Hyperuricemia （HUA） is a common metabolic disorder characterized by persistently elevated serum uric acid levels, leading to uric acid-related renal injury through complex mechanisms involving inflammation, oxidative stress, and fibrosis. Key traditional Chinese medicine （TCM） formulas （e.g., Simiao Powder, Tongfengning） and individual herbal compounds （alkaloids, flavonoids, polysaccharides） with urate-lowering and renal protective properties were systematically summarized, including their mechanisms of regulating uric acid transporters （organic anion transporter 3, urate anion transporter 1, glucose transporter type 9）, inhibiting inflammatory responses （via NF-κB signaling）, reducing oxidative stress （via mitochondrial pathways and antioxidant enzyme enhancement）, and attenuating renal fibrosis （via PI3K/AKT signaling）. The challenges of current studies mainly focus on unclear mechanisms of action and insufficient clinical research. Future research may further explore TCM resources, clarify dual-action mechanisms of urate reduction and renal protection, and identify new therapeutic strategies for hyperuricemia-related renal injury.

Liumotang comes from the Yuan dynasty's Effective Prescription Handed Down for Generations of Physicians. It is composed of six medicinal materials： Arecae Semen， Aquilariae Lignum Resinatum， Aucklandiae Radix， Linderae Radix， Rhei Radix et Rhizoma， and Aurantii Fructus. It is a classical formula for treating abdominal pain due to Qi stagnation and constipation accompanied by heat. This study systematically collated the records of Liumotang in ancient medical books and modern clinical literature and conducted in-depth analysis and textual research on its formula source， main diseases， composition， dosage， medical books， container capacity， processing， preparation method， usage， drug basis， formula meaning， and other key information， so as to provide a powerful reference for the development and clinical application of compound preparations of the classical formula Liumotang. The results show that Liumotang was first seen in Effective Prescription Handed Down for Generations of Physicians， and many medical books of the past dynasties have imitated this. In terms of drug basis， the dried and mature seeds of the palm plant Areca catechu， resin-containing wood of the Daphneaceae plant Aquilaria sinensis， the dried roots of the Asteraceae plant woody Aucklandia lappa， the dried tuber root of the Lauraceae plant Lindera aggregata， the dried roots and rhizomes of the knotweed plant， R. palmatum， R.tangutikum， and R. officinale， and the dried and unripe fruits of the citrus genus C. aurantium and its cultivated varieties from the family Rutaceae were selected. In terms of dosage， through the textual research on bowls in the Ming and Qing dynasties， combined with the conversion of medicines and bowl capacity in the Qing dynasty， it was estimated that the dosage of each drug in the Yuan dynasty was 10.86 g. In the Ming and Qing dynasties， the dosage of drugs was mostly equal， but the dosage of drugs was somewhat different. In terms of processing， preparation method， and usage， in the medical books of the past dynasties， the processing of drugs has slightly changed， but raw drugs are used in all preparations. The preparation method and usage did not change much during the Yuan， Ming， and Qing dynasties， except for certain differences in dosage. In terms of syndrome， Liumotang was first used to treat abdominal pain due to Qi stagnation and constipation accompanied by heat. Medical books of the past dynasties often omit the symptoms of heat. In modern clinical practice， Liumotang is mainly used in the digestive system and urinary system diseases and is mostly used to treat constipation-predominant irritable bowel syndrome， biliary reflux gastritis， functional constipation， slow transit constipation， and other diseases， with no adverse reactions found yet. The above results provide a reliable scientific basis for the development and clinical treatment of Liumotang compound preparations.

