamoxifen were used to induce the construction of NCSTN knockout mice (mice model). The expressions of nicastrin, NICD1, hes1 in skin, brain, and liver tissue in mice model and wild-type (WT) mice were measured by qRT-PCR and IHC. Results The construction of mice model was successfully induced by tamoxifen, knockout efficiency was 93%, there was no difference in knockout efficiency among three doses, injection methods, genders (P > 0.05). HS-like lesions appeared on the skin of NCSTN knockout mice after 1 month of treatment with tamoxifen, male mice had a higher number of skin lesions compared to female mice (male vs female = 76.5% vs 41.7%, P = 0.027). Compared with WT mice, the expressions of nicastrin (skin P = 0.0009, brain P = 0.0194, liver P = 0.0066), NICD1 (skin P = 0.0115, brain P = 0.0307, liver P = 0.008), hes1 (skin P = 0.0476, brain P = 0.0143, liver P = 0.0003) in mice model all decreased. Conclusions The NCSTN knockout mouse might be employed as HS animal model; Reducing nicastrin may affect the expression of notch1–hes1 pathway molecules in skin, brain, and liver tissues; low dose (10 mg/kg/d) tamoxifen could be used to induce the deletion of the target gene in mice.

Abstract Background Carotenoid cleavage oxygenases (CCOs) include the carotenoid cleavage dioxygenase (CCD) and 9-cis-epoxycarotenoid (NCED), which can catalize carotenoid to form various apocarotenoids and their derivatives, has been found that play important role in the plant world. But little information of CCO gene family has been reported in litchi (Litchi chinensis Sonn.) till date. Results In this study, a total of 15 LcCCO genes in litchi were identified based on genome wide lever. Phylogeny analysis showed that LcCCO genes could be classified into six subfamilies (CCD1, CCD4, CCD7, CCD8, CCD-like, and NCED), which gene structure, domain and motifs exhibited similar distribution patterns in the same subfamilies. MiRNA target site prediction found that there were 32 miRNA target sites in 13 (86.7%) LcCCO genes. Cis-elements analysis showed that the largest groups of elements were light response related, following was plant hormones, stress and plant development related. Expression pattern analysis revealed that LcCCD4, LcNCED1, and LcNCED2 might be involving with peel coloration, LcCCDlike-b might be an important factor deciding fruit flavor, LcNCED2 and LcNCED3 might be related to flower control, LcNCED1 and LcNCED2 might function in fruitlet abscission, LcCCD4a1, LcCCD4a2 , LcCCD1, LcCCD4, LcNCED1, and LcNCED2 might participate in postharvest storage of litchi. Conclusion Herein, Genome-wide analysis of the LcCCO genes was conducted in litchi to investigate their structure features and potential functions. These valuable and expectable information of LcCCO genes supplying in this study will offer further more possibility to promote quality improvement and breeding of litchi and further function investigation of this gene family in plant.

Abstract Background This study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH). Methods Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed. Results In group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2–2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up. Conclusion Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.

Abstract Background The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS35 can regulate APP metabolism and Aβ formation, and its levels are reduced in Alzheimer’s disease (AD) brains. We and others demonstrated that VPS35 genetic manipulation modulates the phenotype of mouse models of AD. However, the translational value of this observation remains to be investigated. Methods Triple transgenic mice were randomized to receive a pharmacological chaperone, which stabilizes the retromer complex, and the effect on their AD-like phenotype assessed. Results Compared with controls, treated mice had a significant improvement in learning and memory, an elevation of VPS35 levels, and improved synaptic integrity. Additionally, the same animals had a significant decrease in Aβ levels and deposition, reduced tau phosphorylation and less astrocytes activation. Conclusions Our study demonstrates that the enhancement of retromer function by pharmacological chaperones is a potentially novel and viable therapy against AD.

