Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155.

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.

Transcriptomic profiling and the first spatial expression analysis of candidate genes in the salivary gland of the East Asian medicinal leech, Hirudo nipponia.

Hirudo nipponia, a blood-sucking leech native to East Asia, possesses a rich repertoire of active ingredients in its saliva, showcasing significant medical potential due to its anticoagulant, anti-inflammatory, and antibacterial effects against human diseases. Despite previous studies on the transcriptomic and proteomic characteristics of leech saliva, which have identified medicinal compounds, our knowledge of tissue-specific transcriptomes and their spatial expression patterns remains incomplete. In this study, we conducted an extensive transcriptomic profiling of the salivary gland tissue in H. nipponia based on de novo assemblies of tissue-specific transcriptomes from the salivary gland, teeth, and general head region. Through gene ontology (GO) analysis and hierarchical clustering, we discovered a novel set of anti-coagulant factors-i.e., Hni-Antistasin, Hni-Ghilanten, Hni-Bdellin, Hni-Hirudin-as well as a previously unrecognized immune-related gene, Hni-GLIPR1 and uncharacterized salivary gland specific transcripts. By employing in situ hybridization, we provided the first visualization of gene expression sites within the salivary gland of H. nipponia. Our findings expand on our understanding of transcripts specifically expressed in the salivary gland of blood-sucking leeches, offering valuable resources for the exploration of previously unidentified substances with medicinal applications.

Research status and hotspots of autoimmune gastritis: A bibliometric analysis.

BACKGROUND: As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers. AIM: To analyze the research overview and popular topics in the field of AIG using bibliometrics. METHODS: Relevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic. RESULTS: In total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, Helicobacter pylori, autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of Helicobacter pylori in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG. CONCLUSION: This bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.

An indirect comparison of efficacy including histologic assessment and safety in biologic therapy in ulcerative colitis: Systemic review and network meta-analysis.

BACKGROUNDS AND AIMS: There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head VARSITY trial. The current study employs a network meta-analysis to compare the efficacy, including histologic remission and safety of biologic agents for UC. METHODS: Using four electronic databases, including Pubmed, EMBASE, The Cochrane Library, and ClinicalTrials.gov, a search was conducted of all literature published until September 2022. Included were studies of randomized controlled trials with adult patients with moderate to severe UC using biologics approved by the FDA. An odd ratio with a 95 percent credible interval and ranking information was calculated for each endpoint. RESULTS: The results of the network meta-analysis did not reveal statistically significant differences among biological agents. However, the ranking information for each biological agent exhibited the following patterns. Vedolizumab was ranked first for overall efficacy endpoints in the maintenance phase, including histologic remission. Except for histologic remission, Ustekinumab was identified as the top-ranked drug for induction phase efficacy endpoints other than histologic remission. Adalimumab was identified as the top-ranked drug for maintenance phase corticosteroid-free remission. Vedolizumab was identified as the top-ranked drug in the induction phase for Treatment Emergent Adverse Events (TEAE). Adalimumab was identified as the top-ranked drug in the induction phase for infection. For TEAE and infection in the maintenance phase and Treatment Emergent Severe Adverse Events (TESAE) in both the induction and maintenance phases, Ustekinumab was determined to be the top-ranked medication. CONCLUSIONS: Including histologic remission, for the overall efficacy endpoints in the maintenance phase, VDZ was identified as the first rank drug, but there was no statistically significant difference between biologics. Therefore, the generalization of the results of this study is bounded due to the intrinsic limitations of the study provided.

The Effects of a Mindfulness-Based Intervention on Mental Health Outcomes in Pregnant Woman: A Systematic Review and Meta-Analysis.

