OBJECTIVE: To explore the feasibility of using biomechanical indicators as supplementary evaluation to the Musculoskeletal Tumor Society Scoring System (MSTS) for amputee patients. METHODS: Twenty-four patients who underwent hemipelvectomy between September 2018 and January 2025 were enrolled. There were 15 males and 9 females with an average age of 61.4 years (range, 45-76 years). Participants performed gait tests at self-selected speeds using three assistive devices (prosthesis, single crutch, and double crutches). Motion data were analyzed using a customized OpenSim model. Biomechanical indicators of the intact limb exhibiting common characteristics were screened through correlation and sensitivity analyses. Test-retest reliability [interclass correlation coefficient (ICC)] of selected parameters was assessed to evaluate their potential as MSTS score supplements. RESULTS: All biomechanical indicators showed significant positive correlations with MSTS scores across assistive devices ( P<0.05). Seven indicators demonstrated |Pearson correlation coefficients|>0.8, including walking speed, maximum hip angle, maximum hip moment, peak hip flexion moment, peak hip extension moment, hip flexion impulse, and hip extension impulse. Among these, maximum hip moment, hip flexion impulse, and hip extension impulse exhibited significant between-group differences in adjacent MSTS levels ( P<0.05), indicating high sensitivity, along with excellent test-retest reliability (ICC>0.74, P<0.01). CONCLUSION Biomechanical indicators statistically qualify as potential supplements to MSTS scoring. Maximum hip moment, hip flexion impulse, and hip extension impulse demonstrate particularly high sensitivity to MSTS score variations.
Humans ; Male ; Middle Aged ; Female ; Aged ; Biomechanical Phenomena ; Amputees/rehabilitation* ; Feasibility Studies ; Artificial Limbs ; Reproducibility of Results ; Amputation, Surgical ; Crutches ; Gait

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To investigate the effect of type 2 taste receptor(T2R)38 activation on ferroptosis of human airway epithelium NuLi-1 cells induced by cigarette smoke exposure,and to clarify its possible mechanism.Methods:The human airway epithelial NuLi-1 cells were divided into control group(without any treatment),cigarette smoke extract(CSE)group(treated with 5％CSE for 24 h)and CSE+T2R38 specific agonist phenylthiocarbamide(PTC)group(CSE+PTC group)(treated with 5％CSE and 1 mmol·L-1 PTC for 24 h).The expression levels of T2R38 mRNA and protein in NuLi-1 cells in various groups were determined by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The cell viabilities in various groups were determined by cell counting kit-8(CCK-8)assay.The activities of inducible nitric oxide synthase(iNOS),endothelial nitric oxide synthase(eNOS),and superoxide dismutase(SOD)in the cells in various groups were measured by kits.DAX-J2 red fluorescence probe was used to determine the levels of nitric oxide(NO)in the cells in various groups.The reactive oxygen species(ROS)levels in the cells in various groups were detected by fluorescent probe kit.The levels of malondialdehyde(MDA),Fe2+,and reduced glutathione(GSH)in the cells in various groups were determined by enzyme-linked immunosorbent assay(ELISA)method.Western blotting method was used to determine the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and glutathione peroxidases 4(GPx4)proteins in the cells in various groups.Results:Compared with control group,the expression levels of T2R38 mRNA and protein in NuLi-1 cells in CSE group were increased(P＜0.05).Compared with control group,the viability of NuLi-1 cells in CSE group was decreased(P＜0.05),the activities of iNOS and SOD in cells in CSE group were increased(P＜0.05),the levels of NO and ROS were increased(P＜0.05),the levels of MDA and Fe2+were increased(P＜0.05),and the GSH level and the expression levels of Nrf2 and GPx4 proteins were decreased.Compared with CSE group,the viability of NuLi-1 cells in CSE+PTC group was increased(P＜0.05),the activity of SOD and the GSH level in the cells were increased(P＜0.05),the activity of iNOS in cells was decreased(P＜0.05),the levels of NO and ROS in cells were decreased(P＜0.05),the levels of MDA and Fe2+were decreased(P＜0.05),and the expression levels of Nrf2 and GPx4 proteins were increased(P＜0.05).There was no significant difference in eNOS activity among control group,CSE group,and CSE+PTC group(P＞0.05).Conclusion:Activation of bitter taste receptor T2R38 can inhibit ferroptosis in human airway epithelium NuLi-1 cells induced by cigarette smoke exposure,and its mechanism may be related to the reduction of iNOS activity in the cells.

ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus （T2DM） rats based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） axis. MethodSix ZDF （fa/+） rats were as assigned to the blank group， and 30 ZDF （fa/fa） rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling， the rats were randomly divided into the model group， metformin group （0.18 g·kg^-1）， and low， medium， and high dose groups of modified Dahuang Huanglian Xiexintang （0.54， 1.08， 2.16 g·kg^-1）， with six rats in each group. After 12 weeks of drug intervention， the body mass， liver mass， fasting blood glucose （FBG）， and oral glucose tolerance test （OGTT） levels were measured. Serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， low-density lipoprotein cholesterol （LDL）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the activity of superoxide dismutase （SOD）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， and the level of malondialdehyde （MDA） in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group， the model group showed a significant increase in body mass， liver mass， and liver index （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight， liver mass， and liver index （P<0.01）. Compared with the normal group， the model group showed significantly increased TC， TG， and LDL levels （P<0.01）， and significantly decreased HDL levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels （P<0.01）， and significantly reduced TG levels （P<0.05）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels （P<0.05）. The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels （P<0.05）. Compared with the normal group， the model group showed significantly increased ALT and AST activities （P<0.01）. Compared with the model group， all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities （P<0.05） and significantly reduced AST activities （P<0.01）. Compared with normal group， the model group showed significantly increased FBG at all time points （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8， 10， 12 weeks. The OGTT results showed that compared with the normal group， the model group had significantly increased blood glucose at all time points （P<0.01）. Compared with the model group， the metformin group showed significantly reduced blood glucose at all time points （P<0.01）， and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90， 120 min （P<0.01）. HE pathology showed clear and regular liver cell structure in the normal group， while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang， with fewer necrotic cells. Compared with the normal group， the model group showed significantly reduced SOD and GSH-Px levels （P<0.01）， and significantly increased ROS and MDA levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels （P<0.01）， and significantly reduced MDA levels （P<0.01）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels （P<0.05）. Compared with the normal group， the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels （P<0.05）. Immunohistochemistry showed that compared with the normal group， the model group had significantly reduced positive expression of Nrf2 and HO-1 （P<0.05）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1， with a significant increase in brown-yellow granules around the cell nucleus （P<0.05）. Western blot results showed that compared with the normal group， the model group had significantly reduced protein expression of Nrf2 and HO-1 （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 （P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.

ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus （T2DM） model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups： Model group， metformin group （0.18 g·kg^-1）， and high， medium， and low dose groups of modified Dahuang Huanglian Xiexintang （2.16， 1.08， 0.54 g·kg^-1）， with eight rats in each group. Additionally， eight ZDF （fa/+） rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg^-1， with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose （FBG） was regularly measured. After 12 weeks of intervention， the body weight， epididymal fat weight， and serum levels of glucose （GLU）， glycated serum protein （GSP）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy （TEM） was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α （HIF-1α）， Bcl-2/adenovirus E1B 19 kDa interacting protein 3 （BNIP3）， microtubule-associated protein 1 light chain 3B （LC3B）， p62/SQSTM1， uncoupling protein 1 （UCP1）， iodothyronine deiodinase 2 （Dio2）， and PR domain containing 16 （Prdm16） in epididymal fat. Western blot was used to detect the protein expression of HIF-1α， BNIP3， LC3B， p62， and UCP1 in epididymal fat. ResultCompared with the normal group， the model group showed pathological changes in epididymal fat， with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight， epididymal fat weight， FBG， GLU， GSP， TC， TG， and LDL-C levels （P<0.01）， significantly decreased HDL-C levels （P<0.01）， significantly elevated mRNA and protein expression of HIF-1α， BNIP3， and LC3B （P<0.01）， significantly reduced mRNA and protein expression of p62 and UCP1 （P<0.01）， and significantly reduced mRNA expression of Dio2 and Prdm16 （P<0.01）. Compared with the model group， all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology， clear cristae， uniform matrix， and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight （P<0.01）. The epididymal fat index was reduced in all intervention groups （P<0.05）， and FBG was lowered in all intervention groups （P<0.01）.Serum GSP， GLU， TG， and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.01）， and HDL-C levels were significantly increased in all intervention groups （P<0.05， P<0.01）. The mRNA and protein expression of HIF-1α， BNIP3， and LC3B were significantly reduced， and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The mRNA and protein expression of p62， Dio2， and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway， thereby improving glucose and lipid metabolism in obese T2DM rats.

