Tong Jing Yi Hao Formula Alleviates Ornidazole-Induced Oligoasthenospermia in Rats by Suppressing ROS/MAPK/HIF-1 Pathway.

BACKGROUND: Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem. METHODS: Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway. RESULTS: Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde. In the testicles, an enhancement in the ROS level and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) was observed after Orn challenge. Moreover, the protein expression levels and immunostaining intensity of p38 and HIF-1α increased, indicating the activation of the ROS/MAPK/HIF-1 pathway. All of the aforementioned changes exhibited statistical significance (p < 0.01). Compared with Orn-induced rats, TJYHF effectively rescued the Orn-induced aforementioned disorders. Mechanistically, TJYHF suppressed the ROS level and ERK1/2, JNK and p38 phosphorylation levels. Besides, it reduced the protein expression levels and immunostaining intensity of p38 and HIF-1α, demonstrating the inactivation of the ROS/MAPK/HIF-1 pathway. Notably, the aforementioned enhancements demonstrated statistical significance (p < 0.01). CONCLUSIONS: TJYHF exerted a beneficial effect on reproductive function in OAS rats through the inhibition of the ROS/MAPK/HIF-1 pathway.

Overexpression of PSAT1 is Correlated with Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer.

PURPOSE: Current evidence suggests that phosphoserine aminotransferase 1 (PSAT1) is overexpressed in various tumors. Herein, we investigate the significance of PSAT1 in non-small cell lung cancer (NSCLC) and its correlation with immune infiltration. METHODS: The expression profile of PSAT1 in NSCLC patients and related clinical information was obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA-NSCLC) databases. In silico and experimental validation were conducted to assess the role of PSAT1 in NSCLC. Gene set enrichment analysis (GSEA) was performed to investigate the disparities in biological functions between groups with high and low PSAT1 expression. Additionally, the biological characteristics and immune cell infiltration were compared between these two groups. We also assessed whether PSAT1 expression could predict the sensitivity of NSCLC patients to immunotherapy using the immunophenotype score (IPS) and an anti-PD-L1 immunotherapy cohort (IMvig-or210). Furthermore, the difference in drug sensitivity between PSAT1-high and PSAT1-low expression cell lines was investigated. RESULTS: Analysis of transcriptional expression profiles using TCGA data revealed overexpression of PSAT1 in NSCLC tissues correlated with poor overall survival (OS). GSEA results showed enrichment of DNA recombination and repair, nucleotide biosynthesis, and the P53 signaling pathway in the PSAT1-high group. Experimental validation demonstrated that the knockdown of PSAT1 suppressed cell proliferation, migration, and invasion of NSCLC. Immune cell infiltration analysis revealed an immune-activated tumor microenvironment in the PSAT1-low group. It was also observed that PSAT1-low cell lines were more likely to benefit from immunotherapy and several chemotherapy drugs. CONCLUSIONS: PSAT1 has enormous potential for applications in the prediction of NSCLC patient outcomes and provides the foothold for more precise individualized treatment of this patient population.

Tong Jing Yi Hao Formula Alleviates Ornidazole-Induced Oligoasthenospermia in Rats by Suppressing ROS/MAPK/HIF-1 Pathway

Background: Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem. Methods: Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway.Results: Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde (AU)

Efficacy and safety of combined treatment with pembrolizumab in patients with locally advanced or metastatic esophageal squamous cell carcinoma in the real world.

Background: Treatments for patients with advanced esophageal cancer are still limited. Pembrolizumab has demonstrated antitumor activity in patients with advanced esophageal cancer in previous studies. Few studies have assessed safety and efficacy in routine clinical practice. We investigated the real-world outcomes of pembrolizumab for patients with advanced esophageal cancer. Methods: This retrospective, observational study collected 57 advanced esophageal squamous cell carcinoma (ESCC) patients from October 1, 2019 to October 1, 2021, 57 who received different patterns of treatments according to the staging were collected. Briefly, patients diagnosed with locally advanced and surgically resectable ESCC received neoadjuvant therapy followed by surgery. For patients with locally advanced, unresectable ESCC, the treatment regimen including chemoradiotherapy combined with pembrolizumab was performed. Patients with metastatic ESCC or those not suitable for radiotherapy received pembrolizumab plus chemotherapy. Safety was assessed in all treated patients. The objective response rate (ORR) was used to evaluate the efficacy. Results: The ORR was 74.1% (40/54) among all patients. The most common adverse events (AEs) were leukopenia (36.8%, 21/57), nausea (28.1%, 16/57), and thrombocytopenia (14%, 8/57). Grade III and higher AEs were observed in 9 of the 57 patients (15.8%). Conclusions: For patients with advanced ESCC, combined treatment with pembrolizumab was effective and safe. Multicenter studies should be carried out for further confirmation.

