AIM: To investigate the diagnostic and prognostic value of differential expression of Cyclin D1 and p53 in eyelid tumors.METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(rs=0.71, P<0.05)and TNM stage(rs=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(rs=0.76, P<0.05)and histological subtype(rs=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.

Objective: To investigate the characteristics of temporal and spatial distribution of tuberculosis epidemics in Shache County, Kashgar Region, Xinjiang. Methods: Information on the incidence of tuberculosis in Sacha County from 2019—2021 was collected and spatiotemporally analyzed by applying the circular distribution method, local spatial autocorrelation analysis, hot and cold spot analysis, directional distribution and spatial center of gravity methods. Results : The total number of tuberculosis cases in Shache County in 2019—2021 was 8 345, of which 52.03%were male and 47.97% were female, and the patients were predominantly 60-75 years old. The number of reported incidences of TB in Tagarqi Township, Shache Township, and Chajek Township ranked among the top three in the county. Spring and summer were the disease-prone seasons for TB, and mid-March to mid-July was the period of high disease incidence. Misha Township and Ishkuli Township are the “high and high” gathering areas, while the “low and low” gathering areas are mainly concentrated in Khoshrav Township and Karasu Township. The hotspots of TB incidence in Shache county were Tagarqi township, Misha township, and Ishkuli township. During the study period, the center of gravity of TB incidence in Shache county of Kashgar area gradually shifted from the southwest to the northeast. Conclusion In Shache county, there is a certain degree of aggregation of tuberculosis outbreaks, with more men than women reporting illnesses, a larger proportion of older people, and a strong seasonal incidence of the disease, with Mixia township and Ishikuli township being the key areas of incidence. Relevant departments should continue to strengthen the disease surveillance of key populations and regions during the high incidence of tuberculosis, and take appropriate intervention measures to reduce the risk of tuberculosis transmission.

Organoids have become an important technological platform in cancer research,but simulating the primary tumor tissue structure and function still presents problems.The development of gene-editing technology,especially when combined with tumor organoids,provides a new approach for accurately and comprehensively simulating the in vivo characteristics of tumor models.Introducing specific gene mutations or correcting mutations in tumor organoids through gene-editing technology can allow detailed analysis of the mechanisms of tumor initiation and progression,as well as exploring potential therapeutic targets,accelerating the drug-screening process,and providing new insights for personalized cancer treatment.This article reviews the formation of tumor organoids and the technical aspects of gene-editing strategies,emphasizing their unique applications and prospects in tumor organoids.We also propose that accurately simulating the in vivo microenvironment,promoting the standardization and stability of organoid gene-editing technology,and optimizing the efficiency of gene editing can accelerate the application of organoids in precision medicine research.

Objective To systematically construct patient-derived tumor organoid(PDO)and patient-derived xenograft(PDX)models of prostate cancer(PCa),and to explore the inhibitory effect and mechanism of gambogic acid(GA)on PCa.Methods The PubChem,SwissTargetPrediction,SuperPred,SEA,GeneCards,OMIM,and STRING databases,and the Venny 2.1.0 online website,Cytoscape 3.8.2,and DAVID software were used to construct a protein-protein interaction network.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were carried out,and visualization processing was performed to identify the targets and pathways of GA acting on PCa.GA was applied to PDOs and PCa cells(22Rv1,PC3,and DU145)for 48 hours and its effects on cell viability were assessed by CellTiter-Glo and CCK-8 assays.Changes in gene and protein levels of the targets were analyzed by quantitative real-time polymerase chain reaction and Western Blot,respectively.The PDX model was treated with GA and the tumor volume and weight were measured.Changes in expression levels of the targets in tumor tissues were detected by immunohistochemistry.Results Network pharmacology identified signal transducer and activator of transcription 3(STAT3)as the core target of GA inhibiting PCa,related to the hypoxia-inducible factor(HIF)-1α signaling pathway.GA reduced the viability of cells and PDOs and significantly down-regulated HIF-1α,STAT3,and P-STAT3 protein levels.In vivo experiments,tumor volume and weight were significantly reduced in the GA group,and immunohistochemistry showed that STAT3 and HIF-1α expression levels were decreased.Conclusions The clinically representative PDO and PDX models,combined with cell lines,verified the prediction result of network pharmacology,confirming a significant killing effect of GA on PCa,possibly via a mechanism related to the STAT3/HIF-1α signaling pathway.

