Effect of PEAR1, PTGS1 gene polymorphisms on the recurrence of aspirin-treated patients with ischemic stroke in the Han population of China: A 4-year follow-up study.

Platelet endothelial aggregation receptor 1 (PEAR1) and prostaglandin endoperoxide synthase 1 (PTGS1) polymorphisms can affect laboratory aspirin resistance. However, the impact of genetic polymorphisms on the recurrence of ischemic stroke (IS) patients treated with aspirin is not fully understood. This study aimed to examine the relationship between gene polymorphisms of PEAR1 and PTGS1 and IS recurrence in patients treated with aspirin. Peripheral blood samples were collected from 174 patients with nonrecurrent IS and 34 with recurrent IS after aspirin treatment. Follow-up was performed on all patients. PEAR1 rs12041331 and PTGS1 rs10306114 polymorphisms were determined using the PCR fluorescence probe method. And the correlations of them with the clinical characteristics were examined by multivariable logistic regression analysis. The distribution frequencies of PEAR1 rs12041331 and PTGS1 rs10306114 genotypes were in Hardy-Weinberg equilibrium, and there was no significant difference in the distribution of PEAR1 rs12041331 polymorphism. Compared to the nonrecurrent group, the AA genotype of the PTGS1 polymorphism was more frequent in the recurrent group (59.77% vs 35.29%, P = .003), and the A allele also showed a higher frequency than the G allele in the recurrent group (P = .001). Multivariable logistic regression analysis showed that smoking (OR = 5.228, 95% CI: 1.938-14.102, P = .001), coronary heart disease (OR = 4.754, 95% CI: 1.498-15.089, P = .008), and the polymorphism at PTGS1(A>G) AA/AG + GG (OR = 2.955, 95% CI: 1.320-6.616, P = .008) were independently associated with IS recurrence in Chinese patients. Our findings suggested that PTGS rs10306114 polymorphisms should receive more attention in the use of aspirin in patients with IS.

Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes. EXPERIMENTAL APPROACH: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. KEY RESULTS: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation. CONCLUSIONS AND IMPLICATIONS: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

Expression landscape of cancer-FOXP3 and its prognostic value in pancreatic adenocarcinoma.

FOXP3, a key identifier of Treg, has also been identified in tumor cells, which is referred to as cancer-FOXP3 (c-FOXP3). Human c-FOXP3 undergoes multiple alternative splicing events, generating several isoforms, like c-FOXP3FL and c-FOXP3Δ3. Previous research on c-FOXP3 often ignore its cellular source (immune or tumor cells) and isoform expression patterns, which may obscure our understanding of its clinical significance. Our immunohistochemistry investigations which conducted across 18 tumors using validated c-FOXP3 antibodies revealed distinct expression landscapes for c-FOXP3 and its variants, with the majority of tumors exhibited a predominantly expression of c-FOXP3Δ3. In pancreatic ductal adenocarcinoma (PDAC), we further discovered a potential link between nuclear c-FOXP3Δ3 in tumor cells and poor prognosis. Overexpression of c-FOXP3Δ3 in tumor cells was associated with metastasis. This work elucidates the expression pattern of c-FOXP3 in pan-cancer and indicates its potential as a prognostic biomarker in clinical settings, offering new perspectives for its clinical application.

VENet: Variational energy network for gland segmentation of pathological images and early gastric cancer diagnosis of whole slide images.

