Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A near-resonant excitation strategy to achieve ultra-low threshold GaN polariton lasing.

A near-resonant excitation strategy is proposed and implemented in a 4-µm-thick GaN microcavity to realize an exciton-polariton condensate/lasing with low threshold. Strong exciton-photon coupling is demonstrated, and polariton lasing is realized with an ultra-low threshold excitation power density of about 13.3 W/cm2 at room temperature. Such an ultra-low threshold is ascribed to the implementation of the near-resonant optical excitation strategy, which enables acceleration of the exciton and polariton relaxation and suppression of the heat generation in the cavity, thereby reducing the energy loss and enhance the cavity excitation efficiency.

Application of artificial intelligence in the diagnosis and treatment of cardiac arrhythmia.

The rapid growth in computational power, sensor technology, and wearable devices has provided a solid foundation for all aspects of cardiac arrhythmia care. Artificial intelligence (AI) has been instrumental in bringing about significant changes in the prevention, risk assessment, diagnosis, and treatment of arrhythmia. This review examines the current state of AI in the diagnosis and treatment of atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, hereditary channelopathies, and cardiac pacing. Furthermore, ChatGPT, which has gained attention recently, is addressed in this paper along with its potential applications in the field of arrhythmia. Additionally, the accuracy of arrhythmia diagnosis can be improved by identifying electrode misplacement or erroneous swapping of electrode position using AI. Remote monitoring has expanded greatly due to the emergence of contactless monitoring technology as wearable devices continue to develop and flourish. Parallel advances in AI computing power, ChatGPT, availability of large data sets, and more have greatly expanded applications in arrhythmia diagnosis, risk assessment, and treatment. More precise algorithms based on big data, personalized risk assessment, telemedicine and mobile health, smart hardware and wearables, and the exploration of rare or complex types of arrhythmia are the future direction.

Anterior cervical X-shape-corpectomy and fusion vs. anterior cervical corpectomy and fusion for two-level cervical spondylosis.

PURPOSE: Anterior cervical X-shape-corpectomy and fusion (ACXF) is a novel cervical surgery, designed as partial alternative to the classic technique, anterior cervical corpectomy and fusion (ACCF). The aim of this study was to evaluate the early-stage outcomes of ACXF in treating two-level cervical spondylosis (CS) through comparisons with ACCF. METHODS: A retrospectively comparative study was conducted in two cohorts of patients who underwent single-vertebral ACXF or ACCF to treat two-level CS during September 2019 and October 2021. Clinical and radiological data of all the patients were collected from pre-operation to 1 year after the surgery, following by intra- and intergroup analyses and comparisons. RESULTS: Fifty-seven patients were included, with 24 undergoing ACXF and 33 undergoing ACCF. ACXF group had significantly shorter drainage duration (2.13 ± 0.61 days vs. 3.48 ± 1.30 days, P < 0.001) and less drainage volume (30.21 ± 26.88 ml vs. 69.30 ± 37.65 ml, P < 0.001) than ACCF group. Both techniques significantly improved all the clinical parameters (P < 0.01) with comparable effects (P > 0.05). Each complication rate in ACXF group was lower than that in ACCF group without significant difference (P > 0.05). ACXF showed a significantly smaller transverse decompression range than ACCF (11.93 ± 1.27 mm vs. 16.29 ± 1.88 mm, P < 0.001). Postoperatively, ACXF yielded a comparable fusion rate (P > 0.05) and a significantly lower subsidence rate (P < 0.01) than ACCF technique at all time points. CONCLUSIONS: ACXF is a potential surgical alternative for certain patients with two-level CS, as it provides both adequate decompression range and fewer adverse events than ACCF. The further modifications on ACXF worth exploration.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Value of synthetic MRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate.

