1.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P0.01) and increases in number of platform crossings (P0.05), alternation rate (P0.01), number of entries into the new arm (P0.05), preference index (P0.01), and discrimination index (P0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P0.05) and elevated levels of ACh and DA (P0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
2.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P<0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P<0.01) and increases in number of platform crossings (P<0.05), alternation rate (P<0.01), number of entries into the new arm (P<0.05), preference index (P<0.01), and discrimination index (P<0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P<0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P<0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P<0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P<0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P<0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P<0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P<0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P<0.05) and elevated levels of ACh and DA (P<0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
3.Fabrication and evaluation of an inositol hexaphosphate-zinc hydrogel with dual capabilities of self-mineralization and osteoinduction
LIU Mingyi ; MIAO Xiaoyu ; CAI Yunfan ; WANG Yan ; SUN Xiaotang ; KANG Jingrui ; ZHAO Yao ; NIU Lina
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(1):29-40
Objective:
To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials.
Methods:
The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group
Results:
The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group.
Conclusion
The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.
4.Overview of Chinese Pharmacopoeia 2025 Edition Volume Ⅲ
CAO Yan ; ZHAO Xiong ; WANG Xiaojuan ; CHEN Huiyi ; LI Huiyi
Drug Standards of China 2025;26(1):028-033
“Chinese Pharmacopoeia” is the legal basis for drug development, production, operation, use and management in China, and the Chinese Pharmacopoeia 2025 Edition is going to be issued and implemented. This article introduces the revision and amendment situations, analyzes the characteristics of the new edition of the Pharmacopoeia and the future development direction of national standards for better understanding and implementation of the latest edition of pharmacopoeia.
5.Effect of ultrasound-guided needle-knife release of the ligamentum flavum on the expression of integrin alpha5 and beta1 in degenerative rabbit lumbar intervertebral discs
Can CHEN ; Yu ZHAO ; Binhan HU ; Mengfan DU ; Junning LIU ; Susheng NIU ; Yan ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):331-338
BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.
6.Macrophage efferocytosis:a new target for the treatment of obesity-related metabolic diseases
Fengying YANG ; Yuqing ZHAO ; Huijuan YOU ; Pengyi ZHANG ; Yan CHEN ; Qinglu WANG ; Yingying LIU
Chinese Journal of Tissue Engineering Research 2025;29(2):430-440
BACKGROUND:Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases.Moreover,compounds targeting efferocytosis have shown good therapeutic effects. OBJECTIVE:By reviewing the effects of obesity on macrophage efferocytosis,to analyze the key mechanism by which obesity inhibits efferocytosis,to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases,so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases,aiming to provide new strategies for disease prevention and treatment. METHODS:The English search terms were"efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment,"which were used for literature retrieval in PubMed and Web of Science.The Chinese search term was"efferocytosis,"which was used for literature retrieval in CNKI,VIP and WanFang datebases.Ninety-nine papers were finally included in the review analysis after a rigorous screening process. RESULTS AND CONCLUSION:In the process of efferocytosis,the"Find me"and"Eat me"processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells.The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages,which are crucial for efferocytosis activity.These results suggest that the"Find me"and"Eat me"factors mainly reflect the condition of apoptosis,and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages.Obesity inhibits efferocytosis,and shows an inhibitory effect on most digestive factors,but has a stress-induced activation effect on most"Find me,""Eat me"and cytoskeletal recombination factors,which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of"Find me"and"Eat me"factors.Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis.The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases,but the efferocytosis inhibitors in tumor tissue show good anticancer effects,suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation.Efferocytosis is a relatively new concept proposed in 2003,with a short research history and complex efferocytosis factors.Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.
7.Biocompatibility of poly(vinylidene fluoride)piezoelectric bionic periosteum prepared by electrospinning
Shuai ZHAO ; Dongyao LI ; Suiyan WEI ; Yijing CAO ; Yan XU ; Guoqiang XU
Chinese Journal of Tissue Engineering Research 2025;29(4):730-737
BACKGROUND:Our previous studies have found that poly(vinylidene fluoride)bionic periosteum prepared by electrospinning has good cytocompatibility,but its biocompatibility is unknown. OBJECTIVE:To evaluate the biocompatibility of poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+. METHODS:Poly(vinylidene fluoride),poly(vinylidene fluoride)bionic periosteum doped with 1%Zn2+,doped with 1%Mg2+,and doped with 1%(Zn2++Mg2+)were prepared by electrospinning to make bionic periosteum extract.SD rats were selected as the experimental subjects for hemolysis test,short-term systemic toxicity test,and heat source test.Guinea pigs were selected as the experimental subjects for skin sensitization test.The biocompatibility of bionic periosteum of four groups was tested. RESULTS AND CONCLUSION:(1)The hemolysis test results showed that the hemolysis rates of 1%Zn2+poly(vinylidene fluoride),1%Mg2+poly(vinylidene fluoride),1%Zn2++1%Mg2+poly(vinylidene fluoride)bionic periosteum and poly(vinylidene fluoride)extract were(0.130±0.013)%,(0.149±0.020)%,(0.466±0.018)%,and(0.037±0.018)%,respectively,which met the hemocompatibility standard of biomaterials.(2)The results of short-term systemic toxicity test showed that the four groups of bionic periosteal extract had no toxic signs such as body mass reduction,food intake changes,and dyspnea in SD rats,and had no toxic effects on major organs of rats.(3)Heat source test results showed that after intervention with poly(vinylidene fluoride)bionic periosteum doped with 1%Zn2+,doped with 1%Mg2+,and doped with 1%(Zn2++Mg2+),and poly(vinylidene fluoride)bionic periosteum extract,the elevated body temperature values of SD rats were(0.133±0.058),(0.100±0.010),(0.300±0.010),and(0.300±0.017)℃respectively.All were less than 0.6 ℃and the total temperature increase was less than 1.4 ℃.(4)The results of skin sensitization test showed that no erythema or edema was observed under the skin of guinea pigs after the intervention of bionic periosteum extract of four groups.(5)The results showed that poly(vinylidene fluoride)and poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+had good biocompatibility.
8.Correlation between Mer receptor tyrosine kinase and diabetic peripheral neuropathy in Sprague-Dawley rats
Xiaoyang SU ; Wenting CHEN ; Yidan FU ; Yan ZHAO ; Danfeng LAN ; Qiuping YANG
Chinese Journal of Tissue Engineering Research 2025;29(8):1593-1599
BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.
9.Mechanism of Lijin manipulation regulating scar formation in skeletal muscle injury repair in rabbits
Kaiying LI ; Xiaoge WEI ; Fei SONG ; Nan YANG ; Zhenning ZHAO ; Yan WANG ; Jing MU ; Huisheng MA
Chinese Journal of Tissue Engineering Research 2025;29(8):1600-1608
BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.
10.Mid-long term follow-up reports on head and neck rhabdomyosarcoma in children
Chao DUAN ; Sidou HE ; Shengcai WANG ; Mei JIN ; Wen ZHAO ; Xisi WANG ; Zhikai LIU ; Tong YU ; Lejian HE ; Xiaoman WANG ; Chunying CUI ; Xin NI ; Yan SU
Chinese Journal of Pediatrics 2025;63(1):62-69
Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.


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