BACKGROUND AND OBJECTIVE: Gland segmentation of pathological images is an essential but challenging step for adenocarcinoma diagnosis. Although deep learning methods have recently made tremendous progress in gland segmentation, they have not given satisfactory boundary and region segmentation results of adjacent glands. These glands usually have a large difference in glandular appearance, and the statistical distribution between the training and test sets in deep learning is inconsistent. These problems make networks not generalize well in the test dataset, bringing difficulties to gland segmentation and early cancer diagnosis. METHODS: To address these problems, we propose a Variational Energy Network named VENet with a traditional variational energy Lv loss for gland segmentation of pathological images and early gastric cancer detection in whole slide images (WSIs). It effectively integrates the variational mathematical model and the data-adaptability of deep learning methods to balance boundary and region segmentation. Furthermore, it can effectively segment and classify glands in large-size WSIs with reliable nucleus width and nucleus-to-cytoplasm ratio features. RESULTS: The VENet was evaluated on the 2015 MICCAI Gland Segmentation challenge (GlaS) dataset, the Colorectal Adenocarcinoma Glands (CRAG) dataset, and the self-collected Nanfang Hospital dataset. Compared with state-of-the-art methods, our method achieved excellent performance for GlaS Test A (object dice 0.9562, object F1 0.9271, object Hausdorff distance 73.13), GlaS Test B (object dice 94.95, object F1 95.60, object Hausdorff distance 59.63), and CRAG (object dice 95.08, object F1 92.94, object Hausdorff distance 28.01). For the Nanfang Hospital dataset, our method achieved a kappa of 0.78, an accuracy of 0.9, a sensitivity of 0.98, and a specificity of 0.80 on the classification task of test 69 WSIs. CONCLUSIONS: The experimental results show that the proposed model accurately predicts boundaries and outperforms state-of-the-art methods. It can be applied to the early diagnosis of gastric cancer by detecting regions of high-grade gastric intraepithelial neoplasia in WSI, which can assist pathologists in analyzing large WSI and making accurate diagnostic decisions.

A new medical device applied in a case of acute fecal impaction with overflow diarrhea: a case report.

BACKGROUND: Fecal impaction is a digestive system disease, that is most common in the elderly population and becomes more prevalent with increasing age. Manual removal can successfully remove the impaction in 80% of fecal impaction cases. In severe cases, endoscopy and surgery may be necessary. CASE PRESENTATION: A 78-year-old Han Chinese man living in a nursing home was diagnosed with fecal impaction; his initial symptom was overflow diarrhea, which is a rare occurrence with regard to fecal impaction. Nevertheless, we were able to effectively treat this situation by employing a new medical device that presents a novel method for addressing fecal impaction. CONCLUSION: Early identification of fecal impaction with atypical symptoms is crucial to provide proper emergency management. A safe and noninvasive treatment method, especially for elderly patients with fecal impaction, should be chosen.

Adsorption Mechanisms of TM3 (TM = Mo, Ru, Au)-Decorated Tin Sulfide Monolayers for the Decomposition of Gas Components under Fault Conditions in Oil-Immersed Transformers.

Oil-immersed transformers play a pivotal role owing to their environmentally friendly characteristics, compact footprint, and cost-effectiveness. Ensuring the online monitoring of oil-immersed transformers is a fundamental measure to ensure the secure and stable operation of modern power systems. In this paper, metal particle cluster-doped SnS is firstly used in the adsorption and sensing of decomposition components (CO, C2H2) under fault conditions in oil-immersed transformers. The study comprehensively analyzed band structure, differential charge density, density of states, and molecular orbital theory to unveil the adsorption and sensing mechanisms of target gases. The findings suggest that the modification of metal particle clusters can enhance the surface electronic properties of single-layer SnS. In the regions of metal particle clusters and the gas-surface reaction area, electronic activity is significantly heightened, primarily attributed to the contribution of d-orbital electrons of the metal cluster structures. The modified SnS exhibits adsorption capacity in the following order: Ru3-SnS > Mo3-SnS > Au3-SnS. Additionally, the modified material demonstrates increased competitiveness for C2H2, with adsorption types falling under physical chemistry adsorption. Different metal elements exert diverse effects on the electronic distribution of the entire system, providing a theoretical foundation for the preparation of corresponding sensors. The findings in this work offer numerical insights for the further preparation and development of SnS nanosensors, concurrently shedding light on the online monitoring of faults in oil-immersed transformers.