Objective: To investigate the changes of dentin surface and the effects of different surface treatments on the rebonding effect following non-destructive restoration removal by an Er:YAG laser and to provide reference for oral clinical operation Methods: This study was approved by the ethics review committee of the unit. Using computer-aided design and computer-aided manufacturing (CAD/CAM) technology, 102 zirconia specimens (4 mm × 4 mm × 1.5 mm) were fabricated. In total, 110 impacted third molar teeth were extracted, and 102 dentine blocks (4 mm × 4 mm × 2 mm) were prepared. The zirconia specimen and dentin blocks were bonded with resin cement before removal with an Er: YAG laser. Three disassembled dentin blocks were randomly selected, and the components of dentin surface elements were analyzed by energy dispersive X-ray spectroscopy (EDX). The removed dentin blocks were randomly divided into three groups (n = 33) based on the different surface treatments: control group (no treatment), sandblasting group (50 μm, Al2O3 sandblasting), and laser irradiation group (Er: YAG laser irradiation, parameters were set to 10 Hz, 60 mJ, 0.6 W). Three dentin blocks were randomly selected in each group for scanning electron microscopy (SEM) observation, and the residual resin on dentin surface of remaining 30 dentin blocks in each group were observed under an optical microscope at 20 times magnification. Scores were obtained using the adhesive remnant index (ARI) method. Three groups of dentin blocks (n = 30) that underwent different surface treatments were rebonded with resin cement according to standard procedures and then divided into two subgroups for aging (n = 15). One subgroup was subjected to a 37 ℃ water bath for 24 h, and the other subgroup was subjected to 5 000 thermal cycles after a 37 ℃ water bath for 24 h, and the micro-shear bonding strength of each group was measured. The microshear bonding strength of each group was measured, and fracture modes were analyzed. The differences of dentine surface ARI between the three groups, as well as the inter-group differences in fracture mode, and bonding strength, and the intra-group differences before and after aging were compared between the three groups. Results: When zirconia was removed by Er: YAG laser, there was no obvious damage on the dentin surface, but C and Si elements in dentin increased significantly. After different surface treatments, the ARI scores of the sandblasting and laser irradiation groups were lower than those of the control group (P<0.05), while ARI was not significantly different between the sandblasting and laser irradiation groups (P>0.05). The dentin surface morphology was also different. There was a large amount of residual resin on the dentin surface of the control group. In the sandblasting group, the residual resin was lower, the dentin surface was rough, and the dentin tubules were visible. A large amount of residual resin was observed on the dentin surface of the laser irradiation group. After 24 h of water bath at 37 ℃, the bonding strengths of the control group, sandblasting group, and laser irradiation group were (6.13 ± 2.40) MPa, (9.39 ± 2.00) MPa, and (5.85 ± 1.44) MPa, respectively, and the bonding strength of the sandblasting group was significantly higher than that of the other two groups (P<0.05). After being subjected to 24 h of water bath at 37 ℃ and 5 000 thermal cycles, the bonding strengths of the control group, sandblasting group, and laser irradiation group were (5.39 ± 0.83) MPa, (8.45 ± 1.20) MPa and (4.84 ± 1.43) MPa, respectively. The bonding strength of the sandblasting group was significantly higher than that of the other two groups (P<0.05). There was no significant difference between the control group, sandblasting group, and laser irradiation group before and after 5 000 thermal cycles following 24 h of water bath at 37 ℃ (P>0.05). In the control group, sandblasting group, and laser irradiation group, cohesive fracture was not observed. The fracture mode was mainly adhesive fracture. Before and after 5 000 thermal cycles, the frequency of mixed fracture in the sandblasting group was significantly higher than that in the other two groups (P<0.05). Conclusion Er: YAG laser removal of zirconia does not damage dentin, but a large amount of resin remains on the dentin surface after removal. The sandblasting process can effectively remove these residual resins, thereby improving the dentine rebonding effect.

