OBJECTIVE To explore the effect and potential mechanism of 717 Jiedu decoction in ameliorating local tissue injury induced by Gloydius brevicaudus venom via regulating macrophage phenotype transformation.METHODS Rat blank-serum and drug-containing serum were prepared by intragastric administration of normal saline， tail-vein injection of anti- G. brevicaudus venom serum （0.6 mL per rat）， and intragastric administration of 717 Jiedu decoction at doses of 0.495， 0.99 and 1.98 g/kg （calculated as crude drug）. M0-type macrophages derived from human leukemia monocytic THP-1 cells induced and differentiated by PMA were divided into normal control group， model group， positive control group， and low-， medium- and high-concentration 717 Jiedu decoction drug-containing serum groups. Except for the normal control group， all other groups were treated with 10 μg/mL G. brevicaudus venom working solution and 10% blank or drug-containing serum. After the cultivation period， the cellular ultrastructural changes in each group were observed； the proportions of M1- and M2-type macrophages， as well as the mRNA and protein expression of macrophage phenotype transformation and hypoxia-inducible factor-1α （HIF-1α） were detected.RESULTS Compared with the normal control group， cells in the model group presented ultrastructural injuries including mitochondrial swelling， cristae rupture and cytoplasmic vacuolization. The proportion of M1-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers [inducible nitric oxide synthase， tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β] and HIF-1α were significantly increased （ P ＜0.05），whereas the proportion of M2-type macrophages and the mRNA and protein expression levels of related phenotype transformation markers （arginase-1， IL-10， mannose receptor C type 1 and chitinase-3-like protein 1） were significantly decreased （ P ＜0.05）. Compared with the model group， cellular ultrastructural injuries were obviously alleviated， and the above-mentioned indexes were significantly reversed in the high-concentration 717 Jiedu decoction drug-containing serum group （ P ＜0.05）.CONCLUSIONS717 Jiedu decoction can exert anti-inflammatory and tissue-repairing effects by regulating the balance of M1-， M2-type macrophages phenotype transformation and repairing cellular ultrastructural damage. Its mechanism may be related to inhibiting the excessive activation of the HIF-1α pathway.

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.

Guided by the theory of"kidney generating marrow"and"kidney associating with bladder",the concept of"brain-kidney-bladder"axis was proposed.From the perspective of meridian circulation and physiological function,the conception vessel and governor vessel are the links of the"brain-kidney-bladder"axis.Kidney essence deficiency,brain spirit losing,and dysfunction of bladder are the core pathogenesis of female stress incontinence.From the dysfunction of the"brain-kidney-bladder"axis and the deficiency of conception vessel and governor vessel,an integrated model of"one acupunture,two medication,and three daoyin therapy"was proposed for the treatment of female stress incontinence."One acupunture"is based on the theoretical guidance of"treating on the bone,and even under the navel ying"in Gukong Lun in Suwen,and the regulating conception vessel and dredging governor vessel acupuncture method is used to harmonize yin and yang,replenish qi,and consolidate bladder,using governor vessel points such as Baihui(DU20),Shenting(DU24),Mingmen(DU4),and conception vessel points such as Qihai(RN6),Guanyuan(RN64),Zhongji(RN3),and cooperating with Baliao points(BL31,BL32,BL33,and BL34)of the bladder meridian."Two medication"is guided by the theory that"dispersing conditions should be astringed,and deficient conditions should be warmed"in Zhizhenyao Dalun in Suwen;the treatment method focuses on consolidating conception vessel,dredging governor vessel,and harmonizing and nourishing qi and blood,and the Guren Tongdu Formula is selected."Three daoyin therapy",that is,using the abdominal contraction and anal lifting exercise,the Mawangdui daoyin therapy,and pelvic floor muscle training to cultivate qi,preserve spirit,and maintain the unity of body and mind.

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.

Guided by the theory of"kidney generating marrow"and"kidney associating with bladder",the concept of"brain-kidney-bladder"axis was proposed.From the perspective of meridian circulation and physiological function,the conception vessel and governor vessel are the links of the"brain-kidney-bladder"axis.Kidney essence deficiency,brain spirit losing,and dysfunction of bladder are the core pathogenesis of female stress incontinence.From the dysfunction of the"brain-kidney-bladder"axis and the deficiency of conception vessel and governor vessel,an integrated model of"one acupunture,two medication,and three daoyin therapy"was proposed for the treatment of female stress incontinence."One acupunture"is based on the theoretical guidance of"treating on the bone,and even under the navel ying"in Gukong Lun in Suwen,and the regulating conception vessel and dredging governor vessel acupuncture method is used to harmonize yin and yang,replenish qi,and consolidate bladder,using governor vessel points such as Baihui(DU20),Shenting(DU24),Mingmen(DU4),and conception vessel points such as Qihai(RN6),Guanyuan(RN64),Zhongji(RN3),and cooperating with Baliao points(BL31,BL32,BL33,and BL34)of the bladder meridian."Two medication"is guided by the theory that"dispersing conditions should be astringed,and deficient conditions should be warmed"in Zhizhenyao Dalun in Suwen;the treatment method focuses on consolidating conception vessel,dredging governor vessel,and harmonizing and nourishing qi and blood,and the Guren Tongdu Formula is selected."Three daoyin therapy",that is,using the abdominal contraction and anal lifting exercise,the Mawangdui daoyin therapy,and pelvic floor muscle training to cultivate qi,preserve spirit,and maintain the unity of body and mind.

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.

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.

