Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score-matching analysis.

BACKGROUND: Portal vein tumor thrombosis (PVTT) signifies late-stage hepatocellular carcinoma (HCC) with high-risk progression and poor prognosis. As a standard treatment, sorafenib monotherapy has limited the efficacy in managing HCC with PVTT. Currently, both hepatic arterial infusion chemotherapy (HAIC) and the combination of camrelizumab and rivoceranib have shown favorable survival benefits for advanced HCC, surpassing the standard sorafenib treatment. In this study, we investigate the safety and efficacy of HAIC combined with camrelizumab and rivoceranib in treating HCC patients with PVTT. METHODS: From January 2020 to December 2021, HCC patients with PVTT, who received either a triple regime of HAIC combined with camrelizumab and rivoceranib or a dual regime of camrelizumab and rivoceranib as their first-line treatment, were reviewed for eligibility at four hospital centers in China. To balance any intergroup differences, propensity score matching (PSM) was applied. The aim of this study is to compare the efficacy of the dual and triple combination treatment regimens based on survival prognosis and tumor response and evaluate the safety based on the occurrence of adverse reactions. RESULT: In this study, a total of 411 patients who received either the triple treatment regime (HAIC combined with camrelizumab plus rivoceranib, referred to as the HAICCR group, n = 292) or the dual treatment regime (camrelizumab combined with rivoceranib, referred to as the CR group, n = 119) between January 2020 and December 2021 were included. The results showed that the HAICCR group exhibited significantly better overall survival (mOS: 19.60 months vs. 11.50 months, p < 0.0001) and progression-free survival (mPFS: 10.0 months vs. 5.6 months, p < 0.0001) compared to the CR group in the overall cohort. Moreover, the HAICCR group also had a significantly higher ORR (objective response rate, 55.5% vs. 42.0%, p = 0.013) and DCR (disease control rate, 89.0% vs. 79.0%) compared to the CR group. After PSM, a final matched cohort of 83 pairs was obtained, and the survival benefits were consistent in this cohort as well (mOS: 18.70 months vs. 11.0 months, p < 0.0001; mPFS: 10.0 months vs. 5.6 months, p < 0.0001). However, there was no significant difference in the ORR between the triple and dual combination regimes. Univariate and multivariate analysis showed that CTP (Child-Turcotte-Pugh) stage, ALBI (albumin-bilirubin index) grade, tumor number, and treatment regime were significant risk factors affecting overall survival, while AFP (α-fetoprotein) level, tumor number, metastasis, and treatment regime were significant risk factors affecting progression-free survival. As for safety, hypertension and hand-foot syndrome were the two most common adverse reactions in both groups, with no significant difference in the occurrence of adverse reactions between the two groups (p < 0.05). CONCLUSION: In the context of advanced HCC patients with PVTT, the combination regime of HAIC and camrelizumab plus rivoceranib demonstrates more excellent capacity for prolonging survival and offers a well-tolerated safety compared to the CR dual therapy approach. This triple regime represents a therapeutic modality of broad prospects and vast potential for HCC patients with PVTT.

Correlation Analysis of Serum Lipopolysaccharide, Nuclear Factor Erythroid 2-Related Factor 2 and Haem Oxygenase 1 Levels and Cognitive Impairment in Patients with Obstructive Sleep Apnoea.

Objective: To investigate the correlation between the levels of serum lipopolysaccharide (LPS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cognitive impairment in patients with obstructive sleep apnoea (OSA). Methods: Serum LPS, Nrf2, HO-1 levels and cognitive impairment were measured using the Montreal Cognitive Assessment (MoCA) score in 56 patients in the "severe" group, 67 patients in the "mild-to-moderate" group and 100 healthy people in the "control" group. The differences in general conditions and serological indexes between the three groups were compared, the correlation between the MoCA scores and the serological indexes was explored and the independent predictors of the MoCA scores were analysed. Results: Serum LPS, Nrf2 and HO-1 levels were higher in the severe group than in the mild-to-moderate group and the control group (p < 0.05). A total of 71 patients with OSA had combined cognitive impairment, accounting for 57.7%, and the MoCA scores were lower in the severe group than in the mild-to-moderate group and the control group (p = 0.018). Serum LPS, Nrf2 and HO-1 levels were significantly higher in the severe group and mild-to-moderate group than in the control group (p < 0.05) and were negatively correlated with the MoCA scores. Lipopolysaccharide (p < 0.001) and HO-1 (p = 0.002) could be considered independent predictors of the MoCA score. Conclusion: Serum LPS and HO-1 levels are closely related to cognitive impairment in patients with OSA and have potential clinical value in the diagnosis.