BACKGROUND: Pregnancy stress, anxiety, and depression increase the risk of short-term and long-term health problems for the mother and fetus. Mindfulness-based intervention (MBI) is one of the most popular, nonpharmacological interventions used to treat mental health problems. The results of prior research indicate MBI has a less consistent effect on mental health problems in pregnant women. PURPOSE: The purpose of this systematic review and meta-analysis was to clarify and determine the effect of MBI on mental health outcomes in pregnant women. METHODS: Six databases, including Embase, Ovid MEDLINE, CINAHL, EBSCOhost, Cochrane Library, and ScienceDirect, were searched from their dates of inception to November 2021. Google Scholar was also used for the literature inquiry. The inclusion criteria followed the PICO (Patient/Problem, Intervention, Comparison, and Outcome) model in terms of only including studies that used mindfulness therapy, reported mental health outcomes, and applied randomized controlled trial and quasi-experimental approaches. The Cochrane risk of bias tool was applied to evaluate the quality of the studies. Review Manager 5 software with random effect with a standardized mean difference (SMD) was used to analyze level of effect. RESULTS: Thirteen studies (10 randomized controlled trials and three quasi-experimental studies) were included. MBI was found to have a small effect on mental health outcomes in pregnant women (p < .0001, SMDs = -0.48, 95% CI [-0.74, -0.22], I2 = 87%). Specifically, MBI had moderate effects on stress and anxiety (SMDs = -0.59, 95% CI [-1.09, -0.09], and SMDs = -0.55, 95% CI [-1.00, -0.10], respectively) and no significant effect on depression (SMDs = -0.33, 95% CI [-0.74, 0.08]). CONCLUSIONS: MBIs have a small but notable effect on mental health in pregnant women. The high heterogeneity found in this review may reflect the different types and durations of interventions used. Notably, none of the studies in the review examined intervention effects by trimester. Future research should use larger sample sizes and assess the effects of therapy for each trimester of pregnancy.

Vitamin D supplementation for depression in older adults: a meta-analysis of randomized controlled trials.

Background: In older adults, depression is associated with several other clinical problems such as cognitive impairment and low quality of life. Several studies have evaluated the relationship between vitamin D and depression in older adults; however, the results have been controversial thus far. Objective: This study aimed to investigate the effects of vitamin D supplementation on depressive symptom improvement among individuals aged ≥60 years with or without a diagnosis of depression or depressive symptoms based on a meta-analysis of randomized controlled trials (RCTs). Methods: RCTs were identified to analyze the relationship between vitamin D supplementation and depressive symptoms. MEDLINE, CENTRAL, Embase, and PsycINFO were systematically searched for relevant articles published from inception to November 2022. RCTs that evaluated the effect of vitamin D supplementation in participants aged ≥60 years compared to placebo were included. A random effects model was used in this meta-analysis because of the differences between the included RCTs. The quality of the RCTs was assessed using Risk of Bias 2. Results: Seven trials were included in the analyses. The primary outcome of pre-post score changes included five trials with a total of 752 participants. The secondary outcome of post-intervention score included all seven trials with a total of 4,385 participants. No significant improvement in depressive symptoms in either pre-post score changes [standardized mean difference (SMD) = -0.49; 95% confidence interval (CI) -1.07-0.09; p = 0.10] or post-intervention score (SMD = -0.10; 95% CI -0.28-0.07; p = 0.25) was found. Conclusion: Vitamin D supplementation in older adults was not associated with an improvement in depressive symptoms. More studies in older adults are needed to evaluate the association between vitamin D supplementation and depression.

Mineralized Porphyrin Metal-Organic Framework for Improved Tumor Elimination and Combined Immunotherapy.

Calcium ion therapy is a potential anticancer treatment. However, the cellular calcium-buffering mechanism limited the effectiveness of calcium ion therapy. Here, we constructed a mineralized porphyrin metal-organic framework (PCa) to produce calcium ions and reactive oxygen species (ROS), which destroyed cell calcium buffering capacity and amplified the cell damage caused by calcium overload. In addition, PCa could induce cell immunogenic death to release tumor-associated antigen (TAA) and be used as an adjuvant. Thus, PCa could increase DC maturation and promote the antitumor activity of CD8+ T cells. For mice experiment, PCa not only showed excellent tumor elimination on the subcutaneous breast tumor but also achieved obvious antimetastasis effect in the metastatic tumor model. This nanosystem could eliminate the primary tumor and boost effective antitumor immunotherapy for comprehensive anticancer treatment.

Anticancer Effects of Morusin in Prostate Cancer via Inhibition of Akt/mTOR Signaling Pathway.

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. The majority of PCa incidences eventually progress to castration-resistant PCa (CRPC), thereby establishing an urgent need for new effective therapeutic strategies. This study aims to examine the effects of morusin, a prenylated flavonoid isolated from Morus alba L., on PCa progression and identify the regulatory mechanism of morusin. Cell growth, cell migration and invasion, and the expression of EMT markers were examined. Cycle progression and cell apoptosis were examined using flow cytometry and a TUNEL assay, while transcriptome analysis was performed using RNA-seq with results being further validated using real-time PCR and western blot. A xenograft PCa model was used to examine tumor growth. Our experimental results indicated that morusin significantly attenuated the growth of PC-3 and 22Rv1 human PCa cells; moreover, morusin significantly suppressed TGF-[Formula: see text]-induced cell migration and invasion and inhibited EMT in PC-3 and 22Rv1 cells. Significantly, morusin treatment caused cell cycle arrest at the G2/M phase and induced cell apoptosis in PC-3 and 22Rv1 cells. Morusin also attenuated tumor growth in a xenograft murine model. The results of RNA-seq indicated that morusin regulated PCa cells through the Akt/mTOR signaling pathway, while our western blot results confirmed that morusin suppressed phosphorylation of AKT, mTOR, p70S6K, and downregulation of the expression of Raptor and Rictor in vitro and in vivo. These results suggest that morusin has antitumor activities on regulating PCa progression, including migration, invasion, and formation of metastasis, and might be a potential drug for CRPC treatment.

Effects of Protein Supplementation Combined with Resistance Exercise Training on Walking Speed Recovery in Older Adults with Knee Osteoarthritis and Sarcopenia.

Knee osteoarthritis (KOA) is closely associated with sarcopenia, sharing the common characteristics of muscle weakness and low physical performance. Resistance exercise training (RET), protein supplementation (PS), and PS+RET have promise as treatments for both sarcopenia and KOA. However, whether PS+RET exerts any effect on time to recovery to normal walking speed (WS) in older adults with sarcopenia and KOA remains unclear. This study investigated the treatment efficiency of PS+RET on WS recovery among individuals with KOA and sarcopenia. A total of 108 older adults aged ≥ 60 years who had a diagnosis of radiographic KOA and sarcopenia were enrolled in this prospective cohort study. Sarcopenia was defined on the basis of the cutoff values of the appendicular skeletal muscle mass index for Asian people and a slow WS less than 1.0 m/s. The patients were equally distributed to three groups: PS+RET, RET alone, and usual care. The weekly assessment was performed during a 12-week intervention and a subsequent 36-week follow-up period. A cutoff of 1.0 m/s was used to identify successful recovery to normal WS. Kaplan-Meier analysis was performed to measure the survival time to normal WS among the study groups. Multivariate Cox proportional-hazards regression (CPHR) models were established to calculate the hazard ratios (HRs) of successful WS recovery and determine its potential moderators. After the 3-month intervention, PS+RET as well as RET obtained greater changes in WS by an adjusted mean difference of 0.18 m/s (p < 0.0001) and 0.08 (p < 0.05) m/s, respectively, compared to usual care. Kaplan-Meier analysis results showed both RET and PS+RET interventions yielded high probabilities of achieving normal WS over the 12-month follow-up period. Multivariate CPHR results revealed that PS+RET (adjusted HR = 5.48; p < 0.001), as well as RET (adjusted HR = 2.21; p < 0.05), independently exerted significant effects on WS recovery. PS+RET may accelerate normal WS recovery by approximately 3 months compared with RET. Sex and initial WS may influence the treatment efficiency. For patients with KOA who suffer sarcopenia, 12-week RET alone exerts significant effects on WS recovery, whereas additional PS further augments the treatment effects of RET by speeding up the recovery time of WS toward a level ≥ 1.0 m/s, which facilitates the patients to diminish the disease severity or even free from sarcopenia.

The anti-inflammatory effect of lutein in broilers is mediated by regulating Toll-like receptor 4/myeloid-differentiation-factor 88 signaling pathway.

The anti-inflammatory role of lutein has been widely recognized, however, the underlying mechanism is still not fully elucidated. Hence, the effects of lutein on the intestinal health and growth performance of broilers and the action of mechanism were investigated. 288 male yellow-feathered broilers (1-day old) were randomly allocated to 3 treatment groups with 8 replicates of 12 birds each, and the control group was fed a broken rice-soybean basal diet, while the test groups were fed a basal diet added with 20 mg/kg and 40 mg/kg of lutein (LU20, LU40), respectively. The feeding trial lasted for 21 d. The results showed that 40 mg/kg lutein supplementation tended to increase ADFI (P = 0.10) and ADG (P = 0.08) of broilers. Moreover, the addition of lutein caused a decreasing trend of gene expression and concentration of proinflammatory cytokines IL-1ß (P = 0.08, P = 0.10, respectively) and IL-6 (P = 0.06, P = 0.06, respectively) and also tended to decrease the gene expression of TLR4 (P = 0.09) and MyD88 (P = 0.07) while increasing gene expression and concentration of anti-inflammatory cytokines IL-4 and IL-10 (P < 0.05) in the jejunum mucosa of broilers. Additionally, lutein supplementation increased the jejunal villi height of broilers (P < 0.05) and reduced villi damage. The experiment in vitro showed that lutein treatment reduced the gene expression of IL-1ß, IL-6, and IFN-γ in chicken intestinal epithelial cells (P < 0.05). However, this effect was diminished after knock-down of TLR4 or MyD88 genes using RNAi technology. In conclusion, lutein can inhibit the expression and secretion of proinflammatory cytokines in the jejunum mucosa and promote intestinal development of broilers, and the anti-inflammatory effect may be achieved by regulating TLR4/MyD88 signaling pathway.

Exploring Discomfort Experienced During Chemotherapy in Thai Breast Cancer Patients.

INTRODUCTION: Breast cancer is the most common cancer in females worldwide, and a new era is prevalent in the early stage. A qualitative approach explores discomfort experienced during adjuvant chemotherapy among Thai breast cancer patients. METHOD: The participants were selected by purposive sampling with a variation of two comprehensive cancer centers. Individual in-depth interviews were conducted with fifteen patients who had completed the second cycle of adjuvant chemotherapy prior to the interview. RESULTS: A qualitative content analysis of data revealed two themes, six categories, and 23 sub-categories. The themes defined discomfort characteristics and factors leading to discomfort. Among all the categories were described physical discomfort, environmental discomfort, psychological discomfort, needing to relieve discomfort, lack of socio-cultural support, and lack of mental support. CONCLUSION: There is a need to alleviate discomfort, specifically due to Thai beliefs and culture related to patient self-management and nursing care. These findings may be extended to best practice nursing interventions to enhance comfort outcomes for breast cancer patients and elevate patient satisfaction.

[Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis].

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Renal Clearable Catalytic 2D Au-Porphyrin Coordination Polymer Augmented Photothermal-Gas Synergistic Cancer Therapy.

As a gasotransmitter, carbon monoxide (CO) possesses antitumor activity by reversing the Warburg effect at higher concentrations. The targeted delivery of carbon monoxide-releasing molecules (CORMs) using nanomaterials is an appealing option for CO administration, but how to maintain CO above the threshold concentration in tumor tissue remains a challenge. Herein, a nanozyme-catalyzed cascade reaction is proposed to promote CO release for high-efficacy photothermal therapy (PTT)-combined CO therapy of cancer. A gold-based porphyrinic coordination polymer nanosheet (Au0 -Por) is synthesized to serve as a carrier for CORM. It also possesses excellent glucose oxygenase-like activity owing to ultrasmall zero-valent gold atoms on the nanosheet. The catalytically generated H2 O2 can efficiently catalyze CORM decomposition, which enables in situ generation of sufficient CO for gas therapy. In vivo, the Au0 -Por nanosheets-enhanced photoacoustic imaging (PAI) and fluorescence imaging collectively demonstrate high tumor-targeting efficiency and nanomaterial retention. Proven to have augmented therapeutic efficacy, the nanoplatform can also be easily degraded and excreted through the kidney, indicating good biocompatibility. Thus, the application of rational designed Au0 -Por nanosheet with facile approach and biodegradable property to PAI-guided synergistic gas therapy can provide a strategy for the development of biocompatible and highly effective gaseous nanomedicine.

In Situ Sprayed Biotherapeutic Gel Containing Stable Microbial Communities for Efficient Anti-Infection Treatment.

Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug-resistant bacteria. Here, an in situ-formed biotherapeutic gel that controls multidrug-resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene-polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities-based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria-derived xenograft infection models, as well as in patient-derived multidrug-resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad-spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug-resistant bacterial infections.

Effects of lutein on jejunal mucosal barrier function and inflammatory responses in lipopolysaccharide-challenged yellow-feather broilers.

Broilers are frequently exposed to various immunological stresses, which lead to intestinal damage, weakened immunity, and even growth retardation. Lutein, as a kind of carotenoid, possesses antioxidant and immunomodulatory functions. Therefore, this study was conducted to investigate the effects of lutein on jejunal mucosal barrier function and inflammatory responses of yellow-feather broilers challenged with lipopolysaccharide (LPS). A total of two hundred eight-eight 1-day-old yellow-feather broilers were randomly allocated to 3 groups with 8 replicate cages containing 12 birds each. Birds were fed broken-rice-soybean basal diet containing 0, 20 and 40 mg/kg lutein (CON, LU20 and LU40) for 26 d. On days 21, 23, and 25 of the trial, broilers were intraperitoneally injected with LPS (1 mg/kg body weight). The results showed that, compared with CON group, LU40 supplementations significantly increased the average daily gain (ADG) of broilers at 1 to 21 and 22 to 26 d of age (P < 0.05), significantly decreased the ratio of feed to gain (F/G) of broilers at 22 to 26 d of age (P < 0.05). LU20 and LU40 supplementations increased goblet cell density in jejunum of broilers under LPS challenge, and LU20 supplementation elevated the villus area (P < 0.05). Scanning electron microscopy of jejunal mucosa revealed significant villi damage, while transmission electron microscopy demonstrated severe enterocyte damage and loss of cellular integrity in CON group. In particular, mitochondria were morphologically altered, appearing irregular or swollen. Apical junctional complexes between adjacent enterocytes were obviously shorter and saccular in CON group. LU20 and LU40 supplementations increased the mRNA expressions of Occludin, Claudin-1, and ZO-1 in the jejunal mucosa of broilers under LPS challenge (P < 0.05), restrained TLR4/MyD88/NF-κB pathway activation in the jejunal mucosa, decreased the mRNA expressions of IL-1ß and IL-6, and strengthened the mRNA expressions of IL-4 and IL-10 (P < 0.05). Meanwhile, the protein expressions of p38 and JNK in LU40 group were lower than CON group (P < 0.05). It can be concluded that 40 mg/kg lutein supplementation improved LPS-induced jejunal mucosal barrier function and tamed inflammation of yellow-feather broilers.

Expanding Sorafenib Treatment for Hepatocellular Carcinoma Beyond Barcelona Clinic Liver Cancer Stage C Patients: A National Study.

BACKGROUND/AIM: The reimbursement criteria of sorafenib for advanced hepatocellular carcinoma (HCC) were expanded in 2016 by Taiwan's National Health Insurance (NHI) to include patients without macrovascular invasion or extrahepatic spread. This study explored sorafenib treatment outcomes before and after this expansion. PATIENTS AND METHODS: The NHI database was searched for patients who initiated sorafenib treatment between January 1, 2013, and December 31, 2017. Clinical variables were retrieved from the Taiwan Cancer Registry database. Overall survival (OS) and time to treatment discontinuation (TTD) were calculated as the times from the first sorafenib prescription date until death and the final prescription date, respectively. RESULTS: A total of 13,862 patients were included. The median age was 64 years, 78.1% of patients were male. Approximately a quarter of patients (25.1%) received sorafenib after the criteria expansion and exhibited significantly longer OS (median 7.9 vs. 6.6 months, p<0.001) and TTD (median 3.0 vs. 2.6 months, p=0.003) compared with patients who started before. These results were verified in patients with available data regarding clinical prognostic factors (n=9,378, 67.7% of the entire study population). In the multivariate analysis, sorafenib prescription after criteria expansion remained an independent predictor of longer OS [hazard ratio (HR)=0.87, p<0.001] and TTD (HR=0.93, p=0.004). In the subgroup analysis, these trends were consistently observed across different patient subgroups. CONCLUSION: Patients with HCC who received sorafenib treatment after the reimbursement criteria expansion exhibited longer OS and TTD.

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment.

BACKGROUND: The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapy for patients with advanced hepatocellular carcinoma (HCC), but the prognosis and treatment pattern after its treatment failure are unclear. METHODS: We reviewed the medical records of patients who failed first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021 in four Taiwan medical centers. Post-first-line survival (PFLS) was defined as the date from the failure of Atezo-Bev treatment to the date of death or last follow-up. RESULTS: A total of 41 patients were included in the study. All patients had Child-Pugh A liver reserve before the initiation of Atezo-Bev treatment, but the liver reserve of 6 (15%) and 7 (17%) patients deteriorated to Child-Pugh B and C, respectively, after treatment failure. The median PFLS was 5.9 months. PFLS significantly differed among patients with various liver reserves after the failure of Atezo-Bev treatment (median 9.6 vs 3.8 vs 1.2 months, for Child-Pugh A, B, and C; p < 0.001). In total, 30 (73%) patients received second-line systemic therapy, and they exhibited significantly longer PFLS (median 8.0 vs 1.8 months, p = 0.033) than patients who did not. Deteriorated liver function and not receiving second-line therapy remained associated with inferior PFLS in multivariate analysis. The most common second-line therapies were sorafenib (n = 19, 63%) and lenvatinib (n = 9, 30%), with no significant differences in efficacies. CONCLUSION: Receiving second-line therapy and good liver reserve were associated with favorable PFLS after the failure of first-line Atezo-Bev treatment.

