ObjectiveTransfer RNA-derived fragments (tRFs) are a recently characterized and rapidly expanding class of small non-coding RNAs, typically ranging from 13 to 50 nucleotides in length. They are derived from mature or precursor tRNA molecules through specific cleavage events and have been implicated in a wide range of cellular processes. Increasing evidence indicates that tRFs play important regulatory roles in gene expression, primarily by interacting with target messenger RNAs (mRNAs) to induce transcript degradation, in a manner partially analogous to microRNAs (miRNAs). However, despite their emerging biological relevance and potential roles in disease mechanisms, there remains a significant lack of computational tools capable of systematically predicting the interaction landscape between tRFs and their target mRNAs. Existing databases often rely on limited interaction features and lack the flexibility to accommodate novel or user-defined tRF sequences. The primary goal of this study was to develop a machine learning based prediction algorithm that enables high-throughput, accurate identification of tRF:mRNA binding events, thereby facilitating the functional analysis of tRF regulatory networks. MethodsWe began by assembling a manually curated dataset of 38 687 experimentally verified tRF:mRNA interaction pairs and extracting seven biologically informed features for each pair: (1) AU content of the binding site, (2) site pairing status, (3) binding region location, (4) number of binding sites per mRNA, (5) length of the longest consecutive complementary stretch, (6) total binding region length, and (7) seed sequence complementarity. Using this dataset and feature set, we trained 4 distinct machine learning classifiers—logistic regression, random forest, decision tree, and a multilayer perceptron (MLP)—to compare their ability to discriminate true interactions from non-interactions. Each model’s performance was evaluated using overall accuracy, receiver operating characteristic (ROC) curves, and the corresponding area under the ROC curve (AUC). The MLP consistently achieved the highest AUC among the four, and was therefore selected as the backbone of our prediction framework, which we named tRF Prospect. For biological validation, we retrieved 3 high-throughput RNA-seq datasets from the gene expression omnibus (GEO) in which individual tRFs were overexpressed: AS-tDR-007333 (GSE184690), tRF-3004b (GSE197091), and tRF-20-S998LO9D (GSE208381). Differential expression analysis of each dataset identified genes downregulated upon tRF overexpression, which we designated as putative targets. We then compared the predictions generated by tRF Prospect against those from three established tools—tRFTar, tRForest, and tRFTarget—by quantifying the number of predicted targets for each tRF and assessing concordance with the experimentally derived gene sets. ResultsThe proposed algorithm achieved high predictive accuracy, with an AUC of 0.934. Functional validation was conducted using transcriptome-wide RNA-seq datasets from cells overexpressing specific tRFs, confirming the model’s ability to accurately predict biologically relevant downregulation of mRNA targets. When benchmarked against established tools such as tRFTar, tRForest, and tRFTarget, tRF Prospect consistently demonstrated superior performance, both in terms of predictive precision and sensitivity, as well as in identifying a higher number of true-positive interactions. Moreover, unlike static databases that are limited to precomputed results, tRF Prospect supports real-time prediction for any user-defined tRF sequence, enhancing its applicability in exploratory and hypothesis-driven research. ConclusionThis study introduces tRF Prospect as a powerful and flexible computational tool for investigating tRF:mRNA interactions. By leveraging the predictive strength of deep learning and incorporating a broad spectrum of interaction-relevant features, it addresses key limitations of existing platforms. Specifically, tRF Prospect: (1) expands the range of detectable tRF and target types; (2) improves prediction accuracy through multilayer perceptron model; and (3) allows for dynamic, user-driven analysis beyond database constraints. Although the current version emphasizes miRNA-like repression mechanisms and faces challenges in accurately capturing 5'UTR-associated binding events, it nonetheless provides a critical foundation for future studies aiming to unravel the complex roles of tRFs in gene regulation, cellular function, and disease pathogenesis.

