HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model. Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model. Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.

Homologous polydopamine ameliorates haemolysis of melittin for enhancing its anticancer efficacy.

Despite exhibiting potent anticancer activity, the strong hemolytic properties of melittin (MEL) significantly restrict its delivery efficiency and clinical applications. To address this issue, we have devised a strategy wherein homologous dopamine (DA), an essential component of bee venom, is harnessed as a vehicle for the synthesis of MEL-polydopamine (PDA) nanoparticles (MP NPs). The ingenious approach lies in the fact that MEL is a basic polypeptide, and the polymerization of DA is also conducted under alkaline conditions, indicating the distinctive advantages of PDA in MEL encapsulation. Furthermore, MP NPs are modified with folic acid to fabricate tumor-targeted nanomedicine (MPF NPs). MPF NPs can ameliorate the hemolysis of MEL in drug delivery and undergo degradation triggered by high levels of reactive oxygen species (ROS) within solid tumors, thereby facilitating MEL release and subsequent restoration of anticancer activity. After cellular uptake, MPF NPs induce cell apoptosis through the PI3K/Akt-mediated p53 signaling pathway. The tumor growth inhibitory rate of MPF NPs in FA receptor-positive 4T1 and CT26 xenograft mice reached 78.04% and 81.66%, which was significantly higher compared to that in FA receptor-negative HepG2 xenograft mice (45.79%). Homologous vehicles provide a new perspective for nanomedicine design.

[Characteristics of caries-related oral microorganisms in early childhood caries].

PURPOSE: To study the structural characteristics of oral microorganisms in children with caries by 16S rRNA high-throughput sequencing technology. METHODS: Thirty healthy children aged 3-5 years were enrolled as subjects. According to the index of dmfs, they were divided into caries-free (CF) group (15) and early childhood caries (ECC) group(15). To compare the differences in bacterial community structure, samples of saliva and dental plaque were collected, and high-throughput sequencing was conducted using the Illumina Miseq sequencing platform. Bioinformatics analysis was used to analyze the difference of microbial community structure and diversity with SPSS 23.0 software package. RESULTS: Microbial diversity in ECC group was significantly lower than CF group. At phylum level, Actinobateria was more abundant in saliva samples of ECC group, while Firmicutes was more abundant in plaque samples of CF group. At genus level, the abundance of Lautropia of CF group was higher in saliva samples while Cardiobacterium, Gemella and Granulicatella were abundant in plaque samples. The abundance of Rothia of ECC group was higher in saliva samples and Corynebacterium was abundant of ECC group in plaque samples. CONCLUSIONS: There are significant differences in the species and composition of microbial community in saliva and plaque of children with or without caries. Specific microorganisms are related to the occurrence of ECC, and screening specific microorganisms is helpful for early prediction and prevention of ECC.

P. gingivalis alters lung microbiota and aggravates disease severity of COPD rats by up-regulating Hsp90α/MLKL.

Background: Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear. Methods and Results: A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated. Conclusion: These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in.

Constituents of Chimaphila japonica and Their Diuretic Activity.

Three new phenols (1-3), one new cyclohexanol (4), two known phenols (5-6), and six known flavonoids (7-12) were isolated from the n-butanol of the 75% ethanol extract of all plants of Chimaphila japonica Miq. Among them, compound 5 was named and described in its entirety for the first time, and compounds 9 and 10 were reported in C. japonica for the first time. The structures of all compounds were confirmed using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. Biological results show that compounds 4, 7, and 11 exhibited potent diuretic activity. The modes of interaction between the selected compounds and the target diuretic-related WNK1 kinase were investigated in a preliminary molecular docking study. These results provided insight into the chemodiversity and potential diuretic activities of metabolites in C. japonica.

Metal-Oxo Electronic Tuning via In Situ CO Decoration for Promoting Methane Conversion to Oxygenates over Single-Atom Catalysts.