Comprehensive analysis of the autophagy-dependent ferroptosis-related gene FANCD2 in lung adenocarcinoma.

BACKGROUND: The development of lung adenocarcinoma (LUAD) involves the interactions between cell proliferation and death. Autophagy-dependent ferroptosis, a distinctive cell death process, was implicated in a multitude of diseases, whereas no research revealing the relationship between autophagy-dependent ferroptosis and LUAD pathogenesis was reported. Thus, the primary objective was to explore the role and potential function of the autophagy-dependent ferroptosis-related genes in LUAD. METHODS: Clinical information and transcriptome profiling of patients with LUAD were retrieved and downloaded from open-source databases. Autophagy-dependent ferroptosis-related genes were screened by published articles. The critical gene was identified as the intersection between the differentially expressed genes and prognosis-related genes. Patients were divided into high- and low-risk groups using the expression level of the critical gene. The validity of the key gene prognosis model was verified by survival analysis. The correlation between the clinical characteristics of LUAD and the expression level of the key gene was analyzed to explore the clinical significance and prognosis value. And the roles of the key gene in response to chemotherapy, immune microenvironment, and tumor mutation burden were predicted. The validation of key gene expression levels was further performed by quantitative real-time PCR and immunohistochemistry staining. RESULTS: FANCD2, an essential autophagy-dependent ferroptosis-related gene by searching database, was confirmed as an independent prognostic factor for LUAD occurrence. The high expression level of FANCD2 was associated with an advantaged TNM stage, a less chemotherapy sensitivity, a low ImmuneScore, which indicated a deactivation status in an immune microenvironment, a high tumor mutation burden, and poor survival for LUAD patients. Pathway enrichment analysis showed that FANCD2 responded to oxidative stress and neutrophil-mediated immunity. Quantitative real-time PCR and immunohistochemistry staining showed that the expression level of FANCD2 is higher in LUAD patients than in normal tissue samples, which was in accordance with the database report. CONCLUSION: FANCD2, an essential gene related to autophagy-dependent ferroptosis, could work as a biomarker, predicting the survival, chemotherapy sensitivity, tumor immunity, and mutation burden of LUAD. Researching autophagy-dependent ferroptosis and targeting the FANCD2 may offer a new perspective for treating and improving prognosis in LUAD.

Neuromorphic Devices for Bionic Sensing and Perception.

Neuromorphic devices that can emulate the bionic sensory and perceptual functions of neural systems have great applications in personal healthcare monitoring, neuro-prosthetics, and human-machine interfaces. In order to realize bionic sensing and perception, it's crucial to prepare neuromorphic devices with the function of perceiving environment in real-time. Up to now, lots of efforts have been made in the incorporation of the bio-inspired sensing and neuromorphic engineering in the booming artificial intelligence industry. In this review, we first introduce neuromorphic devices based on diverse materials and mechanisms. Then we summarize the progress made in the emulation of biological sensing and perception systems. Finally, the challenges and opportunities in these fields are also discussed.

Predictive value of integrin α7 for acute myeloid leukemia risk and its correlation with prognosis in acute myeloid leukemia patients.

BACKGROUND: This study aimed to explore the predictive value of integrin α7 (ITGA7) for acute myeloid leukemia (AML) risk and subsequently investigate its correlation with risk stratification and prognosis in AML patients. METHODS: Bone marrow samples were obtained from 196 de novo AML patients prior to initiation of treatment and from 50 subjects underwent bone marrow donation or bone marrow biopsy for non-hematologic malignant disease (as controls). ITGA7 mRNA and protein expressions were detected by real-time quantitative polymerase chain reaction and Western blot assays, respectively. In AML patients, the risk stratification was assessed, and complete remission (CR), event-free survival (EFS), and overall survival (OS) were evaluated. RESULTS: Both ITGA7 mRNA and protein expressions were increased in AML patients compared with controls, and their expressions were correlated with poorer risk stratification. For prognosis, ITGA7 mRNA expression and protein expression were declined in CR patients compared to non-CR patients. Meanwhile, both EFS and OS were shorter in ITGA7 mRNA high expression patients compared to ITGA7 mRNA low expression patients, as well as ITGA7 protein high expression patients compared to ITGA7 protein low expression patients. CONCLUSION: Integrin α7 might serve as a potential biomarker for predicting increased AML risk and worse prognosis in AML patients.

