OBJECTIVE: To assess the impacts of electroacupuncture (EA) on the gait, oxidative stress, inflammatory reaction, and protein degradation in the rats of denervated skeletal muscle atrophy, and explore the potential mechanism of EA for alleviating denervated skeletal muscle atrophy. METHODS: Forty male SD rats, 8 weeks old, were randomly assigned to a sham-surgery group, a model group, an EA group, and a p38 MAPK inhibitor group, with 10 rats in each group. The right sciatic nerve was transected to establish a rat model of denervated skeletal muscle atrophy in the model group, the EA group and the p38 MAPK inhibitor group. In the sham-surgery group, the nerve was exposed without transection. One day after successful modeling, the rats in the EA group received EA at "Huantiao" (GB30) and "Zusanli" (ST36) on the right side, using a continuous wave with a frequency of 2 Hz and current intensity of 1 mA, for 15 min in each session, EA was delivered once a day, 6 times a week. In the p38 MAPK inhibitor group, the rats received the intraperitoneal injection with SB203580 (5 mg/kg), once a day, 6 times a week. The intervention was composed of 3 weeks in each group. After the intervention completion, the CatWalk XT 10.6 animal gait analysis system was used to record the gait parameters of rats. The wet weight ratio of the gastrocnemius muscle was calculated after the sample collected. Using HE staining, the fiber morphology and cross-sectional area of the gastrocnemius muscle were observed; ELISA was employed to measure the content of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in the gastrocnemius muscle; the biochemical hydroxyamine method was adopted to detect the content of superoxide dismutase (SOD) and malondialdehyde (MDA) in the gastrocnemius muscle; with immunohistochemistry and Western blot used, the expression of p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated (p)-p38 MAPK, muscle atrophy F-box gene (Atrogin-1), muscle RING finger 1 (Murf-1), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was detected in the gastrocnemius muscle. RESULTS: Compared to the sham-surgery group, in the model group, the standing duration, the swing time and the step cycle were increased (P<0.001), the footprint area of the maximum contact time, the print area, the average intensity of the maximum contact time, the average intensity, the swing speed, and the step length were decreased (P<0.001); the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were reduced (P<0.001); the content of IL-6, IL-1β, TNF-α and MDA in gastrocnemius muscle elevated (P<0.001), and that of SOD reduced (P<0.001); the positive and protein expression of p-p38 MAPK, Atrogin-1 and Murf-1 elevated (P<0.001) and that of Nrf2 and HO-1 dropped (P<0.001). When compared with the model group, in the EA group and the p38 MAPK inhibitor group, the standing duration, the swing time and the step cycle decreased (P<0.01), the footprint area of the maximum contact time, the print area, the average intensity of the maximum contact time, the average intensity, the swing speed, and the step length increased (P<0.01); the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were improved (P<0.01, P<0.05); the content of IL-6, IL-1β, TNF-α and MDA in gastrocnemius muscle dropped (P<0.05, P<0.01), and that of SOD elevated (P<0.01, P<0.05); the positive and protein expression of p-p38 MAPK, Atrogin-1 and Murf-1 dropped (P<0.01, P<0.05) and that of Nrf2 and HO-1 increased (P<0.01, P<0.05). CONCLUSION Electroacupuncture may alleviate skeletal muscle atrophy in denervated skeletal muscle atrophy rats by mediating the p38 MAPK activity, thereby suppressing oxidative stress, inflammatory reaction, and protein degradation.
