Comparison of Treatment Outcomes Between Thoracoscopic Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

Objective: To compare the risk of death, tumor recurrence, metastasis, and disease progression in early-stage non-small cell lung cancer (NSCLC) patients treated with thoracoscopic surgery and stereotactic body radiotherapy (SBRT). Methods: Patients who underwent radical surgery and SBRT for NSCLC between April 2010 and November 2021 were retrospectively analyzed. Continuous and categorical variables were compared using the Mann-Whitney U and Chi-square test, respectively. Kaplan-Meier curves were used to evaluate the survival outcomes of each patient group. Cox proportional hazard regression analyses were performed to estimate the risk of death, tumor recurrence, metastasis, and disease progression. Results: A total of 167 patients were enrolled, of whom 75 and 92 underwent SBRT and surgery, respectively. The median follow-up was 45 months (range, 4-105 months). SBRT patients were observed to be significantly older (median, 76.0 vs 67.0 years; P < .001), and associated with significantly higher mortality rate (42.7% vs 26.1%, P = .024). However, no significant difference in overall survival duration was seen between the SBRT and surgery groups (45.0 vs 41.0 months; P = .199). SBRT patients demonstrated significantly lower rates of metastasis (12.0% vs 30.4%, P = .004), and significantly longer metastasis-free survival (39.0 months vs 35.5 months, P = .020). The remaining outcomes, including tumor recurrence and disease progression rates, were similar between the groups. Compared to surgery, SBRT did not significantly associate with death, recurrence, or disease progression. Kaplan-Meier curves showed significant differences in overall, tumor recurrence-free, and disease progression-free survival between the groups (log-rank P < .05). Conclusions: SBRT demonstrated similar overall survival compared to radical surgery, and associated with significantly reduced risk of tumor metastasis. Our study thereby suggests SBRT as the best treatment option for patients with inoperable NSCLC.

Corrigendum to "Gallic acid mediates tumor-suppressive effects on osteosarcoma through the H19-Wnt/ß-catenin regulatory axis" [J. Orthop. Translat. 39 (2023) 34-42].

[This corrects the article DOI: 10.1016/j.jot.2022.12.003.].

B13, a well-tolerated inhibitor of hedgehog pathway, exhibited potent anti-tumor effects against colorectal carcinoma in vitro and in vivo.

Abnormal activation of Hedgehog (Hh) signaling pathway mediates the genesis and progression of various tumors [1]. Currently, three drugs targeting the Hh signaling component Smoothened (Smo) have been marketed for the clinical treatment of basal cell tumors or acute myeloid leukemia. However, drug resistance is a common problem in those drugs, so the study of Smo inhibitors that can overcome drug resistance has important guiding significance for clinical adjuvant drugs. MTT assay, clone formation assay and EdU assay were used to detect the proliferation inhibitory activity of the drugs on tumor cells. The effect of B13 on cell cycle and apoptosis were detected by flow cytometry. An acute toxicity test was used to detect the toxicity of B13 in vivo, and xenograft tumor model was used to detect the efficacy of B13 in vivo. The binding of B13 to Smo was studied by BODIPY-cyclopamine competitive binding assay and molecular docking. The effect of B13 on the expression and localization of downstream target gene Gli1/2 of Smo was investigated by Western Blot and immunofluorescence assay. SmoD473H mutant cell line was constructed to study the effect of B13 against drug resistance. (1) B13 had the strongest inhibitory activity against colorectal cancer cells. (2) B13 can effectively inhibit the clone formation and EdU positive rate of colon cancer cells. (3) B13 can block the cell cycle in the G2/M phase and cell apoptosis. (4) B13 has low toxicity in vivo, and its efficacy in vivo is better than that of the Vismodegib. (5) Molecular docking and BODIPY-cyclopamine experiments showed that B13 could bind to Smo protein. (6) B13 can inhibit the protein expression of Gli1, the downstream of Smo, and inhibit its entry into the nucleus. (7) B13 could inhibit the expression of Gli1 in the HEK293 cells with SmoD473H, and the molecular docking results showed that B13 could bind SmoD473H protein. B13 with the best anti-tumor activity was screened out by MTT assay. In vitro, pharmacodynamics experiments showed that B13 could effectively inhibit the proliferation and metastasis of colorectal cancer cells, induce cell cycle arrest, and induce cell apoptosis. In vivo pharmacodynamics experiments showed that B13 was superior to Vismodegib in antitumor activity and had low toxicity in vivo. Mechanism studies have shown that B13 can bind Smo protein, inhibit the expression of downstream Gli1 and its entry into the nucleus. Notably, B13 overcomes resistance caused by SmoD473H mutations.

