Currently, researchers have identified several mutated genes associated with hereditary eye diseases; however, effective therapeutic options remain scarce. The emergence of clustered regularly interspaced short palindromic repeats(CRISPR)and its associated proteins(CRISPR-associated proteins, Cas)offers a promising approach for treating these diseases. CRISPR/Cas9 enables precise targeting and modification of specific genetic sequences, allowing for the correction of mutated genes, as well as knockout or replacement of pathogenic genes to achieve therapeutic effects. In ophthalmology, CRISPR/Cas9 has been applied to various hereditary eye disorders, including corneal dystrophy, congenital cataracts, glaucoma, and retinitis pigmentosa. Additionally, significant progress has been made to utilize CRISPR/Cas9 to develop disease models. Therefore, it has great potential for clinical applications. However, challenges such as delivery efficiency and off-target effects remain. This review summarizes the mechanism of CRISPR/Cas9, its applications in genetic eye diseases and disease models, as well as the existing challenges, aiming to provide new insights for treatment.

OBJECTIVE To investigate the effect of astragaloside Ⅳ（AST） on the injury of arterial endothelial tissue in rats with intracranial aneurysms （IA）， and to explore its mechanism of action based on the nuclear factor κB （NF-κB）/nucleotide- binding domain leucine-rich repeat and pyrin domain-containing protein 3 （NLRP3） signaling pathway. METHODS Rats were divided into Sham group （intragastric administration and intraperitoneal injection of the same volume of normal saline）， IA group （intragastric administration and intraperitoneal injection of the same volume of normal saline）， AST low-dose group （AST-L group， intragastric administration of 40 mg/kg AST）， AST high-dose group （AST-H group， intragastric administration of 80 mg/kg AST）， AST-H+HY-N2485 group [intragastric administration of 80 mg/kg AST and intraperitoneal injection of 25 mg/kg HY-N2485 （activator of NF-κB/NLRP3 signaling pathway）]. They were given relevant medicine， once a day， for 8 consecutive weeks. After last medication， the levels of inflammatory factors [serum tumor necrosis factor-α （TNF-α）， interleukin-18 （IL-18）， IL-6] and vascular endothelial growth factor （VEGF） and endothelin （ET） were detected； the morphology of IA was observed； the expressions of von Willebrand factor （vWF）， vascular cell adhesion molecule-1 （VCAM-1）， endothelial nitric oxide synthase （eNOS）， and NF-κB/NLRP3 pathway related proteins in vascular tissue were also determined. RESULTS Compared with the Sham group， the basilar arterial ring of rats in the IA group had obvious protrusions， and the arterial vascular endothelial cells were significantly damaged. The levels of inflammatory factors， VEGF and ET in serum， as well as the expression levels of vWF， VCAM-1 and NLRP3 proteins and the phosphorylation level of NF-κB protein in vascular tissues were increased significantly （P＜ 0.05）. Aneurysms and ruptures of the internal elastic layer were significantly increased （P＜0.05）， while the expression level of eNOS protein was significantly decreased （P＜0.05）. Compared with IA group， the morphology of IA and the levels of above indexes were all improved significantly in AST-L and AST-H groups （P＜0.05），and the improvement in the AST-H group was more significant than that in the AST-L group （P＜0.05）； HY-N2485 could attenuate the improvement effect of AST on vascular endothelial tissue damage in IA rats （P＜0.05）. CONCLUSIONS AST may inhibit the expression of inflammatory factors， alleviate inflammation and vascular endothelial tissue damage in IA rats by inhibiting NF- κB/NLRP3 signaling pathway，thereby inhibiting the formation of IA. active_999@sina.com

The 2025 European Lung Cancer Congress (ELCC) convened in Paris, France, centering on the optimization and innovation of immunotherapy for non-small cell lung cancer (NSCLC). Key topics at the congress included the application strategies for perioperative immunotherapy, breakthroughs in combination therapy models for advanced NSCLC, and the emerging roles of biomarkers in predicting diverse treatment outcomes. This paper integrates data from several key pivotal studies to systematically analyze the clinical value of neoadjuvant therapy within the perioperative setting, the potential of targeted combination regimens, and the challenges of managing drug resistance, thus offering new directions for clinical practice.