Objective To investigate the ameliorative effect of sulforaphane on inflammatory response and airway remodeling in rats with chronic obstructive pulmonary disease(COPD).Methods Seventy-five SD rats were randomly divided into the normal group,the model group,and the low-,medium-,and high-dose groups of sulforaphane,with 15 rats in each group.Except for the normal group,the COPD model was prepared in the remaining group using aroma smoke inhalation combined with intratracheal droplet lipopolysaccharide(LPS)method.After the successful modelling,the rats were administered the drug by gavage for 28 days.At the end of the administration,the general conditions of the rats in each group were observed,and the lung function[forced vital capacity(FVC),peak expiratory flow-rate(PEF),forceful expiratory volume in 1 second(FEV1)]was examined,and the pathological changes of the lung tissues were observed by hematoxylin-eosin(HE)staining method,and the indexes of airway remodeling(thickness of the bronchial wall,thickness of the smooth muscle)were measured;the enzyme-linked immunosorbent assay(ELISA)was used to examine the lung function of the rats.The levels of inflammatory factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)]were detected in lung tissue by enzyme-linked immunosorbent assay(ELISA),and changes in the protein expressions of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear transcription factor κB(NF-κB)were detected in lung tissue by Western Blot.Results(1)The rats in the model group had dry and lack of glossy fur,obvious coughing and nose scratching,shortness of breath,slow movement,and preferred to arch their backs and lie curled up;the rats in the low-,medium-and high-dose groups of sulforaphane showed significant improvement in shortness of breath,coughing,and other abnormal manifestations.(2)HE staining showed that the airway wall and smooth muscle of rats in the model group were thickened,the airway epithelium was damaged,and alveolar destruction,fusion,and massive infiltration of inflammatory cells were seen;the histopathological changes in the lungs of rats in the low-,medium-and high-dose groups of sulforaphane improved to varying degrees,with the airway wall becoming thinner,the degree of alveolar destruction being reduced,and the infiltration of inflammatory cells being reduced.(3)Compared with the normal group,FVC,PEF and FEV1 were significantly reduced in the model group(P＜0.05),and the levels of TNF-α and IL-1β,bronchial wall thickness,smooth muscle thickness,and the expression levels of TLR4,MyD88 and NF-κB were significantly increased in the model group(P＜0.05);and in comparison with the model group,the levels of FVC,PEF,and FEV1 were significantly increased in the rats in the sulforaphane low-,medium-,and high-dose groups(P＜0.05),and the levels of TNF-α,IL-1β,bronchial wall thickness,smooth muscle thickness,and the expression levels of TLR4,MyD88,and NF-κB were significantly decreased(P＜0.05)compared with the model group.Conclusion Sulforaphane helps to inhibit the inflammatory response,attenuate airway remodeling,and improve the pathological injury and lung function of lung tissue in rats with COPD,and its mechanism may be related to the inhibition of TLR4,MyD88,and NF-κB protein expressions.

Objective To investigate the clinical effect of LUO's Nephropathy Recipe Ⅲ(composed of Sargassum,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Rehmanniae Radix Praeparata,calcined Ostreae Concha,Houttuyniae Herba,Schizonepetae Spica,etc.)combined with conventional western medicine in treating stage 3-5 non-dialysis chronic kidney disease(CKD)of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type.Methods A total of 180 patients with stage 3-5 non-dialysis CKD of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type were randomly divided into observation group and control group,with 90 cases in each group.The control group was given conventional western medicine for symptomatic treatment,and the observation group was treated with LUO's Nephropathy RecipeⅢon the basis of treatment for the control group.The course of treatment for the two groups covered one month.Before and after treatment,the levels of serum inflammatory factors,renal function indicators and urine protein parameters in the two groups were observed.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate in the observation group was 95.56%(86/90)and that in the control group was 81.11%(73/90).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammatory factors of transforming growth factor β1(TGF-β1),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function indicators of blood urea nitrogen(BUN),serum creatinine(Scr),blood uric acid(UA),and cystatin C(Cys-C)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of 24-hour urine protein quantification and urine microalbumin in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.44%(4/90),which was significantly lower than that of 15.56%(14/90)in the control group,and the difference was statistically significant between the two groups(P＜0.05).Conclusion LUO's Nephropathy Recipe Ⅲ combined with conventional western medicine exerts satisfactory efficacy in treating stage 3-5 non-dialysis CKD patients with spleen-kidney deficiency with turbidity-toxin-stasis obstruction syndrome type,and the therapy can significantly alleviate the inflammatory response,improve the renal function,decrease the urinary protein excretion of the patients,with high safety profile.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