Gallic acid mediates tumor-suppressive effects on osteosarcoma through the H19-Wnt/ß-catenin regulatory axis.

Background: Osteosarcoma (OS) is the most common primary malignancy in bone tissues, and effective therapeutics remain absent in clinical practice. Traditional Chinese medicines (TCM) have been used for thousands of years, which provide great insights into OS management. Gallic acid (GA) is a natural phenolic acid enriched in various foods and herbs. Several pharmacological activities of GA such as anti-oxidation and anti-inflammation have been well-established. However, its biological function in OS remains not fully understood. Methods: The potential anti-cancer properties of GA were evaluated in 143 â€‹B, U2OS and MG63 â€‹cells. Its effects on cell growth, cell cycle, apoptosis and migration were examined in these OS cells. The lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR, luciferase activity and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using an orthotopic mouse model. Results: In the present study, GA was found to suppress the tumor growth in vitro via inducing cell cycle arrest and apoptosis in OS cells, and inhibit the invasion and metastasis as well. Using the orthotopic animal model, GA was also found to suppress tumorigenesis in vivo. Long noncoding RNA (lncRNA) H19 was demonstrated to be down-regulated by GA, and thus disrupted the canonical Wnt/ß-catenin signaling in OS cells. Furthermore, the ectopic expression of H19 rescued the GA-induced suppressive effects on tumor growth and metastasis, and partially reversed the inactivation of Wnt/ß-catenin signaling. Conclusions: Taken together, our results indicated that GA inhibited tumor growth through an H19-mediated Wnt/ß-catenin signaling regulatory axis in OS cells. The translational potential of this article: The information gained from this study provides a novel underlying mechanism of GA mediated anti-OS activity, suggesting that GA may be a promising drug candidate for OS patients.

[Mahuang (herbaceous stem of Ephedra spp.): chemistry, pharmacodynamics, and pharmacokinetics].

The Chinese medicinal herb Mahuang is herbaceous stem of Ephedra sinica, E. intermedia, or E. equisetina(Family, Ephedraceae). In China, Mahuang has been used, all the way over a millennium, as a key component herb of many herbal medicines for management of epidemics of acute respiratory illness and is also used in officially recommended herbal medicines for COVID-19. Mahuang is the first-line medicinal herb for cold and wheezing and also an effective diuretic herb for edema. However, Mahuang can also exert significant adverse effects. The key to safety and effectiveness is rational and precise use of the herb. In this review article, we comprehensively summarize chemical composition of Mahuang and associated differences in pharmacognosy, pharmacodynamics and pharmacokinetics of Mahuang compounds, along with the adverse effects of Mahuang compounds and products. Based on full understanding of how Mahuang is used in Chinese traditional medicine, systematic research on Mahuang in line with contemporary standards of pharmaceutical sciences will facilitate promoting Chinese herbal medicines to become more efficient in management of epidemic illnesses, such as COVID-19. To this end, we recommend research on Mahuang of two aspects, i.e., pharmacological investigation for its multicompound-involved therapeutic effects and toxicological investigation for clinical manifestation of the adverse effects, chemicals responsible for the adverse effects, and conditions for safe use of the herb and the herb-containing medicines.

Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen).

