A numerical tool for assessing human thermal safety and thermal comfort in cold-weather activities.

This paper describes a newly developed software tool to evaluate human thermal safety and thermal comfort in cold-weather activities aimed at guiding users to arrange activity plans and select appropriate clothing ensembles. The software inputs include conditions of activity, environment, human body, and clothing ensemble. It outputs physiological temperatures, cold injury risks, thermal sensations, and thermal comforts in intuitive ways like cloud maps and curves. The software tool is characterized by (1) integration of a thermoregulatory model that predicts human thermophysiological responses under exercise conditions in cold environments, (2) the functions of clothing ensemble database and individual parameter database, (3) the human centric outputs that directly reflect human physiological and mental status, and (4) the user-friendly operation interface and output interface, as well as a wide applicability. The software is validated with human test studies covering ambient temperatures from - 30.6 to 5 °C, clothing ensembles from 1.34 to 3.20 clo, and activity intensities from 2 to 9 Mets. The average prediction RMSEs of core temperature, mean skin temperature, thermal sensation, and thermal comfort are 0.16 °C, 0.45 °C, 0.58, and 1.41, respectively. The software is an advanced expansion to current standards and guidance of cold exposure assessment and a meaningful tool for the fields of occupational health care, cold protection, and environmental ergonomics.

Graphitic carbon nitride-based photocatalysts in the applications of environmental catalysis.

Semiconductor photocatalytic technology has shown great prospects in converting solar energy into chemical energy to mitigate energy crisis and solve environmental pollution problems. The key issue is the development of high-efficiency photocatalysts. Various strategies in the state-of-the-art advancements, such as heterostructure construction, heteroatom doping, metal/single atom loading, and defect engineering, have been presented for the graphitic carbon nitride (g-C3N4)-based nanocomposite catalysts to design their surface chemical environments and internal electronic structures to make them more suitable for different photocatalytic applications. In this review, nanoarchitecture design, synthesis methods, photochemical properties, potential photocatalytic applications, and related reaction mechanisms of the modified high-efficiency carbon nitride-based photocatalysts were briefly summarized. The superior photocatalytic performance was identified to be associated with the enhanced visible-light response, fast photoinduced electron-hole separation, efficient charge migration, and increased unsaturated active sites. Moreover, the further advance of the visible-light harvesting and solar-to-energy conversions are proposed.

Clinical characteristics and outcomes of patients with COVID-19 and psoriasis.

To summarize the clinical characteristics and explore the role of treatment types in outcomes among psoriasis patients with coronavirus disease 2019 (COVID-19). The principal summary measures were pooled prevalence and risk ratio (RR) with 95% confidential interval (CI). R statistic software was used for all the analysis. A total of 19 studies including 4073 psoriasis patients with COVID-19 were eligible for the meta-analysis. The overall hospitalization rate is about 20.2% (95% CI: 12.7%-28.7%), and changed to be 18.0% (95% CI: 9.9%-27.6%) or 14.1% (95% CI: 5.9%-24.6%) after systemic or biologic treatment. Moreover, the overall fatality rate is 1.5% (95% CI: 0.4%-3.0%), and turned to be 0.7% (95% CI: 0%-2.0%) or 0.5% (95% CI: 0%-2.2%) after systemic or biologic therapy. Notably, a lower hospitalization RR was found in patients receiving biologic therapy than those receiving other treatments (RR = 0.62, 95% CI: 0.42-0.94). The results were consistent after sensitivity analysis and trim-and-fill analysis. Systemic, especially biologic therapy could lessen the clinical severity in psoriasis patients with COVID-19. Our finding will help to guide current recommendations and provide a reference for clinical decision-making.

Monolithic 6 × 6 transmitter-router with simultaneous sub-nanosecond port and wavelength switching.

A monolithic 6 × 6 transmitter-router with both port and wavelength switching at sub-nanosecond speed is proposed and experimentally demonstrated. Based on an intra-cavity cyclic echelle diffraction grating router (EDGR) and semiconductor optical amplifier (SOA) arrays, each selectable output port can realize a selected multi-wavelength laser (MWL) output. The measurement results show that all 36 input-output combinations have a single-mode emission spectrum with a sidemode suppression ratio (SMSR) over 30 dB. Simultaneous switching of six laser wavelengths is achieved together with the switching of the output port by a single electrode selection. The switching time is less than 1 ns. It can offer a cost-effective solution to multi-wavelength multi-port optical transmitter-routers for fast distributed optical switching in datacenters and high-performance computers (HPCs).

