Construction and Analysis of Risk Prediction Model of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps: A Cross-Sectional Study in Northwest China.

OBJECTIVE: To provide guidance for clinical endotypes by constructing a risk-predictive model of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). DESIGN: A cross-sectional study. SETTING: Single-centre trial at tertiary medical institutions. PARTICIPANTS: A cross-sectional study included 343 CRSwNP patients divided into ECRSwNP (n = 237) and non-ECRSwNP (n = 106) groups using surgical pathology. MAIN OUTCOME MEASURES: Single-factor and multivariate analysis were used to identify statistically significant variables for constructing a nomogram, including the history of AR, hyposmia score, ethmoid sinus score, BEP and BEC. The model's performance was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). RESULTS: Allergic rhinitis, hyposmia score, ethmoid sinus score, peripheral blood eosinophil percentage (BEP) and eosinophil count (BEC) were retained for the construction nomogram of ECRSwNP. The nomogram exhibited a certain accuracy, with an AUC of 0.897 (95% CI: 0.864-0.930), good agreement in the calibration curve and a 0.891 C-index of internal validation. Moreover, the DCA with a threshold probability between 0.0167 and 1.00 indicated a higher net benefit and greater clinical utility. CONCLUSION: The construction of a predictive risk model of ECRSwNP based on easily accessible factors could assist clinicians in more conveniently defining endotypes to make optimal diagnoses and treatment choices.

Framework Nucleic Acids Loaded with Quercetin: Protecting Retinal Neurovascular Unit via the Protein Kinase B/Heme Oxygenase-1 Pathway.

Retinal neovascular disease is a leading cause of vision loss and blindness globally. It occurs when abnormal new blood vessels form in the retina. In this study, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to load quercetin (QUE), a small-molecule flavonoid, forming a deoxyribonucleic acid (DNA) nanocomplex, tFNAs-QUE. Our data show this nanocomplex inhibits pathological neovascularization, reduces the area of retinal nonperfusion area, protects retinal neurons, and preserves the visual function. Further, we discovered that tFNAs-QUE selectively upregulates the AKT/Nrf2/HO-1 signaling pathway, which can suppress pathological vascular growth and exert antioxidative effects. Therefore, this study presents a promising small-molecule-loading mechanism for the treatment of ischemic retinal diseases.

Inoculation of Saccharomyces cerevisiae for facilitating aerobic composting of acidified food waste.

In aerobic composting of food waste, acidification of the material (acidified food waste, AFW) often occurs and consequently leads to failure of fermentation initiation. In this study, we solved this problem by adding Saccharomyces cerevisiae inoculants. The results showed that the inoculation with S. cerevisiae effectively promoted the composting process. In 2 kg composting, inoculation with S. cerevisiae significantly elevated the pile temperatures by 4 ~ 14 °C, accompanied by a rapid increase in pH from 4.5 to 6.0. In 15 kg composting, total acid decreased faster and the thermophilic stage above 50 °C was prolonged by 3 days longer than in the control. The residual oxygen content in the reactor indicated that S. cerevisiae, which proliferated during composting, increased microbial activity and reduced ammonia emission during the thermophilic phase. Cell density analysis showed that compost inoculated with S. cerevisiae promoted thermophilic bacterial propagation. Metagenomic analysis showed that the dominant bacteria in the AFW compost were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria, and the relative abundance of Bacillus, Thermobacillus, and Thermobifida increased when inoculated with S. cerevisiae. These results indicate that the inoculation of S. cerevisiae is an effective strategy to improve the aerobic composting process of AFW by accelerating the initial phase and altering microbial community structure in the thermophilic phase. Our findings suggest that S. cerevisiae can be applied to aerobic composting of organic wastes to effectively address the problem of acidification.

An Interpretable System for Screening the Severity Level of Retinopathy in Premature Infants Using Deep Learning.