Direct methane conversion (DMC) to oxygenates at low temperature is of great value but remains challenging due to the high energy barrier for C-H bond activation. Here, we report that in situ decoration of Pd1-ZSM-5 single atom catalyst (SAC) by CO molecules significantly promoted the DMC reaction, giving the highest turnover frequency of 207 h-1 ever reported at room temperature and ~100 % oxygenates selectivity with H2O2 as oxidant. Combined characterizations and DFT calculations illustrate that the C-atom of CO prefers to coordinate with Pd1, which donates electrons to the Pd1-O active center (L-Pd1-O, L=CO) generated by H2O2 oxidation. The correspondingly improved electron density over Pd-O pair renders a favorable heterolytic dissociation of C-H bond with low energy barrier of 0.48 eV. Applying CO decoration strategy to M1-ZSM-5 (M=Pd, Rh, Ru, Fe) enables improvement of oxygenates productivity by 3.2-11.3 times, highlighting the generalizability of this method in tuning metal-oxo electronic structure of SACs for efficient DMC process.

Anti-PD-1 therapy reverses TIGIT+CD226+NK depletion in immunotherapy resistance of hepatocellular carcinoma through PVR/TIGIT pathway.

Immunotherapy resistance conducts the main reason for failure of PD-1-based immune checkpoint inhibitors (ICIs) in patients with hepatocellular carcinoma (HCC). This study aims to clarify the mechanism of nature kill cells (NK) depletion in immunotherapy resistance of HCC. Cancerous /paracancerous tissues and peripheral blood (PB) of 55 HCC patients were collected and grouped according to differentiation degree, FCM, IHC and lymphocyte culture drug intervention experiments were used to determine NK cell depletion degree. Furthermore, a mouse model of HCC in situ was constructed and divided into different groups according to intervention measures of ICIs. Immunofluorescence thermography was used to observe changes in tumor burden. NK cells in cancerous tissues significantly up-regulated TIGIT expression (P < 0.001). Intervention experiments revealed that TIGIT and PD-1 expression decreased gradually with increased PD-1 inhibitor dose in moderately-highly differentiated patients (P < 0.05). Animal experiment showed that tumors proliferation in experimental group was inhibited after PD-1 blockage, WB indicated that ICIs decreased TIGIT and PVRL1 protein expression while increased CD226 and PVRL3 protein expression. We concluded that TIGIT+NK cells competitively bind to PVR with CD226 and promote NK cell depletion. Anti-PD-1 decreases PVRL1 expression through PD-1/PD-L1 pathway, reducing the PVR/TIGIT inhibitory signal pathway, and enhancing function of PVR/CD226 activation signal.

Modifiable dietary factors in adolescent sleep: A systematic review and meta-analysis.

OBJECTIVE: Sleep problems are prevalent during adolescence, and modifying dietary factors may contribute to better sleep outcomes in adolescents. This systematic review and meta-analysis aimed to evaluate the impact of modifiable dietary factors on sleep health among adolescents. METHODS: A systematic search of records from six databases including MEDLINE, PubMed, Embase, Scopus, CINAHL, and the CENTRAL from inception up to November 2023, identified 33 peer-reviewed publications that assessed the relationship between modifiable dietary factors and sleep outcomes in adolescents aged 12-18 years. The NIH Quality Assessment Tools were used to assess the quality of the included studies. Meta-analysis was performed on a sub-group of studies (n = 6) to ascertain the effect of dietary factors on sleep health. RESULTS: Although the included studies were predominantly cross-sectional and exhibited heterogeneity, relying mainly on self-reported measures, it was observed that consumption of healthy foods was consistently linked with improved sleep outcomes among adolescents, whereas higher intake of fat-rich or sugar-rich foods and red meats or processed food was associated with poorer sleep features. The meta-analysis further substantiated that adolescents with higher caffeine intake faced increased odds of sleep problems (OR = 1.67, 95% CI: 1.28-2.17), while alcohol consumption was significantly associated with insomnia (OR = 1.17, 95% CI: 1.07-1.27). CONCLUSION: Overall, despite high heterogeneity among studies, this systematic review underscores the promising role of healthy dietary factors in enhancing both the quality and quantity of sleep in adolescents. The meta-analysis results also highlight that reducing caffeine and alcohol intake holds potential for supporting better sleep in this population. However, further validation through intervention studies is warranted.