Modelling and experimental study of thermo-physiological responses of human exercising in cold environments.

A numerical human thermo-physiological model is developed with the consideration of characteristics of exercising people in cold environments. The developed model is characterized by: 1) the concept of net exercise efficiency which is used to correct the calculation of metabolic heat production by excluding mechanical energy; 2) the effects of low temperature on basal metabolic rate and basal blood flow rate; 3) the integration with a multi-layer clothing model to calculate the heat and moisture transfer through the clothing system, which takes into account the air gaps between the clothing layers to reflect the ventilation and air penetration effect from the ambient wind. Human subject experiment is conducted in a climate chamber to validate the proposed model. The human subject experiment is also carried out in a cold environment (-5 °C) combined with different air velocity conditions (still air, 2 m/s), taking into account the activities of different intensities (standing statically, 2 km/h walking and 7 km/h running). Thermo-physiological parameters including the core temperature, 8-point local skin temperatures and the clothing layer temperatures, are measured during the experiment. Comparison between the predicted and experimental results gives the root mean squared error (RMSE) of core temperature and mean skin temperature of 0.06-0.10 °C and 0.17-0.27 °C, respectively. RMSE values for local skin and clothing layer temperatures are no higher than 1.5 °C and most within 0.8 °C. The model is also validated with published data under various ambient temperature and activity intensity conditions. The proposed model is shown to be capable of predict the thermo-physiological responses of people exposed and exercising in cold environments.

Nomogram based on autophagy related genes for predicting the survival in melanoma.

BACKGROUND: Autophagy, a highly conserved lysosomal degradation pathway, is associated with the prognosis of melanoma. However, prognostic prediction models based on autophagy related genes (ARGs) have never been recognized in melanoma. In the present study, we aimed to establish a novel nomogram to predict the prognosis of melanoma based on ARGs signature and clinical parameters. METHODS: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were extracted to identify the differentially expressed ARGs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate analysis were used to select the prognostic ARGs. ARGs signature, age and stage were then enrolled to establish a nomogram to predict the survival probabilities of melanoma. The nomogram was evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram and TNM stage model. The nomogram was validated in GEO cohorts. RESULTS: Five prognostic ARGs were selected to construct ARGs signature model and validated in the GEO cohort. Kaplan-Meier survival analysis suggested that patients in high-risk group had significantly worse overall survival than those in low-risk group in TCGA cohort (P = 5.859 × 10-9) and GEO cohort (P = 3.075 × 10-9). We then established and validated a novel promising prognostic nomogram through combining ARGs signature and clinical parameters. The C-index of the nomogram was 0.717 in TCGA training cohort and 0.738 in GEO validation cohort. TCGA/GEO-based ROC curve and decision curve analysis (DCA) demonstrated that the nomogram was better than traditional TNM staging system for melanoma prognosis. CONCLUSION: We firstly developed and validated an ARGs signature based-nomogram for individualized prognosis prediction in melanoma patients, which could assist with decision making for clinicians.

g-C3N4/Pt/BiVO4 nanocomposites for highly efficient visible-light photocatalytic removal of contaminants and hydrogen generation.

Inspired by natural photosynthesis, artificial heterojunction photocatalysts have been extensively studied. Herein, a novel ternary graphitic carbon nitride/platinum/bismuth vanadate (g-C3N4/Pt/BiVO4) photocatalytic system was successfully synthesized, where Pt/BiVO4 nanosheet is anchored on the surface of layered g-C3N4, as evidenced by structural observations. Ultraviolet photoelectron spectroscopy and ultraviolet-visible diffuse reflectance spectroscopy are carried out to identify the position of the conduction band and valence band. A Z-scheme is used to interpret the superior photocatalytic performance of g-C3N4/Pt/BiVO4 and further verified by the capture of free radicals and terephthalic acid photoluminescence experiments. Compared with the g-C3N4/BiVO4 binary system, the Z-scheme g-C3N4/Pt/BiVO4 photocatalyst not only possesses enhanced carrier separation efficiency but also maintains sufficient redox properties, thus inducing superior photocatalytic activity. More importantly, the novel Z-scheme photocatalyst exhibits excellent recycle stability, which could provide inspiration for the rational design of efficient and practical photocatalysts for environmental pollution treatment. The ternary photocatalyst also exhibits significantly enhanced visible-light photocatalytic hydrogen production performance.

