Comprehensive pan-cancer analysis of KLRB1-CLEC2D pair and identification of small molecule inhibitors to disrupt their interaction.

The interplay between immune checkpoints KLRB1 and CLEC2D is crucial for tumor progression and immune evasion, yet the interaction dynamics are not fully understood. This study aims to elucidate the interaction across various cancers and identify small molecule inhibitors that can disrupt it. We perform a comprehensive pan-cancer analysis of the KLRB1-CLEC2D pair, including mRNA expression patterns, pathological stages, survival outcomes, and single-cell omics, immune infiltration, copy number variations, and DNA methylation profiles. Our findings reveal a consistently higher CLEC2D/KLRB1 ratio in most cancer types compared to normal tissues, and this ratio also increased with advancing pathological stages. Lower KLRB1 expression correlated with higher mortality in most cancers, opposite to CLEC2D. Expression variations were attributed to differential lymphocyte infiltration, CNV, and DNA methylation. Structure-based virtual screening analysis identified compounds including forsythiaside A and RGD peptides as effective inhibitors of the KLRB1-CLEC2D interaction, validated through microscale thermophoresis. This research advances understanding of the KLRB1-CLEC2D interaction within the tumor microenvironment and introduces novel therapeutic strategies to modulate this interaction.

Visual Recovery and Prognosis in the Treatment of Submacular Hemorrhage due to Polypoidal Choroidal Vasculopathy and Retinal Arterial Macroaneurysm: A Retrospective Study.

Purpose: This study was carried out to evaluate the visual acuity (VA), complications, and prognosis of patients diagnosed with submacular hemorrhage (SMH) from polypoidal choroidal vasculopathy (PCV) and retinal arterial macroaneurysm (RAM) treated by pars plana vitrectomy (PPV), subretinal tissue plasminogen activator (tPA), and air tamponade in vitreous cavity. It facilitates the development of generic treatment methods that can be widely used to improve vision and treat potential complications in patients with SMH, regardless of the underlying pathophysiological condition, such as PCV or RAM. Methods: In this retrospective study, SMH patients were divided into two groups based on their diagnosis: (1) polypoidal choroidal vasculopathy (PCV) and (2) retinal arterial macroaneurysm (RAM). The visual recovery and complications of patients with PCV and RAM after PPV + tPA (subretinal) surgery were analyzed. Results: A total of 36 eyes of 36 patients were included: PCV (47.22%, 17/36) and RAM (52.78%, 19/36). The mean age of the patients was 64 years, and 63.89% of the patients (23/36) were female. The median VA was 1.85 logMAR before surgery, 0.93 and 0.98 logMAR at 1 and 3 months after surgery, respectively, indicating that most patients' vision improved after surgery. At the 1 and 3 months postoperative follow-up, each patient was diagnosed with rhegmatogenous retinal detachment at 1 month and 3 months postoperatively, and four patients had vitreous hemorrhage at 3 months postoperatively. Preoperatively, patients exhibited macular subretinal hemorrhage, retinal bulge, and exudation around the blood clot. Postoperatively, most patients showed dispersal of subretinal hemorrhage. Optical coherence tomography results revealed retinal hemorrhage involving the macula and hemorrhagic bulges under both the neuroepithelium and the pigment epithelium under the fovea preoperatively. After surgery, the air injected into the vitreous cavity was completely absorbed and the subretinal hemorrhage was dispersed. Conclusion: PPV combined with subretinal tPA injection and air tamponade in the vitreous cavity can facilitate modest visual recovery in patients with SMH due to PCV and RAM. However, some complications may occur, and their management remains challenging.

Telomerase-initiated three-dimensional DNAzyme motor for monitoring of telomerase activity in living cells.

