Development and validation of a novel craniofacial statistical shape model for the virtual reconstruction of bilateral maxillary defects.

Bilateral maxillary defects are a challenge for fibula free flap reconstruction (FFFR) surgery due to limitations in virtual surgical planning (VSP) workflows. While meshes of unilateral defects can be mirrored to virtually reconstruct missing anatomy, Brown class c and d defects lack a contralateral reference and associated anatomical landmarks. This often results in poor placement of osteotomized fibula segments. This study was performed to improve the VSP workflow for FFFR using statistical shape modeling (SSM) - a form of unsupervised machine learning - to virtually reconstruct premorbid anatomy in an automated, reproducible, and patient-specific manner. A training set of 112 computed tomography scans was sourced from an imaging database by stratified random sampling. The craniofacial skeletons were segmented, aligned, and processed via principal component analysis. Reconstruction performance was validated on a set of 45 unseen skulls containing various digitally generated defects (Brown class IIa-d). Validation metrics demonstrated promising accuracy: mean 95th percentile Hausdorff distance of 5.47 ± 2.39 mm, mean volumetric Dice coefficient of 48.8 ± 14.5%, compactness of 7.28 × 105 mm2, specificity of 1.18 mm, and generality of 8.12 × 10-6 mm. SSM-guided VSP will allow surgeons to create patient-centric treatment plans, increasing FFFR accuracy, reducing complications, and improving postoperative outcomes.

Lung cancer screening study from a smoking population in Kunming.

OBJECTIVE: Yunnan, China, is a central tobacco-producing region with a large smoking population and an increasing incidence of lung cancer in recent years. This study aimed to understand the incidence of lung cancer and the characteristics of lung nodules on low-dose computed tomography (LDCT) scans of the chest in a long-term smoking population in Kunming. PATIENTS AND METHODS: Long-term smokers in Kunming who were not at risk of evident lung disease symptoms were recruited through recommendation and publicity by the Kunming University of Science and Technology. RESULTS: Among 375 cases eligible for inclusion,14 cases of lung cancer were detected with a detection rate of 3.73% (95% CI: 2.55%-4.27%), including one case of squamous carcinoma, one case of small cell lung cancer, seven cases of adenocarcinoma of the lung and five cases of early-stage lung cancer (35.71%). In the group of < 6 mm solid nodules and < 5 mm non-solid nodules, no lung cancer was detected in 201 cases; lung cancer was detected in 14 cases in 61 cases, and there was a statistical difference between the two groups (p < 0.05). CONCLUSIONS: The lung cancer detection rate in long-term smokers was high, with the type predominantly adenocarcinoma and a high incidence of lung nodules, and increased when solid nodules≥6 mm or non-solid nodules ≥ 5 mm were present. It is recommended that screening for lung cancer by LDCT of the chest be introduced in the male smoking population who meet the risk factors and that screening for lung cancer in women should be redefined as a high-risk factor.

Remdesivir as a broad-spectrum antiviral drug against COVID-19.

OBJECTIVE: List the clinical data of the role of remdesivir in COVID-19, and try to make an objective evaluation and analyze its feasibility. MATERIALS AND METHODS: The keywords of "remdesivir", "COVID-19" and "SARS-CoV-2" were systematically searched in PubMed and Web of Science. After removing the repetitions, we summarize articles, letters, and comments on remdesivir in the treatment of COVID-19. RESULTS: In this review, we summarize clinical case of using remdesivir in the treatment of COVID-19, analyzed the final treatment results, and judged whether the drug was effective for the treatment of COVID-19. Also, attention was paid to the side effects of the drug. CONCLUSIONS: According to the clinical results, it was found that remdesivir was effective in the treatment of COVID-19. The drug has side effects, but the symptoms were mild and disappeared immediately after discontinuation of medication.

Cost-effectiveness analysis of capecitabine plus bevacizumab versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer from Chinese societal perspective.

PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.

CXCR4 antagonist AMD3100 enhances the response of MDA-MB-231 triple-negative breast cancer cells to ionizing radiation.

Radiation therapy (RT) is one of the primary modalities for triple-negative breast cancer (TNBC) treatment. However, due to the pro-metastatic potential of radiation and the intrinsic radiation resistance of some tumors, many patients experience RT failure, which leads to cancer relapse and distant metastasis. This preclinical study evaluated the efficacy of the antagonist of the SDF-1 receptor CXCR4, AMD3100, as a radiosensitizer in TNBC models. The combined effect of ionizing radiation and AMD3100 was determined in vitro by surviving fraction, cell cycle distribution, Bax and Bcl-2 expression, and apoptosis assays in a TNBC cell line (MDA-MB-231). For in vivo studies, human xenograft athymic nude mice were used. Treatment of TNBC cells with AMD3100 significantly augmented cellular radiosensitivity. Radiosensitivity was enhanced specifically through increased Bax expression, reduced Bcl-2 expression, prolonged G2-M arrest, and increased apoptosis. Combined treatment with AMD3100 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.5 to 1.8. These findings support the evaluation of antagonists of the SDF-1 receptor CXCR4, such as AMD3100, as potent radiosensitizers in TNBC.

[Effects of metalloproteinases-1 (TIMP-1) cDNA transfection on biological behaviors of PG cells].

A recombinant plasmid, which contains a full length cDNA of human tissue inhibitor of metalloproteinases-1 (TIMP-1), was constructed by using gene recombinant technique, and introduced into a highly metastatic human giant cell carcinoma (PG) by lipofectin technique. Two of the transfectants, PG-T2 and PG-T4, were studied thoroughly. Northern blot showed an increased level of TIMP-1 mRNA in PG-T2 and PG-T4, compared with PG and PG-MV1 (vector-transfected control). The two transfectants also exhibited higher TIMP-1 protein activities. Moreover, they showed significant reduction in their proliferation rate and invasive abilities. The abilities of forming colonies in soft agar and tumorigenecity in athymic nude mice were abrogated in PG-T2 and PG-T4. The preliminary results suggest that a specific upregulation of TIMP-1 expression in metastatic cells could not only suppress their invasive and metastatic phenotype, but also inhibit their proliferation and tumorigenecity.