Pericyte in retinal vascular diseases: A multifunctional regulator and potential therapeutic target.

Retinal vascular diseases (RVDs), in particular diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity, are leading contributors to blindness. The pathogenesis of RVD involves vessel dilatation, leakage, and occlusion; however, the specific underlying mechanisms remain unclear. Recent findings have indicated that pericytes (PCs), as critical members of the vascular mural cells, significantly contribute to the progression of RVDs, including detachment from microvessels, alteration of contractile and secretory properties, and excessive production of the extracellular matrix. Moreover, PCs are believed to have mesenchymal stem properties and, therefore, might contribute to regenerative therapy. Here, we review novel ideas concerning PC characteristics and functions in RVDs and discuss potential therapeutic strategies based on PCs, including the targeting of pathological signals and cell-based regenerative treatments.

Mapping Capillary Infiltration-Induced Potential in Water-Triggered Electric Generator Using an Electrical Probe Integrated Microscope.

Power generation from water-triggered capillary action in porous structures has recently geared extensive attention, offering the potential for generating electricity from ubiquitous water evaporation. However, conclusively establishing the nature of electrical generation and charge transfer is extremely challenging arising from the complicated aqueous solid-liquid interfacial phenomenon. Here, an electric probe-integrated microscope is developed to on-line monitor the correlation between water capillary action and potential values at any desired position of an active layer. With a probe spatial resolution reaching up to fifty micrometers, the internal factors prevailing over the potential distribution across the whole wet and dry regions are comprehensively identified. Further, the self-powered sensing capabilities of this integrated system are also demonstrated, including real-time monitoring of wind speed, environmental humidity, ionic strength, and inclination angle of generators. The combination of electric potential and chemical color indicator suggests that charge generation is likely correlated with ion-selective transport in the nanoporous channel during the water infiltration process. And unipolar ions (for instance protons) should be the dominant charge-transfer species. The work reveals the fundamental principles regulating charge generation/transfer during the water-triggered electric generation process.

Intestinal microbiota and metabolome perturbations in ischemic and idiopathic dilated cardiomyopathy.

BACKGROUND: Various clinical similarities are present in ischemic (ICM) and idiopathic dilated cardiomyopathy (IDCM), leading to ambiguity on some occasions. Previous studies have reported that intestinal microbiota appeared dysbiosis in ICM, whether implicating in the IDCM remains unclear. The aim of this study was to assess the alterations in intestinal microbiota and fecal metabolites in ICM and IDCM. METHODS: ICM (n = 20), IDCM (n = 22), and healthy controls (HC, n = 20) were enrolled in this study. Stool samples were collected for 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Both ICM and IDCM exhibited reduced alpha diversity and altered microbial community structure compared to HC. At the genus level, nine taxa including Blautia, [Ruminococcus]_torques_group, Christensenellaceae_R-7_group, UCG-002, Corynebacterium, Oceanobacillus, Gracilibacillus, Klebsiella and Citrobacter was specific to ICM, whereas one taxa Alistipes uniquely altered in IDCM. Likewise, these changes were accompanied by significant metabolic differences. Further differential analysis displayed that 18 and 14 specific metabolites uniquely changed in ICM and IDCM, respectively. The heatmap was generated to display the association between genera and metabolites. Receiver operating characteristic curve (ROC) analysis confirmed the predictive value of the distinct microbial-metabolite features in disease status. The results showed that microbial (area under curve, AUC = 0.95) and metabolic signatures (AUC = 0.84) were effective in discriminating ICM from HC. Based on the specific microbial and metabolic features, the patients with IDCM could be separated from HC with an AUC of 0.80 and 0.87, respectively. Furthermore, the gut microbial genus (AUC = 0.88) and metabolite model (AUC = 0.89) were comparable in predicting IDCM from ICM. Especially, the combination of fecal microbial-metabolic features improved the ability to differentiate IDCM from ICM with an AUC of 0.96. CONCLUSION: Our findings highlighted the alterations of gut microbiota and metabolites in different types of cardiomyopathies, providing insights into the pathophysiological mechanisms of myocardial diseases. Moreover, multi-omics analysis of fecal samples holds promise as a non-invasive tool for distinguishing disease status.