【Objective】 To explore the distribution of serological markers related to samples whose serological test results were inconsistent with HBV DNA test results among voluntary blood donors in Xi′an. 【Methods】 A total of 71 HBsAg ELISA positive and NAT non-reactive (ELISA+ /NAT-)blood samples were collected from Shaanxi Blood Center from November 1, 2022 to April 30, 2023. The serological markers of hepatitis B were detected by electrochemiluminescence method, and the HBV S region and C region gene fragments were amplified by nested-PCR. 【Results】 The positive rate of nested-PCR in double ELISA+ /NAT- group(n=30) was statistically higher than that of ELISA+ /NAT- group(n=41)(60% vs 24.4%, P<0.05). Donors in double ELISA+ /NAT- group were all first-time blood donors, with the positive rate of anti-HBc in serum of 100%, and the serological pattern was mainly positive for items 1, 4 and 5 items(80%). Among the ELISA+ /NAT- group, 31.7% were repeat blood donors, with the positive rate of anti-HBc in serum of only 19.51%, and the serological patterns were mainly single anti-HBs positive (43.90%) and all negative (36.58%). 【Conclusion】 There are false positives in the test results of ELISA+ /NAT- group, which leads to unnecessary blood discarding. Meanwhile, the samples with negative NAT may have low levels of HBV DNA, which may lead to missed detection. It is suggested that multiple systems and methods should be applied to trace the blood donors who are HBsAg positive and NAT non-reactive, so as to improve the accuracy of HBV screening of blood donors and reduce blood waste.

BACKGROUND:Previous studies have confirmed that the new compound cottonrose hibiscus leaf gel plaster has a good effect in the treatment of acute soft tissue swelling. OBJECTIVE:To observe the clinical efficacy of compound cottonrose hibiscus leaf gel plaster in the treatment of synovitis of the knee joint. METHODS:Seventy-two patients with knee synovitis were selected from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to May 2021.These patients were randomly divided into a trial group and a control group,with 36 cases in each group.The trial group was treated with compound cottonrose hibiscus leaf gel plaster,once a day,12 hours each time,while the control group was treated with Diclofenac Diethylamine Emulgel,twice a day.After 28 days of treatment,visual analog scale score,WOMAC Osteoarthritis Index score,quality of life score(SF-36),thickness of knee synovium and comprehensive curative effect were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores after treatment were lower than those before treatment(P<0.05).Visual analog scale scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).The WOMAC Osteoarthritis Index scores of the two groups after treatment were lower than those before treatment(P<0.05),and the WOMAC Osteoarthritis Index scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).(3)The SF-36 quality of life score in the two groups after 28 days of treatment was higher than that before treatment(P<0.05).SF-36 quality of life score in the trial group after 28 days of treatment was higher than that in the control group(P<0.05).(4)After 28 days of treatment,the thickness of knee synovium in the trial group was less than that in the control group(P<0.05),and the effective rate in the trial group was higher than that in the control group(P<0.05).(5)These findings indicate that compared with Diclofenac Diethylamine Emulgel,the compound cottonrose hibiscus leaf gel plaster can better relieve knee pain,enhance knee joint function,reduce synovial hyperplasia,and elevate the overall quality of life of patients.

Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.