1.Erjingwan Alleviate Inflammatory Response and Apoptosis in Skeletal Muscle Cells of Sarcopenia via SIRT1/Nrf2/HO-1 Signaling Pathway
Long SHI ; Yang LI ; Hongyu YAN ; Tianle ZHOU ; Zhiwen ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):57-66
ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group, a model group, and groups with different doses of Erjingwan (8,16,32 g·kg-1). The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum samples of mice, and biochemical tests were conducted to quantify the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the serum. The protein and mRNA levels of SIRT1, Nrf2, B-cell lymphoma (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsAfter 4 weeks of drug intervention, the model group exhibited significant reductions in body weight and grip strength (P0.01) compared with the control group. Compared with the model group, all doses of Erjingwan increased the body weight in mice at week 8 (P0.01) and grip strength from week 6 (P0.01). HE staining revealed clear muscle fiber structure in the control group, muscle fiber rupture and atrophy in the model group, and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group, collagen fiber proliferation and severe fibrosis in the model group, and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group (P0.01). After intervention, the low-dose Erjingwan group exhibited a decreased TNF-α level (P0.05), while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels (P0.01). Biochemical assays revealed that the model group had decreased SOD and GSH levels (P0.01) and an increased MDA level (P0.01) compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels (P0.01) and decreases in MDA level (P0.01), compared with the model group. WB and Real-time PCR results showed that compared with the control group, the model group presented down-regulated protein and mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 in the muscle tissue (P0.01) and up-regulated protein and mRNA levels of Bax (P0.01). Compared with the model group, Erjingwan at different doses up-regulated the protein levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01) and down-regulated the protein and mRNA levels of Bax (P0.01) in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 (P0.05, P0.01), and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01). ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells, improved the antioxidant capacity, and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway, inflammatory response, and apoptosis network.
2.Erjingwan Alleviate Inflammatory Response and Apoptosis in Skeletal Muscle Cells of Sarcopenia via SIRT1/Nrf2/HO-1 Signaling Pathway
Long SHI ; Yang LI ; Hongyu YAN ; Tianle ZHOU ; Zhiwen ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):57-66
ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group, a model group, and groups with different doses of Erjingwan (8,16,32 g·kg-1). The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum samples of mice, and biochemical tests were conducted to quantify the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the serum. The protein and mRNA levels of SIRT1, Nrf2, B-cell lymphoma (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsAfter 4 weeks of drug intervention, the model group exhibited significant reductions in body weight and grip strength (P0.01) compared with the control group. Compared with the model group, all doses of Erjingwan increased the body weight in mice at week 8 (P0.01) and grip strength from week 6 (P0.01). HE staining revealed clear muscle fiber structure in the control group, muscle fiber rupture and atrophy in the model group, and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group, collagen fiber proliferation and severe fibrosis in the model group, and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group (P0.01). After intervention, the low-dose Erjingwan group exhibited a decreased TNF-α level (P0.05), while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels (P0.01). Biochemical assays revealed that the model group had decreased SOD and GSH levels (P0.01) and an increased MDA level (P0.01) compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels (P0.01) and decreases in MDA level (P0.01), compared with the model group. WB and Real-time PCR results showed that compared with the control group, the model group presented down-regulated protein and mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 in the muscle tissue (P0.01) and up-regulated protein and mRNA levels of Bax (P0.01). Compared with the model group, Erjingwan at different doses up-regulated the protein levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01) and down-regulated the protein and mRNA levels of Bax (P0.01) in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 (P0.05, P0.01), and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1, Nrf2, HO-1, and Bcl-2 (P0.01). ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells, improved the antioxidant capacity, and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway, inflammatory response, and apoptosis network.
