Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Lung cancer is one of the most common and deadliest cancers globally, with its incidence and mortality rates rising each year. Therefore, finding new, safe, and effective alternative therapies poses a significant research challenge in this field. Programmed cell death refers to the process by which cells actively self-destruct in response to specific stimuli, regulated by genetic mechanisms. Modern research indicates that dysregulation of programmed cell death is widespread in the occurrence and progression of lung cancer, allowing cancer cells to evade death while continuing to proliferate and metastasize. Thus, inducing the death of lung cancer cells can be considered a novel therapeutic strategy for treating the disease. In recent years, research on traditional Chinese medicine(TCM) in the field of oncology has gained widespread attention, becoming a focal point. An increasing number of studies have demonstrated that TCM can inhibit the progression of lung cancer and exert anti-cancer effects by inducing apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis. This paper provided a comprehensive review of the molecular mechanisms of programmed cell death in lung cancer, along with the potential mechanisms and research advancements related to the regulation of these processes by TCM, so as to establish a theoretical foundation and direction for future basic and clinical research on lung cancer.
Humans ; Lung Neoplasms/pathology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Apoptosis/drug effects* ; Animals ; Autophagy/drug effects*

Objective:To investigate the efficacy and safety of fluoroscopically-guided percutaneous gastrostomy (FGPG) for establishing enteral nutrition access in the treatment of esophageal fistula after radiotherapy for cervical esophageal cancer (CEC).Methods:A retrospective analysis was conducted on the clinical data of 54 patients who underwent FGPG due to esophageal fistula after radiotherapy for CEC at our department from November 2009 to August 2019. All patients received endoscopy before radiotherapy, and CEC was pathologically confirmed. Enteral nutrition support was offered through a gastrostomy tube postoperatively. The success rate of FGPG, complications, and healing of perforation were recorded and analyzed.Results:FGPG was successfully performed in all 54 patients (100%). During the 12-month follow-up, 50 patients (92.6) survived while four (7.4%) died. Among 36 patients with esophagomediastinal fistula, 32 (88.9%) healed in a median of 12 weeks; of 18 patients with esophagotracheal fistula, 8 (44.4%) healed in a median of 18 weeks. Thus, patients with esophagomediastinal fistula had a significantly higher healing rate ( P<0.01) and shorter healing time ( P=0.017). Gastrostomy tube-related complications were minimal, and no serious complication was noted. Conclusions:FGPG is effective for the treatment of esophageal fistula after CEC radiotherapy and may be an alternative treatment for esophageal fistula.

Mussel adhesive protein (MAP) is increasingly utilized in the biomedical field for the development of various bio-inspired products such as adhesives, protective films, and coatings with diverse properties, owing to its excellent biocompatibility, low immunogenicity, broad-spectrum adhesiveness, and biodegradability. The biological effects and mechanisms of MAP include adhesive film formation, cell migration and proliferation, anti-inflammatory and antioxidant activities, and inhibition of pigment formation. In dermatological applications, MAP demonstrates a significant potential in antibacterial and antipruritic effects, wound healing, barrier repair, and scar regeneration. In recent years, advances in understanding the secretion, distribution, and adhesion mechanisms of MAP, along with innovations in extraction methods, have led to the development of various natural MAP, recombinant MAP, mussel-inspired, and mussel-mimetic biomedical products. However, the biosafety, tissue compatibility, and functionality of these products remain subjects of debate. Further investigation is needed to elucidate the interactions between MAP-based products and various organ tissues and cells within complex biological systems, as well as to thoroughly evaluate their safety and efficacy. Such efforts are essential to achieve high-value utilization of MAP and to explore broader application prospects. Future research may focus on integrating MAP with emerging technologies such as nanotechnology and smart materials to further develop its multifunctional applications in the field of dermatology.

Objective:To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer.Methods:PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results:Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion:Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.

Aim To investigate the role of RNF8 in the proliferation,invasion and migration of hepatocellular carcinoma and in the promotion of epithelial-mesenchy-mal transition(EMT);to clarify the regulatory mecha-nism of RNF8 on hepatocellular carcinoma cells.Methods Immunohistochemistry was used to detect the expression of RNF8 and RhoA in human hepatocel-lular carcinoma tissues and adjacent tissues;Western blot and RT-PCR were used to detect the expression levels of RNF8 and RhoA in human normal hepatocytes and hepatocellular carcinoma cells.RNF8 was overex-pressed in HepG2 cells,and siRNA interference was used to downregulate the expression of RNF8.The cell experimental groups were as follows:control group(Control,normal HepG2 cells),RNF8 overexpression group,RNF8 low expression group(siRNA RNF8),RNF8 overexpression+Rhosin(20 μmol·L-1,RhoA blocker)group.The cell proliferation ability was detected by CCK-8 method;the cell migration ability was detected by scratch test;the cell invasion ability was detected by Transwell test;finally,the expression levels of RNF8,RhoA,PCNA,CyclinD1,N-cadherin,vimentin,Slug,and E-cadherin proteins and mRNA were detected by Western blot and RT-PCR.Results The expression of RNF8 and RhoA in liver cancer tissues and liver cancer cells significantly increased;after RNF8 knockdown,the proliferation,migration,in-vasion and EMT of liver cancer cells were significantly inhibited,while overexpression of RNF8 significantly increased the proliferation,migration,invasion ability of liver cancer cells and promoted EMT.RhoA showed a positive correlation with knockdown and overexpression of RNF8.When RNF8 was overexpressed and RhoA blocker was given at the same time,the phenomenon of overexpression of RNF8 increasing the proliferation,mi-gration,invasion ability and promoting EMT of liver cancer cells was significantly reversed.Conclusions RNF8 can promote the proliferation,migration,invasion and EMT of liver cancer cells,and at the same time promote the expression of RhoA.RNF8 promotes the progression of hepatocellular carcinoma by regulating RhoA to promote EMT.