Research on the removal characteristics of surface error with different spatial frequency based on shear thickening polishing method.

X-ray mirrors, which are essential for constructing synchrotron radiation light sources, are highly required for full-range spatial wavelength errors. This paper investigated power-law non-Newtonian fluids and pointed out that both three-body removal and shear removal existed in the shear thickening polishing process. Subsequently, this paper calculates the shear force of the power-law non-Newtonian fluid polishing fluid in polishing the surface with different frequency errors. It establishes an MRR model of shear thickening polishing in the frequency domain by combining it with the Archard equation. Then, this model is also applied to optimize the polishing fluid formulation and processing parameters. Finally, the removal effect of the optimized polishing fluid on the mid-frequency ripple error is experimentally verified. On Ф50 mm monocrystalline silicon, the removal of mid-frequency ripple error with a spatial wavelength of 1 mm was achieved by shear thickening polishing technique while converging the surface roughness to 0.14 nm. Finally, the experimental results were applied to monocrystalline silicon with a length of 500 mm. This work provides a new research idea for the existing shear thickening polishing process. It provides theoretical and technical support for removing the mid- and high-frequency errors in high-precision X-ray mirrors.

First-principles study of magnetic properties and electronic structure of 3d transition-metal atom-adsorbed SnSSe monolayers.

We investigated the electronic structure and magnetic characteristics of 3d transition metal elements (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) adsorbed onto monolayer SnSSe by employing first-principles calculations. After the calculation, we found that Sc, Ti, V, Cu, and Zn atoms adsorbed onto monolayer SnSSe do not have magnetic moments, while the rest of the atoms adsorbed onto SnSSe are able to produce magnetic moments, and their magnetic moments in the adsorption systems are in the range of 1.0-3.0 µB, in which the magnetic distance of Mn is the largest. The results of MAE calculations indicate that there is a big difference in the MAE of the systems with TM atoms adsorbed to the S-side and the Se-side; for V adsorbed to the S-side on the Sn atoms, the MAE is the largest, which reaches 8.277 meV f.u.-1, showing an in-plane magnetic anisotropy, and for Co adsorbed to the Se-side on the Sn atoms, the MAE is the smallest, which is -0.673 meV f.u.-1, showing a perpendicular magnetic anisotropy. Calculations of binding energies show that all atoms are able to adsorb stably. Our results indicate the potential application of TM-adsorbed SnSSe monolayers in spintronics and magnetic memory devices.

Disparities in Genetic Diversity Drive the Population Displacement of Two Invasive Cryptic Species of the Bemisia tabaci Complex in China.

Within the whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) complex, two cryptic species, namely Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED), are important invasive pests affecting global agriculture and horticulture. They were introduced into China sequentially in the mid-1990s and around 2003, respectively. Subsequently, the latter invader MED has outcompeted the earlier invader MEAM1, becoming the dominant population in the field. Although extensive studies have explored the underlying mechanisms driving this shift, the contribution of population genetics remains notably underexplored. In this study, we analyzed the genetic diversity and structure of 22 MED and 8 MEAM1 populations from various regions of China using mitochondrial DNA sequencing and microsatellite genotyping. Our results indicate low and moderate levels of genetic differentiation among geographically separate populations of MED and MEAM1, respectively. Median-joining network analysis of mtCOI gene haplotypes revealed no clear geographic structuring for either, with common haplotypes observed across provinces, although MED had more haplotypes. Comparative analyses revealed that MED presented greater genetic diversity than MEAM1 on the basis of two markers. Furthermore, analysis of molecular variance supported these findings, suggesting that while some genetic variation exists between populations, a significant amount is also present within populations. These findings reveal the population genetics of the two invasive cryptic species of the B. tabaci complex in China and suggest that the disparities in genetic diversity drive the displacement of their populations in the field. This work also provides valuable information on the genetic factors influencing the population dynamics and dominance of these invasive whitefly species.

Fluorine Passivation Inhibits "Particle Talking" Behaviors under Thermal and Electrical Conditions of Pure Blue Mixed Halide Perovskite Nanocrystals.