Objective: To design and evaluate a new method for measuring the center of rotation of the hip joint, and to compare it with the traditional methods. Methods: Data of healthy hips of 120 total hip arthroplasty (THA) patients (120 hips) and bilateral hips of 20 healthy volumteers (40 hips) were collected. A series of X-rays and magnetic resonance imaging (MRI) were taken from each patient with the hip joint abductted at differenct angles (0°, 7.5°, 15°, and 22.5°). The motion track of rotation center was obtained by comparing these X-ray and MRI images. The preoperative and postoperative data of 67 surgical patients who underwent two different measurement methods before surgery were compared. Results: Compared with traditional measurement methods, the accuracy of our new method was significantly improved; the results of hip MRI verified the objectivity and accuracy of our new method; preoperative measurements and postoperative follow-up results showed that our new method had a better clinical effect than traditional measurements. Conclusions The team′s innovative new measurement method based on pelvic orthotopic X-ray photographs with different abduction angles of the hip shows more accurate data than traditional measurement methods and shows better clinical results.

Objective: To investigate the effect of Kamistad gel on oral ulcer healing and the expression of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and epidermal growth factor (EGF) after oral administration in ulcer tissue of rats and to provide animal experimental data for the clinical application of Kamistad gel. Methods: The oral ulcer rat model was established by chemical cauterization. The rats were randomly divided into four groups: Kamistad group (Kamistad gel), befuxin group (befuxin gel), lidocaine group (lidocaine cream), blank control group (normal saline), with 12 rats in each group. The ulcer area of the rats in each group was measured before and 1, 3 and 5 days after treatment; at 1 day after treatment, the duration of swabbing behavior within 3 minutes of intraoral capsaicin infusion was recorded to evaluate the degree of pain; the ulcer tissue was collected at 5 days after treatment, and the histopathological changes were observed by HE staining, the expression of TNF-α, IL-6 and EGF in the ulcer tissue was detected by immunohistochemistry and ELISA. Results: At 1 day after treatment, the duration of mouth wiping induced by capsaicin was significantly shorter in the Kamistad group than in the blank control and befuxin groups (P < 0.05), but there was no significant difference between the Kamistad and lidocaine groups (P >0.05). At 5 days after treatment, the ulcer area was significantly smaller in the Kamistad group than in the blank control and lidocaine groups (P < 0.05), and there was no significant difference between the Kamistad and befuxin groups (P >0.05). At 5 days after treatment, H&E staining of the oral ulcer tissue sections showed significantly reduced levels of inflammatory cells and significantly proliferated fibroblasts and better epithelial hyperplasia in the Kamistad group compared with those in the lidocaine and blank control groups, and there were no differences between the Kamistad and befuxin groups. At 5 days after treatment, the expression levels of TNF-α, IL-6 and EGF in the ulcer tissue of rats in each group were significantly different (P < 0.05). Compared with the blank control and lidocaine groups, the expression of TNF-α and IL-6 was significantly decreased and the expression of EGF was significantly increased in the Kamistad group (P < 0.05); there were no significant differences in the expression of the above three factors between the Kamistad and befuxin groups (P > 0.05). Conclusion Kamistad gel exhibited anti-inflammatory, analgesic and healing effects on experimental oral ulcers.

Objective To investigate the relationship between vascular endothelial cell nitric oxide synthase (eNOS) gene polymorphism and the pathogenesis of avascular femoral head necrosis (ANFH).Methods The eNOS full-length CDS fragments,containing 894G or 894T separately,was subcloned into lentiviral expression vector,and then infect the human umbilical vein endothelial cells (HUVEC).The contents of nitric oxide NO and cyclic guanosine monophosphate (cGMP) in cell culture supernatant were detected in a time-dependent manner.The luciferase-labeled reporter plasmid pNF-κB-luc was co-transfected with the reference control plasmid pRL-TK into HUVEC cells infected with LV-eNOS-894G,LV-eNOS-894T,and control lentivirus (LV-NC) for 48 h.The luciferase activity of each group was detected.The expression of nuclear factor (NF)-κB protein and eNOS protein in HUVEC cells were detected by Western blot assay.The HUVEC cells in each group were co-cultured with hFOB1.19 cells,and the concentration of alkaline phosphatase (ALP) or osteocalcin (OCN) in the supernatant were detected at different time points.Results The contents of NO and cGMP in the cell culture supernatant of the full-length lentivirus expressing eNOS gene (containing 894G or 894T) were significantly higher than that in the empty cell group and the empty vector group,and the contents of NO and cGMP in the cell culture supernatant of the 894G group were significantly higher than that of 894T group (P ＜ 0.01).Compared with blank cells,the expression levels of NF-κB/p65 protein and eNOS protein were significantly increased in cells expressing eNOS,and the expression of NF-κB/p65 protein in 894G group was significantly increased than 894T group,but there was no difference in eNOS protein expression between the 894G and 894T groups;each group of HUVEC cells were co-cultured with hFOB1.19 osteoblasts,and at each of the same time points,the concentrations of ALP and OCN in the cell culture supernatant expressing lentivirus were significantly higher than that in the empty cell group and the empty vector group,and the ALP and OCN concentrations in the cell culture supernatant of the 894G group were significantly higher than those in the 894T group.Conclusions The eNOS gene exon G894T mutation reduces the levels of nitric oxide and cGMP produced by vascular endothelial cells through the eNOS-NO pathway,affecting the expression levels of NF-κB/p65 protein and eNOS protein,and reducing osteoblast activity,and blood supply to blood vessels.It may be one of the pathogenic mechanisms leading to femoral head necrosis.