1.Apoptosis Regulation by Buzhong Yiqitang via PERK/eIF2α/ATF4/CHOP Pathway to Enhance Pulmonary Surfactant-associated Protein C Expression and Ameliorate Lung Injury in CIH Mice
Luyao ZHANG ; Yangjing WANG ; Bingbing LIU ; Jieru LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):19-27
ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C (SFTPC) and lung injury induced by chronic intermittent hypoxia (CIH) and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups: a normoxia group, a CIH group, and low-, medium-, and high-dose Buzhong Yiqitang groups, with eight mice in each group. During the modeling, mice in the normoxia group were housed under standard oxygen concentrations, while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session, mice in the low-, medium-, and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses (8.1, 16.2, 32.4 g·kg-1·d-1 of crude drug, respectively), while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung tissue were evaluated using hematoxylin-eosin (HE) staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Protein expression of SFTPC, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), activating transcript factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group, mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels increased, while SFTPC expression in lung tissue was reduced (P<0.05, P<0.01). The rate of apoptotic cells in lung tissue increased, and the expression of endoplasmic reticulum stress markers p-PERK, p-eIF2α, ATF4, and CHOP was upregulated (P<0.05, P<0.01). Compared with the CIH group, Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels were decreased, and lung tissue SFTPC expression was recovered (P<0.05, P<0.01). The apoptotic rate of lung tissue cells was significantly reduced, with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression (P<0.05, P<0.01). Activation and expression of p-PERK, p-eIF2α, ATF4, and CHOP were also decreased (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion, which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.
2.Changes of corneal densitometry and higher-order aberrations in high myopia patients after small incision lenticule extraction
Yangjing ZHANG ; Liwei MA ; Guohua CAI ; Su LIU ; Ruifu WANG ; Lipye ZU
International Eye Science 2025;25(6):894-899
AIM: To observe the changes of corneal densitometry(CD)and higher-order aberrations after small incision lenticule extraction(SMILE), and to explore their correlations and influencing factors.METHODS: Prospective study. A total of 62 high-degree myopia and compound myopic astigmatism patients(62 eyes)who underwent SMILE in Urumqi Aier Eye Hospital from December 2022 to November 2023 were collected. The CD, root mean square of corneal higher-order aberrations(RMS HOA), spherical aberration, vertical coma, horizontal coma, and corneal epithelial thickness(CET)of the patients were measured before surgery, and at 1 d, 1 wk, 1, 3, and 6 mo after surgery, respectively.RESULTS:There were 4 patients lost to follow-up during the period, all due to failure to attend scheduled reexaminations. The number of complete and valid cases was 58 eyes. The CD in the central and paracentral regions of the anterior, middle, and total layer of the cornea increased significantly on the first day after surgery(all P<0.003). At 6 mo after surgery, there was a slight but statistically significant decrease in the CD of the central and paracentral regions of the anterior and the total anterior layer(all P<0.003). Compared with the preoperative baseline values, the RMS HOA, spherical aberration, and vertical coma significantly increased at 6 mo after surgery(all P<0.003), while the change in horizontal coma was not statistically significant. Compared with the preoperative baseline values, the CET in the central, paracentral, and peripheral regions of the cornea, as well as the total average CET in the 0-7 mm range of the cornea increased at 6 mo after surgery(all P<0.003). At 1 d after surgery, CD of the anterior layer and total layer in the central region of the cornea were positively correlated with the CET in the central region(rs=0.327, rs=0.250, all P<0.05). At 6 mo after the surgery, the CD of the middle layer and posterior layer in the central corneal region were negatively correlated with the preoperative spherical equivalent and the change of RMS HOA(all P<0.05).CONCLUSION:The anterior CD decreases at 6 mo after SMILE for high myopia correction, and there is a certain correlation between the changes in CD and some clinical parameters.
3.CAO Yuxia's Experience in Treating Congenital Preauricular Fistula Infection and Abscess with SHI's Thick Fire Needle Based on the Theory of"Treating Fire Depression with Effusion"
Qianqian LIU ; Yanlin ZHANG ; Yangjing DUAN
Journal of Zhejiang Chinese Medical University 2025;49(6):747-750
[Objective]To introduce Director CAO Yuxia's experience in treating congenital preauricular fistula infection and abscess with SHI's thick fire needle based on the thought of"treating fire depression with effusion".[Methods]By following the clinical works and case collation,the basic pathomechanism of congenital preauricular fistula infection and abscess was elaborated,and the innovative use of SHI's thick fire needle based on the therapeutic principle of"treating fire depression with effusion"to implement the"burnt needle robbing and stabbing"method was analyzed,and Director CAO's clinical experience in treating this disease by using SHI's thick fire needle and robbing stabbing method based on the therapeutic principle of"treating fire depression with effusion"was summarized,and a medical case was presented to support it.[Results]Director CAO believes that the disease was caused by the accumulation of heat and the decay into pus.The treatment should be based on the theory of"treating fire depression with effusion".For the first time,she proposes and adopts one of the new nine needles,SHI's thick fire needle,to quickly stab and eliminate pus,which can obtain the effect of"discharging heat,expelling pus,eliminating pathogens and stopping pain".In the medical case cited,the patient was suffered from this disease,combining the tongue and pulse with symptoms,he was identified as the syndrome of the accumulation of fire-heat toxin.Therefore,the key treatment principle was to eliminate pathogens and expel pus,relieve heat and resolve toxin,and after once fire needle treatment,good effect was obtained.[Conclusion]Director CAO treats congenital preauricular fistula infection and abscess,focusing on the"treating fire depression with effusion"principle,taking the fire and heat nature of fire needle and exerting the effect of"opening the way to eliminate pathogens,and expelling heat with heat",and achieves better clinical efficacy.The experience can provide ideas for the treatment of fire-heat and toxicity-containing diseases,which is worthy of clinical reference.