Objective To study the influence of the radius of the active zone of the plane source and the horizontal distance between the source center and the center of the detection window on the detection efficiency of low-background α/β measuring instruments. Methods The geometric factor was calculated under different conditions in MATLAB, and a traceable plane source was used to test and analyze two commonly used measuring instruments. Results With the other parameters unchanged, when the radius of the active zone R₁ = 9 mm, the G value was greatest; and when the horizontal distance a = 0 mm, the G value was greatest. According to the calculation formula of the verification regulation, for the ⁹⁰Sr-⁹⁰Y planar source, at the maximum value of a, the detection efficiency of FYFS-400X was 1.2% lower, and that of MPC-9604 was 3.2% lower; for the ²⁴¹Am planar source, the detection efficiency of MPC-9604 was 1.9% lower at the maximum value of a. Conclusion The geometric factor decreases with the increase in the radius of the active zone and the horizontal distance between the source center and the center of the detection window. At the central position, the geometric factor has less influence on the relative standard uncertainty of detection efficiency. When using a standard plane source for counting, measures should be taken to ensure that the plane source is always centrally located in the sample tray.

OBJECTIVE To establish HPLC fingerprint of Shuangdong capsules， and to study the spectral effect relationship of its anti-inflammatory effect. METHODS The fingerprints of 15 batches of Shuangdong capsules were established by HPLC，and the similarity evaluation was carried out； the foot swelling model was established to investigate the anti-inflammatory activity of Shuangdong capsules. The gray correlation analysis method was used to construct the spectral effect relationship for the anti- inflammatory effect of Shuangdong capsules using the swelling rate of rat foot and the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， prostaglandin E2 （PGE2）， interleukin-6 （IL-6）， IL-8， IL-1β and tumor necrosis factor-α （TNF-α） in right hindfoot tissues as the pharmacodynamic indexes of anti-inflammatory effects. RESULTS Overall 15 batches of Shuangdong capsules identified 20 common peaks， the similarities were all greater than 0.97， and a total of 8 chromatographic peaks were identified. According to the gray correlation analysis， the correlation degrees between the peak area and the foot swelling rate and the levels of MDA， SOD， PGE2， IL-6， IL-8， IL-1β and TNF-α in 15 batches of Shuangdong capsules were 0.621 1- 0.783 5， 0.564 3-0.827 9， 0.581 0-0.845 3， 0.564 9-0.855 0， 0.583 1-0.856 4， 0.576 5-0.863 5， 0.564 1-0.838 0 and 0.572 5- 0.851 3， respectively. Among them， the chemical components represented by peak 4 （geniposidic acid）， peak 10 （chlorogenic acid） and the chemical composition represented by peak 2 were strongly correlated with anti-inflammatory efficacy indicators. CONCLUSIONS In this study， HPLC fingerprints of 15 batches of Shuangdong capsules were successfully established. Among them， geniposidic acid， chlorogenic acid may be its anti-inflammatory ingredients.

