1.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.Clinical study on the treatment of chronic atrophic gastritis with spleen and stomach weakness syndrome by Piwei Peiyuan Pill combined with moxibustion
Kairui WU ; Yu YE ; Bei PEI ; Biao SONG ; Yi ZHANG ; Tingting LI ; Qi YANG ; Yun LIU ; Xuejun LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):280-290
Objective:
To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome.
Methods:
Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared.
Results:
There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05).
Conclusion
The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.
4.Effects of the prolyl hydroxylase 2 inhibitor cpd17 on mouse osteogenic precursor cells
Zhongqiu DU ; Xiaoyang QI ; Ping YANG ; Jianglin YU ; Yixin CHEN ; Linjian ZHANG ; Xusheng QIU
Chinese Journal of Tissue Engineering Research 2025;29(2):238-244
BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.
5.Relationships Between Exercise Components and Social Anxiety Levels Among Chinese College Students
Qi CHENG ; Wenbing YU ; Mingxiao JU ; Duo YANG ; Jiannan FU ; Shilong SONG
Psychiatry Investigation 2025;22(2):196-203
Objective:
This study aimed to explore the relationships between various exercise components (frequency, intensity, duration) and social anxiety.
Methods:
A sample of 844 college students in China participated in this study. The Physical Activity Rating Scale-3 assessed participants’ daily physical activity. Social anxiety levels were measured using the Liebowitz Social Anxiety Scale. A questionnaire was developed to collect demographic information and examine the relationships between exercise components and social anxiety levels.
Results:
One-way analysis of variance revealed significant differences in social anxiety levels across varying physical activity intensities. Specifically, students engaging in high levels of physical activity exhibited the lowest social anxiety. Post hoc analyses identified that exercise frequency F3 (p<0.01), exercise duration D5 (p<0.01), and exercise intensity I3 (p<0.01) were significantly associated with the lowest social anxiety levels. Among these components, regression analysis indicated that exercise duration (p<0.01) had the most substantial impact on social anxiety levels, followed by exercise frequency (p<0.05). In contrast, exercise intensity (p>0.05) did not significantly affect social anxiety levels.
Conclusion
The most influential factors associated with decreased social anxiety were: 1) moderate to high exercise intensity, 2) exercise duration of at least one hour, and 3) exercise frequency of at least 1–2 times per week. Among these factors, exercise duration and frequency demonstrated significantly stronger associations with reduced social anxiety. Therefore, it is advisable to prioritize exercise duration and frequency in physical activity programs for college students to reduce social anxiety and achieve more substantial outcomes.
6.Asia-Pacific Menopause Federation Consensus Statement on the Management of Menopause 2024
Seng Bin ANG ; Stella Rizalina Sasha SUGIANTO ; Felicia Clara Jun Hui TAN ; Sonia DAVISON ; Qi YU ; Masakazu TERAUCHI ; Mee-Ran KIM ; Jignesh SHAH ; Shaikh Zinnat Ara NASREEN ; Choon Moy HO ; Enkhee SODNOMDORJ ; Muhammad Fidel Ganis SIREGAR ; Rubina HUSSAIN ; Ma Corazon Zaida NOBLEJAS-GAMILLA ; Yang CHUA ; Yung-Chieh TSAI ; Unnop JAISAMRARN
Journal of Menopausal Medicine 2025;31(1):3-11
Objectives:
This study aimed to achieve expert consensus on menopause management in the Asia-Pacific region, taking into account patient diversity, the latest evidence, and current treatment options.
Methods:
A focused literature search was performed to identify clinical practice statements on menopause management. Menopause experts were nominated by members of the Asia-Pacific Menopause Federation (APMF) society. A modified Delphi methodology, involving iterative rounds of anonymous surveys, was employed until consensus was reached for each statement. Consensus was defined as ≥ 70% of experts voting ‘agree’ or ‘strongly agree’ for a given clinical practice statement.