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective:To observe any effect of warm acupuncture on chondrocyte apoptosis and the miR-27a-mediated PI3K/AKT/mTOR signaling pathway using a rat model of early knee osteoarthritis (KOA).Methods:Fifty Sprague-Dawley rats were randomly divided into a control group, a model group, a warm acupuncture group, an inhibitor group, and an inhibitor + warm acupuncture group (the combined group), each of 10. Three days before the modeling, both the inhibitor and combined groups were injected with miR-27a inhibitor. Papain was then injected in all groups except the control group to establish the early KOA model. After successful modeling, the combined and warm acupuncture groups were given 30 minutes of warm acupuncture at the medial and lateral Xiyan points daily for 14 days. The model and inhibitor groups were fixed for 30 minutes during those sessions. After the 2 weeks, hematoxylin-eosin staining was used to observe any pathological changes in the cartilage tissue. Terminal deoxynucleoitidyl transferase-mediated nick end labeling was used to detect chondrocyte apoptosis, and enzyme-linked immunosorbent assays were employed to observe the levels of interleukin 1β (IL-1β) and IL-6. Western blotting was used to evaluate the expression of p-PI3K, p-AKT, p-mTOR, PI3K, AKT, mTOR, LC3-II, and Beclin1 proteins in the cartilage tissue, while quantitative real-time polymerase chain reactions detected the content of miR-27a.Results:After the intervention, the morphology of the chondrocytes in the warm acupuncture group had improved significantly compared to the model group, while that of the inhibitor and combined groups was better than among the warm acupuncture group. The rate of chondrocyte apoptosis in the warm acupuncture group was significantly lower than in the model group, while the rates of the inhibitor and combined groups were lower still. There was no significant difference between the inhibitor and the combination group on average. The average expression of IL-6, IL-1β, LC3-II and Beclin1 protein and of miR-27a were significantly lower in the warm acupuncture, inhibitor and combined groups than among the model group, with those of the inhibitor and combined groups significantly lower than among the warm acupuncture group, on average. The average p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR levels of the warm acupuncture, inhibitor and combined groups were significantly higher than those of the model group, with those of the inhibitor and combined groups significantly higher, on average, than among the warm acupuncture group. However, there was no significant difference between the inhibitor group and the combined group in their protein expression and mRNA levels.Conclusions:Warm acupuncture may down-regulate the expression of miR-27a to promote the activation of the PI3K/AKT/mTOR signaling pathway, inhibiting excessive autophagy and apoptosis. That would relieve inflammation and damage, and delay degeneration in early KOA, at least in rats.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

The development,progression,and curative efficacy of head and neck squamous cell carcinoma(HNSCC)are influenced by complex interactions between epithelial and immune cells.Nevertheless,the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood.Cuproptosis,a form of programmed cell death that is dependent on copper,has been implicated in cancer pathogenesis.However,the understanding of cuproptosis in the context of HNSCC remains limited.In this study,we have discovered that cuproptosis-related long non-coding RNAs(CRLs)known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator(PLAU)by competitively binding to miR-193b-3p in HNSCC.The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation,migration,and invasion in HNSCC.Moreover,the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR,predominantly expressed on macrophages,thereby influencing the abnormal epithelial-immune interactome in HNSCC.Notably,the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor(EGFR)and cyclin-dependent kinase(CDK4/6)for the treatment of HNSCC.

Autologous serum skin test (ASST) is commonly used as a screening test to assess immune subtypes of chronic spontaneous urticaria (CSU) in clinical practice, but its immunological mechanisms and associations with clinical features and prognosis of CSU are not yet clear. Studies have shown that positive ASST is associated with increased immunoglobulin G autoantibodies, decreased eosinophil and basophil counts, increased CD63 expression on basophils, and changes in circulating inflammatory cytokine levels in CSU patients, but not associated with age, disease duration, and personal or family history of CSU patients, and may be a predictor of severity of chronic urticaria. ASST-positive patients may respond poorly to second-generation H1 antihistamines, slowly to omalizumab, but respond well to cyclosporine and autologous whole blood/serum injections. This review summarizes the immunological and clinical characteristics of ASST-positive patients, and discusses the predictive value of positive ASST for the efficacy of different treatment regimens.

As the first marketed epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib plays an important role in the targeted therapy of malignant tumors such as non-small cell lung cancer, but this drug can cause serious adverse effects such as liver toxicity. If the reaction occurs, the drug must be stopped for liver protection treatment, which greatly affects the treatment process of cancer. However, the mechanism of gefitinib-induced hepatotoxicity is still unclear, and clinical treatment measures are very limited. This article aims to review the molecular mechanism of gefitinib-induced hepatotoxicity and the commonly used clinical therapeutic drugs, so as to provide scientific basis for clinical prevention and rational drug use.