Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC). METHODS: During 2012-2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores. RESULTS: After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant. CONCLUSION: Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching.

BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.

Tertiary lymphoid structure formation induced by LIGHT-engineered and photosensitive nanoparticles-decorated bacteria enhances immune response against colorectal cancer.

Tertiary lymphoid structures (TLSs) are known to enhance the prognosis of patients with colorectal cancer (CRC) by fostering an immunologically active tumor microenvironment (TME). Inducing TLS formation therapeutically holds promise for treating immunologically cold CRC, though it poses technical challenges. Here, we design and fabricate a photosensitive bacterial system named E@L-P/ICG. This system is engineered bacteria internally loaded with the cytokine LIGHT and surface-modified with PLGA/ICG nanoparticles (P/ICG NPs). Once accumulated in orthotopic colonic tumors in mice, E@L-P/ICG generates a mild photothermal effect under laser irradiation due to the photosensitive P/ICG NPs. This photothermal effect triggers the self-rupture of E@L-P/ICG and the death of surrounding tumor cells to release adjuvants and antigens, respectively, which in turn synergistically activate the adaptive immune responses. Furthermore, the cytokine LIGHT released from ruptured E@L-P/ICG stimulates the generation of high endothelial vessels (HEVs), promoting lymphocyte recruitment within the TME. These mechanisms lead to the TLS formation in CRC, which further boosts adaptive immune responses through effective infiltration of T cells and B cells, resulting in effectively inhibited tumor growth and extended survival of mice. Our study shows the potential of the E@L-P/ICG system in photosensitively inducing the TLS formation to treat CRC in clinic.

Accelerating diabetic wound healing with Ramulus Mori (Sangzhi) alkaloids via NRF2/HO-1/eNOS pathway.

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus. Ramulus Mori (Sangzhi) alkaloids (SZ-A), an approved oral medication for type 2 diabetes, have not been explored for their potential to enhance the processes involved in diabetic wound healing. This study aims to investigate SZ-A's role in diabetic wound healing mechanisms. The in vivo experimentation involves dividing the subjects into NC and SZ-A groups, with SZ-A dosed at 200 and 400 mg/kg, to assess the therapeutic efficacy of SZ-A. The results of the animal studies show that SZ-A intervention accelerates the processes of diabetic angiogenesis and wound healing in a manner dependent on its concentration. Additionally, a pathological model using advanced glycation end products (AGEs) in HUVECs demonstrates SZ-A's cytoprotective effect. In vitro, SZ-A intervention significantly increases cell proliferation, migration and tube formation, protecting HUVECs from oxidative stress injury induced by AGEs. Mechanistically, SZ-A exerts a protective effect on HUVECs from oxidative stress damage through the activation of the NRF2/HO-1/eNOS signaling pathway. The findings suggest that SZ-A exhibits considerable potential as a promising candidate for treating DFUs, which will aid in more effectively integrating plant-based therapies into clinical settings.

Artificial intelligence (AI) -integrated educational applications and college students' creativity and academic emotions: students and teachers' perceptions and attitudes.

BACKGROUND: Integrating Artificial Intelligence (AI) in educational applications is becoming increasingly prevalent, bringing opportunities and challenges to the learning environment. While AI applications have the potential to enhance structured learning, they may also significantly impact students' creativity and academic emotions. OBJECTIVES: This study aims to explore the effects of AI-integrated educational applications on college students' creativity and academic emotions from the perspectives of both students and teachers. It also assessed undergraduate students' and faculty's attitudes to AI-integrated applications. METHODOLOGY: A mixed-method research design was used. In the first phase, a qualitative research approach was employed, utilizing theoretical sampling to select informants. Data were collected through in-depth interviews with undergraduate students and university lecturers to gain comprehensive insights into their experiences and perceptions. A scale was developed, validated, and administered to 120 students and faculty in the quantitative phase. Descriptive statistics was used to analyze the data. FINDINGS: The study revealed that AI applications often impose rigid frameworks that constrain creative thinking and innovation, leading to emotional disengagement due to AI interactions' repetitive and impersonal nature. Additionally, constant AI assessments heightened performance anxiety, and technical frustrations disrupted the learning process. Conversely, AI applications stimulated creativity by introducing new ideas and problem-solving techniques, enhanced engagement through interactive elements, provided personalized feedback, and supported emotional well-being with gamified elements and constant availability. Quantitative data also verified that teachers and students have positive attitudes toward the benefits and challenges of these applications. CONCLUSIONS: AI integration in educational applications has a dual-edged impact on college students' creativity and academic emotions. While there are notable benefits in stimulating creativity and enhancing engagement, significant challenges such as creativity constraints, emotional disengagement, and performance anxiety must be addressed. Balancing these factors requires thoughtful implementation and continuous evaluation to optimize the role of AI in education.