Type 2 diabetes mellitus （T2DM） is based on insulin resistance （IR） and insulin secretion deficiency， with the specific mechanisms still unclear. Current research involves mechanisms such as glycolipid toxicity， inflammatory response， oxidative stress damage， and mitochondrial dysfunction. Modern traditional Chinese medicine （TCM） scholars have named it "blood glucose collateral disease" based on the clinical characteristics and natural progression of T2DM. This condition is primarily manifested as abnormal blood sugar levels in the early stages， and as the disease progresses， it gradually causes widespread damage to the body's veins and collaterals， ultimately leading to lesions in vessels and collaterals. Among these， "spleen heat" （obesity type） is the most common clinical type of T2DM. The concept of "internal heat-induced elimination" runs through both the onset and complications of T2DM， with internal heat being a key factor in its pathogenesis. The clinical application of Dahuang Huanglian Xiexintang and its modifications has achieved significant therapeutic effects. This paper reviews the origins and treatment characteristics of Dahuang Huanglian Xiexintang， along with clinical application research and experimental studies related to T2DM treatment， involving mechanisms for regulating glucose and lipid metabolism disorders， improving IR， modulating inflammatory responses， combating oxidative stress damage， regulating autophagy-related signaling pathways， modulating intestinal flora， inhibiting pyroptosis， and alleviating endoplasmic reticulum stress， with the purpose to provide direction for further research on the prevention and treatment of T2DM and its related complications， to offer reference for developing Dahuang Huanglian Xiexintang as a rapid hypoglycemic Chinese patent medicine for obese T2DM， and to better guide the clinical promotion of this drug.

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg^-1） groups and metformin group （0.26 g·kg^-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

