Liver diseases cannot be easily detected in the early stage， and although invasive diagnostic methods， such as liver biopsy， are relatively accurate， they tend to have a low degree of acceptance， which greatly limits the improvement in diagnosis and treatment techniques for liver diseases. Therefore， it is of great importance to search for new biomarkers and therapeutic targets. As an emerging biomarker for liquid biopsy， tRNA-derived small RNA （tsRNA） is abnormally expressed in various liver diseases including viral hepatitis， fatty liver disease， liver injury， and liver cancer， and it can affect the development and progression of liver diseases by regulating the biological functions such as gene expression， epigenetic regulation， and protein translation. This article reviews the origin， classification， and biological function of tsRNA， as well as the research advances in tsRNA as biomarkers and potential therapeutic targets for liver diseases， so as to provide ideas for the early diagnosis and treatment of liver diseases.

Objective To investigate the weight loss efficacy and mechanisms of oligopeptide-herbal medicine composite,and to provide new approaches for obesity treatment.Methods Twenty-three SPF female SD rats were randomly divided into control group(n=3)and modeling group(n=20).The control group was fed an ordinary diet for 6 consecutive weeks,and the modeling group was fed a high-fat diet for 6 consecutive weeks to establish a simple obesity rat model.After successful modeling,the modeling group was randomly divided into model group(n=10)and treatment group(n=10).The treatment group started anoint-and-massage therapy with oligopeptide-herbal medicine composite(3 g per rat per time,once a day,20 min each time),which was recorded as day 1.The control group and model group were not treated with oligopeptide-herbal medicine composite but received the same massage,and continued to be fed ordinary feed and high-fat feed respectively.Ten rats in the model group and ten in the treatment group were each divided into 3 groups,with 3,3,and 4 rats in each group.On days 3,6,and 9 after treatment,the rats in the three groups were weighed and cardiac blood collection was performed after isoflurane respiratory anesthesia.After euthanasia by cardiac bloodletting,abdominal subcutaneous adipose tissue(aSAT)and perirenal white adipose tissue(pWAT)samples were collected and weighed.Serum triglycerides(TG)and high-density lipoprotein cholesterol(HDL-C)levels were measured.Image J software was used to measure aSAT thickness and the diameter and area of perirenal white adipocytes and abdominal subcutaneous adipocytes.Immunofluorescence technique was used to observe the number of telocytes(TCs),cell junctions and exosomes per unit area of aSAT.Transmission electron microscopy was used to measure the length of telopodes(Tps)of dermal and subcutaneous TCs in abdominal skin,and to observe the distribution of exosome vesicles,rough endoplasmic reticulum,mitochondria,and cell junctions.Results Compared with the control group,the body weight of rats in the modeling group increased significantly(P＜0.05).Compared with the control group,rats in the model group showed a significant increase in serum TG level,a significant decrease in HDL-C level,and a significant increase in pWAT mass(all P＜0.05).Compared with the model group,the treatment group showed a significantly increased rate of body weight reduction,significantly decreased pWAT mass,significantly decreased serum TG level,and significantly increased HDL-C level(all P＜0.05).Compared with the model group,the treatment group showed significant reductions in aSAT thickness,as well as cell diameter and area in both aSAT and pWAT(all P＜0.05).Compared with the model group,the treatment group showed significantly increased number of TCs per unit area of aSAT,number of exosomes from TCs in aSAT,and Tps length(all P＜0.05).The treatment group showed an increasing trend in the numbers of mitochondria,rough endoplasmic reticulum,and cell junctions in TCs.Conclusion Oligopeptide-herbal medicine composite applied via anoint-and-massage therapy effectively improves obesity-related symptoms such as dyslipidemia and fat accumulation in obese rats by regulating TCs and their intercellular communication.