Accurate evaluation of retinopathy of prematurity (ROP) severity is vital for screening and proper treatment. Current deep-learning-based automated AI systems for assessing ROP severity do not follow clinical guidelines and are opaque. The aim of this study is to develop an interpretable AI system by mimicking the clinical screening process to determine ROP severity level. A total of 6100 RetCam Ⅲ wide-field digital retinal images were collected from Guangdong Women and Children Hospital at Panyu (PY) and Zhongshan Ophthalmic Center (ZOC). A total of 3330 images of 520 pediatric patients from PY were annotated to train an object detection model to detect lesion type and location. A total of 2770 images of 81 pediatric patients from ZOC were annotated for stage, zone, and the presence of plus disease. Integrating stage, zone, and the presence of plus disease according to clinical guidelines yields ROP severity such that an interpretable AI system was developed to provide the stage from the lesion type, the zone from the lesion location, and the presence of plus disease from a plus disease classification model. The ROP severity was calculated accordingly and compared with the assessment of a human expert. Our method achieved an area under the curve (AUC) of 0.95 (95% confidence interval [CI] 0.90-0.98) in assessing the severity level of ROP. Compared with clinical doctors, our method achieved the highest F1 score value of 0.76 in assessing the severity level of ROP. In conclusion, we developed an interpretable AI system for assessing the severity level of ROP that shows significant potential for use in clinical practice for ROP severity level screening.

Predictors and clinical outcomes of permanent pacemaker implantation after transcatheter aortic valve implantation.

OBJECTIVE: This study aimed to identify the incidence, risk factors, and outcomes of permanent pacemaker (PPM) implantation after transcatheter aortic valve implantation (TAVI) procedures. METHODS: A retrospective analysis was conducted on 70 patients who underwent TAVI at the Department of Cardiology, Fujian Provincial Hospital, from January 2018 to March 2022. Based on whether a new PPM was implanted after TAVI, all patients were divided into two groups: NEW PPM and NO PPM. Baseline characteristics and clinical data were compared between the two groups. Univariate analysis was used to analyze different variables between the two groups. A binary logistic regression analysis was used to evaluate independent correlates for PPM implantation after TAVI. RESULTS: The mean age of the 70 patients was 73.1 ± 8.8 years. The incidence of PPM implantation was 17.1%. Patients with diabetes and chronic kidney disease were more likely to require PPM (50% vs. 20.7%, p = 0.042, 25% vs. 5.2%, p = 0.042). Our study did not identify any significant differences in the incidence of electrocardiographic conduction disturbances except for the previous right bundle branch block (RBBB) (NO PPM 6.9% vs. NEW PPM 33.3%, p < 0.05). We found that prosthesis size, implantation depth, procedural duration, and length of hospital and intensive care unit (ICU) stays were comparable between the two groups. The leading independent predictors of PPM implantation were previous RBBB (odds ratio 10.129, p = 0.034). CONCLUSION: The previous RBBB was the leading independent predictor of PPM implantation. New PPM was not associated with significantly new-onset left BBB, extended post-procedure hospitalization, ICU stay, or procedural duration.

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway.

The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

Geriatric nutrition risk index in the prediction of all-cause and cardiovascular mortality in older adults with hyperlipidemia: NHANES 1999-2018.

BACKGROUND: Malnutrition is linked to a higher risk of unfavorable outcomes in various illnesses. The present investigation explored the correlation between inadequate nutritional condition and outcomes in older individuals diagnosed with hyperlipidemia. METHODS: The geriatric nutritional risk index (GNRI) was used to evaluate the nutritional status. All patients were divided into two groups according to GNRI. A Kaplan-Meier analysis was used to assess the survival rates of different groups at risk of malnutrition. In addition, GNRI was used in COX proportional risk regression models to evaluate its predictive effect on both overall mortality and cardiovascular mortality among patients with hyperlipidemia. Furthermore, the study employed restricted cubic splines (RCS) to examine the nonlinear correlation between GNRI and mortality. RESULTS: The study included 4,532 elderly individuals diagnosed with hyperlipidemia. During a median follow-up duration of 139 months, a total of 1498 deaths from all causes and 410 deaths from cardiovascular causes occurred. The Kaplan-Meier analysis demonstrated significantly poorer survival among individuals at risk of malnutrition, as indicated by the GNRI. In the malnutrition risk group, the modified COX proportional hazards model revealed that a decrease in GNRI was associated with a higher risk of all-cause mortality (HR=1.686, 95% CI 1.212-2.347) and cardiovascular mortality (HR=3.041, 95% CI 1.797-5.147). Furthermore, the restricted cubic splines revealed a non-linear association between GNRI and both all-cause mortality and cardiovascular mortality (p-value for non-linearity = 0.0039, p-value for non-linearity=0.0386). CONCLUSIONS: In older patients with hyperlipidemia, lower levels of GNRI are associated with mortality. The GNRI could potentially be used to predict all-cause mortality and cardiovascular mortality.