Atomic-scale observation of localized phonons at FeSe/SrTiO3 interface.

In single unit-cell FeSe grown on SrTiO3, the superconductivity transition temperature features a significant enhancement. Local phonon modes at the interface associated with electron-phonon coupling may play an important role in the interface-induced enhancement. However, such phonon modes have eluded direct experimental observations. The complicated atomic structure of the interface brings challenges to obtain the accurate structure-phonon relation knowledge. Here, we achieve direct characterizations of atomic structure and phonon modes at the FeSe/SrTiO3 interface with atomically resolved imaging and electron energy loss spectroscopy in an electron microscope. We find several phonon modes highly localized (~1.3 nm) at the unique double layer Ti-O terminated interface, one of which (~ 83 meV) engages in strong interactions with the electrons in FeSe based on ab initio calculations. This finding of the localized interfacial phonon associated with strong electron-phonon coupling provides new insights into understanding the origin of superconductivity enhancement at the FeSe/SrTiO3 interface.

Stereocontrol in an intermolecular Schmidt reaction of equilibrating hydroxyalkyl allylic azides.

A selective intermolecular Schmidt reaction of equilibrating hydroxyalkyl allylic azides is reported to afford N-hydroxyalk-1-en-3-yl lactams in modest to high yields. For prochiral and chiral ketones, modest to high 1,5-diastereoselectivity was achieved, and the mechanistic analysis is supported by DFT calculation.

Photorewriting, Time-Resolved Encryption, and Unclonable Anticounterfeiting with Artificial Intelligence Authentication via a Reversible Photoswitchable System.

In the fields of photolithographic patterning, optical anticounterfeiting, and information encryption, reversible photochromic materials with solid-state fluorescence are emerging as a potential class of systems. A design strategy for reversible photochromic materials has been proposed and synthesized through the introduction of photoactive thiophene groups into the molecular backbone of aryl vinyls, compounds with unique aggregation-induced emission properties, and solid-state reversible photocontrollable fluorescence and color-changing properties. This work develops novel photochromic inks, films, and cellulose hydrogels for enhancing the security of information encryption and anticounterfeiting technologies. They achieve rapid and reversible color change under ultraviolet light irradiation. Dependent upon the rate of color change, higher levels of time-resolved security can be achieved. This feature is important for enhancing the confidentiality of encrypted information and the reliability of security labels. Color-changing cellulose hydrogels, inks, and films consisting of three photochromic fluorescent molecules have quick photoactivity, great photoreversibility and photostability, and good processability, making them ideal for time-delayed anticounterfeiting and smart encryption. Furthermore, specialized algorithms are used to construct convolutional neural networks, and image analysis is performed on these systems, thus solving the current problem of the time-consuming information decryption process. This artificial intelligence method offers new opportunities for enhanced data encryption.

The Impact of Different Regions of Interest on Shear Wave Elastography Assessment of the Meniscus in the Knee Joint.

RATIONALE AND OBJECTIVES: To investigate the impact of different regions of interest (ROI) on the assessment of shear wave elastography (SWE) in evaluating the meniscus of the knee joint. MATERIALS AND METHODS: After ethical approval, a total of 141 participants were enrolled in this prospective study from February to October 2023. SWE was utilized to evaluate the anterior horn of the lateral meniscus (LM) and medial meniscus (MM), using two different ROIs (ROI-Small and ROI-Trace) to measure the elastic mean value (Emean) and elastic maximum value (Emax). The differences in elasticity values between the normal menisci and torn menisci were compared, and the impact of different ROI selection methods on the diagnostic performance of elastic parameters in the torn menisci was assessed using receiver operating characteristic (ROC) curves. RESULTS: In Emean comparison, only MM in the tear group showed higher ROI-S than ROI-T. When comparing Emax, all ROI-T values were higher than the ROI-S values, and this difference was statistically significant. Different sizes of ROI did not significantly impact the diagnostic performance of Emean in LM and MM, nor the diagnostic effectiveness of Emax in LM. However, only the area under the curve (AUC) of MM for Emax in both ROI-S and ROI-T showed a statistically significant difference. CONCLUSION: The shear wave elasticity values and diagnostic performance may vary depending on the ROI settings. Therefore, it is recommended to use a 2 mm diameter ROI placed at the central position of the meniscus, with Emean as the elasticity index.

