1.Clinical Efficacy and Radiographic Outcomes of Manipulative Reduction Combined with Small Splint Fixation for Distal Radius Fractures:A Retrospective Multicenter Study with Propensity Score Matching
Mao WU ; Guoda DAI ; Yang SHAO ; Shaoshuo LI ; Zhen HUA ; Hengyan CUI ; Tingchen ZHU ; Dipeng LI ; Jintao LIU ; Ming ZHOU ; Peimin WANG ; Liyong ZHANG ; Jianwei WANG
Journal of Traditional Chinese Medicine 2026;67(10):1086-1092
ObjectiveTo observe the clinical efficacy and radiographic outcomes of manipulative reduction combined with small splint fixation in the treatment of distal radius fractures. MethodsThe clinical data of 1051 patients with distal radius fractures were retrospectively collected from five hospitals included in the Jiangsu Diagnosis and Treatment Data Platform for Traditional Chinese Medicine(TCM) Dominant Diseases. Propensity score matching at a 1∶4 ratio was applied, resulting in 580 cases selected for final analysis, which comprised 448 patients in the TCM group(manipulative reduction plus small splint fixation) and 132 in the surgical treatment group(open reduction and internal fixation). Each group was further stratified into type A, B, and C subgroups based on AO fracture classification. Radiographic indicators including palmar tilt, radial inclination, and radial height were compared between groups before treatment and 1 day, 1 week, and 4-6 weeks after treatment, and pain visual analog scale(VAS) scores before treatment and 1 week and 4-6 weeks after treatment were also compared. Wrist joint function was assessed 12 weeks after treatment, using the Dienst wrist function score and the Gartland and Werley(G-W) wrist function score. Additionally, the radiographic indicators at different timepoints and the 12-week wrist function levels were compared between groups across different fracture types. ResultsNo statistically significant difference was observed in radiographic indicators and VAS scores at all timepoints before and after treatment, as well as wrist joint function grades assessed by the Dienst score and the G-W score at 12 weeks after treatment (P>0.05). Compared to those before treatment, both groups showed increased palmar tilt, radial inclination, and radial height 1 week and 4-6 weeks after treatment, and decreased VAS scores (P<0.05). Compared to those 1 week after treatment, both groups showed a decrease in palmar tilt, an increase in radial inclination and radial height, and a reduction in VAS score 4-6 weeks after treatment(P<0.05). In type A and B subgroups, the surgical treatment group had a higher radial inclination than the TCM group 4-6 weeks after treatment, while in the type C subgroup, a higher radial height was shown in the surgical treatment group than in the TCM group 4-6 weeks after treatment(P<0.05). In type C subgroup, there was significant difference between groups in the wrist joint function by G-W scores 12 weeks after treatment(P<0.05). ConclusionManipulative reduction combined with small splint fixation can maintain fracture alignment and alleviate pain in treating distal radius fractures, which achieves therapeutic outcomes comparable to surgical treatment. It is particularly suitable for type A and B fractures and can be considered an effective treatment option for distal radius fractures.
2.Establishment and Evaluation of Different Disease-Syndrome Combination Mice Models of Knee Osteoarthritis with Cold-Dampness Stagnation Syndrome
Enrui HU ; Yibao WEI ; Deren LIU ; Aobuliaisan MAIMAITITUXUN ; Licheng ZHANG ; Jiachen SONG ; Jun MAO ; Taiyang LIAO ; Peimin WANG
Journal of Traditional Chinese Medicine 2026;67(19):2120-2129
ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis (KOA) with cold-dampness obstruction syndrome, and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group, a treadmill plus climate chamber group, an anterior cruciate ligament transection (ACLT) plus climate chamber group, an ACLT group, a destabilization of the medial meniscus (DMM) plus climate chamber group, a DMM group, an intra-articular injection plus climate chamber group, and an intra-articular injection group, with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model, while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee, and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate (MIA) into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber, DMM plus climate chamber, and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber (relative humidity 60%, temperature 4 ℃, wind speed 6 m/s) simultaneously with aforementioned interventions, once daily for 2 h each time, for 14 consecutive days. Mice in the control group underwent sham surgery, involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity, followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation, undergoing high-intensity treadmill exercise at a speed of 20 m/min, an inclination of 5°, for 30min per session, 5 times per week for 28 consecutive days, while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling, knee joint pathological changes were observed using HE and Safranin O-Fast Green staining, and quantified using Mankin and Osteoarthritis Research Society International (OARSI) scores. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA. Protein and mRNA expression levels of pain-related markers, including calcitonin gene-related peptide (CGRP), protein gene product 9.5 (PGP9.5), and cellular proto-oncogene Fos (c-Fos), and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential melastatin 8 (TRPM8) in the dorsal root ganglion (DRG) tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group, the remaining groups showed decreased cold pain thresholds in the cold plate tese, increased cold pain thresholds in the acetone low-temperature test, elevated Mankin and OARSI scores, and increased serum TNF-α and IL-1β levels, upregulated protein and mRNA expression levels of CGRP, PGP9.5, c-Fos, TRPA1, and TRPM8 in the DRG, and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue (P<0.05 or P<0.01), along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT, DMM, and intra-articular injection groups, the ACLT plus climate chamber, DMM plus climate chamber, and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators (P<0.01). Furthermore, changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group, DMM plus climate chamber and intra-articular injection plus climate chamber group (P<0.01), exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome, with the ACLT combined with the artificial climate chamber being the optimal modeling approach.