Owing to outstanding optoelectronic properties, lead halide perovskite nanocrystals (PNCs) are considered promising emitters for next-generation displays. However, the development of pure blue (460-470 nm) perovskite nanocrystal light-emitting diodes (PNC-LEDs), which correspond to the requirements of Rec. 2020 standard, lag far behind that of their green and red counterparts. Here, pure blue CsPb(Br/Cl)3 nanocrystals with remarkable optical performance are demonstrated by a facile fluorine passivation strategy. Prominently, the fluorine passivation on halide vacancies and strong bonding of Pb-F intensely enhance crystal structure stability and inhibit "particle talking" behaviors under both thermal and electrical conditions. Fluorine-based PNCs with high resistance of luminescence thermal quenching retain 70% of photoluminescent intensity when heated to 343 K, which can be attributed to the elevated activation energy for carrier trapping and unchanged grain size. Fluorine-based PNC-LEDs also exhibit stable pure blue electroluminescence (EL) emission with sevenfold promoted luminance and external quantum efficiencies (EQEs), where the suppression of ion migration is further evidenced by a lateral structure device with applied polarizing potential.

Synergistic Solar-Driven Freshwater Generation and Electricity Output Empowered by Wafer-Scale Nanostructured Silicon.

Electricity generation triggered by the ubiquitous water evaporation process provides an intriguing way to harvest energy from water. Meanwhile, natural water evaporation is also a fundamental way to obtain fresh water for human beings. Here, a wafer-scale nanostructured silicon-based device that takes advantage of its well-aligned configuration that simultaneously realizes solar steam generation (SSG) for freshwater collection and hydrovoltaic effect generation for electricity output is developed. An ingenious porous, black carbon nanotube fabric (CNF) electrode endows the device with sustainable water self-pumping capability, excellent durable conductivity, and intense solar spectrum harvesting. A combined device based on the CNF electrode integrated with nanostructured silicon nanowire arrays (SiNWs) provided an aligned numerous surface-to-volume water evaporation interface that enables a recorded continuous short-circuit current 8.65 mA and a water evaporation rate of 1.31 kg m-2 h-1 under one sun illumination. Such wafer-scale SiNWs-based SSG and hydrovoltaic integration devices would unchain the bottleneck of the weak and discontinuous electrical output of hydrovoltaic devices, which inspires other sorts of semiconductor-based hydrovoltaic device designs to target superior performance.

Novel models by machine learning to predict prognosis of breast cancer brain metastases.

BACKGROUND: Breast cancer brain metastases (BCBM) are the most fatal, with limited survival in all breast cancer distant metastases. These patients are deemed to be incurable. Thus, survival time is their foremost concern. However, there is a lack of accurate prediction models in the clinic. What's more, primary surgery for BCBM patients is still controversial. METHODS: The data used for analysis in this study was obtained from the SEER database (2010-2019). We made a COX regression analysis to identify prognostic factors of BCBM patients. Through cross-validation, we constructed XGBoost models to predict survival in patients with BCBM. Meanwhile, a BCBM cohort from our hospital was used to validate our models. We also investigated the prognosis of patients treated with surgery or not, using propensity score matching and K-M survival analysis. Our results were further validated by subgroup COX analysis in patients with different molecular subtypes. RESULTS: The XGBoost models we created had high precision and correctness, and they were the most accurate models to predict the survival of BCBM patients (6-month AUC = 0.824, 1-year AUC = 0.813, 2-year AUC = 0.800 and 3-year survival AUC = 0.803). Moreover, the models still exhibited good performance in an externally independent dataset (6-month: AUC = 0.820; 1-year: AUC = 0.732; 2-year: AUC = 0.795; 3-year: AUC = 0.936). Then we used Shiny-Web tool to make our models be easily used from website. Interestingly, we found that the BCBM patients with an annual income of over USD$70,000 had better BCSS (HR = 0.523, 95%CI 0.273-0.999, P < 0.05) than those with less than USD$40,000. The results showed that in all distant metastasis sites, only lung metastasis was an independent poor prognostic factor for patients with BCBM (OS: HR = 1.606, 95%CI 1.157-2.230, P < 0.01; BCSS: HR = 1.698, 95%CI 1.219-2.365, P < 0.01), while bone, liver, distant lymph nodes and other metastases were not. We also found that surgical treatment significantly improved both OS and BCSS in BCBM patients with the HER2 + molecular subtypes and was beneficial to OS of the HR-/HER2- subtype. In contrast, surgery could not help BCBM patients with HR + /HER2- subtype improve their prognosis (OS: HR = 0.887, 95%CI 0.608-1.293, P = 0.510; BCSS: HR = 0.909, 95%CI 0.604-1.368, P = 0.630). CONCLUSION: We analyzed the clinical features of BCBM patients and constructed 4 machine-learning prognostic models to predict their survival. Our validation results indicate that these models should be highly reproducible in patients with BCBM. We also identified potential prognostic factors for BCBM patients and suggested that primary surgery might improve the survival of BCBM patients with HER2 + and triple-negative subtypes.