Animals ; Electroacupuncture ; Male ; Rats ; p38 Mitogen-Activated Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Muscular Atrophy/metabolism* ; Muscle, Skeletal/metabolism* ; Humans ; Signal Transduction ; Superoxide Dismutase/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Oxidative Stress ; MAP Kinase Signaling System ; Acupuncture Points

BACKGROUND:While antivenom has provided hope for treating snakebites,it is not always effective for local tissue damage caused by venomous snakes.Additionally,antivenom has several limitations,including the risk of hypersensitivity,immune reactions like"serum sickness,"and accessibility issues in some regions.Consequently,there is an urgent need to explore complementary or alternative therapies and therapeutic targets for snakebites in clinical settings.OBJECTIVE:To observe the effect of the 717 Jiedu Decoction on the expression of extracellular matrix proteins and matrix metalloproteinases/tissue inhibitors of metalloproteinases in the local tissues of rats bitten by Agkistrodon halys.METHODS:SD rats were randomly divided into a control group,a model group,an anti-viper venom serum group,and 717 Jiedu Decoction low-,medium-and high-dose groups.Except for the control group,all other groups received an injection of 1.25 mL/kg of viper venom into the gastrocnemius muscle of the left hind limb to create a model.The 717 Jiedu Decoction low-,medium-and high-dose groups were administered a preventive oral gavage of 1.98,3.96,and 7.92 g/kg daily for seven consecutive days prior to the viper venom injection.The anti-viper venom serum group received a tail vein injection of 0.6 mL of antivenom serum two hours after the venom injection.Twenty-four hours post-injection,the pathological changes in the gastrocnemius muscle were observed using hematoxylin-eosin staining.The expression levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 proteins,as well as their mRNA in serum and gastrocnemius muscle,were evaluated using ELISA and qPCR.The expression levels of type Ⅰ collagen,type Ⅳ collagen,fibronectin,laminin,α-smooth muscle actin,transforming growth factor-β1,CD31,and vascular endothelial growth factor in the gastrocnemius muscle were analyzed by immunohistochemistry.RESULTS AND CONCLUSION:(1)Compared to the control group,the model group displayed significant local inflammatory cell infiltration,hemorrhage,muscle structure disruption,and myocyte degeneration and necrosis.The protein and mRNA levels of matrix metalloproteinase-2,matrix metalloproteinase-9,and tissue inhibitor of metalloproteinase-1 in serum and gastrocnemius muscle were elevated(P＜0.05 or P＜0.01),while the mRNA expression of tissue inhibitor of metalloproteinase-2 was reduced(P＜0.01).The protein levels of type Ⅰ collagen and type Ⅳ collagen in the gastrocnemius muscle were significantly decreased(P＜0.01),whereas the protein levels of laminin,vascular endothelial growth factor,and CD31 were increased(P＜0.05 or P＜0.01);however,there were no significant changes in the protein levels of fibronectin,α-smooth muscle actin,and transforming growth factor-β1(P＞0.05).(2)In contrast to the model group,the 717 Jiedu Decoction low-,medium-and high-dose groups and the anti-viper venom serum group demonstrated alleviated myocyte damage,with improved reduction in inflammatory cell infiltration and hemorrhage.The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,and tissue inhibitor of metalloproteinase-1 in serum and gastrocnemius muscle were significantly reduced(P＜0.05 or P＜0.01).In the high-dose 717 Jiedu Decoction group,the protein level of tissue inhibitor of metalloproteinase-2 was upregulated(P＜0.05).Type Ⅰ collagen,type Ⅳ collagen,laminin,α-smooth muscle actin,and transforming growth factor B1 protein expression were elevated(P＜0.05 or P＜0.01),and there was a dose-effect relationship;vascular endothelial growth factor expression was decreased(P＜0.05 or P＜0.01),there was no significant difference in the expression of fibronectin(P＞0.05);the expression of CD31 protein was elevated in the 717 Jiedu Decoction low-dose group(P＜0.01).The results showed that 717 Jiedu Decoction could promote the production of α-smooth muscle actin and transforming growth factor β1 by regulating the expression of matrix metalloproteinase 2,matrix metalloproteinase 9 with tissue metalloproteinase inhibitory factor 1,and tissue metalloproteinase inhibitory factor 2,so as to make the synthesis of extracellular matrix greater than the degradation,maintain the extracellular matrix homeostasis,and then promote the repair of local tissue damage in pit viper bites.

