1.Effects of Electro-Acupuncture Based on the Midnight-Noon Ebb-Low Method with Hour-Prescription on BMAL1 Protein and NETs Markers in Lung Tissue of Chronic Obstructive Pulmonary Disease Model Rats with Lung-Qi Deficiency Syndrome
Changtian JIAO-LI ; Nise Pantaleo SHIO ; Lianqing CAI ; Qingyao JIANG ; Siyu TANG ; Qianqian WAN ; Mengchen WAN ; Yuqi YE ; Jie ZHU
Journal of Traditional Chinese Medicine 2026;67(13):1422-1430
ObjectiveTo explore the potential mechanism underlying electroacupuncture therapy with the midnight-noon ebb-low method with hour-prescription for chronic obstructive pulmonary disease (COPD) with lung-qi deficiency syndrome from the perspective of brain and muscle basic helix-loop-helix ARNT-like 1 (BMAL1) as well as neutrophil extracellular traps (NETs). MethodsThe experiment was conducted in two phases. For the therapeutic effectiveness observation, 24 rats were randomly allocated into control group 1, model group 1, midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group, with 6 rats per group. Rat models of COPD with lung-qi deficiency syndrome were established via cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide (LPS). After successful modelling, rats in midnight-noon electro-acupuncture group 1 received electro-acupuncture at acupoints "Taiyuan (LU 9)", "Feishu (BL 13)" and "Zusanli (ST 36)" during 05:00—07:00, 30 minutes per treatment once every other day for 14 consecutive days (7 sessions in total). Rats in the conventional electro-acupuncture group received identical electroacupuncture manipulation at random daytime hours (08:00—18:00). Pulmonary function parameters including forced expiratory volume in 0.3 second (FEV0.3), forced vital capacity (FVC) and FEV0.3/FVC ratio were detected. Pulmonary histopathological changes were observed via hematoxylin-eosin (HE) staining. Plasma levels of pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well as pulmonary reactive oxygen species (ROS) content, BMAL1 protein expression and the levels of neutrophil extracellular traps (NETs) biomarkers such as myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (CitH3) in lung tissue were determined. For the mechanistic verification phase, 36 rats were divided into control group 2, model group 2, midnight-noon electro-acupuncture group 2, overexpression empty group, overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group, with 6 rats in each group. At the 5th week of model construction, rats in the overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group received intratracheal instillation of 100 μl adenoviral suspension carrying overexpressed Bmal1 gene. Rats in the overexpression empty group were injected with an equal titer and equal volume of blank adenovirus without the Bmal1 coding sequence into the lung at the identical time point. Midnight-noon electro-acupuncture group 2 and overexpression with midnight-noon electro-acupuncture group were consistent with the aforementioned protocol. Finally, pulmonary levels of MPO, NE and CitH3 were measured in all groups. ResultsCompared with the control group 1, the model group 1 exhibited decreased FEV0.3, FVC and FEV0.3/FVC ratio, elevated plasma IL-1β, TNF-α and pulmonary ROS levels, downregulated lung BMAL1 protein expression, and increased contents of MPO, NE and CitH3 (all P<0.05); typical NETs-like structures with sparse granular substances attached to fibrous networks were observed under scanning electron microscopy; HE staining revealed damaged alveolar architecture accompanied by inflammatory cell infiltration. Compared with model group 1, both the midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group achieved obvious improvements in all above indicators, with superior therapeutic effects in midnight-noon electro-acupuncture group 1 (P<0.05). Consistently, midnight-noon electro-acupuncture group 1 showed more prominent alleviation of NETs-like structure formation and lung pathological injury compared to the conventional electro-acupuncture group. Mechanistic validation results demonstrated that compared with model group 2, the average optical density of MPO as well as the protein levels of MPO, NE and CitH3 were markedly reduced in midnight-noon electro-acupuncture group 2, overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group (P<0.05); furthermore, these parameters were significantly lower in the overexpression with midnight-noon electro-acupuncture group than in midnight-noon electro-acupuncture group 2 (P<0.05). ConclusionElectro-acupuncture based on the midnight-noon ebb-low method with hour-prescription may alleviate pulmonary inflammation in COPD by upregulating the expression of clock protein BMAL1 and inhibiting excessive accumulation of NETs in lung tissue.
2.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
3.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
4.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
5.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
6.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
7.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.
