1.Effect of Modified Chaihu Shugansan on CaMKⅡ/CREB Signaling Pathway in Rats with Myocardial Ischemia and Depression
Fen WAN ; Xiaohong LI ; Ying CHEN ; Yangyu PAN ; Yanna LUO ; Fangge LU ; Chuncheng ZHENG ; Pengyun KONG ; Chengxiang WANG ; Liqiang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):1-11
ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response element binding protein (CREB) signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet, intraperitoneal injection of isoproterenol (ISO), and chronic unpredictable mild stress (CUMS). A total of 108 SD male rats were randomly divided into normal group, model group, high (23.4 g·kg-1), medium (11.7 g·kg-1), and low (5.85 g·kg-1) dose groups of modified Chaihu Shugansan, CaMKⅡ inhibitor (KN93) group, and KN93 + high, medium, and low dose groups of modified Chaihu Shugansan, with 12 rats in each group. From the first day of modeling to the end of modeling, drugs were administered once a day. In the seventh and eighth weeks, the KN93 group and the KN93 + high, medium, and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week, behavioral tests including sucrose preference, open field, and elevated plus maze were conducted. Electrocardiogram (ECG) lead Ⅱ changes were observed in each group of rats, and hematoxylin-eosin (HE) staining was performed to observe changes in heart tissue. Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lactate dehydrogenase (LDH) were measured by using an enzyme-labeled instrument. Creatine kinase (CK) and creatine kinase-MB (CK-MB) were detected by ultraviolet spectrophotometry, while serum monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue, and Western blot was performed to assess protein expression of CaMKⅡ, phosphorylated (p)-CaMKⅡ, CREB, and p-CREB. ResultsCompared to the normal group, the model group showed significant reductions in sucrose preference rate, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01). The ECG showed ST-segment elevation, and HE staining showed serious degeneration of myocardial fibers, disordered arrangement, and infiltration of a large number of inflammatory cells. In addition, serum TC and LDL levels increased (P<0.01), and HDL level decreased (P<0.01). CK, CK-MB, LDH, and MCP-1 levels significantly increased (P<0.05, P<0.01). The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue (P<0.05, P<0.01), but those increased in the heart tissue (P<0.01). Compared to the model group, the high, medium, and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01), as well as decreased serum CK, CK-MB, LDH, and MCP-1 levels (P<0.05, P<0.01). KN93 also reduced ST-segment elevation, alleviated the degeneration degree of myocardial fibrosis, and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced (P<0.05, P<0.01). The KN93 + high, medium, and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression, possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway, with the high-dose modified Chaihu Shugansan showing the best effects.
2.Technology optimization and in vitro anti-tumor effect evaluation of reactive oxygen species-responsive metho-trexate-modified paclitaxel/icariin micelles
Naijian ZOU ; Liang KONG ; Lei CHANG ; Pengbo WAN ; Xiaolin JIANG ; Mingdian YUAN ; Yingqiang LU
China Pharmacy 2025;36(3):285-292
OBJECTIVE To prepare reactive oxygen species (ROS)-responsive methotrexate (MTX)-modified paclitaxel (PTX)/icariin (ICA) micelles (MTX-oxi-Ms@PTX/ICA), and perform technology optimization and in vitro anti-tumor effect evaluation. METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test. The micelles were prepared by thin film hydration method, and their technology was optimized by response surface methodology. The fundamental characteristics of the micelles prepared by the optimal technology were evaluated. The micelles’ cytotoxicity, targeting ability to renal carcinoma RENCA cells of mice, and their inhibitory effects on invasion and migration were assessed. RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L. The optimal technology of MTX-oxi-Ms@PTX/ ICA was determined to include 80 mg Soluplus®, Soluplus® and TPGS1000 mass ratio of 4∶1 (mg/mg), 2 mg DSPE-PEG2000-TK- PEG5000, 2 mg DSPE-PEG2000-MTX, 1 mg PTX, and 1.5 mg ICA, with a hydration temperature of 35 ℃ and a formulation volume of 5 mL. Under the optimal conditions, average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi- Ms@PTX/ICA reached 92.75%, the critical micelle concentration (CMC) was 0.007 9 mg/mL, the particle size was (62.09±1.68) nm, the polydispersity index (PDI) was 0.046±0.032, and the Zeta potential was (-2.47±0.15) mV. Within 30 days of placement, there was no significant change E-mail:yingqiang_1126@163.com in particle size and polydispersity index of micelle. In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments. The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was (5.170±0.036) μmol/L. In vitro cellular uptake experiments indicated that compared with unmodified micelles, MTX modified micelles had stronger targeting effects on cancer cells, and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells (P<0.05). CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared, which exhibit high encapsulation efficiency, low critical micelle concentration, and good stability. These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.
