1.Curcumin extraction and preparation and optimization of curcumin nanoparticles
Yuhang WANG ; Han ZHANG ; Chaojing ZHANG ; Xurong KOU ; Tongtong JING ; Rimei LIN ; Xinyu LIU ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Tissue Engineering Research 2026;30(2):362-374
BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57%,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10%.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5%,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61%.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)%,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.
2.Flavonoids Intervene in Diabetic Nephropathy by Regulating TGF-β/Smad Signaling Pathway: A Review
Qihui QIU ; Chang LIU ; Xiaotong YAN ; Jinwei HAN ; Hui SUN ; Fengting YIN ; Yuhang WANG ; Mengmeng WANG ; Xijun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):300-309
Diabetic nephropathy (DKD), as a common microvascular complication of diabetes mellitus (DM), is a major cause of end-stage renal disease (ESRD). Its clinical manifestations include increased urinary protein excretion, thickening of the glomerular basement membrane, and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors, including disordered glucose metabolism, hemodynamic alterations, and oxidative stress. Although modern medical approaches can alleviate certain symptoms, they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad (TGF-β/Smad) signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years, but also regulates multiple protein molecules, including the glomerular podocyte slit diaphragm protein Podocin, interleukin-1β (IL-1β), and superoxide dismutase (SOD), thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds, owing to their sustained pharmacological effects, broad spectrum of action, and high safety profile, have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis, alleviate inflammatory responses, protect podocytes, and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules, thereby maintaining renal structure and function, reducing proteinuria, and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway, elucidates the mechanisms by which this pathway regulates DKD, and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore, it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease, aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.
3.Longitudinal cohort study on pubertal development trajectories of testicular and breast development among children
Chinese Journal of School Health 2026;47(3):408-412
Objective:
To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation.
Methods:
Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method.
Results:
Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years.
Conclusion
Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.
4.Effect and Mechanisms of Ermiao Formula Analogs and Their Active Components in Treating Dampness-heat Type Gouty Arthritis: A Review
Xueping ZHAO ; Xinya ZHANG ; Le YANG ; Ye SUN ; Xin SUN ; Hui SUN ; Qimeng ZHANG ; Guangli YAN ; Xijun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):276-285
Gouty arthritis (GA) is caused by monosodium urate(MSU) deposition due to purine metabolism disorders. In traditional Chinese medicine (TCM), it falls under the category of "dampness-heat Bi syndrome", with core pathogenesis involving dampness-heat accumulation and dysfunction of the spleen and kidney. The dampness-heat syndrome is the most common and the primary syndrome type during acute attacks. In Western medicine, GA is associated with purine metabolism imbalance and inflammation triggered by MSU crystals, involving pathways such as NOD-like receptor protein 3 (NLRP3) inflammasome activation and Toll-like receptor 2/4 (TLR2/4) signaling. Clinically, colchicine and similar drugs are commonly used to treat GA, although long-term use carries potential side effects. Ermiao Formula analogs originate from ancient prescriptions, including Ermiao, Sanmiao, and Simiao compound formulas. All contain Atractylodis Rhizoma and Phellodendri Chinensis Cortex. Ermiaowan follow a 1∶1 formulation ratio. Sanmiaowan add Cyathulae Radix. Simiaowan further incorporate Coicis Semen. These formulas are rich in active ingredients, including alkaloids, terpenoids, flavonoids, and sterols, and treat GA through multi-component, multi-pathway, and multi-target mechanisms. Ermiaosan primarily exerts anti-inflammatory effects by inhibiting pathways such as TLR4/nuclear factor kappa-B (NF-κB) or regulating immune responses to reduce the release of inflammatory mediators, while also suppressing xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activity to decrease uric acid production. Sanmiaowan enhance uric acid-lowering and anti-inflammatory effects through the guiding herb Cyathulae Radix, while also protecting cartilage from damage. Simiaowan utilizes Coicis Semen to regulate intestinal flora, alleviate dampness-heat symptoms, and exert multi-pathway anti-inflammatory and uric acid-lowering effects. The active ingredients contribute differently to uric acid metabolism regulation, anti-inflammation, antioxidant activity, and bone repair, resulting in varying therapeutic effects due to differences in formula composition. In summary, formulas derived from Ermiaosan demonstrate significant efficacy in treating dampness-heat type GA. This review summarizes their research progress and mechanisms, providing a reference for clinical application, new drug development, and further studies.
5.Curcumin extraction and preparation and optimization of curcumin nanoparticles
Yuhang WANG ; Han ZHANG ; Chaojing ZHANG ; Xurong KOU ; Tongtong JING ; Rimei LIN ; Xinyu LIU ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Tissue Engineering Research 2026;30(2):362-374
BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57%,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10%.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5%,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61%.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)%,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.
6.An Attention-weighted Tri-modal Ultrasound Network (TUS-Net) for Screening of Atypical Hepatocellular Carcinoma From LR-M Liver Nodules
He-Chong ZHANG ; Liang-Hui HUANG ; Xue-Hua WANG ; Shang-Lin JIANG ; Ying-Ying CHEN ; Ya-Guang ZENG ; Wei ZHENG
Progress in Biochemistry and Biophysics 2026;53(5):1485-1498
ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.
7.An Attention-weighted Tri-modal Ultrasound Network (TUS-Net) for Screening of Atypical Hepatocellular Carcinoma From LR-M Liver Nodules
He-Chong ZHANG ; Liang-Hui HUANG ; Xue-Hua WANG ; Shang-Lin JIANG ; Ying-Ying CHEN ; Ya-Guang ZENG ; Wei ZHENG
Progress in Biochemistry and Biophysics 2026;53(5):1485-1498
ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.
