Clinical evaluation of the three-dimensional printed strut-type prosthesis combined with autograft reconstruction for giant cell tumor of the distal femur

ProposeThis study aimed to describe the design and surgical techniques of a three-dimensional (3D) printed strut-type prosthesis with a porous titanium surface for distal femur giant cell tumors of bone (GCTB) and evaluate the short-term clinical outcomes.MethodsFrom June 2018 to January 2021, 9 consecutive patients with grade I or II GCTB in the distal femur underwent extended intralesional curettage followed by 3D-printed strut-type prosthesis combined with autograft reconstruction were retrospectively reviewed to assess their clinical and radiographic outcomes.ResultsAll patients were followed up for 30.8 ± 7.5 months (18–42 months) after surgery. The mean affected subchondral bone percentage and the mean subchondral bone thickness before surgery was 31.8% ± 9.6% (range, 18.2% ~50.2%) and 2.2 ± 0.8 mm (range, 1.2-4.0 mm), respectively. At the final follow-up, all the patients were alive without local recurrence; no postoperative complications were observed. Patients had significant improvements in postoperative MSTS-93 score [(26.7 ± 2.4) vs. (18.8 ± 3.7), P < 0.05], and ROM [(122.8° ± 9.1°) vs. (108.3° ± 6.1°), P < 0.05] compared with their preoperative statuses. Furthermore, the mean subchondral bone thickness has increased to 10.9 ± 1.3 mm (range, 9.1-12.1 mm).Conclusion3D-printed strut-type prosthesis combined with autograft reconstruction provides acceptable early functional and radiographic outcomes in patients with grade I or II GCTB in distal femur due to the advantages of the prosthesis such as good biocompatibility, osseointegration capacity, and subchondral bone protection. If our early outcomes can be further validated in studies with more patients and sufficient follow-up, this method may be evaluated as an alternative for the treatment of grade I or II GCTB in the distal femur

Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma

Accumulating evidence reveals that ferroptosis and pyroptosis play pivotal roles in tumorigenesis of low-grade glioma (LGG). In this research, we aimed to classify molecular subtypes and further identify and verify a novel multigene signature in LGG on the basis of ferroptosis and pyroptosis-related genes (FPRGs). Raw sequencing data and corresponding clinical data of LGG samples retrieved from the TCGA and CGGA databases were obtained for the training and validation datasets. Non-negative matrix factorization (NMF) clustering defined by FPRGs associated with prognosis was performed to classify molecular subtypes of LGG patients. LASSO-SVM-Random Forest analysis was carried out to develop an FPRG signature to predict the survival and benefit of immunotherapy of LGG patients. NMF clustering defined by FPRGs with prognostic values acted to categorize LGG patients into two molecular subtypes with different prognosis, clinical traits and immune microenvironments. A six-FPRG prognostic signature was constructed, accompanied by the optimal p-value. The AUC values of our signature exhibited great prognostic performances. Our signature was superior to other four well-recognized signatures in predicting the survival probability of LGG patients. Immune characteristics, tumor mutation profile, tumor stemness indices, MGMT methylation and immunotherapy response biomarkers showed significant differences between high- and low-risk populations. Finally, a nomogram was created for quantitative prediction of the survival probability of LGG patients, with the AUC values of the nomogram being 0.916, 0.888 and 0.836 for 1-, 3- and 5-year survival, sequentially. Overall, the FPRG signature may function as an effective indicator for the prognosis prediction and immunotherapy response of LGG patients

Anthropogenic influence on 2018 summer persistent heavy and daily extreme rainfall in central western China

Anthropogenic forcing has reduced the probability of summer persistent heavy rainfall in central western China similar to 2018 by ~47%, but increased that of daily extremes by ~1.5 times, based on HadGEM3-GA6 ensembles

High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99 = 207 µM). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99 = 70.7 µM), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic

Immunogenicity and safety of an inactivated enterovirus 71 vaccine coadministered with trivalent split-virion inactivated influenza vaccine: A phase 4, multicenter, randomized, controlled trial in China