Survival comparison of first-line treatment regimens in patients with braf-mutated advanced colorectal cancer: a multicenter retrospective study.

BACKGROUND: Patients with V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E-mutated advanced colorectal cancer (CRC) have a poor prognosis, and treatment options that can improve outcome are still under investigation. The purpose of this study was to discuss the differences of overall survival (OS) and progression-free survival (PFS) between patients with BRAF V600E-mutated advanced CRC who were treated with chemotherapy alone and chemotherapy combined with targeted therapy in advanced first-line therapy. METHODS: Grouping of 61 patients according to first-line treatment regimen (chemotherapy alone/chemotherapy combined with bevacizumab). Kaplan-Meier method and log-rank test were used to compare OS and PFS. Cox proportional hazards regression model was used to measure the risk of first-line medication therapies while correcting for confounding factors that may affect PFS and OS. RESULTS: There was no significant difference in OS between patients treated with chemotherapy alone and those treated with chemotherapy combined with bevacizumab (P = 0.93; HR, 1.027; 95% CI, 0.555-1.901). Likewise, there was no significant difference in PFS between the two groups (P = 0.29; HR, 0.734; 95% CI, 0.413-1.304). Subgroup analysis showed that OS and PFS of different treatment regimens were not significantly different among subgroups. Multivariate analysis suggested that surgical treatment of primary tumor (P = 0.001; HR, 0.326; 95% CI, 0.169-0.631) and presence of liver metastasis (P = 0.009; HR, 2.399; 95% CI, 1.242-4.635) may serve as independent prognostic indicators in patients with BRAF-mutated advanced CRC. Surgical treatment of the primary tumor (P = 0.041; HR, 0.523; 95% CI, 0.280-0.974) was significantly associated with PFS too. CONCLUSION: For patients with BRAF V600E-mutated advanced CRC, chemotherapy alone did not differ significantly in OS and PFS compared with chemotherapy + bevacizumab for advanced first-line therapy. Chemotherapy combined with targeted therapy did not render a survival benefit to these patients, demonstrating that the importance of developing new treatment options for this population.

SIRT2 inhibition attenuates the vasculopathy and vision impairment via Akt signaling in retinopathy of prematurity.

Despite decades of researches, the underlying mechanism of retinopathy of prematurity (ROP) remains unclear. The role of Sirt2, which is involved in both angiogenesis and inflammation, both pivotal in ROP, was investigated in an animal model of ROP known as oxygen-induced retinopathy (OIR). Our study found that Sirt2 was overexpressed and colocalized with microglia in OIR. Furthermore, it demonstrated that the level of Sirt2 was upregulated in hypoxia microglia BV-2 in vitro. Subsequently, our results elucidated that administration of the Sirt2 antagonist AGK2 attenuated the avascular and neovascular area and downregulated the expression of IGF-1. The phosphorylation of Akt and the expression of IGF-1 were upregulated in hypoxia BV-2 and conditional media collected from BV-2 under hypoxia promoted the migration and tube formation of retinal capillary endothelial cells, which were suppressed with AGK2. Notably, our findings are the first to demonstrate the deleterious role of Sirt2 in ROP, as Sirt2 inhibition led to the downregulation of Akt/IGF-1 and ameliorated vasculopathy, ultimately improving visual function. These results suggest that Sirt2 may be a promising therapeutic target for ROP.

Stress granule activation attenuates lipopolysaccharide-induced cardiomyocyte dysfunction.