BACKGROUND: Transrectal ultrasonography (TRUS)/magnetic resonance imaging (MRI) fusion-guided biopsy has a high clinical application value. However, this technique has some limitations, which limit its use in routine clinical practice. Therefore, the selection of suitable proatate lesions for this technique is worthy of our attention. Synthetic MRI (SyMRI) is capable of quantifying multiple relaxation parameters, which might have potential value in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. The aim of our study is to examine the value of SyMRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. METHODS: We prospectively selected 148 lesions in 137 patients who underwent prostate biopsy in our hospital. Next, 2-4 needles of TRUS/MRI fusion-guided biopsy combined with 10 needles of system biopsy (SB) were used as the protocol for prostate biopsy. Before biopsy, the MAGiC sequences of the MRI images of the enrolled patients underwent post-processing, and the longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) were extracted. The biopsy pathology results were used as a gold standard to compare the differences in SyMRI quantitative parameters between benign and malignant prostate lesions in the peripheral and transitional zones. The receiver operating characteristic (ROC) curves were plotted to confirm the optimal SyMRI quantitative parameter for prostate lesion benignancy/malignancy performance, and the cutoff values of these parameters were used for grouping the lesions. The single-needle biopsy prostate cancer (PCa)-positivity rates (number of positive biopsy needles/total biopsy needles) and PCa overall detection rates by TRUS/MRI fusion-guided biopsy and SB were compared in different subgroups. RESULTS: The T1 and T2 values can determine the benignancy/malignancy of prostate transition lesions(p < 0.01), and the T2 value has a greater diagnostic performance (p = 0.0376). The T2 value can determine the benignancy/malignancy of prostate peripheral lesions. The optimal diagnostic cutoff values for T2 were 77 and 81 ms, respectively. The single-needle PCa positivity rate of TRUS/MRI fusion-guided biopsy was higher than SB for any prostate lesions in different subgroups (p < 0.01). However, only in the subgroup of transition zone lesions with T2 ≤ 77 ms, the PCa overall detection rate of TRUS/MRI fusion-guided biopsy was significantly higher than that of SB (p = 0.031). CONCLUSION: SyMRI-T2 value can provide a theoretical basis for the selection of suitable lesions for TRUS/MRI fusion-guided biopsy.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation.

BACKGROUND: Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. METHODS: Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. RESULTS: We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. CONCLUSIONS: Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression.

An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming.

Matrix stiffness promotes hepatocellular carcinoma (HCC) metastasis. This study examined the contribution of lipid metabolic reprogramming to matrix stiffness-induced HCC metastasis. HCC cells were cultured on mechanically tunable polyacrylamide gels and subjected to lipidomic analysis. The key enzyme that responded to matrix stiffness and regulated lipid metabolism was identified. The comparative lipidomic screening revealed that stearoyl-CoA desaturase 1 (SCD1) is a mechanoresponsive enzyme that reprogrammed HCC cell lipid metabolism. The genetic and pharmacological inhibition of SCD1 expression/activity altered the cellular lipid composition, which in turn impaired plasma membrane fluidity and inhibited in vitro invasive motility of HCC cells in response to high matrix stiffness. Knockdown of SCD1 suppressed HCC invasion and metastasis in vivo. Conversely, the overexpression of SCD1 or exogenous administration of its product oleic acid augmented plasma membrane fluidity and rescued in vitro invasive migration in HCC cells cultured on soft substrates, mimicking the effects imposed by high matrix stiffness. In human HCC tissues, collagen content, a marker of increasing matrix stiffness, and increased expression of SCD1 together predicted poor survival of HCC patients. An SCD1-dependent mechanoresponsive pathway that responds to increasing matrix stiffness in the tumor microenvironment promotes HCC invasion and metastasis through lipid metabolic reprogramming.

Assessment of peripapillary retinal nerve fiber layer thickness and vessel density in newly diagnosed SLE patients without ocular symptoms.

