AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective: To understand the needs of parents of kindergarten children in urban areas for online training on sexuality education, so as to provide a basis for the development of parent training courses. Methods: In May 2023, a multistage cluster random sampling method was used to select 3 516 parents of young children from 12 kindergartens in urban areas of Changshou District, Chongqing. A self designed questionnaire on Knowledge, Attitude and Practice of Early Childhood Sexuality Education (Parents) was used for the survey, and χ 2 test and multi factor Logistic regression model were used for data analysis. Results: The online training demand rate of urban parents for early childhood sexuality education was 57.05%. The results of the multi factor Logistic regression analysis showed that age, education level, occupation, whether or not they were the main caregivers, total score level of the scale, awareness of their own responsibility, communication with family and friends about early childhood sexuality education and young children s participation in kindergarten sexuality education activities were the influencing factors of parents online training demand on sexuality education ( OR =1.18, 1.44, 1.42, 0.83, 1.19, 0.51, 0.75, 0.75, P <0.05). Conclusion Urban parents have a high demand for online training on early childhood sexuality education, and training courses should be developed according to the specific needs and characteristics of parents of young children.

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

【Objective】 To investigate the effect of total flavone of oldenlandia diffusa(FOD) on the stemness, proliferation and apoptosis of breast cancer(BC) stem cells sorted from MDA-MB-231. 【Methods】 Human BC cell lines MDA-MB-231 was cultured in vitro; MDA-MB-231 was stimulated by different concentrations(0 μg/mL, 100 μg/mL, 200 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h and 72 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on MDA-MB-231 proliferation; CD44⁺/CD24^-MDA-MB-231 cell line were tested by flow cytometry and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting; Annexin V-PE/7-AAD was used to detect the effect of FOD on MDA-MB-231 apoptosis and Bcl2, cleaved-caspase3 and Bax were tested by Western blotting. 【Results】 Cell proliferation of MDA-MB-231 was significantly inhibited by FOD, with the significant suppression at concentrations of 400 μg/mL for 72 h compared with negative control group(P<0.05). The apoptosis rate was significantly upregulated than the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and cleaved-caspae3 increased, and stemness markers such as Nanog, Sox2 and Oct4 decreased in FOD-treated cells. Moverover, Akt-GSK3β-β-catenin axis was inhibited in FOD-treated cells. 【Conclusion】 FOD could significantly inhibit the stemness and proliferation and promote the apoptosis of MDA-MB-231.

【Objective】 To investigate the effects of total flavone of oldenlandia diffusa (FOD) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) stem cells sorted from Huh7. 【Methods】 Human HCC cell lines Huh7 was cultured in vitro; CD133 positive (CD133⁺) stem cells in Huh7 cell line were sorted by flow cytometry, and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting. CD133⁺-Huh7 was stimulated by different concentrations (0 μg/mL, 50 μg/mL, 100 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h, 72 h and 96 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on CD133⁺-Huh7 proliferation while Annexin V-PE/7-AAD was used to detect the effect of FOD on CD133⁺-Huh7 apoptosis. Western blotting was used to detect the protein expressions of protein 53 (P53), factor associated suicide-Fas-associating protein with a novel death domain (Fas-FADD), B-cell lymphoma-2 (Bcl-2), Cleaved-Caspase3, and Bcl-2 associated X protein (Bax). 【Results】 More than 95% of stem cells were purified for further experiments. Cell proliferation of CD133⁺-Huh7 was significantly inhibited by FOD, with the significant suppression at the concentration of 100 μg/mL for 72 h compared with negative control group (P<0.05). The apoptosis rate was significantly upregulated than that in the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and Cleaved-Caspae3 increased via FAS/FADDD and P53 axis. 【Conclusion】 FOD can significantly inhibit the proliferation and promote the apoptosis of CD133⁺-Huh7.