Objective To investigate the weight loss efficacy and mechanisms of oligopeptide-herbal medicine composite,and to provide new approaches for obesity treatment.Methods Twenty-three SPF female SD rats were randomly divided into control group(n=3)and modeling group(n=20).The control group was fed an ordinary diet for 6 consecutive weeks,and the modeling group was fed a high-fat diet for 6 consecutive weeks to establish a simple obesity rat model.After successful modeling,the modeling group was randomly divided into model group(n=10)and treatment group(n=10).The treatment group started anoint-and-massage therapy with oligopeptide-herbal medicine composite(3 g per rat per time,once a day,20 min each time),which was recorded as day 1.The control group and model group were not treated with oligopeptide-herbal medicine composite but received the same massage,and continued to be fed ordinary feed and high-fat feed respectively.Ten rats in the model group and ten in the treatment group were each divided into 3 groups,with 3,3,and 4 rats in each group.On days 3,6,and 9 after treatment,the rats in the three groups were weighed and cardiac blood collection was performed after isoflurane respiratory anesthesia.After euthanasia by cardiac bloodletting,abdominal subcutaneous adipose tissue(aSAT)and perirenal white adipose tissue(pWAT)samples were collected and weighed.Serum triglycerides(TG)and high-density lipoprotein cholesterol(HDL-C)levels were measured.Image J software was used to measure aSAT thickness and the diameter and area of perirenal white adipocytes and abdominal subcutaneous adipocytes.Immunofluorescence technique was used to observe the number of telocytes(TCs),cell junctions and exosomes per unit area of aSAT.Transmission electron microscopy was used to measure the length of telopodes(Tps)of dermal and subcutaneous TCs in abdominal skin,and to observe the distribution of exosome vesicles,rough endoplasmic reticulum,mitochondria,and cell junctions.Results Compared with the control group,the body weight of rats in the modeling group increased significantly(P＜0.05).Compared with the control group,rats in the model group showed a significant increase in serum TG level,a significant decrease in HDL-C level,and a significant increase in pWAT mass(all P＜0.05).Compared with the model group,the treatment group showed a significantly increased rate of body weight reduction,significantly decreased pWAT mass,significantly decreased serum TG level,and significantly increased HDL-C level(all P＜0.05).Compared with the model group,the treatment group showed significant reductions in aSAT thickness,as well as cell diameter and area in both aSAT and pWAT(all P＜0.05).Compared with the model group,the treatment group showed significantly increased number of TCs per unit area of aSAT,number of exosomes from TCs in aSAT,and Tps length(all P＜0.05).The treatment group showed an increasing trend in the numbers of mitochondria,rough endoplasmic reticulum,and cell junctions in TCs.Conclusion Oligopeptide-herbal medicine composite applied via anoint-and-massage therapy effectively improves obesity-related symptoms such as dyslipidemia and fat accumulation in obese rats by regulating TCs and their intercellular communication.

Objective:To evaluate the clinical efficacy of the Masquelet technique (induced membrane technique) combined with an antibiotic-impregnated bone cement-coated plate for the treatment of infected nonunion following internal fixation of clavicle fractures.Methods:A retrospective analysis was conducted on 12 patients with clavicular infected nonunion who underwent staged treatment using the Masquelet technique combined with an antibiotic-loaded bone cement-coated plate between May 2021 and May 2023 in the Second Ward of Traumatic Orthopedics at Gansu Provincial People's Hospital. The cohort included 8 males and 4 females, with a mean age of 28.8±3.1 years (range: 12-48 years). Among them, 10 cases had mid-third clavicular defects, and 2 cases had lateral third defects. All 12 cases involved nonunion due to bone infection following internal fixation of clavicle fractures, with 6 cases initially fixed with Kirschner wires and 6 with plates. The induced membrane technique was applied in two stages. Stage One: Radical debridement was performed, including removal of the original internal fixation and infected necrotic tissue. A plate was implanted, and the bone defect area was filled with antibiotic-loaded bone cement, fully encapsulating the plate. Stage Two: Bone graft reconstruction was carried out 6-8 weeks later, after infection control was confirmed. The induced membrane was incised, the bone cement was removed, and a bone graft was placed within the membrane. Outcomes included infection control, bone union time, pain visual analogue scale (VAS), and Constant-Murley shoulder score (CMS) at the final follow-up.Results:The interval between the first and second surgeries was 7.42±1.17 weeks (range: 6-10 weeks). All 12 patients were followed up for a mean duration of 16.4±3.9 months (range: 12-24 months). One patient experienced recurrent infection after the first-stage surgery, which was controlled after repeat debridement and replacement of antibiotic-loaded bone cement, with no recurrence during follow-up. All 12 patients achieved bony union, with a mean healing time of 3.42±0.67 months (range: 3-5 months). Radiographs showed continuous bone cortex with no visible fracture lines. At the final follow-up, the mean VAS score was 0.42±0.51, significantly lower than the preoperative score of 6.68±1.12 ( t=18.711, P<0.001). The mean CMS score was 88.93±3.94, significantly higher than the preoperative score of 44.41±7.15 ( t=20.786, P<0.001). Conclusion:The Masquelet technique combined with an antibiotic-loaded bone cement-coated plate is effective in treating infected nonunion after internal fixation of clavicle fractures, significantly improving acromioclavicular joint function.