PURPOSE: This study aims to assess peripapillary retinal nerve fiber layer thickness (pRNFLT) and peripapillary vessel density (PVD) in patients with newly diagnosed active and inactive systemic lupus erythematosus (SLE) by optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: This is a cross-sectional study, in which 77 newly diagnosed SLE patients without ocular symptoms (including 36 active SLE patients and 41 inactive SLE patients) and 72 age- and gender-matched healthy subjects were recruited. All participants underwent OCT and OCTA to evaluate pRNFLT, PVD, and radial peripapillary capillary density (RPCD), respectively. Clinical data at the time of initial diagnosis of SLE, including erythrocyte, leukocyte, platelet, albumin-globulin ratio, erythrocyte sedimentation rate, C-reactive protein, serum complement 3, serum complement 4, anti-dsDNA antibody, and 24-h proteinuria, were collected. RESULTS: No difference was found in pRNFLT between active SLE patients, and healthy controls, average pRNFLT, superonasal RNFLT, and inferonasal pRNFLT were reduced in inactive SLE patients than in healthy controls (p≤0.008). Temporal PVD, inferotemporal PVD, and inferotemporal RPCD in active SLE patients were significantly lower than those in healthy controls (p≤0.043). There also was a trend towards lower temporal RPCD in active SLE than healthy controls (p=0.089). Average PVD, average RPCD, superonasal RPCD, inferonasal RPCD, and inferotemporal RPCD were decreased in inactive SLE patients than in healthy controls (p≤0.047). Additionally, inferotemporal RPCD in active SLE patients was positively associated with albumin-globulin ratio (p=0.041). Temporal RPCD was negatively correlated with anti-dsDNA antibody (p=0.012) and 24-h proteinuria (p=0.006). CONCLUSIONS: PRNFL and PVD damage existed in newly diagnosed SLE patients without ocular symptoms. Temporal and inferotemporal RPCD were associated with the laboratory indicators of impaired renal function in active SLE patients, respectively.

Global, regional, and national burden of kidney dysfunction from 1990 to 2019: a systematic analysis from the global burden of disease study 2019.

OBJECTIVE: We aim to explore the prevalence and temporal trends of the burden of kidney dysfunction (KD) in global, regional and national level, since a lack of related studies. DESIGN: Cross-sectional study. MATERIALS: The data of this research was obtained from Global Burden of Diseases Study 2019. The estimation of the prevalence, which was measured by the summary exposure value (SEV), and attributable burden of KD was performed by DisMod-MR 2.1, a Bayesian meta-regression tool. The Spearman rank order correlation method was adopted to perform correlation analysis. The temporal trends were represented by the estimated annual percentage change (EAPC). RESULTS: In 2019, there were total 3.16 million deaths and 76.5 million disability-adjusted life years (DALYs) attributable to KD, increased by 101.1% and 81.7% compared with that in 1990, respectively. From 1990 to 2019, the prevalence of KD has increased in worldwide, but decreased in High-income Asia Pacific. Nearly 48.5% of countries globally, such as South Africa, Egypt and Mexico had increased mortality rates of KD from 1990 to 2019 while 44.6% for disability rate. Countries with lower socio-demographic index (SDI) are facing a higher prevalence as well as mortality and disability rate compared with those with higher SDI. Compared with females, the prevalence of KD was lower in males, however the attributable mortality and disability rate were higher in all years from 1990 to 2019. CONCLUSION: With the progress of senescent, we will face more severe challenges of reducing the prevalence and attributable burden of KD, especially in regions with lower SDI. Effective measures are urgently required to alleviate the prevalence and burden of KD.

Impact of bone-implant gap size on the interfacial osseointegration: an in vivo study.

BACKGROUND: The bone-implant gap resulted from morphological mismatch between cervical bony endplates and implant footprint may have adverse impact on bone-implant interfacial osseointegration of cervical disc arthroplasty (CDA). The purpose of the study was to evaluate the impact of bone-implant gap size on the interfacial osseointegration in a rabbit animal model. METHODS: A series of round-plate implants with different teeth depth (0.5 mm, 1.0 mm, 1.5 mm and 2.0 mm) was specifically designed. A total of 48 New Zealand white rabbits were randomly categorized into four groups by the implants they received (0.5 mm: group A, 1.0 mm: group B, 1.5 mm: group C, 2.0 mm: group D). At 4th and 12th week after surgery, animals were sacrificed. Micro-CT, acid fuchsin and methylene blue staining and hematoxylin and eosin (HE) staining were conducted. RESULTS: At 4th week and 12th week after surgery, both micro-CT and HE staining showed more new bone formation and larger bone coverage in group A and group B than that in group C and group D. At 12th week, the bone biometric parameters were significantly superior in group C when compared with group D (p < 0.05). At 12th week, hard tissue slicing demonstrated larger portion of direct contact of new bone to the HA coating in group A and group B. CONCLUSIONS: Bone-implant gap size larger than 1.0 mm negatively affected bone-implant osseointegration between compact bone and HA coated implant surface.

STING mediates neuroinflammatory response by activating NLRP3-related pyroptosis in severe traumatic brain injury.