Prevalence and patterns of the concurrent use of anticholinergics for the motor symptoms of Parkinson's disease and acetylcholinesterase inhibitors in Parkinson's disease patients with dementia: a cross-sectional study using Korea National Health Insurance claims data.

BACKGROUND: The concurrent use of anticholinergics and acetylcholinesterase inhibitors (ACHEIs) in Parkinson's disease (PD) patients with dementia should be avoided because the opposing pharmacological actions of both drugs reduce the treatment efficacy. We aimed to investigate the prevalence of the concurrent use of these two types of drugs in Korean patients. METHODS: In the 2017 Health Insurance Review and Assessment Service-National Aged Patient Sample data, comprising insurance claims records for a 10% random sample of patients aged ≥ 65 years in Korea, "concurrent use" was defined as the overlapping of anticholinergic and ACHEI doses for at least 2 months. RESULTS: Among 8,845 PD patients with dementia, 847 (9.58%) were co-administered anticholinergics, used to treat the motor symptoms of PD, and ACHEIs for a mean duration of 7.7 months. A total of 286 (33.77% of all co-administered) patients used both drug types concurrently all year. About 80% of concurrent users were prescribed each drug by the same prescriber, indicating that coadministration may not be due to a lack of information sharing between providers. Logistic regression analysis showed that patients mainly treated at clinics (odds ratio (OR), 1.541; 95% confidence interval (CI), 1.158-2.059), hospitals (OR, 2.135; 95% CI, 1.586-2.883), and general hospitals (OR, 1.568; 95% CI, 1.221-2.028) were more likely to be co-prescribed anticholinergics and ACHEIs than those mainly treated at tertiary-care hospitals. PD patients with dementia treated at healthcare organizations located in areas other than the capital city had an approximately 22% higher risk of concurrent use (OR: 1.227, 95% CI: 1.046-1.441). CONCLUSIONS: The concurrent use of anticholinergics for the motor symptoms of PD and ACHEIs in elderly Korean PD patients with dementia cannot be ignored, and strategies that mitigate potentially inappropriate concurrent drug use are required.

Calibrated Regression Models Based on the Risk of Clinical Nodal Metastasis Should be Used as Decision Aids for Prostate Cancer Staging to Reduce Unnecessary Imaging.

INTRODUCTION: Radionuclide imaging will change the role of computed tomography and magnetic resonance imaging (CT/MRI) for prostate cancer (CaP) staging. Current guidelines recommend abdominopelvic imaging for new cases of CaP categorized as unfavorable intermediate risk (UIR) or higher. We assessed the performance characteristics of CT/MRI based on the National Comprehensive Cancer Network (NCCN) guidelines and developed a model that predicts cN1 disease using conventional imaging. PATIENTS AND METHODS: We selected patients in the National Cancer Database diagnosed with CaP from 2010 to 2016 with available age, prostate specific antigen, clinical locoregional staging, biopsy Gleason grading, and core information. Multivariate logistic regression (MLR) was used on a undersampled training dataset using cN1 as the outcome. Performance characteristics were compared to those of the three most recent versions of the NCCN guidelines. RESULTS: A total of 443,640 men were included, and 2.5% had cN1 disease. Using CT/MRI only, the current NCCN guidelines have a sensitivity of 99%, and the number needed to image (NNI) is 24. At the same sensitivity, the cN1 risk was 1.6% using the MLR. The NNI for UIR alone is 341. Using the MLR model and a threshold of 10%, the PPV is 10.3% and 64% of CTs/MRIs could be saved at a cost of missing 6% of cN1 patients (or 0.15% of all patients). CONCLUSION: The NCCN guidelines are sensitive for detecting cN1 with CT/MRI, however, the number needed to image is 24. Obtaining CT/MRI for nodal staging when patients have a cN1 risk of 10% would reduce total imaging while still remaining sensitive. As novel PET tracers becomes increasingly used for initial CaP staging, well calibrated prediction models trained on the outcome of interest should be developed as decision aids for obtaining imaging.