BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

Objective:To explore the effectiveness of LEARNS model combined with video health education in patients undergoing painless gastrointestinal endoscopy.Methods:From February 2021 to November 2022, convenience sampling was used to select 128 patients who underwent painless gastrointestinal endoscopy at the Endoscopy Center of Affiliated Hospital of Shaoxing University as research subjects. A total of 64 patients admitted from February to December 2021 served as control group, while 64 patients admitted from January to November 2022 served as observation group. Control group patients received routine health education, while observation group was treated with LEARNS model combined with video health education on the basis of control group. The degree of cooperation, psychological state, and satisfaction with health education were compared between two groups of patients.Results:The proportion of patients in observation group who actively cooperated was higher than that in control group, and there was a statistically significant difference in the degree of cooperation between the two groups ( P<0.05). Thirty minutes before and after the endoscopy, the scores of both subscales of the State-Trait Anxiety Inventory (STAI) in observation group were lower than those in the control group, and the difference was statistically significant ( P<0.05). The satisfaction scores of observation group patients with health education in all dimensions were higher than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:LEARNS model combined with video health education can effectively improve the cooperation of patients undergoing painless gastrointestinal endoscopy, alleviate their pre-examination anxiety, and enhance their satisfaction with health education, which is worthy of clinical practice.