Objective To systematically construct patient-derived tumor organoid(PDO)and patient-derived xenograft(PDX)models of prostate cancer(PCa),and to explore the inhibitory effect and mechanism of gambogic acid(GA)on PCa.Methods The PubChem,SwissTargetPrediction,SuperPred,SEA,GeneCards,OMIM,and STRING databases,and the Venny 2.1.0 online website,Cytoscape 3.8.2,and DAVID software were used to construct a protein-protein interaction network.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were carried out,and visualization processing was performed to identify the targets and pathways of GA acting on PCa.GA was applied to PDOs and PCa cells(22Rv1,PC3,and DU145)for 48 hours and its effects on cell viability were assessed by CellTiter-Glo and CCK-8 assays.Changes in gene and protein levels of the targets were analyzed by quantitative real-time polymerase chain reaction and Western Blot,respectively.The PDX model was treated with GA and the tumor volume and weight were measured.Changes in expression levels of the targets in tumor tissues were detected by immunohistochemistry.Results Network pharmacology identified signal transducer and activator of transcription 3(STAT3)as the core target of GA inhibiting PCa,related to the hypoxia-inducible factor(HIF)-1α signaling pathway.GA reduced the viability of cells and PDOs and significantly down-regulated HIF-1α,STAT3,and P-STAT3 protein levels.In vivo experiments,tumor volume and weight were significantly reduced in the GA group,and immunohistochemistry showed that STAT3 and HIF-1α expression levels were decreased.Conclusions The clinically representative PDO and PDX models,combined with cell lines,verified the prediction result of network pharmacology,confirming a significant killing effect of GA on PCa,possibly via a mechanism related to the STAT3/HIF-1α signaling pathway.

Objective To investigate the effect of four traditional Chinese drugs for reinforcing kidney combined with Tongqiao Huoxue Decoction on serum neurotransmitters and neurological func-tion in patients with post-stroke cognitive impairment(PSCI).Methods A total of 110 patients with PSCI were randomly divided into treatment group and control group,with 55 cases in each group.The control group was treated with donepezil tablet,while the treatment group was treated with four tradi-tional Chinese drugs for reinforcing kidney and Tongqiao Huoxue Decoction on the basis of the control group.The total effective rate,the Mini-Mental State Examination(MMSE)score,the Montreal Cogni-tive Assessment(MoCA)score,the National Institutes of Health Stroke Scale(NIHSS)score and the Barthel Index(BI)as well as serum levels of acetylcholine(ACh),dopamine(DA),norepinephrine(NE),5-hydroxytryptamine(5-HT),neuron-specific enolase(NSE),visinin-like protein-1(VILIP-1),myelin basic protein(MBP),and heat shock protein 70(HSP70)before and after treatment were compared between the two groups.Adverse reactions in both groups were recorded.Results The total effective rate was 90.91％in the treatment group,which was significantly higher than 76.36％in the control group(P＜0.05).After treatment,the MMSE score,MoCA score and BI as well as serum levels of ACh,DA,NE,5-HT and HSP70 in the treatment group were significantly higher than those in the control group,while the NIHSS score and serum levels of NSE,VILIP-1 and MBP were significantly lower than those in the control group(P＜0.05).The total incidence rate of adverse reactions in the treatment group and the control group was 12.73％and 9.09％respectively,which showed no significant between-group difference(P＞0.05).Conclusion Four traditional Chinese drugs for reinforcing kidney combined with Tongqiao Huoxue Decoction can promote the secretion of cognition-related neurotransmitters in patients with PSCI,accelerate the repair of neurological damage,and safety is relatively high.