Preparation of nanocellulose light porous material adsorbed with tannic acid and its application in fresh-keeping pad.

This study fabricated nanocellulose lightweight porous material (TOCNF-G-LPM-TA) as absorbent fresh-keeping pad for meat products, using TEMPO-oxidized cellulose nanofibril (TOCNF) and gelatin as structural skeleton and tannic acid (TA) as antibacterial component of TOCNF lightweight porous material (TOCNF-G-LPM). The adsorption kinetics, capacity and mechanism of TOCNF-G-LPM in different initial concentrations of TA solutions were investigated, the antioxidant and antibacterial properties of TOCNF-G-LPM-TA and its fresh-keeping effect on refrigerated pork at 4 ℃ were studied. Due to strong hydrogen bonding and porous structure, TOCNF-G-LPM exhibited excellent TA adsorption ability (230 mg/g) conforming with pseudo-second-order kinetic and Langmuir isotherm models. TA endowed TOCNF-G-LPM with good antioxidant and antibacterial activities. According to changes in appearance, pH and TVB-N values of pork during storage at 4 ℃, TOCNF-G-LPM-TA effectively extended the shelf life of refrigerated pork. This work provides a facile method for preparing nanocellulose based absorbent fresh-keeping pads.

[Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma].

OBJECTIVE: To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma (MS). METHODS: Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, The First People's Hospital of Lianyungang from September 2010 to December 2021. AML1-ETO fusion, PML-RARα fusion and CBFß breakage were detected by fluorescence in situ hybridization (FISH), and the mutations of NPM1, CEBPA, FLT3, RUNX1, ASXL1, KIT and TP53 genes were detected by new generation sequencing (NGS). RESULTS: Among 14 patients, the MS occurred in bone, breast, epididymis, lung, chest wall, cervix, small intestine, ovary, lymph nodes and central nervous system. The tumor cells expressed MPO (13 cases), CD34 (7 cases), CD43 (8 cases), CD68 (7 cases), CD99 (8 cases) and CD117 (6 cases). Cytogenetic abnormalities were observed in 4 cases, including 3 cases of AML1-ETO fusion and 1 case of CBFß breakage, while no PML-RARα fusion was detected. There were no significant differences in overall survival (OS) and leukemia-free survival (LFS) between patients with and without AML1-ETO fusion/CBFß breakage (both P >0.05). Among the 14 patients, the number of NPM1, CEBPA, FLT3-ITD, RUNX1, ASXL1, KIT and TP53 gene mutations was 5, 3, 5, 3, 2, 2, 1, respectively, of which 7 cases had at least one mutation in FLT3-ITD, RUNX1, ASXL1 and TP53 gene. The OS and LFS of patients with FLT3-ITD, RUNX1, ASXL1 or TP53 mutation were shorter than those without mutations (both P <0.01). CONCLUSION: The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques. FLT3-ITD, RUNX1, ASXL1 or TP53 mutation indicates a worse prognosis, but further clinical studies are needed to confirm it.

Artificial tumor matrices and bioengineered tools for tumoroid generation.

The tumor microenvironment (TME) is critical for tumor growth and metastasis. The TME contains cancer-associated cells, tumor matrix, and tumor secretory factors. The fabrication of artificial tumors, so-called tumoroids, is of great significance for the understanding of tumorigenesis and clinical cancer therapy. The assembly of multiple tumor cells and matrix components through interdisciplinary techniques is necessary for the preparation of various tumoroids. This article discusses current methods for constructing tumoroids (tumor tissue slices and tumor cell co-culture) for pre-clinical use. This article focuses on the artificial matrix materials (natural and synthetic materials) and biofabrication techniques (cell assembly, bioengineered tools, bioprinting, and microfluidic devices) used in tumoroids. This article also points out the shortcomings of current tumoroids and potential solutions. This article aims to promotes the next-generation tumoroids and the potential of them in basic research and clinical application.

Erratum to: circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis.

