1.Huayu Mingmu Prescription Downregulates PI3K/Akt/mTOR-HIF-1α/VEGFA Signaling Pathway to Intervene in Retinal Angiogenesis of DR Rats
Xiaoqiu MA ; Lei ZHAO ; Huimin ZHOU ; Fanghui ZHENG ; Guoqing YANG ; Tao ZUO ; Xiande MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):78-87
ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR)-hypoxia inducible factor-1α/vascular endothelial growth factor A (HIF-1α/VEGFA) signaling pathway in diabetic retinopathy (DR) rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group, while the remaining 53 rats were fed a high-sugar, high-fat diet combined with low-dose streptozotocin (STZ) intraperitoneal injection to establish a type 2 diabetes mellitus (T2DM) rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model, low-dose, medium-dose, and high-dose groups of Huayu Mingmu prescription (9.29, 18.57, 37.14 g·kg-1), and a calcium dobesilate group (0.16 g·kg-1), with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography, and pathological changes in retinal tissue were evaluated using hematoxylin-eosin (HE) staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff (PAS) staining. Immunofluorescence (IF) was used to detect the expression of VEGFA and angiopoietin-2 (Ang-2) in retinal tissue. Western blot was employed to detect the protein expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. ResultsCompared with the normal group, the model group exhibited significant pathological changes in retinal tissue, including the appearance of acellular capillaries, as well as significant endothelial cell (E) proliferation and pericyte (P) loss (P<0.01). The E/P was significantly elevated (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly increased (P<0.01), and the expression of Ang-2 protein was significantly elevated (P<0.01). In contrast, retinal tissue in the treatment groups showed alleviated pathological changes, with reduced endothelial cell proliferation and pericyte loss (P<0.05, P<0.01). Among the treatment groups, the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly reduced (P<0.05, P<0.01), and the expression of Ang-2 protein was significantly decreased (P<0.01). ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats, delay the progression of DR, and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.
2.Protective Effect of Liuwei Dihuangwan on Mitochondrial Damage in AD Model of Caenorhabditis Elegans
Jinfeng ZHANG ; Yuliang TONG ; Jiapeng WANG ; Ting SU ; Deping ZHAO ; Hao YU ; Kun ZUO ; Ziyue ZHU ; Meiling JIN ; Ning ZHANG ; Xia LEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):18-25
ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan (LW) on mitochondrial damage in the Alzheimer's disease (AD) model of Caenorhabditis elegans (C. elegans). MethodC. elegans transfected with human β-amyloid protein (Aβ) 1-42 gene was used as an AD model. The rats were divided into blank group, model group, metformin group (50 mmol·L-1), and low, medium, and high dose (1.04, 2.08, 4.16 g·kg-1) LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine (5-HT) in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate (ATP) kit, and mitochondrial membrane potential was detected by the JC-1 method. In addition, the mRNA expression of Aβ expression gene (Amy-1), superoxide dismutase-1 (SOD-1), mitochondrial transcription factor A homologous gene-5 (HMG-5), mitochondrial power-associated protein 1 (DRP1), and mitochondrial mitoprotein 1 (FIS1) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT (P<0.05) and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group, in the model group, the mRNA expression of Aβ protein and Amy-1 increased (P<0.01), and the mRNA expression of SOD-1 and HMG-5 decreased (P<0.01). The mRNA expression of DRP1 and FIS1 increased (P<0.01), and the level of mitochondrial membrane potential decreased (P<0.05). The content of ATP decreased (P<0.01). Compared with the model group, in the positive medicine group and medium and high dose LW groups, the mRNA expression of Aβ protein and Amy-1 decreased (P<0.05,P<0.01), and the mRNA expression of SOD-1 and HMG-5 increased (P<0.01). The mRNA expression of DRP1 decreased (P<0.05,P<0.01), and that of FIS1 decreased (P<0.01). The level of mitochondrial membrane potential increased (P<0.01), and the content of ATP increased (P<0.05,P<0.01). ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria, protect mitochondrial DNA, reduce the fragmentation of mitochondrial division, repair the damaged mitochondria, adjust the mitochondrial membrane potential, restore the level of neuronal ATP, and reduce the neuronal damage caused by Aβ deposition.
3.Effect of Liuwei Dihuang Tang on ferroptosis pathway in retinal tissue of aging model rats
International Eye Science 2024;24(3):338-344
AIM: To observe the effects of Liuwei Dihuang Tang on the expression levels of ferritin, recombinant solute carrier family 7 member 11(SLC7A11), glutathione(GSH), and glutathione peroxidase 4(GPX4)in retinal of aging model rats.METHODS: A total of 45 SD rats were randomly divided into a blank group, a model group, and a traditional Chinese medicine(TCM)group, with 15 rats in each group. The blank group was intraperitoneally injected with physiological saline, while the model group and TCM group were intraperitoneally injected with D-galactose [500 mg/(kg·d)]. At the same time, the TCM group was orally administered with Liuwei Dihuang Tang [6.75 g/(kg·d)], while the blank group and model group were orally administered with equal volume of physiological saline for 8 consecutive wk. The expression levels of ferritin, SLC7A11, GSH, and GPX4 in the retinal tissues of rats in each group were detected.RESULTS: The expression of ferritin in the retinal tissue of the model group was increased compared to the blank group(P<0.05), while the expression of GSH, SLC7A11, and GPX4 was reduced(P<0.05). The expression of GSH, SLC7A11, and GPX4 in the retina tissue of rats in the TCM group was higher than that in the model group(P<0.05).CONCLUSIONS: Liuwei Dihuang Tang may exert a delaying effect on retinal aging by regulating the ferroptosis pathway.