BACKGROUND: Sepsis is the leading cause of death in intensive care units. Sepsis-induced myocardial dysfunction, one of the most serious complications of sepsis, is associated with higher mortality rates. As the pathogenesis of sepsis-induced cardiomyopathy has not been fully elucidated, there is no specific therapeutic approach. Stress granules (SG) are cytoplasmic membrane-less compartments that form in response to cellular stress and play important roles in various cell signaling pathways. The role of SG in sepsis-induced myocardial dysfunction has not been determined. Therefore, this study aimed to determine the effects of SG activation in septic cardiomyocytes (CMs). METHODS: Neonatal CMs were treated with lipopolysaccharide (LPS). SG activation was visualized by immunofluorescence staining to detect the co-localization of GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and T cell-restricted intracellular antigen 1 (TIA-1). Eukaryotic translation initiation factor alpha (eIF2α) phosphorylation, an indicator of SG formation, was assessed by western blotting. Tumor necrosis factor alpha (TNF-α) production was assessed by PCR and enzyme-linked immunosorbent assays. CMs function was evaluated by intracellular cyclic adenosine monophosphate (cAMP) levels in response to dobutamine. Pharmacological inhibition (ISRIB), a G3BP1 CRISPR activation plasmid, and a G3BP1 KO plasmid were employed to modulate SG activation. The fluorescence intensity of JC-1 was used to evaluate mitochondrial membrane potential. RESULTS: LPS challenge in CMs induced SG activation and resulted in eIF2α phosphorylation, increased TNF-α production, and decreased intracellular cAMP in response to dobutamine. The pharmacological inhibition of SG (ISRIB) increased TNF-α expression and decreased intracellular cAMP levels in CMs treated with LPS. The overexpression of G3BP1 increased SG activation, attenuated the LPS-induced increase in TNF-α expression, and improved CMs contractility (as evidenced by increased intracellular cAMP). Furthermore, SG prevented LPS-induced mitochondrial membrane potential dissipation in CMs. CONCLUSION: SG formation plays a protective role in CMs function in sepsis and is a candidate therapeutic target.

Experimental Evidence of Superdiffusive Thermal Transport in Si0.4Ge0.6 Thin Films.

Superdiffusive thermal transport represents a unique phenomenon in heat conduction, which is characterized by a size (L) dependence of thermal conductivity (κ) in the form of κ ∝ Lß with a constant ß between 0 and 1. Although superdiffusive thermal transport has been theoretically predicted for SiGe alloys, direct experimental evidence is still lacking. Here, we report on a systematic experimental study of the thickness-dependent thermal conductivity of Si0.4Ge0.6 thin films grown by molecular beam epitaxy. The cross-plane thermal conductivity of Si0.4Ge0.6 thin films spanning a thickness range from 20 to 1120 nm was measured in the temperature range 120-320 K via a differential three-omega method. Results show that the thermal conductivity follows a consistent κ ∝ t0.26 power law with the film thickness (t) at different temperatures, providing direct experimental evidence that alloy-scattering dominated thermal transport in SiGe is superdiffusive.

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target.

Galectin-3 is the most studied member of the Galectin family, with a large range of mediation in biological activities such as cell growth, proliferation, apoptosis, differentiation, cell adhesion, and tissue repair, as well as in pathological processes such as inflammation, tissue fibrosis, and angiogenesis. As is known to all, inflammation, aberrant cell apoptosis, and neovascularization are the main pathophysiological processes in retinal degeneration and many ocular diseases. Therefore, the review aims to conclude the role of Gal3 in the retinal degeneration of various diseases as well as the occurrence and development of the diseases and discuss its molecular mechanisms according to research in systemic diseases. At the same time, we summarized the predictive role of Gal3 as a biomarker and the clinical application of its inhibitors to discuss the possibility of Gal3 as a novel target for the treatment of ocular diseases.

The Roles of CDPKs as a Convergence Point of Different Signaling Pathways in Maize Adaptation to Abiotic Stress.