Results:
A total of 39 participants from 14 different APMF member societies were involved. Eighty-five clinical practice statements reached a consensus. Based on the clinical practice statements, an algorithm was created as a tool to guide clinicians on menopause management. APMF experts agreed that, in addition to vasomotor symptoms, Asian women experiencing somatic or psychological symptoms may also benefit from treatment with menopausal hormone therapy (MHT). MHT should also be considered for the prevention of osteoporosis in asymptomatic peri- and postmenopausal women.
Conclusions
This APMF consensus statement supersedes the previous one published in 2008. It provides guidance to gynecologists, endocrinologists, family physicians, and other healthcare professionals in delivering optimal care to menopausal women in the ethnically and culturally diverse Asia-Pacific region.
7.Relationships Between Exercise Components and Social Anxiety Levels Among Chinese College Students
Qi CHENG ; Wenbing YU ; Mingxiao JU ; Duo YANG ; Jiannan FU ; Shilong SONG
Psychiatry Investigation 2025;22(2):196-203
Objective:
This study aimed to explore the relationships between various exercise components (frequency, intensity, duration) and social anxiety.
Methods:
A sample of 844 college students in China participated in this study. The Physical Activity Rating Scale-3 assessed participants’ daily physical activity. Social anxiety levels were measured using the Liebowitz Social Anxiety Scale. A questionnaire was developed to collect demographic information and examine the relationships between exercise components and social anxiety levels.
Results:
One-way analysis of variance revealed significant differences in social anxiety levels across varying physical activity intensities. Specifically, students engaging in high levels of physical activity exhibited the lowest social anxiety. Post hoc analyses identified that exercise frequency F3 (p<0.01), exercise duration D5 (p<0.01), and exercise intensity I3 (p<0.01) were significantly associated with the lowest social anxiety levels. Among these components, regression analysis indicated that exercise duration (p<0.01) had the most substantial impact on social anxiety levels, followed by exercise frequency (p<0.05). In contrast, exercise intensity (p>0.05) did not significantly affect social anxiety levels.
Conclusion
The most influential factors associated with decreased social anxiety were: 1) moderate to high exercise intensity, 2) exercise duration of at least one hour, and 3) exercise frequency of at least 1–2 times per week. Among these factors, exercise duration and frequency demonstrated significantly stronger associations with reduced social anxiety. Therefore, it is advisable to prioritize exercise duration and frequency in physical activity programs for college students to reduce social anxiety and achieve more substantial outcomes.
8.Relationships Between Exercise Components and Social Anxiety Levels Among Chinese College Students
Qi CHENG ; Wenbing YU ; Mingxiao JU ; Duo YANG ; Jiannan FU ; Shilong SONG
Psychiatry Investigation 2025;22(2):196-203
Objective:
This study aimed to explore the relationships between various exercise components (frequency, intensity, duration) and social anxiety.
Methods:
A sample of 844 college students in China participated in this study. The Physical Activity Rating Scale-3 assessed participants’ daily physical activity. Social anxiety levels were measured using the Liebowitz Social Anxiety Scale. A questionnaire was developed to collect demographic information and examine the relationships between exercise components and social anxiety levels.
Results:
One-way analysis of variance revealed significant differences in social anxiety levels across varying physical activity intensities. Specifically, students engaging in high levels of physical activity exhibited the lowest social anxiety. Post hoc analyses identified that exercise frequency F3 (p<0.01), exercise duration D5 (p<0.01), and exercise intensity I3 (p<0.01) were significantly associated with the lowest social anxiety levels. Among these components, regression analysis indicated that exercise duration (p<0.01) had the most substantial impact on social anxiety levels, followed by exercise frequency (p<0.05). In contrast, exercise intensity (p>0.05) did not significantly affect social anxiety levels.
Conclusion
The most influential factors associated with decreased social anxiety were: 1) moderate to high exercise intensity, 2) exercise duration of at least one hour, and 3) exercise frequency of at least 1–2 times per week. Among these factors, exercise duration and frequency demonstrated significantly stronger associations with reduced social anxiety. Therefore, it is advisable to prioritize exercise duration and frequency in physical activity programs for college students to reduce social anxiety and achieve more substantial outcomes.