3.Central nervous mechanisms underlying effects of cognitive impairment on dual-task stance:functional near-infrared spectroscopy analysis
Zhiwen DONG ; Cong YU ; Yan CHEN ; Jianjun DING
Chinese Journal of Tissue Engineering Research 2025;29(17):3579-3587
BACKGROUND:Elderly people with mild cognitive impairment experience a decline in postural control ability due to cognitive function decline,making them more prone to falls.The dual-task paradigm,which more closely mirrors daily life,is often used to assess postural control ability.However,previous dual-task studies on cognition and postural control in elderly people with mild cognitive impairment have mainly focused on the external manifestations of postural control,with direct evidence of central nervous mechanisms still lacking.OBJECTIVE:To investigate the activation characteristics of the cerebral somatic sensorimotor cortex in the elderly people with mild cognitive impairment while performing the dual task of stance postural control and spatial working memory.METHODS:Participants were screened using the Montreal Cognitive Assessment,enrolling 16 elderly people with mild cognitive impairment and 17 healthy older people.They performed five task tests:spatial working memory,dual-feet balance stance,Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory.Functional near-infrared spectroscopy and a three-dimentional force platform were used simultaneously to collect data on cerebral cortex(20 channels)hemodynamics and center of pressure swing trajectory.RESULTS AND CONCLUSION:In Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory tasks,center of pressure displacements in anterior-posterior and medial-lateral directions were significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of dual-feet balance stance and spatial working memory task,ΔHbO2 at channel 15(right pre-motor cortex and supplementary motor area)was significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of Romberg stance and spatial working memory task,ΔHbO2 at channels 15 and 17(right pre-motor cortex and supplementary motor area)was significantly greater in the elderly people with mild cognitive impairment compared with the healthy older people(P<0.05).In dual task of Romberg stance and spatial working memory task,a significantly positive correlation in the elderly people with mild cognitive impairment(r=0.659,P<0.05)and a strong positive correlation in the healthy older people were observed between center of pressure displacement in medial-lateral direction and ΔHbO2 at channel 15(r=0.840,P<0.05).The results indicate that compared with the cognitively normal healthy older people,the elderly people with mild cognitive impairment showed weaker stance postural control capability during the dual task of stance postural control and spatial working memory,with higher activation levels in the right pre-motor cortex and supplementary motor area.The increased brain resource allocation for lateral postural control may represent the brain compensation mechanism in the elderly people with mild cognitive impairment due to cognitive decline leading to weakened stance postural control ability.
4.Research on emotion recognition methods based on multi-modal physiological signal feature fusion.
Zhiwen ZHANG ; Naigong YU ; Yan BIAN ; Jinhan YAN
Journal of Biomedical Engineering 2025;42(1):17-23
Emotion classification and recognition is a crucial area in emotional computing. Physiological signals, such as electroencephalogram (EEG), provide an accurate reflection of emotions and are difficult to disguise. However, emotion recognition still faces challenges in single-modal signal feature extraction and multi-modal signal integration. This study collected EEG, electromyogram (EMG), and electrodermal activity (EDA) signals from participants under three emotional states: happiness, sadness, and fear. A feature-weighted fusion method was applied for integrating the signals, and both support vector machine (SVM) and extreme learning machine (ELM) were used for classification. The results showed that the classification accuracy was highest when the fusion weights were set to EEG 0.7, EMG 0.15, and EDA 0.15, achieving accuracy rates of 80.19% and 82.48% for SVM and ELM, respectively. These rates represented an improvement of 5.81% and 2.95% compared to using EEG alone. This study offers methodological support for emotion classification and recognition using multi-modal physiological signals.
Humans
;
Emotions/physiology*
;
Electroencephalography
;
Support Vector Machine
;
Electromyography
;
Signal Processing, Computer-Assisted
;
Galvanic Skin Response/physiology*
;
Machine Learning
;
Male
5.Central nervous mechanisms underlying effects of cognitive impairment on dual-task stance:functional near-infrared spectroscopy analysis
Zhiwen DONG ; Cong YU ; Yan CHEN ; Jianjun DING
Chinese Journal of Tissue Engineering Research 2025;29(17):3579-3587
BACKGROUND:Elderly people with mild cognitive impairment experience a decline in postural control ability due to cognitive function decline,making them more prone to falls.The dual-task paradigm,which more closely mirrors daily life,is often used to assess postural control ability.However,previous dual-task studies on cognition and postural control in elderly people with mild cognitive impairment have mainly focused on the external manifestations of postural control,with direct evidence of central nervous mechanisms still lacking.OBJECTIVE:To investigate the activation characteristics of the cerebral somatic sensorimotor cortex in the elderly people with mild cognitive impairment while performing the dual task of stance postural control and spatial working memory.METHODS:Participants were screened using the Montreal Cognitive Assessment,enrolling 16 elderly people with mild cognitive impairment and 17 healthy older people.They performed five task tests:spatial working memory,dual-feet balance stance,Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory.Functional near-infrared spectroscopy and a three-dimentional force platform were used simultaneously to collect data on cerebral cortex(20 channels)hemodynamics and center of pressure swing trajectory.RESULTS AND CONCLUSION:In Romberg stance,dual task of dual-feet balance stance and spatial working memory,and dual task of Romberg stance and spatial working memory tasks,center of pressure displacements in anterior-posterior and medial-lateral directions were significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of dual-feet balance stance and spatial working memory task,ΔHbO2 at channel 15(right pre-motor cortex and supplementary motor area)was significantly greater in mild cognitive impairment elderly people than that in normal elder people(P<0.05).In dual task of Romberg stance and spatial working memory task,ΔHbO2 at channels 15 and 17(right pre-motor cortex and supplementary motor area)was significantly greater in the elderly people with mild cognitive impairment compared with the healthy older people(P<0.05).In dual task of Romberg stance and spatial working memory task,a significantly positive correlation in the elderly people with mild cognitive impairment(r=0.659,P<0.05)and a strong positive correlation in the healthy older people were observed between center of pressure displacement in medial-lateral direction and ΔHbO2 at channel 15(r=0.840,P<0.05).The results indicate that compared with the cognitively normal healthy older people,the elderly people with mild cognitive impairment showed weaker stance postural control capability during the dual task of stance postural control and spatial working memory,with higher activation levels in the right pre-motor cortex and supplementary motor area.The increased brain resource allocation for lateral postural control may represent the brain compensation mechanism in the elderly people with mild cognitive impairment due to cognitive decline leading to weakened stance postural control ability.