3.Establishment and Evaluation of Different Disease-Syndrome Combination Mice Models of Knee Osteoarthritis with Cold-Dampness Stagnation Syndrome
Enrui HU ; Yibao WEI ; Deren LIU ; Aobuliaisan MAIMAITITUXUN ; Licheng ZHANG ; Jiachen SONG ; Jun MAO ; Taiyang LIAO ; Peimin WANG
Journal of Traditional Chinese Medicine 2026;67(19):2120-2129
ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis (KOA) with cold-dampness obstruction syndrome, and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group, a treadmill plus climate chamber group, an anterior cruciate ligament transection (ACLT) plus climate chamber group, an ACLT group, a destabilization of the medial meniscus (DMM) plus climate chamber group, a DMM group, an intra-articular injection plus climate chamber group, and an intra-articular injection group, with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model, while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee, and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate (MIA) into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber, DMM plus climate chamber, and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber (relative humidity 60%, temperature 4 ℃, wind speed 6 m/s) simultaneously with aforementioned interventions, once daily for 2 h each time, for 14 consecutive days. Mice in the control group underwent sham surgery, involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity, followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation, undergoing high-intensity treadmill exercise at a speed of 20 m/min, an inclination of 5°, for 30min per session, 5 times per week for 28 consecutive days, while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling, knee joint pathological changes were observed using HE and Safranin O-Fast Green staining, and quantified using Mankin and Osteoarthritis Research Society International (OARSI) scores. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA. Protein and mRNA expression levels of pain-related markers, including calcitonin gene-related peptide (CGRP), protein gene product 9.5 (PGP9.5), and cellular proto-oncogene Fos (c-Fos), and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential melastatin 8 (TRPM8) in the dorsal root ganglion (DRG) tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group, the remaining groups showed decreased cold pain thresholds in the cold plate tese, increased cold pain thresholds in the acetone low-temperature test, elevated Mankin and OARSI scores, and increased serum TNF-α and IL-1β levels, upregulated protein and mRNA expression levels of CGRP, PGP9.5, c-Fos, TRPA1, and TRPM8 in the DRG, and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue (P<0.05 or P<0.01), along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT, DMM, and intra-articular injection groups, the ACLT plus climate chamber, DMM plus climate chamber, and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators (P<0.01). Furthermore, changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group, DMM plus climate chamber and intra-articular injection plus climate chamber group (P<0.01), exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome, with the ACLT combined with the artificial climate chamber being the optimal modeling approach.
4.A Randomized Controlled Clinical Study on the Treatment of Knee Osteoarthritis with Cold-Dampness Arthralgia Obstruc-tion by Shangke Lengtong Patch
Li ZHANG ; Liang DING ; Zhengquan HUANG ; Wei MEI ; Runlin XING ; Songjiang YIN ; Peng WU ; Xi-aochen LI ; Zhenyuan MA ; Nongshan ZHANG ; Jun MAO ; Peimin WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(3):393-398
OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.
5.TCM Treatment of Lung Cancer Based on AMPK Signaling Pathway: A Review
Chengzhi WANG ; Yifan LIU ; Zhenyao YANG ; Wenjun LI ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):291-298
As a common malignant tumor of the respiratory system, the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex, the prognosis is poor, and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms, problems such as postoperative recurrence and metastasis, numerous adverse reactions, and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore, it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway can regulate the growth, differentiation, apoptosis, and autophagy of lung cancer cells, and is extensively involved in the occurrence and development of lung cancer, thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine (TCM) exerts anti-lung cancer effects through multiple pathways, mechanisms, and targets, with advantages such as preventing postoperative recurrence and metastasis, alleviating the adverse reactions of radiotherapy and chemotherapy, and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine, including flavonoids, saponins, polyphenols, and terpenes, as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract, Qingzao Jiufei decoction, and Yiqi Fuzheng formula, have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells, modulating macrophage polarization, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and blocking the cell cycle, thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM, and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer, with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.
6.TCM Treatment of Lung Cancer Based on AMPK Signaling Pathway: A Review
Chengzhi WANG ; Yifan LIU ; Zhenyao YANG ; Wenjun LI ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):291-298
As a common malignant tumor of the respiratory system, the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex, the prognosis is poor, and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms, problems such as postoperative recurrence and metastasis, numerous adverse reactions, and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore, it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway can regulate the growth, differentiation, apoptosis, and autophagy of lung cancer cells, and is extensively involved in the occurrence and development of lung cancer, thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine (TCM) exerts anti-lung cancer effects through multiple pathways, mechanisms, and targets, with advantages such as preventing postoperative recurrence and metastasis, alleviating the adverse reactions of radiotherapy and chemotherapy, and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine, including flavonoids, saponins, polyphenols, and terpenes, as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract, Qingzao Jiufei decoction, and Yiqi Fuzheng formula, have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells, modulating macrophage polarization, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and blocking the cell cycle, thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM, and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer, with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.
