ObjectiveTo explore the protective effect and mechanism of Gegen Qianliantang （GQT） on intestinal mucosal barrier function in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） model mice. MethodsA UC model was established in C57BL/6 mice using a 2.5% DSS solution. Mice were randomly divided into five groups （n=8 per group）： blank group， model group， mesalazine sustained-release granule group （0.52 g·kg^-1）， high-dose GQT group （2.23 g·kg^-1）， and low-dose GQT group （1.12 g·kg^-1）. Fecal characteristics and body weight changes were observed before and after treatment. The body weight loss and disease activity index （DAI） of UC mice were calculated to evaluate symptom severity. Hematoxylin-eosin （HE） staining and Alizarin blue-periodic acid-Schiff （AB-PAS） staining were used to detect histological changes in colon tissue. Immunohistochemistry was used to detect the expression of zonula occludens-1 （ZO-1） and mucin 2 （MUC2）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pro-inflammatory cytokines interferon-γ （IFN-γ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-17A， and anti-inflammatory cytokine IL-10. Flow cytometry was used to detect the activation of helper T lymphocyte subsets （Th1， Th17）， regulatory T cells （Treg）， and regulatory B cells （Breg） in spleen and colon tissues. Western blot was used to detect the expression levels of T-bet， forkhead box protein P3（FoxP3）， nuclear transcription factor（NF）-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， signal transducer and activator of transcription 3（STAT3）， and phosphorylated STAT3 （p-STAT3）. ResultsCompared with the model group， both high- and low-dose GQT groups significantly improved the body weight loss and DAI scores （P<0.05）， alleviated colonic inflammation， and showed optimal efficacy in the high-dose group. AB-PAS staining showed that compared with the model group， both the high- and low-dose GQT groups significantly increased goblet cell proliferation and mucin secretion， indicating improved mucosal barrier function. GQT upregulated the expression of ZO-1 and MUC2 in colon tissue （P<0.05）， suppressed IFN-γ， IL-6， and TNF-α secretion （P<0.05）， elevated IL-10 secretion （P<0.05）， but had no significant effect on IL-17A. At the same time， high- and low-dose GQT intervention increased the activation of CD4⁺ FoxP3⁺ Treg cells （P<0.05） and suppressed activation of CD4⁺ IFN-γ⁺ Th1 cells （P<0.05）. Western blot showed that GQT downregulated T-bet， NF-κB p65， and STAT3 protein expression （P<0.05）， upregulated FoxP3 （P<0.05）， and also reduced phosphorylation levels of p-NF-κB p65 and p-STAT3 （P<0.05）. ConclusionGQT can upregulate the activation of CD4⁺ FoxP3⁺ Treg cells， reduce the activation of CD4⁺ IFN-γ⁺ Th1 cells， inhibit the secretion of IFN-γ， IL-6， and TNF-α， and increase the secretion of IL-10. It enhances the expression of MUC2 and ZO-1 in colon tissue， thereby alleviating inflammatory damage to the intestinal mucosa and restoring mucosal barrier integrity. These effects may be related to its regulation of NF-κB p65 and STAT3 signaling pathways， ultimately regulating the activation of transcription factors T-bet and FoxP3.

The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

The dysregulation of cyclin-dependent kinase 12(CDK12),which may result from genomic alterations or modulation by upstream effectors,is implicated in cancer oncogenesis and progression.CDK12 over-expression or activation is sufficient to induce tumor initiation,recurrence,and therapeutic resistance.However,CDK12 may also exert tumor-suppressive functions in a context-dependent manner.Therefore,caution is warranted when targeting CDK12 in future clinical trials.A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance pre-cision oncology.This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer.Subsequently,we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts.Finally,we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology,offering insights into future directions for innovative cancer treatment strategies.

