BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

The lingnan liver-soothing and spirit-regulating acupuncture and moxibustion technique,developed by Professor FU Wen-Bin,a renowned traditional Chinese medicine expert in Guangdong Province,represents an innovative achievement in acupuncture therapy for depression-related disorders.Drawing upon the rich legacy of master scholars,meticulous study of medical literature,and over three decades of continuous research and innovation,Professor FU has formulated this technique with profound influence and widespread application.By tracing the developmental trajectory of the Lingnan liver-soothing and spirit-regulating technique,this paper sheds light on its significant guiding principles and reference value for the development of other distinctive acupuncture techniques.Furthermore,it offers insights and inspiration for advancement in various fields of traditional Chinese medicine.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

The 2-(2-phenylethyl)chromones were separated from agarwood of Aquilaria agallocha Roxb. and their anti-KRAS mutant non-small cell lung cancer (NSCLC) activities were evaluated. 2-(2-Phenyethyl)chromones in agarwood were separated and purified by silica gel, RP-18 reverse phase silica gel, MCI gel CH20P, Diol, and semi preparative HPLC chromatography techniques, while the structures of the compounds were identified by extensive spectroscopic analysis, such as 1D and 2D NMR and ESI-MS. The cell counting kit 8 (CCK-8) assay was used to screen the anti-tumor activity of the isolated monomeric compounds on three KRAS-mutant NSCLC cells. The cell proliferation, cloning formation, adhesion ability, and cell cycle arrest activity of compound 8 were analyzed. Molecular docking and Western blot experiments were used to study the mechanism of compound 8. The in vivo anti-tumor activity of the compound 8 was evaluated by zebrafish cell derived xenograft (CDX) model. Nineteen known 2-(2-phenylethyl)chromones were isolated from the ethyl acetate extract of agarwood. On A549 (KRAS G12S) cells, compounds 8, 10, and 19 showed good inhibitory activity, on H23 (KRAS G12C) cells, compounds 7, 8, and 19 showed good inhibitory activity, and on H358 (KRAS G12C) cells, compounds 8, 10, and 16 showed good inhibitory activity. Compound 8 had the best inhibitory activity in all three cell lines. It effectively inhibited cell proliferation, clone formation, adhesion ability, and arrested the H23 cell cycle at G2/M phase. Compound 8 could also inhibit the expression of c-Met and its downstream signaling pathways, effectively inhibiting tumor growth in zebrafish CDX model. In conclusion, among the nineteen known 2-(2-phenylethyl)chromones, compound 8 had the best activity and significantly inhibited the proliferation of KRAS-mutant NSCLC cells by arresting the cells in the G2/M phase.

Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.

Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.