Observation of the nonanalytic behavior of optical phonons in monolayer hexagonal boron nitride.

Phonon splitting of the longitudinal and transverse optical modes (LO-TO splitting), a ubiquitous phenomenon in three-dimensional polar materials, will break down in two-dimensional (2D) polar systems. Theoretical predictions propose that the LO phonon in 2D polar monolayers becomes degenerate with the TO phonon, displaying a distinctive "V-shaped" nonanalytic behavior near the center of the Brillouin zone. However, the full experimental verification of these nonanalytic behaviors has been lacking. Here, using monolayer hexagonal boron nitride (h-BN) as a prototypical example, we report the comprehensive and direct experimental verification of the nonanalytic behavior of LO phonons by inelastic electron scattering spectroscopy. Interestingly, the slope of the LO phonon in our measurements is lower than the theoretically predicted value for a freestanding monolayer due to the screening of the Cu foil substrate. This enables the phonon polaritons in monolayer h-BN/Cu foil to exhibit ultra-slow group velocity (~5 × 10-6 c, c is the speed of light) and ultra-high confinement (~ 4000 times smaller wavelength than that of light). These exotic behaviors of the optical phonons in h-BN presents promising prospects for future optoelectronic applications.

Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis.

PURPOSE: To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between groups were compared. RESULTS: Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC-PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC-PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression-free survival (median progression-free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC-PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC-PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression-free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival. CONCLUSION: The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.

Distribution characteristics of intestinal flora in patients with OSAHS and the relationship between different intestinal flora and sleep disorders, hypoxemia and obesity.

OBJECTIVE: To investigate the distribution characteristics of intestinal flora in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS) of different severities and the relationship between different intestinal flora and sleep structure disorder, hypoxemia and obesity. METHODS: A total of 25 healthy volunteers and 80 patients with OSAHS were enrolled in this study. The control group was healthy, and the experimental group comprised patients with OSAHS. The apnoea-hypopnea index (AHI), minimum saturation of peripheral oxygen (SpO2min), mean saturation of peripheral oxygen, body mass index, maximum apnoea time and other indicators were collected in clinical practice. The patients with OSAHS were divided into 20 mild and 42 moderate OSAHS cases, as well as 18 patients with severe OSAHS according to the AHI classification. Bioinformatics-related statistics were analysed using the QIIME2 software, and clinical data were analysed with the SPSS 22.0 software. RESULTS: The changes in microbial alpha diversity in the intestinal flora of patients with OSAHS showed that richness, diversity and evenness decreased, but the beta diversity did not change significantly. The Thermus Anoxybacillus, Anaerofustis, Blautia, Sediminibacterium, Ralstonia, Pelomonas, Ochrobactrum, Thermus Sediminibacterium, Ralstonia, Coccidia, Cyanobacteria, Anoxic bacilli and Anaerobes were negatively correlated with AHI (r = -0.38, -0.36, -0.35, -0.33, -0.31, -0.29, -0.22, -0.18) and positively correlated with SpO2min (r =0.38, 0.2, 0.25, 0.22, 0.24, 0.11, 0.23, 0.15). CONCLUSION: Some bacteria showed a significant correlation with clinical sleep monitoring data, which provides a possibility for the assessment of disease risk, but the mechanisms of their actions in the intestinal tract are not clear at present. Further research and observations are needed.

Separated Electron-Phonon and Phonon-Phonon Scatterings Across Interface in Thin Film LaCoO3 /SrTiO3.

Electron-phonon coupling (EPC) and phonon-phonon scattering (PPS) are at the core of the microscopic physics mechanisms of vast quantum materials. However, to date, there are rarely reports that these two processes can be spatially separated, although they are usually temporally detached with different characteristic lifetimes. Here, by employing ultrafast spectroscopy to investigate the photo-carrier ultrafast dynamics in a LaCoO3 thin film on a (100) SrTiO3 substrate, intriguing evidence is found that the two interactions are indeed spatially separated. The EPC mainly occurs in the thin film, whereas PPS is largely in the substrate, especially at the several atomic layers near the interface. Across-interface penetration and decay of optical phonons into acoustic phonons thus naturally occur. An EPC strength λEg  = 0.30 is also obtained and an acoustic phonon mode at 45.3 GHz is observed. The finding lays out a cornerstone for future quantum nano device designs.

