1.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
2.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
3.Influencing factors of stroke complicated with hypertension and its compliance with antihypertensive drugs
Mei LI ; Xiaoli LIU ; Fan ZHANG ; Fujuan YUE ; Tiantian GUO ; Xiuli NIU ; Jixin SUN ; Dongsheng JIANG
Journal of Public Health and Preventive Medicine 2026;37(3):94-98
Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients. Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs. Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09). Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.
4.Professor ZHU Shengliang's Clinical Experience in Differentiating and Treating Gastroesophageal Reflux Disease with Qi Constraint and Phlegm Obstruction Syndrome
Xiuli YAN ; Xiaoyu YU ; Xiulian ZHANG ;
Journal of Traditional Chinese Medicine 2026;67(11):1153-1156
This paper summarizes professor ZHU Shengliang's academic idea and clinical experience in treating gastroesophageal reflux disease (GERD) with qi constraint and phlegm obstruction syndrome. It is believed that the core pathogenesis of GERD is the dysfunction of the liver, gallbladder, spleen and stomach, with binding of phlegm and stasis. The basic pathogenesis is the liver and gallbladder failing to dredge and disperse, the stomach failing to harmonize and descend, and the stomach qi counterflowing upward. In clinical practice, the treatment principle of regulating qi as the priority, resolving phlegm as the key, and activating blood as the assistant is applied, with harmonizing the stomach and directing counterflow downward throughout the whole process. A self-made Shugan Hewei Huatan Formula (疏肝和胃化痰方) is employed with the function of soothing the liver and rectifying qi, opening constraint and dissipating knot, dissolving phlegm and dispelling stasis, harmonizing stomach and directing counterflow downward, with an emphasis on flexible modification according to the syndrome as well as careful protection of stomach qi.
5.From Bedside to Molecular Diagnosis-Multidisciplinary Treatment of a Rare Case of Autoinflammatory Disease Presenting with Skin Induration and Limb Weakness
Hanhui FU ; Wenjun WANG ; Yaping LIU ; Hui YOU ; Tao WANG ; Wen ZHANG ; Xuejun ZENG ; Liying CUI ; Huijuan ZHU ; Xiuli ZHAO ; Min SHEN ; Yicheng ZHU
JOURNAL OF RARE DISEASES 2026;5(2):207-213
This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.
6.Development and evaluation of the Children's Screen Interaction Quality Questionnaire for Children aged 0-4
Lifang JIN ; Yan LUO ; Chengwei SHEN ; Huiling QIN ; Kexin TU ; Lanyin JIAN ; Fan ZHANG ; Jiacai ZHANG ; Xin ZHOU ; Xiuli CHEN
Chongqing Medicine 2025;54(5):1118-1122,1127
Objective To develop the Children's Screen Interaction Quality Questionnaire(CSIQ)suit-able for measuring Chinese children aged 0 to 4 years,and to test its reliability and validity.Methods The purposive sampling method was used,and the guardians of 30 normal children aged 0 to 4 years undergoing physical examinations in the Department of Child Health Care of Guiyang Maternal and Child Health Care Hospital from February to April 2023 were selected as the interview objects.25 initial items were constructed through literature review,semi-structured interviews,and the Delphi expert consultation method.With the convenience sampling method,2 242 guardians of children aged 0 to 4 years old in the small and middle classes of 9 kindergartens in Guiyang City,Zunyi City,and Renhuai City were surveyed for item analysis,exploratory factor analysis,confirmatory factor analysis,and reliability and validity analysis.Results Exploratory factor a-nalysis extracted three factors,namely screen content interaction,reality interaction,and media interaction,with a total of 12 items.The cumulative variance explained rate of the 3-factor model was 69.829%.Confirma-tory factor analysis supported the three-factor model of CSIQ:x2/df=4.424,root mean square error of ap-proximation(RMSEA)=0.066,normed fit index(NFI)=0.955,comparative fit index(CFI)=0.965,incre-mental fit index(IFI)=0.965,Tucker-Lewis index(TLI)=0.955,goodness-of-fit index(GFI)=0.955,and the CSIQ had good convergent validity and discriminant validity.Conclusion The CSIQ has good reliability and validity.
