ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo evaluate the therapeutic effects of modified Buwangsan on cognitive dysfunction in the rat model of type 2 diabetes mellitus with mild cognitive impairment （T2DM-MCI） and explore the underlying mechanism. MethodsThirty-six 5-week-old SPF-grade SD rats were randomly assigned into 6 groups： Normal （Con， fed with a normal diet）， model （DM， fed with a high-sugar and high-fat diet）， low-dose modified Buwangsan （L-BWS， 1.86 g·kg^-1）， medium-dose modified Buwangsan （M-BWS， 3.72 g·kg^-1）， high-dose modified Buwangsan （H-BWS，7.44 g·kg^-1）， and huperzine A （SSJJ， 0.018 mg·kg^-1）. The rats were treated by gavage once a day for 12 weeks. The body weight and blood glucose level were monitored dynamically. Morris water maze was employed to test the cognitive function of rats. Hematoxylin-eosin and Nissl staining were employed to observe the pathological changes of the hippocampus. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the serum and hippocampus were assessed by enzyme-linked immunosorbent assay. Western blotting was employed to determine the expression levels of key autophagy-related proteins including microtubule-associated protein 1 light chain 3 （LC3）， type Ⅲ phosphatidylinositol 3-kinase complex regulatory subunit （Beclin1）， and phosphorylated UNC-51-like kinase （p-ULK） 1/2 in the hippocampus. Immunofluorescence staining was employed to observe the regulation of p-PI3K/PI3K， p-mTOR/mTOR， and p-Akt/Akt ratios. ResultsCompared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups showed increases in body weight at the end of the experiment （P<0.05）， and the M-BWS， H-BWS and SSJJ groups showed declines in fasting blood glucose level （P<0.05）. In the water maze test， compared with the DM group， the M-BWS， H-BWS， and SSJJ groups presented shortened escape latency （P<0.001）. The L-BWS， M-BWS， H-BWS， and SSJJ group showcased regularly arranged cells in the hippocampus and cortex， markedly increased number of neurons， and significantly recovered Nissl bodies. Compared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups had reductions in the levels of IL-1β and IL-6 in the serum and hippocampus （P<0.05）， increases in the LC3-II/LC3-I ratio and expression level of beclin1 in the hippocampus （P<0.05） and the p-ULK level （P<0.05）. The p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR ratios in the hippocampus decreased in the M-BWS， H-BWS， and SSJJ groups （P<0.01）. ConclusionModified Buwangsan significantly ameliorates cognitive dysfunction and neurological damage in the rat model of T2DM through multiple mechanisms. It regulates metabolic disorders， lowers the blood glucose level， improves lipid metabolism， and alleviates oxidative stress. It promotes the protection and repair of neurons by inhibiting inflammatory responses and activating the autophagy pathway in the hippocampus. At the same time， modified Buwangsan relieves autophagy inhibition by regulating the PI3K/Akt/mTOR signaling pathway to alleviate the brain tissue injury.

