Precision Identification of Locally Advanced Rectal Cancer in Denoised CT Scans Using EfficientNet and Voting System Algorithms.

BACKGROUND AND OBJECTIVE: Local advanced rectal cancer (LARC) poses significant treatment challenges due to its location and high recurrence rates. Accurate early detection is vital for treatment planning. With magnetic resonance imaging (MRI) being resource-intensive, this study explores using artificial intelligence (AI) to interpret computed tomography (CT) scans as an alternative, providing a quicker, more accessible diagnostic tool for LARC. METHODS: In this retrospective study, CT images of 1070 T3-4 rectal cancer patients from 2010 to 2022 were analyzed. AI models, trained on 739 cases, were validated using two test sets of 134 and 197 cases. By utilizing techniques such as nonlocal mean filtering, dynamic histogram equalization, and the EfficientNetB0 algorithm, we identified images featuring characteristics of a positive circumferential resection margin (CRM) for the diagnosis of locally advanced rectal cancer (LARC). Importantly, this study employs an innovative approach by using both hard and soft voting systems in the second stage to ascertain the LARC status of cases, thus emphasizing the novelty of the soft voting system for improved case identification accuracy. The local recurrence rates and overall survival of the cases predicted by our model were assessed to underscore its clinical value. RESULTS: The AI model exhibited high accuracy in identifying CRM-positive images, achieving an area under the curve (AUC) of 0.89 in the first test set and 0.86 in the second. In a patient-based analysis, the model reached AUCs of 0.84 and 0.79 using a hard voting system. Employing a soft voting system, the model attained AUCs of 0.93 and 0.88, respectively. Notably, AI-identified LARC cases exhibited a significantly higher five-year local recurrence rate and displayed a trend towards increased mortality across various thresholds. Furthermore, the model's capability to predict adverse clinical outcomes was superior to those of traditional assessments. CONCLUSION: AI can precisely identify CRM-positive LARC cases from CT images, signaling an increased local recurrence and mortality rate. Our study presents a swifter and more reliable method for detecting LARC compared to traditional CT or MRI techniques.

Research advances on molecular mechanism and natural product therapy of iron metabolism in heart failure.

The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.

Prediction of jaw opening function after mandibular reconstruction using subject-specific musculoskeletal modelling.

BACKGROUND: Mandibular reconstruction patients often suffer abnormalities in the mandibular kinematics. In silico simulations, such as musculoskeletal modelling, can be used to predict post-operative mandibular kinematics. It is important to validate the mandibular musculoskeletal model and analyse the factors influencing its accuracy. OBJECTIVES: To investigate the jaw opening-closing movements after mandibular reconstruction, as predicted by the subject-specific musculoskeletal model, and the factors influencing its accuracy. METHODS: Ten mandibular reconstruction patients were enrolled in this study. Cone-beam computed tomography images, mandibular movements, and surface electromyogram signals were recorded preoperatively. A subject-specific mandibular musculoskeletal model was established to predict surgical outcomes using patient-averaged muscle parameter changes as model inputs. Jaw bone geometry was replaced by surgical planning results, and the muscle insertion sites were registered based on the non-rigid iterative closest point method. The predicted jaw kinematic data were validated based on 6-month post-operative measurements. Correlations between the prediction accuracy and patient characteristics (age, pathology and surgical scope) were further analysed. RESULTS: The root mean square error (RMSE) for lower incisor displacement was 31.4%, and the error for peak magnitude of jaw opening was 4.9 mm. Age, post-operative infection and radiotherapy influenced the prediction accuracy. The amount of masseter detachment showed little correlation with jaw opening. CONCLUSION: The mandibular musculoskeletal model successfully predicted short-range jaw opening functions after mandibular reconstruction. It provides a novel surgical planning method to predict the risk of developing trismus.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Genetic mutation patterns among glioblastoma patients in the Taiwanese population - insights from a single institution retrospective study.

This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.

General anesthesia with local infiltration reduces urine retention rate and prolongs analgesic effect than spinal anesthesia for hemorrhoidectomy.

Introduction: Postoperative pain and complications pose significant challenges following a hemorrhoidectomy. Attaining effective anesthesia with minimal complications is crucial. The ideal anesthesia method for ambulatory hemorrhoidectomy remains uncertain. This study aimed to investigate whether the combination of general anesthesia plus local infiltration (GAL) is associated with lower complications and reduced pain compared to spinal anesthesia (SA) in the context of hemorrhoidectomy. Methods: This retrospective single-center cohort study, conducted in a tertiary medical center in East Asia, evaluated excisional hemorrhoidectomies performed between January 1, 2017, and March 31, 2023, utilizing GAL or SA. Data on the six most common complications-pain, constipation, acute urine retention (AUR), bleeding, nausea, and headache-were extracted from medical records. A total of 550 hemorrhoidectomies were included: 220 in the GAL group and 330 in the SA group. Patient characteristics were comparable between the two groups. Results: The AUR rate was significantly lower in the GAL group compared to the SA group (15.5% vs. 32.1%, P < 0.001). Although the proportion of pain scores ≥4 did not differ significantly between the GAL and SA groups (36.2% vs. 39.8%, P = 0.429), the pain score curve indicated a stable trend. Overall, the GAL group exhibited a lower rate of adverse effects (56.9% vs. 67.4%, P = 0.023). There were no significant differences in the rates of other complications and emergency department readmission between the GAL and SA groups. Discussion: GAL emerges as a favorable choice for anesthesia in hemorrhoidectomy, demonstrating a lower incidence of urine retention and a prolonged analgesic effect in multiple hemorrhoidectomies. These findings support the conclusion that GAL represents an optimal anesthetic method for enhancing the postoperative experience in patients undergoing hemorrhoidectomy.

Evaluation of joint kinematics in patients with condylar reconstruction using mandibular motion simulation based on intraoral scanning registration.

AIM: To summarize the features of condylar kinematics in patients with condylar reconstruction using a mandibular motion simulation method based on intraoral scanning registration. MATERIALS AND METHODS: Patients undergoing unilateral segmental mandibulectomy and autogenous bone reconstruction as well as healthy volunteers were enrolled in the study. Patients were grouped based on whether the condyles were reconstructed. Mandibular movements were recorded using a jaw tracking system, and kinematic models were simulated after registration. The path inclination of the condyle point, margin of border movement, deviation, and chewing cycle were analyzed. A t test and one-way analysis of variance (ANOVA) were carried out. RESULTS: A total of 20 patients, including 6 with condylar reconstruction and 14 with condylar preservation as well as 10 healthy volunteers were included. The patients with condylar reconstruction showed flatter movement paths of the condyle points. The mean inclination angle of the condylar movement paths of the patients with condylar reconstruction (0.57 ± 12.54 degrees) was significantly smaller than that of those with condylar preservation (24.70 ± 3.90 degrees, P = 0.014) during both maximum opening and protrusion (7.04 ± 12.21 degrees and 31.12 ± 6.79 degrees, respectively, P = 0.022). The inclination angle of the condylar movement paths of the healthy volunteers was 16.81 ± 3.97 degrees during maximum opening and 21.54 ± 2.80 degrees during protrusion; no significant difference compared with the patients. The condyles of the affected side tended to deviate laterally in all patients during mouth opening and protrusion. Patients with condylar reconstruction showed more severe symptoms of mouth opening limitation and mandibular movement deviation as well as shorter chewing cycles than patients with condylar preservation. CONCLUSION: Patients with condylar reconstruction showed flatter movement paths of the condyle points, greater lateral motion range, and shorter chewing cycles than those with condylar preservation. The method of mandibular motion simulation based on intraoral scanning registration was feasible to simulate condylar movement.

Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. METHODS: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. RESULTS: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). CONCLUSION: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3-5: a randomized controlled trial.

BACKGROUND: Although combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3-5 CKD. METHODS: In this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records. RESULTS: This study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups. CONCLUSIONS: Compared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3-5 helped relieve physical deterioration and increased micronutrient intake after three months. TRIAL REGISTRATION: ClinicalTrials.gov NCT05318014 (retrospectively registered on 08/04/2022).

Giant Mandibular Ameloblastoma with Rare Hypercalcemia: A Case Report and Literature Review.

Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common paraneoplastic syndrome that is commonly observed in patients with malignancies but rarely encountered in patients with benign tumors. Thus far, not many cases of ameloblastoma with hypercalcemia have been reported, and the pathogenic mechanism has not been studied in depth. This paper presents a case report of a 26-year-old male diagnosed with giant ameloblastoma of the mandible, accompanied by rare hypercalcemia. Additionally, a review of the relevant literature is conducted. This patient initially underwent marsupialization, yet this treatment was not effective, which indicated that the selection of the appropriate operation is of prime importance for improving the prognosis of patients with ameloblastoma. The tumor not only failed to shrink but gradually increased in size, accompanied by multiple complications including hypercalcemia, renal dysfunction, anemia, and cachexia. Due to the contradiction between the necessity of tumor resection and the patient's poor systemic condition, we implemented a multi-disciplinary team (MDT) meeting to better evaluate this patient's condition and design an individualized treatment strategy. The patient subsequently received a variety of interventions to improve the general conditions until he could tolerate surgery, and finally underwent the successful resection of giant ameloblastoma and reconstruction with vascularized fibular flap. No tumor recurrence or distance metastasis was observed during 5 years of follow-up. Additionally, the absence of hypercalcemia recurrence was also noted.

The Effectiveness of an Upper Limb Rehabilitation Program on Quality of Life in Breast Cancer Patients after Mastectomy: A Randomized Controlled Trial.

OBJECTIVE: This study aims to investigate the effectiveness of an upper limb rehabilitation program on the quality of life in patients who had been first diagnosed breast cancer and subsequently underwent mastectomy. DATA SOURCES: This randomized controlled trial enrolled 48 breast cancer patients who underwent mastectomy at a medical center in Taiwan. The patients were randomly assigned to either the intervention group (n = 24) or control group (n = 24). The patients in the intervention group participated in a 12-week upper limb rehabilitation program involving face-to-face upper limb rehabilitation education and once-a month monitoring of their upper extremity activity. The control group received standard nursing care. Quality of life was assessed through EORTC QLQ-C30 and QLQ-BR 23 questionnaires at baseline and weeks 4, 8, and 12 after enrollment. RESULTS: Both the intervention and control groups had significantly improved their levels of functioning, symptoms, and quality of life from baseline to week 12 after enrollment. The intervention group showed greater improvements in functioning and symptom levels after the intervention compared to the control group; however, no statistically significant differences were found. Additionally, the levels of global health status/quality of life in both groups gradually increased from baseline to week 12 CONCLUSION: An upper limb rehabilitation program is effective in improving the functioning and symptoms of breast cancer patients who have undergone mastectomy. IMPLICATIONS FOR NURSING PRACTICE: Patients are encouraged to undergo upper limb rehabilitation in order to improve their functioning, symptoms and quality of life.

Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme.

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR-RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Cascade Amplification of Pyroptosis and Apoptosis for Cancer Therapy through a Black Phosphorous-Doped Thermosensitive Hydrogel.

Cell pyroptosis has a reciprocal relationship with various cancer treatment modalities such as chemotherapy. However, the tumor microenvironment, characterized by hypoxia, substantially restricts the development and application of tumor therapies that integrate cell pyroptosis. Therefore, the cascade amplification of oxidative stress by interfering with redox homeostasis in tumors may be a promising approach. In this study, black phosphorus (BP) nanosheets and a glutathione peroxidase 4 inhibitor (RSL3) were coloaded into a thermosensitive PDLLA-PEG-PDLLA (PLEL) hydrogel (RSL3/BP@PLEL). Owing to the photothermal property of BP nanosheets, the RSL3/BP@PLEL hydrogel may trigger the release of loaded drugs in a more controllable and on-demand manner. Investigation of the antitumor effect in a mouse liver tumor model demonstrated that local injection of the hydrogel formulation in combination with near infrared laser irradiation could efficiently suppress tumor growth by interfering with the redox balance in tumors. Mechanistic study indicated that the combined treatment of photothermal therapy and glutathione depletion based on this hydrogel efficiently induced cell pyroptosis through both caspase-1/GSDMD and caspase-3/GSDME pathways, thereby triggering the repolarization of tumor-associated macrophages from M2 to M1. Overall, we developed a biocompatible and biodegradable hydrogel formulation for application in combination cancer treatment, providing a new platform for enhancing the efficacy of cancer therapy by amplifying cell pyroptosis and apoptosis.