7.Research progress on mechanism of monomeric saponins in Chinese herbal medicine in anti-tumor immunity
Mingyang HE ; Chengzhi WANG ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Immunology 2025;41(2):495-502
The incidence and mortality rates of malignant tumors continue to rise,which posing a serious threat to the physical and mental health of the global population,and becoming a significant scientific problem in urgent need of resolution.Tumor immuno-therapy,as a novel anti-tumor treatment,optimizes the treatment modalities for tumors.Currently,combination of immunotherapy with chemotherapy and targeted therapy has shown promising results in anti-tumor treatment.Traditional Chinese medicine is widely used in comprehensive anti-tumor treatments,demonstrating significant effectiveness and distinct advantages.Among them,monomeric saponins in Chinese herbal medicine exhibit remarkable anti-tumor effects with the notable advantages of high efficiency and low tox-icity.This has made them a focal point of research for many oncologists.Studies have revealed that a large number of monomeric sapo-nins from Chinese herbal medicine can directly or indirectly affect the functions of immune cells by regulating the innate immune sys-tem,adaptive immune system,and related immune cell factors.This enhances the immune cytotoxicity against tumor cells,thereby better exerting the anti-tumor immune effects.This paper summarizes the research findings on the anti-tumor effects of monomeric sapo-nins in recent years.It elaborates on the specific mechanisms by which monomeric saponins from Chinese herbal medicine regulate im-mune cells to exert anti-tumor effects.The aim of this paper is to provide new research perspectives for tumor immunotherapy,further harness the crucial role of traditional Chinese medicine in anti-tumor treatment,and propel the modernization of traditional Chinese medicine.
8.A Randomized Controlled Clinical Study on the Treatment of Knee Osteoarthritis with Cold-Dampness Arthralgia Obstruc-tion by Shangke Lengtong Patch
Li ZHANG ; Liang DING ; Zhengquan HUANG ; Wei MEI ; Runlin XING ; Songjiang YIN ; Peng WU ; Xi-aochen LI ; Zhenyuan MA ; Nongshan ZHANG ; Jun MAO ; Peimin WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(3):393-398
OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.
9.Research progress on mechanism of monomeric saponins in Chinese herbal medicine in anti-tumor immunity
Mingyang HE ; Chengzhi WANG ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Immunology 2025;41(2):495-502
The incidence and mortality rates of malignant tumors continue to rise,which posing a serious threat to the physical and mental health of the global population,and becoming a significant scientific problem in urgent need of resolution.Tumor immuno-therapy,as a novel anti-tumor treatment,optimizes the treatment modalities for tumors.Currently,combination of immunotherapy with chemotherapy and targeted therapy has shown promising results in anti-tumor treatment.Traditional Chinese medicine is widely used in comprehensive anti-tumor treatments,demonstrating significant effectiveness and distinct advantages.Among them,monomeric saponins in Chinese herbal medicine exhibit remarkable anti-tumor effects with the notable advantages of high efficiency and low tox-icity.This has made them a focal point of research for many oncologists.Studies have revealed that a large number of monomeric sapo-nins from Chinese herbal medicine can directly or indirectly affect the functions of immune cells by regulating the innate immune sys-tem,adaptive immune system,and related immune cell factors.This enhances the immune cytotoxicity against tumor cells,thereby better exerting the anti-tumor immune effects.This paper summarizes the research findings on the anti-tumor effects of monomeric sapo-nins in recent years.It elaborates on the specific mechanisms by which monomeric saponins from Chinese herbal medicine regulate im-mune cells to exert anti-tumor effects.The aim of this paper is to provide new research perspectives for tumor immunotherapy,further harness the crucial role of traditional Chinese medicine in anti-tumor treatment,and propel the modernization of traditional Chinese medicine.
10.Mechanism of Small Molecules of Traditional Chinese Medicine Targeting Tumor-associated Macrophages in Gastrointestinal Tumors: A Review
Yumeng CAI ; Xiaoqing ZHANG ; Gelei ZHAO ; Shan ZHANG ; Peimin LIU ; Dongdong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):271-278
Tumor-associated macrophages (TAMs), as the main immune cells in the human body, are key factors in maintaining the homeostasis of the tumor microenvironment. With high plasticity, they can polarize into the classically activated (M1) macrophages or alternatively activated (M2) macrophages under different conditions. M1 macrophages can inhibit tumor growth by phagocytosis, and M2 can inhibit the immune microenvironment to promote tumorigenesis and immune escape. Small molecules of traditional Chinese medicine have been widely studied in gastrointestinal tumors. These small molecules exert anti-tumor activity by enhancing TAM activity and promoting the polarization of macrophages. Targeted intervention in TAMs with these molecules has the potential to inhibit the development of gastrointestinal tumors. This article summarizes the research status and significance of small molecules of traditional Chinese medicine targeting TAMs against gastrointestinal tumors, aiming to provide reference for the future studies in this field.

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