Preoperative Volumetric Modulated Arc Therapy With Simultaneous Integrated Boost for Locally Advanced Distal Rectal Cancer.

The aim of this study was to evaluate the safety and clinical efficacy of a combined preoperative regimen consisting of volumetric modulated arc therapy-simultaneous integrated boost and capecitabine chemotherapy for distal rectal cancer. A total of 26 patients with locally advanced distal rectal cancer were enrolled from March 2015 to May 2016. The radiation dose fractionation was 58.75 Gy/25 fractions (2.35 Gy/fraction) for rectal tumor and pelvic lymph node metastasis and 50 Gy/25 fractions for pelvic lymph node stations, accompanied with simultaneous capecitabine chemotherapy. Completion of the simultaneous chemotherapy was ensued by 1 week of rest and then another cycle of induction chemotherapy with capecitabine. A radical rectal cancer surgery was performed 6 to 8 weeks after the simultaneous chemoradiotherapy. The primary end points were the complete pathological response rate and the postoperative sphincter preservation rate. All 26 patients completed the neoadjuvant chemoradiotherapy, among which 25 received surgical treatment. The postoperative complete pathological response rate was as high as 32% (8/25), while the sphincter preservation rate was 60% (15/25), the overall tumor/node (T/N) downstaging rate was 92% (23/25), and the R0 resection rate was 100%. During the chemoradiation, the most common adverse events were grade 1 and 2; grade 3 radiodermatitis occurred in 2 cases but no occurrence of acute adverse events occurred that were grade 4 and above. After the surgery, there was one case of ureteral injury and one case of intestinal obstruction, but no perioperative deaths occurred. In conclusion, the chemoradiation regimen of preoperative volumetric modulated arc therapy-simultaneous integrated boost (VMAT-SIB58.75Gy) and a single cycle of induction chemotherapy with capecitabine for patients with distal rectal cancer is safe and feasible with a satisfactory complete pathological response rate, sphincter preservation rate, and R0 resection rate.

[Kangle Decoction for erectile dysfunction with liver-qi stagnation and kidney deficiency].

OBJECTIVE: To observe the clinical efficacy of Kangle Decoction in the treatment of erectile dysfunction (ED) with liver-qi stagnation and kidney deficiency. METHODS: A total of 79 ED patients with liver-qi stagnation and kidney deficiency were randomly assigned to an experimental group (aged ï¼»36.62±8.05ï¼½ yr and with a disease course of ï¼»18.15±6.41ï¼½ mo) and a control group (aged ï¼»37.44±8.10ï¼½ yr and with a disease course of ï¼»17.51±6.79ï¼½ mo), the former treated orally with Kangle Decoction at 0.5 dose bid while the latter with Cialis at 10 mg qd alt, both for 8 weeks. Before treatment, after 4 and 8 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the scores of the patients in the International Index of Erectile Function-5 (IIEF-5), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Short-Form Psychological and Interpersonal Relationship Scales (SF-PAIRS), and compared the indexes between the two groups of patients. RESULTS: The IIEF-5 score was dramatically increased in both the treatment and control groups after 4 weeks (13.40±2.42 and 16.00±2.68) and 8 weeks of medication (18.60±3.50 and 18.59±3.80) and at 4 weeks after drug withdrawal (17.00±3.05 and 13.95±2.61) as compared with the baseline (10.78±2.28 and 10.77±2.33) (P<0.05 ), even higher in the treatment than in the control group after drug withdrawal (P<0.05 ). The EDITS scores in the treatment and control groups were (28.88±3.31 and 28.90±3.31) after 4 weeks of intervention, (29.68±3.30 and 29.13±3.32) after 8 weeks of intervention, and (29.20±2.92 and 26.82±3.23) at 4 weeks after drug withdrawal, all significantly higher in the former than in the latter group after drug withdrawal (P<0.05 ). The sexual self-confidence score (SSCS), sexual spontaneity score (SSS), and sexual time-concern score (STCS) were all improved in the treatment and control groups after medication as compared with the baseline (P<0.05 ), even higher in the former than in the latter group after drug withdrawal (P<0.05 ). CONCLUSIONS: Kangle Decoction has a definite efficacy in the treatment of ED with liver-qi stagnation and kidney deficiency, with few adverse reactions and long-term post-withdrawal effect, and therefore deserves a wide clinical application.