Organoids have become an important technological platform in cancer research,but simulating the primary tumor tissue structure and function still presents problems.The development of gene-editing technology,especially when combined with tumor organoids,provides a new approach for accurately and comprehensively simulating the in vivo characteristics of tumor models.Introducing specific gene mutations or correcting mutations in tumor organoids through gene-editing technology can allow detailed analysis of the mechanisms of tumor initiation and progression,as well as exploring potential therapeutic targets,accelerating the drug-screening process,and providing new insights for personalized cancer treatment.This article reviews the formation of tumor organoids and the technical aspects of gene-editing strategies,emphasizing their unique applications and prospects in tumor organoids.We also propose that accurately simulating the in vivo microenvironment,promoting the standardization and stability of organoid gene-editing technology,and optimizing the efficiency of gene editing can accelerate the application of organoids in precision medicine research.

Objective To construct a patient-derived pancreatic tumor organoid(PDO)and evaluate its effectiveness.Methods We collected fresh surgical specimens from pancreatic cancer patients for PDO culture and compared the pathological and genetic characteristics of the PDO model with those of primary tumors.The PDO model was used to evaluate the efficacy of clinical chemotherapy drugs,and the effectiveness of the model was assessed.Results A PDO model of pancreatic cancer was successfully established.Histomorphological analysis indicated that the PDO model maintained the basic pathological characteristics of the primary tumor.Whole-exon sequencing showed that both the organoids and original tumor tissue remained consistent in their gene mutation type and characteristics.Drug screening tests revealed that the PDO model had good sensitivity to gemcitabine and irinotecan.Conclusions A pancreatic cancer PDO was successfully constructed that reflected the histological and genetic characteristics of the original tumor.The model was shown to be effective for drug sensitivity experiments in vitro and is expected to have implications for precision medicine assays.

Objective To evaluate the effectiveness of a 1470 nm semiconductor laser therapeutic instrument(referred to as a curestar therapeutic instrument)for prostatectomy in Beagle dogs.Methods Twenty-eight adult male Beagle dogs were randomly divided into three groups:sham(n=3),experimental(n=15),and control(n=10).The experimental group was further divided into three subgroups:120 W/50 W,150 W/50 W,and 160 W/50 W for vaporization cutting/coagulation hemostasis.The control group was divided into two subgroups:120 W/50 W and 150 W/50 W with five in each subgroup.Experimental and control groups underwent canine prostatectomy through the entrance of the bladder neck under electrocision.The operational suitability and effectiveness of the product during surgery were assessed.After the operation,the general condition of the dogs was observed,and blood biochemical and hematological indicators were measured before,immediately after,and at 3,7,and 28 days after the operation.At 1 h and 4 weeks after surgery,B-ultrasound and electric resection were performed under anesthesia to observe the conditions of the urethra and prostate,and prostatic tissue was subjected to HE staining for pathological observations.The thickness of the coagulation layer at 1 h after the operation and repair of the urothelial epithelium at 4 weeks were analyzed.Results During the operation,experimental and control groups had good operability and showed good vaporization cutting and coagulation hemostasis performance.After the operation,no significant effects were observed on the general condition,and blood biochemical and hematological indicators of the dogs.Ultrasound showed that the urethral expansion was visible immediately after the operation,and the echo of the urethral epithelium was slightly enhanced.At 4 weeks,the prostate tissue had a slightly low echo with uniformly distributed small point-like echoes inside,and the capsule had a linearly high echo,consistent with the sham group.The weight of the vaporized prostate tissue in experimental and control groups was 0.91～1.33 g with a resection rate of 17.11％～20.27％.As the power of vaporization cutting increased,the laser emission time gradually decreased,while the vaporization cutting speed and efficiency both increased.However,no significant difference was found between experimental and control groups(P＞0.05).Under the electrocision microscope,a burn-like change was observed in the surgical wounds of the prostate urethra in experimental and control groups at 1 h after surgery,and the boundary between the wound and normal urothelium was visible.At 4 weeks,the urothelium of the prostate had been repaired and flattened,and the boundary with the surrounding normal urothelium was blurred.Similarly,pathological observations showed that experimental and control groups had significant damage to the prostate urethral orifice at 1 h after surgery with a small amount of carbonization and coagulative necrosis on the surface of the wound,a small amount of inflammatory cell infiltration,and a coagulation layer thickness of approximately 0.4 mm.At 4 weeks,the prostate urethral morphology of the sham group was normal,whereas experimental and control groups showed new epithelial growth covering the wound with a uniform thickness and no coagulative necrosis tissue attached to the wound.A mild inflammatory reaction was still present in the surrounding area,fibroblast proliferation was obvious,and stromal and epithelial cell proliferation was visible in the surrounding prostate,some of which showed squamous metaplasia.The prostate capsule was intact and the morphology of the surrounding nerves and blood vessels was normal.Conclusions The curestar therapy instrument is effective for prostatectomy in Beagle dogs with good vaporization cutting and coagulation hemostasis performance.No significant difference was found in postoperative physiological indicators compared with the sham group.