Abstract Background Periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is a serious complication for patients. Some joint surgeons have tried to use vancomycin powder (VP) in total knee and total hip arthroplasty to prevent postoperative PJI, but its effect is still not clear. At present, there is no meta-analysis that specifically analyses the effect of different doses of vancomycin powder on the incidence of PJI. Methods We carried out a search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and identified the studies we needed. Review Manager (RevMan) 5.3 software was employed for statistical analysis. Results The analysis of primary TKA (PTKA) showed that using 1 g (RR 0.38, 95% CI 0.22–0.67 [P = 0.0008]) and 2 g (RR 0.48, 95% CI 0.31–0.74 [P = 0.0008]) of vancomycin powder in primary TKA (PTKA) could all significantly prevent PJI. The analysis of primary THA (PTHA) showed that using 1 g (RR 0.37, 95% CI 0.17–0.80 [P = 0.01]) of vancomycin powder effectively decreased the incidence of PJI, while using 2 g (RR 1.02, 95% CI 0.53–1.97 [P = 0.94]) of vancomycin powder had no significant effect on preventing PJI. Because the data were abnormal, we believed the conclusion that using 2 g of vancomycin powder in primary THA had no effect on preventing PJI was doubtful. Using vancomycin powder in revision TKA (RTKA) significantly reduced the PJI rate (RR 0.33, 95% CI 0.14–0.77 [P = 0.01]), similar to revision THA (RTHA) (RR 0.37, 95% CI 0.14–0.96 [P = 0.04]). Conclusions In primary TKA, both 1 g and 2 g of vancomycin powder can effectively prevent PJI. In primary THA, using 1 g of vancomycin powder is a better choice, while the effect of using 2 g of vancomycin powder is not clear, and a more prospective randomized controlled trial should be done to verify it. In revision TKA and revision THA, vancomycin powder is a good choice to prevent PJI.

Abstract Background The incidence of patient dissatisfaction due to anterior knee pain (AKP) and patellar crepitus after total knee arthroplasty (TKA) remains a concern. However, it has been shown that improvements in the femoral component of traditional prostheses could reduce these instances of pain in the case of TKA performed with patellar resurfacing. This study aims to investigate whether TKA without patellar resurfacing can also benefit from the aforementioned femoral component modification in reducing AKP and patellar crepitus post-TKA. Methods Sixty-two patients (85 knees) who underwent TKA using the modern prosthesis and 62 age- and sex-matched patients (90 knees) fitted with the traditional prosthesis were enrolled in this study. The occurrence of AKP and patellar crepitus as well as the Knee Society Score (KSS) were consequently recorded, and the data was analyzed in order to determine whether there was a statistically significant difference between the two groups. Results The incidence of AKP was significantly lower in the study group compared with the control group at the 3-month and 1-year follow-ups (4.7% vs. 13.3% [p = 0.048] and 3.5% vs. 13.3% [p = 0.021], respectively). In addition, the incidence of patellar crepitus was also significantly lower in the study group compared with the control group at the 3-month and 1-year follow-ups (15.3% vs. 34.4% [p = 0.004] and 10.6% vs. 28.9% [p = 0.002], respectively). There was no significant difference in the KSS between the two groups. Conclusions These results revealed that TKA without patellar resurfacing will indeed benefit from the modified femoral implant design in reducing AKP and patellar crepitus, a finding that may be beneficial to surgeons who select implants for their patients when patellar resurfacing is not planned or not possible due to other reasons.

Abstract Background Precise measurement of lateral femoral bowing is important to achieve postoperative lower limb alignment. We aimed to investigate factors that affect the precision of the radiographic lateral femoral bowing (RLFB) angle using three-dimensional (3D) models and whether the angle affects surgery design. Methods Forty femurs in total were divided into two groups based on their preoperative RLFB angle. The flexion contracture angle, preoperative and postoperative RLFB angles, and intersection angle between the mechanical and anatomical axes were compared. The angle between the arc and sagittal planes, varus and valgus angles, and intersection angle between the mechanical and anatomical axes were measured on a 3D model. Results There was no significant between-group difference in 3D model measurements of the angle between the arc and sagittal planes (p = 0.327). There was no significant difference between the mechanical and anatomical axes measured by both imaging modalities (p > 0.258). When the RLFB was >5°, the flexion contracture angle and radiographic femoral bowing angle were positively correlated (r = 0.535, p