4.Clinical evaluation of Ultra Q Nd:YAG laser vitreous ablation for vitreous opacity based on decision tree analysis
Zhengzhou ZHANG ; Ruifu WANG ; Zulipiya ; Yangjing ZHANG ; Xiaxia JIANG ; Haifan LI ; Yating ZHAO
Chongqing Medicine 2025;54(6):1394-1398
Objective To investigate factors that affect the treatment effect of laser vitrectomy for vit-reous opacity and the related factors that affect patient satisfaction,so as to evaluate its clinical value.Methods A total of 196 patients with vitreous opacity treated using the Ultra Q ReflexTM Nd:YAG laser system at our hospital between October 2019 and February 2024 were enrolled.Patient medical records and satisfaction questionnaires were analyzed.Investigational data underwent machine-coded classification,and a Python-based decision tree prediction model was employed to identify factors affecting treatment outcomes.Stata18.0 OLS linear regression was used to assess correlations between patient satisfaction and variables such as healthcare provider quality,treatment accessibility,and medical environment.Results After laser vitrectomy,95.3%of patients with vitreous opacity showed significant improvement in symptoms,and 90.3%expressed satisfac-tion with the improvement in postoperative visual quality.Patients'gender,age,preoperative vitreous opacity morphology,and refractive error below-6.00D had an impact on the treatment outcome(P<0.05).Python decision tree analysis demonstrated superior efficacy in patients aged>30-45 years with 6-12 months of symptom duration and refractive error<-6.00D.Stata18.0 OLS linear regression analysis showed that all examined variables were positively correlated at the 1%significance level,with patients'expected feelings having the greatest impact on postoperative satisfaction with treatment(r=1.053).Conclusion Ultra Q Nd:YAG laser vitreous ablation demonstrates high safety and patient satisfaction for vitreous opacity treatment.
5.The role of inhibitor of DNA binding 1 in hematologic malignancies
Yangjing Zhao ; Yue You ; Jiaxin Xu ; Yan Pan ; Tingjuan Zhang ; Jingdong Zhou
Acta Universitatis Medicinalis Anhui 2025;60(12):2384-2390
Abstract
Inhibitor of DNA binding 1(ID1) is a crucial regulator of cell differentiation and plays a significant role in maintaining normal hematopoietic differentiation and development. Due to the lack of DNA-binding motif, ID1 functions as a dominant-negative inhibitor of basic helix-loop-helix factors to antagonize their abilities to bind to DNA and transcriptionally regulate target genes. Abnormal expression of ID1 is strongly associated with various hematologic disorders, including myeloid and lymphoblastic leukemia, multiple myeloma and myeloproliferative neoplasms. ID1 acts as a potential oncogene by participating in multiple signaling pathways that promote the malignant proliferation, invasion and therapy resistance in leukemic cells. Significant strides have yielded promising antileukemic effects of ID1 inhibitors, both alone and in combination with targeted therapies against oncogenic signaling pathways. Here, we review the relationship between ID1 expression and the initiation and progression of blood disorders, and summarize the clinical significance of ID1 as a novel therapeutic target and potential prognostic biomarker for hematologic malignancies.
6.Clinical research on corneal epithelium remodeling after small incision lenticule extraction and femtosecond laser-assisted in situ keratomileusis
Yangjing ZHANG ; Liwei MA ; Fan ZHANG ; Chunmei KE ; Ruifu WANG ; Lipye ZU
International Eye Science 2025;25(1):37-41
AIM: To compare the changes in corneal epithelial thickness(CET)after small incision lenticule extraction(SMILE)and femtosecond laser-assisted in situ keratomileusis(FS-LASIK).METHODS: A total of 187 patients(187 eyes)who underwent either SMILE or FS-LASIK at Urumqi Aier Eye Hospital between December 2022 and November 2023 were collected. The patients were divided into SMILE group and FS-LASIK group according to surgical methods. The CET of the patients was measured by optical coherence tomography(OCT)system before surgery and at 1 wk, 1, 3, and 6 mo postoperatively.RESULTS: Changes in corneal epithelial thickness(△CET)in the central, paracentral, and mid-peripheral regions were compared at 6 mo postoperatively. The SMILE group was characterized by the most significant thickening in the central area and the least thickening in the mid-peripheral area; while the FS-LASIK group was characterized by the most significant thickening in the paracentral area and the least thickening in the mid-peripheral region. At 1 wk, 1, 3, and 6 mo postoperatively, within the 0-7 mm corneal area, the △CET for both the SMILE and FS-LASIK groups was correlated with the preoperative spherical equivalent.CONCLUSION: Within 6 mo postoperatively, both SMILE and FS-LASIK showed a similar trend in epithelial thickening but with distinct characteristics. The change in corneal epithelial thickness for both procedures was positively correlated with the preoperative diopter.