Phenolic acids are cardiovascular constituents (originating from the Chinese medicinal herb Salvia miltiorrhiza root/Danshen) of DanHong and many other Danshen-containing injections. Our earlier pharmacokinetic investigation of DanHong suggested that hepatic and/or renal uptake of the Danshen compounds was the crucial steps in their systemic elimination. This investigation was designed to survey the molecular basis underlying hepatobiliary and renal excretion of the Danshen compounds, i.e., protocatechuic acid, tanshinol, rosmarinic acid, salvianolic acid D, salvianolic acid A, lithospermic acid, and salvianolic acid B. A large battery of human hepatic and renal transporters were screened for transporting the Danshen compounds and then characterized for the uptake kinetics and also compared with associated rat transporters. The samples were analyzed by liquid chromatography/mass spectrometry. Because the Danshen phenolic acids are of poor or fairly good membrane permeability, their elimination via the liver or kidneys necessitates transporter-mediated hepatic or renal uptake from blood. Several human transporters were found to mediate hepatic and/or renal uptake of the Danshen compounds in a compound-molecular-mass-related manner. Lithospermic acid and salvianolic acid B (both >500 Da) underwent systemic elimination, initiated by organic anion-transporting polypeptide (OATP)1B1/OATP1B3-mediated hepatic uptake. Rosmarinic acid and salvianolic acids D (350-450 Da) underwent systemic elimination, initiated by OATP1B1/OATP1B3/organic anion transporter (OAT)2-mediated hepatic uptake and by OAT1/OAT2-mediated renal uptake. Protocatechuic acid and tanshinol (both <200 Da) underwent systemic elimination, initiated by OAT1/OAT2-mediated renal uptake and OAT2-mediated hepatic uptake. A similar scenario was observed with the rat orthologs. The investigation findings advance our understanding of the disposition of the Danshen phenolic acids and could facilitate pharmacokinetic research on other Danshen-containing injections.

Clustering- and Transformer-Based Networks for the Style Analysis of Logo Images.

In the design field, designers need to investigate and collect logo materials before designing logos and search a large number of design materials on well-known logo websites to find logos with similar styles as reference images. However, manual work is time-consuming and labor-intensive. To solve this problem, we propose a clustering method that uses K-Means clustering and visual transformer model to group the styles of the logo database. Specifically, we use the visual transformer model as a feature extractor to convert logo images into feature vectors and perform K-Means clustering, use the clustering results as pseudo-labels to further train the feature extractor, and continue to iterate the above process to finally obtain reliable clustering results. We validate our approach by creating the logo image dataset JN Logo, a proposed database for image quality and style attributes, containing 14922 logo design images. Our proposed deep transformer-based cluster (DTCluster) automatic style grouping method is used in JN Logo; the DBI reaches 0.904, and the DI reaches 0.189, which are better than those of other K-Means clustering methods and other clustering algorithms. We perform a subjective analysis of five features of the clustering results to obtain a semantic description of the clusters. Finally, we provide six styles and five semantic descriptions for the logo database.

The Value of Artificial Intelligence Film Reading System Based on Deep Learning in the Diagnosis of Non-Small-Cell Lung Cancer and the Significance of Efficacy Monitoring: A Retrospective, Clinical, Nonrandomized, Controlled Study.

Objective: To explore the value of artificial intelligence (AI) film reading system based on deep learning in the diagnosis of non-small-cell lung cancer (NSCLC) and the significance of curative effect monitoring. Methods: We retrospectively selected 104 suspected NSCLC cases from the self-built chest CT pulmonary nodule database in our hospital, and all of them were confirmed by pathological examination. The lung CT images of the selected patients were introduced into the AI reading system of pulmonary nodules, and the recording software automatically identified the nodules, and the results were compared with the results of the original image report. The nodules detected by the AI software and film readers were evaluated by two chest experts and recorded their size and characteristics. Comparison of calculation sensitivity, false positive rate evaluation of the NSCLC software, and physician's efficiency of nodule detection whether there was a significant difference between the two groups. Results: The sensitivity, specificity, accuracy, positive predictive rate, and false positive rate of NSCLC diagnosed by radiologists were 72.94% (62/85), 92.06% (58/63), 81.08% (62+58/148), 92.53% (62/67), and 7.93% (5/63), respectively. The sensitivity, specificity, accuracy, positive prediction rate, and false positive rate of AI film reading system in the diagnosis of NSCLC were 94.12% (80/85), 77.77% (49/63), 87.161% (80 + 49/148), 85.11% (80/94), and 22.22% (14/63), respectively. Compared with radiologists, the sensitivity and false positive rate of artificial intelligence film reading system in the diagnosis of NSCLC were higher (P < 0.05). The sensitivity, specificity, accuracy, positive prediction rate, and negative prediction rate of artificial intelligence film reading system in evaluating the efficacy of patients with NSCLC were 87.50% (63/72), 69.23% (9/13), 84.70% (63 + 9)/85, 94.02% (63/67), and 50% (9/18), respectively. Conclusion: The AI film reading system based on deep learning has higher sensitivity for the diagnosis of NSCLC than radiologists and can be used as an auxiliary detection tool for doctors to screen for NSCLC, but its false positive rate is relatively high. Attention should be paid to identification. Meanwhile, the AI film reading system based on deep learning also has a certain guiding significance for the diagnosis and treatment monitoring of NSCLC.