Long-term neurological deficits after severe traumatic brain injury (TBI), including cognitive dysfunction and emotional impairments, can significantly impair rehabilitation. Glial activation induced by inflammatory response is involved in the neurological deficits post-TBI. This study aimed to investigate the role of the stimulator of interferon genes (STING)-nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) signaling in a rodent model of severe TBI. Severe TBI models were established using weight-drop plus blood loss reinfusion model. Selective STING agonist ADU-S100 or antagonist C-176 was given as a single dose after modeling. Further, NLRP3 inhibitor MCC950 or activator nigericin, or caspase-1 inhibitor VX765, was given as an intracerebroventricular injection 30 min before modeling. After that, a novel object recognition test, open field test, force swimming test, western blot, and immunofluorescence assays were used to assess behavioral and pathological changes in severe TBI. Administration of C-176 alleviated TBI-induced cognitive dysfunction and emotional impairments, neuronal loss, and inflammatory activation of glia cells. However, the administration of STING agonist ADU-S100 exacerbated TBI-induced behavioral and pathological changes. In addition, STING activation exacerbated pyroptosis-associated neuroinflammation via promoting glial activation, as evidenced by increased cleaved caspase-1 and GSDMD N-terminal expression. In contrast, the administration of C-176 showed anti-pyroptotic effects. The neuroprotective effects of C-176 were partially reversed by the NLRP3 activator, nigericin. Collectively, glial STING is responsible for neuroinflammation post-TBI. However, pharmacologic inhibition of STING led to a remarkable improvement of neuroinflammation partly through suppressing NLRP3 signaling. The STING-NLRP3 signaling is a potential therapeutic target in TBI-induced neurological dysfunction.

lncRNA-AC079061.1/VIPR1 axis may suppress the development of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. METHODS: Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. RESULTS: lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. CONCLUSION: The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.

The Value of Chinese Thyroid Imaging Report and Data System Combined With Contrast-Enhanced Ultrasound Scoring in Differential Diagnosis of Benign and Malignant Thyroid Nodules.

OBJECTIVES: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. METHODS: A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. RESULTS: Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P < .001), respectively. CONCLUSIONS: The CEUS feature of mild enhancement in the arterial phase and rapid wash-out pattern are suggestive of malignancy and isochronous wash-out pattern is suggestive of benignity. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.

Fatty infiltration in cervical extensor muscle: is there a relationship with cervical sagittal alignment after anterior cervical discectomy and fusion?

PURPOSE: To investigate the relationship between the preoperative paraspinal Goutalier grade of fatty infiltration and postoperative cervical sagittal alignment in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: A total of 101 patients who underwent single-level ACDF with the Zero-profile implant system between March 2011 and April 2020 were included in this study. Cervical sagittal alignment parameters, including the C2-C7 Cobb angle, functional spinal unit (FSU) angle, cervical sagittal vertical axis (SVA), and T1 slope (T1S), were assessed. Preoperative magnetic resonance images were used to classify patients according to Goutalier grade. Clinical outcomes including Neck Disability Index (NDI) scores, Japanese Orthepaedic Association (JOA) scores and Visual Analogue Scale (VAS) scores were collected and analyzed. RESULTS: According to the Goutalier grade, 33 patients were classified as Goutalier 0-1 (Group A), 44 were classified as Goutalier 1.5-2 (Group B), and 24 were classified as Goutalier 2.5-4.0 (Group C). The mean age among the three groups showed significant differences (P = 0.007). At the last follow-up, the C2-C7 Cobb angle, FSU angle, and T1S improved after the surgery among the groups. Although there were varying degrees of loss of curvature among the different groups during the follow-up period, the postoperative cervical sagittal alignment parameters demonstrated no statistical differences among the three groups (P > 0.05). In addition, patients in all groups experienced significant relief of their symptoms, and the clinical scores were comparable among the groups (P > 0.05). CONCLUSION: The complex nature of anterior cervical surgery requires surgical attention both in decompression and sagittal alignment. Our study demonstrates satisfactory postoperative cervical sagittal alignment of patients despite different grades of fatty infiltration of the multifidus muscle following single-level ACDF. Based on our results, the improvement and maintenance of cervical sagittal alignment after ACDF remains a complex problem that spine surgeons should consider before surgery.

