ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Objective:To investigate the effect of Xuefu Zhuyu Decoction on myocardial protection and the interaction between Cadherin-NrF2 pathway and ferroptosis in patients with chronic heart failure resulting from qi deficiency and blood stasis. Methods:A case-control study was conducted on 100 patients with heart failure resulting from qi deficiency and blood stasis who received treatment at The First People's Hospital of Huzhou from February 2021 to May 2022. These patients were divided into a basic western medicine group and a Xuefu Zhuyu Decoction group with 50 patients per group using the random number table method. The basic western medicine group received conventional treatment, while the Xuefu Zhuyu Decoction group received treatment with Xuefu Zhuyu Decoction in addition to conventional treatment. Both groups were treated continuously for 8 weeks. Interleukin-13, intercellular adhesion molecule-1, nitric oxide, cystatin C, thromboxane B2, soluble cluster of differentiation 40 ligand, vascular endothelial cadherin were detected before and after treatment, and soluble tyrosine kinase receptor AXL (sAXL), soluble stromal lysin-2, and ferric ion levels were determined. The mRNA expression levels of glutathione peroxidase 4 and NrF2 were detected. Syndrome scores were evaluated. Clinical efficacy was compared between the two groups. Results:After treatment, the levels of interleukin-13 [(7.63 ± 1.85) ng/L], intercellular adhesion molecule-1 [(41.71 ± 6.25) ng/L], and cystatin C [(0.61 ± 0.17) ng/L] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(10.56 ± 2.13) ng/L, (50.11 ± 8.34) ng/L, (1.03 ± 0.22) ng/L, t = 7.34, 5.69, 10.68, all P < 0.05]. The levels of soluble cluster of differentiation 40 ligand [(14.61 ± 1.19) μg/L] and thromboxane B2 [(40.18 ± 7.24) ng/L] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(16.03 ± 1.47) μg/L, (53.37 ± 10.16) ng/L, t = 5.30, 7.47, both P < 0.05], while the level of nitric oxide [(59.92 ± 6.16) μmol/L] in the Xuefu Zhuyu Decoction group was significantly higher than that in the basic Western medicine group [(53.17 ± 5.49) μmol/L, t = 5.78, P < 0.05]. The level of ferric ion [(0.23 ± 0.08) μg/L] in the Xuefu Zhuyu Decoction group was significantly higher than that in the basic western medicine group [(0.16 ± 0.05) μg/L, t = 5.24, P < 0.05]. The levels of vascular endothelial cadherin [(3.02 ± 0.72) ng/L], NrF2 mRNA [(2.11 ± 0.43)], and glutathione peroxidase 4 mRNA [(4.65 ± 0.74)] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(4.34 ± 1.05) ng/L, (2.93 ± 0.56), (5.16 ± 0.88), t = 7.33, 8.21, 3.13, all P < 0.05]. The levels of Galectin-3 [(62.48 ± 6.09) μg/L], soluble stromal lysin-2 [(0.98 ± 0.24) ng/L], and sAXL [(42.16 ± 7.54) ng/L] in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group [(70.96 ± 8.15) μg/L, (1.57 ± 0.46) ng/L, (56.11 ± 10.02) ng/L, t = 5.89, 8.04, 7.86, all P < 0.05]. The Xuefu Zhuyu Decoction group had lower scores for shortness of breath or wheezing [(1.06 ± 0.24) points], palpitations [(0.92 ± 0.15) points], fatigue [(0.75 ± 0.17) points], low voice [(0.68 ± 0.16) points], spontaneous sweating [(0.83 ± 0.21) points], fatigue and laziness [(0.73 ± 0.20) points], prone to fatigue [(0.66 ± 0.14) points], and dark complexion or lips [(0.61 ± 0.16) points] compared with the basic western medicine group [(1.65 ± 0.49) points, (1.15 ± 0.27) points, (1.16 ± 0.31) points, (1.12 ± 0.29) points, (1.28 ± 0.32) points, (1.28 ± 0.37) points, (1.01 ± 0.21) points, (0.96 ± 0.25) points, t = 7.64, 5.26, 8.20, 9.39, 8.31, 9.24, 9.80, 8.33, all P < 0.05]. The total response rate of the Xuefu Zhuyu Decoction group was significantly higher than that of the basic western medicine group [(96.00% (48/50) vs. 88.00% (44/50), Z = 1.91, P < 0.05). Conclusion:Treating patients with heart failure with Xuefu Zhuyu Decoction can inhibit inflammation, improve vascular endothelial cell function, regulate Cadherin-NrF2 pathways, reduce oxidative stress injury, further inhibit ferroptosis, reduce the levels of Galectin-3, soluble stromal lysin-2, and sAXL, protect myocardium, relieve clinical symptoms, and improve its efficacy.