Background: The global rise in visual impairment, driven by population aging, the increasing prevalence of lifestyle-related chronic diseases, and environmental factors, has made it a critical public health concern, highlighting the urgent need for effective preventive strategies and eye health maintenance. Cuscutae Semen (CS), a traditional Chinese herbal medicine long regarded for its vision-enhancing properties, has been widely used to support ocular health. However, its underlying molecular mechanisms and bioactive constituents remain poorly understood, limiting its modernization and broader clinical application. Objective: This study aims to investigate the restorative effects of CS on visual impairment, elucidate its underlying mechanisms, and identify potential active components. Methods: A zebrafish model of visual impairment was established using mepanipyrim to simulate retinal structural damage and visual dysfunction. The therapeutic effects of CS were systematically evaluated through behavioral analyses and histomorphological observations. To elucidate the underlying mechanisms, an integrated approach was employed, combining transcriptome sequencing (RNA-seq), reverse transcription quantitative polymerase chain reaction validation, and immunofluorescence staining to identify critical genes and pathways involved. Furthermore, macroporous resin column chromatography was employed for the fractionation and screening of potential active components. Results: CS treatment significantly alleviated mepanipyrim-induced ocular abnormalities in zebrafish, restoring approximately 82% of the observed morphological defects. Behavioral assessments revealed that CS-treated zebrafish exhibited markedly increased swimming speed and distance, indicating enhanced visual light sensitivity. Histopathological analysis demonstrated that CS effectively repaired the structure of retinal cell layers. RNA-seq revealed that CS broadly reversed mepanipyrim-induced gene expression disturbances, suggesting a restorative effect on transcriptomic homeostasis. Gene Ontology enrichment analysis identified the phototransduction pathway as a key mediator of CS’s therapeutic effects. This was further supported by reverse transcription quantitative polymerase chain reaction validation of critical genes and immunofluorescence staining, which confirmed the restored expression of Pde6a and Gnat2, key proteins involved in photic signal transmission. Active component screening indicated that high-polar constituents, including chlorogenic acid, may constitute one of the major bioactive fractions responsible for the observed therapeutic effects. Conclusion: This study provides evidence of the vision-protective effects of CS in a zebrafish model, demonstrating that its therapeutic mechanism involves modulation of the phototransduction pathway. Chlorogenic acid was identified as one of the key bioactive constituents contributing to this effect. These findings not only provide scientific validation for the traditional use of CS in ocular protection but also present promising therapeutic prospects for the prevention and treatment of visual impairment.

Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

A case is presented involving a patient with a history of pelvic fracture who experienced progressive difficulty in urination following the removal of a urethral catheter. Attempt to retain the catheter was unsuccessful, leading to an ultrasound-guided suprapubic puncture cystostomy. Subsequently, the patient developed persistent abdominal pain, distension, nausea, and vomiting. Analysis of turbid greyish-yellow thin purulent fluid obtained during abdominal paracentesis indicated the presence of peritonitis. Urgent surgical exploration revealed that the diversion tube had passed through the abdominal cavity and into the bladder. The entire abdominal cavity was filled with yellowish-thin purulent fluid. Intraoperatively, the patient presented with worsening hypotension, tachycardia, oliguria, and decreased skin temperature, suggestive of septic shock resulting from peritonitis. Prompt management, including antimicrobial therapy, hemodynamic support, and fluid resuscitation, successfully controlled the infectious symptoms, leading to complete recovery. In clinical practice, the emphasis is often placed on assessing injuries to intra-abdominal organs, whereas awareness and understanding of peritoneal injuries remain limited. As a result, postoperative peritonitis is frequently attributed solely to intra-abdominal organ damage, overlooking the potentially grave consequences of pure peritoneal injury. Therefore, it is imperative to enhance our recognition and knowledge regarding peritoneal injuries, enabling timely diagnosis and treatment to prevent the occurrence of complications.

