Fat body-derived juvenile hormone acid methyltransferase functions to maintain iron homeostasis in Drosophila melanogaster.

Iron homeostasis is of critical importance to living organisms. Drosophila melanogaster has emerged as an excellent model to study iron homeostasis, while the regulatory mechanism of iron metabolism remains poorly understood. Herein, we accidently found that knockdown of juvenile hormone (JH) acid methyltransferase (Jhamt) specifically in the fat body, a key rate-limiting enzyme for JH synthesis, led to iron accumulation locally, resulting in serious loss and dysfunction of fat body. Jhamt knockdown-induced phenotypes were mitigated by iron deprivation, antioxidant and Ferrostatin-1, a well-known inhibitor of ferroptosis, suggesting ferroptosis was involved in Jhamt knockdown-induced defects in the fat body. Further study demonstrated that upregulation of Tsf1 and Malvolio (Mvl, homolog of mammalian DMT1), two iron importers, accounted for Jhamt knockdown-induced iron accumulation and dysfunction of the fat body. Mechanistically, Kr-h1, a key transcription factor of JH, acts downstream of Jhamt inhibiting Tsf1 and Mvl transcriptionally. In summary, the findings indicated that fat body-derived Jhamt is required for the development of Drosophila by maintaining iron homeostasis in the fat body, providing unique insight into the regulatory mechanisms of iron metabolism in Drosophila.

Intrauterine chilled saline instillation reduces endometrial impairment on MRI after ultrasound-guided percutaneous microwave ablation of uterine adenomyosis.

OBJECTIVE: To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. METHODS: An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. RESULTS: The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2-139.6%) and 99.7 ± 15.7% (range: 71.5-129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort. CONCLUSION: Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis. CRITICAL RELEVANCE STATEMENT: This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice. KEY POINTS: Endometrial impairment occurs in the PMWA treatment of adenomyosis. Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis. An intrauterine catheter is a practical endometrial protecting method during thermal ablation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090 .

Disulfidptosis: A new type of cell death.

Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.

BRAFV600E-Mutant Metastatic Colorectal Cancer: Current Evidence, Future Directions, and Research Priorities.

BRAFV600E-mutant metastatic colorectal cancer represents a distinct molecular phenotype known for its aggressive biological behavior, resistance to standard therapies, and poor survival rates. Improved understanding of the biology of the BRAF oncogene has led to the development of targeted therapies that have paved the way for a paradigm shift in managing this disease. However, despite significant recent advancements, responses to targeted therapies are short-lived, and several challenges remain. In this review, we discuss how progress in treating BRAFV600E-mutant metastatic colorectal cancer has been made through a better understanding of its unique biological and clinical features. We provide an overview of the evidence to support current treatment approaches and discuss critical areas of need and future research strategies that hold the potential to refine clinical practice further. We also discuss some challenging aspects of managing this disease, particularly the complexity of acquired resistance mechanisms that develop under the selective pressure of targeted therapies and rational strategies being investigated to overcome them.

A Case Report on Alpha-Fetoprotein-Positive Colorectal Cancer.

Alpha-fetoprotein (AFP) is commonly produced by hepatocellular carcinoma and yolk sac tumors, while AFP in colorectal cancer (CRC) is a rare association. We report a case of a patient with primary AFP-producing CRC, which was successfully treated with surgery and adjuvant chemotherapy. This case highlighted the importance of recognizing a case of AFP-producing CRC.  This case report discussed a 59-year-old male who had a history of hepatitis B infection, with two months of intermittent fresh per rectal bleeding. Given his previous burden of hepatitis B infection, and the serum AFP level on admission was high (212.6 ng/mL), this raised suspicions of possible hepatocellular carcinoma. Therefore, a triphasic computed tomography of the liver was performed, which revealed an incidental hepatic flexure lesion with no involvement of the liver. Subsequent colonoscopy revealed a large friable tumor obstructing the whole lumen of the proximal transverse colon. He then underwent an emergency extended right hemicolectomy. Histopathological examination showed a Duke C mucinous adenocarcinoma (T3N2b), with a satisfactory resected margin. Immunohistochemical analysis indicated that the tumor exhibited positivity for MLH1/MSH2/MSH6/PMS2 (+++) and human epidermal growth factor receptor 2 (HER2), and notably, it also stained positive for AFP. The postoperative period was uneventful, and serum AFP level eventually normalized. The patient completed eight cycles (four months) of adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) regimen. A follow-up CT scan and colonoscopy showed no evidence of local or distant recurrence after 12 months of surveillance. AFP may be useful for not only hepatocellular carcinoma but also CRC. In particular, this case report has fully demonstrated the unexpected incidence and emphasized the importance of early recognition and appropriate treatment to prevent potential oversights in the diagnosis of CRC.

Validity and reliability of the Malay language Perception Towards Smoking Questionnaire (BM-PTSQ) among secondary school adolescents: Further validation using Confirmatory Factor Analysis.

INTRODUCTION: Perception is an essential factor influencing smoking among adolescents. Thus, a valid tool for measuring perception is a requisite in smoking studies. This study further establishes the validity and reliability of a Malay language version of the Perception Towards Smoking Questionnaire (BM-PTSQ) for assessing the perception of smoking among secondary school-going adolescents in Malaysia. METHODS: We administered the BM-PTSQ to 669 secondary school students selected through multistage sampling; 60% of respondents were male (n=398), and 69.9% (n=463) were from rural areas. Respondents were aged 13-16 years, 36.4% (n=241) were 13 years, 40.0% (n=265) were 14 years, and 23.6% (n=156) were 16 years old. We used parallel and exploratory factor analysis (EFA) to determine the domains of the questionnaire. In addition, we also employed EFA, confirmatory factor analyses (CFA), and Cronbach's alpha to evaluate the construct validity and reliability of the BM-PTSQ. RESULTS: EFA and parallel analysis identified two domains in the BM-PTSQ that accounted for 62.9% of the observed variance, and CFA confirmed the two-domain structure. The two domains' internal consistency scores ranged from 0.702 to 0.80, which suggested adequate reliability. CONCLUSIONS: The BM-PTSQ has acceptable psychometric validity and is appropriate for assessing smoking perception and intention among Malaysian secondary school-aged youth. Researchers should further evaluate this tool's applicability in a more sociodemographically diverse population.

Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice.

BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. CONCLUSIONS: Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

Exclusive Core-Janus Satellite Assembly Based on Au-Ag Janus Self-Aligned Distributions with Abundant Hotspots for Ultrasensitive Detection of CA19-9.

The development of surface-enhanced Raman scattering (SERS) probes with high sensitivity and stability is imminent to improve the accuracy of cancer diagnosis. Here, an exclusive core-Janus satellite (CJS) assembly was constructed by a hierarchical assembly strategy in which the Au-Ag Janus satellite is vertically self-aligned on the core surface. In the process, a silica shell template was ingeniously employed to asymmetrically mask the presatellites for the in situ formation of the Janus structure, and a series of Janus satellites with different morphologies were developed by regulating the encapsulated area of the presatellites. The ordered-oriented arrangement of Au-Ag Janus and unique heterojunction morphology permit CJS assemblies, featuring two types of plasmonic nanogaps, including intrananocrevices for individual Janus and internanogaps between neighboring Janus, thereby multiplying the "hotspots" compared to conventional core-monotonous satellites, which contributes to superior SERS activity. As anticipated, the enhancement factor of CJS assemblies was as high as 3.8 × 108. Moreover, it is intriguing that the directional distribution and head physically immobilized by Janus provided uniform and stable SERS signals. The SERS probe based on the CJS assembly for the detection of carbohydrate antigen 19-9 resulted in an ultrahigh sensitivity with a limit of detection of 3.7 × 10-5 IU·mL-1, which is nearly 10 times lower than other SERS probes, and a wide detection range of 3 × 10-5 to 1 × 104 IU·mL-1. The CJS assembly with excellent SERS performance is promising to advance further development of the early diagnosis of pancreatic cancer.

Adjuvant Chemotherapy for Older Patients With Stage III Colorectal Cancer: A Real-World Analysis of Treatment Recommendations, Treatment Administered and Impact on Cancer Recurrence.

BACKGROUND: A substantial proportion of patients with stage III colorectal cancer (CRC) are older than 70 years. Optimal adjuvant chemotherapy (AC) for older patients (OP) continues to be debated, with subgroup analyses of randomized trials not demonstrating a survival benefit from the addition of oxaliplatin to a fluoropyrimidine backbone. PATIENTS AND METHODS: We analyzed the multisite Australian ACCORD registry, which prospectively collects patient, tumor and treatment data along with long term clinical follow-up. We compared OP (≥70) with stage III CRC to younger patients ([YP] <70), including the proportion recommended AC and any reasons for not prescribing AC. AC administration, regimen choice, completion rates, and survival outcomes were also examined. RESULTS: One thousand five hundred twelve patients enrolled in the ACCORD registry from 2005 to 2018 were included. Median follow-up was 57.0 months. Compared to the 827 YP, the 685 OP were less likely to be offered AC (71.5% vs. 96.5%, P < .0001) and when offered, were more likely to decline treatment (15.1% vs. 2.8%, P < .0001). Ultimately, 60.0% of OP and 93.7% of YP received AC (P < .0001). OP were less likely to receive oxaliplatin (27.5% vs. 84.7%, P < .0001) and to complete AC (75.9% vs. 85.7%, P < .0001). The probability of remaining recurrence-free was significantly higher in OP who received AC compared to those not treated (HR 0.73, P = .04) but not significantly improved with the addition of oxaliplatin (HR 0.75, P = .18). CONCLUSION: OP were less likely than YP to receive AC. Receipt of AC reduced recurrences in OP, supporting its use, although no significant benefit was observed from the addition of oxaliplatin.

Inhibition of ferroptosis underlies EGCG mediated protection against Parkinson's disease in a Drosophila model.

Ferroptosis, a new type of cell death accompanied by iron accumulation and lipid peroxidation, is implicated in the pathology of Parkinson's disease (PD), which is a prevalent neurodegenerative disorder that primarily occurred in the elderly population. Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea with known neuroprotective effects in PD patients. But whether EGCG-mediated neuroprotection against PD involves regulation of ferroptosis has not been elucidated. In this study, we established a PD model using PINK1 mutant Drosophila. Iron accumulation, lipid peroxidation and decreased activity of GPX, were detected in the brains of PD flies. Additionally, phenotypes of PD, including behavioral defects and dopaminergic neurons loss, were ameliorated by ferroptosis inhibitor ferrostatin-1 (Fer-1). Notably, the increased iron level, lipid peroxidation and decreased GPX activity in the brains of PD flies were relieved by EGCG. We found that EGCG exerted neuroprotection mainly by restoring iron homeostasis in the PD flies. EGCG inhibited iron influx by suppressing Malvolio (Mvl) expression and simultaneously promoted the upregulation of ferritin, the intracellular iron storage protein, leading to a reduction in free iron ions. Additionally, EGCG downregulated the expression of Duox and Nox, two NADPH oxidases that produce reactive oxygen species (ROS) and increased SOD enzyme activity. Finally, modulation of intracellular iron levels or regulation of oxidative stress by genetic means exerted great influence on PD phenotypes. As such, the results demonstrated that ferroptosis has a role in the established PD model. Altogether, EGCG has therapeutic potentials for treating PD by targeting the ferroptosis pathway, providing new strategies for the prevention and treatment of PD and other neurodegenerative diseases.

Characterization the prognosis role and effects of snoRNAs in melanoma patients.

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

Elevated serum neuropeptide Y levels are associated with carotid plaque formation in Chinese adults: a cross-sectional study.

BACKGROUND: Carotid plaque (CP) formation is an important consequence of atherosclerosis and leads to significant complications. Levels of neuropeptide Y (NPY), which is a sympathetic neurotransmitter, are elevated in cardiovascular diseases. It also has important roles in inflammatory conditions. This study aimed to explore the relationship between serum NPY and CP and to study further the influence of NPY and inflammatory factors on CP. METHODS: This cross-sectional study was conducted among 300 adults who underwent a health examination at the Second Affiliated Hospital of Fujian Medical University in Fujian Province, of whom 177 were finally enrolled. The participants were divided into the CP (n = 120) and non-CP (NCP) or control (n = 57) groups according to the results of carotid artery color Doppler ultrasound. The CP group was further classified into stable plaque (SP, n = 80) and vulnerable plaque (VP, n = 40) groups based on plaque characteristics. Serum NPY and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) levels were examined. Univariate and correlation analyses were used to evaluate the correlation between serum NPY levels, pro-inflammatory cytokines, and the CP phenotype. RESULTS: The serum NPY and TNF-α levels of patients in the CP group were significantly higher than those in individuals from the NCP group [ (177.30 ± 43.29) pg.mL- 1 vs. (121.53 ± 40.16)pg.mL- 1, P < 0.001; (41.94 ± 14.19) pg.mL- 1 vs.(33.54 ± 13.37)pg.mL- 1, P = 0.003]. The serum NPY levels of the patients in the VP group were significantly higher than those in patients from the SP group [(191.67 ± 39.87)ng.L- 1 vs.(170.12 ± 43.37)ng.L- 1, P = 0.01, P < 0.05]. Serum TNF-α and NPY levels were positively correlated among patients from the CP group (r = 0.184, P = 0.044). The binary logistic regression analysis showed that serum NPY and TNF-α were independent influencing factors of CP [(OR = 1.029, P < 0.001);(OR = 1.030, P = 0.023)]. The area under the ROC curve of NPY predicting the CP showed statistical significance at a value of 0.819. CONCLUSION: Together, elevated serum NPY levels seem to be associated with the occurrence of coronary atherosclerosis in Chinese adults.

Ratio of hemoglobin to mean corpuscular volume: A new index for discriminating between iron deficiency anemia and thalassemia trait.

BACKGROUND: Iron deficiency anemia (IDA) and thalassemia trait (TT) are the most common microcytic and hypochromic anemias. Differentiation between mild TT and early IDA is still a clinical challenge. AIM: To develop and validate a new index for discriminating between IDA and TT. METHODS: Blood count data from 126 patients, consisting of 43 TT patients and 83 IDA patients, was retrospectively analyzed to develop a new index formula. This formula was further validated in another 61 patients, consisting of 48 TT patients and 13 IDA patients. RESULTS: The new index is the ratio of hemoglobin to mean corpuscular volume. Its sensitivity, specificity, accuracy, Youden's Index, area under the receiver operating characteristic curve, and Kappa coefficient in discriminating between IDA and TT were 93.5%, 78.4%, 83.3%, 0.72, 0.97, and 0.65, respectively. CONCLUSION: This new index has good diagnostic performance in discriminating between mild TT and early IDA. It requires only two results of complete blood count, which can be a very desirable feature in under-resourced scenarios.

Abrogation of ATR function preferentially augments cisplatin-induced cytotoxicity in PTEN-deficient breast cancer cells.

Targeting replication stress response is currently emerging as new therapeutic strategy for cancer treatment, based on monotherapy and combination approaches. As a key sensor in response to DNA damage, ataxia telangiectasia and rad3-related (ATR) kinase has become a potential therapeutic target as tumor cells are to rely heavily on ATR for survival. The tumor suppressor phosphatase and tensin homolog (PTEN) plays a crucial role in maintaining chromosome integrity. Although ATR inhibition was recently confirmed to show a synergistic inhibitory effect in PTEN-deficient triple-negative breast cancer cells, the molecular mechanism needs to be further elucidated. Additionally, whether the PTEN-deficient breast cancer cells are more preferentially sensitized than PTEN-wild type breast cancer cells to cisplatin plus ATR inhibitor remains unanswered. We demonstrate PTEN dysfunction promotes the killing effect of ATR blockade through the use of RNA interference for PTEN and a highly selective ATR inhibitor VE-821, and certify that VE-821 (1.0 µmol/L) aggravates cytotoxicity of cisplatin on breast cancer cells, especially PTEN-null MDA-MB-468 cells which show more chemoresistance than PTEN-expressing MDA-MB-231 cells. The co-treatment with VE-821 and cisplatin significantly reduced cell viability and proliferative capacity compared with cisplatin mono-treatment (P < 0.05). The increased cytotoxic activity is tied to the enhanced poly (ADP-ribose) polymerase (PARP) cleavage and consequently cell death due to the decrease in phosphorylation levels of checkpoint kinases 1 and 2 (CHK1/2), the reduction of radiation sensitive 51 (RAD51) foci and the increase in phosphorylation of the histone variant H2AX (γ-H2AX) foci (P < 0.05) as well. Together, these findings suggest combination therapy of ATR inhibitor and cisplatin may offer a potential therapeutic strategy for breast tumors.

[Clinical Characteristics and Prognosis of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze the clinical manifestations, therapeutic response and prognosis of patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). METHODS: Thirty-eight patients with PT-DLBCL were enrolled, who hospitalized from January 2010 to April 2021, and their clinical characteristics, treatment regimen and efficacy were collected and analyzed retrospectively. RESULTS: The median age of the patients was 56 years old (ranged from 38 to 79 years). There were 4 cases (10.5%) with bilateral lesions, 13 cases (34.2%) with left lesions, and 21 cases (55.3%) right lesions. There were 2 cases(5.3%) with B symptoms, 6 cases (15.8%) of germinal center B-cell-like(GCB) subtype and 32 cases(84.2%) of non-GCB subtype. Efficacy was evaluated in 36 cases, including 10 cases with CHOP regimen, 21 cases with R-CHOP regimen (7 cases were treated with rituximab combined with high-dose methotrexate injection chemotherapy at intervals of R-CHOP regimen), and 5 cases with other regimens. In 36 patients, the efficacy evaluation of initial chemotherapy showed that the overall response rate (ORR) was 86.1%, 29 cases (80.6%) reached complete response (CR), and 2 cases (5.5%) reached partial response (PR). The R-CHOP group was superior to CHOP group in ORR (95.2% vs 60.0%, P=0.027) and CR (90.4% vs 50.0%, P=0.022). Of the 36 patients, 7 cases had central nervous system(CNS) recurrence and 4 cases had contralateral testicular recurrence. Compared with the CHOP group, the CNS recurrence rate in the R-CHOP group was significantly lower (4.8% vs 50.0%, P=0.007), and the testicular recurrence rate in the R-CHOP group was also lower than the CHOP group, but the difference was not statistically significant (4.8% vs 30.0%, P=0.087). The median follow-up time was 27(3-135) months, and the 5-year PFS and OS were 71% and 74%, respectively. Kaplan-Meier univariate analysis showed that the R-CHOP regimen significantly improved the patients' PFS (P=0.024) and OS (P=0.025) compared with the CHOP regimen. CONCLUSION: PT-DLBCL is mainly treated with comprehensive treatment. Compared with CHOP regimen, R-CHOP regimen can improve the CR rate and ORR, reduce CNS recurrence and contralateral testicular recurrence, and improve the patients' survival. Patients may benefit from high-dose methotrexate combined with rituximab interlaced with R-CHOP regimen.

[Factors influencing the chronic post-surgical pain after laparoscopic surgery for elderly patients with urinary tract tumors].

OBJECTIVE: To investigate the incidence and potential influence factors that contribute to chronic post-surgical pain (CPSP) in elderly patients with urinary tract tumors who underwent laparoscopic procedures. METHODS: A retrospective study was conducted to collect the clinical data of 182 elderly patients with urinary tract tumors who were ≥65 years and underwent laparoscopic surgery from October 2021 to March 2022 in Peking University Third Hospital. The patients'demographic information, medical history and the severity of postoperative pain were collected. Telephone follow-ups were made 6 months after surgery, and the patients' CPSP conditions were recorded. The diagnostic criteria of CPSP were referred to the definition made by the International Association for the Study of Pain (IASP): (1) Pain that developed or increased in intensity after surgical procedure and persisted for at least 3 months after surgery; (2) Pain that localized to the surgical field or projected to the innervation territory of a nerve situated around the surgical area; (3) Pain due to pre-existing pain conditions or infections and malignancy was excluded. The patients were divided into two groups based on CPSP diagnosis. Risk factors that predisposed the patients to CPSP were identified using univariate analysis. A multivariate Logistic regression model using back-forward method was designed, including both variables that significantly associated with CPSP in the univariate analysis (P < 0.1), and the variables that were considered to have significant clinical impact on the outcome. RESULTS: Two hundred and sixteen patients with urinary tract tumors who had undergone laparoscopic surgery were included, of whom, 34 (15.7%) were excluded from the study. For the remaining 182 patients, the average age was (72.6±5.2) years, with 146 males and 36 females. The incidence of CPSP at the end of 6 months was 31.9% (58/182). Multiva-riate regression analysis revealed that age ≥75 years (OR=0.29, 95% CI: 0.12-0.73, P=0.008) was the protecting factors for postoperative chronic pain in the elderly patients with urinary tract tumors undergoing surgical treatment, while renal cancer (compared with other types of urinary tract tumors) (OR=3.68, 95% CI: 1.58-8.58, P=0.003), and the 24 h postoperative moderate to severe pain (OR=2.57, 95% CI: 1.14-5.83, P=0.024) were the independent risk factors affecting CPSP. CONCLUSION: Age < 75 years, renal cancer and the 24 h postoperative moderate to severe pain are influence factors of the occurrence of CPSP after laparoscopic surgery in elderly patients with urinary tract tumors. Optimum postoperative multimodal analgesia strategies are suggested to prevent the occurrence of CPSP.

Effects of BPA Exposure and Recovery on the Expression of Genes Involved in the Hepatic Lipid Metabolism in Male Mice.

Exposure to Bisphenol A (BPA) has led to an increased risk of obesity and nonalcoholic fatty liver diseases (NAFLDs). However, it is as yet unclear if the damage caused by BPA is able to be repaired sufficiently after exposure has ceased. Therefore, this project aims to investigate the effects of BPA on the hepatic lipid metabolism function and its potential mechanisms in mice by comparing the BPA exposure model and the BPA exposure + cessation of drug treatment model. Herein, the male C57BL/6 mice were exposed in the dose of 50 µg/kg/day and 500 µg/kg/day BPA for 8 weeks, and then transferred to a standard chow diet for another 8 weeks to recover. Based on our previous RNA-seq study, we examined the expression patterns of some key genes. The results showed that the mice exposed to BPA manifested NAFLD features. Importantly, we also found that there was a significant expression reversion for SCD1, APOD, ANGPT4, PPARß, LPL and G0S2 between the exposure and recovery groups, especially for SCD1 and APOD (p < 0.01). Notably, BPA could significantly decrease the level of APOD protein (p < 0.01) whereas there was an extremely significant increase after the exposure ceased. Meanwhile, APOD over-expression suppressed TG accumulation in the AML12 cells. In conclusion, the damage caused by BPA is able to be repaired by the upregulation of APOD and exposure to BPA should be carefully examined in chronic liver metabolic disorders or diseases.