Telomerase (TE) is recognized as a potential biomarker for early diagnosis, monitoring and treatment of cancer. At present, most of the methods for TE detection are only applicable to in vitro assays, and unsuitable for in vivo applications. Though a few intracellular probes have been reported to have good specificity for TE, they do not involve signal amplification, which hinders their applicability in scenarios requiring high sensitivity. It is rather challenging to develop highly sensitive biosensors for intracellular TE detection due to the difficulty in design TE probes with both high specificity and compatibility with signal amplification in living cells. Herein, a highly sensitive and selective three-dimensional DNAzyme motor for monitoring of TE activity in living cells was developed by innovatively integrating TE-mediated chain replacement reaction with a three-dimensional DNA walker. Specifically, the DNAzyme motor was constructed by assembling both DNAzyme substrates and swing arms made up of a hairpin-structured DNAzyme and a telomeric primer onto gold nanoparticles. TE in cells can activate the DNAzyme motor to carry out continuous chain replacement and substrate cutting reactions, and hence realize signal amplification in living cells. The DNAzyme motor was successfully utilized to monitor the dynamic changes of TE activity in four types of cells. Due to the advantages of simple synthesis, good biocompatibility and high sensitivity and specificity for TE, the proposed DNAzyme motor is expected to have great application potential in the early diagnosis of cancer.

Effects of Low-dose Splenic Irradiation on T lymphocyte Immune Function.

ABSTRACT: Relevant studies have confirmed that the stimulation of spleen function caused by low-dose splenic irradiation can have positive effects on tumors and other diseases. This study aimed to determine radiation-induced changes in spleen index, lymphocyte subsets, spleen cell apoptosis, and pathological features of the spleen in mice. The mouse model was established by irradiating the spleen at different doses. The mice were divided into the following groups: blank control, low-dose, low-dose fractionated irradiation, and challenge dose irradiation. The mice were sacrificed under humanitarian conditions, and spleen tissue and peripheral blood were collected. The spleen index was calculated, and flow cytometry was used to analyze spleen T lymphocyte subsets and spleen apoptosis. The pathological changes in the spleen were determined by hematoxylin and eosin (H&E) staining. The spleen index of mice in the low-dose fractionated irradiation group was significantly increased compared with that in the blank control group. The spleen indexes of the low-dose irradiation and low-dose fractionated irradiation groups were much higher than that of the challenge dose irradiation group. Compared with the blank control group, the percentage of CD3+ and CD4+ T lymphocytes in the peripheral blood and spleen tissues in the low-dose irradiation and low-dose fractionated irradiation groups was significantly increased, whereas that from the challenge dose irradiation group was obviously decreased. CD8+ T lymphocytes in the peripheral blood and spleen tissues in the low-dose irradiation, low-dose fractionated irradiation, and challenge dose irradiation groups were significantly lower than those in the blank control group. The apoptosis rate of the spleen in the challenge dose irradiation group was significantly higher than that in the blank control, low-dose irradiation, and low-dose fractionated irradiation groups. H&E staining analysis of the spleen showed pathological changes in the different irradiation groups compared with the blank control group. Low-dose irradiation and low-dose fractionated irradiation can change the T lymphocyte subsets in the peripheral blood and spleen of mice, which can promote immune excitation and improve immune effects.

Clinical characteristics of primary pars plana vitrectomy combined with air filling for rhegmatogenous retinal detachment.

To detect the prognostic factors associated with initial reattachment after primary pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD). We retrospectively reviewed 92 eyes of 92 patients with RRD. All eyes underwent PPV with air tamponade and a follow-up of at least 6 months. Initial anatomical success was defined as reattachment of the retina by a single operation. We performed univariate analysis to detect the presence of any difference between eyes with a successful initial reattachment and those that failed. We also performed multivariate logistic regression analysis to assess the influence of each preoperative factor on initial success. The rate of initial reattachment success was 93.5%. The percentage of retinal detachment involving the inferior quadrants in the initial success group was less than that in the initial failure group, and the difference was statistically significant (P = 0.043). There were no significant differences noted for other factors, such as symptom duration (P = 0.078) or location of retinal breaks (P = 0.065). Multiple logistic regression analysis using preoperative factors indicated that older age (odds ratio, 0.90; 95% confidence interval, 0.82-0.97; P = 0.010) and non-involvement of inferior quadrants (odds ratio, 9.90; 95% confidence interval, 1.36-71.92; P = 0.023) were significantly associated with initial success. PPV combined with air may be an effective treatment for some simple RRDs (proliferative vitreoretinopathy [PVR] grade ≤ C1). Non-involvement of the inferior quadrants and older age at presentation are associated with a greater likelihood of anatomic success. The volume of air in the eye after surgery is also very important, which may also affect the reduction of retinal detachment.