Objective:To investigate the clinical efficacy of Yiqi Yangyin decoction combined with metformin and irbesartan in treating type 2 diabetes complicated by hypertension with qi and yin deficiency syndrome. Methods:A case-control study was performed to retrospectively analyze the clinical data of 92 patients with type 2 diabetes complicated by hypertension with qi and yin deficiency syndrome. These patients received treatment at the First People's Hospital of Huzhou from February 2021 to April 2023. They were divided into two groups, with 46 patients in each group, based on different treatment methods. The control group received metformin and irbesartan, while the observation group was treated with Yiqi Yangyin decoction in addition to the treatment provided to the control group. Both groups underwent treatment for 1 month. The clinical efficacy of the two groups was evaluated, and the changes in traditional Chinese medicine symptom scores, blood glucose levels, blood pressure, and the occurrence of adverse reactions were compared between the two groups before and after treatment. Results:The total response rate of the observation group was 93.48% (43/46), which was significantly higher than that of the control group [82.61% (38/46), χ2 = 5.63, P < 0.05). After treatment, the traditional Chinese medicine symptom score for the observation group was (9.43 ± 2.11) points, which was significantly lower than that of the control group [(12.11 ± 2.32) points, t = 11.34, P < 0.001]. The fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin levels in the observation group were (7.51 ± 1.34) mmol/L, (9.06 ± 2.11) mmol/L, and (6.23 ± 0.76)%, respectively, all of which were significantly lower than those in the control group [(8.75 ± 2.12) mmol/L, (11.15 ± 2.43) mmol/L, (7.11 ± 1.02)%, t = 4.13, 6.14, 4.01, all P < 0.05]. The systolic blood pressure in the observation group was (125.48 ± 8.14) mmHg (1 mmHg = 0.133 kPa), which was significantly lower than that in the control group [(131.32 ± 9.22) mmHg, t = 6.76, P < 0.001]. The difference in the incidence of adverse reactions between the two groups was not statistically significant ( P > 0.05). Conclusion:Yiqi Yangyin decoction combined with metformin and irbesartan is highly effective in treating type 2 diabetes complicated by hypertension with qi and yin deficiency syndrome. This combined therapy can effectively lower the traditional Chinese medicine symptom score, improve patients' blood glucose and blood pressure levels, and has a low incidence of adverse reactions.

Objective To observe the effects of Renshen Yimai Prescription on oxidative stress and vascular aging in ApoE-/-mice;To explore its mechanism of intervention in vascular aging.Methods Forty ApoE-/-mice were divided into model group,Western medicine group(rosuvastatin,2.6 mg/kg),TCM low-and high-dosage group(Renshen Yimai Prescription,4.29,8.58 g/kg),with 10 mice in each group.Another 10 C57BL/6J mice were set as normal group.A vascular aging model was established by ApoE-/-mice fed with a Western diet.Each medication group was given corresponding drugs by gavage for 12 consecutive weeks,the normal group and model group were given equivalent volume of pure water.HE staining and Masson staining were used to observe the morphological changes of aortic tissue,and ox-LDL content in serum was detected by ELISA,the contents of ROS,GSH,GPX and NAD+in serum were detected by colorimetric method,the expressions of SIRT1,p53,p21 and NOX4 protein in aortic tissue were detected by Western blot.Results Compared with the normal group,the model group mice showed significant fat deposition in the aorta,thickening of the intima and media,a significant decrease in elastic fibers,and an increase in collagen fibers;the serum contents of ox-LDL and ROS significantly increased(P<0.01),while the contents of GSH,GPX and NAD+significantly decreased(P<0.01);the expression of SIRT1 protein in the aortic tissue significantly decreased(P<0.05),the expressions of p21 and p53 protein significantly increased(P<0.01,P<0.05).Compared with the model group,a small amount of lipid deposition was observed in the intima of aorta in each medication group,with clearer membrane structures in each layer and reduced collagen fiber;the serum contents of ox-LDL and ROS in each medication group were significantly decreased(P<0.01),while the GSH content significantly increased(P<0.05,P<0.01),the NAD+content in TCM low-dosage group significantly increased(P<0.05);the expressions of p21 and NOX4 protein in aortic tissue of the TCM high-dosage group significantly increased(P<0.05,P<0.01).Compared with the Western medicine group,the TCM high-dosage group showed a significant decrease in ROS content(P<0.01)and a significant decrease in p53 protein expression(P<0.05).Compared with the TCM low-dosage group,the TCM high-dosage group showed a significant decrease in p21 protein expression(P<0.01)and a significant increase in NOX4 protein expression(P<0.01).Conclusion Renshen Yimai Prescription may reduce vascular endothelial damage by regulating oxidative stress levels and related protein expression,thereby playing a role in improving vascular aging.