[Erratum to: BMB Reports 2023; 56(3): 184-189, PMID: 36617466, PMCID: PMC10068343] The BMB Reports would like to correct in BMB Rep. 56(3): 184-189, titled "circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis". The original version of this article unfortunately contained image error in the Fig. 3. This article has been updated to correct an error in the image in Fig. 3D. The author apologizes for any inconvenience or confusion this error may cause. Author information has been modified in the original PDF version.

Discovery of Highly Potent Small-Molecule PD-1/PD-L1 Inhibitors with a Novel Scaffold for Cancer Immunotherapy.

Inhibition of the PD-1/PD-L1 interaction through small-molecule inhibitors is a promising therapeutic approach in cancer immunotherapy. Herein, we utilized BMS-202 as the lead compound to develop a series of novel PD-1/PD-L1 small-molecule inhibitors with a naphthyridin scaffold. Among these compounds, X14 displayed the most potent inhibitory activity for the PD-1/PD-L1 interaction (IC50 = 15.73 nM). Furthermore, X14 exhibited good binding affinity to both human PD-L1 (KD = 14.62 nM) and mouse PD-L1 (KD = 392 nM). In particular, X14 showed favorable pharmacokinetic properties (oral bioavailability, F = 58.0%). In the 4T1 (mouse breast cancer cells) syngeneic mouse model, intragastric administration of X14 at 10 mg/kg displayed significant antitumor efficacy (TGI = 66%). Mechanistic investigations revealed that X14 effectively enhanced T-cell infiltration within the tumor microenvironment. Our study demonstrates that compound X14 exhibits potential as a candidate compound for the development of orally effective small-molecule inhibitors targeting PD-1/PD-L1.

Microenvironment-induced CREPT expression by cancer-derived small extracellular vesicles primes field cancerization.

Rationale: Cancer local recurrence increases the mortality of patients, and might be caused by field cancerization, a pre-malignant alteration of normal epithelial cells. It has been suggested that cancer-derived small extracellular vesicles (CDEs) may contribute to field cancerization, but the underlying mechanisms remain poorly understood. In this study, we aim to identify the key regulatory factors within recipient cells under the instigation of CDEs. Methods: In vitro experiments were performed to demonstrate that CDEs promote the expression of CREPT in normal epithelial cells. TMT-based quantitative mass spectrometry was employed to investigate the proteomic differences between normal cells and tumor cells. Loss-of-function approaches by CRISPR-Cas9 system were used to assess the role of CREPT in CDEs-induced field cancerization. RNA-seq was performed to explore the genes regulated by CREPT during field cancerization. Results: CDEs promote field cancerization by inducing the expression of CREPT in non-malignant epithelial cells through activating the ERK signaling pathway. Intriguingly, CDEs failed to induce field cancerization when CREPT was deleted, highlighting the importance of CREPT. Transcriptomic analyses revealed that CDEs elicited inflammatory responses, primarily through activation of the TNF signaling pathway. CREPT, in turn, regulates the transduction of downstream signals of TNF by modulating the expression of TNFR2 and PI3K, thereby promoting inflammation-to-cancer transition. Conclusion: CREPT not only serves as a biomarker for field cancerization, but also emerges as a target for preventing the cancer local recurrence.

A Grading System of Microvascular Invasion for Patients with Hepatocellular Carcinoma Undergoing Liver Resection with Curative Intent: A Multicenter Study.

