1.Research progress on the mechanism of action and clinical application of Shenqi dihuang decoction in the treatment of diabetic nephropathy
Jiajie LI ; Jiaqi WANG ; Jie ZHAO ; Zezhu LI ; Yaping WANG ; Guirong ZHANG ; Heguo YAN ; Jiabao LIAO ; Weibo WEN
China Pharmacy 2026;37(8):1085-1091
Diabetic nephropathy(DN) is a common and severe microvascular complication of diabetes. In recent years, the classical herbal formula Shenqi dihuang decoction has demonstrated unique advantages in the clinical treatment of DN. This article conducts a systematic review of the mechanisms of action and clinical applications of Shenqi dihuang decoction in the treatment of DN. It reveals that the mechanism by which this formula improves DN involves multi-target synergistic regulation. For instance, Shenqi dihuang decoction exerts multiple pharmacological effects by regulating signaling pathways including phosphatidy linostiol 3-kinase/protein kinase B, AMP-activated protein kinase/silent information regulator 1/forkhead box O1, and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathways.These effects include regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing inflammation, improving insulin resistance, modulating cell death (apoptosis/autophagy/ferroptosis/pyroptosis), and preventing renal fibrosis. Existing clinical studies indicate that Shenqi dihuang decoction and its modified formulas, alone or in combination with other therapeutic methods, can significantly improve glucose and lipid metabolism, reduce proteinuria, and delay renal function decline in patients with DN. These effects are superior to those of Western medicines such as irbesartan, valsartan, and empagliflozin, and the treatment demonstrates good safety. Future research should leverage systems biology and artificial intelligence technologies to further elucidate the integrated mechanisms in the treatment of DN by Shenqi dihuang decoction, thereby advancing the precision and standardization of its clinical application.
2.Application of nickel-titanium shape memory staples in treatment of multiple metatarsal fractures.
Jie CHEN ; Zhen YIN ; Weibo ZHOU ; Wen TAN ; Fulin ZHOU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(2):146-150
OBJECTIVE:
To investigate the effectiveness of nickel-titanium shape memory staples in treating multiple metatarsal fractures.
METHODS:
The clinical data of 27 patients with multiple metatarsal fractures who were treated between January 2022 and June 2023 and met the selection criteria were retrospectively analysed. The cohort consisted of 16 males and 11 females, aged 33-65 years (mean, 47.44 years). The causes of injury included heavy object impact in 11 cases, traffic accidents in 9 cases, and crush in 7 cases. Simultaneous fractures of 2, 3, 4, and 5 bones occurred in 6, 6, 4, and 8 cases, respectively, with tarsometatarsal joint injury in 3 cases. Fixation was performed using staples for 16, 22, and 9 fractures in the metatarsal neck, shaft, and the base, respectively, and 5 tarsometatarsal joint injuries. Preoperative soft tissue injuries were identified in 8 cases and classified according to the Tscherne-Oestern closed soft tissue injury classification as type Ⅰ in 5 cases and type Ⅱ in 3 cases. One case of type Ⅱexhibited preoperative skin necrosis. The patients were treated with fixation using nickel-titanium shape memory staples. Complications and fracture healing were documented. At last follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was used to evaluate the function, and the visual analogue scale (VAS) score was used to evaluate the pain.
RESULTS:
The 27 patients were followed up 9-19 months (mean, 12.4 months). Postoperative X-ray films revealed no loss of fracture reduction, and all fractures achieved bony union. No internal fixator loosening, breakage, or other mechanical failures was observed. The mean fracture healing time was 3.13 months (range, 3-4 months). Postoperatively, 4 cases (2 of Tscherne-Oestern type Ⅰ, 2 of type Ⅱ) developed superficial skin necrosis, which resolved with dressing changes. No infection was observed in the remaining patients, and all wounds healed. At last follow-up, the AOFAS forefoot score ranged from 70 to 95, with an average of 86.6, of which 19 cases were excellent, 6 cases were good, and 2 cases were fair, with an excellent and good rate of 92.6%; the VAS score ranged from 0 to 3, with an average of 0.9, of which 24 cases were excellent, and 3 cases were good, with an excellent and good rate of 100%.
CONCLUSION
The use of nickel-titanium shape memory staples in the treatment of multiple metatarsal fractures can effectively protect local skin and soft tissues and minimize secondary damage associated with internal fixator insertion. It is a viable surgical option for management of multiple metatarsal fractures.