Sec-Eliminating the SARS-CoV-2 by AlGaN Based High Power Deep Ultraviolet Light Source.

The world-wide spreading of coronavirus disease (COVID-19) has greatly shaken human society, thus effective and fast-speed methods of non-daily-life-disturbance sterilization have become extremely significant. In this work, by fully benefitting from high-quality AlN template (with threading dislocation density as low as ≈6×108 cm-2) as well as outstanding deep ultraviolet (UVC-less than 280 nm) light-emitting diodes (LEDs) structure design and epitaxy optimization, high power UVC LEDs and ultra-high-power sterilization irradiation source are achieved. Moreover, for the first time, a result in which a fast and complete elimination of SARS-CoV-2 (the virus causes COVID-19) within only 1 s is achieved by the nearly whole industry-chain-covered product. These results advance the promising potential in UVC-LED disinfection particularly in the shadow of COVID-19.

Development and validation of nomograms to intraoperatively predict metastatic patterns in regional lymph nodes in patients diagnosed with esophageal cancer.

BACKGROUND: An accurate intraoperative prediction of lymph node metastatic risk can help surgeons in choosing precise surgical procedures. We aimed to develop and validate nomograms to intraoperatively predict patterns of regional lymph node (LN) metastasis in patients with esophageal cancer. METHODS: The prediction model was developed in a training cohort consisting of 487 patients diagnosed with esophageal cancer who underwent esophagectomy with complete LN dissection from January 2016 to December 2016. Univariate and multivariable logistic regression were used to identify independent risk factors that were incorporated into a prediction model and used to construct a nomogram. Contrast-enhanced computed tomography reported LN status and was an important comparative factor of clinical usefulness in a validation cohort. Nomogram performance was assessed in terms of calibration, discrimination, and clinical usefulness. An independent validation cohort comprised 206 consecutive patients from January 2017 to December 2017. RESULTS: Univariate analysis and multivariable logistic regression revealed three independent predictors of metastatic regional LNs, three independent predictors of continuous regional LNs, and two independent predictors of skipping regional LNs. Independent predictors were used to build three individualized prediction nomograms. The models showed good calibration and discrimination, with area under the curve (AUC) values of 0.737, 0.738, and 0.707. Application of the nomogram in the validation cohort yielded good calibration and discrimination, with AUC values of 0.728, 0.668, and 0.657. Decision curve analysis demonstrated that the three nomograms were clinically useful in the validation cohort. CONCLUSION: This study presents three nomograms that incorporate clinicopathologic factors, which can be used to facilitate the intraoperative prediction of metastatic regional LN patterns in patients with esophageal cancer.

Low initial trough concentration of rituximab is associated with unsatisfactory response of first-line R-CHOP treatment in patients with follicular lymphoma with grade 1/2.

For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a prospective pharmacokinetic (PK) study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals. Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix® NLMETM. The first cycle trough concentration (C1-trough) of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis, rather than the concentrations in later cycles; the recommendatory minimum optimal C1-trough was 13.60 µg/mL. Patients with grade 1/2 had significantly lower C1-trough compared with grade 3 (12.21 µg/mL vs. 23.45 µg/mL, P < 0.001), only 30% patients with grade 1/2 could reach 13.60 µg/mL, compared with 91.67% in patients with grade 3, which was in accord with its unsatisfactory CR rates (43.33% vs. 76.32%). The stage indicating the tumor burden (the target) was a crucial influence factor for C1-trough, accounting for 40.70% of its variability, 70% patients with grade 1/2 were stage IV in this study, since the systemic therapy only started at the disseminated disease stage. The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2. In summary, low C1-trough accounted for low-grade FL's unsatisfactory CR rate, designing the first dosage of rituximab should be a very important component of individualized therapy for FL.

Albumin-to-alkaline phosphatase ratio as a predictor of tumor recurrence and prognosis in patients with early-stage hepatocellular carcinoma undergoing radiofrequency ablation as initial therapy.

OBJECTIVE: Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy. METHODS: This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated. RESULTS: Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65-0.79) in the training cohort and 0.72 (95% CI: 0.63-0.81) in the validation cohort, which significantly outperformed other existing staging systems. CONCLUSIONS: AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.