Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective To investigate the CT and MRI findings of different types of small round cell tumor(SRCT)in the nasal cavity and sinuses.Methods A retrospective analysis was conducted on the imaging data and clinical data of 35 SRCT patients confirmed by pathology.Thirty-one SRCT patients underwent CT examination,and 19 SRCT patients underwent MRI examination.Results There were 20 cases of tumors that invaded the nasal cavity and 19 cases involved the sinuses,including 11 cases of the maxillary sinus,7 cases of the ethmoid sinus,2 cases of the sphenoid sinus,and 1 case of the frontal sinus.CT findings of SRCT were all soft tissue masses.Lymphoma was relatively homogeneous with mild bone destruction,and usually involved nasal vestibular skin.Rhabdomyosarcoma(embryonic type)happened at an early age and easily caused bone destruction and metastasis.Melanoma generally occurred in the nasal septum and nasal cavity,which was prone to bleeding.Small cell neuroendocrine carcinoma was heterogeneous,with moderate to significant enhancement,bone absorption and destruction were often noticed.The MRI manifestations of SRCT were equal or long signal on T1WI,high signal on T2WI,and significant diffusion limitation on diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)except for melanoma.On contrast-enhanced images,lymphoma showed mild to moderate enhancement,rhabdomyosarcoma showed typical"grape sign",and small cell neuroendocrine carcinoma showed"sieve"and"map-like"obvious enhancement.Typical melanoma showed a high signal on T1WI and a low signal on T2WI and usually caused bleeding.The MRI findings were related to the presence of melanoma and hemorrhage within the lesion.Conclusion SRCT of the nasal cavity and sinuses have a high degree of malignancy and poor prognosis,CT and MRI have many similar manifestations.Combining clinical data,bone destruction,MRI enhancement,and DWI sequence can effectively distinguish different types of SRCT,as well as squamous cell carcinoma of the nasal cavity and sinuses and adenoid cystic carcinoma.

Objective:To compare the testing effects of different testing methods in the functional inspection of precision surgical scissors and needle holders.Methods:By consulting relevant literature and professional books,three testing methods and materials for precision surgical scissors and needle holders were selected.The cutting performance of the precision surgical scissors were tested by gauze cloth,cotton wool,and silicone film method in the Interlock surgical instrument testing set.The clamping performance of precision needle holder was tested by using light,needle clips,and thread clamping method in the Interlock surgical instrument testing set.100 pieces of precision surgical scissors and needle holders which were qualified for cleaning and disinfection in the hospital were selected for effectiveness testing,and a self-made satisfaction questionnaire to investigate the satisfaction of surgeons with the use of instruments.Results:After 100 precision surgical scissors tested using three methods of gauze,cotton wool,and silicone film,the qualified number of cutting performance was 94,76,and 58,respectively,the difference was statistically significant(x2=36.526,P<0.05).The satisfaction rate of surgeons with the use of precision surgical scissors passed the silicone film test was the highest at 100%,followed by cotton wool cloth at 82.0%,and the gauze method at the worst at 67.0%,the difference was statistically significant(x2=48.439,P<0.05).After 100 precision needle holders were tested by using three methods of light irradiation,needle clamping,and wire clamping,the qualified number of clamping performance was 96,78,and 62,respectively,the difference was statistically significant(x2=38.160,P<0.05).The satisfaction rate of surgeons with the precision needle holders passed the clamp line test was the highest at 100.0%,followed by the clamp needle at 79.0%,and the worst under light at 62.0%,the difference was statistically significant(x2=57.705,P<0.05).Conclusion:The function and quality of precision surgical scissors and needle holders tested by the test objects in Interlock Surgical Instrument Test Suite can objectively and accurately reflect the functional status of surgical scissors and needle holders,provide reference for regular maintenance and upkeep of instruments,and ensure safe use of instruments.