Humans
;
Male
;
Female
;
Middle Aged
;
Adult
;
Titanium
;
Nickel
;
Retrospective Studies
;
Fracture Fixation, Internal/instrumentation*
;
Aged
;
Metatarsal Bones/surgery*
;
Fractures, Bone/surgery*
;
Treatment Outcome
;
Sutures
;
Fractures, Multiple/surgery*
3.Research Progress on Animal Models of Gastric Ulcer of Spleen-Stomach Deficiency Cold Type
Ziqi LIU ; Yunying LI ; Qin LI ; Yuanhan LI ; Fangyan HE ; Weibo WEN
Laboratory Animal and Comparative Medicine 2025;45(5):574-585
Gastric ulcer(GU)is one of the common,frequently-occurring and intractable diseases of the digestive system.Spleen-stomach deficiency cold type is the most common and hard-to-cure syndrome pattern of GU,and is both a focus and a challenge in medical research.Therefore,constructing a scientific,reasonable,and clinically practical animal model of GU with spleen-stomach deficiency cold type and formulating objective and effective evaluation criteria are of great significance for in-depth research on the pathogenesis and treatment of GU.In this paper,the methods for constructing GU animal models of spleen-stomach deficiency cold type are comprehensively introduced by systematically reviewing the relevant literature.Firstly,the construction methods of pathological models of GU in Western medicine are introduced,including pyloric ligation method,water immersion-restraint stress method,ethanol-induced method,acetic acid-induced method,etc.This paper expounds the establishment methods for spleen-stomach deficiency cold syndrome type model in traditional Chinese medicine(TCM),including diet disorder method,bitter cold diarrhea method,excessive fatigue method,Qi consumption and Qi impairment method,and overeating sour-flavor method.This paper focuses on the construction methods for disease-syndrome combination GU models of spleen-stomach deficiency cold type,including two-factor modeling method and three-factor modeling method.Meanwhile,the evaluation indices of GU animal models of spleen-stomach deficiency cold type were summarized from various aspects,including animal physical signs(appearance symptoms,animal behavior,and metabolic indices),as well as tissue morphology and molecular biology-related indicators(gastric function,oxidative stress,inflammatory factors,other cytokines,four coagulation parameters,intestinal flora detection),for constructing a comprehensive evaluation system.From the perspective of prescription-based verification,this paper further analyzes the drug composition and pharmacological effects to infer the syndrome type of the treated animal model,so as to verify whether the target animal model is successfully constructed.This review aims to provide a valuable reference for establishing a syndrome-specific GU animal model that closely aligns with clinical reality and embodies the principles of Chinese medicine.This will further advance research on TCM-pattern GU syndromes and deepen the exploration of herbal medicine-based treatments for GU,ultimately promoting the clinical integration and advancement of Chinese medicine in GU therapy.
4.Application of arthroscopy-assisted posterior malleolar reduction in the surgical management of ankle fracture-dislocation
Jie CHEN ; Zhen YIN ; Weibo ZHOU ; Wen TAN ; Fulin ZHOU
Chinese Journal of Orthopaedics 2025;45(6):343-350
Objective:To investigate the surgical techniques and clinical efficacy of arthroscopic-assisted posterior malleolus reduction for the management of ankle fracture-dislocation.Methods:A retrospective analysis was performed on the clinical data of 27 patients who underwent arthroscopy-assisted posterior malleolar reduction via the posterior approach for the surgical management of ankle fracture-dislocation at the Third Affiliated Hospital of Nanjing Medical University (Changzhou No.2 People's Hospital) between January 2022 and June 2023. The cohort comprised 17 males and 10 females, with a mean age of 43.67±9.56 years (range, 25-63 years). Based on the Bartonícek and Rammelt classification, there were 15 type II cases, 9 type III cases, and 3 type IV cases. The operation time, posterior ankle arthroscopy duration, and postoperative complications, such as neurovascular injury, wound infection, or skin necrosis, were recorded. X-ray and 3D CT imaging were utilized to assess joint surface reduction quality, tibiofibular matching and fracture healing status. The ankle plantarflexion, dorsiflexion and hallux flexion contractures were recorded at the last follow-up. Functional outcomes were measured using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the Olerud-Molander ankle score (OMAS), while pain was evaluated using the visual analogue scale (VAS).Results:All 27 patients were followed up postoperatively, with a mean follow-up duration of 14.30±1.38 months (range, 12-18 months). Postoperatively, one patient experienced wound exudation, while another developed intermuscular venous thrombosis in the calf. No cases of neurovascular injury, wound infection, skin necrosis, or hallux flexion contracture occurred, and no reduction loss was observed. The mean operation time was 96.11±11.55 min (range, 80-120 min), and the posterior ankle arthroscopy duration was 35.74±5.67 min (range, 30-45 min). Postoperative X-ray evaluations demonstrated no loss of fracture reduction, and all fractures achieved bony union. The mean fracture healing time was 3.78±0.75 months (range, 3-5 months). Postoperative CT evaluations showed no joint surface malalignment, and distal tibiofibular matching was satisfactory. At the final follow-up, mean ankle plantarflexion was 46.74°±4.73° (range, 33°-50°), and dorsiflexion was 20.96°±3.29° (range, 14°-26°). There was no hallux flexion contracture occurred. The mean AOFAS ankle-hindfoot score was 92.11±7.19 (range, 74-100), with 20 excellent, 5 good, and 2 fair, yielding an excellent-good rate of 93%. The mean OMAS score was 94.44±7.25 (range, 75-100), comprising 20 excellent and 7 good results, yielding an excellent-good rate of 100%. The mean VAS score was 0.70±0.95 (range, 0-3).Conclusion:Arthroscopy-assisted posterior malleolar reduction in ankle fracture-dislocation surgery provides optimal soft tissue protection and ensures precise fracture reduction and fixation.