Objective To investigate the relationship between hemoglobin glycation index(HGI)and metabolic syndrome(MS)and its components.Methods A cross-sectional study was conducted to randomly select 823 patients from the First People's Hospital of Huzhou from September 2022 to September 2023.HGI is calculated based on fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)values.The patients were divided into low HGI group(HGI<-0.250%,274 cases),medium HGI group(-0.250%≤HGI≤0.214%,275 cases)and high HGI group(HGI>0.214%,274 cases)by HGI quantile method.The general data and metabolic indexes of each group were compared,and the correlation between HGI and MS and its components was analyzed by multiple Logistic regression.Results With the increase of HGI level,the prevalence rate of MS showed an upward trend(P<0.05).The prevalence rate of MS in low,medium and high HGI groups was 24.8%,42.5%and 55.5%,respectively.Multiple Logistic regression analysis showed that elevated HGI level was risk factor for MS,central obesity,hypertension,hyperglycemia,hypertriglyceridemia and low high-density lipoprotein hyperlipidemia(P<0.05).The risk of MS,central obesity,hypertension,hyperglycemia,hypertriglyceridemia and low high-density lipoprotein hyperlipidemia in high HGI group was 4.005 times(95%CI:2.763-5.808),3.765 times(95%CI:2.604-5.443),1.596 times(95%CI:1.089-2.337),2.655 times(95%CI:1.809-3.895),2.024 times(95%CI:1.404-2.918)and 2.247 times(95%CI:1.537-3.284)of that in low HGI group,respectively.Conclusion HGI is related to MS and its components,and HGI may be a new indicator to prevent and monitor MS.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

OBJECTIVE To optimize the processing technology of honey bran-fried Atractylodis Rhizoma， and to compare the anti-gastric ulcer effect before and after processing. METHODS Combing with entropy-weight and technique for order preference by similarity to ideal solution model， L（9 34） orthogonal experiment design was adopted to optimize the processing technology of honey bran-fried Atractylodis Rhizoma using the comprehensive score of the contents of atractylone， β-cineole， atractylenolide Ⅲ and atractylodine as evaluation index， using the ratio of excipients to medicine， frying temperature and frying time as factors. The validation tests were conducted. The gastric ulcer model of mice was induced by intragastrical administration of anhydrous ethanol； using Compound aluminum hydroxide tablet as positive control， anti-gastric ulcer effect of Atractylodis Rhizoma was compared with that of honey bran-fried Atractylodis Rhizoma using the contents of serum inflammatory factors [interleukin-2 （IL-2）， IL-6， tumor necrosis factor-α （TNF-α）]， ulcer index and inhibitory rate of gastric ulcer as evaluation indexes. RESULTS The optimal processing technology of honey bran-fried Atractylodis Rhizoma was as follows：ratio of adjuvant and medicinal materials of 3∶10 （g/g）， frying temperature at 140 ℃ and frying time of 4 min. Results of 3 validation tests showed that the contents of 4 components （including atractylone）， in honey bran-fried Atractylodis Rhizoma processed by the optimal technology kept stable （RSDs were 3.47%-5.80%， n＝3）； the comprehensive scores were 95.53%-95.89% （RSD＝0.21%， n＝3）. Atractylodis Rhizoma and honey bran-fried Atractylodis Rhizoma could increase the serum content of IL-2 in mice， but reduce serum contents of IL-6 and TNF-α to varying degrees； honey bran-fried Atractylodis Rhizoma could significantly decrease its ulcer indexes （P＜0.05 or P＜ 0.01）； the improvement effect of honey bran-fried Atractylodis Rhizoma on the above indicators was generally better than that of the same dosage of Atractylodis Rhizoma （P＜0.05 or P＜ 0.01）. The inhibitory rates of low-dose， medium-dose and high-dose Atractylodis Rhizoma and honey bran-fried Atractylodis Rhizoma to gastric ulcer in mice were 9.18%， 19.30%， 30.70%， and 50.32%， 61.39%， 53.16%， respectively. CONCLUSIONS The optimal processing technology of honey bran-fried Atractylodis Rhizoma is stable and feasible， and the anti-gastric ulcer effect of Atractylodis Rhizoma has been enhanced after being fried with honey bran.

Objective: To develop a native adaptive behavior scale for children with autism spectrum disorder(ASD) and to explore its reliability and validity. Methods: Items of ASD adaptive behavior rating scale were selected based on the scale development theory, ASD knowledge and adaptive behavior concept through preliminary survey and statistical, and 301 ASD children aged 2 to 12 from hospitals in Guangzhou, Huizhou, Shenzhen who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were selected, data was analyzed by the item analysis. Results: After item analysis and exploratory factor analysis, the final version of the scale contains 58 items, and 64.24% of the total variation could be explained by 6 factors; The Cronbach’s α coefficient of the full scale was 0.98, and the coefficient value of dimen sional factors were 0.94，0.93，0.91，0.95，0.88，0.94. The test-test reliability r of full scale was 0.86, the r of the factor were 0.88，0.81，0.81，0.87，0.88，0.79. The criterion-related validity r with the ABAS-Ⅱ scale was -0.77, the criterion-related validity r with the CARS scale was 0.64. Conclusion The ASD Child Adaptive Behavior Scale showed good reliability and validity, and could be used widely.