BACKGROUND:Clinical skin wound healing continues to be a significant concern,and tissue repair research has moved to the forefront with the development of biomaterials with immunomodulatory properties.Therefore,it is crucial to research wound dressings that have immunomodulatory properties. OBJECTIVE:To prepare chitosan hydrogels that have been modified by arginine with different configurations and assess their capacity to speed up wound healing in a rat animal model. METHODS:(1)In vitro trial:Chitosan modified by pure L-arginine,pure D-arginine,and L-arginine and D-arginine was synthesized by EDC/NHS system,which was then crosslinked with aldehyde-modified four-arm polyethylene glycol.Different chitosan-based hydrogels(CS-L,CS-D,and CS-DL)were finally formed via the Schiff base reaction.Three kinds of hydrogel extracts were co-cultured with fibroblasts respectively.Hydrogel cytocompatibility was assessed using the CCK-8 assay and live/dead staining.The effect of hydrogel on the migration capacity of fibroblasts was assessed by using a scratch test.Three kinds of hydrogels were incubated with rat erythrocyte suspension respectively to evaluate the hemocompatibility of the hydrogels.The hydrogel extract was co-cultured with RAW264.7 macrophages to test the hydrogels'capacity to enhance macrophage NO generation and polarize macrophage phenotype.(2)In vivo experiment:A total of 36 adult SD rats were divided into 4 groups with 9 rats in each group by the random number table method.Two full-layer skin defect wounds of 2 cm×2 cm were made on the back of each rat.Normal saline was added to the wounds of the control group,and corresponding hydrogel was added to the wounds of the CS-L,CS-D,and CS-DL groups,respectively,and then bandaged and fixed.The wound healing was observed regularly after operation.Hematoxylin-eosin staining was performed at 3,10,and 21 days after operation.The samples were collected 10 days after operation and M2 macrophage immunofluorescence staining was performed. RESULTS AND CONCLUSION:(1)In vitro experiments:Under scanning electron microscopy,the three kinds of hydrogels exhibited obvious interpenetrating network structures with pore sizes ranging from 70-200 μm.The three kinds of hydrogels have good swelling performance,degradation performance,self-healing performance,and suitable mechanical strength.The three kinds of hydrogels had good cytocompatibility and hemocompatibility and could promote the migration of fibroblasts.All three kinds of hydrogels had the ability to promote the polarization of macrophages,and CS-D hydrogels had the strongest ability to promote the polarization of macrophages.CS-L hydrogel could significantly promote the production of NO in macrophages.(2)In vivo experiment:3 and 10 days after operation,the wound healing rate in the CS-L and CS-D groups was higher than that in the control group(P<0.05).After 21 days,the wound healing rate of the three hydrogel groups was higher than that of the control group.Hematoxylin-eosin staining displayed that a large number of inflammatory cells were infiltrated in the wound tissue of rats in all groups,accompanied by neovessels and fibroblasts 3 days after operation.10 days after operation,there was still more inflammatory cell infiltration in the wound of the control group,and the inflammation of the other three groups was improved,especially the decrease of inflammatory cells in the CS-D group was more obvious.21 days after operation,the wound epithelium of each group was well repaired,and there was basically no inflammatory cell infiltration in the CS-L and CS-D groups,while there was still a small amount of inflammatory cell infiltration in the control group.Immunofluorescence staining revealed that the number of M2-type macrophages in the CS-D group was higher than that in the other three groups(P<0.05).(3)The results conclude that chitosan hydrogels modified by different configurations of arginine can promote wound healing through different mechanisms.

BACKGROUND:Distal tibial tuberosity-high tibial osteotomy is a surgical treatment for knee osteoarthritis,but there is still a lack of clinical studies on its effect on ankle joints. OBJECTIVE:To observe the effects of distal tibial tuberosity-high tibial osteotomy on ankle angle on coronal plane of the radiography of the full length of lower limb in weight loading. METHODS:Data of 40 patients(41 knees)with distal tibial tuberosity-high tibial osteotomy from March 2021 to March 2022 were retrospectively analyzed,including 31 females and 9 males,20 left knees and 21 right knees,aged 49-75 years,mean(63.44±6.57)years.The radiographic data of the full length of the lower limb in weight loading were collected before,week 2 and week 48 postoperatively.Hip-knee-ankle angle,talar tilt angle,tilt angle of the ankle,tibiocrural angle,and tibial articular surface angle were measured before and after surgery. RESULTS AND CONCLUSION:(1)Hip-knee-ankle angle improved from(-6.24±3.69)° before operation to(2.59±3.49)° week 2 postoperatively and(2.15±3.49)° week 48 postoperatively.The tilt angle of the ankle changed from(-7.90±3.11)° before operation to(-2.51±2.59)° week 2 postoperatively and(-2.46±2.42)° week 48 postoperatively,with statistically significant difference(P<0.001).(2)There was no significant difference in talar tilt angle,tibiocrural angle,and tibial articular surface angle before and week 2 postoperatively.(3)No significant difference in the angle changes was detected between week 2 and week 48 postoperatively.(4)It is indicated that distal tibial tuberosity-high tibial osteotomy can not only correct genu varus but also improve ankle angle.This result remains stable after 48 weeks of weight-bearing activities.