5.Application of arthroscopy-assisted posterior malleolar reduction in the surgical management of ankle fracture-dislocation
Jie CHEN ; Zhen YIN ; Weibo ZHOU ; Wen TAN ; Fulin ZHOU
Chinese Journal of Orthopaedics 2025;45(6):343-350
Objective:To investigate the surgical techniques and clinical efficacy of arthroscopic-assisted posterior malleolus reduction for the management of ankle fracture-dislocation.Methods:A retrospective analysis was performed on the clinical data of 27 patients who underwent arthroscopy-assisted posterior malleolar reduction via the posterior approach for the surgical management of ankle fracture-dislocation at the Third Affiliated Hospital of Nanjing Medical University (Changzhou No.2 People's Hospital) between January 2022 and June 2023. The cohort comprised 17 males and 10 females, with a mean age of 43.67±9.56 years (range, 25-63 years). Based on the Bartonícek and Rammelt classification, there were 15 type II cases, 9 type III cases, and 3 type IV cases. The operation time, posterior ankle arthroscopy duration, and postoperative complications, such as neurovascular injury, wound infection, or skin necrosis, were recorded. X-ray and 3D CT imaging were utilized to assess joint surface reduction quality, tibiofibular matching and fracture healing status. The ankle plantarflexion, dorsiflexion and hallux flexion contractures were recorded at the last follow-up. Functional outcomes were measured using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the Olerud-Molander ankle score (OMAS), while pain was evaluated using the visual analogue scale (VAS).Results:All 27 patients were followed up postoperatively, with a mean follow-up duration of 14.30±1.38 months (range, 12-18 months). Postoperatively, one patient experienced wound exudation, while another developed intermuscular venous thrombosis in the calf. No cases of neurovascular injury, wound infection, skin necrosis, or hallux flexion contracture occurred, and no reduction loss was observed. The mean operation time was 96.11±11.55 min (range, 80-120 min), and the posterior ankle arthroscopy duration was 35.74±5.67 min (range, 30-45 min). Postoperative X-ray evaluations demonstrated no loss of fracture reduction, and all fractures achieved bony union. The mean fracture healing time was 3.78±0.75 months (range, 3-5 months). Postoperative CT evaluations showed no joint surface malalignment, and distal tibiofibular matching was satisfactory. At the final follow-up, mean ankle plantarflexion was 46.74°±4.73° (range, 33°-50°), and dorsiflexion was 20.96°±3.29° (range, 14°-26°). There was no hallux flexion contracture occurred. The mean AOFAS ankle-hindfoot score was 92.11±7.19 (range, 74-100), with 20 excellent, 5 good, and 2 fair, yielding an excellent-good rate of 93%. The mean OMAS score was 94.44±7.25 (range, 75-100), comprising 20 excellent and 7 good results, yielding an excellent-good rate of 100%. The mean VAS score was 0.70±0.95 (range, 0-3).Conclusion:Arthroscopy-assisted posterior malleolar reduction in ankle fracture-dislocation surgery provides optimal soft tissue protection and ensures precise fracture reduction and fixation.