Objective·To explore the role of advanced platelet-rich fibrin(A-PRF)in osteochondral regeneration.Methods·Bone-marrow mesenchymal stem cells(BMSCs)and knee joint chondrocytes were obtained from New Zealand rabbits.A-PRF was obtained by low-speed centrifugation of the heart blood of rabbits.The histological structure of A-PRF was observed by an optical microscope.The release of growth factors in A-PRF was detected by ELISA,including platelet-derived growth factor,transforming growth factor-β,insulin-like growth factor,vascular endothelial growth factor,epidermal growth factor and fibroblast growth factor.A-PRF's cytotoxicity and capability for promoting the proliferation of rabbit BMSCs were detected by live/dead double staining and MTT methods.The effect of A-PRF on the gene expression of type Ⅱ collagen,aggrecan,alkaline phosphatase(ALP)and osteocalcin(OCN)in rabbit BMSCs was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Transwell chambers were used to determine the effect of A-PRF on the migration ability of rabbit BMSCs and the chondrocytes.Rabbit knee osteochondral defect models were established,and 18 rabbits were randomly divided into 3 groups.The A-PRF group(n=6)was implanted with A-PRF in the defect,the A-PRF+BMSCs group(n=6)was implanted with rabbit BMSCs on A-PRF,and the control group(n=6)did not undergo implantation.The rabbits were sacrificed 12 weeks after surgery and the knee joint specimens were stained with hematoxylin-eosin(H-E),toluidine blue and safranin O/fast green.Based on the surface morphology and histology of the knee joints,the International Cartilage Repair Society(ICRS)scoring system was used for macroscopic and histological scoring.Results·A-PRF had a loose network structure and can slowly release growth factors.No cytotoxicity to rabbit BMSCs was observed after adding A-PRF,and the the capability for promoting the proliferation of rabbit BMSCs was significantly increased at 24,48 and 72 h after adding A-PRF(all P<0.05).Chondrogenesis-related gene Ⅱ collagen and aggrecan,as well as osteogenesis-related genes ALP and OCN were significantly up-regulated(all P<0.05).After adding A-PRF,the migration abilities of rabbit BMSCs and chondrocytes were significantly enhanced(both P<0.05),and the migration ability of rabbit BMSCs was significantly higher than that of chondrocytes(P=0.025).The joint surface morphology in the rabbit knee joint defect models was observed.It can be seen that the defects in the A-PRF group and the A-PRF+BMSCs group were basically restored,while the the defects in the control group were only covered by soft tissue.In the ICRS macroscopic score,there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group,but the scores of the two groups were all significantly higher than those of the control group(all P<0.05).According to the histological results,both the A-PRF group and the A-PRF+BMSCs group formed osteochondral repair,but the cartilage in the A-PRF group was more mature,while the control group formed fibrous repair.In the ICRS histological score,there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group,but the scores of both the groups were significantly higher than those of the control group(both P<0.05).Conclusion·Autologous A-PRF has good biocompatibility and the capability for promoting the proliferation of BMSCs.It can promote the repair of cartilage and subchondral bone both in vitro and in vivo.

Chronic myelomonocytic leukemia(CMML)complicated with immune thrombocytopenia(ITP)is rare.This article reports the clinical data of a patient with CMML complicated with ITP treated with a combination of venetoclax,ripertamab(an anti-CD20 monoclonal antibody),and hetrombopag.The coexistence mechanism of CMML and ITP needs to be further clarified.Venetoclax combined with anti-CD20 monoclonal antibody and thrombopoietin receptor agonist may be an effective strategy for the treatment of this complication.

Objective To investigate the correlation between MEX3A and differentiation characteristics of gastric cancer and intestinal metaplasia,and its combination with caudal-related homeobox transcription factor 2(CDX2)and mucin 2(MUC2)and mucin 5AC(MUC5AC)to determine the role of carcinogenic intestinal metaplasia.Methods From January 2010 to December 2014,a total of 410 cases of gastric cancer and paracarcinoma paraffin-embedded tissue samples were selected from the Central Hospital Affiliated to Shenyang Medical College and the Second Hospital Affiliated to Shenyang Medical College.According to pathological diagnosis,they were divided into control group(mild superficial gastritis,79 cases),intestinal metaplasia group(149 cases)and gastric cancer group(182 cases).The expressions of MEX3A,CDX2,MUC2 and MUC5AC were detected by immunohistochemistry.Results MEX3A was highly expressed in gastric cancer group and intestinal metaplasia group,especially diffuse gastric cancer,poorly differentiated gastric cancer and type Ⅲ intestinal metaplasia(P<0.05).CDX2 and MUC2 were highly expressed in gastric cancer group and intestinal metaplasia group,especially intestinal type gastric cancer,highly and moderately differentiated gastric cancer,type Ⅰ and type Ⅱ intestinal metaplasia(P<0.05).The expression of MUC5AC was high in control group and low in gastric cancer group and intestinal metaplasia group,especially in intestinal type gastric cancer,type Ⅰ and type Ⅲ intestinal metaplasia(P<0.05).Gastric cancer and intestinal metaplasia differentiation were negatively correlated with MEX3A and MUC5AC expression,but positively correlated with CDX2 and MUC2 expression(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2,and positively correlated with the expression of MUC5AC in gastric cancer(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2 in intestinal metaplasia(P<0.05),while CDX2 was positively correlated with the expression of MUC2(P<0.05).Conclusion MEX3A is negatively correlated with gastric cancer and intestinal metaplasia differentiation.Gastric cancer is characterized by high MEX3A expression and low CDX2 and MUC2 expression.

ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter （PM_2.5） and ozone （O₃） and systemic inflammatory indicators in patients with pneumonia， and to identify the susceptible populations. MethodsFrom September 2018 to April 2020， data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models （GAMs） were used to explore the associations between PM_2.5 and O₃ exposure and inflammatory indicators of patients with pneumonia； and to explore the susceptibility factors and susceptible populations to PM_2.5 and O₃ exposures through stratified analyses. ResultsThe short-term exposure to PM_2.5 was associated with changes in peripheral blood C-reation protein （CRP）， erythrocyte sedimentation （ESR）， easinophil （EOS）， neutrophil （NEU） and neutrophil-lymphocyte ratio （NLR） in patients with pneumonia， and there were different degrees of hysteresis effects， with the effect values reaching a maximum at lag03， lag03， lag0， lag03， lag03， respectively， which were 4.13% （95%CI： 0.43%‒7.84%）， 3.10% （95%CI： 0.24%‒5.97%）， 5.27% （95%CI： 3.12%‒7.42%）， 1.85% （95%CI： 0.36%‒3.34%）， and 2.53% （95%CI： 0.53%‒4.74%） for every 10 μg·m^-3 of PM_2.5. The changes in O₃ concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia， and their effect values all reached the maximum at lag01 d， every 1 μg·m^-3 of O₃ elevation increased by 0.38% （95%CI： 0.04%‒0.73%） and 0.47% （95%CI： 0.19%‒0.76%）， respectively. Stratified analyses showed that the associations of PM_2.5 with peripheral blood CRP， ESR， NEU， and NLR in pneumonia patients were more significant in males， the elderly， and those with onset in the cold season； the associations of O₃ with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season， and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O₃. ConclusionShort-term exposure to atmospheric PM_2.5 and O₃ are positively associated with changes in inflammatory indicators in patients with pneumonia， and the effects of PM_2.5 on patients with pneumonia are more extensive than those of O₃， with a longer lag effect. In addition， elderly patients with pneumonia are more sensitive to air pollution， male patients with pneumonia are more sensitive to PM_2.5， and female patients with pneumonia are more sensitive to O₃. Cold and warm seasons can exacerbate the effects of PM_2.5 and O₃ on inflammatory indicators in patients with pneumonia， respectively， and the patients must be protected well.

[Objective]To summarize the clinical experience of Professor JIA Yingjie,a renowned traditional Chinese medicine practitioner in the treatment of esophageal cancer.[Methods]Through clinical following up,collect and analyze Professor JIA's understanding of the etiology and pathogenesis of esophageal cancer and related medication,and a case of was attached as evidence.[Results]Professor JIA believes that the pathogenesis of esophageal cancer can be summarized as"phlegm coagulation and Qi stagnation"in the early stage,"primitive deficiency"in the late stage as a whole,"phlegm and blood stasis intermingle,Qi and blood stasis obstruct the diaphragm"in local areas,phlegm,Qi,and blood stasis solidify and poison transform into cancer turbidity,and block and form tumors.Clinical differentiation and treatment should always focus on"Qi",with a particular emphasis on regulating the"Qi mechanism".The lungs,spleen and liver are in sync,and dynamic differentiation and treatment should be carried out based on the characteristics of the patient's tongue and pulse.Medication should emphasize the use of"strengthening the body resistance righting"and"dispelling pathogenic factors"to achieve the dissipation of blood stasis,the elimination of cancer toxins and the opening of the diaphragm.[Conclusion]Based on the characteristics of esophageal cancer and the patient's physical constitution,Professor JIA combines disease and syndrome differentiation in treating esophageal cancer,providing a certain reference value and new path for clinical medication.