Changes in lipids and medium- and long-chain fatty acids during the spontaneous fermentation of ripened pu-erh tea.

During the fermentation of ripened pu-erh tea (RPT), the composition of lipids and other compounds changes significantly. In this study, we conducted industrial fermentation of RPT and observed that the levels of water extract, tea polyphenols, free amino acids, catechins, caffeine, rutin, theophylline, luteolin, and myricetin decreased, while the level of soluble sugar increased. Additionally, the levels of gallic acid, quercetin, ellagic acid, and kaempferol first increased and then decreased during fermentation. We identified a total of 731 lipids, which were classified into seven categories using a lipomics method. Among these lipids, 85 with relatively high contents decreased, while 201 lipids with low contents increased after fermentation. This led to an overall decrease in the sum contents of lipids and dominant lipids, including glycerophospholipids and saccharolipids. We also detected 33 medium- and long-chain fatty acids, with α-linolenic acid (881.202 ± 12.13-1322.263 ± 19.78 µg/g), palmitic acid (797.275 ± 19.56-955.180 ± 30.49 µg/g), and linoleic acid (539.634 ± 15.551-706.869 ± 12.14 µg/g) being the predominant ones. Coenzymes Q9 (62.76-63.57 µg/g) and Q10 (50.82-59.33 µg/g) were also identified in the fermentation process. Our findings shed light on the changes in lipids during the fermentation of RPT and highlight the potential bio-active compounds, such as α-linolenic acid, linoleic acid, Coenzymes Q9, and Q10, in ripened pu-erh tea. This contributes to a better understanding of the fermentation mechanism for RPT.

Bidirectional association identified between synovitis and knee and hand osteoarthritis: a general population-based study.

Background: Synovitis has long been considered a common and modifiable inflammatory feature of osteoarthritis (OA), but current disease-modifying anti-inflammatory treatments appear ineffective in OA clinical trials. Elucidating the temporal relationship between synovitis and OA could provide insight into the role of synovitis in OA. Methods: We conducted a prospective cohort study based on the baseline and three-year follow-up data from the Xiangya Osteoarthritis (XO) Study. We assessed bidirectional associations between ultrasound-detected synovitis and radiographic and symptomatic OA at knee and hand sites using generalized estimating equations. Additionally, we performed bidirectional Mendelian randomization (MR) analyses to test these hypotheses utilising whole-genome sequencing data in the XO population. Age, sex, body mass index, smoking, alcohol consumption, educational level, physical activity, and joint injury history were adjusted for these analyses. Findings: A total of 2211, 2420, 2280, and 2600 participants were enrolled for analyses of radiographic knee OA (RKOA), symptomatic knee OA (SKOA), radiographic hand OA (RHOA) and symptomatic hand OA (SHOA), respectively. The baseline synovitis (i.e., with synovitis vs. without synovitis) was associated with the incident RKOA (76/277 vs. 557/3674 knees), SKOA (49/387 vs. 287/4213 knees), RHOA (171/358 vs. 686/3664 hands) and SHOA (35/689 vs. 76/4327 hands), with adjusted odds ratio (aORs) of 2.2 (95% CI 1.7-3.1), 2.0 (1.3-2.9), 3.4 (2.7-4.4), and 2.4 (1.5-3.8), respectively. The baseline RKOA (with OA vs. without OA: 409/1246 vs. 481/3758 knees), SKOA (200/576 vs. 675/4356 knees), RHOA (192/778 vs. 410/3723 hands), and SHOA (41/162 vs. 548/4285 hands) were also associated with the incident synovitis, with aORs of 3.4 (95% CI 2.9-4.1), 2.7 (2.1-3.4), 2.3 (1.8-2.9) and 1.9 (1.2-2.8), respectively. These bidirectional associations were stronger when more active synovitis was compared with the reference group (all P < 0.05). MR analyses further supported bidirectional associations that synovitis significantly increased the odds of incident OA at both sites and vice versa (all ORs ranged from 1.2-1.7). Interpretation: Our population-based cohort study found novel evidence of a bidirectional association between synovitis and OA, which was further validated through MR analysis and suggested that the bidirectional association is likely causal. Our findings indicated that synovitis is both a risk factor and a consequence of the OA rather than solely a risk factor. Funding: The National Key Research and Development Plan, the National Natural Science Foundation of China, the Key Research and Development Program of Hunan Province, the Natural Science Foundation of Hunan Province, the Central South University Innovation-Driven Research Programme, and the Fundamental Research Funds for the Central Universities of Central South University.