7.Co-culture with human umbilical cord-derived mesenchymal stem cells ameliorates allergic inflammation in mouse lung tissues
Yanghe HAO ; Xiuli LIU ; Chaoran ZHAO ; Chengshuo WANG ; Luo ZHANG ; Ming WANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(5):299-303
OBJECTIVE To explore the therapeutic effect of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in mouse model of allergic lung inflammation.METHODS hUC-MSCs were isolated and cultured from umbilical cord of healthy neonates.The expression of MSC cell surface markers were assessed by flow cytometry in the fifth generation of hUC-MSCs.Mice were sensitized by intraperitoneal injection of ovalbumin and challenged via inhalation of aerosolized ovalbumin to establish an allergic airway inflammation model.The same dose of normal saline was used in the control group.After 14 days of nebulization,lung tissues and bronchoalveolar lavage fluid(BALF)were collected from the mice.Hematoxylin and eosin staining and Luminex multiplex assay were performed to assess the levels of allergic inflammation.Lung tissues were minced,homogenized,and digested into single-cell suspensions for cell culture.hUC-MSCs or human nasal epithelial cells were co-cultured with mouse lung cells at a ratio of 1:5 or 1:10(cell number ratio).After 18 hours,the supernatants were collected,and Luminex multiplex assay was performed to assess the expression of inflammatory cytokines interleukin-5(IL-5)and IL-6.RESULTS Cultured hUC-MSCs showed an elongated spindle-shaped morphology.The positive markers CD105,CD73,and CD90 showed positive rates of>95%respectively,while the negative markers CD45,CD34,and CD11b exhibited positive rates of<2%respectively.Compared with the controls,the allergic mice showed significant infiltration of eosinophils in the peribronchial regions of lung tissues,and increased expression levels of IL-5(P<0.01)and IL-6(P<0.05)in BALF.Compared with the control group,mouse lung cells co-cultured with hUC-MSCs significantly decreased the levels of IL-5 and IL-6 in the supernatant(both P<0.05 in 1∶5 group and 1∶10 group).CONCLUSION Co-culture with hUC-MSCs can significantly ameliorate allergic inflammation in lung tissue of mouse model,indicating the therapeutic potential of hUC-MSCs in airway allergic inflammation.
8.Retrospective epidemiological analysis of fungal infection of a hospital from 2018 to 2024
Zhihao LIU ; Yali LIU ; Lina GUO ; Yao WANG ; Ying ZHAO ; Xiuli XIE ; Wenjing LIU ; Renyuan ZHU ; Hongli SUN ; Hongtao DOU ; Dingding LI ; Lingli LIU ; Shuying YU ; Menglan ZHOU ; Qiwen YANG ; Yingchun XU ; Li ZHANG
International Journal of Laboratory Medicine 2025;46(21):2588-2594
Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5%(2 576/4 479)]was higher than that of female patients[42.5%(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0%(2 241/4 479)].About 90.0%of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6%of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5%of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8%.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6%).98.6%of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.
9.Spectral CT multi-parameter imaging for diagnosing bronchial anthracofibrosis complicated with active pulmonary tuberculosis
Jingjing YANG ; Xiuli WU ; Liping ZHANG ; Baosheng HUANG
Chinese Journal of Medical Imaging Technology 2025;41(9):1526-1530
Objective To explore the value of spectral CT multi-parameter imaging for diagnosing bronchial anthracofibrosis(BAF)complicated with active pulmonary tuberculosis.Methods Totally 77 patients with BAF complicated with atelectasis were retrospectively enrolled.According to undergoing anti-tuberculosis treatment or not during hospitalization,26 patients complicated with active pulmonarg tuberculosis were divided into group A(n=26),while 51 cases without active pulmonarg tuberculosis were divided into group B.Signs indicating active pulmonary tuberculosis(i.e.tree-in-bud sign or centrilobular nodules)on chest spectral CT images were analyzed.Non-enhanced CT(NECT)values,single-energy CT values at 40 keV(CT40 kev)and 70 keV(CT70 kev),as well as effective atomic number(Zeff),iodine concentration(IC),calcium concentration(CC)and hydroxyapatite concentration(HAP)in the arterial phase and venous phase of enhancement at the site of bronchial obstruction and in subcarinal lymph nodes were measured.the slope of spectral line(λ40-70keV)was calculated and compared between groups.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was used to evaluate the efficacy of the above parameter alone and their combinations for diagnosing BAF complicated with active pulmonarg tuberculosis.Results The displaying rate of active pulmonary tuberculosis CT signs in group A was higher than that in group B(P=0.005).NECT values,enhanced venous phase CT40kev,λ40-70 kev,as well as Zeff,IC,CC and HAP at the site of bronchial obstruction in group A were all lower than those in group B(all P<0.05).The AUC of active pulmonary tuberculosis CT signs for assessing BAF complicated with active pulmonary tuberculosis was 0.659,of the combination of CT quantitative parameters at the site of bronchial obstruction was 0.769,while of the combination of CT signs and CT quantitative parameters was 0.825,higher than of active pulmonary tuberculosis CT signs alone(P<0.05).Conclusion Spectral CT multi-parameter imaging could be used to effectively diagnose BAF complicated with active pulmonary tuberculosis.
10.Erratum: Author correction to "Generation of αGal-enhanced bifunctional tumor vaccine" Acta Pharm Sin B 12 (2022) 3177-3186.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2025;15(2):1207-1207
[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].


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