Urinary tract infection (UTI) is one of the most common infectious diseases. It has the characteristics of high recurrence rate and prolonged course. At present, the problem of antibiotic resistance is becoming more and more serious, the incidence of adverse reactions is high, and the disadvantages of long-term administration appear, which brings severe challenges to the treatment of recurrent urinary tract infection. The prevention and treatment of UTI recurrence has become the focus of research. Recurrent urinary tract infection is related to the immune regulation mechanism of the body. Administration of immune regulation can provide new ideas for prevention and treatment. The vaccine based on immune regulation to prevent rUTI has made some progress. It can not only reduce the frequency of recurrences, but also decrease related symptoms. At the same time, the vaccine has good tolerance, high safety and good application prospect. This paper aims to summarize the progress of immune regulation and immune vaccines in vivo and clinical research.

Objective:To compare the outcomes of combined lingual mucosal graft with buccal mucosal graft urethroplasty and combined lingual mucosal graft with ADM (acellular dermal matrix) urethroplasty for the treatment of repair failed hypospadias.Methods:From February 2017 to February 2019, 26 patients with failed hypospadias repairs were treated with combined lingual mucosal graft with buccal mucosal graft urethroplasty (14 cases in Group A), and combined lingual mucosal graft with ADM urethroplasty (12 cases in Group B). The mean age of Group A was (29.5±1.2) years (range 18.0-41.0 years), and (26.5±0.8) years (range 20.0-38.0 years) in Group B. The previous operation times was mean (3.6±0.7)(range 2-5 times) and (4.6±0.8)(range 3-5 times) in Group A and Group B respectively. Operation method: All patients were nasally intubated, the remaining curvature was corrected, the fibrous tissue or scar was removed, and the defected urethra was measured. In Group A, the lingual mucosa was spread and fixed to the corpora cavernosa over the midline as the urethral plate, the buccal mucosa was covered the lingual mucosa as ventral urethra, both the mucosa lateral edges was sutured. In Group B, the lingual mucosa was harvested and fixed to the corpora cavernosa the same as in Group A, the ADM was made appropriate length and width, covered and sutured with the lingual mucosa. The lingual mucosa was harvested mean (5.0±0.2)cm(range 4-6cm)long, mean (1.2±0.2)cm (range 1.0-1.5cm)wide and mean (5.0±0.2)cm(range 5-6cm)long, mean (1.2±0.2)cm (range 1.0-1.5cm)wide in Group A and Group B respectively( P<0.05). In Group A, the buccal mucosa was harvested mean (4.1±0.2)cm(range 3.5-5.5cm)long, mean (1.2±0.2)cm wide. Criteria for successful repair of hypospadias were set as: ①The appearance of the penis is nearly normal; ②The penis curvature was corrected; ③Urethra orifice in normal position; ④Urine flow line is normal. The outcomes of the two groups were analyzed and compared, statistical analysis was done using SPSS 18.0 software. Results:The mean follow-up time was (16.3±1.6)(8-24) months. The age, number of preoperative surgeries, number of previous oral mucous membranes, and length of urethral defects were no statistically significant differences between the two groups in A and B( P>0.05). The length of oral mucosa was harvested during the operation between group A and Group B were statistically significant differences( P<0.05). The incidence of oral complications in group A and B: Oral pain 7/14, 1/12; The feeling of tension in mouth 8/14, 1/12; The numbness in the oral 8/14, 1/12, A and Group B were statistically significant differences( P<0.05). The incidence of urethral complications in group A and Group B: the urethra fistula 1/14, 4/12; the urethral stricture 2/14, 6/12, there were statistically significant differences between the two groups ( P<0.05). Penile curvature 2/14, 1/12, ( P>0.05). The success rate was 12/14 and 5/12 in Group A and B respectively, with statistical difference( P<0.05). Conclusions:Combined lingual mucosal graft with buccal mucosal graft urethroplasty could be a good choice for repeated failed hypospadias repairs. Combined lingual mucosal graft with ADM urethroplasty has many complications and less success, should be performed in caution.

Testicular/paratesticular mucinous cystadenoma is a rare type of ovarian epithelial tumor. This paper reported a patient with enlarged left testicle , and CT showed a multifocal cystic mass in left testis. Radical left testis orchiectomy was performed, and the pathology showed testicular borderline mucinous cystadenoma. The patient was followed up for 3 years and no recurrence and metastasis was observed.