With the rapid development of artificial intelligence technology,small molecule generation models have emerged as a significant research direction in the field of drug discovery.These models,including Generative Adversarial Networks(GANs),Variational Autoencoders(VAEs),and diffusion models,have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures.This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process,demonstrating how they supplement and enhance traditional drug design methods.At the same time,it addresses the challenges facing current methods in terms of data quality,model complexity,computational cost,and generalization ability,with a prospect of future research directions.

Objective To investigate the effect and mechanism of naringin on acute lung injury(ALI)in septic mice.Methods The acute lung injury mouse model of sepsis was established by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide.The mice were randomly divided into control group(injected with equal amounts of saline and phosphate buffer),model group(mouse model of sepsis acute lung injury),naringin group(50 mg·kg-1 naringin injected intraperitoneally 1 hour prior to lipopolysaccharide modeling)and BzATP group(50 mg·kg-1 naringin+5 mg·kg-1 BzATP injected intraperitoneally 1 hour prior to lipopolysaccharide modeling).After modeling,lung tissues were taken 24 h later,lung coefficients were calculated;lung tissue interleukin(-ILβ-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay;the expression of purinergic 2X7 receptor(P2X7R),nucleotide-binding oligomerization structural domain-like receptor protein 3(NLRP3)and nuclear factor-κB(NF-κB)proteins were detected by Western blotting.Results The lung coefficients in the control,model,naringin and BzATP groups were(6.26±0.31),(9.09±1.02),(7.02±0.45)and(8.79±0.55)mg·g-1;the contents of TNF-α were(56.41±0.35),(174.68±1.58),(85.23±1.68)and(162.97±3.42)pg·mL-1;the contents of IL-1β were(44.18±7.37),(119.91±17.16),(85.41±2.14)and(104.57±3.39)pg·mL-1;the contents of IL-10 were(50.82±2.89),(28.31±1.86),(42.82±1.98)and(25.19±1.69)pg·mL-1;P2X7 protein expression levels were 0.45±0.16,1.33±0.10,0.64±0.09 and 1.05±0.18;NF-κB protein expression levels were 0.38±0.19,1.29±0.09,0.57±0.11 and 0.92±0.07;NLRP3 protein expression levels were 0.72±0.14,1.28±0.23,0.75±0.09 and 1.27±0.23.Compared with the model group in the control group and naringin group,compared with the naringin group in the BzATP group,the differences of the above indexes were statistically significant(P＜0.01,P＜0.05).Conclusion Naringin attenuates acute lung injury in septic mice by inhibiting the P2X7 receptor-mediated NF-κB/NLRP3 signaling pathway.

Micro vesicles(MVs)are the membrane structures produced by the direct outgrowth of the cell membrane,which can be involved in the pathogenesis of many diseases;MVs can also be used in the diagnosis of diseases and the prediction of prognosis.In recent years,there are more and more researches related to MVs in the field of sepsis,and the mechanism of MVs in sepsis is now reviewed.

Objective:To investigate the clinical and genetic features of a child with Dyschromatosis symmetrica hereditaria (DSH) and variant of the ADAR1 gene. Methods:A child who was admitted to the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University in June 2020 due to irregular pigmented maculopapular rash on the dorsum of hands was selected as the study subject. Whole exome sequencing (WES) was carried out for the child and his similarly affected father, and Sanger sequencing was used to verify the candidate variant. SWISS-MODEL was used to predict the secondary and tertiary structures of the wild-type and mutant ADAR1 proteins.Results:The child, a 13-year-old boy, had symmetrical hyperpigmented and depigmented spots on the back of his hands and was clinically diagnosed with DSH. WES and Sanger sequencing results showed that he and his father had both harbored a heterozygous c. 2858dup (p.T954Dfs*20) truncating variant in exon 10 of the ADAR1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted as pathogenic (PVS1+ PM2_Supporting+ PM1+ PP3). Conclusion:The c. 2858dup (p.T954Dfs*20) variant of the ADAR1 gene probably underlay the DSH in this pedigree.