BACKGROUND:While antivenom has provided hope for treating snakebites,it is not always effective for local tissue damage caused by venomous snakes.Additionally,antivenom has several limitations,including the risk of hypersensitivity,immune reactions like"serum sickness,"and accessibility issues in some regions.Consequently,there is an urgent need to explore complementary or alternative therapies and therapeutic targets for snakebites in clinical settings.OBJECTIVE:To observe the effect of the 717 Jiedu Decoction on the expression of extracellular matrix proteins and matrix metalloproteinases/tissue inhibitors of metalloproteinases in the local tissues of rats bitten by Agkistrodon halys.METHODS:SD rats were randomly divided into a control group,a model group,an anti-viper venom serum group,and 717 Jiedu Decoction low-,medium-and high-dose groups.Except for the control group,all other groups received an injection of 1.25 mL/kg of viper venom into the gastrocnemius muscle of the left hind limb to create a model.The 717 Jiedu Decoction low-,medium-and high-dose groups were administered a preventive oral gavage of 1.98,3.96,and 7.92 g/kg daily for seven consecutive days prior to the viper venom injection.The anti-viper venom serum group received a tail vein injection of 0.6 mL of antivenom serum two hours after the venom injection.Twenty-four hours post-injection,the pathological changes in the gastrocnemius muscle were observed using hematoxylin-eosin staining.The expression levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 proteins,as well as their mRNA in serum and gastrocnemius muscle,were evaluated using ELISA and qPCR.The expression levels of type Ⅰ collagen,type Ⅳ collagen,fibronectin,laminin,α-smooth muscle actin,transforming growth factor-β1,CD31,and vascular endothelial growth factor in the gastrocnemius muscle were analyzed by immunohistochemistry.RESULTS AND CONCLUSION:(1)Compared to the control group,the model group displayed significant local inflammatory cell infiltration,hemorrhage,muscle structure disruption,and myocyte degeneration and necrosis.The protein and mRNA levels of matrix metalloproteinase-2,matrix metalloproteinase-9,and tissue inhibitor of metalloproteinase-1 in serum and gastrocnemius muscle were elevated(P＜0.05 or P＜0.01),while the mRNA expression of tissue inhibitor of metalloproteinase-2 was reduced(P＜0.01).The protein levels of type Ⅰ collagen and type Ⅳ collagen in the gastrocnemius muscle were significantly decreased(P＜0.01),whereas the protein levels of laminin,vascular endothelial growth factor,and CD31 were increased(P＜0.05 or P＜0.01);however,there were no significant changes in the protein levels of fibronectin,α-smooth muscle actin,and transforming growth factor-β1(P＞0.05).(2)In contrast to the model group,the 717 Jiedu Decoction low-,medium-and high-dose groups and the anti-viper venom serum group demonstrated alleviated myocyte damage,with improved reduction in inflammatory cell infiltration and hemorrhage.The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,and tissue inhibitor of metalloproteinase-1 in serum and gastrocnemius muscle were significantly reduced(P＜0.05 or P＜0.01).In the high-dose 717 Jiedu Decoction group,the protein level of tissue inhibitor of metalloproteinase-2 was upregulated(P＜0.05).Type Ⅰ collagen,type Ⅳ collagen,laminin,α-smooth muscle actin,and transforming growth factor B1 protein expression were elevated(P＜0.05 or P＜0.01),and there was a dose-effect relationship;vascular endothelial growth factor expression was decreased(P＜0.05 or P＜0.01),there was no significant difference in the expression of fibronectin(P＞0.05);the expression of CD31 protein was elevated in the 717 Jiedu Decoction low-dose group(P＜0.01).The results showed that 717 Jiedu Decoction could promote the production of α-smooth muscle actin and transforming growth factor β1 by regulating the expression of matrix metalloproteinase 2,matrix metalloproteinase 9 with tissue metalloproteinase inhibitory factor 1,and tissue metalloproteinase inhibitory factor 2,so as to make the synthesis of extracellular matrix greater than the degradation,maintain the extracellular matrix homeostasis,and then promote the repair of local tissue damage in pit viper bites.