Colonic Endoscopic Tubing Is Safe and Effective Approach for Washed Microbiota Transplantation in Autistic Children.

Background: Washed microbiota transplantation (WMT) as the improved methods of fecal microbiota transplantation has been employed as a therapeutic approach for ameliorating symptoms associated with autism spectrum disorder (ASD). In this context, colonic transendoscopic enteral tubing (TET) has been utilized as a novel procedure for administering WMT. Methods: Data of children with ASD who received WMT by TET were retrospectively reviewed, including bowel preparation methods, TET operation time, success rate, tube retention time, the comfort of children, adverse events, and parent satisfaction. Results: A total of 38 participants underwent 124 colonic TET catheterization procedures. The average time of TET operation was 15 minutes, and the success rate was 100% (124/124). There was no significant difference in TET operation time between high-seniority physicians and low-seniority physicians. In 123 procedures (99%), the TET tube allowed the completion of WMT treatment for 6 consecutive days. In 118 procedures (95.2%), the tube was detached spontaneously after the end of the treatment course, and the average TET tube retention time was 8 days. There was no incidence of tube blockage during the treatment course. No severe adverse events occurred during follow-up. Parents of all participants reported a high level of satisfaction with TET. Conclusion: Colonic TET is a safe and feasible method for WMT in children with ASD.

Assessment of Knee Menisci in Healthy Adults Using Shear Wave Elastography.

OBJECTIVES: The aim of this study was to explore the application value of shear wave elastography in healthy adults with knee meniscus. METHODS: One hundred adult subjects who underwent health checkups at our hospital from December 2022 to February 2023 were selected as research participants. Shear wave elastography was used to evaluate the periphery of the lateral and medial meniscus in both knees. To assess the mean differences in Young's modulus values between male and female groups, a one-way analysis of variance (ANOVA) and independent samples t-test were conducted. In addition, a Pearson correlation coefficient test was used to analyze the correlation between the elastic values of the meniscus and age, height, weight, and body mass index (BMI). RESULTS: There were no significant differences in elastic values between the lateral meniscus of the left and right sides or between the medial meniscus of the left and right sides within the same gender group (P > .05). Stiffness values of the medial meniscus were higher in each gender group than those of the lateral meniscus (P < .01). Additionally, males demonstrated higher stiffness values than females (P < .01). As age increased, the Young's modulus of the meniscus increased significantly (r > .75, P < .01). CONCLUSION: Shear wave elastography can serve as an adjunctive tool to aid in the assessment of knee meniscal elasticity.

Multiparametric MRI-based model for prediction of local progression of hepatocellular carcinoma after thermal ablation.

PURPOSE: To develop a deep learning radiomics of multiparametric magnetic resonance imaging (DLRMM)-based model that incorporates preoperative and postoperative signatures for prediction of local tumor progression (LTP) after thermal ablation (TA) in hepatocellular carcinoma (HCC). METHODS: From May 2017 to October 2021, 417 eligible patients with HCC were retrospectively enrolled from three hospitals (one primary cohort [PC, n = 189] and two external test cohorts [ETCs][n = 135, 93]). DLRMM features were extracted from T1WI + C, T2WI, and DWI using ResNet18 model. An integrative model incorporating the DLRMM signature with clinicopathologic variables were further built to LTP risk stratification. The performance of these models were compared by areas under receiver operating characteristic curve (AUC) using DeLong test. RESULTS: A total of 1668 subsequences and 31,536 multiparametric MRI slice including T1WI, T2WI, and DWI were collected simultaneously. The DLRMM signatures were extracted from tumor and ablation zone, respectively. Ablative margin, multiple tumors, and tumor abutting major vessels were regarded as risk factors for LTP in clinical model. The AUC of DLRMM model were 0.864 in PC, 0.843 in ETC1, and 0.858 in ETC2, which was higher significantly than those in clinical model (p < 0.001). After integrating clinical variable, DLRMM model obtained significant improvement with AUC of 0.870-0.869 in three cohorts (all, p < 0.001), which can provide the risk stratification for overall survival of HCC patients. CONCLUSIONS: The DLRMM model is essential to identify LTP risk of HCC patients who underwent TA and may potentially benefit personalized decision-making.