The calcium ion (Ca2+), as a well-known second messenger, plays an important role in multiple processes of growth, development, and stress adaptation in plants. As central Ca2+ sensor proteins and a multifunctional kinase family, calcium-dependent protein kinases (CDPKs) are widely present in plants. In maize, the signal transduction processes involved in ZmCDPKs' responses to abiotic stresses have also been well elucidated. In addition to Ca2+ signaling, maize ZmCDPKs are also regulated by a variety of abiotic stresses, and they transmit signals to downstream target molecules, such as transport proteins, transcription factors, molecular chaperones, and other protein kinases, through protein interaction or phosphorylation, etc., thus changing their activity, triggering a series of cascade reactions, and being involved in hormone and reactive oxygen signaling regulation. As such, ZmCDPKs play an indispensable role in regulating maize growth, development, and stress responses. In this review, we summarize the roles of ZmCDPKs as a convergence point of different signaling pathways in regulating maize response to abiotic stress, which will promote an understanding of the molecular mechanisms of ZmCDPKs in maize tolerance to abiotic stress and open new opportunities for agricultural applications.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Real-world outcomes of regorafenib combined with immune checkpoint inhibitors in patients with advanced or metastatic microsatellite stable colorectal cancer: A multicenter study.

BACKGROUND: Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice. METHODS: We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715). RESULTS: Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07-3.69, P = 0.03) and neutrophil-lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00-7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%). CONCLUSION: The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.

Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer.

OBJECTIVE: To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy. METHODS: Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan-Meier curves. RESULTS: The median OS and PFS were 16.135 months (95% CI: 9.211-22.929) and 6 months (95% CI: 5.425-6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3-4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils. CONCLUSION: Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P = 0.0084) was associated with improved OS.Clinical Research Registration Number: ChiCTR1800015308.

The effect of HPV DNA and p16 status on the prognosis of patients with hypopharyngeal carcinoma: a meta-analysis.

OBJECTIVE: To evaluate whether the presence of human papillomavirus (HPV) DNA and p16 might be associated with better prognosis in patients with hypopharyngeal carcinoma (HPC), especially on overall survival (OS) and disease-free survival (DFS). METHOD: PubMed, the Cochrane Library, the Web of Science and EMBASE were searched from inception to April 2021 to search for HPV DNA- and p16-related prognostic articles on HPC. Meta-analysis was performed on the selected articles according to the inclusion and exclusion criteria. Publication bias was assessed for the included studies with Egger's test. All studies were analyzed by using Stata 16.0 statistical software. RESULTS: A total of 18 studies were included, including 12 HPV DNA studies and 11 p16 studies. Meta-analysis showed that HPV DNA positivity was a strong prognostic factor for improved OS in patients with HPC, with a pooled hazard ratio (HR) of 0.61 (95% CI, 0.54-0.69), but there was no statistically significant difference in DFS (HR, 0.60; 95% CI, 0.31-1.16). Patients with p16-positive tumors had better OS (HR, 0.66; 95% CI, 0.49-0.89) and DFS (HR, 0.59; 95% CI, 0.44-0.78) than patients with p16-negative tumors. CONCLUSIONS: This study suggests that the presence of HPV DNA leads to better OS in patients with HPC, and the presence of p16 also corresponds to better OS and DFS. Our results provide up-to-date evidence to clinicians and researchers. Larger studies adjusting for prognostic factors are needed in subsequent studies.

Rhodohalobacter sulfatireducens sp. nov., isolated from a marine solar saltern.

A novel Gram-stain-negative, oxidase-positive, catalase-positive, non-motile, facultatively anaerobic, rod-shaped bacterium, designated WB101T, was isolated from a marine solar saltern located in Wendeng, PR China. Strain WB101T shared a high level of 16S rRNA gene sequence similarity with Rhodohalobacter barkolensis 15182T (93.5%), R. halophilus JZ3C29T (93.2%), and 'R. mucosus' 8A47T (92.1%). Strain WB101T formed a species-level branch within the genus Rhodohalobacter in both phylogenetic and phylogenomic topologies. The DNA G + C content was 42.0%. Strain WB101T was found to have menaquinone-7 as the only respiratory quinone. The dominant cellular fatty acid (≥ 10%) was iso-C15:0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. Characterisation based on phylogenetic, physiological, and biochemical properties indicated that strain WB101T represents a novel species of the genus Rhodohalobacter, and the name Rhodohalobacter sulfatireducens sp. nov. is proposed. The type strain is WB101T (= KCTC 92204T = MCCC 1H00518T).