Snake bites are characterized by acute onset,rapid changes in condition,and high disability and mortality rates.The effects of snake venom on the human body are divided into systemic and local toxic effects.The popu-larity of antivenom has greatly reduced the mortality of snake bites,but local tissue damage and permanent dysfunction are still problems to be solved urgently.Studies have found that snake venom metalloproteinases,hyaluronidases,phospholi-pases and other venoms participate in a variety of local pathological effects by interfering with the degradation and remodel-ing of extracellular matrix(ECM).This article reviews the mechanism of ECM in the development of local tissue damage caused by snake bites,in order to find effective therapeutic targets and provide reference and ideas for the clinical research and prevention of local tissue damage caused by snake bites.

Snakebite is a common clinical emergency with the characteristics of acute onset,rapid changes in condition,and high disability and mortality rates.In addition to the common systemic and local tissue damage,snake envenomation can cause significant complications,including immediate and delayed effects.These complications are the main causes of disability and even death caused by snakebites,which seriously affect the long-term prognosis and quality of life.This article summarizes the symptoms,diagnosis,and treatment of snakebite complications from the aspects of blood,nervous,motor,endocrine,and reproductive systems and other aspects to provide references for effective and precise treatment of snakebite in clinical practice.

Objective:To investigate the relationship between the activation level of Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and the change of cognitive functions in patients with acute ischemic stroke.Methods:A total of 88 patients with acute ischemic stroke in Department of Neurology from October 2018 to July 2020 were selected as case group and 100 healthy physical examinees were selected as control group.Peripheral blood of the case group and the control group was collected, and peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation.Then the NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and interleukin-1β (IL-1β) expression were detected by Western blot.The cognitive function of patients with acute ischemic stroke was detected by Montreal Cognitive Assessment (MoCA). The differences in expression levels of NLRP3, ASC, Caspase-1 and IL-1β were compared between the case group and the control group.Pearson correlation analysis was used to analyze the correlation between expression levels of NLRP3, ASC, Caspase-1, IL-1β and MoCA score.Logistic multivariate regression was used to analyze the relationship between expression levels of NLRP3, ASC, caspase-1, IL-1β and the cognitive dysfunction.Results:(1)Western blot results showed that NLRP3, ASC, Caspase-1 and IL-1β expressions in PBMCs cells in the case group were higher than those in the control group (all P<0.05). (2)The expression level of NLRP3 in stroke patients with hypertension, hyperlipidemia, National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 points was significantly higher than that in patients without hypertension, hyperlipidemia and NIHSS score<8 points ( P<0.05); (3)The incidence of cognitive dysfunction in the case group was 34.09% (30/88). The MoCA scores of the cognitive dysfunction group and the non-cognitive dysfunction group were 20 (24, 28) and 27 (26, 28) points respectively, and the difference between the groups was statistically significant ( P<0.05); (4)Pearson correlation analysis showed that NLRP3, ASC, caspase-1 and IL-1β expression in PBMCs cells were negatively correlated with MoCA scores ( r=-0.426, -0.396, -0.417, -0.320 respectively, all P<0.05). (5)Logistic regression analysis showed that hyperlipidemia, NIHSS scores, frontotemporal lobe infarction, and NLRP3 expression were the influencing factors for the occurrence of cognitive dysfunction (all P<0.05). Conclusion:Patients with acute ischemic stroke have high activated NLRP3 inflammasome, and its activation degree is closely related to the condition and the occurrence of cognitive dysfunction after stroke.Targeted inhibition or regulation of NLRP3 inflammasome activation may become a new idea of neuroprotection for acute ischemic stroke.