4.Multimodal analgesia in the treatment of a case of pediatric primary erythromelalgia with infection and pharma-ceutical care
Mengqiu LI ; Lei ZUO ; Xin RAN ; Qing LI ; Xinyu LI ; Ning LUO
China Pharmacy 2024;35(13):1658-1662
OBJECTIVE To explore a multimodal analgesia regimen based on spinal cord electrical stimulation for children with primary erythromelalgia and the key points of pharmaceutical care. METHODS Clinical pharmacists participated in the treatment of a child with primary erythromelalgia complicated with skin infection. After reviewing domestic and foreign literature, multimodal analgesia was formulated and pharmaceutical care was carried out to address the difficulties in treating the patient’s illness. RESULTS The treatment team applied multimodal analgesia based on spinal cord electrical stimulation for the child, including a multi-drug combination involving different analgesic pharmacological targets, multiple administration routes (oral, intravenous, epidural, percutaneous), multiple technologies (spinal cord electrical stimulation, local nerve block, patient- controlled analgesia), individualized schemes of adjuvant therapy, and the child was monitored for the safety of drug use. The pain was controlled during the treatment and follow-up period, the wound was healed, and no serious adverse drug reactions occurred. CONCLUSIONS Multimodal analgesia based on spinal cord electrical stimulation is a safe and effective treatment for children with primary erythromelalgia.
5.Environmental contamination related to the first patient with carbapenem-resistant Acinetobacter baumannii infection and the infection status of pa-tients in the intensive care unit in Tibetan areas
Cuo-Ta QIE ; Ding-Ying HE ; Fu-Yan LONG ; Xiao-Hua ZHANG ; Chun-Hua PENG ; Xiang-Xiang JIANG ; Ming-Lei DENG ; Cong FU ; Guo-Ping ZUO
Chinese Journal of Infection Control 2024;23(2):220-224
Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for>48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06%,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.
6.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
7.A case of recurrent renal pelvic sarcomatoid carcinoma treated with PD-1 inhibitor achieved complete remission
Lei GAO ; Chao LU ; Xiaokai SHI ; Yangyang SUN ; Xiaoli ZHOU ; Xiaopeng WU ; Lifeng ZHANG ; Li ZUO
Chinese Journal of Urology 2024;45(1):55-56
Sarcomatoid carcinoma of the renal pelvis accounts for a very low percentage of malignant tumors in the renal pelvis and has a poor prognosis. This article reported a patient with sarcomatoid carcinoma of the renal pelvis. The patient presented with macroscopic hematuria as the first symptom, and CT suggested left renal occupancy, unilateral nephrectomy was performed, and pathology suggested sarcomatoid carcinoma of the renal pelvis. Three weeks after surgery, a follow-up CT showed tumor recurrence. Programmed death 1(PD-1)inhibitor was given once every 3 weeks. Repeated CT examination after 24 weeks of continuous treatment suggested that the recurrent tumor disappeared. The patients was followed-up for 42 months without tumor recurrence or metastasis.