Targeted degradation of CD147 proteins in melanoma.

CD147 is a transmembrane glycoprotein and a member of immunoglobulin superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6a could be used as the novel type of anticancer agent or as a part of the molecular biology research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.

Registration of Vehicle-Borne Point Clouds and Panoramic Images Based on Sensor Constellations.

A mobile mapping system (MMS) is usually utilized to collect environmental data on and around urban roads. Laser scanners and panoramic cameras are the main sensors of an MMS. This paper presents a new method for the registration of the point clouds and panoramic images based on sensor constellation. After the sensor constellation was analyzed, a feature point, the intersection of the connecting line between the global positioning system (GPS) antenna and the panoramic camera with a horizontal plane, was utilized to separate the point clouds into blocks. The blocks for the central and sideward laser scanners were extracted with the segmentation feature points. Then, the point clouds located in the blocks were separated from the original point clouds. Each point in the blocks was used to find the accurate corresponding pixel in the relative panoramic images via a collinear function, and the position and orientation relationship amongst different sensors. A search strategy is proposed for the correspondence of laser scanners and lenses of panoramic cameras to reduce calculation complexity and improve efficiency. Four cases of different urban road types were selected to verify the efficiency and accuracy of the proposed method. Results indicate that most of the point clouds (with an average of 99.7%) were successfully registered with the panoramic images with great efficiency. Geometric evaluation results indicate that horizontal accuracy was approximately 0.10-0.20 m, and vertical accuracy was approximately 0.01-0.02 m for all cases. Finally, the main factors that affect registration accuracy, including time synchronization amongst different sensors, system positioning and vehicle speed, are discussed.

Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time.

It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC50: 149 ± 6.0 µmol/L; hesperidin, 52.4 µmol/L; kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time, IC50 notably reached 2.9 ± 0.5 µmol/L), two polyphenols (chlorogenic acid, 3150 ± 120 µmol/L; caffeic acid, 1394 ± 52 µmol/L), two lignans (phillyrin, promoter; arctigenin, 2129 ± 10.5 µmol/L), and two phenethyl alcohol (forsythiaside A, 2155 ± 8.5 µmol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase.

Exposure to various abscission-promoting treatments suggests substantial ERF subfamily transcription factors involvement in the regulation of cassava leaf abscission.

BACKGROUND: Cassava plants (Manihot esculenta Crantz) have obvious abscission zone (AZ) structures in their leaf pulvinus-petioles. Cassava leaf abscission can be triggered by either 17 days of water-deficit stress or 4 days of ethylene treatment. To date, little is known about cassava AP2/ERF factors, and less is known regarding their roles in regulating abscission zone development. RESULTS: Here, the cassava and Arabidopsis AP2/ERF genes were compared, finding that the cassava genome contains approximately 1.54-fold more ERF subfamily than the Arabidopsis genome. Microarray analysis was used to identify the AP2/ERF genes that are expressed in cassava leaf pulvinus-petiole abscission zones by comparing the AP2/ERF gene expression profiles of ethylene- and water-deficit stress-induced leaf abscission. In total, 99 AP2/ERF genes were identified as expressed in AZs across six time points during both ethylene- and water-deficit stress-induced leaf abscission. Comparative expression profile analysis of similar SOTA (Self Organizing Tree Algorithm) clusters at six time points during ethylene- and water-deficit stress-induced leaf abscission demonstrated that 20 ERF subfamily genes had similar expression patterns in response to both treatments. GO (Gene Ontology) annotation confirmed that all 20 ERF subfamily genes participate in ethylene-mediated signalling. Analysis of the putative ERF promoter regions shown that the genes contained primarily ethylene- and stress-related cis-elements. Further analysis of ACC oxidase activity in AZs across six time points during abscission shown increased ethylene production in response to both ethylene and water-deficit stress; however, the difference was more dramatic for water-deficit stress. Finally, the expression ratios of 20 ERF subfamily genes were analysed in two cassava cultivars, 'KU50' and 'SC5', that exhibit different levels of leaf abscission when challenged with the same water-deficit stress. The analysis indicated that most of the ERF genes were expressed at higher levels in the precocious abscission 'KU50' cultivar than in the delayed abscission 'SC5' cultivar. CONCLUSION: Ccomparative analysis of both ethylene- and water-deficit stress-induced leaf abscission shown that the ERF subfamily functions in the regulation of cassava abscission zone development.