Objective:To examine the clinical characteristics and abnormal reflux branches of primary isolated chylopericardium.Methods:Totally 43 patients with primary isolated chylopericardium at Department of Lymphatic Surgery, Affiliated Beijing Shijitan Hospital,Capital Medical University from June 2007 to January 2018 were recruited in this study. There were 21 males and 22 females, aging (23.0±15.9) years (range: 2 to 57 years). The levels of triglyceride, total cholesterol, total protein and albumin in pericardial effusion and blood were compared by paired- t test, and the characteristics of lymphatic system in direct lymphangiography and postoperative CT were analyzed. Results:Pericardial effusion was mainly milky white and monocytes, and 95.3%(41/43) were positive for Rivalta test. The level of triglyceride in pericardial effusion was significantly higher than that of blood ((9.67±5.11) mmol/L vs. (1.28±0.89) mmol/L, t=10.557, P<0.01), and the levels of total cholesterol ((2.19±0.52) mmol/L vs. (4.12±1.06) mmol/L, t=-3.732, P<0.01), total protein ((61.25±16.17) g/L vs. (68.26±8.30) g/L, t=-2.958, P=0.005) and albumin ((36.63±7.06) g/L vs. (42.32±4.73) g/L, t=-5.747, P<0.01) were significantly lower than that of blood. In the direct lymphangiography, the imaging of iliac and retroperitoneal lymphatics showed dilated or tortuous in 90.7% (39/43), the thoracoabdominal segment of thoracic duct showed dilation in 46.5% (20/43), and cervical thoracic duct imaging showed dilation in 44.2% (19/43) and stenosis in 55.8% (24/43). The image of lipiodol flowing into the vein showed obstruction at the venous angle. There were 60.5%(26/43) of the patients with lipiodol reflux through the bronchomediastinal trunk (type Ⅰ), 11.6%(5/43) with lipiodol diffusion to the pericardium through the abnormal pathway from the thoracic segment of the thoracic duct (type Ⅱ), while no communication pathway between the thoracic duct and the pericardial cavity (type Ⅲ) found in 27.9%(12/43). CT images obtained after the direct lymphangiography showed 34.9%(15/43) had abnormal distribution of lipiodol in pericardium, mediastinal lymph nodes and lung hilar lymph nodes, 46.5%(20/43) in mediastinal lymph nodes and lung hilar lymph nodes, 14.0%(6/43) only mediastinal lymph nodes, 4.6%(2/43) had no lipiodol in the above areas. Conclusions:Pericardial effusion compared with same period blood, has higher triglyceride, lower total cholesterol, total protein and albumin. The obstruction of the cervical segment of the thoracic duct and the formation of abnormal reflux branches would be corelative to primary isolated chylopericardium.

Objective:To examine the clinical characteristics and abnormal reflux branches of primary isolated chylopericardium.Methods:Totally 43 patients with primary isolated chylopericardium at Department of Lymphatic Surgery, Affiliated Beijing Shijitan Hospital,Capital Medical University from June 2007 to January 2018 were recruited in this study. There were 21 males and 22 females, aging (23.0±15.9) years (range: 2 to 57 years). The levels of triglyceride, total cholesterol, total protein and albumin in pericardial effusion and blood were compared by paired- t test, and the characteristics of lymphatic system in direct lymphangiography and postoperative CT were analyzed. Results:Pericardial effusion was mainly milky white and monocytes, and 95.3%(41/43) were positive for Rivalta test. The level of triglyceride in pericardial effusion was significantly higher than that of blood ((9.67±5.11) mmol/L vs. (1.28±0.89) mmol/L, t=10.557, P<0.01), and the levels of total cholesterol ((2.19±0.52) mmol/L vs. (4.12±1.06) mmol/L, t=-3.732, P<0.01), total protein ((61.25±16.17) g/L vs. (68.26±8.30) g/L, t=-2.958, P=0.005) and albumin ((36.63±7.06) g/L vs. (42.32±4.73) g/L, t=-5.747, P<0.01) were significantly lower than that of blood. In the direct lymphangiography, the imaging of iliac and retroperitoneal lymphatics showed dilated