The relationship of the tertiary lymphoid structures with the tumor-infiltrating lymphocytes and its prognostic value in gastric cancer.

Introduction: To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC). Material and methods: The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40. Results: The TLS distribution was significantly higher in the tumor invasive edge than the tumor center (p < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs (p = 0.007), peri-CD8+ (p = 0.019) and peri-GrB+TILs (p = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs (p = 0.019) and TLSs (p = 0.037) were independent prognostic predictor for GC patients. Conclusions: We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.

A Systematic Review of Technique, Satisfaction, and Complications of Acellular Dermal Matrix in Rhinoplasty.

OBJECTIVE: Acellular dermal matrix (ADM) is a new dermal transplant replacement material prepared from allogeneic or xenograft skin through bioengineering technology. This is provided for patients who are unwilling to kill part of their autologous cartilage or autologous dermal tissue and require rhinoplasty and improvement in the appearance of the nasal tip. This systematic review aims to introduce the main techniques of ADM for rhinoplasty and related patient satisfaction and complications to further guide doctors. METHODS: Systematic reviews were conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. The authors searched PubMed, Web of Science, Embase, and Cochrane Library using appropriate keywords. Data collected for each study included patient satisfaction and complications in addition to relevant technology. RESULTS: After full-text screening of inclusion and exclusion criteria, 10 studies were included, with a total of 324 patients receiving ADM with different transplantation methods. Primary rhinoplasty or secondary rhinoplasty study for dorsal ridge augmentation, smooth contour irregularities, autograft camouflage including tip grafts. The incidence of dorsal implant distortion was 0.72% in patients. The incidence of deviation was 2.17% in patients. The incidence of mild edema was 5.17% in patients. The incidence of partial resorption was 10.87% in patients. The incidence of significant resorption was 13.04% in patients. The incidence of seroma was 0.72% in patients. The incidence of partial prolapse was 0.72% in patients. The incidence of overcorrection and reoperation was 0.72% in patients. The incidence of erythema was 0.72% in patients. The incidence of undercorrection was 0.72% in patients. The incidence of infection was 0.72% in patients. The incidence of high-lying implants was 1.45% in patients. CONCLUSION: The current research results show that ADM is long-term effective in improving nasal dorsum enhancement, nasal contour deformity, and nasal tip appearance, with high patient satisfaction and low overall complication rate. Overcorrection should be considered during surgery to deal with postoperative partial absorption.

Catechol chitosan coated dual-loaded liposomes based on oxidation and saccharification mechanisms for enhancing skin anti-aging effects.

Skin aging has become a major urgent problem to be solved. Evidence reveals that oxidation and glycosylation are two dominant inducements of aging. Resveratrol (RES) with outstanding anti-oxidant effect and carnosine (CAR) with superb anti-glycation property were selected as two model drugs to evaluate the feasibility of their synergistic anti-aging effect. RES and CAR at the most desired mass ratio, supplying the most superior synergistic anti-aging effects were further encapsulated in liposomes (LP), which were separately coated with chitosan (CS) and catechol chitosan (Cat-CS) to increase the transdermal penetration. Their anti-aging efficacy was explored in human skin fibroblast (HSF) and human immortalized keratinocytes (HaCaT) cells, as well as the back skin of guinea pigs. Herein, RES and CAR at the mass ratio of 2:1 exhibited the most ideal synergistic anti-aging effect. The constructed liposomes have been shown to possess excellent fundamental properties and sustained-release properties. The aging-related indicator levels in the two cells and guinea pigs were obviously improved for the RES + CAR@Cat-CS-LP group. Additionally, skin appearance, tissue morphology, and collagen content were visibly improved, indicating its perfect anti-aging effect. In conclusion, RES + CAR@Cat-CS-LP is expected to be exploited as a potential anti-aging drug delivery system.

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review).

