Mapping the Characteristics of Respiratory Infectious Disease Epidemics in China Based on the Baidu Index from November 2022 to January 2023.

Introduction: Infectious diseases pose a significant global health and economic burden, underscoring the critical need for precise predictive models. The Baidu index provides enhanced real-time surveillance capabilities that augment traditional systems. Methods: Baidu search engine data on the keyword "fever" were extracted from 255 cities in China from November 2022 to January 2023. Onset and peak dates for influenza epidemics were identified by testing various criteria that combined thresholds and consecutive days. Results: The most effective scenario for indicating epidemic commencement involved a 90th percentile threshold exceeded for seven consecutive days, minimizing false starts. Peak detection was optimized using a 7-day moving average, balancing stability and precision. Discussion: The use of internet search data, such as the Baidu index, significantly improves the timeliness and accuracy of disease surveillance models. This innovative approach supports faster public health interventions and demonstrates its potential for enhancing epidemic monitoring and response efforts.

Establishment and validation of circulating cell-free DNA signatures for nasopharyngeal carcinoma detection.

BACKGROUND: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). METHODS: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5'-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case-control analysis, we developed a diagnostic model for NPC, and validated its detection capability. FINDINGS: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%-100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. INTERPRETATION: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. FUNDING: A full list of funding bodies that contributed to this study can be found in Funding section.

"The Psychiatric Domain of Post-Intensive Care Syndrome: A Review for the Intensivist".

Post-intensive care syndrome (PICS) is a clinical syndrome characterized by new or worsening changes in mental health, cognition, or physical function that persist following critical illness. The psychiatric domain of PICS encompasses new or worsened psychiatric burdens following critical illness, including post-traumatic stress disorder (PTSD), depression, and anxiety. Many of the established predisposing and precipitating factors for the psychiatric domain of PICS are commonly found in the setting of critical illness, including mechanical ventilation (MV), exposure to sedating medications, and physical restraint. Importantly, previous psychiatric history is a strong risk factor for the development of the psychiatric domain of PICS and should be considered when screening patients to diagnose psychiatric impairment and interventions. Delirium has been associated with psychiatric symptoms following ICU admission, therefore prevention warrants careful consideration. Dexmedetomidine has been shown to have the lowest risk for development of delirium when compared to other sedatives and has been the only sedative studied in relation to the psychiatric domain of PICS. Nocturnal dexmedetomidine and intensive care unit (ICU) diaries have been associated with decreased psychiatric burden after ICU discharge. Studies evaluating the impact of other intra-ICU practices on the development of the psychiatric domain of PICS, including the ABCDEF bundle, depth of sedation, and daily spontaneous awakening trials, have been limited and inconclusive. The psychiatric domain of PICS is difficult to treat and may be less responsive to multidisciplinary post-discharge programs and targeted interventions than the cognitive and physical domains of PICS. Given the high morbidity associated with the psychiatric domain of PICS, intensivists should familiarize themselves with the risk factors and intra-ICU interventions that can mitigate this important and under-recognized condition.

An adaptive spatiotemporal filter for ultrasound localization microscopy based on density canopy clustering.

Ultrasound Localization Microscopy (ULM) facilitates structural and hemodynamic imaging of microvessels with a resolution of tens of micrometers. In ULM, the extraction of effective microbubble signals is crucial for image quality. Singular Value Decomposition (SVD) is currently the most prevalent method for microbubble signal extraction in ULM. Most existing ULM studies employ a fixed SVD filter threshold using empirical values which will lead to imaging quality degradation due to the insufficient separation of blood signals. In this study, we propose an adaptive and non-threshold SVD filter based on canopy-density clustering, termed DCC-SVD. This filter automatically classifies the components of the SVD based on the density of their spatiotemporal features, eliminating the need for parameter selection. In in vitro tube phantom, DCC-SVD demonstrated its ability to adaptive separation of blood and bubble signal at varying microbubble concentrations and flow rates. We compared the proposed DCC-SVD method with the Block-match 3D (BM3D) filter and a classical adaptive method called spatial similarity matrix (SSM), using concentration-variable in vivo rat brain data, as well as open-source rat kidney and mouse tumor datasets. The proposed DCC-SVD improved the global spatial resolution by approximately 4 µm from 30.39 µm to 26.02 µm. It also captured vessel structure absent in images obtained by other methods and yielded a smoother vessel intensity profile, making it a promising spatiotemporal filter for ULM imaging.