or tortuous in 90.7% (39/43), the thoracoabdominal segment of thoracic duct showed dilation in 46.5% (20/43), and cervical thoracic duct imaging showed dilation in 44.2% (19/43) and stenosis in 55.8% (24/43). The image of lipiodol flowing into the vein showed obstruction at the venous angle. There were 60.5%(26/43) of the patients with lipiodol reflux through the bronchomediastinal trunk (type Ⅰ), 11.6%(5/43) with lipiodol diffusion to the pericardium through the abnormal pathway from the thoracic segment of the thoracic duct (type Ⅱ), while no communication pathway between the thoracic duct and the pericardial cavity (type Ⅲ) found in 27.9%(12/43). CT images obtained after the direct lymphangiography showed 34.9%(15/43) had abnormal distribution of lipiodol in pericardium, mediastinal lymph nodes and lung hilar lymph nodes, 46.5%(20/43) in mediastinal lymph nodes and lung hilar lymph nodes, 14.0%(6/43) only mediastinal lymph nodes, 4.6%(2/43) had no lipiodol in the above areas. Conclusions:Pericardial effusion compared with same period blood, has higher triglyceride, lower total cholesterol, total protein and albumin. The obstruction of the cervical segment of the thoracic duct and the formation of abnormal reflux branches would be corelative to primary isolated chylopericardium.

Objective: To investigate the imaging features and etiology of lymphatic trunk in primary facial lymphedema. Methods: 26 patients with primary facial lymphedema patients (F/M, 13/13, ages 21.8 ± 13.9 years old) were recruited from January 2015 to October 2017 in this study, with 32 sides facial lymphedema reported, including 6 right facial lymphedema, 14 left facial lymphedema, and 6 bilateral facial lymphedema. And all the patient data and imaging were retrospective analysis to summarize the MR imaging features of thoracic duct and right lymphatic duct, meanwhile compared with surgical results. Results: For all 26 patients, MR imaging result in thoracic duct manifests 32 lymphatic duct, including 20 thoracic duct and 12 right lymphatic duct. The imaging features demonstrate two typical findings: dilated(13 cases) and slim(7 cases) demonstrations. While for right lymphatic duct, the MR result included three types: dilated(6 cases), slim(4 cases) and no sign of manifestations(2 cases). In surgery, the thoracic duct in cervical segment demonstrated abnormal structures, including capsulated by fibrous tissues in peripheral area(30 sides), surrounded by internal jugular vein sheath(11 sides), external pressed by venae cervicalis transversa(5 sides) and lymphatic trunk dysplasia(2 sides). Conclusions MR thoracic duct and right lymphatic duct imaging can be used as an effective diagnostic imaging method for primary facial lymphedema, and the structural anomaly of the upper cervical catheter and the right lymphatic catheter may be one of the pathogenic factors of primary facial lymphedema.

Under the guidance of meridian theory, the acupoints heat-sensitive moxibustion is a treatment method which applies moxa stick to perform mild moxibustion at heat-sensitive acupoints, which can arouse the meridian sensation transmission and promote the movement of meridian qi; consequently, the qi can be extended to the diseases. For its many advantages, such as no direct contact on skin, no injuries, no pains, fewer side effects, easy operating and moderate cost, the acupoints heat-sensitive moxibustion is widely accepted in dermatology, male urology disease, rectum and anus diseases and breast diseases. The application and research status of the acupoints heat-sensitive moxibustion in traditional Chinese surgery in recent years is reviewed, and several problems and suggestions in its clinical application and research are proposed, aiming to provide clinical basis for its further development and clinical application in traditional Chinese surgery.
Acupuncture Points ; Clinical Trials as Topic ; General Surgery ; Humans ; Moxibustion ; Sensation