The National Comprehensive Cancer Network (NCCN) released the latest version 1, 2022 of "NCCN guidelines for the clinical diagnosis and treatment of small cell lung cancer" (hereinafter referred to as "guideline"). Based on high-quality evidence-based medicine, this guideline provides references of clinical diagnosis and treatment for clinicians around the world. Compared with the version 3, 2021 of the "guideline", updates and revisions mainly focused on the progress of radiotherapy and systemic treatment. This article will interpret the updated therapy content in this new version of the "guideline".

Objective:To explore the clinical predictive effect of the preoperative ratio of C reactive protein to albumin (CAR) on perioperative delirium (POD) in geriatric patients with femoral intertrochanteric fracture.Methods:The clinical data were analyzed retrospectively of the 398 patients who had undergone surgery for femoral intertrochanteric fractures at Department of Orthopedics, Xuanwu Hospital from January 2013 to March 2016. According to the presence or absence of POD, all the patients were divided into 2 groups: a delirium group and a normal group. The 2 groups were compared in terms of general clinical data like gender, age, body mass index, blood routine, CAR, biochemical indicators, blood coagulation indicators and concomitant internal diseases. After a single factor logistic regression analysis of the general clinical data of the patients, factors with P<0.10 were introduced into the multivariate logistic binary regression model to screen out the risk factors for POD in geriatric patients with femoral intertrochanteric fracture. The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value and optimal cut-off point of CAR for POD in geriatric patients with femoral intertrochanteric fracture. Results:The incidence of POD in this cohort was 14.32%(57/398). The age, C-reactive protein, CAR, platelet and probability of pulmonary infection in the delirium group were significantly higher than those in the normal group, but the hemoglobin, albumin and prealbumin in the former were significantly lower than those in the latter ( P< 0.05). The multivariate logistic binary regression analysis showed that hemoglobin ( OR=0.975, 95% CI: 0.957 to 0.993, P=0.006) and CAR( OR=53.713, 95% CI: 17.713 to 162.876, P<0.001) were risk factors for POD in geriatric patients with femoral intertrochanteric fracture. The area under ROC of CAR in predicting POD in geriatric patients with femoral intertrochanteric fracture was 0.906 (95% CI: 0.873 to 0.933, P<0.001), and the cut-off point was 2.06. When CAR>2.06, its predicted incidence of POD was 50.50%, with a sensitivity of 89.47% and a specificity of 85.34%. Conclusion:As CAR is a risk factor for POD in geriatric patients with femoral intertrochanteric fracture, it can be used as an effective indicator to predict POD.

Background::Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis.Methods::In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted. Results::Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism. Conclusions::Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.

Based on new clinical evidence, the National Comprehensive Cancer Network (NCCN) annually updates and releases the "NCCN Guidelines for the Clinical Diagnosis and Treatment of Non-Small Cell Lung Cancer" which has become the reference for clinical diagnosis and treatment approved and complied by clinicians worldwide. On November 25, 2020, the latest 2021 V1 version of "NCCN Clinical Diagnosis and Treatment Guidelines for Non-Small Cell Lung Cancer" (hereinafter referred to as "Guidelines") was released. Compared with the 8th edition of the "Guidelines" in 2020, many updates focused on the progress of targeted and immunotherapy. This article will provide the interpretations of the updated therapy content of this edition of the guidelines.

Segmentectomy is the removal of certain segments of the lung with lesions and retaining the normal lung tissue of the lobe. Lung segmentectomy is considered difficult due to the lack of clear anatomical boundaries between lung segments. Segmentectomy has a variety of indications, such as lung cancer, metastatic lung tumors, and many non-malignant diseases. In the treatment of early stage lung cancer, segmentectomy was initially considered only as a treatment option for patients not suitable for conventional lobectomy. As more evidence emerged, the indications for segmentectomy have continued to change over time, and segmentectomy has been widely performed in patients with early stage lung cancer. Theoretically, segmentectomy leads to better preservation of lung function than lobectomy, but the risk of incomplete tumor resection is higher, so the indication of segmentectomy has become a focus of debate. This article will introduce the surgical techniques of segmentectomy and summarize the published and unpublished clinical studies on segmentectomy for the treatment of early stage lung cancer.

Creatinine levels in biological fluids are important indicators for the clinical evaluation of renal function. Creatinase (CRE, EC3.5.3.3) is one of the key enzymes in the enzymatic measurement of creatinine concentration, and it is also the rate-limiting enzyme in the whole enzymatic cascade system. The poor catalytic activity of CRE severely limits its clinical and industrial applications. To address this issue, a semi-rational design is applied to increase the activity of a creatinase from Alcaligenes sp. KS-85 (Al-CRE). By high-throughput screen of saturation mutagenesis libraries on the selected hotspot mutations, multiple variant enzymes with increased activity are obtained. The five-point best variant enzyme (I304L/F395V/K351V/Y63S/Q88A) were further obtained by recombine the improved mutations sites that to showed a 2.18-fold increased specific activity. Additionally, structure analysis is conducted to understand the mechanism of the activity change. This study paves the way for a better practical application of creatinase and may help further understand its catalytic mechanism.
Creatinine ; Mutagenesis, Site-Directed ; Ureohydrolases/genetics* ; Catalysis

With the development of precision diagnosis and treatment of lung cancer, anatomical segmentectomy has become an important surgical procedure for the treatment of early-stage lung cancer. After the widespread popularization of video-assisted thoracoscopic surgery (VATS), the treatment of lung cancer has entered the era of minimally invasive surgery. Since it was first reported in 2012, uniportal video-assisted anatomical segmentectomy has gained increasing clinical application. Uniportal VATS is less invasive than thoracotomy and traditional VATS. At present, the main research hotspots around uniportal video-assisted anatomical segmentectomy include specific indications, short-term and long-term efficacy, and learning curve. This article will introduce the characteristics, indications and surgical techniques of this procedure, then summarize and discuss the latest research progress of uniportal video-assisted anatomical segmentectomy based on the latest evidence-based evidence.

Genome-wide association studies (GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts (OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability, suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line (HIOEC) using RNA-seq, ATAC-seq, H3K27ac ChIP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only (NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification pipeline. In total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epithelium-expressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.
Chromatin ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Epithelium ; Genome-Wide Association Study ; Humans