Histone methylatic modification mediates the tumor-suppressive activity of curcumol in hepatocellular carcinoma via an Hotair/EZH2 regulatory axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma kwangsiensis S. G. Lee & C. F. Liang (Guangxi ezhu, in Chinese) has been used as a traditional Chinese medicine (TCM) for approximately 2000 years. Curcumol is one of the major bioactive components of this herb, which has been demonstrated possesses anti-cancer properties, and was recorded in the Chinese Pharmacopoeia 2020 edition. However, most studies mainly focused on the superficial anti-cancer activity, the underlying mechanism remains poorly understood. AIM OF THE STUDY: In the present study, we aimed to investigate the anti-tumor effect of Curcumol on hepatocellular carcinoma (HCC), and elucidate its underlying mechanism from the perspective of epigenetic modification. MATERIALS AND METHODS: The potential anti-cancer properties of Curcumol were evaluated in HepG2 and SMMC-7721 cells. Its effects on cell growth, cell cycle, apoptosis and migration were examined in these HCC cells. Moreover, the lncRNA HOX transcript antisense intergenic RNA (Hotair) and histone methylatic modification were detected by qPCR and Western blotting assays. RESULTS: In the present study, Curcumol was illustrated to suppress cell growth in HCC cells via inducing apoptosis and cell cycle arrest. And it was also found that Curcumol inhibited the invasion and metastasis of HCC as well. As for the mechanism investigation, it was showed that lncRNA Hotair was significantly downregulated by Curcumol in HCC cells. As is well known, Hotair recruited histone methyltransferase enhancer of zeste homolog 2 (EZH2) to exert transcriptional regulation. Our results showed that EZH2 were downregulated by Curcumol in HCC cells, and thus disrupted the trimethylation of H3K9 and H3K27 which were specifically catalyzed by EZH2. CONCLUSIONS: In conclude, our results demonstrated that Curcumol suppressed tumor growth and metastasis via an Hotair/EZH2/histone modification regulatory axis.

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

Discovery of [1,2,4]triazolo[4,3-a]pyridines as potent Smoothened inhibitors targeting the Hedgehog pathway with improved antitumor activity in vivo.

Triple-negative breast cancer (TNBC), a subset of breast cancers, have poorer survival than other breast cancer types. Recent studies have demonstrated that the abnormal Hedgehog (Hh) pathway is activated in TNBC and that these treatment-resistant cancers are sensitive to inhibition of the Hh pathway. Smoothened (Smo) protein is a vital constituent in Hh signaling and an attractive drug target. Vismodegib (VIS) is one of the most widely studied Smo inhibitors. But the clinical application of Smo inhibitors is limited to adult patients with BCC and AML, with many side effects. Therefore, it's necessary to develop novel Smo inhibitor with better profiles. Twenty [1,2,4]triazolo[4,3-a]pyridines were designed, synthesized and screened as Smo inhibitors. Four of these novel compounds showed directly bound to Smo protein with stronger binding affinity than VIS. The new compounds showed broad anti-proliferative activity against cancer cell lines in vitro, especially triple-negative breast cancer cells. Mechanistic studies demonstrated that TPB15 markedly induced cell cycle arrest and apoptosis in MDA-MB-468 cells. TPB15 blocked Smo translocation into the cilia and reduced Smo protein and mRNA expression. Furthermore, the expression of the downstream regulatory factor glioma-associated oncogene 1 (Gli1) was significantly inhibited. Finally, TPB15 demonstrated greater anti-tumor activity in our animal models than VIS with lower toxicity. Hence, these results support further optimization of this novel scaffold to develop improved Smo antagonists.

