Myopia has become a significant eye health problem, which is thought to result from the complex interactions of genetic and environmental factors. This review focuses on two types of hereditary retinal diseases caused by mutations in photoreceptor genes, including rod-cone cell dystrophy(retinitis pigmentosa)and cone dysfunction syndromes(achromatopsia, blue cone monochromatism and Bornholm eye disease). It systematically explores the intrinsic connection between these diseases and the myopia phenotype, and elaborates on the core mechanisms by which pathogenic genes such as RPGR and OPN1LW/OPN1MW, which cause defects in ciliary structure and protein transport and interfere with the visual signal pathway, jointly induce choroidal thinning and scleral remodeling, ultimately driving the elongation of axial length and the occurrence of myopia. By tracing the association of photoreceptor gene mutations with myopia, this article provides a new perspective for in-depth understanding of the genetic mechanism of myopia and is of great significance for the development of early risk warning and targeted intervention strategies.

ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

AIM:To observe the clinical efficacy of intravitreal injection of conbercept in the treatment of macular edema secondary to non-ischemic retinal vein occlusion(RVO).METHODS: Single center retrospective study. ME patients secondary to non-ischemic RVO admitted to the hospital from January 2023 to March 2024 were selected, and were divided into central retinal vein occlusion(CRVO)group and branch retinal vein occlusion(BRVO)group according to the location of obstruction. All patients were treated with intravitreal injection of conbercept once a month for 3 mo. The best corrected visual acuity(BCVA), macular foveal thickness(CMT), superficial capillary density(SVD), deep capillary density(DVD), and foveal avascular zone(FAZ)area were recorded before and after treatment(with 3 injections per course)at 1, 3, and 6 mo.RESULTS:This study included a total of 120 ME secondary to non-ischemic RVO patients(128 eyes), who were divided into CRVO group(51 cases, 56 eyes, 31 males, 20 females, mean age 61.39±10.32 y)and BRVO group(69 cases, 72 eyes, 41 males, 28 females, mean age 61.48±10.41 y)based on the location of obstruction. There was no significant difference in general data between the two groups before treatment(both P>0.05). After 1, 3, and 6 mo of treatment, both groups showed improvement in BCVA, CMT, SVD, and DVD compared to before treatment(all P<0.05). BCVA in the BRVO group was better than that in the CRVO group at all time points after treatment(all P<0.05), while there was no difference in CMT, SVD, and DVD between the two groups(all P>0.05); There was no significant difference in FAZ area between the two groups before and after treatment(both P>0.05). Follow up for 6 mo showed no significant difference in the incidence of complications between the two groups of patients(both P>0.05), but there was a significant difference in the recurrence rate(P<0.05).CONCLUSION: The first intravitreal injection of conbercept is effective in treating macular edema caused by non-ischemic CRVO and BRVO, improving visual function, reducing macular edema, and repairing retinal structure and blood flow perfusion. Notably, the recovery of visual function and improvement of capillary density are more significant in BRVO patients.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

ObjectiveTo investigate whether there exists an independent association beyond shared risk factors between colorectal space-occupying lesions and metabolic associated fatty liver disease （MAFLD）， and to provide new ideas for early identification of colorectal space-occupying lesions in the MAFLD population. MethodsA retrospective analysis was performed for 12 252 patients who were hospitalized in The First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） and underwent both colonoscopy and abdominal imaging （abdominal ultrasound， magnetic resonance imaging， or computed tomography） from September 1， 2018 to August 31， 2023. According to colonoscopy findings， the patients were divided into colorectal space-occupying lesion group with 6 545 patients and non-colorectal space-occupying lesion group with 5 707 patients. Baseline data were compared between the two groups. The univariate and multivariate Logistic regression analyses were used to identify influencing factors for colorectal space-occupying lesions， and further analysis was performed to investigate the association of MAFLD and liver fibrosis （assessed by fibrosis-4 ［FIB-4］， nonalcoholic fatty liver disease fibrosis score ［NFS］， and aspartate aminotransferase-to-platelet ratio index） with colorectal space-occupying lesions. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThe univariate analysis showed that compared with the non-colorectal space-occupying lesion group， the colorectal space-occupying lesion group had significantly higher age （Z=-95.628， P<0.001）， proportion of male patients （χ²=406.910， P<0.001）， body weight （Z=-24.928， P<0.001）， body mass index （BMI） （Z=-21.367， P<0.001）， diastolic blood pressure （Z=-15.527， P<0.001）， systolic blood pressure （Z=-16.965， P<0.001）， proportion of patients with history of coronary heart disease （χ²=28.112， P<0.001）/hypertension （χ²=152.993， P<0.001）/diabetes （χ²=52.175， P<0.001）/cerebral infarction （χ²=14.097， P<0.001）， white blood cell count （WBC） （Z=-12.801， P<0.001）， hemoglobin （HGB） （Z=-19.258， P<0.001）， aspartate aminotransferase （Z=-6.673， P=0.001）， alanine aminotransferase （Z=-10.375， P<0.001）， alkaline phosphatase （Z=-10.496， P<0.001）， gamma-glutamyl transpeptidase （GGT） （Z=-18.893， P<0.001）， blood urea nitrogen （Z=-13.291， P<0.001）， creatinine （Z=-16.798， P<0.001）， uric acid （Z=-16.822， P<0.001）， triglyceride （Z=-10.186， P<0.001）， and fasting blood glucose （Z=-15.761， P<0.001）. The multivariate Logistic regression analysis showed that age （odds ratio ［OR］=1.052， 95% confidence interval ［CI］： 1.045 — 1.057， P<0.001）， sex （OR=0.523， 95%CI： 0.466 — 0.587， P<0.001）， BMI （OR=1.031， 95%CI： 1.018 — 1.046， P<0.001）， history of hypertension （OR=1.140， 95%CI： 1.019 — 1.276， P=0.022）， WBC （OR=1.057， 95%CI： 1.028 — 1.087， P<0.001）， GGT （OR=1.001， 95%CI： 1.000 — 1.002， P=0.021）， Alb （OR=0.982， 95%CI： 0.969 — 0.995， P=0.008）， and HGB （OR=1.004， 95%CI： 1.001 — 1.008， P=0.019） were independent influencing factors for colorectal space-occupying lesions. In the MAFLD population， after adjustment for age， sex， BMI， history of hypertension， WBC， HGB， GGT， and Alb， intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 and NFS was still an influencing factor for colorectal space-occupying lesions （FIB-4： OR=1.457， 95%CI： 1.176 — 1.810， P<0.05； NFS： OR=1.499， 95%CI： 1.244 — 1.809， P<0.05）. Liver fibrosis degree based on FIB-4 was not significantly associated with the pathological type， location， size， or number of colorectal space-occupying lesions （all P>0.05）. While intermediate-to-high risk of advanced liver fibrosis based on NFS was not associated with pathological type， location， or size， it might be associated with the number of lesions （χ²=9.770， P<0.05）. ConclusionAge， sex， BMI， history of hypertension， WBC， HGB， GGT， and Alb are independent influencing factors for colorectal space-occupying lesions. Intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 or NFS is independently associated with colorectal space-occupying lesions， and liver fibrosis assessed by NFS might be associated with the increase in the number of lesions.