Corrigendum: Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress.

[This corrects the article DOI: 10.3389/fphar.2024.1303123.].

Phenanthrene-induced hyperuricemia with intestinal barrier damage and the protective role of theabrownin: Modulation by gut microbiota-mediated bile acid metabolism.

Hyperuricemia is prevalent globally and potentially linked to environmental pollution. As a typical persistent organic pollutant, phenanthrene (Phe) poses threats to human health through biomagnification. Although studies have reported Phe-induced toxicities to multiple organs, its impact on uric acid (UA) metabolism remains unclear. In this study, data mining on NHANES 2001-2016 indicated a positive correlation between Phe exposure and the occurrence of hyperuricemia in population. Subsequently, adolescent Balb/c male mice were orally exposed to Phe at a dosage of 10 mg/kg bw every second day for 7 weeks, resulting in dysfunction of intestinal UA excretion and disruption of the intestinal barrier. Utilizing intestinal organoids, 16S rRNA sequencing of gut microbiota, and targeted metabolomic analysis, we further revealed that an imbalance in bile acid metabolism derived from gut microbiota might mediate the intestinal barrier damage. Additionally, the tea extract theabrownin (TB) effectively improved Phe-induced hyperuricemia and intestinal dysfunction at a dose of 320 mg/kg bw per day. In conclusion, this study demonstrates that Phe exposure is positively associated with hyperuricemia and intestinal damage, which provides new insights into the toxic effects induced by Phe. Furthermore, the present study proposes that supplementation with TB would be a healthy and effective improvement strategy for patients with hyperuricemia and intestinal injury caused by environmental factors.

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials.

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

RDLR: A Robust Deep Learning-Based Image Registration Method for Pediatric Retinal Images.

Retinal diseases stand as a primary cause of childhood blindness. Analyzing the progression of these diseases requires close attention to lesion morphology and spatial information. Standard image registration methods fail to accurately reconstruct pediatric fundus images containing significant distortion and blurring. To address this challenge, we proposed a robust deep learning-based image registration method (RDLR). The method consisted of two modules: registration module (RM) and panoramic view module (PVM). RM effectively integrated global and local feature information and learned prior information related to the orientation of images. PVM was capable of reconstructing spatial information in panoramic images. Furthermore, as the registration model was trained on over 280,000 pediatric fundus images, we introduced a registration annotation automatic generation process coupled with a quality control module to ensure the reliability of training data. We compared the performance of RDLR to the other methods, including conventional registration pipeline (CRP), voxel morph (WM), generalizable image matcher (GIM), and self-supervised techniques (SS). RDLR achieved significantly higher registration accuracy (average Dice score of 0.948) than the other methods (ranging from 0.491 to 0.802). The resulting panoramic retinal maps reconstructed by RDLR also demonstrated substantially higher fidelity (average Dice score of 0.960) compared to the other methods (ranging from 0.720 to 0.783). Overall, the proposed method addressed key challenges in pediatric retinal imaging, providing an effective solution to enhance disease diagnosis. Our source code is available at https://github.com/wuwusky/RobustDeepLeraningRegistration .

Enhancing Dengue Virus Production and Immunogenicity with Celcradle™ Bioreactor: A Comparative Study with Traditional Cell Culture Methods.