Copper-based electro-catalytic nitrate reduction to ammonia from water: Mechanism, preparation, and research directions.

Global water bodies are increasingly imperiled by nitrate pollution, primarily originating from industrial waste, agricultural runoffs, and urban sewage. This escalating environmental crisis challenges traditional water treatment paradigms and necessitates innovative solutions. Electro-catalysis, especially utilizing copper-based catalysts, known for their efficiency, cost-effectiveness, and eco-friendliness, offer a promising avenue for the electro-catalytic reduction of nitrate to ammonia. In this review, we systematically consolidate current research on diverse copper-based catalysts, including pure Cu, Cu alloys, oxides, single-atom entities, and composites. Furthermore, we assess their catalytic performance, operational mechanisms, and future research directions to find effective, long-term solutions to water purification and ammonia synthesis. Electro-catalysis technology shows the potential in mitigating nitrate pollution and has strategic importance in sustainable environmental management. As to the application, challenges regarding complexity of the real water, the scale-up of the commerical catalysts, and the efficient collection of produced NH3 are still exist. Following reseraches of catalyst specially on long term stability and in situ mechanisms are proposed.

Enhanced electrochemical nitrate reduction on copper nitride with moderate intermediates adsorption.

Nitrate in surface and underground water caused systematic risk to the ecological environment. The electrochemically reduction of nitrate into ammonia (NO3RR), offering a sustainable route for nitrate containing wastewater treatment and ammonia fertilizer conversion. Exploration of catalyst with improved catalytic activity with lower energy barriers is still challenging. Here, we report a copper nitride (Cu3N) catalyst with moderate *NOx and *H2O intermediates adsorptions showed enhanced NO3RR performance. Density functional theory calculations reveals that the unique electronic structure of Cu3N provides efficient active sites for NO3RR, thus enabled balanced adsorption of *NO3 and *H2O (ΔE descriptor), sufficient active hydrogen, and moderate intermediate (*NO3 â†’ HNO3, *NH2→*NH3) adsorption energy. Notably, the in-situ analysis technology revealed potential-driven reconstruction and rehabilitation of Cu3N, forming possible nitrogen vacancy, thus implied for better mechanism understanding. The NO3RR activity of Cu3N surpasses that of most recent catalysts and demonstrates superior stability and implies the application for NH4+ fertilizer recovery, which maintaining an NH3 Faradaic efficiency of 93.1 % and high yield rate of 2.9 mg cm2h-1 at -0.6 V versus RHE. These findings broaden the application scenarios of Cu3N catalyst for ammonia synthesis and provide strategy on improving NO3RR performance.

Numerical study of transient indoor airflow and virus-laden droplet dispersion: Impact of interactive human movement.

Human movement affects indoor airflow and the airborne transmission of respiratory infectious diseases, which has attracted scholars. However, the interactive airflow between moving and stationary people has yet to be studied in detail. This study used the numerical method validated by experimental data to explore the transient indoor airflow and virus-laden droplet dispersion in scenes with interactive human movement. Human-shaped numerical models and the dynamic mesh method were adopted to realize human movement in scenes with different lateral distances (0.2-1.2 m) between a moving person and stationary (standing/sitting) persons. The interactive human movement obviously impacts other persons' respiratory airflow, and the lateral fusion ranged about 0.6 m. The interactive human movement strengthens the indoor airflow convection, and some exhaled virus-laden droplets were carried into wake flow and enhanced long-range airborne transmission. The impact of interactive human movement on sitting patients' exhalation airflow seems more evident than on standing patients. The impact might last over 2 min after movement stopped, and people in the affected area might be at a higher exposure. The results can provide a reference for epidemic control in indoor environments.

Design, synthesis and evaluation of a myricetin and nobiletin hybrid compound for alleviating hyperuricemia based on metabolomics and gut microbiota.