RNA methylation modifications are closely linked to tumor development, migration, invasion and responses to various therapies. Recent studies have shown notable advancements regarding the roles of RNA methylation in tumor immunotherapy, the tumor microenvironment and metabolic reprogramming. However, research on the association between tumor chemoresistance and N6­methyladenosine (m6A) methyltransferases in specific cancer types is still scarce. Colorectal cancer (CRC) is among the most common gastrointestinal cancers worldwide. Conventional chemotherapy remains the predominant treatment modality for CRC and chemotherapy resistance is the primary cause of treatment failure. The expression levels of m6A methyltransferases, including methyltransferase­like 3 (METTL3), METTL14 and METTL16, in CRC tissue samples are associated with patients' clinical outcomes and chemotherapy efficacy. Natural pharmaceutical ingredients, such as quercetin, have the potential to act as METTL3 inhibitors to combat chemotherapy resistance in patients with CRC. The present review discussed the various roles of different types of key RNA methylation enzymes in the development of CRC, focusing on the mechanisms associated with chemotherapy resistance. The progress in the development of certain inhibitors is also listed. The potential of using natural remedies to develop antitumor medications that target m6A methylation is also outlined.

Vascular smooth muscle cell-specific miRNA-214 deficiency alleviates simulated microgravity-induced vascular remodeling.

The human cardiovascular system has evolved to accommodate the gravity of Earth. Microgravity during spaceflight has been shown to induce vascular remodeling, leading to a decline in vascular function. The underlying mechanisms are not yet fully understood. Our previous study demonstrated that miR-214 plays a critical role in angiotensin II-induced vascular remodeling by reducing the levels of Smad7 and increasing the phosphorylation of Smad3. However, its role in vascular remodeling evoked by microgravity is not yet known. This study aimed to determine the contribution of miR-214 to the regulation of microgravity-induced vascular remodeling. The results of our study revealed that miR-214 expression was increased in the forebody arteries of both mice and monkeys after simulated microgravity treatment. In vitro, rotation-simulated microgravity-induced VSMC migration, hypertrophy, fibrosis, and inflammation were repressed by miR-214 knockout (KO) in VSMCs. Additionally, miR-214 KO increased the level of Smad7 and decreased the phosphorylation of Smad3, leading to a decrease in downstream gene expression. Furthermore, miR-214 cKO protected against simulated microgravity induced the decline in aorta function and the increase in stiffness. Histological analysis showed that miR-214 cKO inhibited the increases in vascular medial thickness that occurred after simulated microgravity treatment. Altogether, these results demonstrate that miR-214 has potential as a therapeutic target for the treatment of vascular remodeling caused by simulated microgravity.

Simulated spaceflight-induced cardiac remodeling is modulated by gut microbial-derived trimethylamine N-oxide.

Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.

Ginseng-derived nanoparticles reprogram macrophages to regulate arginase-1 release for ameliorating T cell exhaustion in tumor microenvironment.

BACKGROUND: Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear. METHODS: The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry. RESULTS: GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8+ T cells expansion. CONCLUSIONS: By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment.

Association between ozone and influenza transmissibility in China.

BACKGROUND: Common air pollutants such as ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter play significant roles as influential factors in influenza-like illness (ILI). However, evidence regarding the impact of O3 on influenza transmissibility in multi-subtropical regions is limited, and our understanding of the effects of O3 on influenza transmissibility in temperate regions remain unknown. METHODS: We studied the transmissibility of influenza in eight provinces across both temperate and subtropical regions in China based on 2013 to 2018 provincial-level surveillance data on influenza-like illness (ILI) incidence and viral activity. We estimated influenza transmissibility by using the instantaneous reproduction number ([Formula: see text]) and examined the relationships between transmissibility and daily O3 concentrations, air temperature, humidity, and school holidays. We developed a multivariable regression model for [Formula: see text] to quantify the contribution of O3 to variations in transmissibility. RESULTS: Our findings revealed a significant association between O3 and influenza transmissibility. In Beijing, Tianjin, Shanghai and Jiangsu, the association exhibited a U-shaped trend. In Liaoning, Gansu, Hunan, and Guangdong, the association was L-shaped. When aggregating data across all eight provinces, a U-shaped association was emerged. O3 was able to accounted for up to 13% of the variance in [Formula: see text]. O3 plus other environmental drivers including mean daily temperature, relative humidity, absolute humidity, and school holidays explained up to 20% of the variance in [Formula: see text]. CONCLUSIONS: O3 was a significant driver of influenza transmissibility, and the association between O3 and influenza transmissibility tended to display a U-shaped pattern.