Objective:To investigate the safety and efficacy of pulsed Thulium fiber laser enucleation (ThuFLEP) in the treatment of benign prostatic hyperplasia (BPH).Methods:Clinical data of 238 BPH patients who underwent ThuFLEP from November 2022 to November 2023 at Peking University First Hospital were retrospectively analyzed. Patients were divided into two groups based on different surgical techniques: 199 patients underwent traditional continuous-wave Thulium fiber laser prostatectomy (C-ThuFLEP group), and 39 patients underwent Thulium fiber laser enucleation with pulse modulation (P-ThuFLEP group). Propensity score matching was used to balance baseline characteristics between the two groups. Operative time, resected tissue weight, pre- and postoperative hemoglobin decrease, postoperative hospital stay, and postoperative catheterization time were recorded and compared between the matched groups. Intraoperative and short-term postoperative complications were also recorded and compared between the two groups. Follow-up assessments at 1 month postoperatively were conducted to compare the maximum urinary flow rate (Q max), international prostate symptom score (IPSS), international index of erectile function (IIEF-5) score, quality of life (QOL) score, and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) score between the two groups, as well as changes in Q max and IPSS, IIEF-5, and QOL before and after surgery. Results:After matching, a total of 60 patients were included, with 30 patients in each group. There were no statistically significant differences between the two groups in terms of age [(68.73±6.91) years vs. (71.07±7.34) years], American Society of Anesthesiologists (ASA) score (1-2/3-4: 23/7 vs. 23/7), comorbidity count (0-1/>1: 15/15 vs. 15/15), prostate volume [68.3 (50.0, 105.3) ml vs. 63.3 (45.7, 106.0) ml], preoperative IPSS score [24 (21, 29) vs. 23 (14, 26)], IIEF-5 score [5 (0, 15) vs. 5 (0, 13)], and QOL score [5 (4, 6) vs. 5 (5, 6)] (all P>0.05). The tissue removal rate in the P-ThuFLEP group was higher than that in the C-ThuFLEP group [0.82 (0.71, 1.18) g/min vs. 0.72 (0.46, 0.95) g/min, P=0.026], while there were no statistically significant differences between the two groups in operative time [47 (37, 79) min vs. 65 (33, 87) min], resected tissue weight [45 (31, 75) g vs. 33 (22, 65) g], postoperative hemoglobin decrease [17 (10, 23) g/L vs. 12 (7, 19) g/L], postoperative hospital stay [4 (3, 5) days vs. 4 (3, 5) days], and postoperative catheterization time [3 (3, 5) days vs. 3 (3, 6) days]. The incidence of intraoperative complications in both groups was 10% (3/30), with no statistically significant difference ( P=1.000), and no severe complications of grade Ⅲ or above occurred. There were no statistically significant differences in Q max [24 (15, 33) ml/s vs. 16 (10, 32) ml/s], IPSS score [14 (12, 15) vs. 9 (7, 12)], QOL score [2 (1, 3) vs. 2 (1, 3)], and IIEF-5 score [3 (0, 5) vs. 3 (0, 6)] between the C-ThuFLEP and P-ThuFLEP group at 1 month postoperatively (all P > 0.05), and both showed significant improvement compared to preoperative values (all P < 0.05). The ICIQ-SF score in the P-ThuFLEP group was lower than that in the C-ThuFLEP group [0 (0, 4) vs. 4 (3, 8)], with a statistically significant difference ( P=0.033). Conclusions:Compared with traditional continuous-wave Thulium fiber laser prostatectomy, pulse-modulated Thulium fiber laser enucleation demonstrates higher efficiency in tissue removal, lower early postoperative ICIQ-SF score for urinary incontinence, similar risk of intraoperative complications, and can be safely and effectively applied in the surgical treatment of BPH patients.