The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In recent decades, the prevalence of dengue fever has increased markedly, presenting substantial public health challenges. Consequently, the development of an efficacious vaccine against dengue remains a critical goal for mitigating its spread. Our research utilized Celcradle™, an innovative tidal bioreactor optimized for high-density cell cultures, to grow Vero cells for dengue virus production. By maintaining optimal pH levels (7.0 to 7.4) and glucose concentrations (1.5 g/L to 3.5 g/L) during the proliferation of cells and viruses, we achieved a peak Vero cell count of approximately 2.46 × 109, nearly ten times the initial count. The use of Celcradle™ substantially decreased the time required for cell yield and virus production compared to conventional Petri dish methods. Moreover, our evaluation of the immunogenicity of the Celcradle™-produced inactivated DENV4 through immunization of mice revealed that sera from these mice demonstrated cross-reactivity with DENV4 cultured in Petri dishes and showed elevated antibody titers compared to those from mice immunized with virus from Petri dishes. These results indicate that the dengue virus cultivated using the Celcradle™ system exhibited enhanced immunogenicity relative to that produced in traditional methods. In conclusion, our study highlights the potential of the Celcradle™ bioreactor for large-scale production of inactivated dengue virus vaccines, offering significant promise for reducing the global impact of dengue virus infections and accelerating the development of effective vaccination strategies.

Insights into the function of metallic 1T phase tungsten disulfide as cocatalyst decorated zinc indium sulfide for enhanced photocatalytic hydrogen production activity.

Improving the separation efficiency of carriers is an important part of enhancing photocatalytic activity. Herein, we successfully decorated metallic 1T phase tungsten disulfide (1T-WS2) on the surface of zinc indium sulfide (ZnIn2S4) and investigated the synergistic effect of 1T-WS2 on ZnIn2S4. The characterization results show that 1T-WS2 improves the light absorption capacity and utilization efficiency, increases the catalytic active site, improves the photogenerated charge separation efficiency, and optimizes the reduction potential of ZnIn2S4. Theoretical calculations show that compared with ZnIn2S4, 1T-WS2/ZnIn2S4 has a smaller adsorption Gibbs free energy of the intermediate state H*, which is conducive to the catalytic reaction. Under simulated solar irradiation, the hydrogen (H2) production rate of 1T-WS2/ZnIn2S4 with a loading of 12 wt% reaches 30.90 mmol h-1 g-1, which is 3.38 times higher than that of single ZnIn2S4 (9.13 mmol h-1 g-1). In addition, the apparent quantum efficiency of 1T-WS2/ZnIn2S4 with a loading of 12 wt% reaches 21.14 % under monochromatic light at a wavelength of λ = 370 nm. This work analyzes the light absorption and carrier separation to the catalytic site, and elucidates the mechanism for the enhancement of the photocatalytic hydrogen production performance.

WWC1 upregulation accelerates hyperuricemia by reduction in renal uric acid excretion through Hippo signaling pathway.

Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA), primarily attributed to the hepatic overproduction and renal underexcretion of UA. Despite the elucidation of molecular pathways associated with this underexcretion, the etiology of HUA remains largely unknown. In our study, using by Uox knockout rats, HUA mouse, and cell line models, we discovered that the increased WWC1 levels were associated with decreased renal UA excretion. Additionally, using knockdown and overexpression approaches, we found that WWC1 inhibited UA excretion in renal tubular epithelial cells. Mechanistically, WWC1 activated the Hippo pathway, leading to phosphorylation and subsequent degradation of the downstream transcription factor YAP1, thereby impairing the ABCG2 and OAT3 expression through transcriptional regulation. Consequently, this reduction led to a decrease in UA excretion in renal tubular epithelial cells. In conclusion, our study has elucidated the role of upregulated WWC1 in renal tubular epithelial cells inhibiting the excretion of UA in the kidneys and causing HUA.

Risk factors and patterns for progression of fellow-eye myopic traction maculopathy: a 3-year retrospective cohort study.