The value of phenylalanine in predicting atrial fibrillation risk in chronic heart failure.

Backgrounds: Atrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF. Methods: The cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography-tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months). Results: Serum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P < 0.001). Serum Phe value was the independent risk factor for predicting AF in HF [odds ratio (OR), 1.640; 95% CI: 1.150-2.339; P = 0.006]. Phe levels were correlated positively with hsCRP value in HF patients with AF (r = 0.577, P < 0.001). The elevated Phe levels were associated with a higher risk of HF endpoint events in HF patients with AF (log-rank P = 0.005). Conclusions: In HF with AF subjects, elevated Phe value confers an increased risk for prediction AF and was more related to poor HF endpoint events. Phe can be a valuable index of AF in HF.

Mouse testicular macrophages can independently produce testosterone and are regulated by Cebpb.

BACKGROUND: Testicular macrophages (TM) have long been recognized for their role in immune response within the testicular environment. However, their involvement in steroid hormone synthesis, particularly testosterone, has not been fully elucidated. This study aims to explore the capability of TM to synthesize and secrete testosterone de novo and to investigate the regulatory mechanisms involved. RESULTS: Transcriptomic analysis revealed significant expression of Cyp11a1, Cyp17a1, Hsd3b1, and Hsd17b3 in TM, which are key enzymes in the testosterone synthesis pathway. qPCR analysis and immunofluorescence validation confirmed the autonomous capability of TM to synthesize testosterone. Ablation of TM in mice resulted in decreased physiological testosterone levels, underscoring the significance of TM in maintaining testicular testosterone levels. Additionally, the study also demonstrated that Cebpb regulates the expression of these crucial genes, thereby modulating testosterone synthesis. CONCLUSIONS: This research establishes that TM possess the autonomous capacity to synthesize and secrete testosterone, contributing significantly to testicular testosterone levels. The transcription factor Cebpb plays a crucial role in this process by regulating the expression of key genes involved in testosterone synthesis.

siRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr-/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

Comparison of the Accuracy of HSV1 and HSV2 Antibody Tests with PCR in the Diagnosis of Recurrent Genital Herpes.

Objective: To assess the accuracy of HSV1and HSV2 antibody testing in identifying genital herpes infection. Methods: A cohort of 299 patients previously diagnosed with recurrent genital herpes, confirmed via PCR, were tested using ELISA for HSV1 and HSV2 IgM and IgG antibodies. The study compared the accuracy of HSV1 and HSV2 antibody tests in diagnosing genital herpes. Results: Among 299 patients, 14 tested positives for HSV1 DNA. Of these, 9 had HSV1 IgG antibodies, but none had HSV2 IgG antibody. Among 278 patients with HSV2 DNA, 149 had HSV1 IgG, 9 had HSV2 IgG, and 97 had both. Seven patients had both HSV1 and HSV2 DNA; 3 had HSV1 IgG, 1 had HSV2 IgG, and 3 had both. The accuracy of HSV1 IgG for HSV1 infection was 64.2%, and for HSV1 and HSV2 co-infection, 85.7%. The accuracy of HSV2 IgG for HSV2 infection was 38.1%, and for HSV1 and HSV2 co-infection, 57.1%. The combined antibody positivity accuracy was 34.9%. Conclusion: Genital herpes is primarily caused by HSV2 (92.98%). A smaller percentage is HSV1 (4.67%) or co-infection (2.34%). Despite relatively low diagnostic accuracy (34.9-85.7%) for antibody detection, combined antibody testing is necessary. Herpes DNA testing is recommended for accurate diagnosis. Absence of antibodies does not rule out genital herpes and clinical assessment is essential.