3.Prevalence of menopausal syndrome among postmenopausal women in Pan'an County
YING Huizhen ; JI Li ; KONG Wenjuan ; WANG Yuan ; CHEN Xiaoxia ; HU Caihong ; FU Haiying ; LU Yuanyuan ; CHE Xiuli
Journal of Preventive Medicine 2025;37(3):312-315
Objective:
To investigate the prevalence and influencing factors of menopausal syndrome among postmenopausal women in Pan'an County, Zhejiang Province, so as to provide the basis for guiding the health management of postmenopausal women.
Methods:
From May 2023 to April 2024, the postmenopausal women aged 40 to 69 years in Pan'an County were selected using the random cluster sampling method. Demographic information, lifestyle and prevalence of gynecological diseases were collected through questionnaire surveys. The prevalence of menopausal syndrome was assessed by modified Kupperman Score Scale. Factors affecting menopausal syndrome were analyzed by a multivariable logistic regression model.
Results:
A total of 816 postmenopausal women were surveyed, with an mean age of (57.63±2.92) years and a mean natural menopause age of (49.85±2.13) years. There were 574 cases with menopausal syndrome, with a prevalence of 70.34%. Flashes and sweating, insomnia and irritability were common symptoms, accounting for 62.87%, 47.43% and 41.18%, respectively. Multivariable logistic regression analysis showed that monthly personal income of ≤5 000 yuan (<3 000 yuan, OR=3.124, 95%CI: 1.829-5.335; 3 000-5 000 yuan, OR=2.399, 95%CI: 1.370-4.201) and having gynecological diseases (OR=1.970, 95%CI: 1.292-3.004) were associated with a higher risk of menopausal syndrome, while average (OR=0.141, 95%CI: 0.072-0.276) or sufficient sleep quality (OR=0.095, 95%CI: 0.049-0.185) were associated with a lower risk of menopausal syndrome.
Conclusion
The prevalence of menopausal syndrome among postmenopausal women in Pan'an County is relatively high, and is mainly influenced by personal economic status, sleep quality and the presence of gynecological diseases.
4.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
5.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
6.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
7.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
8.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
9.Neuronal intranuclear inclusion disease with the main manifestations of tremor and disturbance of consciousness: A case report and literature review
Journal of Apoplexy and Nervous Diseases 2025;42(2):174-177
Case data were collected from an adult patient with sporadic neuronal intranuclear inclusion disease who were diagnosed in Affiliated Hospital of Jining Medical University. The patient was an elderly woman aged 64 years, with the main clinical manifestations of limb tremor and paroxysmal disturbance of consciousness. Skin biopsy of the patient showed the presence of eosinophilic inclusion bodies, head MRI diffusion sequences showed abnormal hyperintensity signals in the corticomedullary junction area, and genetic testing showed pathogenic genes NOTCH2NLC positive. The patient was diagnosed with neuronal intranuclear inclusion disease and was given symptomatic treatment. This case report suggests that for patients with limb tremor or paroxysmal disturbance of consciousness, if MRI diffusion sequences show abnormal hyperintensity signals in the corticomedullary junction area, the possibility of this disease should be considered, and skin biopsy and genetic testing should be performed to make a confirmed diagnosis, in order to provide early treatment.
10.Survey on the awareness and clinical application of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians
Yuanyuan KONG ; Yujie GUO ; Yujuan GUAN ; Xuan LIANG ; Zhongjie HU ; Xiaobo LU ; Mingqin LU ; Yongfeng YANG ; Meifang HAN ; Hong YOU ; Zhiyun YANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(6):1068-1074
ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. MethodsFrom July 19 to December 31, 2024, a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide, including their awareness and practice based on 18 questions regarding testing and referral, diagnosis and treatment, and follow-up. ResultsAmong all respondents, only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B, with an overall awareness rate of 22.0%. Only 20% — 40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy, while 80% — 100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year, 3 years, and 5 years were 67.5% 57.5% and 47.5%,respectively, showing a trend of gradual reduction, which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians, insufficient awareness of the disease among patients, and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection, diagnosis, treatment, and management” for patients with chronic hepatitis B in healthcare institutions, in order to promote the implementation of the guidelines.


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