Direct Observation of Topological Phonons in Graphene.

Phonons, as the most fundamental emergent bosons in condensed matter systems, play an essential role in the thermal, mechanical, and electronic properties of crystalline materials. Recently, the concept of topology has been introduced to phonon systems, and the nontrivial topological states also exist in phonons due to the constraint by the crystal symmetry of the space group. Although the classification of various topological phonons has been enriched theoretically, experimental studies were limited to several three-dimensional (3D) single crystals with inelastic x-ray or neutron scatterings. The experimental evidence of topological phonons in two-dimensional (2D) materials is absent. Here, using high-resolution electron energy loss spectroscopy following our theoretical predictions, we directly map out the phonon spectra of the atomically thin graphene in the entire 2D Brillouin zone, and observe two nodal-ring phonons and four Dirac phonons. The closed loops of nodal-ring phonons and the conical structure of Dirac phonons in 2D momentum space are clearly revealed by our measurements, in nice agreement with our theoretical calculations. The ability of 3D mapping (2D momentum space and energy space) of phonon spectra opens up a new avenue to the systematic identification of the topological phononic states. Our work lays a solid foundation for potential applications of topological phonons in superconductivity, dynamic instability, and phonon diode.

A High-Potential Bipolar Phenothiazine Derivative Cathode for Aqueous Zinc Batteries.

Aqueous zinc ion batteries (AZIBs) are gaining popularity as advanced energy storage devices that are economical, safe, and use resource-abundant storage options. In this study, we have synthesized a bipolar phenothiazine organic scaffold known as 3,7-bis(melaminyl)phenothiazin-5-ium iodide (PTDM), which is obtained by undergoing nucleophilic substitution through phenothiazinium tetraiodide hydrate (PTD) and melamine. Electrochemical results indicate that PTDM can act as a high-potential cathode material for rechargeable AZIBs. In detail, the aqueous PTDM//Zn full cell exhibits a high average voltage of approximate 1.13 V, along with a specific capacity of 118.3 mAh g-1 at 0.1 A g-1 . Furthermore, this demonstrated cell displays moderate long-term cycling stability over 6400 cycles, which is encouraging and suggests potential for developing advanced organic electrode materials for rechargeable AZIBs.

USP7 Inhibits Osteoclastogenesis via Dual Effects of Attenuating TRAF6/TAK1 Axis and Stimulating STING Signaling.

Ubiquitination is a reversible post-translational modification implicated in cell differentiation, homeostasis, and organ development. Several deubiquitinases (DUBs) decrease protein ubiquitination through the hydrolysis of ubiquitin linkages. However, the role of DUBs in bone resorption and formation is still unclear. In this study, we identified DUB ubiquitin-specific protease 7 (USP7) as a negative regulator of osteoclast formation. USP7 combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its ubiquitination by impairing the Lys63-linked polyubiquitin chain. Such impairment leads to the suppression of receptor activator of NF-κB ligand (RANKL)-mediated nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation without affecting TRAF6 stability. USP7 also protects the stimulator of interferon genes (STING) against degradation, inducing interferon-ß (IFN-ß) expression in osteoclast formation, thereby inhibiting osteoclastogenesis cooperatively with the classical TRAF6 pathway. Furthermore, USP7 inhibition accelerates osteoclast differentiation and bone resorption both in vitro and in vivo. Contrarily, USP7 overexpression impairs osteoclast differentiation and bone resorption in vitro and in vivo. Additionally, in ovariectomy (OVX) mice, USP7 levels are lower than those in sham-operated mice, suggesting that USP7 plays a role in osteoporosis. Altogether, our data reveal the dual effect of USP7-mediated TRAF6 signal transduction and USP7-mediated protein degradation of STING in osteoclast formation.