Diabetic peripheral neuropathy based on Schwann cell injury: mechanisms of cell death regulation and therapeutic perspectives.

Diabetic peripheral neuropathy (DPN) is a complication of diabetes mellitus that lacks specific treatment, its high prevalence and disabling neuropathic pain greatly affects patients' physical and mental health. Schwann cells (SCs) are the major glial cells of the peripheral nervous system, which play an important role in various inflammatory and metabolic neuropathies by providing nutritional support, wrapping axons and promoting repair and regeneration. Increasingly, high glucose (HG) has been found to promote the progression of DPN pathogenesis by targeting SCs death regulation, thus revealing the specific molecular process of programmed cell death (PCD) in which SCs are disrupted is an important link to gain insight into the pathogenesis of DPN. This paper is the first to review the recent progress of HG studies on apoptosis, autophagy, pyroptosis, ferroptosis and necroptosis pathways in SCs, and points out the crosstalk between various PCDs and the related therapeutic perspectives, with the aim of providing new perspectives for a deeper understanding of the mechanisms of DPN and the exploration of effective therapeutic targets.

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.

BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

Combination of traditional Chinese medicine and standard biomedical treatment for rosacea: a systematic review and a meta-analysis.

Background: A combination of standard biomedical treatment and traditional Chinese medicine (TCM) has been suggested as a therapeutic approach for rosacea that may significantly lower the recurrence rate and clinical symptom scores. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of this combination treatment on clinical symptom and TCM syndrome scores, as well as on the scores of the Dermatology Life Quality Index (DLQI), erythema index (EI), and interleukin 37 (IL-37) levels in patients with rosacea. Methods: The PROSPERO registration number for the study is CRD42023472737. We systematically searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure Wanfang Database, China Biomedical Medicine database (CBM), and the VIP information resource integration service platform (cqvip) databases for RCTs (published from the beginning to September 2023, regardless of the language used) that compared the traditional Chinese medicine and standard biomedical treatment combination treatment to conventional anti-rosacea treatments. Our primary outcomes comprised the clinical symptom and TCM syndrome scores, and the scores of Dermatology Life Quality Index, erythema index, and IL-37 levels. We used a random-effects model to evaluate the pooled data. Results: We identified 260 studies. Of these, 13 eligible studies were employed for analysis (N = 1,348 participants). Compared with other anti-rosacea treatments, the TCM and standard biomedical treatment combination treatment yielded an improved mean reduction in the clinical symptom score -2.24% [95% CI (-3.02 to -1.46), p < 0.00001], TCM syndrome score -4.42 [95% CI (-5.33 to -3.50), p < 0.00001], and the score of DLQI of -2.55 [95% CI (-3.73 to -1.36), p < 0.00001], EI of -151.97 [95% CI (-276.59 to -27.36), p < 0.00001], and IL-37 level -4.23 [95% CI (-4.95 to -3.51), p = 0.854], as well as in the overall effective rate risk ratio (RR) = 1.25 [95%CI (1.18, 1.32), p = 0.994] and the recurrence rate = 0.27 [95%CI (0.15, 0.46), p = 0.297]. Conclusion: The TCM and standard biomedical treatment combination treatment can provide a better outcome, including a reduction in the TCM syndrome and clinical symptom scores, and in the scores of DLQI, EI, and IL-37. Hence, this combination is a viable and more effective therapeutic approach for rosacea. However, these results should be considered cautiously because of uncertain evidence and the low quality of the study reports considered in this meta-analysis. Systematic Review Registration: website, identifier CRD42023472737.

The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis.

BACKGROUND: MOTS-c is known as mitochondrial open reading frame (ORF) of the twelve S c, produced by a small ORF-encoded peptides (SEPs) in mitochondrial 12S rRNA region. There is growing evidence that MOTS-c has a strong relationship with the expression of inflammation- and metabolism-associated genes and metabolic homeostasis, and even offering some protection against insulin resistance (IR). However, studies have reported inconsistent correlations between different population characteristics and MOTS-c levels. This meta-analysis aims to elucidate MOTS-c levels in physiological and pathological states, and its correlation with metabolic features in various physiological states. METHODS: We conducted a systematic review and meta-analysis to synthesize the evidence of changes in blood MOTS-c concentration, and any association between MOTS-c and population characteristic. The Web of Science, PubMed, EMBASE, CNKI, WANGFANG and VIP databases were searched from inception to April 2023. The statistical analysis was summarized using the standardized mean difference (SMD) and 95% confidence interval (95% CIs). Pearson correlation coefficient was used to analyze the correlation and generate forest plots through a random-effects model. Additional analyses as sensitivity and subgroup analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger's test. All related statistical analyses were performed using Revman 5.3 and Stata 15 statistical software. RESULT: There are 6 case-control studies and 1 cross-sectional study (11 groups) including 602 participants in our current meta-analysis. Overall analysis results showed plasma MOTS-c concentration in diabetes and obesity patients was significantly reduced (SMD = - 0.37; 95% CI- 0.53 to - 0.20; P < 0.05). After subgroup analysis, the present analysis has yielded opposite results for MOTS-c changes in obesity (SMD = 0.51; 95% CI 0.21 to 0.81; P < 0.05) and type 2 diabetes mellitus (T2DM) (SMD = - 0.89; 95% CI - 1.12 to - 0.65; P < 0.05) individuals. Moreover, the correlation analysis was performed to identify that MOTS-c levels were significantly positively correlated with TC (r = 0.29, 95% CI 0.20 to 0.38) and LDL-c (r = 0.30, 95% CI 0.22 to 0.39). The subgroup analysis results showed that MOTS-c decreased significantly in patients with diabetes (SMD = - 0.89; 95% CI- 1.12 to - 0.65; P < 0.05). In contrast, the analysis result for obesity persons (BMI > 28 kg/ m2) was statistically significant after overweight people (BMI = 24-28 kg/ m2) were excluded (SMD = 0.51; 95% CI 0.21 to 0.81; P < 0.05), which is completely different from that of diabetes. Publication bias was insignificant (Egger's test: P = 0.722). CONCLUSION: Circulating MOTS-c level was significantly reduced in diabetic individuals but was increased significantly in obesity patients. The application of monitoring the circulating levels variability of MOTS-c in routine screening for obesity and diabetes is prospects and should be taken into consideration as an important index for the early prediction and prevention of metabolic syndrome in the future. PROSPERO registration number CRD42021248167.

The Economic Burden of Brucellosis Care in China: Socioeconomic Status Inequality.

The economic burden of brucellosis care on patients can lead to significant financial strain, despite partial coverage by medical insurance. However, there is limited research on the out-of-pocket costs faced by brucellosis patients. Therefore, our study aimed to investigate the costs and out-of-pocket expenses of brucellosis care, specifically examining the varying socioeconomic status of patients in Xinjiang, China. We collected cost and demographic data from 563 respondents and their hospital bills and employed latent variable analysis to assess socioeconomic status. The majority of patients belonged to the middle and lower socioeconomic status categories (85.97%), and they were primarily farmers and herders (82.77%). The median direct cost per brucellosis episode was USD 688.65, with out-of-pocket expenses amounting to USD 391.44. These costs exceeded both the 2020 Xinjiang and national per capita health expenditures (USD 233.66 and USD 267.21, respectively). Notably, the overall medical reimbursement rate was 48.60%, and for outpatient costs, it was merely 12.82%. Despite higher out-of-pocket costs among high socioeconomic status patients, the percentage of income spent was higher (37.23%) for patients in the lower socioeconomic status group compared to other groups (16.25% and 12.96%). In conclusion, our findings highlight that brucellosis patients are predominantly from the middle and lower socioeconomic status, with high out-of-pocket expenses placing them under significant financial pressure. Moreover, there is notable inequity in economic consequences across different socioeconomic status groups. These results call for policy interventions aimed at reducing brucellosis-related poverty and promoting equitable access to care.

The causal relationship between autoimmune diseases and rhinosinusitis, and the mediating role of inflammatory proteins: a Mendelian randomization study.

Observational studies have linked autoimmune diseases (ADs) with rhinosinusitis (RS) manifestations. To establish a causal relationship between ADs and RS, and to explore the potential mediating role of inflammatory mediators between ADs and RS, we utilized Mendelian randomization (MR) analysis. Using a two-sample MR methodology, we examined the causality between multiple sclerosis (MS), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), type 1 diabetes (T1D), Sjogren's syndrome (SS), celiac disease (CeD), Crohn's disease (CD), hypothyroidism (HT), Graves' disease (GD), and Hashimoto's thyroiditis and their association with chronic and acute rhinosinusitis (CRS and ARS, respectively).To achieve this, we employed three distinct MR techniques: inverse variance weighting (IVW), MR-Egger, and the weighted median method. Our analysis also included a variety of sensitivity assessments, such as Cochran's Q test, leave-one-out analysis, MR-Egger intercept, and MR-PRESSO, to ensure the robustness of our findings. Additionally, the study explored the role of inflammation proteins as a mediator in these relationships through a comprehensive two-step MR analysis. Among the ADs, MS, RA, T1D, CeD, and HT were determined as risk factors for CRS. Only CeD exhibited a causal relationship with ARS. Subsequent analyses identified interleukin-10 (IL-10) as a potential mediator for the association of MS, RA and HT with CRS, respectively., while C-X-C motif chemokine 10 levels (CXCL10) and T-cell surface glycoprotein CD6 isoform levels (CD6) were found to influence HT's effect on CRS. Our findings demonstrate a causative link between specific autoimmune diseases and rhinosinusitis, highlighting IL-10, CXCL10, and CD6 as potential mediators in this association.

An exploration of the causal relationship between 731 immunophenotypes and osteoporosis: a bidirectional Mendelian randomized study.

Background: There are complex interactions between osteoporosis and the immune system, and it has become possible to explore their causal relationship based on Mendelian randomization methods. Methods: Utilizing openly accessible genetic data and employing Mendelian randomization analysis, we investigated the potential causal connection between 731 immune cell traits and the risk of developing osteoporosis. Results: Ten immune cell phenotypes were osteoporosis protective factors and three immune cell phenotypes were osteoporosis risk factors. Specifically, the odds ratio (OR) of IgD+ CD24+ %B cell (B cell panel) risk on Osteoporosis was estimated to be 0.9986 (95% CI = 0.9978~0.9996, P<0.01). The OR of CD24+ CD27+ %B cell (B cell panel) risk on Osteoporosis was estimated to be 0.9991 (95% CI = 0.9984~0.9998, P = 0.021). The OR of CD33- HLA DR+AC (Myeloid cell panel) risk on Osteoporosis was estimated to be 0.9996 (95% CI = 0.9993~0.9999, P = 0.038). The OR of EM CD8br %CD8br (Maturation stages of T cell panel) risk on Osteoporosis was estimated to be 1.0004 (95% CI = 1.0000~1.0008, P = 0.045). The OR of CD25 on IgD+ (B cell panel) risk on Osteoporosis was estimated to be 0.9995 (95% CI = 0.9991~0.9999, P = 0.024). The OR of CD25 on CD39+ activated Treg+ (Treg panel) risk on Osteoporosis was estimated to be 1.001 (95% CI = 1.0001~1.0019, P = 0.038). The OR of CCR2 on CD62L+ myeloid DC (cDC panel) risk on Osteoporosis was estimated to be 0.9992 (95% CI = 0.9984~0.9999, P = 0.048). The OR of CCR2 on CD62L+ plasmacytoid DC (cDC panel) risk on Osteoporosis was estimated to be 0.9993 (95% CI = 0.9987~0.9999, P = 0.035). The OR of CD45 on CD33dim HLA DR+ CD11b- (Myeloid cell panel) risk on Osteoporosis was estimated to be 0.9988 (95% CI = 0.9977~0.9998, P = 0.031). The OR of CD45 on Mo MDSC (Myeloid cell panel) risk on Osteoporosis was estimated to be 0.9992 (95% CI = 0.9985~0.9998, P = 0.017). The OR of SSC-A on B cell (TBNK panel) risk on Osteoporosis was estimated to be 0.9986 (95% CI = 0.9972~0.9999, P = 0.042). The OR of CD11c on CD62L+ myeloid DC (cDC panel) risk on Osteoporosis was estimated to be 0.9987 (95% CI = 0.9978~0.9996, P<0.01). The OR of HLA DR on DC (cDC panel) risk on Osteoporosis was estimated to be 1.0007 (95% CI = 1.0002~1.0011, P<0.01). No causal effect of osteoporosis on immune cells was observed. Conclusions: Our study identified 13 unreported immune phenotypes that are causally related to osteoporosis, providing a theoretical basis for the bone immunology doctrine.

19F MRI/CEUS Dual Imaging-Guided Sonodynamic Therapy Enhances Immune Checkpoint Blockade in Triple-Negative Breast Cancer.

Treatment of highly aggressive triple-negative breast cancer (TNBC) in the clinic is challenging. Here, a liposome nanodrug (LP@PFH@HMME) integrating imaging agents and therapeutic agents for bimodal imaging-guided sonodynamic therapy (SDT) is developed, which boosted immunogenicity to enable potent immunotherapy via immune checkpoint blockade (ICB) in TNBC. In the acidic tumor microenvironment (TME), LP@PFH@HMME undergoes "nano-to-micro" transformation due to a pH-responsive lipid fusion, which makes droplets much more sensitive to ultrasound (US) in contrast-enhanced ultrasound (CEUS) and SDT studies. The nanodrug demonstrates robust bimodal imaging ability through fluorine-19 magnetic resonance imaging (19F MRI) and CEUS bimodal imaging, and it exhibits excellent solubility in aqueous solution with relatively high 19F content and desirable long transverse relaxation time (T2 = 1.072 s), making it suitable for high-performance 19F MRI, in addition to effective accumulation of nanodrugs after tail vein injection. Thus, 19F MRI/CEUS dual imaging is achievable to show adequate time points for US irradiation of tumor sites to induce highly effective SDT, which produces abundant reactive oxygen species (ROS) triggering immunogenic cell death (ICD) to assist ICB-based immunotherapy. The combination treatment design of sonodynamic therapy with immunotherapy effectively inhibited TNBC growth and recurrence, highlighting the promise of multifunctional nanodrugs in treating TNBC.

Novel Diagnostic Biomarkers Related to Necroptosis and Immune Infiltration in Coronary Heart Disease.

Purpose: Necroptosis, a monitored form of inflammatory cell death, contributes to coronary heart disease (CHD) progression. This study examined the potential of using necroptosis genes as diagnostic markers for CHD and sought to elucidate the underlying roles. Methods: Through bioinformatic analysis of GSE20680 and GSE20681, we first identified the differentially expressed genes (DEGs) related to necroptosis in CHD. Hub genes were identified using least absolute shrinkage and selection operator (LASSO) regression and random forest analysis after studying immune infiltration and transcription factor-miRNA interaction networks according to the DEGs. Quantitative polymerase chain reaction and immunohistochemistry were used to further investigate hub gene expression in vivo, for which a diagnostic model was constructed and the predictive efficacy was validated. Finally, the CHD group was categorized into high- and low-score groups in accordance with the single-sample gene set enrichment analysis (ssGSEA) score of the necroptosis genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GSEA, and further immune infiltration analyses were performed on the two groups to explore the possible roles of hub genes. Results: Based on the results of the LASSO regression and random forest analyses, four genes were used to construct a diagnostic model to establish a nomogram. Additionally, an extensive analysis of all seventeen necroptosis genes revealed notable distinctions in expression between high-risk and low-risk groups. Evaluation of immune infiltration revealed that neutrophils, monocytes, B cells, and activated dendritic cells were highly distributed in the peripheral blood of patients with CHD. Specifically, the high CHD score group exhibited greater neutrophil and monocyte infiltration. Conversely, the high-score group showed lower infiltration of M0 and M2 macrophages, CD8+ T, plasma, and resting mast cells. Conclusion: TLR3, MLKL, HMGB1, and NDRG2 may be prospective biomarkers for CHD diagnosis. These findings offer plausible explanations for the role of necroptosis in CHD progression through immune infiltration and inflammatory response.