ObjectiveTo evaluate the therapeutic effects of modified Buwangsan on cognitive dysfunction in the rat model of type 2 diabetes mellitus with mild cognitive impairment （T2DM-MCI） and explore the underlying mechanism. MethodsThirty-six 5-week-old SPF-grade SD rats were randomly assigned into 6 groups： Normal （Con， fed with a normal diet）， model （DM， fed with a high-sugar and high-fat diet）， low-dose modified Buwangsan （L-BWS， 1.86 g·kg^-1）， medium-dose modified Buwangsan （M-BWS， 3.72 g·kg^-1）， high-dose modified Buwangsan （H-BWS，7.44 g·kg^-1）， and huperzine A （SSJJ， 0.018 mg·kg^-1）. The rats were treated by gavage once a day for 12 weeks. The body weight and blood glucose level were monitored dynamically. Morris water maze was employed to test the cognitive function of rats. Hematoxylin-eosin and Nissl staining were employed to observe the pathological changes of the hippocampus. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the serum and hippocampus were assessed by enzyme-linked immunosorbent assay. Western blotting was employed to determine the expression levels of key autophagy-related proteins including microtubule-associated protein 1 light chain 3 （LC3）， type Ⅲ phosphatidylinositol 3-kinase complex regulatory subunit （Beclin1）， and phosphorylated UNC-51-like kinase （p-ULK） 1/2 in the hippocampus. Immunofluorescence staining was employed to observe the regulation of p-PI3K/PI3K， p-mTOR/mTOR， and p-Akt/Akt ratios. ResultsCompared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups showed increases in body weight at the end of the experiment （P<0.05）， and the M-BWS， H-BWS and SSJJ groups showed declines in fasting blood glucose level （P<0.05）. In the water maze test， compared with the DM group， the M-BWS， H-BWS， and SSJJ groups presented shortened escape latency （P<0.001）. The L-BWS， M-BWS， H-BWS， and SSJJ group showcased regularly arranged cells in the hippocampus and cortex， markedly increased number of neurons， and significantly recovered Nissl bodies. Compared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups had reductions in the levels of IL-1β and IL-6 in the serum and hippocampus （P<0.05）， increases in the LC3-II/LC3-I ratio and expression level of beclin1 in the hippocampus （P<0.05） and the p-ULK level （P<0.05）. The p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR ratios in the hippocampus decreased in the M-BWS， H-BWS， and SSJJ groups （P<0.01）. ConclusionModified Buwangsan significantly ameliorates cognitive dysfunction and neurological damage in the rat model of T2DM through multiple mechanisms. It regulates metabolic disorders， lowers the blood glucose level， improves lipid metabolism， and alleviates oxidative stress. It promotes the protection and repair of neurons by inhibiting inflammatory responses and activating the autophagy pathway in the hippocampus. At the same time， modified Buwangsan relieves autophagy inhibition by regulating the PI3K/Akt/mTOR signaling pathway to alleviate the brain tissue injury.

BACKGROUND:Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair.However,the mechanism of action and effects of this compound in osteoblasts need to be further explored. OBJECTIVE:To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway. METHODS:Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours,and the optimal intervention concentrations were screened.Osteoblasts were treated with dexamethasone,pinoresinol diglucoside and inhibitor XAV-939.Then,control group,dexamethasone group,XVA-939 group,pinoresinol diglucoside group,pinoresinol diglucoside+XVA-939 group were set up.Cell counting kit-8 assay was used to detect cell activity.Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected.Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation.Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen,respectively. RESULTS AND CONCLUSION:After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours,10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition,and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L.Compared with the dexamethasone group,alkaline phosphatase activity was significantly enhanced(P<0.05)and caspase3/7 enzyme activity was significantly reduced(P<0.05)in the pinoresinol diglucoside group.Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention.The mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups(P<0.05).To conclude,pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention,protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway,which may play a role in delaying steroid-induced osteonecrosis of the femoral head.

BACKGROUND:Crosslinked sodium hyaluronate gel has good mechanical property,biocompatibility,and biodegradability,and can be used as an isolated protective material in tumor radiation therapy to protect endangered organs from damage caused by excess radiation dose. OBJECTIVE:To investigate the safety and efficacy of crosslinked sodium hyaluronate gel in reducing the dose of radiation to dangerous organs during brachytherapy. METHODS:A total of 16 specific pathogen-free Kunming mice of the same age and similar body weight were selected as experimental subjects and divided into experimental group and control group by the random number table method,with 8 mice in each group.125I seeds were implanted subcutaneously in the back of mice in the experimental group,and then crosslinked sodium hyaluronate gel was injected around the radioactive particles.Only 125I seeds were implanted subcutaneously in the back of mice in the control group.After injection,the distance between the radioactive particles and the epidermis was measured by spiral CT scan,and the surface radiation dose was measured by radiation dosimeter.Within 10 weeks after injection,the growth state,survival rate,skin radiation damage,and gel retention of mice were observed. RESULTS AND CONCLUSION:(1)Spiral CT scan showed that the implanted gel was relatively concentrated and created an effective distance between the radioactive seeds and the epidermis.The body surface radiation dose of the experimental group was significantly lower than that of the control group(P<0.01).(2)During the experimental observation period,mice in both groups survived;mice in the control group showed obvious irritability and other unstable behavior in the late experimental period,and some mice in the experimental group showed similar behavior.The daily food intake of mice in the two groups had no significant change,and the body mass showed the same increasing trend.After implantation of radioactive seeds,the two groups of mice showed different degrees of radioactive skin injury.From day 23 after injection to the end of the experiment,the skin radiation injury score of the experimental group was lower than that of the control group(P<0.01).At week 10 after implantation,6 mice in the experimental group had no obvious gel residue under their skin,and 2 mice had a very small amount of scattered gel-like samples under their skin.(3)Therefore,the crosslinked sodium hyaluronate injection technique can increase the space between the radioactive target area of 125I seeds and the organ at risk outside the target through physical space occupying,which can effectively reduce the dose of the organ at risk,and play a role in the isolation and protection of the organ at risk.

ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction （祛风通窍止咳方， QTCD） in the treatment of upper airway cough syndrome （UACS）. MethodsTwenty-four guinea pigs were randomly divided into blank group， model group， traditional Chinese medicine （TCM） group， and inhibitor group， with six guinea pigs in each group. Except for the blank group， guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection， followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling， the TCM group was administered QTCD 0.9 g/（100 g·d） by gavage， the inhibitor group received the transient receptor potential vanilloid receptor 4 （TRPV4） inhibitor GSK2193874 1 mmol/L， 5 min by nebulisation， and the blank group and model group were given 2 ml/（100 g·d） normal saline by gavage once daily. After 7 days of treatment， a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines， including interleukin-6 （IL-6）， interleukin-8 （IL-8） in serum， bronchoalveolar lavage fluid （BALF）， and nasal lavage fluid （NLF） were detected by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the protein levels of TRPV4， substance P （SP）， and calcitonin gene-related peptide （CGRP） in lung and nasal mucosal tissues. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRPV4， SP， and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group， while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group， the model group showed increased cough frequency， serum IgE level， and IL-6 and IL-8 levels in serum， BALF， and NLF. The protein levels of TRPV4， SP， and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated （P＜0.05 or P＜0.01）. Compared with the model group， the TCM group and inhibitor group showed reduced cough frequency， serum IgE level， and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， reduced IL-6 in BALF， reduced IL-8 in NLF， and decreased TRPV4， SP， and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues （P＜0.05 or P＜0.01）. Compared with the TCM group， the inhibitor group had increased serum IgE， IL-6， and IL-8 levels， increased IL-6 level in BALF， and increased IL-8 levle in NLF， but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues （P＜0.01）. ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway， improving airway neurogenic inflammation， alleviating inflammatory responses， and reducing cough hypersensitivity.

ObjectiveTo investigate the association of menopausal time and menopausal age with the risk of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for the early prevention and treatment of NAFLD in clinical practice. MethodsRelated data were collected from 373 postmenopausal women who attended the outpatient service of Department of Spleen， Stomach， Liver and Gallbladder Diseases， The First Affiliated Hospital of Henan University of Chinese Medicine， from January 2017 to December 2021， including general information， menopausal age， menopausal time， and presence or absence of NAFLD. The chi-square test was used for comparison of categorical data； the independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. A Logistic regression analysis was used to calculate the association intensity and 95% confidence interval （95%CI） of menopausal time and menopausal age for the risk of NAFLD， and the restricted cubic spline （RCS） method was used to investigate the dose-response relationship between menopausal time/age and the risk of NAFLD. ResultsCompared with the women with normal menopause or late menopause， the women with early menopause had a higher prevalence rate of NAFLD and a higher degree of steatosis and fibrosis （all P<0.05）. After adjustment for the confounding factors such as age and age of menarche， the risk of NAFLD in women with a menopausal time of >3 years was 4.80 （95%CI： 1.93‍ ‍—‍‍ ‍11.95， P=0.001） times that in women with a menopausal time of ≤3 years， and the risk of NAFLD in women with early or late menopause was 8.14 times （95%CI： ‍1.77 ‍— ‍37.58， P=0.007） and 0.09 times （95%CI： 0.03 ‍— ‍0.32， P<0.001）， respectively， that in those with a normal menopausal age. There is a dose-response relationship between menopausal time/age and the risk of NAFLD. Menopausal time is positively correlated with the association intensity of NAFLD， while menopausal age is negatively correlated with the association intensity of NAFLD. ConclusionThe longer the menopause time and the earlier the menopause age， the ligher the risk of NAFLD.