Significance of pyroptosis-related gene in the diagnosis and classification of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, is often characterized by persistent morning stiffness, joint pain, and swelling. Early diagnosis and timely treatment of RA can effectively delay the progression of the condition and significantly reduce the incidence of disability. In the study, we explored the function of pyroptosis-related genes (PRGs) in the diagnosis and classification of rheumatoid arthritis based on Gene Expression Omnibus (GEO) datasets. Method: We downloaded the GSE93272 dataset from the GEO database, which contains 35 healthy controls and 67 RA patients. Firstly, the GSE93272 was normalized by the R software "limma" package. Then, we screened PRGs by SVM-RFE, LASSO, and RF algorithms. To further investigate the prevalence of RA, we established a nomogram model. Besides, we grouped gene expression profiles into two clusters and explored their relationship with infiltrating immune cells. Finally, we analyzed the relationship between the two clusters and the cytokines. Result: CHMP3, TP53, AIM2, NLRP1, and PLCG1 were identified as PRGs. The nomogram model revealed that decision-making based on established model might be beneficial for RA patients, and the predictive power of the nomogram model was significant. In addition, we identified two different pyroptosis patterns (pyroptosis clusters A and B) based on the 5 PRGs. We found that eosinophil, gamma delta T cell, macrophage, natural killer cell, regulatory T cell, type 17 T helper cell, and type 2 T helper cell were significant high expressed in cluster B. And, we identified gene clusters A and B based on 56 differentially expressed genes (DEGs) between pyroptosis cluster A and B. And we calculated the pyroptosis score for each sample to quantify the different patterns. The patients in pyroptosis cluster B or gene cluster B had higher pyroptosis scores than those in pyroptosis cluster A or gene cluster A. Conclusion: In summary, PRGs play vital roles in the development and occurrence of RA. Our findings might provide novel views for the immunotherapy strategies with RA.

Identification of five hub immune genes and characterization of two immune subtypes of osteoarthritis.

Background: Osteoarthritis (OA) is one of the most prevalent chronic diseases, leading to degeneration of joints, chronic pain, and disability in the elderly. Little is known about the role of immune-related genes (IRGs) and immune cells in OA. Method: Hub IRGs of OA were identified by differential expression analysis and filtered by three machine learning strategies, including random forest (RF), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM). A diagnostic nomogram model was then constructed by using these hub IRGs, with receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) estimating its performance and clinical impact. Hierarchical clustering analysis was then conducted by setting the hub IRGs as input information. Differences in immune cell infiltration and activities of immune pathways were revealed between different immune subtypes. Result: Five hub IRGs of OA were identified, including TNFSF11, SCD1, PGF, EDNRB, and IL1R1. Of them, TNFSF11 and SCD1 contributed the most to the diagnostic nomogram model with area under the curve (AUC) values of 0.904 and 0.864, respectively. Two immune subtypes were characterized. The immune over-activated subtype showed excessively activated cellular immunity with a higher proportion of activated B cells and activated CD8 T cells. The two phenotypes were also seen in two validation cohorts. Conclusion: The present study comprehensively investigated the role of immune genes and immune cells in OA. Five hub IRGs and two immune subtypes were identified. These findings will provide novel insights into the diagnosis and treatment of OA.

Efficacy and safety of HAIC alone vs. HAIC combined with lenvatinib for treatment of advanced hepatocellular carcinoma.

To investigate efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib (HAIC-Len) and HAIC alone for the treatment of advanced hepatocellular carcinoma (Ad-HCC). Totally 349 patients with Ad-HCC participated in the research from February 2018 to October 2020. On the basis of propensity score matching (PSM), 132 and 110 cases were assigned to the HAIC group and the HAIC-Len group, respectively, with a ratio of 1:1. Progression-free survival (PFS), overall survival (OS), and complications were compared between two groups. The Kaplan-Meier method and log-rank test were utilized to estimate cumulative OS and PFS. Additionally, uni- and multi-variate Cox regression models were employed to identify significant independent factors. The median follow-up period in this study was set to be 20.8 months. Following PSM, the one-, two- and three-year cumulative OS rates in the HAIC-Len and HAIC groups were 63.6%, 12.1%, and 3.0%, and 47.2%, 11.8%, and 2.7%, respectively, with a significant difference (P < 0.001). The first-three-year cumulative incidence rates PFS in the HAIC-Len and the HAIC groups were 15.2%, 1.5%, and ND, and 11.8%, 4.5%, and 3.6%, respectively, with no significant difference detected (P = 0.092). BMI (HR 0.709. 95% CI 0.549, 0.915. P = 0.008) and AST (HR 1.005. 95% CI 1.003, 1.007. P < 0.001) represented independent prognostic factors for OS. Additionally, the two groups exhibited no significant difference in the incidence rates of adverse events. HAIC-Len significantly improved survival outcomes of patients with Ad-HCC and demonstrated acceptable toxicity compared to HAIC alone.