Electric-Field-Driven Localization of Molecular Nanowires in Wafer-Scale Nanogap Electrodes.

As integrated circuits continue to scale toward the atomic limit, bottom-up processes, such as epitaxial growth, have come to feature prominently in their fabrication. At the same time, chemistry has developed highly tunable molecular semiconductors that can perform the functions of ultimately scaled circuit components. Hybrid techniques that integrate programmable structures comprising molecular components into devices however are sorely lacking. Here we demonstrate a wafer-scale process that directs the localization of a conductive polymer, Mw = 20 kg mol-1 polyaniline, from dilute solutions into 50 nm vertical nanogap device architectures using electric-field-driven self-assembly. The resulting metal-polymer-metal junctions were characterized by electron microscopy, Raman spectroscopy and transport measurements demonstrating that our technique is highly selective, assembling conductive polymers only in electrically activated nanogaps. Our results represent a step toward scalable hybrid nanoelectronics that seamlessly integrate established lithographic top-down fabrication with bottom-up synthesized molecular functional circuit components.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

Utilizing bifurcated allogeneic vein grafts: a novel approach for preventing sinistral portal hypertension following Pancreaticoduodenectomy. a 10-year before and after study.

BACKGROUND: Sinistral portal hypertension (SPH) may occurs in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) cofluence resection. This study aimed to evaluate outcomes with the bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients. MATERIALS AND METHODS: A total of 81 patients were included. We retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from Jan. 2011 to Dec. 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, we prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from Jan. 2021 to Jan. 2023. RESULTS: In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups (P>0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group (P<0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15). CONCLUSION: Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma.

Exploring the Lagged Correlation Between Baidu Index and Influenza-Like Illness - China, 2014-2019.

Introduction: This study investigated the lagged correlation between Baidu Index for influenza-related keywords and influenza-like illness percentage (ILI%) across regions in China. The aim is to establish a scientific foundation for utilizing Baidu Index as an early warning tool for influenza-like illness epidemics. Methods: In this study, data on ILI% and Baidu Index were collected from 30 provincial-level administrative divisions (PLADs) spanning April 2014 to March 2019. The Baidu Index was categorized into Overall Index, Ordinary Index, Prevention Index, Symptom Index, and Treatment Index based on search query themes. The lagged correlation between the Baidu Index and ILI% was examined through the cross-correlation function (CCF) method. Results: Correlating the Baidu Overall Index of 30 PLADs with ILI% revealed CCF values ranging from 0.46 to 0.86, with a median lag of 0.5 days. Subcategory analysis indicated that the Prevention Index and Symptom Index exhibited quicker responses to ILI%, with median lags of -9 and -0.5 days, respectively, compared to 0 and 3 days for the Ordinary and Treatment Indexes. The median lag days between the Baidu Index and the ILI% were earlier in the northern PLADs compared to the southern PLADs. Discussion: The Prevention and Symptom Indexes show promising predictive capabilities for influenza-like illness epidemics.

Comparison Between Threshold Method and Artificial Intelligence Approaches for Early Warning of Respiratory Infectious Diseases - Weifang City, Shandong Province, China, 2020-2023.

Introduction: Respiratory infectious diseases, such as influenza and coronavirus disease 2019 (COVID-19), present significant global public health challenges. The emergence of artificial intelligence (AI) and big data offers opportunities to improve traditional disease surveillance and early warning systems. Methods: The study analyzed data from January 2020 to May 2023, comprising influenza-like illness (ILI) statistics, Baidu index, and clinical data from Weifang. Three methodologies were evaluated: the adaptive dynamic threshold method (ADTM) for dynamic threshold adjustments, the machine learning supervised method (MLSM), and the machine learning unsupervised method (MLUM) utilizing anomaly detection. The comparison focused on sensitivity, specificity, timeliness, and warning consistency. Results: ADTM issued 37 warnings with a sensitivity of 71% and a specificity of 85%. MLSM generated 35 warnings, with a sensitivity of 82% and a specificity of 87%. MLUM produced 63 warnings with a sensitivity of 100% and specificity of 80%. The initial warnings from ADTM and MLUM preceded those from MLSM by five days. The Kappa coefficient indicated moderate agreement between the methods, with values ranging from 0.52 to 0.62 (P<0.05). Discussion: The study explores the comparison between traditional methods and two machine learning approaches for early warning systems. It emphasizes the validation of machine learning's reliability and underscores the unique advantages of each method. Furthermore, it stresses the significance of integrating machine learning models with various data sources to enhance public health preparedness and response, alongside acknowledging limitations and the need for broader validation.