Expression of Long Non-Coding RNA (lncRNA) SNHG5 in Patients with Refractory Diabetic Macular Edema and Its Regulatory Mechanism.

BACKGROUND The aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME). MATERIAL AND METHODS Optical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro. RESULTS Patients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated. CONCLUSIONS SNHG5 correlates with the development of DME and is a potential target for therapy.

The preliminary comparative results between Covid-19 and non-Covid-19 patients in Western China.

BACKGROUND: This study aims to investigate the comparative clinical characteristics of Covid-19 and non-Covid-19 patients. METHODS: Fifteen Covid-19 and 93 non-Covid-19 patients were included in RNA testing. All epidemiological and clinical data were collected and analyzed, and then comparative results were carried out. RESULTS: Covid-19 patients were older (46.40 ± 18.21 years vs 34.43 ± 18.80 years) and had a higher body weight (70.27 ± 10.67 kg vs 60.54 ± 12.33 kg, P < 0.05). The main symptoms that were similar between Covid-19 and non-Covid-19 patients, and Covid-19 patients showed a lower incidence of sputum production (6.67% vs 45.16%, P < 0.01) and a lower white-cell count (4.83 × 109/L vs 7.43 × 109/L) and lymphocyte count (0.90 × 109/L vs 1.57 × 109/L, P < 0.01). Although there were no differences, C-reactive protein and interleukin-6 were elevated in Covid-19 patients. The sensitivity and negative predictive value of CT images were 0.87 and 0.97, respectively. Covid-19 patients showed a higher contact history of Wuhan residents (80% vs 30.11%) and higher familial clustering (53.33% vs 8.60%, P < 0.001). Covid-19 patients showed a higher major adverse events (ARDS, 13.33%; death, 6.67%; P < 0.05). CONCLUSION: Our results suggested that Covid-19patients had a significant history of exposure and familial clustering and a higher rate of severe status; biochemical indicators showed lymphocyte depletion.

Effect of vascular simulation training on practice performance in residents: a retrospective cohort study.

OBJECTIVE: This study aims to investigate the teaching effect of vascular simulation training (ST) in rotating vascular residents. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 95 vascular residents were included from 2015 to 2018 in a university affiliated centre western China, and divided into an ST group and a conventional training (CT) group. The ST group received ST and CT, and the CT group only received CT. PRIMARY OUTCOME MEASURES: Theoretical scores were assessed, and the technique parameters, complications and radiation damage of the procedures were analysed. RESULTS: The mean scores (8.74±1.09 vs 8.13±1.31) and the rate of willingness for retraining (93.62% vs 79.17%) in residents were higher in the ST group than in the conventional training (CT) group (p<0.05). The success rate of arterial puncture was significantly higher in the ST group (78.72% vs 58.33%, p=0.03); however, the incidence of complications was similar between the two groups (p>0.05). The time of the puncture procedure was significantly lower (9.56±5.24 vs 12.15±6.87 min), and the comfort score of the patient (5.49±1.72 vs 4.71±1.57) was higher in the ST group than in the CT group (p<0.05). At the end of the assessment, the learning time for angiography (3.65±0.64 vs 4.07±0.77 months) and the complete procedure time (33.81±10.11 vs 41.32±12.56 min) were lower in the ST group than in the CT group (p<0.01). The fluo time for angiography (489.33±237.13 vs 631.47±243.65 s) and the cumulative air kerma (401.30±149.06 vs 461.16±134.14 mGy) were significantly decreased in ST group (p<0.05). CONCLUSION: The application of a vascular simulation system can significantly improve the clinical performance of residents and reduce the radiation damage from a single intervention procedure in patients.