Objective To establish a rat model of hyperuricemic nephropathy(HN)using a multifactorial induction method of potassium oxazinate combined with adenine and yeast feed to observe the intervention effect of Qiling granules(QLG).Methods Fifty-eight SPF-grade male SD rats were selected,and 10 rats were randomly allocated to the normal control(NC)group.The remaining rats were induced by multiple factors to establish HN rat models.After 2 weeks of modeling,submandibular blood samples were taken to detect serum UA,CREA,BUN,TG,and TC.Forty HN rats with bleeding clearance UA and body weight close to the mean were selected.They were randomly divided into a model(M)group,QLG low dose(QLG-L)groups,QLG high dose(QLG-H)group,and a positive control(PC)group,with 10 rats in each group,using a stratified randomization method.Each group was given corresponding drugs by gavage daily,and after continuous administration for 4 weeks,submandibular blood samples were taken to detect serum UA,CREA,BUN,TG,and TC.After euthanasia of the rats,liver tissue was taken to detect XOD and ADA activity.Renal tissue was taken for HE and Gomori hexamine silver staining,and the protein expression of GLUT9,OAT1,VCAM-1,and TGF-β in the kidneys was observed using immunohistochemistry and Western blot method.Results Compared with the NC group,the M group's serum levels of UA,CREA,BUN,TC,and TG,as well as liver XOD and ADA activities,were significantly increased(P＜0.01).The renal tissue of the model rats showed significant pathological changes.The area of renal tubules positive for urate and the expression of GLUT9,VCAM-1,and TGF-β proteins in the kidneys were significantly increased(P＜0.01,P＜0.05),while the expression of OAT1 was significantly reduced(P＜0.01).Compared with the M group,each treatment group showed significantly reduced serum UA levels,liver XOD,ADA activity,and renal VCAM-1 protein expression(P＜0.01,P＜0.05).The serum CREA and BUN levels and renal TGF-β protein expression of rats in the QLG-L group were significantly reduced(P＜0.05,P＜0.01).The serum CREA and BUN levels and renal GLUT9 protein expression of rats in the QLG-H group were also significantly reduced(P＜0.01,P＜0.05).The urate deposition and renal injury caused by each treatment were reduced to varying degrees,but there were no significant differences among groups(P＞0.05).Conclusions A stable HN rat model can be induced by gavage of potassium oxyzinate and adenine in combination with yeast feed.QLG can effectively treat HN by improving UA metabolic disorders,reducing the renal inflammation and urate deposition that cause renal damage in HN model rats.Its mechanism of action is related to a reduction in serum UA,CREA,BUN,and TG levels;liver XOD and ADA activities;and the expression of GLUT9,OAT1,VCAM-1,and TGF-β proteins in the kidneys.