Breast cancer is a common clinical gy-necological tumor.According to the 2022 global cancer data statistics,breast cancer ranks second in terms of incidence among newly diagnosed cancer cases worldwide.Modern medicine often adopts surgical operation,chemotherapy,and other meth-ods,which have certain efficacy but also many problems such as high drug resistance rates and sig-nificant adverse reactions.Chinese patent medi-cines exhibit extensive anticancer effects.The study found that Shenyi Capsule,Pingxiao Capsule,and Zhenqi Fuzheng Granules were widely used in the treatment of breast cancer,exerting therapeu-tic effects on breast cancer by inhibiting cell prolif-eration,invasion,and metastasis,suppressing an-giogenesis,reversing cellular drug resistance,and inhibiting precancerous lesions.Meanwhile,the oral administration of Chinese patent medicines in combination with other traditional Chinese medi-cine(TCM)compounds,TCM decoctions,or mod-ern medical treatments can improve patients' quali-ty of life and reduce adverse reactions.Currently,there are numerous studies on the treatment of breast cancer with Chinese patent medicines,but a systematic summary is lacking.Therefore,this study conducted a systematic review of the mecha-nisms of action and clinical applications of Chinese patent medicines as adjuvant therapy for breast cancer,aiming to provide guidance for clinical medi-cation.

OBJECTIVE To understand the current status of prevention and control of traditional Chinese medicine(TCM)diagnosis and treatment technique-related infections in various grades of hospitals in Jiangsu Province so as to provide bases for management departments to put forward the norms.METHODS The questionnaire was de-signed by the methods such as Delphic correspondence,the current status of prevalence,prevention and control of TCM diagnosis and treatment technique-related infections among the health care workers in the hospitals of Jiang-su Province was investigated by using convenience sampling method.RESULTS A total of 508 questionnaires were collected from 13 cities of Jiangsu Province.The results showed that the TCM treatment room(63.64％)was the most common operation site for minimally invasive TCM diagnosis and treatment techniques,the bedside(62.50％)of the patients was the major operation site for Chinese medicine enema,and the central sterile supply department(55.31％)was the preferred choice of cleaning and disinfection site for daily recycled TCM apparatu-ses.'One person used for once,airing and preparing for later use after cleaning and disinfection for once'was the major approach taken for the cleaning and disinfection of Gua Sha boards(82.45％)and TCM pots(87.50％).67.87％of the health care workers said that they wound cleaned and disinfected the medical apparatuses of dress-ing,ironing and fumigation every time after the use.The natural ventilation and ultraviolet light(50.39％)was the major method that was taken for the ventilation and disinfection of the treatment rooms for TCM operations.Quick-drying hand disinfectant and non-touch hand-washing equipment(39.37％)were the most commonly e-quipped hand hygiene facilities.CONCLUSIONS The prevention and control of TCM diagnosis and treatment tech-nique-related infections and the health care workers' capabilities for prevention and control of the infection have made remarkable progress in the various grades of hospitals in Jiangsu Province.However,there is still room for further improvement,and the standardized management and construction should be completed so as to safeguard the TCM diagnosis and treatment techniques.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.