The clinical characteristics and outcomes of carotid body tumors in Chinese patients: A STROBE-compliant observational study.

This study aims to investigate the clinical characteristics and outcomes of carotid body tumors in Chinese patients in the last decade. A systematic search was conducted without limits and included studies published between January 2006 and December 2016 according to PubMed, the Chinese Science Citation Database, the China Science Periodical Database and the China National Knowledge Infrastructure. Relevant synonyms for the search terms "paraganglioma" and "carotid body tumor" were applied, and the clinical data were evaluated and analyzed. There were 1810 cases of CBTs reported in the last decade, of which females accounted for 60.22%, and the mean age was 40.60 years, with most cases being sporadic (98.51%). Surgical resection was performed in 1791 cases: vessel repair occurred in 38.88% of the cases, carotid ligation occurred in 1.42% of the cases, and 1.05% of the patients refused treatment. Some patients underwent selective embolization, and the results showed that embolization could decrease procedure time and blood loss (P < .01). Stroke and death occurred in 1.95% and 0.39% of patients, respectively. Malignant CBTs accounted for 4.30% of cases, and the metastatic sites involved were local metastasis (46.88%), lung (31.25%), bone (21.88%), liver (12.50%), and brain (9.38%). The overall survival rate was 98.87% 36 months after the procedure, and the survival rate of metastatic cases was 56.25% 6 months after recurrence; however, only 21.88% of metastatic cases received radiotherapy. The CBTs of Chinese patients showed some clinical features that were different from those of Western patients.

Surgical resection of carotid body tumors with versus without preoperative embolization: Retrospective case-control study.

BACKGROUND: The purpose of this study was to investigate the outcomes of surgical resection of carotid body tumors with and without preoperative embolization. METHODS: There were 31 patients who underwent surgical resection combined with preoperative embolization (SRE group), and 27 patients who underwent conventional surgical resection (SR group); all clinical data were included and reviewed. RESULTS: There was no difference in the approach for carotid reconstruction in either group (P > .05). The mean surgical time (110.65 ± 35.77 minutes vs 188.33 ± 66.44 minutes) and intraoperative blood loss (140.32 ± 57.12 mL vs 396.43 ± 272.82 mL) were significantly less in the SRE group (P < .05). The volume of blood transfusions required (475 ± 301.18 mL vs 0 mL) and incidence rate of total complications (33.3% vs 9.7%) were higher in the SR group (P < .05). However, the length of hospital stay was similar in both groups (P > .05). CONCLUSION: Our results demonstrate that preoperative embolization of a carotid body tumor can reduce blood loss and complications and improve tumor excision.

Protective effects of extracts of Schisandra chinensis stems against acetaminophen-induced hepatotoxicity via regulation of MAPK and caspase-3 signaling pathways.

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g-1, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg-1) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.

Bornyl acetate suppresses ox-LDL-induced attachment of THP-1 monocytes to endothelial cells.

Leukocyte recruitment to the surface of the endothelium plays a pivotal role in the development of cardiovascular diseases. Bornyl acetate is the main volatile constituent present in numerous conifer oils, which has displayed its anti-oxidant and anti-inflammatory properties in different types of tissues and cells. However, little information regarding the effects of bornyl acetate on vascular endothelial inflammation has been reported before. In the current study, we aimed to investigate the pharmacological roles of bornyl acetate against ox-LDL-induced leukocyte adhesion to the endothelium. Our findings indicate that bornyl acetate ameliorated ox-LDL-induced reduction in cell viability of HUVECs. Additionally, bornyl acetate inhibited the attachment of THP-1 monocytes to HUVECs induced by treatment with ox-LDL through ameliorating the expression of ICAM-1, VCAM-1, and E-selectin. Mechanistically, we found that bornyl acetate could suppress activation of the IκBα/NF-κB signaling pathway. Lastly, our results indicate that bornyl acetate mitigated expression of the pro-inflammatory cytokines TNF-α and IL-1ß. Our results suggest the therapeutic potential of bornyl acetate in patients with atherosclerosis.