6.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
7.Research Progress on Animal Models of Gastric Ulcer of Spleen-Stomach Deficiency Cold Type
Ziqi LIU ; Yunying LI ; Qin LI ; Yuanhan LI ; Fangyan HE ; Weibo WEN
Laboratory Animal and Comparative Medicine 2025;45(5):574-585
Gastric ulcer(GU)is one of the common,frequently-occurring and intractable diseases of the digestive system.Spleen-stomach deficiency cold type is the most common and hard-to-cure syndrome pattern of GU,and is both a focus and a challenge in medical research.Therefore,constructing a scientific,reasonable,and clinically practical animal model of GU with spleen-stomach deficiency cold type and formulating objective and effective evaluation criteria are of great significance for in-depth research on the pathogenesis and treatment of GU.In this paper,the methods for constructing GU animal models of spleen-stomach deficiency cold type are comprehensively introduced by systematically reviewing the relevant literature.Firstly,the construction methods of pathological models of GU in Western medicine are introduced,including pyloric ligation method,water immersion-restraint stress method,ethanol-induced method,acetic acid-induced method,etc.This paper expounds the establishment methods for spleen-stomach deficiency cold syndrome type model in traditional Chinese medicine(TCM),including diet disorder method,bitter cold diarrhea method,excessive fatigue method,Qi consumption and Qi impairment method,and overeating sour-flavor method.This paper focuses on the construction methods for disease-syndrome combination GU models of spleen-stomach deficiency cold type,including two-factor modeling method and three-factor modeling method.Meanwhile,the evaluation indices of GU animal models of spleen-stomach deficiency cold type were summarized from various aspects,including animal physical signs(appearance symptoms,animal behavior,and metabolic indices),as well as tissue morphology and molecular biology-related indicators(gastric function,oxidative stress,inflammatory factors,other cytokines,four coagulation parameters,intestinal flora detection),for constructing a comprehensive evaluation system.From the perspective of prescription-based verification,this paper further analyzes the drug composition and pharmacological effects to infer the syndrome type of the treated animal model,so as to verify whether the target animal model is successfully constructed.This review aims to provide a valuable reference for establishing a syndrome-specific GU animal model that closely aligns with clinical reality and embodies the principles of Chinese medicine.This will further advance research on TCM-pattern GU syndromes and deepen the exploration of herbal medicine-based treatments for GU,ultimately promoting the clinical integration and advancement of Chinese medicine in GU therapy.
8.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
9.Current situation and suggestions for research on laboratory animal welfare and ethics in China
Huiping LI ; Jinchun YANG ; Jinyin WEN ; Weibo ZHAO
Chinese Journal of Comparative Medicine 2024;34(10):78-87
Objective Exploring the current research status,research context,evolution,and future research directions of laboratory animal welfare and ethics in China.Methods Literature related to laboratory animal welfare and ethics was collected from journals in the China National Knowledge Infrastructure(CNKI)database from 2001 to 2023.A combination of a qualitative description based on a literature review and CiteSpace visual bibliometric analysis was used to summarize the achievements,hot topics,and directions of laboratory animal welfare and ethics research.Results The literature shows that the overall popularity of research into laboratory animal welfare and ethics is on the rise in China.The hot research topics in this field include basic theories of laboratory animal welfare and ethics,the legislation of laboratory animal welfare and ethics,technologies for improving laboratory animal welfare and ethics,reviews of laboratory animal welfare and ethics,and laboratory animal welfare and ethics education.In response to the ethical issues arising from emerging interdisciplinary fields,continuous innovation is being made via research into this topic.Conclusions Suggestions are put forward regarding changes to the legal system,review mechanisms,education and training,and innovative research using laboratory animals welfare and ethics to provide a reference and guidance on the welfare and ethics of laboratory animals.
10.Advances in clinical studies of ictal asystole in epileptic seizure
Ming WEN ; Chuan LIN ; Zhanhui FENG ; Weibo WANG
Chinese Journal of Neurology 2024;57(12):1377-1381
Ictal asystole in epileptic seizure (IA) is one of the severe complications of epilepsy, which is associated with falls and traumatic injuries related to seizures. Epileptic patients with IA may require adjustment to their treatment, including antiseizure medications adjustment, evaluation for epilepsy surgery and consideration of cardiac pacemaker implantation. However, there is no consensus on treatment options for these patients. This review focuses on the mechanisms, clinical features, auxiliary examinations and the outcomes of different treatments in the IA patients. Machine learning has some application values in analyzing the long-term video electroencephalogram (EEG) results of such patients and exploring the correlated characteristics between EEG and heart rate variability, which may provide a new perspective for the research.

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