Hyperuricemia (HUA) is the fourth most common basic metabolic disease that can cause damage to multiple organs throughout the body. In this study, a hybrid compound consisting of myricetin and nobiletin was synthesized and its biological activity was evaluated. We named the hybrid compound MNH, and its structure was confirmed by spectroscopy. This study used serum metabolomics profiling with LC/MS and 16S rRNA gene sequencing analysis to explore the anti-HUA efficacy of MNH on a yeast paste-induced mouse model. The results showed that serum uric acid (UA), creatinine (CRE) and urea nitrogen (BUN) levels were significantly decreased after the intervention of MNH. The efficacy of MNH in lowering UA was somewhat greater than that of myricetin and nobiletin. In addition, MNH could repair the renal histopathological damage. Moreover, serum metabolomics demonstrated that MNH regulated the metabolic pathways involved in glycerophospholipid metabolism, arachidonic acid metabolism and alanine etc. Furthermore, MNH supplementation restored the composition of gut microbiota with remarkable reductions in Lactobacillus and Limosilactobacillus and significant elevations in norank_f_Muribaculaceae and Bacteroides at the genus level. Taken together, these results indicated that MNH might represent a protective effect against HUA via modulating gut microbiota and metabolomics.

BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.

Targeting bromodomain and extra-terminal domain (BET) proteins has shown a promising therapeutic effect on melanoma. The development of strategies to better kill melanoma cells with BET inhibitor treatment may provide new clinical applications. Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. We further demonstrated that BET inhibitors synergize with sunitinib in melanoma by inducing apoptosis and cell cycle arrest. Mechanistically, BET inhibitors sensitize melanoma cells to sunitinib by inhibiting GDF15 expression. Strikingly, GDF15 is transcriptionally regulated directly by BRD4 or indirectly by the BRD4/IL6/STAT3 axis. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.

Identification of a Novel Tumor Inflammation Signature for Risk Stratification, Prognosis Prediction, and Immune Status in Colorectal Cancer.

Background: Inflammation and immune cell dysfunction have been widely known as an essential role in the tumorigenesis of colorectal cancer (CRC). Yet, the role of tumor inflammation signature (TIS) associated with CRC prognosis, immune infiltration, and drug resistance remained unknown. Method: The transcriptome sequencing data, as well as clinical data of CRC from the public dataset, were acquired for further investigation. Inflammation-related gene expression patterns were obtained and analyzed. Bioinformatics methods were used to build a prognostic TIS, and its prediction accuracy was verified by using ROC curve analyses. The independent prognostic factors in CRC were identified through multivariable Cox regression analysis. In addition, the specific features of the immunological landscape between low- and high-risk CRC cohorts were analyzed. Results: We firstly screened the differentially expressed inflammation-related genes in CRC and constructed a prognostic TIS. We further classified CRC patients into high or low TIS score groups based on the optimal cutoff of prognostic TIS, and patients with high-risk scores had shorter overall survival (OS) than those in the low-risk cohort. The diagnostic accuracy of TIS was evaluated and confirmed with ROC analysis. The result of the univariate and multivariate analysis found that TIS was directly and independently linked to OS of CRC. Otherwise, an optimal nomogram model based on TIS exhibited a better prognostic accuracy in OS. Finally, the immunological status and immune cell infiltration were observed different in the two-risk cohorts. Conclusion: In summary, the risk model of the TIS in CRC was found to be useful for predicting patient prognosis and guiding individual treatment. This risk signature could also serve as potential biomarkers and immunotherapeutic targets and indicate immunotherapy response for patients with CRC.

Melanoma survivors are at increased risk for second primary keratinocyte carcinoma.

BACKGROUND: Recent large cohorts have reported that melanoma survivors are at risk of developing second keratinocyte carcinoma (KC). However, the detailed proportion and risk are still unknown. We aimed to comprehensively analyze the risk of developing keratinocyte carcinoma after primary melanoma. METHODS: We conducted systematic literature research in PubMed, Embase, Web of Science, and Cochrane Library published prior to September 13, 2021. Proportion and standardized incidence ratios (SIR) with its corresponding 95% confidence interval (CI) were pooled for assessing the risk. RESULTS: A total of 15 studies encompassing 168,286 patients were included in our analysis. The pooled proportions of melanoma survivors that developed a subsequent basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and KC were 4.11% (95% CI, 1.32-6.90), 2.54% (95% CI, 1.78-3.31), and 5.45% (95% CI, 3.06-7.84), respectively. The risks of developing a second BCC, SCC, and KC in melanoma survivors were 5.3-fold (SIR 5.30; 95% CI, 4.87-5.77), 2.6-fold (SIR 2.58; 95% CI, 1.33-5.04), and 6.2-fold (SIR 6.17; 95% CI, 3.66-10.39) increased in comparison with the general population. Both fixed effects and random effects models were applied in conducting meta-analysis and reached a consistent conclusion. CONCLUSIONS: Our results indicated melanoma survivors are at elevated risk of experiencing second primary BCC and SCC, which suggested the significance of surveillance for second primary KC and efforts for prevention in patients with a history of melanoma.