Influenza Epidemic Trend Surveillance and Prediction Based on Search Engine Data: Deep Learning Model Study.

BACKGROUND: Influenza outbreaks pose a significant threat to global public health. Traditional surveillance systems and simple algorithms often struggle to predict influenza outbreaks in an accurate and timely manner. Big data and modern technology have offered new modalities for disease surveillance and prediction. Influenza-like illness can serve as a valuable surveillance tool for emerging respiratory infectious diseases like influenza and COVID-19, especially when reported case data may not fully reflect the actual epidemic curve. OBJECTIVE: This study aimed to develop a predictive model for influenza outbreaks by combining Baidu search query data with traditional virological surveillance data. The goal was to improve early detection and preparedness for influenza outbreaks in both northern and southern China, providing evidence for supplementing modern intelligence epidemic surveillance methods. METHODS: We collected virological data from the National Influenza Surveillance Network and Baidu search query data from January 2011 to July 2018, totaling 3,691,865 and 1,563,361 respective samples. Relevant search terms related to influenza were identified and analyzed for their correlation with influenza-positive rates using Pearson correlation analysis. A distributed lag nonlinear model was used to assess the lag correlation of the search terms with influenza activity. Subsequently, a predictive model based on the gated recurrent unit and multiple attention mechanisms was developed to forecast the influenza-positive trend. RESULTS: This study revealed a high correlation between specific Baidu search terms and influenza-positive rates in both northern and southern China, except for 1 term. The search terms were categorized into 4 groups: essential facts on influenza, influenza symptoms, influenza treatment and medicine, and influenza prevention, all of which showed correlation with the influenza-positive rate. The influenza prevention and influenza symptom groups had a lag correlation of 1.4-3.2 and 5.0-8.0 days, respectively. The Baidu search terms could help predict the influenza-positive rate 14-22 days in advance in southern China but interfered with influenza surveillance in northern China. CONCLUSIONS: Complementing traditional disease surveillance systems with information from web-based data sources can aid in detecting warning signs of influenza outbreaks earlier. However, supplementation of modern surveillance with search engine information should be approached cautiously. This approach provides valuable insights for digital epidemiology and has the potential for broader application in respiratory infectious disease surveillance. Further research should explore the optimization and customization of search terms for different regions and languages to improve the accuracy of influenza prediction models.

Clinical Value of Mean Platelet Volume to Platelet Ratio (MPR) in Distinguishing Mass-Forming Chronic Pancreatitis and Pancreatic Cancer.

BACKGROUND: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

Corrigendum: Application of cholecystic duct plasty in the prevention of biliary complications following orthotopic liver transplantation.

[This corrects the article DOI: 10.3389/fsurg.2023.1087327.].

HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation.

Bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoblast function play critical roles in bone formation, which is a highly regulated process. Long noncoding RNAs (lncRNAs) perform diverse functions in a variety of biological processes, including BMSC osteogenic differentiation. Although several studies have reported that HOX transcript antisense RNA (HOTAIR) is involved in BMSC osteogenic differentiation, its effect on bone formation in vivo remains unclear. Here, by constructing transgenic mice with BMSC (Prx1-HOTAIR)- and osteoblast (Bglap-HOTAIR)-specific overexpression of HOTAIR, we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo. Specifically, Prx1-HOTAIR mice showed delayed bone formation, while Bglap-HOTAIR mice showed increased bone formation. HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro. Furthermore, we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts. HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation. We first identified that the RNA-binding protein human antigen R (HuR) is responsible for HOTAIR nucleocytoplasmic translocation. HOTAIR is essential for osteoblast function, and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function. Bglap-HOTAIR mice, but not Prx1-HOTAIR mice, showed alleviation of bone loss induced by unloading. This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation, which provides new insights into precise regulation as a target for bone loss.