[Silencing RRM1 gene reverses paclitaxel resistance in human breast cancer cell line MCF- 7/R by inducing cell apoptosis].

OBJECTIVE: To investigate the effects of ribonucleotide reductase catalytic subunit M1 (RRM1) gene silencing on drug resistance of human breast cancer cell line MCF-7/R. METHODS: We established a paclitaxel-resistant breast cancer MCF-7 cell line (MCF-7/R) by exposing the cells to high-concentration paclitaxel in a short time. Small interfering RNAs (siRNAs) targeting RRM1 were designed to silence RRM1 expression in human breast cancer MCF-7/R cells. MTT assay was used to detect the IC50 values and the sensitivity to paclitaxel in the cells with or without siRNA transfection. The changes in the proliferative activity of MCF7 and MCF-7/R cells following RRM1 gene silencing were evaluated using EdU assay. Flow cytometry was used to analyze the cell apoptosis and cell cycle changes. We assessed the effect of RRM1 gene silencing and paclitaxel on the tumor growth in a nude mouse model bearing subcutaneous xenografts with or without siRNA transfection. RESULTS: We detected significantly higher expressions of RRM1 at both the mRNA and protein levels in the drug-resistant MCF- 7/R cells than in the parental MCF-7 cells (P < 0.01). Transfection with the specific siRNAs significantly reduced the expression of RRM1 in MCF-7/R cells (P < 0.05), which showed a significantly lower IC50 value of paclitaxel than the cells transfected with the negative control siRNA (P < 0.05). RRM1 silencing significantly inhibited the proliferation (P < 0.01) and enhanced the apoptosis-inducing effect of paclitaxel in MCF-7/R cells (P < 0.001); RRM1 silencing also resulted in obviously reduced Akt phosphorylation, suppressed Bcl-2 expression and promoted the expression of p53 protein in MCF-7/R cells. In the tumor-bearing nude mice, the volume of subcutaneously transplanted tumors was significantly smaller in MCF-7/R/siRNA+ PTX group than in the other groups (P < 0.001). CONCLUSIONS: RRM1 gene silencing can reverse paclitaxel resistance in human breast cancer cell line MCF-7/R by promoting cell apoptosis.

Capsaicin-loaded folic acid-conjugated lipid nanoparticles for enhanced therapeutic efficacy in ovarian cancers.

In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.

Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. METHODS: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). RESULTS: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. CONCLUSIONS: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease.

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties.

Study of krypton laser-induced choroidal neovascularization in a Guinea pig model of high anisometropia.

PURPOSE: To investigate the association between high anisometropia and the area of choroidal neovascularization (CNV) induced by krypton laser in guinea pigs and better understand the pathogenesis and prevention of myopic CNV. METHODS: Nine 3-week old male guinea pigs with anisometropia >6.00D were randomly assigned to three groups according to examination date after laser photocoagulation (7d, 14d and 28d). All animals underwent refraction. The eye with higher myopia was used as the experimental eye, and the other as the control eye. All eyes received repeated multi-wavelength krypton laser photocoagulation treatments (wavelength: 532nm; laser power: 400mW; spot diameter: 50µm; exposure time: 0.1s). Fundus photography and indocyanine green angiography (ICGA) were performed. Afterwards, the animals were sacrificed immediately, and the eyes were enucleated and processed for histopathologic examination and flat mounts. RESULTS: CNV appeared at 7d after laser treatment. The area of CNV peaked at 14d, and decrease in area and the presence of scarring was noted at 28 d. CNV was present in 66.7% of eyes by ICGA at 14 d. CNV could be observed under light microscopy at all three time points. At 14d, flat mount showed the neovascular plexus around the lesion. Semi-quantitative analysis revealed that the area of CNV in treated eyes was greater than that of control eyes. CONCLUSION: Since the mechanism of CNV in this study resembles that of CNV in pathological myopia, this model can be used to investigate the etiology, pathogenesis and treatment of CNV in pathological myopia.