Progression of m6A in the tumor microenvironment: hypoxia, immune and metabolic reprogramming.

Recently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.

Integrated single-cell and bulk RNA sequencing revealed an epigenetic signature predicts prognosis and tumor microenvironment colorectal cancer heterogeneity.

BACKGROUND: Colorectal cancer (CRC) prognosis prediction is currently a major challenge. Epigenetic regulation has been widely reported for its role in cancer development. AIM: To construct a robust prognostic signature, we used developed and validated across datasets. METHODS: After constructing the signature, the prognostic value of the signature was evaluated in the TCGA cohort and six independent datasets (GSE17526, GSE17537, GSE33113, GSE37892, GSE39048 and GSE39582). The clinical, genomic and transcriptomic features related to the signature were identified. The correlations of the signature score with immune cell infiltration and cell-cell interactions were analyzed. The correlations between the signature score and the sensitivity to different drugs were also predicted. RESULTS: In the TCGA cohort, patients in the low-risk group according to the signature score had longer survival than those in the high-risk group, and this finding was validated in the validation datasets. The signature was a prognostic factor independent of age and sex and was correlated with stage and PD-1/PD-L1 expression. Area under the receiving operating characteristic curve was 0.72. Genomic association analyses revealed that samples from high-risk patients exhibited chromosomal instability. Transcriptomic analyses revealed that the signature score was significantly associated with multiple cellular pathways. Bulk RNA-seq and single-cell sequencing data revealed that the signature reflected differences in infiltrating immune cell-tumor cell interactions, especially for macrophages. The signature also predicted the putative drug sensitivity of CRC samples. CONCLUSION: The signature is a valuable biomarker for predicting CRC prognosis and reflects multiple features of CRC, especially macrophage infiltration in the microenvironment.

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.

Enhancing infectious diseases early warning: A deep learning approach for influenza surveillance in China.

Objective: This study aimed to develop a universally applicable, feedback-informed Self-Excitation Attention Residual Network (SEAR) model. This model dynamically adapts to evolving disease trends and surveillance system changes, accommodating various scenarios. Thereby enhancing the effectiveness of early warning systems. Methods: Surveillance data on influenza-like illness (ILI) was collected from various regions including Northern China, Southern China, Beijing, and Yunnan. The reproduction number (Rt) was estimated to determine the threshold for issuing warnings. The Self-Excitation Attention Residual Network (SEAR) was devised employing deep learning algorithms and was trained, validated, and tested. The SEAR model's efficacy was assessed based on five metrics: accuracy rate, recall rate, F1 score, confusion matrix, and the receiver operating characteristic curve. Results: With an advance warning set at three days, the SEAR model outperformed five primary models - logistic regression, support vector machine, random forest, Extreme Gradient Boosting, and Long Short-Term Memory model - in all five evaluation metrics. Notably, the model's warning performance declined with an increase in the early warning value and the number of warning days, albeit maintaining a ROC value over 0.7 in all scenarios. Conclusion: The SEAR model demonstrated robust early warning performance for influenza in diverse Chinese regions with high accuracy and specificity. This novel model, augmenting traditional systems, supports widespread application for respiratory disease outbreak monitoring. Future evaluations could incorporate alternative indicators, with the model continuously updating through data feedback, thus enhancing its universal applicability. Ongoing optimization, using iterative feedback and expert judgment, heralds a transformative approach to surveillance-based early warning strategies.

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.

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.

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.

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.

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.