Improvement of Cisplatin-induced renal dysfunction by Schisandra chinensis stems via anti-inflammation and anti-apoptosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill is a frequently used traditional Chinese medicine, and modern pharmacological research has proven that S. chinensis has antioxidant, anti-hepatotoxity, anti-inflammatory, and anti-nephrotoxic effects. Cisplatin is widely used as antineoplastic drug at present, but the clinical application is limited owing to its nephrotoxicity. AIM OF THE STUDY: To demonstrate the renoprotective activity of the extract of the stems of S. chinensis (SCE) in mice established by cisplatin-triggering acute kidney injury (AKI). The possible molecular mechanism of nephroprotection exhibited by SCE was evaluated for the first time. MATERIALS AND METHODS: Mice in SCE groups were pre-treated with SCE for 10 consecutive days, and on 7th day 1 h after final administration, following intraperitoneal injection of cisplatin with 20 mg/kg was treated to cisplatin group and SCE groups. On the 10th day, renal function, histopathological change, and oxidative stress markers were investigated. RESULTS: Renal oxidative stress level characterized by elevated heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) expression was obviously reduced by SCE pre-treatment. In addition, SCE was found to suppress inflammatory response through the reduction of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) p65 activation. SCE treatment also inhibited activation of apoptotic pathways through down-regulating Bax, cleaved caspase-3, 8, 9 and up-regulating Bcl-2 expression levels. CONCLUSION: These findings illustrated that SCE possessed powerful protective effect on AKI caused by cisplatin via amelioration of oxidative stress, inflammation and apoptosis.

Functionalized magnetic iron oxide/polyacrylonitrile composite electrospun fibers as effective chromium (VI) adsorbents for water purification.

Inorganic/organic composite electrospun fibers have been extensively investigated as adsorbents for the wastewater treatment. In this study, branched polyethylenimine (b-PEI) functionalized magnetic iron oxide (Fe3O4)/polyacrylonitrile (PAN) composite electrospun fiber adsorbent (b-PEI-FePAN) was fabricated and systematically explored for the removal of toxic hexavalent chromium [Cr(VI)]. b-PEI grafted PAN organic component not only acted as the flexible substrate to load Fe3O4 particles but also made a contribution to the improved adsorption capacity. In the batch adsorption test, the maximum adsorption capacity based on Langmuir fitting was 684.93mg/g, which was higher than most of the reported adsorbents. The removal efficiency could reach above 98% with a dosage of 0.5mg/mL in the real water samples. Moreover, the filtration efficiency was also above 98.5% even at a high flux of 765L·m-2·h-1 in dynamic filtration experiment. According to mechanism analysis, both electrostatic adsorption and reduction action were involved in the Cr(VI) removal processes. These results demonstrate that b-PEI functionalized Fe3O4/PAN composite electrospun fibers have promising potential in water purification field.

Nephroprotective Effects of Saponins from Leaves of Panax quinquefolius against Cisplatin-Induced Acute Kidney Injury.

Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) level and decline of glutathione (GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by PQS pretreatment. The suppression of inflammatory response by PQS was realized through the decrease the mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in kidney tissues, which were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western blotting demonstrated that PQS administration significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), suggesting the inhibition of apoptosis and inflammation response. Overall, PQS may possess protective effects in cisplatin-induced AKI through suppression of oxidative stress, inflammation and apoptosis.