The Prognostic Significance of Baseline Neutrophil-to-Lymphocyte Ratio in Melanoma Patients Receiving Immunotherapy.

Immunotherapy has revolutionized the treatment in metastatic melanoma, but alternative biomarkers that are economical, simple and reliable still need to be clarified. In this study, we aimed to comprehensively analyze the prognostic significance of baseline neutrophil-to-lymphocyte ratio (NLR) in melanoma patients with immunotherapy. We searched PubMed, Embase, and Cochrane Library until September 16, 2020. Hazard ratio (HR) and 95% confidence intervals (CIs) were pooled to investigate the association of baseline NLR with overall survival (OS) and progression-free survival (PFS). Sensitivity analysis, subgroup analyses, publication bias assessment, and the Duval and Tweedie trim-and-fill method were used to evaluate the stability of results. A total of 18 studies including 2054 patients were included in our analysis. Pooled data demonstrated that higher baseline NLR was associated with a poorer OS (HR=2.46, 95% CI=1.77, 3.43) and PFS (HR=2.38, 95% CI=1.95, 2.89) of melanoma patients receiving immunotherapy. Subgroup analysis according to immunotherapy type showed that the prognostic effects of baseline NLR existed in all the subtypes of immunotherapy, including anticytotoxic T lymphocyte-associated protein 4 therapy (OS HR=2.26, 95% CI=1.43, 3.59; PFS HR=2.68, 95% CI=1.79, 4.02), antiprogrammed cell death-1 therapy (OS HR=3.08, 95% CI=2.21, 4.27; PFS HR=2.01, 95% CI=1.64, 2.47), and combination therapy (OS HR=1.75, 95% CI=1.13, 2.72; PFS HR=3.13, 95% CI=1.63, 6.03). Conclusions were still consistent in subgroup analyses stratified by study year, region, study type, sample size, analysis of HR and cuttoff of baseline NLR. Altogether, baseline NLR is a promising prognostic biomarker for melanoma patients receiving immunotherapy.

The risk of developing second primary malignancies among colorectal cancer patients.

BACKGROUND: The increasing number of young colorectal cancer (CRC) survivors has led to ongoing concerns about the risk of secondary primary malignancies (SPMs). Here, we intended to comprehensively explore the pooled standardized incidence rates (SIRs) for total and site-specific SPMs in CRC survivors with different restriction to lag period. METHODS: Pubmed, Embase, Cochrane Library, and Web of science databases were searched to identify any studies reporting the SIRs of SPM following CRC until August 2021. Total and site-specific SIRs with different restriction to lag period were pooled using fixed/random effect models. RESULTS: A total of 42 full-text publications with more than 1, 524, 236 CRC survivors and 166, 210 SPM patients were included in the meta-analysis. Pooled data showed an increased SIRs for all SPMs in CRC survivors with different restriction to lag period (no restriction to lag period, SIR = 1.15, 95% CI = [1.08-1.23]; 1-year lag, 1.16 [1.10-1.23]; 5-year lag, 1.18 [1.09-1.28]; 10-year lag, 1.24 [1.11-1.39]). The conclusions were consistent for neoplasms of colorectum, corpus uteri, and small intestine with different restriction to lag period. However, limited evidence was presented for associations between CRC survivors and SPM for prostate, breast (female), ovarian, stomach, urinary bladder, kidney, thyroid, bone and soft tissue. CONCLUSION: CRC survivors are associated with an increased risk of SPMs, especially neoplasms of colorectum, corpus uteri, and small intestine. Further studies should explore the risks for these neoplasms in CRC survivors, thus providing the reference for future follow-up care.