Association of Hydroxychloroquine Use with a Dose-Dependent Decrease in Mortality Risk in Patients with Elderly-Onset Rheumatoid Arthritis.

INTRODUCTION: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. METHODS: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. RESULTS: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5 mg. CONCLUSION: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings.

Chronic kidney disease, preoperative use of antispasmodics and lower resected prostate volume ratios are risk factors for postoperative use of adrenergic Alpha-blockers and antispasmodics.

OBJECTIVES: Transurethral resection of prostate (TURP) and laser prostate surgery are common surgeries for benign prostate hyperplasia (BPH). We conducted an investigation using hospital database to evaluate the clinical factors associated with post-operative usage of alpha-blockers and antispasmodics. METHODS: This study was conducted using retrospective clinical data from the hospital database, which contained newly diagnosed BPH patients between January 2007 and December 2012 who subsequently received prostate surgery. The study end-point was the use of alpha-blockers or antispasmodics for at least 3 months duration after 1 month of surgery. The exclusion criteria was prostate cancer diagnosed before or after the surgery, recent transurethral surgeries, history of open prostatectomy, and history of spinal cord injury. Clinical parameters, including age, body mass index, preoperative prostate specific antigen value, comorbidities, preoperative usage of alpha-blockers, anstispasmodics and 5-alpha reductase inhibitors, surgical methods, resected prostate volume ratios, and preoperative urine flow test results, were evaluated. RESULTS: A total of 250 patients receiving prostate surgery in the database and confirmed pathologically benign were included. There was significant association between chronic kidney disease (CKD) and the usage of alpha-blockers after prostate surgery (OR = 1.93, 95% CI 1.04-3.56, p = 0.036). Postoperative antispasmodics usage was significantly associated with preoperative usage of antispasmodics (OR = 2.33, 95% CI 1.02-5.36, p = 0.046) and resected prostate volume ratio (OR = 0.12, 95% CI 0.02-0.63, p = 0.013). CONCLUSIONS: BPH patients with underlying CKD were more likely to require alpha-blockers after surgery. In the meantime, BPH patients who required antispasmodics before surgery and who received lower prostate volume resection ratio were more liable to antispasmodics after prostate surgery.

Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis.

Objective: To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases. Methods: Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis. Results: Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn's disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn's disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups. Conclusion: Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.

Thiopurine S-Methyltransferase Polymorphisms Predict Hepatotoxicity in Azathioprine-Treated Patients with Autoimmune Diseases.

Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation between TPMT polymorphisms and AZA-related hepatotoxicity. This study enrolled the patients who had prior exposure to AZA from the Taichung Veterans General Hospital (TCVGH)-Taiwan Precision Medicine Initiative (TPMI) cohort. Genetic variants were determined using a single nucleotide polymorphism (SNP) array. Participants were accordingly categorized into normal metabolizer (NM) and non-normal metabolizer (non-NM) groups. From the TCVGH-TPMI cohort, we included 50 TPMT non-NM patients, including 1 poor metabolizer (PM), 49 intermediate metabolizers (IMs), and 1000 NM patients. The non-NM genotype was associated with hepatotoxicity compared with the NM genotype (hazard ratio (HR): 3.85, 95% confidence interval (CI): 1.83−8.10). In the non-NM group, the 3-year cumulative incidence of hepatotoxicity was higher than that in the NM group at 8.5% in the first year and 18.6% in the second and third years (p < 0.001). A TPMT non-NM genotype was associated with the occurrence of hepatotoxicity following AZA therapy. Preemptive testing helps individualize AZA therapy by minimizing the risk of hepatotoxicity.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.