8.Evaluation of the reliability and validity of the Chinese listening self-efficacy questionnaire
Wenling JIANG ; Junyan ZHU ; Qian ZHOU ; Yuqi JIN ; Yan REN ; Haifeng LI ; Zhi-wu HUANG
Journal of Audiology and Speech Pathology 2025;33(2):134-139
Objective To develop and translate the Chinese listening self-efficacy questionnaire(C-LSEQ)and to test its reliability and validity.Methods A total of 172 subjects aged≥60 years with age-related hearing loss completed the C-LSEQ questionnaire via direct interviews.Pure tone hearing threshold test,Mandarin hearing in noise test,and the hearing handicap inventory for elderly-screening(HHIE-S)were evaluated.Twenty subjects were randomly selected from the original group to complete the C-LSEQ questionnaire in 2 weeks after the initial evaluation.Results ① Reliability:The Cronbach's a coefficients of the three sub-dimensions and the overall ques-tionnaire were all>0.8,and the test-retest reliability coefficients of the three sub-dimensions and the overall ques-tionnaire were all>0.9(P<0.001).② Validity:The experts collectively evaluated the representativeness of the statements with good content validity.The convergent validity test showed that the composite reliability(CR)of the 2 sub-dimensions and the overall questionnaire were all>0.7,and the average variance extracted(AVE)were all>0.5.The CR value of the complex listening dimension was 0.655,and the AVE value was 0.937.The criterion validity test showed that the overall questionnaire and the three sub-dimensions of the C-LSEQ were significantly correlated with the pure-tone average,speech recognition thresholds in noise,and HHIE-S(P<0.001).Conclusion The C-LSEQ exhibits stable structure,with good reliability and validity.It can be used to assess listen-ing self-efficacy in adults with hearing loss,especially in the elderly with age-related hearing loss.
9.Practical exploration on the responsibilities and operation specifications of assistants in robotic radical gastrectomy
Yulong TIAN ; Yuqi SUN ; Xiaoning KANG ; Yan WANG ; Shougen CAO ; Xiaodong LIU ; Zequn LI ; Gan LIU ; Xiaojie TAN ; Cheng MENG ; Haitao JIANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Gastrointestinal Surgery 2025;28(8):937-941
Robot-assisted surgery with its advantages such as three-dimensional high-definition vision, dexterous robotic arms, and tremor filtration, is increasingly being applied to complex radical gastrectomy. However, the role of the surgical assistant remains crucial during the procedure. The assistant is responsible for tasks outside the console, including adjusting robotic arms, changing instruments, exposing the surgical field, and addressing unexpected situations. The technical proficiency of the assistant and their collaboration efficiency with the primary surgeon directly impact the smoothness of surgery and patients' outcomes. With the expansion of robot-assisted surgical indications, the establishment of a standardized training system and the optimization of team collaboration models have become urgent challenges to address. This article draws on the author's practical experience as an assistant in robot-assisted gastric cancer surgeries, conducting an in-depth analysis of the responsibilities and operational skills of surgical assistants in robot-assisted procedures. The aim is to develop a relatively comprehensive set of operational guidelines for surgical assistants in robot-assisted radical gastrectomy, providing valuable references for enhancing the overall efficiency of surgical teams and improving surgical outcomes.
10.Evaluation of the reliability and validity of the Chinese listening self-efficacy questionnaire
Wenling JIANG ; Junyan ZHU ; Qian ZHOU ; Yuqi JIN ; Yan REN ; Haifeng LI ; Zhi-wu HUANG
Journal of Audiology and Speech Pathology 2025;33(2):134-139
Objective To develop and translate the Chinese listening self-efficacy questionnaire(C-LSEQ)and to test its reliability and validity.Methods A total of 172 subjects aged≥60 years with age-related hearing loss completed the C-LSEQ questionnaire via direct interviews.Pure tone hearing threshold test,Mandarin hearing in noise test,and the hearing handicap inventory for elderly-screening(HHIE-S)were evaluated.Twenty subjects were randomly selected from the original group to complete the C-LSEQ questionnaire in 2 weeks after the initial evaluation.Results ① Reliability:The Cronbach's a coefficients of the three sub-dimensions and the overall ques-tionnaire were all>0.8,and the test-retest reliability coefficients of the three sub-dimensions and the overall ques-tionnaire were all>0.9(P<0.001).② Validity:The experts collectively evaluated the representativeness of the statements with good content validity.The convergent validity test showed that the composite reliability(CR)of the 2 sub-dimensions and the overall questionnaire were all>0.7,and the average variance extracted(AVE)were all>0.5.The CR value of the complex listening dimension was 0.655,and the AVE value was 0.937.The criterion validity test showed that the overall questionnaire and the three sub-dimensions of the C-LSEQ were significantly correlated with the pure-tone average,speech recognition thresholds in noise,and HHIE-S(P<0.001).Conclusion The C-LSEQ exhibits stable structure,with good reliability and validity.It can be used to assess listen-ing self-efficacy in adults with hearing loss,especially in the elderly with age-related hearing loss.

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