Objective: On the basis of the dominant frequency index of functional connectivity, the "brain age" analysis method was used to explore abnormal development patterns of sensorimotor networks in boys with autism spectrum disorder(ASD). Methods: The resting state functional magnetic resonance data (7-12 years old) for 105 boys with ASD and 102 matched boys with normal development from the ABIDE public database were screened. Functional connection networks in different frequency bands of sensorimotor related brain regions were constructed for each individual, and the frequency of the strongest connection were constructed as the optimal frequency of the connection. Brain age analysis was used to explore the difference between brain age and chronological age in boys with ASD. Results: The brain sensorimotor network of boys with ASD showed an abnormal development pattern of overdevelopment followed by underdevelopment, and the transition between the two patterns occurred at approximately 7.8 years of age. Older boys with ASD (older than 10 years) whose underdevelopment trend was suppressed had lower ASD severity( r=-0.43, P < 0.05 ). Conclusion The brain sensorimotor network in boys with ASD has an abnormal development process, and the brain chronological age difference in the sensorimotor network has potential as a neuroimaging marker to measure the development of ASD.

ObjectiveTo observe the effect of Simiaowan on the intestinal ATP-binding cassette superfamily G （White） member 2 （ABCG2） expression and the intestinal uric acid excretion in hyperuricemia rats. MethodA total of 48 SD male rats were randomized into the normal， model， benzbromarone （4.7 mg·kg^-1）， and high-， medium-， low-dose Simiaowan groups （2 260.6， 1 130.3， 565.2 mg·kg^-1， respectively）， with 8 rats in each group. Potassium oxonate and hypoxanthine was employed to induce hyperuricemia in rats （21 days）. On the 8^th day， administration began （once a day for 14 days）. Rats were killed on the 21^st day， and serum uric acid， serum creatinine， blood urea nitrogen， and intestinal uric acid were detected. The protein expression of ABCG2 in the small intestine was detected by Western blot. The ABCG2 protein expression and localization in intestinal tissues were determined by immunohistochemistry. The ABCG2 mRNA expression in small intestine was measured by quantitative real-time PCR. ResultThe levels of serum uric acid， serum creatinine， and blood urea nitrogen in the model group were higher than those in the normal group （P<0.01）. Low level of serum uric acid in the three Simiaowan groups and benzbromarone group （P<0.01）， high level of intestinal uric acid in medium-dose and low-dose Simiaowan groups （P<0.05， P<0.01）， high level of serum creatinine in benzbromarone group （P<0.01）， and low level of blood urea nitrogen in low-dose Simiaowan group （P<0.05） were observed as compared with those in the model group. Serum uric acid showed insignificant difference between the low-dose Simiaowan group and benzbromarone group. The expression of ABCG2 protein in the model group was lower than that in the normal group （P<0.05）. The expression of ABCG2 protein in the medium-dose and low-dose Simiaowan groups （P<0.05， P<0.01）， the high-dose Simiaowan group， and benzbromarone group increased as compared with that in the model group. ABCG2 mRNA expression was insignificantly different between the model group and the normal group， while the expression in the medium-dose and low-dose Simiaowan groups was higher than that in the model group （P<0.05）. ABCG2 protein was mainly distributed in intestinal villi， and ABCG2 protein expression demonstrated no significant difference between the model group and the normal group. The ABCG2 protein expression in the three Simiaowan groups increased as compared with that in the model group （P<0.05）. ConclusionSimiaowan can significantly reduce the serum uric acid level in hyperuricemia rats. Particularly， the low-dose Simiaowan shows similar efficacy to benzbromarone in lowering uric acid and protects renal function. The mechanism is the likelihood that it up-regulates intestinal ABCG2 expression to promote intestinal excretion of uric acid.

Conversion therapy has become the core in the treatment of borderline resectable or unresectable liver cancer, which provides resectable opportunities for more advanced liver cancer patients. In accordance with the first-choice treatment regimen recommended by the guidelines, the authors reported a successful case of Atezolizumab and Bevacizumab (T+A regimen) conversion therapy. The patient with initially borderline resectable advanced liver cancer was performed liver segment resection sucessfully after conversion therapy, and non-tumor recurrence was observed at postoperative 9 months. Postoperative pathological examination showed combined hepatocellular-cholangiocarcinoma, which also indicated the important value of T+A regimen in the conversion therapy of combined hepatocellular-cholangiocarcinoma.