7.Dihuang Yinzi Improves Cognitive Function of Mouse Model of Learning and Memory Impairments by Regulating Synaptic Plasticity via SIRT2
Wenting WANG ; Yangjing HAO ; Wenna SU ; Qinqing LI ; Shifeng CHU ; Junlong ZHANG ; Wenbin HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):9-17
ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine (SCOP) and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups: control (0.9% NaCl, n=10), model (SCOP 1 mg·kg-1·d-1, n=10), low-, medium-, and high-dose Dihuang Yinzi (SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5, 11.0, and 22.0 g·kg-1·d-1, n=10), and donepezil (SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1, n=10). Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week, and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week, 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 (SIRT2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 1 (GluA1), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated-CREB (p-CREB), postsynaptic density protein 95 (PSD95), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin (DCX) in the hippocampal dentate gyrus (DG) region. ResultsCompared with the control group, the model group showed impaired learning and memory (P<0.01), obvious neuronal damage in the hippocampal CA1 region, a reduction in neuron survival (P<0.01), a decrease in DCX expression in the hippocampal DG region (P<0.01), down-regulated proteins levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 in the hippocampal tissue (P<0.05, P<0.01), and an up-regulated protein level of SIRT2 (P<0.01). Compared with the model group, the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory (P<0.05, P<0.01), while the low-, medium-, and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival (P<0.05, P<0.01). The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression (P<0.05, P<0.01). The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 (P<0.05, P<0.01) and down-regulation in the protein level of SIRT2 (P<0.01). ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2, activating the PKA/CREB signaling pathway, improving synaptic plasticity, and reducing hippocampal neuronal damage.
8.Establishment and evaluation of a disease-syndrome combined rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome
Zhuoxiu LIU ; Yangjing HAO ; Hao FU ; Qinqing LI ; Jianjun ZHANG ; Shifeng CHU ; Zhao ZHANG ; Zhuoqing CAO ; Wenbin HE
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1091-1104
Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.
9.Establishment and evaluation of a disease-syndrome combined rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome
Zhuoxiu LIU ; Yangjing HAO ; Hao FU ; Qinqing LI ; Jianjun ZHANG ; Shifeng CHU ; Zhao ZHANG ; Zhuoqing CAO ; Wenbin HE
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1091-1104
Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.
10.CAO Yuxia's Experience in Treating Congenital Preauricular Fistula Infection and Abscess with SHI's Thick Fire Needle Based on the Theory of"Treating Fire Depression with Effusion"
Qianqian LIU ; Yanlin ZHANG ; Yangjing DUAN
Journal of Zhejiang Chinese Medical University 2025;49(6):747-750
[Objective]To introduce Director CAO Yuxia's experience in treating congenital preauricular fistula infection and abscess with SHI's thick fire needle based on the thought of"treating fire depression with effusion".[Methods]By following the clinical works and case collation,the basic pathomechanism of congenital preauricular fistula infection and abscess was elaborated,and the innovative use of SHI's thick fire needle based on the therapeutic principle of"treating fire depression with effusion"to implement the"burnt needle robbing and stabbing"method was analyzed,and Director CAO's clinical experience in treating this disease by using SHI's thick fire needle and robbing stabbing method based on the therapeutic principle of"treating fire depression with effusion"was summarized,and a medical case was presented to support it.[Results]Director CAO believes that the disease was caused by the accumulation of heat and the decay into pus.The treatment should be based on the theory of"treating fire depression with effusion".For the first time,she proposes and adopts one of the new nine needles,SHI's thick fire needle,to quickly stab and eliminate pus,which can obtain the effect of"discharging heat,expelling pus,eliminating pathogens and stopping pain".In the medical case cited,the patient was suffered from this disease,combining the tongue and pulse with symptoms,he was identified as the syndrome of the accumulation of fire-heat toxin.Therefore,the key treatment principle was to eliminate pathogens and expel pus,relieve heat and resolve toxin,and after once fire needle treatment,good effect was obtained.[Conclusion]Director CAO treats congenital preauricular fistula infection and abscess,focusing on the"treating fire depression with effusion"principle,taking the fire and heat nature of fire needle and exerting the effect of"opening the way to eliminate pathogens,and expelling heat with heat",and achieves better clinical efficacy.The experience can provide ideas for the treatment of fire-heat and toxicity-containing diseases,which is worthy of clinical reference.


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