8.Effect of Heat-Sensitive Moxibustion on Apoptosis of Gastric Mucosal Tissue in Chronic Atrophic Gastritis Model Rats:Based on PI3K/Akt Signaling Pathway
Qi ZHANG ; Yanping ZHOU ; Qide WANG ; Shujuan CHEN ; Yu SUN ; Fang LI ; Hongbin GONG ; Mingjun XIE ; Hui LIU ; Haifeng ZHANG
Journal of Traditional Chinese Medicine 2026;67(15):1650-1658
ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis (CAG) through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group (n=14) and modeling group (n=44). Rats in the blank group were fed routinely, while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at a concentration of 140 μg/ml, combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling, the rats were randomly divided into model group (n=10), inhibitor group (n=10) and moxibustion group (n=20). After 40 minutes of suspended moxibustion at "Zhongwan" (CV 12) daily, the rats in the moxibustion group were divided into heat-sensitive moxibustion group (n=10) and non-heat-sensitive moxibustion group (n=9) according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily, and then administered with PI3K/Akt signaling pathway inhibitor, rapamycin solution, by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days, while the blank group received no intervention. After the intervention finished, the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 (MMP7), vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR) in gastric mucosa. The mRNA expression levels of PI3K, Akt and mammalian target of rapamycin (mTOR) in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR) in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group, rats in all other groups exhibited decreased body weight, significantly increased gastric mucosal cell apoptosis-positive rates, elevated protein levels of MMP7, VEGFA and EGFR in gastric mucosa, increased mRNA expression levels of PI3K, Akt and mTOR, and enhanced protein expression levels of p-Akt and p-mTOR (P<0.05 or P<0.01). Histopathological examination revealed thinning of the gastric mucosa, glandular disorganization and atrophy, accompanied by intestinal metaplasia.Compared to the model group, the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators (P<0.05 or P<0.01). Compared to the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis; the non-heat-sensitive moxibustion group showed increased protein levels of MMP7, VEGFA and EGFR, as well as mRNA expression levels of PI3K, Akt and mTOR, and protein expressions of p-Akt and p-mTOR; the inhibitor group exhibited elevated protein expression level of EGFR (P<0.05 or P<0.01). Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly, with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway, thereby reducing gastric mucosal cell apoptosis.
9.Research Progress on the Regulation of Growth Plate Endochondral Ossification by Mechanical Loading
Xiaoyuan GUO ; Yuxin SUN ; Yutong WANG ; Shi CHEN ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2026;17(4):1126-1134
The endochondral ossification of the growth plate is crucial for the longitudinal growth of long bones. Mechanical loading plays an important regulatory role in endochondral ossification. Absence or improper mechanical loading can inhibit growth plate development, while moderate mechanical stimuli promote chondrocyte proliferation and differentiation, thereby facilitating long bone growth. Mechanosensitive structures, such as primary cilia, mechanosensitive ion channels, integrins, and the cytoskeleton, play key roles in the regulation of mechanical loading. This review summarizes how mechanical loading influences growth plate endochondral ossification and discusses potential underlying mechanisms, offering theoretical insights for the management and research of bone development disorders in children and adolescents.
10.Effect of Heat-Sensitive Moxibustion on Apoptosis of Gastric Mucosal Tissue in Chronic Atrophic Gastritis Model Rats:Based on PI3K/Akt Signaling Pathway
Qi ZHANG ; Yanping ZHOU ; Qide WANG ; Shujuan CHEN ; Yu SUN ; Fang LI ; Hongbin GONG ; Mingjun XIE ; Hui LIU ; Haifeng ZHANG
Journal of Traditional Chinese Medicine 2026;67(15):1650-1658
ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis (CAG) through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group (n=14) and modeling group (n=44). Rats in the blank group were fed routinely, while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at a concentration of 140 μg/ml, combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling, the rats were randomly divided into model group (n=10), inhibitor group (n=10) and moxibustion group (n=20). After 40 minutes of suspended moxibustion at "Zhongwan" (CV 12) daily, the rats in the moxibustion group were divided into heat-sensitive moxibustion group (n=10) and non-heat-sensitive moxibustion group (n=9) according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily, and then administered with PI3K/Akt signaling pathway inhibitor, rapamycin solution, by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days, while the blank group received no intervention. After the intervention finished, the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 (MMP7), vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR) in gastric mucosa. The mRNA expression levels of PI3K, Akt and mammalian target of rapamycin (mTOR) in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR) in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group, rats in all other groups exhibited decreased body weight, significantly increased gastric mucosal cell apoptosis-positive rates, elevated protein levels of MMP7, VEGFA and EGFR in gastric mucosa, increased mRNA expression levels of PI3K, Akt and mTOR, and enhanced protein expression levels of p-Akt and p-mTOR (P<0.05 or P<0.01). Histopathological examination revealed thinning of the gastric mucosa, glandular disorganization and atrophy, accompanied by intestinal metaplasia.Compared to the model group, the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators (P<0.05 or P<0.01). Compared to the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis; the non-heat-sensitive moxibustion group showed increased protein levels of MMP7, VEGFA and EGFR, as well as mRNA expression levels of PI3K, Akt and mTOR, and protein expressions of p-Akt and p-mTOR; the inhibitor group exhibited elevated protein expression level of EGFR (P<0.05 or P<0.01). Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly, with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway, thereby reducing gastric mucosal cell apoptosis.


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