Ultrasound-guided percutaneous microwave ablation for adenomyosis with abnormal uterine bleeding: clinical outcome and associated factors.

OBJECTIVE: To investigate the factors affecting the efficacy of ultrasound (US)-guided percutaneous microwave ablation (PMWA) for adenomyosis with abnormal uterine bleeding (AUB-A). METHODS: Baseline data of patients with AUB-A who underwent US-guided PMWA treatment between October 2020 and October 2021, including demography characteristics, laboratory and imaging examination results were retrospectively analyzed. 3D reconstruction of magnetic resonance imaging (MRI) was applied to quantitatively assess the local treatment responses, including ratio of non-perfusion volume to adenomyosis volume (NPVr), ablation rate of the endometrial-myometrial junction (EMJ), and surface area (SA) of the ablated part of the EMJ. Patients were followed up at 3, 6, and 12 months after treatment, and divided into two groups: group with complete relief (CR), and group with partial relief (PR) or no relief (NR). Data were compared between them. RESULTS: Thirty-one patients were analyzed with a mean age of 38.7 ± 6.8 years (range: 24-48): 48.4% (15/31), 63.3% (19/30), and 65.5% (19/29) achieved CR at 3, 6, and 12 months, respectively. In univariate analysis, compared with the PR/NR group, serum CA125 levels were significantly lower in CR group at 3 months, while ablation rates of EMJ and SA of the ablated part of the EMJ were significantly higher at the three time points. Other baseline characteristics and NPVr did not differ between the two groups. CONCLUSION: Baseline CA125 and ablation rate of the EMJ and SA of the ablated part of the EMJ are associated with the outcome of AUB-A patients after US-guided PMWA treatment.

Chronic heat stress induces lung injury in broiler chickens by disrupting the pulmonary blood-air barrier and activating TLRs/NF-κB signaling pathway.

As an important respiratory organ, the lung is susceptible to damage during heat stress due to the accelerated breathing frequency caused by an increase in environmental temperature. This can affect the growth performance of animals and endanger their health. This study aimed to explore the mechanism of lung tissue damage caused by heat stress. Broilers were randomly divided into a control group (Control) and a heat stress group (HS). The HS group was exposed to 35°C heat stress for 12 h per d from 21-days old, and samples were taken from selected broilers at 28, 35, and 42-days old. The results showed a significant increase in lactate dehydrogenase (LDH) activity in the serum and myeloperoxidase (MPO) activity in the lungs of broiler chickens across all 3 age groups after heat stress (P < 0.01), while the total antioxidant capacity (T-AOC) was significantly enhanced at 35-days old (P < 0.01). Heat stress also led to significant increases in various proinflammatory factors in serum and expression levels of HSP60 and HSP70 in lung tissue. Histopathological results showed congestion and bleeding in lung blood vessels, shedding of pulmonary epithelial cells, and a large amount of inflammatory infiltration in the lungs after heat stress. The mRNA expression of TLRs/NF-κB-related genes showed an upward trend (P < 0.05) after heat stress, while the mRNA expression of MLCK, a gene related to pulmonary blood-air barrier, significantly increased after heat stress, and the expression levels of MLC, ZO-1, and occludin decreased in contrast. This change was also confirmed by Western blotting, indicating that the pulmonary blood-air barrier is damaged after heat stress. Heat stress can cause damage to the lung tissue of broiler chickens by disrupting the integrity of the blood-air barrier and increasing permeability. This effect is further augmented by the activation of TLRs/NF-κB signaling pathways leading to an intensified inflammatory response. As heat stress duration progresses, broiler chickens develop thermotolerance, which gradually mitigates the damaging effects induced by heat stress.