9.Asia-Pacific Menopause Federation Consensus Statement on the Management of Menopause 2024
Seng Bin ANG ; Stella Rizalina Sasha SUGIANTO ; Felicia Clara Jun Hui TAN ; Sonia DAVISON ; Qi YU ; Masakazu TERAUCHI ; Mee-Ran KIM ; Jignesh SHAH ; Shaikh Zinnat Ara NASREEN ; Choon Moy HO ; Enkhee SODNOMDORJ ; Muhammad Fidel Ganis SIREGAR ; Rubina HUSSAIN ; Ma Corazon Zaida NOBLEJAS-GAMILLA ; Yang CHUA ; Yung-Chieh TSAI ; Unnop JAISAMRARN
Journal of Menopausal Medicine 2025;31(1):3-11
Objectives:
This study aimed to achieve expert consensus on menopause management in the Asia-Pacific region, taking into account patient diversity, the latest evidence, and current treatment options.
Methods:
A focused literature search was performed to identify clinical practice statements on menopause management. Menopause experts were nominated by members of the Asia-Pacific Menopause Federation (APMF) society. A modified Delphi methodology, involving iterative rounds of anonymous surveys, was employed until consensus was reached for each statement. Consensus was defined as ≥ 70% of experts voting ‘agree’ or ‘strongly agree’ for a given clinical practice statement.
Results:
A total of 39 participants from 14 different APMF member societies were involved. Eighty-five clinical practice statements reached a consensus. Based on the clinical practice statements, an algorithm was created as a tool to guide clinicians on menopause management. APMF experts agreed that, in addition to vasomotor symptoms, Asian women experiencing somatic or psychological symptoms may also benefit from treatment with menopausal hormone therapy (MHT). MHT should also be considered for the prevention of osteoporosis in asymptomatic peri- and postmenopausal women.
Conclusions
This APMF consensus statement supersedes the previous one published in 2008. It provides guidance to gynecologists, endocrinologists, family physicians, and other healthcare professionals in delivering optimal care to menopausal women in the ethnically and culturally diverse Asia-Pacific region.
10.Relationships Between Exercise Components and Social Anxiety Levels Among Chinese College Students
Qi CHENG ; Wenbing YU ; Mingxiao JU ; Duo YANG ; Jiannan FU ; Shilong SONG
Psychiatry Investigation 2025;22(2):196-203
Objective:
This study aimed to explore the relationships between various exercise components (frequency, intensity, duration) and social anxiety.
Methods:
A sample of 844 college students in China participated in this study. The Physical Activity Rating Scale-3 assessed participants’ daily physical activity. Social anxiety levels were measured using the Liebowitz Social Anxiety Scale. A questionnaire was developed to collect demographic information and examine the relationships between exercise components and social anxiety levels.
Results:
One-way analysis of variance revealed significant differences in social anxiety levels across varying physical activity intensities. Specifically, students engaging in high levels of physical activity exhibited the lowest social anxiety. Post hoc analyses identified that exercise frequency F3 (p<0.01), exercise duration D5 (p<0.01), and exercise intensity I3 (p<0.01) were significantly associated with the lowest social anxiety levels. Among these components, regression analysis indicated that exercise duration (p<0.01) had the most substantial impact on social anxiety levels, followed by exercise frequency (p<0.05). In contrast, exercise intensity (p>0.05) did not significantly affect social anxiety levels.
Conclusion
The most influential factors associated with decreased social anxiety were: 1) moderate to high exercise intensity, 2) exercise duration of at least one hour, and 3) exercise frequency of at least 1–2 times per week. Among these factors, exercise duration and frequency demonstrated significantly stronger associations with reduced social anxiety. Therefore, it is advisable to prioritize exercise duration and frequency in physical activity programs for college students to reduce social anxiety and achieve more substantial outcomes.


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