8. Effect Xuefu Zhuyu decoction on endothelial-to-mesenchymal transition of pulmonary artery endothelial cells and its mechanism
Zuo-Mei ZENG ; Xin-Yue WANG ; Lei-Yu TIAN ; Li-Dan CUI ; Jian GUO ; Yu-Cai CHEN
Chinese Pharmacological Bulletin 2024;40(1):155-161
Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L
9.A prediction model for coronal malalignment of the lower extremity in middle-aged and young people based on body surface big data
Xizhen ZUO ; Liming LIU ; Kai LEI ; Pengfei YANG ; Dejie FU ; Lin GUO
Journal of Army Medical University 2024;46(8):868-877
Objective To construct a prediction model for coronal malalignment of lower limb in middle-aged and young people in China based on body surface big data in order to provide a faster and more accurate tool for predicting the malalignment in clinical practice.Methods A cross-sectional trial was adopted on 915 patients with knee meniscus tears admitted to the Sports Medical Center of our hospital from May 2022 to December 2023.The coronal force line of lower limb was measured,and according to the lower limb force line grading standards,the patients were divided into neutral force line group and malalignment lower limb group,and assigned randomly into training set and validation set in a ratio of 7∶3.Seven indicators,such as gender,age,and body surface big data (including BMI,lower limb length,distance between both knee joints,distance between both ankle joints,and subcutaneous fat thickness)were used to analyze the training set to predict the value of malalignment force line.Logistic regression model and nomogram model were constructed to visualize our prediction model. Then calibration curves,receiver operating characteristic (ROC)curve,and decision curve analysis (DCA)were applied to evaluate the diagnostic efficacy of the constructed model.Results In the training set of 640 cases,there were 299 males and 341 females,with a median age of 41 .5 years old,and for the validation set,there are 275 patients,including 128 males and 147 females,with a median age of 41 .0 years old.Significant differences were observed in above mentioned 7 indicators between the 2 groups in the training set (P<0.01 ).Based on the results of multiple logistic regression analysis,a prediction model for malalignment of lower limb was constructed,including BMI (24.31±3.58 kg/m2,OR=1 .12,95%CI:1 .06~1 .19,P<0.001 ),lower limb length[82.00 (78.00~87.00)cm,OR=0.95,95%CI:0.92~0.98,P=0.002],distance between both knee joints[30.00 (16.00~45.25)cm,OR=1 .06,95%CI:1 .05~1 .07,P<0.001],distance between both ankle joint[23.00 (8.00~30.00)mm,OR=0.98,95%CI:0.96~1 .00,P=0.078]and gender[man 299 (46.72%),OR=0.70,95%CI:0.46~1 .06,P=0.089].The area under the subject curve (AUC)value of our constructed model for predicting malalignment of lower limb was 0.808 and 0.770,respectively,in the training and validation sets.Conclusion Based on body surface big data,we primarily construct a prediction model for malalignment of lower limb for middle-aged and young people in China,which shows a good diagnostic performance on malalignment of lower limb.
10.Study of the characteristics and correlation of the chin and airway in skeletal Class Ⅱ adult female patients with mandibular retraction
Yijiao YUAN ; Wen HAN ; Lei ZHEN ; Zhigang ZUO ; Yanhong ZHAO
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):863-870
Objective To explore the characteristics and correlation of the chin and airway in females with skeletal Class Ⅱ mandibular retraction for reference for clinical diagnosis and therapy.Methods This study was approved by the hospital Medical Ethics Committee.Forty cases of skeletal Class Ⅱ mandibular retraction adult females with aver-age angle were selected as the research group,and sixty cases of skeletal Class Ⅰ patients with average angle were se-lected as the control group.Cone-beam computed tomography(CBCT)images for all subjects were analyzed using three-dimensional modeling software.Measurements included the chin morphology,position,and upper airway morphology.Results Compared with skeletal Class Ⅰ patients,patients with skeletal Class Ⅱ mandibular retraction had smaller an-terior chin thickness,base bone volume,chin total volume,and larger chin angle,chin depression,chin curvature,and alveolar area with statistically significant differences(P<0.05).Gn-V,Gn-H,Po-NB distance,and facial angle were smaller,and the Y-axis angle was larger in patients with skeletal Class Ⅱ mandibular retraction with statistically signifi-cant differences(P<0.05).Upper airway total volume,transverse and sagittal diameter of the glossopharynx upper boundary were smaller in patients with skeletal Class Ⅱ mandibular retraction with statistically significant differences(P<0.05).The correlation analysis between the morphology and position of the chin and the morphology of the upper airway in patients with Class Ⅱ mandibular retraction showed that there was a negative correlation between chin angle and laryngopharynx length in patients with Class Ⅱ mandibular retraction(r=-0.277,P<0.01).There was a negative correlation between Po-NB distance and palatopharyngeal length(r=-0.222,P<0.05).Chin height(r=-0.261,P<0.01)and basal bone area(r=-0.225,P<0.05)were negatively correlated with the transverse diameter of the palato-pharyngeal upper boundary.The minimum chin thickness(r=0.245,P<0.05),chin angle(r=0.249,P<0.05),and al-veolar area(r=0.213,P<0.05)were positively correlated with the sagittal diameter of the palatopharyngeal upper boundary.Gn-V(r=0.217,P<0.05)and Po-NB distance(r=0.208,P<0.05)were positively correlated with the trans-verse diameter of the glossopharynx upper boundary.Anterior chin thickness was negatively correlated with the sagittal diameter of the laryngopharynx upper boundary(r=-0.211,P<0.05).Chin depression was negatively correlated with the sagittal diameter of the laryngopharynx lower boundary(r=-0.237,P<0.05).Chin curvature was positively corre-lated with the transverse diameter of the laryngopharynx lower boundary(r=0.231,P<0.05).Conclusion Patients with skeletal Class Ⅱ mandibular retraction exhibit thinner chins.The sagittal position of the chin is backward,and the vertical position is upward.Patients with skeletal Class Ⅱ mandibular retraction have a narrow glossopharyngeal airway.There is a correlation between the morphology and position of the chin and the morphology of the upper airway in pa-tients with Class Ⅱ mandibular retraction.

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