By elaborating on the theoretical framework of the pulse acupuncture based on systematic syndrome differentiation， this paper briefly analyzes the correspondence between pulse and acupuncture， and further explores its core principle of "establishing acupuncture based on pulse， and applying acupuncture when the pulse is balanced". This therapeutic system employs a three-step acupoint selection method， relying on the systematic integration and analysis of pulse elements at different levels to determine the nature of disease， syndrome type， and location. Treatment principles are guided by the concepts of form and spirit transformation， aiming to treat both simultaneously. Pulse diagnosis also serves as a standard for evaluating therapeutic efficacy and predicting prognosis， providing a theoretical basis for clinical acupuncture. Using stroke as a case example， this paper illustrates the practical clinical application of this approach， offering valuable insight for acupuncture.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To explore the clinical efficacy of membrane induction technique in the treatment of chronic bone infection after internal fixation of intertrochanteric fracture in adults.Methods:The data were retrospectively analyzed of the 15 adult patients who had been treated for chronic bone infection after internal fixation of intertrochanteric fracture at Department of Traumatic Orthopaedics Ⅱ, Gansu Provincial People's Hospital from May 2019 to May 2022. There were 13 males and 2 females with an age of (55.8±2.6) years. By the Cierny-Mader anatomical classification, 6 cases were type Ⅲ and 9 cases type Ⅳ; by the physiological classification, 10 cases were type A and 5 cases type B. Course of bone infection was (22.1±8.1) months. All patients were treated by membrane induction technique in 2 stages. In the first stage, antibiotic bone cement was implanted after debridement into the defects [(4.50±0.54) cm in length] followed by temporary fixation of broken ends of the fracture. After 6 to 8 weeks when infection was controlled, the second stage repair and reconstruction of bone defects was carried out. Infection control, complications, bone healing time, and Samantha X-ray bone healing score, visual analogue scale (VAS) at standing, Sanders hip score and Paley score for bone defect healing at the last follow-up were recorded.Results:The 15 patients were followed up for (27.5±2.5) months. Infection recurred after the first-stage operation in 2 cases, but was effectively controlled after debridement and follow-up observed no recurrence. Follow-up showed no such complications as donor site infection, deformation or collapse of the bone reconstructed, limb shortening, re-fracture or internal fixation failure in the 15 patients who achieved bony union after (10.3±2.1) months. At the last follow-up, the Samantha X-ray score was 6.0(5.0, 6.0) points and VAS at standing 1.0(1.0, 3.0) point for the 15 patients; by Sanders hip score, the hip function was rated as excellent in 10 cases and as fine in 5 cases; by Paley score for bone defect healing, the efficacy was rated as excellent in 7 cases, as good in 2 cases and as fair in 6 cases.Conclusion:In the treatment of chronic bone infection after internal fixation of intertrochanteric fracture in adults, membrane induction technique can effectively control infection and improve the hip function of the affected limb, leading to good clinical efficacy.

Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that, in addition to the classical signaling cascade regulation, biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review, we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation, with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore, we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates, which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
Humans ; Signal Transduction ; Hippo Signaling Pathway ; Protein Serine-Threonine Kinases/physiology* ; Animals ; Biomolecular Condensates/metabolism* ; Transcription Factors/metabolism* ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/metabolism* ; Neoplasms ; Transcriptional Activation ; Intracellular Signaling Peptides and Proteins/metabolism*