Background: Microvascular invasion (MVI) is closely correlated with poor clinical outcomes in patients with hepatocellular carcinoma (HCC). A grading system of MVI is needed to assist in the management of HCC patient. Methods: Multicenter data of HCC patients who underwent liver resection with curative intent was analyzed. This grading system was established by detected number and distance from tumor boundary of MVI. Survival outcomes were compared among patients in each group. This system was verified by time-receiver operating characteristic curve, time-area under the curve, calibration curve, and decision curve analyses. Cox regression analysis was performed to study the associated factors of prognosis. Logistic analysis was used to study the predictive factors of MVI. Results: All patients were classified into 4 groups: M0: no MVI; M1: 1~5 proximal MVIs (≤1 cm from tumor boundary); M2a: >5 proximal MVIs (≤1 cm from tumor boundary); M2b: ≥1 distal MVIs (>1 cm from tumor boundary). The recurrence-free survival (RFS), overall survival (OS), and early RFS rates among all the individual groups were significantly different. Based on the number of proximal MVI (0~5 vs >5), patients in the M2b group were further divided into two subgroups which also showed different prognosis. Multiple methods showed this grading system to be significantly better than the MVI two-tiered system in prognostic evaluation. Four multivariate models for RFS, OS, early RFS, late RFS, and a predictive model of MVI were then established and were shown to satisfactorily evaluate prognosis and have a great discriminatory power, respectively. Conclusion: This MVI grading system could precisely evaluate prognosis of HCC patients after liver resection with curative intent and it could be employed in routine pathological reports. The severity of MVI from both adjacent and distant from tumor boundary should be stated. A hypothesis about two occurrence modes of distal MVI was proposed.

Non-targeted metabolomics study for discovery of hepatocellular carcinoma serum diagnostic biomarker.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Due to the asymptomatic features of HCC at early stages, patients are often diagnosed at advanced stages and missed effective treatment. Thus, there is an urgent need to identify sensitive and specific biomarkers for HCC early diagnosis. In the present study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was used to profile serum metabolites from HCC patients, liver cirrhosis (LC) patients, and normal controls (NC). Univariate and multivariate statistical analyses were performed to obtain the metabolomic differences of the three groups and select significantly changed metabolites that can be used as diagnostic biomarkers. In total, 757 differential metabolites were quantified among the three groups, and pathway enrichment analysis of these metabolites indicated that glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism were the most altered pathways involved in HCC development. Receiver operating characteristic (ROC) curve analysis was performed to select and evaluate the diagnostic biomarker performance. Seven metabolites were identified as potential biomarkers that can differentiate HCC from LC and NC, and LC from NC with the good diagnostic performance of area under the curve (AUC) from 0.890 to 0.990. In summary, our findings provide highly effective biomarker candidates to differentiate HCC from LC and NC, LC, and NC, which shed insight into HCC pathological mechanisms and will be helpful in better understanding and managing HCC.

Discovery of Highly Selective PARP7 Inhibitors with a Novel Scaffold for Cancer Immunotherapy.

PARP7 plays a crucial role in cancer immunity. The inhibition of PARP7 has shown potential in boosting the immune response against cancer, making it an attractive target for cancer immunotherapy. Herein, we employed a rigid constraint strategy (reduction in molecular flexibility) to design and synthesize a series of novel indazole-7-carboxamide derivatives based on the structure of RBN-2397. Among these derivatives, (S)-XY-05 was identified as the most promising PARP7 inhibitor (IC50: 4.5 nM). Additionally, (S)-XY-05 showed enhanced selectivity toward PARP7 and improved pharmacokinetic properties (oral bioavailability: 94.60%) compared with RBN-2397 (oral bioavailability: 25.67%). In the CT26 syngeneic mouse model, monotherapy with (S)-XY-05 displayed a strong antitumor effect (TGI: 83%) by activating T-cell-mediated immunity within the tumor microenvironment. Collectively, we confirmed that (S)-XY-05 has profound effects on tumor immunity, which paves the way for future studies of PARP7 inhibitors that could be utilized in cancer immunotherapy.

Successful Interventional Treatment of Pyopneumothorax Caused by Streptococcus constellatus Associated with Hashimoto's Thyroiditis: A Case Report and Literature Review.