6.Propensity matching study of robot-assisted intracorporeal versus extracorporeal orthotopic neobladder reconstruction
Bing YAN ; Yuan LIU ; Xiaozhou ZHOU ; Yang LIU ; Yuwei LI ; Xuemei LI ; Zhiwen CHEN
Chinese Journal of Urology 2024;45(12):893-898
Objective:To compare the surgical efficacy and perioperative complications of total intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) reconstruction during robot-assisted radical cystectomy.Methods:We retrospectively reviewed our single-institutional, prospectively collected database for consecutive patients who underwent RARC with an ileum neobladder from January 2017 to June 2022. A total of 265 patients were collected, 158 in ICNB group and 107 in ECNB group. The two groups were matched 1∶1 according to gender, age, BMI, ASA score, NAC, history of abdominal surgery and tumor characteristics using propensity score matching (PSM) method. After PSM, operating time, estimated blood loss and perioperative complications were compared between ICNB and ECNB group. A total of 186 patients were paired (93 patients in each group). There were 91 males and 2 females in ICNB group. The median age of ICNB group was 64(55, 68) years; median BMI was 23.54(22.39, 25.39) kg/m 2; There were 91 cases with Clinical stage ≤T 2 stage and 15 cases with ASA score ≥3; 25 cases received neoadjuvant chemotherapy. There were 91 males and 2 females in ECNB group. The median age of ECNB group was 63(52, 67) years; median BMI was 23.31(20.76, 24.80) kg/m 2; There were 90 cases with Clinical stage ≤T 2 stage and 8 cases with ASA score ≥3; 12 cases received neoadjuvant chemotherapy. In the ECNB group, after completing the radical cystectomy and pelvic lymph node dissection with robot assistance, the traditional lower abdominal incision was used to pull the intestinal tube outside the body to complete the preparation of the new bladder and then restore it to the pelvic cavity for anastomosing, while in the ICNB group, the reconstruction of the new bladder in situ was always completed in the body cavity with robot assistance. The operative time, intraoperative blood loss and perioperative complications were compared between the two groups. Results:The median operative time in ICNB and ECNB groups was 302(261, 350) min and 337(285, 397) min, respectively ( P=0.003); median intraoperative blood loss was 300(225, 500) ml and 500(300, 650) ml, respectively ( P<0.01); perioperative blood transfusion rates were 4.3%(4/93) and 14.0%(13/93), respectively ( P=0.022); all the differences between the 2 groups were statistically significant. 90-d overall complications rate was significant lower in ICNB group (38.7% vs. 61.3%, P=0.002). There was no difference in 90-d major complications (8.6% vs. 16.1%, P=0.119). On multivariate logistic regression analysis, operating time( OR=1.004, 95% CI 1.000-1.007, P=0.040), surgical approach (ICNB/ECNB)( OR=2.248, 95% CI 1.220-4.141, P=0.009) and age( OR=1.036, 95% CI 1.002-1.072, P=0.037) were associated with 90-day overall complications. Operating time( OR=1.036, 95% CI 1.002-1.072, P=0.037), neoadjuvant chemotherapy( OR=0.198, 95% CI 0.059-0.663, P=0.009) and ASA score( OR=0.167, 95% CI 0.044-0.634, P=0.009) were associated with 90-day high-grade complications. Conclusion:Intracorporeal neobladder during robot-assisted radical cystectomy is safe and feasible. Compared with ECNB, ICNB significantly improved perioperative outcomes such as shorter operating time, fewer estimated blood loss and perioperative complications.
7.Research progress of totally intracorporeal orthotopic neobladder reconstruction in robot-assisted radical cystectomy
Chinese Journal of Urology 2024;45(11):881-884
With the development of robotic surgical system, the application of robot-assisted radical cystectomy(RARC) has become more and more popular. However, for neobladder reconstruction phase, most surgeons still use open technique through abdominal incision. In recent years, some institutions have explored the feasibility and safety of total intracorporeal orthotopic neobladder(ICNB). Based on relevant important literatures, this paper reviewed the RARC plus ICNB from the aspects of surgical principle, complications and functional outcomes, learning curve, and existing controversies.