BackgroundFew data exist on the immunogenicity and safety of an inactivated enterovirus 71 vaccine (EV71 vaccine) coadministered with trivalent split-virion inactivated influenza vaccine (IIV3) in infants.MethodsThis trial was a phase 4, randomized, controlled trial. Infants aged 6-11 months were eligible, with no history of hand, foot and mouth disease (HFMD) and no history of EV71 vaccine or any influenza vaccine. Eligible infants were randomly assigned to EV71+IIV3 group, EV71 group or IIV3 group. Blood samples were collected on day 0 and 56.ResultsBetween September 2019 and June 2020, 1151 infants met eligibility criteria and 1134 infants were enrolled. 1045 infants were included in the per-protocol population, including 347 in the EV71+IIV3 group, 343 in the EV71 group, and 355 in the IIV3 group. The seroconversion rate (98.56% vs 98.54%; seroconversion rates difference of 0.02% [95% CI: 0.70-0.98]) and GMT (419.05 vs 503.72; GMT ratio of 0.83 [95% CI 0.70 - 0.98]) of EV71 neutralizing antibodies in the EV71+IIV3 group was not inferior to those in the EV71 group. The non-inferiority results for influenza virus antibodies (A/H1N1, A/H3N2 and B) showed that the seroconversion rates and GMTs of the EV71+IIV3 group were non-inferiority to those of the IIV3 group. Systemic and local adverse event rates were similar between groups. None of serious adverse events (SAEs) were related to vaccination.ConclusionsCoadministration of the EV71 vaccine with IIV3 was safe and did not interfere with immunogenicity. These findings support a viable immunization strategy for infants with the EV71 vaccine coadministered with IIV3 in China. This trial is registered with ClinicalTrials.gov, number NCT04091880

Adenovirus-mediated stromal cell-derived factor-1 alpha gene transfer improves cardiac structure and function after experimental myocardial infarction through angiogenic and antifibrotic actions

Stromal cell-derived factor 1α (SDF-1) is not only a major chemotactic factor, but also an inducer of angiogenesis. The effects of SDF-1α on the left ventricular remodeling in a rat myocardial infarction (MI) model were analyzed. Myocardial infarction was induced by ligation of the left coronary artery in rats. 0.5 × 1010 pfu/ml AdV-SDF-1 or 0.5 × 1010 pfu/ml Adv-LacZ were immediately injected into the infarcted myocardium, 120 μl cell-free PBS were injected into the infarcted region or the myocardial wall in control, and sham group, respectively. We found that AdV-SDF-1 group had higher LVSP and ±dP/dtmax, lower LVEDP compared to control or Adv-LacZ group. The number of c-Kit+ stem cells, and gene expression of SDF-1, VEGF and bFGF were obviously increased, which was associated with reduced infarct size, thicker left ventricle wall, greater vascular density and cardiocytes density in infarcted hearts of AdV-SDF-1 group. Furthermore, the expression of collagen type I and type III mRNA, and collagen accumulation in the infarcted area was lower, which was associated with decreased TGF-β1, TIMP-1 and TIMP-2 expression in AdV-SDF-1 group. Conclusion: SDF-1α could improve cardiac structure and function after Myocardial infarction through angiogenic and anti-fibrotic actions

Application of Pullulan and Chitosan Multilayer Coatings in Fresh Papayas

In this work, some multilayer coatings (two-layer, four-layer or six-layer) based on pullulan and chitosan for protecting papayas were prepared by the layer-by-layer technique. The papayas were coated by immersion and stored at 25 °C, 50% relative humidity or up to 14 days. Uncoated and monolayer-coated papayas were used as controls. The pullulan/chitosan coatings decreased the papaya weight loss, softening, color change (b*, ΔE), and pH, retarded the fall of titratable acidity and vitamin C, and maintained respiratory rate and soluble solid contents. Sensory quality evaluation demonstrated that pullulan/chitosan coatings effectively preserved papaya flavor and overall acceptance. In general, the four-layer coatings provided the best fruit preservation. In conclusion, multilayer pullulan/chitosan coatings are efficient in maintaining the post-harvest quality and prolonging the shelf life of fresh papaya

Linguistic Weighted Aggregation under Confidence Levels

We develop some new linguistic aggregation operators based on confidence levels. Firstly, we introduce the confidence linguistic weighted averaging (CLWA) operator and the confidence linguistic ordered weighted averaging (CLOWA) operator. These two new linguistic aggregation operators are able to consider the confidence level of the aggregated arguments provided by the information providers. We also study some of their properties. Then, based on the generalized means, we introduce the confidence generalized linguistic ordered weighted averaging (CGLOWA) operator. The main advantage of the CGLOWA operator is that it includes a wide range of special cases such as the CLOWA operator, the confidence linguistic ordered weighted quadratic averaging (CLOWQA) operator, and the confidence linguistic ordered weighted geometric (CLOWG) operator. Finally, we develop an application of the new approach in a multicriteria decision-making under linguistic environment and illustrate it with a numerical example