Background: Streptococcus constellatus rarely causes pyopneumothorax, which is a serious state and requires a surgery. However, not every patient can tolerate surgery and individualized solutions are needed. Furthermore, many known situations are risk factors of S. constellatus infection, but S. constellatus pyopneumothorax associated with Hashimoto's thyroiditis has not been reported. Case Presentation: We present the case of a 74-year-old male with multiple encapsulated pyopneumothorax caused by S. constellatus. Given his respiratory failure, we provided two-stage percutaneous right empyema radiography for catheter drainage in the radiology interventional department instead of surgery. Moreover, an occult Hashimoto's thyroiditis was discovered in the patient, which was possibly associated with S. constellatus pyopneumothorax. Levothyroxine was administered to improve his situation. Conclusion: To our knowledge, it is the first case described in this context. We provided an alternative treatment for S. constellatus encapsulated pyopneumothorax in patient who might not tolerate surgery. We also revealed the possible relationship between S. constellatus pyopneumothorax and Hashimoto's thyroiditis.

Organic anion transporting polypeptide 3a1 is a novel influx pump for Perfluorooctane sulfonate in Sertoli cells and contributes to its reproductive toxicity.

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the 14C-PFOS uptake experiment, we showed that 14C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.

Patient satisfaction with humanistic nursing in Chinese secondary and tertiary public hospitals: a cross-sectional survey.

Background: Humanistic care pertains to the abilities, attitudes, and behaviors central to patient-centered care, contributing to patients' sense of safety and wellbeing. This study aimed to assess the satisfaction of patients with humanistic nursing care in Chinese secondary and tertiary public hospitals. Methods: A national cross-sectional survey was conducted across 30 provinces and 83 hospitals in China. Patient satisfaction with humanistic care was assessed using the Methodist Health Care System Nurse Caring Instrument (NCI), which encompasses 20 items across 12 dimensions. Each item was rated on a 7-point Likert scale, yielding a total score of 140. Multiple linear regression analysis was employed to identify factors associated with patients' satisfaction. Results: Moderate satisfaction (mean score 91.26 ± 13.14) with humanistic nursing care was observed among the 17,593 participants. Factors significantly associated with patient satisfaction included age, hospital type, presence of children, educational attainment, place of residence, family monthly income, and medical insurance type. Conclusion: The study findings highlight the importance of tailored interventions, evidence-based practice guidelines, and patient-centered care in improving patients' satisfaction with humanistic nursing care. Continuous emphasis on nursing education and professional development is crucial for enhancing humanistic care and patient satisfaction.

Multiple refractory intracellular pathogen infections in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibodies: a case report.

BACKGROUND: The clinical presentation of adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies with intracellular pathogens can be highly variable, which can lead to misdiagnosis during the early stage of disease. CASE PRESENTATION: We report a complex case of a 54-year-old Chinese male who was human immunodeficiency virus-negative. He had a presence of anti-IFN-γ autoantibodies and suffered from various intracellular pathogenic infections. The patient was admitted to our hospital for the first time in July 2016 with severe pneumonia, and he experienced multiple pneumonia infections between 2017 and 2019. In March 2019, the patient was hospitalized due to pulmonary lesions and multiple-bone destruction. During hospitalization, the patient was confirmed to have disseminated Talaromyces marneffei infection and was successfully treated with antifungal therapy for 1 year. In June 2021, Mycobacterium kansasii infection was detected by positive culture and progressive bone destruction. A high concentration of anti-IFN-γ antibodies was observed in the patient's serum. In addition, Listeria monocytogenes was isolated by blood culture, and the presence of L. monocytogenes in cerebrospinal fluid was confirmed by next-generation sequencing. Following anti-non-tuberculous mycobacteria (NTM) therapy and anti-bacterial therapy, the patient's symptoms, pulmonary lesions, and bone destruction gradually improved. CONCLUSIONS: Although the clinical presentation of adult-onset immunodeficiency with anti-IFN-γ autoantibodies can be highly variable, the diagnosis should be considered if patients suffer from unexplained repeated bacterial or opportunistic infections. Conventional and advanced molecular testing should be used, as needed, for microbiological diagnoses among this special immunodeficient population.