Does the presence of blind-ended vas deferens and spermatic vessels in laparoscopic exploration of non-palpable testes conclusively indicate testicular absence?

Objective: The purpose of this study was to determine whether the presence of blind-ended vas deferens and spermatic vessels (VDSV) during laparoscopic exploration of non-palpable testes (NPT) indicates testicular absence or atrophy. Materials and methods: A retrospective analysis was conducted on clinical data of patients diagnosed with NPT and treated with surgical intervention at our center from April 2013-April 2023. The dataset encompassed information such as the children's age, affected side, size of the contralateral testis, surgical procedures employed, outcomes, and histopathological examination results. All patients underwent physical examination and ultrasonography preoperatively, followed by a combination of laparoscopic exploration and exploration through inguinal or scrotal incisions during surgery. Long-term follow-up was conducted postoperatively. Results: A total of 476 cases comprising 504 NPT were included in this study: 302 cases on the left side, 146 cases on the right side, and 28 cases bilaterally. All patients underwent surgical treatment within 6-126 months (median 13 months). During laparoscopic exploration, blind-ended VDSV were found in 90 testes (72 on the left side, 18 on the right side), while exploration through inguinal or scrotal incisions revealed 52 (57.8%) testicular nodules with atrophy, which were excised, leaving 38 (42.2%) without any findings. Histopathological examination of atrophic nodules revealed fibrosis as the most common finding in 41 cases (78.8%), followed by involvement of the vas deferens in 33 cases (63.5%), calcification in 24 cases (46.2%), epididymis in 23 cases (44.2%), and hemosiderin deposition in 7 cases (13.6%). Fibrosis, calcification, hemosiderin deposition, involvement of the vas deferens, and epididymis were found in combination in 47 specimens (90.4%). Seminiferous tubules (SNT) were found in 3 specimens (5.7%), and germ cells (GC) were found in 1 specimen (1.9%). Conclusion: The presence of blind-ended VDSV during laparoscopic exploration of NPT does not necessarily indicate testicular absence or disappearance. It is possible that atrophic testicular nodules are located within the inguinal canal or scrotum. This understanding contributes to the management of non-palpable testes. Considering their unpredictable malignant potential, we recommend excision.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

LINC00525 enhances ZNF460-regulated CD24 expression through the sponge miR-125a-5p to promote malignant progression of breast cancer.

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.

Anti-Interleukin 17A Biologic Therapy Attempts on Livedoid Vasculopathy: A Report of Case Series.

The application of biologics such as anti-tumor necrosis factor (TNF) has shown great efficacy in livedoid vasculopathy (LV). However, new biological options need to be identified for those with a high tuberculosis reactivation risk. In this study, we evaluated the efficacy of anti-17A biologics for LV therapy. Two patients with LV who were irresponsive to traditional anticoagulation therapy were studied at the outpatient dermatology clinic of Peking Union Medical College Hospital. All patients received anti-17A biological therapy for at least two-four weeks. Both patients reported an exacerbation of the skin lesions, which might indicate that the IL-17 pathway plays a critical role in LV pathogenesis.

Risk factors and early detection of joint damage in patients with psoriasis: a case-control study.

BACKGROUND: Our aim was to target the unsatisfied need for early detection of the at-risk population and determine the subgroup of patients whose psoriasis (PsO) could transform into psoriatic arthritis (PsA). METHODS: A retrospective and longitudinal case-control study was conducted at Beijing Chao-yang Hospital. It included 75 patients who were clinically diagnosed with PsA in the case group and 345 who solely suffered from PsO without PsA in the control group. A variety of baseline covariates were gathered from every patient with PsO. Univariate and multivariate analyses and receiver operating characteristic (ROC) curves were used to identify underlying risk factors and determine whether it was necessary to examine the imaging of PsO patients. RESULTS: In multivariate logistic regression analysis, age ≥40 (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.06, P < 0.01), nail involvement (OR: 1.17, 95% CI: 1.09-1.32, P < 0.01), erythrocyte sedimentation rate (ESR) (OR: 1.03, 95% CI: 1.01-1.06, P < 0.05) and elevated high-sensitivity C-reactive protein (hs-CRP) (OR: 1.31, 95% CI: 1.13-1.53, P < 0.01) were perceived to be risk factors for the transformation from PsO into clinical PsA. By combining magnetic resonance imaging (MRI)-detected enthesitis with tenosynovitis, combined predictors demonstrated better diagnostic efficacy, with an improvement in specificity (94.3% vs. 69%) and similarities in sensitivity (89% vs. 84.6%). The areas under the ROC curve (AUCs) amounted to 0.925 (95% CI: 0.882-0.967, P < 0.01) and 0.858 (95% CI: 0.814-0.903, P < 0.01). CONCLUSIONS: It was identified that age ≥40, nail involvement, as well as an elevated ESR, and hs-CRP served as independent risk factors for PsO transforming into PsA. Additionally, MRI provides additional value for the early recognition of PsA.

Predictors of quitting support from nonsmoking mothers for smoking fathers: a cross-sectional study from Chinese pupils' families.

BACKGROUND: Quitting support from smokers' partners can predict quit attempts and smoking abstinence but research on factors that predict such support has been limited. To add more evidence for partner support and the improved interventions for smoking cessation, we analyzed some new potential predictors of quitting support from smokers' spouses. METHOD: This cross-sectional study was conducted in in 2022 and 2023, selecting the students' families in which fathers smoked and mothers didn't smoke from grade 1-5 of 13 primary schools in Qingdao, China. Parents who met the criteria completed the online questionnaires and 1018 families were included in the analysis. We measured personal information related to smokers and their spouses such as age, education and nicotine dependence, and variables related to family and marital relationship such as family functioning, perceived responsiveness and power in decision-making of quitting smoking. Quitting support from smokers' spouses was measured by Partner Interaction Questionnaire and generalized linear model was used to explore the potential predictors of partner support. RESULTS: In this study, the mean age of smokers was 39.97(SD = 5.57) and the mean age of smokers' spouses was 38.24(SD = 4.59). The regression analysis showed that for smokers and their spouses, the older age groups showed the lower ratio of positive/negative support(P < 0.05) and smokers with high education showed the less positive and negative partner support(P < 0.05). Nicotine dependence was positively associated with negative support (ß = 0.120, P < 0.01), and perceived responsiveness (ß = 0.124, P < 0.05) as well as family functioning (ß = 0.059, P < 0.05) was positively associated with positive support. These three factors were associated with ratio of positive/negative support(P < 0.05). In addition, power of smoker's spouse in decision-making of quitting smoking was positively associated with the positive (ß = 0.087, P < 0.001) and negative support (ß = 0.084, P < 0.001). CONCLUSIONS: Nicotine dependence, family functioning, power in decision-making of quitting smoking and perceived responsiveness were found to be the predictors of quitting support from smokers' spouses. By incorporating predictors of partner support and integrating some established theories that can improve family functioning and marital relationships, smoking cessation interventions can be further improved.

Protein Kinase A Is a Master Regulator of Physiological and Pathological Cardiac Hypertrophy.

BACKGROUND: The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors. If and how PKA plays a role in physiological cardiac hypertrophy (PhCH) and pathological CH (PaCH) are not clear. METHODS: Transgenic mouse models expressing the PKA inhibition domain (PKAi) of PKA inhibition peptide alpha (PKIalpha)-green fluorescence protein (GFP) fusion protein (PKAi-GFP) in a cardiac-specific and inducible manner (cPKAi) were used to determine the roles of PKA in physiological CH during postnatal growth or induced by swimming, and in PaCH induced by transaortic constriction (TAC) or augmented Ca2+ influx. Kinase profiling was used to determine cPKAi specificity. Echocardiography was used to determine cardiac morphology and function. Western blotting and immunostaining were used to measure protein abundance and phosphorylation. Protein synthesis was assessed by puromycin incorporation and protein degradation by measuring protein ubiquitination and proteasome activity. Neonatal rat cardiomyocytes (NRCMs) infected with AdGFP (GFP adenovirus) or AdPKAi-GFP (PKAi-GFP adenovirus) were used to determine the effects and mechanisms of cPKAi on myocyte hypertrophy. rAAV9.PKAi-GFP was used to treat TAC mice. RESULTS: (1) cPKAi delayed postnatal cardiac growth and blunted exercise-induced PhCH; (2) PKA was activated in hearts after TAC due to activated sympathoadrenergic system, the loss of endogenous PKIα (PKA inhibition peptide α), and the stimulation by noncanonical PKA activators; (3) cPKAi ameliorated PaCH induced by TAC and increased Ca2+ influxes and blunted neonatal rat cardiomyocyte hypertrophy by isoproterenol and phenylephrine; (4) cPKAi prevented TAC-induced protein synthesis by inhibiting mTOR (mammalian target of rapamycin) signaling through reducing Akt (protein kinase B) activity, but enhancing inhibitory GSK-3α (glycogen synthase kinase-3α) and GSK-3ß signals; (5) cPKAi reduced protein degradation by the ubiquitin-proteasome system via decreasing RPN6 phosphorylation; (6) cPKAi increased the expression of antihypertrophic atrial natriuretic peptide (ANP); (7) cPKAi ameliorated established PaCH and improved animal survival. CONCLUSIONS: Cardiomyocyte PKA is a master regulator of PhCH and PaCH through regulating protein synthesis and degradation. cPKAi can be a novel approach to treat PaCH.

Immunotyping of peripheral blood lymphocytes by flow cytometry reveals Th cell as a potential prognostic biomarker for extranodal NK/T-cell lymphoma.

This study aimed to explore the distribution, characteristics and prognostic value of baseline peripheral blood lymphocyte subsets in patients with extranodal NK/T-cell lymphoma (NKTCL). We conducted this cross-sectional study of 205 newly-diagnosed NKTCL patients receiving first-line chemotherapy and radiation at our institute between 2010 and 2020. Baseline peripheral blood lymphocytes were detected using flow cytometry, and the clinical value was analyzed. Compared with healthy controls, patients with NKTCL presented with a distinct peripheral immunity with higher levels of cytotoxic CD8+ T cells (33.230 ± 12.090% vs. 27.060 ± 4.010%, p < 0.001) and NKT cells (7.697 ± 7.219% vs. 3.550 ± 2.088%, p < 0.001) but lower proportions of suppressive regulatory T cells (Treg, 2.999 ± 1.949% vs. 3.420 ± 1.051%, p = 0.003) and CD4+ helper T cells (Th, 33.084 ± 11.361% vs. 37.650 ± 3.153%, p < 0.001). Peripheral lymphocytes were differentially distributed according to age, stage, and primary site in patients with NKTCL. The proportion of Th cells/lymphocytes was associated with tumor burden reflected by stage (p = 0.037), serum lactate dehydrogenase (p = 0.0420), primary tumor invasion (p = 0.025), and prognostic index for NK/T-cell lymphoma (PINK) score (p = 0.041). Furthermore, elevated proportions of T cells (58.9% vs. 76.4%, p = 0.005), Th cells (56.3% vs. 68.8%, p = 0.047), or Treg cells (49.5% vs. 68.9%, p = 0.040) were associated with inferior 5-year progression-free survivals (PFS) via univariable survival analysis. Multivariate cox regression revealed elevated Th cells as an independent predictor for unfavorable PFS (HR = 2.333, 95% CI, 1.030-5.288, p = 0.042) in NKTCL. These results suggested the proportion of Th cells positively correlated with tumor burden and was a potential non-invasive biomarker for inferior survival for patients with NKTCL.

Comparison of the properties of phenolic resin synthesized from different aldehydes and evaluation of the release and health risks of VOCs.

Different amounts of glyoxal and paraformaldehyde were used to synthesize phenol-glyoxal (PG) and phenol-paraformaldehyde (PPF) resins, which were compared with conventional phenol-formaldehyde (PF) resins. Glyoxal oxidation leads to a pH value of 9.83 for PG 2.2. With the addition of polyformaldehyde, PPF 2.2 exhibited the highest viscosity at 17333.33 mPa s. The PPF 2.0 plywood has a maximum bonding strength of 1.94 MPa. The formaldehyde emission of PG 1.8 plywood is found to have a minimum value of 0.025 mg/m3, reaching the ENF limit (≤0.025 mg/m3). Acetaldehyde is found only in volatile organic compound (VOC) emissions from PG plywood and is associated with increased glyoxal. PPF plywood emitted more aromatic and total VOC (TVOC) than the other two plywood types. The measured TVOC for PPF 2.2 is 196.07 µg/m3. The results showed that the total cancer risk (TCR) values of PPF 1.8, PPF 2.0, and PG 1.8 were above the threshold of 1.00E-4, indicating a definite carcinogenic risk. Acetaldehyde in the PG plywood exceeded the safety threshold for noncarcinogenic risk. The use of paraformaldehyde in the wood-based panel production is been considered a possible means of improving the bonding strength of plywood. Glyoxal has also been shown to be a viable method for lowering the formaldehyde emissions from plywood. The VOC emissions from plywood changed significantly depending on the aldehyde used. Limiting VOCs that present high health hazards is crucial for reducing the negative impact of plywood on both indoor environments and human health.

A pyroptosis-related gene expression signature predicts immune microenvironment and prognosis in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive malignancy with a poor prognosis. Pyroptosis triggered by gasdermins family proteins is reported vital for tumor microenvironment and cancer progression. However, pyroptosis-related gene expression and its relationship with immune infiltration and prognosis of HNSCC have not been fully defined. MATERIAL AND METHODS: RNA-sequencing data of HNSCC patients were acquired from The Cancer Genome Atlas (TCGA) database. A pyroptosis-related gene expression signature and infiltrated immune cells were analyzed. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and nomogram analyses were used to construct a clinical-molecular risk model for survival prognosis. RESULTS: HNSCC was classified into three different molecular subtypes based on the expression information of pyroptosis-related genes. Immune cell infiltration was demonstrated to be distinct between the three subtypes. The segregation of patients into the high-risk group and low-risk group, were carried out using the signature of differential expression genes (DEGs) signature among the three molecular subtypes. The precision of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the 3-year area under time-dependent ROC curve (AUC) reaching 0.711. The risk model was validated in another dataset from the Gene Expression Omnibus (GEO) database. Subsequently we established a clinical-molecular nomogram which combined the risk score with age and stage. The calibration plots for predicting the overall survival rate of 1-, 3-, and 5-years indicated that the nomogram performs well. CONCLUSION: The expression signature that encompasses pyroptosis-related genes could be used as molecular classification for HNSCC and pyroptosis might be a promising therapeutic target in HNSCC.

Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Treatment and prognosis of newly diagnosed advanced-stage extranodal natural killer / T cell lymphoma: a single-center real-world study across two decades.

INTRODUCTION: Although there is now a consensus on asparaginase-based chemotherapy regimens in treatment of advanced-stage extranodal natural killer / T cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. METHODS: Newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. RESULTS: The study included 83 newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase- compared to non-asparaginase-based regimens significantly prolonged PFS (P=0.007; HR=0.48, P=0.020) and showed a tendency to improve OS (P=0.064; HR=0.74, P=0.359). Gemcitabine-based regimens also exhibited a trend towards improved PFS (P=0.048; HR=0.59, P=0.164) and OS (P=0.008; HR=0.67, P=0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (P=0.020; HR=0.40, P=0.022) and slightly better OS (P=0.054; HR=0.79, P=0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (P=0.051) and OS (P=0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. CONCLUSION: Asparaginase and gemcitabine alone brought favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.

Unraveling shared risk factors for diabetic foot ulcer: a comprehensive Mendelian randomization analysis.

INTRODUCTION: Diabetic foot ulcer (DFU) stands as a severe diabetic lower extremity complication, characterized by high amputation rates, mortality, and economic burden. We propose using Mendelian randomization studies to explore shared and distinct risk factors for diabetic lower extremity complications. RESEARCH DESIGN AND METHODS: We selected uncorrelated genetic variants associated with 85 phenotypes in five categories at the genome-wide significance level as instrumental variables. Genetic associations with DFU, diabetic polyneuropathy (DPN), and diabetic peripheral artery disease (DPAD) were obtained from the FinnGen and UK Biobank studies. RESULTS: Body mass index (BMI) emerged as the only significant risk factor for DPAD, DPN, and DFU, independent of type 2 diabetes, fasting glucose, fasting insulin, and HbA1c. Educational attainment stood out as the sole significant protective factor against DPAD, DPN, and DFU. Glycemic traits below the type 2 diabetes diagnosis threshold showed associations with DPAD and DPN. While smoking history exhibited suggestive associations with DFU, indicators of poor nutrition, particularly total protein, mean corpuscular hemoglobin, and mean corpuscular volume, may also signal potential DFU occurrence. CONCLUSIONS: Enhanced glycemic control and foot care are essential for the diabetic population with high BMI, limited education, smoking history, and indicators of poor nutrition. By focusing on these specific risk factors, healthcare interventions can be better tailored to prevent and manage DFU effectively.