8.Propensity matching study of robot-assisted intracorporeal versus extracorporeal orthotopic neobladder reconstruction
Bing YAN ; Yuan LIU ; Xiaozhou ZHOU ; Yang LIU ; Yuwei LI ; Xuemei LI ; Zhiwen CHEN
Chinese Journal of Urology 2024;45(12):893-898
Objective:To compare the surgical efficacy and perioperative complications of total intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) reconstruction during robot-assisted radical cystectomy.Methods:We retrospectively reviewed our single-institutional, prospectively collected database for consecutive patients who underwent RARC with an ileum neobladder from January 2017 to June 2022. A total of 265 patients were collected, 158 in ICNB group and 107 in ECNB group. The two groups were matched 1∶1 according to gender, age, BMI, ASA score, NAC, history of abdominal surgery and tumor characteristics using propensity score matching (PSM) method. After PSM, operating time, estimated blood loss and perioperative complications were compared between ICNB and ECNB group. A total of 186 patients were paired (93 patients in each group). There were 91 males and 2 females in ICNB group. The median age of ICNB group was 64(55, 68) years; median BMI was 23.54(22.39, 25.39) kg/m 2; There were 91 cases with Clinical stage ≤T 2 stage and 15 cases with ASA score ≥3; 25 cases received neoadjuvant chemotherapy. There were 91 males and 2 females in ECNB group. The median age of ECNB group was 63(52, 67) years; median BMI was 23.31(20.76, 24.80) kg/m 2; There were 90 cases with Clinical stage ≤T 2 stage and 8 cases with ASA score ≥3; 12 cases received neoadjuvant chemotherapy. In the ECNB group, after completing the radical cystectomy and pelvic lymph node dissection with robot assistance, the traditional lower abdominal incision was used to pull the intestinal tube outside the body to complete the preparation of the new bladder and then restore it to the pelvic cavity for anastomosing, while in the ICNB group, the reconstruction of the new bladder in situ was always completed in the body cavity with robot assistance. The operative time, intraoperative blood loss and perioperative complications were compared between the two groups. Results:The median operative time in ICNB and ECNB groups was 302(261, 350) min and 337(285, 397) min, respectively ( P=0.003); median intraoperative blood loss was 300(225, 500) ml and 500(300, 650) ml, respectively ( P<0.01); perioperative blood transfusion rates were 4.3%(4/93) and 14.0%(13/93), respectively ( P=0.022); all the differences between the 2 groups were statistically significant. 90-d overall complications rate was significant lower in ICNB group (38.7% vs. 61.3%, P=0.002). There was no difference in 90-d major complications (8.6% vs. 16.1%, P=0.119). On multivariate logistic regression analysis, operating time( OR=1.004, 95% CI 1.000-1.007, P=0.040), surgical approach (ICNB/ECNB)( OR=2.248, 95% CI 1.220-4.141, P=0.009) and age( OR=1.036, 95% CI 1.002-1.072, P=0.037) were associated with 90-day overall complications. Operating time( OR=1.036, 95% CI 1.002-1.072, P=0.037), neoadjuvant chemotherapy( OR=0.198, 95% CI 0.059-0.663, P=0.009) and ASA score( OR=0.167, 95% CI 0.044-0.634, P=0.009) were associated with 90-day high-grade complications. Conclusion:Intracorporeal neobladder during robot-assisted radical cystectomy is safe and feasible. Compared with ECNB, ICNB significantly improved perioperative outcomes such as shorter operating time, fewer estimated blood loss and perioperative complications.
9.Research progress of totally intracorporeal orthotopic neobladder reconstruction in robot-assisted radical cystectomy
Chinese Journal of Urology 2024;45(11):881-884
With the development of robotic surgical system, the application of robot-assisted radical cystectomy(RARC) has become more and more popular. However, for neobladder reconstruction phase, most surgeons still use open technique through abdominal incision. In recent years, some institutions have explored the feasibility and safety of total intracorporeal orthotopic neobladder(ICNB). Based on relevant important literatures, this paper reviewed the RARC plus ICNB from the aspects of surgical principle, complications and functional outcomes, learning curve, and existing controversies.
10.Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.
Jiawen ZHOU ; Xinyue SUN ; Xuelian CHEN ; Huimin LIU ; Xiulian MIAO ; Yan GUO ; Zhiwen FAN ; Jie LI ; Yong XU ; Zilong LI
Acta Pharmaceutica Sinica B 2024;14(1):256-272
Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

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