AIMS: To investigate the effect of preretinal tractional structures (PTS) and posterior scleral structures (PSS) on myopic traction maculopathy (MTM) progression. METHODS: This retrospective cohort study included 185 fellow highly myopic eyes of 185 participants who underwent surgery for MTM. PTS included epiretinal membrane, incomplete posterior vitreous detachment and their combination. PSS included posterior staphyloma and dome-shaped macula (DSM). The MTM stage was graded according to the Myopic Traction Maculopathy Staging System. Optical coherence tomography was used to identify MTM progression, defined as an upgrade of MTM. The Kaplan-Meier method with log-rank test was used to assess MTM progression over the 3-year follow-up period. Risk factors for progression were identified using Cox regression analysis. RESULTS: MTM progression was observed in 48 (25.9%) eyes. Three-year progression-free survival (PFS) rates for eyes with PTS, staphyloma and DSM were 53.7%, 58.2% and 90.7%, respectively. Eyes with PTS and staphyloma exhibited lower 3-year PFS rates than those without PTS or staphyloma (P log-rank test =0.002 and <0.001), while eyes with DSM had a higher 3-year PFS rate than eyes without DSM (P log-rank test=0.01). Multivariate Cox regression analysis showed that PTS (HR, 3.23; p<0.001) and staphyloma (HR, 7.91; p<0.001) were associated with MTM progression, whereas DSM (HR, 0.23; p=0.046) was a protective factor. CONCLUSION: Both PTS and PSS play a critical role in the progression of MTM. Addressing these factors can aid in the management of MTM.

Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy.

BACKGROUND: X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1-associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS. METHODS: hiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy. RESULTS: ROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation. CONCLUSIONS: The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.

Choroidal neovascularisation secondary toX-linked retinoschisis.

AIMS: Choroidal neovascularisation (CNV) in patients with X-linked retinoschisis (XLRS) has been poorly documented. This study aims to investigate the prevalence and clinical characteristics of CNV in patients with XLRS, as well as analyse the preliminary genotype-phenotype correlation. METHODS: A retrospective case series of patients with genetically confirmed XLRS was included. Demographic, clinical and genetic features were analysed, with a comparison between CNV and non-CNV eyes. RESULTS: Among 185 eyes of 129 patients with XLRS, the prevalence of CNV was 8.1% (15/185). The mean diagnostic age of all patients with CNV is 5.1±2.56 years. CNV eyes exhibited a mean best-corrected visual acuity (BCVA) (logarithm of the minimal angle of resolution) of 1.37±0.74. All CNVs were classified as subretinal and active. Peripapillary CNVs accounted for 80.0% (12/15), while subfoveal CNVs accounted for 20.0% (3/15). In CNV eyes, the prevalence of macular atrophy (5/15, 33.3%, p=0.013) and bullous peripheral schisis (14/15, 93.3%, p=0.000) was higher compared with non-CNV eyes. Additionally, CNV eyes exhibited poorer integrity of the outer retina and BCVA (p=0.007) compared with non-CNV eyes. All 15 eyes with CNV underwent anti-vascular endothelial growth factor (anti-VEGF) therapy. Genotype analysis revealed that 7 of 10 patients (70.0%, 10 eyes) were predicted to have missense variants, while 3 of 10 patients (30.0%, 5 eyes) exhibited severe variants. CONCLUSIONS: The prevalence of CNV in XLRS eyes was found to be 8.1%. All CNVs secondary to XLRS were active and classified as type 2. CNV eyes demonstrated poorer visual function and compromised retinal structures. Anti-VEGF therapy demonstrated effectiveness in treating XLRS-CNVs. No significant genotype-phenotype correlation was established.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors.

Background and aim: Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Methods: Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Results: Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. Conclusion: The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China.

BACKGROUND: To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. METHODS: We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. RESULTS: Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were -3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. CONCLUSIONS: For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don't meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

This is the first study to evaluate the effectiveness, cost, and safety of four regimens recommended by the WHO for RR/MDR-TB treatment in China.For RR/MDR-TB patients in China who meet the criteria for the short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO.