Identification of tumor-specific T cell signature predicting cancer immunotherapy response in bladder cancer by multi-omics analysis and experimental verification.

BACKGROUND: Numerous gene signatures predicting the prognosis of bladder cancer have been identified. However, a tumor-specific T cell signature related to immunotherapy response in bladder cancer remains under investigation. METHODS: Single-cell RNA and TCR sequencing from the Gene expression omnibus (GEO) database were used to identify tumor-specific T cell-related genes in bladder cancer. Subsequently, we constructed a tumor-specific T cell signature (TstcSig) and validated its clinical relevance for predicting immunotherapy response in multiple immunotherapy cohorts. Further analyses explored the immune characteristics of TstcSig in bladder cancer patients from other cohorts in the TCGA and GEO databases. Western blot (WB), multicolor immunofluorescence (MIF), qRT-PCR and flow cytometry assays were performed to validate the results of bioinformatics analysis. RESULTS: The established TstcSig, based on five tumor-specific T cell-related genes, could predict outcomes in a bladder cancer immunotherapy cohort. This was verified using two additional immunotherapy cohorts and showed better predictive performance compared to 109 published T cell signatures. TstcSig was strongly correlated with immune characteristics such as immune checkpoint gene expression, tumor mutation burden, and T cell infiltration, as validated by single-cell and spatial transcriptomics datasets. Notably, the positive correlation between TstcSig and T cell infiltration was confirmed in the TCGA cohort. Furthermore, pan-cancer analysis demonstrated the heterogeneity of the prognostic value of TstcSig. Tumor-specific T cells highly expressed CD27, IFNG, GZMB and CXCL13 and secreted more effector cytokines for tumor cell killing, as validated experimentally. CONCLUSION: We developed a five-gene signature (including VAMP5, TIGIT, LCK, CD27 and CACYBP) based on tumor-specific T cell-related genes to predict the immunotherapy response in bladder cancer patients.

Fe Single Atom Catalysts Promoting Polysulfide Redox Reduction in Quantum Dot Photovoltaics.

Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.

Determination of Blast Vibration Safety Criteria for Buried Polyethylene Pipelines Adjacent to Blast Areas, Using Vibration Velocity and Strain Data.

In order to ensure the safe operation of buried polyethylene pipelines adjacent to blasting excavations, controlling the effects of blasting vibration loads on the pipelines is a key concern. Model tests on buried polyethylene pipelines under blasting loads were designed and implemented, the vibration velocity and dynamic strain response of the pipelines were obtained using a TC-4850 blast vibrometer and a UT-3408 dynamic strain tester, and the distribution characteristics of blast vibration velocity and dynamic strain were analyzed based on the experimental data. The results show that the blast load has the greatest effect on the circumferential strain of the polyethylene pipe, and the dynamic strain response is greatest at the section of the pipe nearest to the blast source. Pipe peak vibration velocity (PPVV), ground peak particle velocity (GPPV), and the peak dynamic strain of the pipe were highly positively correlated, which verifies the feasibility of using GPPV to characterize pipeline vibration and strain level. According to the failure criteria and relevant codes, combined with the analysis of experimental results, the safety threshold of additional circumferential stress on the pipeline is 1.52 MPa, and the safety control vibration speed of the ground surface is 21.6 cm/s.

Weight loss-induced improvement of body weight and insulin sensitivity is not amplified by a subsequent 12-month weight maintenance intervention but is predicted by adaption of adipose atrial natriuretic peptide system: 48-month results of a randomized controlled trial.

BACKGROUND: Behavioral weight loss interventions are frequently hampered by long-term inefficacy. As metabolic improvements and health-related quality of life (HRQoL) are diminished by weight regain, effective long-term strategies are highly desirable. We aimed to analyze whether an additional weight maintenance intervention could delay body weight regain and can induce a long-term improvement of metabolism and HRQoL for up to 48 months in humans. Given the short-term metabolic effects of natriuretic peptides (NP), we also investigated the role of the adipose atrial NP (ANP) system in this long-term context. METHODS: After a successful 12-week weight reduction program 143 subjects (age>18; BMI≥27 kg/m2) were randomized (1:1) to a control group or a 12-month multimodal weight maintenance intervention focusing on nutritional counseling and physical exercises. Secondary trial outcomes including course of BMI, HOMA-IR, glucose response after oGTT (glucoseAUC), and HRQoL (SF-36) were analyzed yearly for 48 months. Adipose ANP receptor mRNA expression was analyzed during weight loss. RESULTS: Initial weight loss (- 4.7±1.5 kg/m2) improved glucoseAUC, HOMA-IR, and HRQoL. Although BMI was still reduced after 48 months (-1.98 [95% CI -2.61, -1.35] kg/m2), benefits on HOMA-IR, glucoseAUC, and mental health disappeared after 36 (-0.49 [-1.00, 0.02]), 18 (0.61 [-9.57, 10.79] mg dl-1 min-1), and 18 months (2.06 [-0.08, 4.20]), respectively, while improved physical health persisted up to months 48 (2.95 [0.49, 5.40]). Weight maintenance intervention inhibited weight regain and delayed impairment of HOMA-IR and glucoseAUC (but not HRQoL) for up to 12 months. However, no metabolic long-term effect was seen beyond the intervention period. Lower adipose NPR-C and higher NPR-A mRNA expression after weight loss predicted smaller regain of weight (r=0.398; p<0.05)/fat mass (FM) (r=0.391; p<0.05) and longer improvement of HOMA-IR (r=-0.422; p<0.05), respectively. CONCLUSIONS: Additional benefits of a behavioral 12-month weight maintenance intervention after weight loss regarding body weight regain and metabolic improvement does not persist beyond the intervention period. However, weight loss-induced modulation of the adipose ANP system is probably involved in the long-term control of body weight regain and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00850629 . Registered on February 25, 2009.

Executive summary of the American Radium Society appropriate use criteria for management of uterine clear cell and serous carcinomas.

BACKGROUND: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies. OBJECTIVE: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas. RESULTS: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy. CONCLUSION: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence.

Executive summary of the American Radium Society® Appropriate Use Criteria for management of uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS. An extensive analysis of current medical literature from peer-reviewed journals was performed. A well-established methodology (modified Delphi) was used to rate the appropriate use of imaging and treatment procedures for the management of UCS. These guidelines are intended for the use of all practitioners who desire information about the management of UCS. RESULTS: The majority of patients with UCS will present with advanced extra uterine disease, with 10% presenting with metastatic disease. They have worse survival outcomes when compared to uterine high-grade endometrioid adenocarcinomas. The primary treatment for non-metastatic UCS is complete surgical staging with total hysterectomy, salpingo-oophorectomy and lymph node staging. Patients with UCS appear to benefit from adjuvant multimodality therapy to reduce the chance of tumor recurrence with the potential to improve overall survival. CONCLUSION: Women diagnosed with uterine UCS should undergo complete surgical staging. Adjuvant multimodality therapies should be considered in the treatment of both early- and advanced stage patients. Long-term surveillance is indicated as many of these women may recur. Prospective clinical studies of women with UCS are necessary for optimal management.

Induction of labor in patients with an unfavorable cervix after a cesarean using an osmotic dilator versus vaginal prostaglandin.

BACKGROUND: Trial of labor after cesarean (TOLAC) is a viable option for safe delivery. In some cases cervical ripening and subsequent labor induction is necessary. However, the commonly used prostaglandins are not licensed in this subgroup of patients and are associated with an increased risk of uterine rupture. METHODS: This cohort study compares maternal and neonatal outcomes of TOLAC in women (n=82) requiring cervical ripening agents (osmotic dilator vs. prostaglandins). The initial Bishop scores (BSs) were 2 (0-5) and 3 (0-5) (osmotic dilator and prostaglandin group, respectively). In this retrospective analysis, Fisher's exact test, the Kruskal-Wallis rank sum test and Pearson's chi-squared test were utilized. RESULTS: Vaginal birth rate (including operative delivery) was 55% (18/33) in the osmotic dilator group vs. 51% (25/49) in the dinoprostone group (P 0.886). Between 97% and 92% (32/33 and 45/49) (100%, 100%) of neonates had an Apgar score of >8 after 1 min (5, 10 min, respectively). The time between administration of the agent and onset of labor was 36 and 17.1 h (mean, Dilapan-S® group, dinoprostone group, respectively). Time from onset of labor to delivery was similar in both groups with 4.4 and 4.9 h (mean, Dilapan-S® group, dinoprostone group, respectively). Patients receiving cervical ripening with Dilapan-S® required oxytocin in 97% (32/33) of cases. Some patients presented with spontaneous onset of labor, mostly in the dinoprostone group (24/49, 49%). Amniotomy was performed in 64% and 49% (21/33 and 24/49) of cases (Dilapan-S® group and dinoprostone group, respectively). CONCLUSIONS: This pilot study examines the application of an osmotic dilator for cervical ripening to promote vaginal delivery in women who previously delivered via cesarean section. In our experience, the osmotic dilator gives obstetricians a chance to perform induction of labor in these women.

Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ.

OBJECTIVE: The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. METHODS: Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. RESULTS: The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. CONCLUSIONS: Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

Effects of diabetes mellitus on biomechanical properties of the rabbit cornea.

To investigate the effects of diabetes on the biomechanical behavior of cornea in alloxan-induced diabetic rabbits. Diabetes mellitus (DM) was induced in 20 rabbits using alloxan, while another 20 age- and weight-matched non-diabetic rabbits served as controls. Eyes were enucleated after 8 weeks of inducing diabetes and the whole cornea was removed with a 3 mm wide scleral ring and tested under inflation conditions with an internal pressure range of 2.0-30.0 mmHg to determine their stress-strain behavior using an inverse analysis process. The blood glucose level (BG), advanced glycosylation end products (AGEs), central corneal thickness (CCT) and intraocular pressure (IOP) increased significantly in the DM group. There were statistically significant correlations between BG and AGEs (r = 0.768, p = 0.00), and between AGEs and CCT variation upon induction of DM (r = 0.594, p = 0.00). The tangent modulus (Et) of the cornea at four stress levels (1-4 kPa, equivalent to approximately IOP of 7.5, 15, 22.5 and 30 mmHg, respectively) was significantly higher in diabetic rabbits than in the control group (p < 0.05). Further, Et at stress of 2 kPa (which corresponded to the average IOP for the control group) was significantly correlated with BG (r = 0.378, p < 0.05), AGEs (r = 0.496, p < 0.05) and CCT variation upon induction of DM (r = 0.439, p < 0.05). IOP, as measured by contact tonometry, was also significantly correlated with both CCT (r = 0.315, p < 0.05) and Et at 2 kPa (r = 0.329, p < 0.05), and even after correcting for the effects of CCT and Et, IOP still significantly increased with both AGEs (r = 0.772, p = 0.00) and BG (r = 0.762, p = 0.00). The cornea of diabetic rabbits showed a significant increase in mechanical stiffness as evidenced by increases in corneal thickness and tangent modulus. The Et increase may be explained by a non-enzymatic cross-linking of collagen fibrils mediated by AGEs due to the high blood glucose levels in diabetes. The study also found significant IOP increases with higher blood glucose level even after controlling the effects of both corneal thickness and tangent modulus.

Access to 8-Azachromones via Activation of C-H in N-Oxides.

A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or Ac2O activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.

Mobility impairment, social engagement, and life satisfaction among the older population in China: a structural equation modeling analysis.

PURPOSE: Revealing the relationship between mobility impairment and life satisfaction can help to propose effective interventions to secure mobility and life satisfaction. However, the relationship remains unclear and lacks quantitative evidence in China. This study therefore assesses the association of mobility impairment, social engagement, and life satisfaction among the older population in China. METHODS: Based on the sample of China Health and Retirement Longitudinal Survey database in 2013, a structural equation modeling is established. The sample size is 4245 with 55.9% with mobility impairment. RESULTS: The model shows that the length of suffering from disability is significantly related to mobility impairment (ß = 0.058, p < 0.001). Mobility impairment is inversely related to social engagement (ß = -0.300, p < 0.001) and life satisfaction (ß = -0.311, p < 0.001). Social engagement is positively related to life satisfaction (ß = 0.211, p < 0.001). Moreover, the relationships have some differences for the seniors with different sociodemographic characteristics and living in different residential areas. CONCLUSIONS: As seniors get older, they tend to have more severe mobility impairment and participate less in social activities. Those with higher mobility impairment are more likely to report lower life satisfaction partly because they usually participate less in social activities. Different strategies are suggested to be adopted to improve the life satisfaction of the older population from the aspects of promoting mobility and social engagement, including improving the design of transport facilitates, providing assistive facilities for the seniors with severe mobility impairment, promoting the accessibility of community leisure and healthcare services, and constructing more community senior activity centers.

Synthesis, biological evaluation, and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors.

Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4-7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC50 0.68µM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI50 8.54µM), as well as other human tumor cell lines (GI50<20µM), and a desirable druglike property profile with low logP value (2.54) and high aqueous solubility (95.6µg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound.

ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.

ACR Appropriateness Criteria® Adjuvant Therapy in Vulvar Cancer.

These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy.

Anticancer activity of tuftsin-derived T peptide in postoperative residual tumors.

Immune adjuvants have been used in cancer biotherapies to stimulate immune response to tumor cells. Despite their potential as anticancer reagents, there are several impediments to their use in clinical applications. In this study, we aim to modify the existing tuftsin structure and evaluate its antitumor activity in preclinical models. We synthesized a novel tuftsin derivative, namely, the T peptide (TP), by linking four tuftsin peptides, which showed enhanced stability in vivo. We then evaluated its anticancer activity in a postoperative residual tumor model in mice, where we surgically removed most of the primary tumor from the host, a procedure mimicking clinically postoperative patients. Despite the limited effect in intact solid tumors, TP strongly inhibited relapsed growth of residual tumors in postsurgical mice. Surgical resection of tumors accelerated residual tumor growth, but TP slowed down this process significantly. Interestingly, TP showed similar effects in human xenograft residual models. As an immunomodulator, TP could synergize the functions of macrophages, thus inhibiting the growth of cocultured tumor cells in vitro. Furthermore, TP could shift the macrophages to the tumor-suppressive M1 type and mobilize them to produce elevated cytotoxic TNF-α and NO. As a result, TP effectively prolonged the survival time of tumor-resected mice. Using the postoperative residual tumor models, we provide a body of evidence showing the antitumor activity of TP, which causes no obvious toxicity. Our study highlights the potential of TP as a postoperative adjuvant in cancer therapies.

Multidisciplinary therapy of stage IIIA non-small-cell lung cancer: long-term outcome of chemoradiation with or without surgery.

BACKGROUND: Stage IIIA non-small-cell lung cancer (NSCLC) is highly heterogeneous due to differences in the size of the primary tumor and the extent and location of nodal disease. Although the addition of surgery to chemoradiation did not improve overall survival (OS) for stage IIIA patients in a randomized intergroup trial (INT 0139), subset analyses of the trial suggest that a trimodality approach incorporating lobectomy may be superior to bimodality therapy with chemoradiation alone. METHODS: We analyzed the outcomes of patients with stage IIIA NSCLC (T3N1, T1-3N2) treated at our center between January 2000 and December 2008. We compared OS for those undergoing definitive chemoradiation to those undergoing chemoradiation followed by either lobectomy or pneumonectomy. Demographic variables were balanced by propensity score analysis method. RESULTS: In our analysis of 249 patients, the median age was 65 years, 43% were men, and 96.5% had N2 disease. Chemoradiation followed by lobectomy yielded superior OS compared with chemoradiation (median OS 39 months vs 22 months, P = .038 after propensity score adjustment). There was no significant survival benefit for pneumonectomy over chemoradiation (median survival 28 months vs 22 months, P = .534). CONCLUSIONS: Our data corroborate the findings of the INT 0139 trial. We propose that a formal randomized trial be performed comparing chemoradiation followed by lobectomy vs definitive chemoradiation in patients with stage IIIA disease whose tumors are resectable by lobectomy. Our data do not support the incorporation of pneumonectomy in the management of stage IIIA patients with N2 disease.

Lactylation signature identifies liver fibrosis phenotypes and traces fibrotic progression to hepatocellular carcinoma.

Introduction: Precise staging and classification of liver fibrosis are crucial for the hierarchy management of patients. The roles of lactylation are newly found in the progression of liver fibrosis. This study is committed to investigating the signature genes with histone lactylation and their connection with immune infiltration among liver fibrosis with different phenotypes. Methods: Firstly, a total of 629 upregulated and 261 downregulated genes were screened out of 3 datasets of patients with liver fibrosis from the GEO database and functional analysis confirmed that these differentially expressed genes (DEGs) participated profoundly in fibrosis-related processes. After intersecting with previously reported lactylation-related genes, 12 DEGs related to histone lactylation were found and narrowed down to 6 core genes using R algorithms, namely S100A6, HMGN4, IFI16, LDHB, S100A4, and VIM. The core DEGs were incorporated into the Least absolute shrinkage and selection operator (LASSO) model to test their power to distinguish the fibrotic stage. Results: Advanced fibrosis presented a pattern of immune infiltration different from mild fibrosis, and the core DEGs were significantly correlated with immunocytes. Gene set and enrichment analysis (GSEA) results revealed that core DEGs were closely linked to immune response and chemokine signaling. Samples were classified into 3 clusters using the LASSO model, followed by gene set variation analysis (GSVA), which indicated that liver fibrosis can be divided into status featuring lipid metabolism reprogramming, immunity immersing, and intermediate of both. The regulatory networks of the core genes shared several transcription factors, and certain core DEGs also presented dysregulation in other liver fibrosis and idiopathic pulmonary fibrosis (IPF) cohorts, indicating that lactylation may exert comparable functions in various fibrotic pathology. Lastly, core DEGs also exhibited upregulation in HCC. Discussion: Lactylation extensively participates in the pathological progression and immune infiltration of fibrosis. Lactylation and related immune infiltration could be a worthy focus for the investigation of HCC developed from liver fibrosis.

The effect of targeted palliative care interventions on depression, quality of life and caregiver burden in informal caregivers of advanced cancer patients: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy of targeted palliative care interventions on depression, quality of life and caregiver burden in informal caregivers of advanced cancer patients, along with the consequences of various intervention types. DESIGN: This study performed a comprehensive review and a meta-analysis of randomized controlled trials. METHOD: An extensive search was carried out across eight databases, namely, PubMed, Embase, CLNAHL, PsyclNFO, Cochrane, VIP, CNKI, and WANFANG, spanning from the inception of the library to May 4, 2024. Two examiners independently screened the articles and extracted the data according to the eligibility criteria formulated in accordance with the PICOS principles. The meta-analysis was conducted utilizing the StataCorp (version 16.0), estimating the impacts of the interventions through the computation of the standardized mean difference (SMD) and the 95 % confidence interval (CI). Sensitivity analysis was carried out using a one-way-out method. Egger's test and the Duval and Tweedie trim-and-fill methods were used to explore the potential publication bias. The Cochrane risk-of-bias tool was used to evaluate the methodological quality of the included studies, and the overall quality of evidence was evaluated using the GRADE method. RESULTS: This study pooled 16 RCTs (including 2046 informal caregivers) that were published from 2007 to 2023. The meta-analysis results indicated that the targeted palliative care interventions significantly improved depression (SMD = -0.74, 95 % CI: [-1.25, -0.23], P < 0.01) and quality of life (SMD = 0.63, 95 % CI: [0.08, 1.17], P = 0.03), though not in terms of caregiver burden (SMD = -0.33, 95 % CI: [-0.95, 0.29], P = 0.30) among informal caregivers of advanced cancer patients. Analysis of the subgroups revealed a correlation between short-term interventions, under three months, and the improvement of depression. Strategies focused solely on caregivers have proven effective in alleviating depression. Interventions utilizing offline methods have been shown to not only lower depression levels but also improve the quality of life for caregivers. CONCLUSIONS: The targeted palliative care interventions effectively improved informal caregivers' depression and quality of life, yet they fail to markedly lessen the caregiver burden. To better support informal caregivers, interveners ought to adopt personalized strategies based on comprehensive consideration of the duration, format, and delivery methods of the interventions. Simultaneously, further exploration and effort from scholars are necessary to enhance the accessibility of palliative care services, and to effectively incorporate academic research findings into clinical practice. REGISTRATION: CRD42023475620.

Acupuncture as adjunctive treatment for linezolid-induced peripheral neuropathy: a case series report.

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.