Plasma hepatocyte growth factor as a noninvasive biomarker in small cell lung cancer.

BACKGROUND: Hepatocyte growth factor (HGF) is a peptide-containing multifunctional cytokine, which is overexpressed and/or activated in multiple malignancies and is reported to be associated with tumor development and inferior survival. At present, the role of HGF in small cell lung cancer (SCLC) has not been fully explored yet. MATERIALS AND METHODS: The expression of HGF and its value in predicting survival in SCLC were explored from GEO database and in pan-cancer analysis. Furthermore, we detected the expression of HGF using tumor tissue and paired plasma samples from a validation cohort of 71 SCLC patients at our institute. Correlation between tumor and plasma HGF expression and the prognostic values were analyzed. RESULTS: GEO database analysis revealed that tumor tissue had lower HGF expression than paired normal tissue in SCLC. At our institute, immunohistochemical staining showed negative expression of HGF in tumor tissue of SCLC at our institute (47/47, 100%). The average baseline plasma HGF was 1.28 (range,0.42-4.35) ng/ml. However, plasma HGF was higher in SCLC patients with patients with N3, M1, liver metastasis (LM) and bone metastasis (BM) disease compared with those N0 - 2 (1.25 vs. 1.75 ng/mL, P = 0.000), M0 (1.26 vs. 1.63 ng/mL, P = 0.003), non-LM (1.32 vs. 2.06 ng/mL, P = 0.009), and non-BM (1.35 vs. 1.77 ng/mL, P = 0.047), respectively. Multivariate analysis revealed plasma HGF was an independent predictor for LM and prognostic factor of OS. CONCLUSION: Our results revealed that plasma HGF rather than tumor HGF exhibited a potential role in predicting metastasis and survival in SCLC. Plasma HGF might be used as a non-invasive detecting and monitoring tool for SCLC.

Mouse Slfn8 and Slfn9 genes complement human cells lacking SLFN11 during the replication stress response.

The Schlafen (SLFN)11 gene has been implicated in various biological processes such as suppression of HIV replication, replication stress response, and sensitization of cancer cells to chemotherapy. Due to the rapid diversification of the SLFN family members, it remains uncertain whether a direct ortholog of human SLFN11 exists in mice. Here we show that mSLFN8/9 and hSLFN11 were rapidly recruited to microlaser-irradiated DNA damage tracks. Furthermore, Slfn8/9 expression could complement SLFN11 loss in human SLFN11-/- cells, and as a result, reduced the growth rate to wild-type levels and partially restored sensitivity to DNA-damaging agents. In addition, both Slfn8/9 and SLFN11 expression accelerated stalled fork degradation and decreased RPA and RAD51 foci numbers after DNA damage. Based on these results, we propose that mouse Slfn8 and Slfn9 genes may share an orthologous function with human SLFN11. This notion may facilitate understanding of SLFN11's biological role through in vivo studies via mouse modeling.

Overexpression of KLF4 Suppresses Pulmonary Fibrosis through the HIF-1α/Endoplasmic Reticulum Stress Signaling Pathway.

The hypoxia-inducible factor-1α/endoplasmic reticulum stress signaling pathway (HIF-1α/ERS) has a crucial role in the pathogenetic mechanism of pulmonary fibrosis (PF). However, the upstream regulatory mediators of this pathway remain unclear. In the present study, by conducting bioinformatics analysis, we found that Krüppel-like factor 4 (KLF4) expression was decreased in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF) as compared to that in patients with non-IPF. Furthermore, KLF4 expression was significantly reduced (p = 0.0331) in bleomycin-induced fibrotic HFL-1 cells. Moreover, in mice with bleomycin-induced PF, the degree of fibrosis was significantly reduced in mice overexpressing KLF4 as compared to that in wild-type mice. In mice and HFL-1 cells, KLF4 overexpression significantly reduced bleomycin-induced protein expression of HIF-1α (p = 0.0027) and ERS markers, particularly p-IRE1α (p = 0.0255) and ATF6 (p = 0.0002). By using the JASPAR database, we predicted that KLF4 has five binding sites for the HIF-1α promoter. The results of in vitro and in vivo studies suggest that KLF4 may inhibit PF through the HIF-1α/ERS pathway. This finding could guide the development of future therapies for PF and facilitate the identification of appropriate biomarkers for routine clinical diagnosis of PF.

Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data.

ABSTRACT: The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.