1.Improvement effects and mechanism of urinastatin on cisplatin-induced myocardial injury
Jiafu REN ; Pengfei CHEN ; Rong A ; Jing LI
China Pharmacy 2025;36(8):920-925
OBJECTIVE To investigate the improvement effects and potential mechanism of ulinastatin (UTI) on cisplatin (CP)-induced myocardial injury. METHODS Rabbits were used as study subjects and randomly divided into blank group (normal saline 2 mL/d, for consecutive 7 d), CP group (150 mg/m2, on the 1st and 4th day), UTI low-dose/high-dose group (UTIL/UTIH group, UTL 25 000 or 50 000 IU/kg, once a day, for consecutive 7 d), c-Jun N-terminal kinase (JNK) inhibitor group (JNKi group, SP600125 15 mg/kg, on the 1st and 4th day+CP 150 mg/m2, on the 1st and 4th day+normal saline 2 mL/d, on the other 5 days). Except for the blank group, rabbits in the other groups were injected with relevant medicine and/or normal saline via a marginal ear vein on one side. The serum level of cardiac troponin Ⅰ (cTnⅠ) in rabbits on the 1st and 8th days of the detection experiment, as well as the levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in myocardial tissue on the 8th day of the experiment, were all measured in each group. The pathological changes and myocardial cell apoptosis in myocardial tissue were observed, and the protein expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), JNK, phosphorylated JNK (P-JNK), mitochondrial fission factor (Mff), and dynamin-related protein 1 (Drp1) in myocardial tissue were all determined. RESULTS Compared with the blank group, the CP group showed significant myocardial injury. The cell apoptotic rate, the levels of cTnⅠ in serum and MDA in myocardial tissue, as well as protein expressions of Bax, JNK, p-JNK, Mff, and Drp1, were all significantly increased or up-regulated, SOD level and protein expression of Bcl-2 significantly reduced or down+regulated(P<0.05). Compared with the CP group, the myocardial injury in rabbits from each drug treatment group showed improvement. The cell apoptosis index, the levels of cTnⅠ in serum and MDA in myocardial tissue, as well as protein expressions of Bax, JNK, p-JNK, Mff (except for UTIL group), and Drp1, were all significantly reduced or down-regulated, while SOD, GSH level and protein expression of Bcl-2 significantly increased or up-regulated (P<0.05); moreover, the improvement in some indicators was significantly better in the UTIH group and the JNKi group compared to the UTIL group (P<0.05). CONCLUSIONS UTI may ameliorate CP-induced myocardial injury, the potential mechanism of which may be associated with antagonizing oxidative stress and inhibiting the JNK/Mff signaling pathway.
2.Xiaoyao Shukun Decoction Treats Sequelae of Pelvic Inflammatory Disease by Regulating Neutrophil Extracellular Traps via PI3K/Akt/mTOR Pathway
Jing PAN ; Bing ZHANG ; Chunxiao DANG ; Jinxiao LI ; Pengfei LIU ; Xiao YU ; Yuchao WANG ; Jinxing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):69-78
ObjectiveTo investigate how Xiaoyao Shukun decoction (XYSKD) regulates the formation and release of neutrophil extracellular traps (NETs) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, thereby reducing inflammation, inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue, decreasing adhesion and fibrosis, and repairing the tissue damage in sequelae of pelvic inflammatory disease (SPID). MethodsA total of 84 Wistar rats were randomly allocated into seven groups: blank, model, XYSKD (8 mg·kg-1), mTOR agonist (10 mg·kg-1), mTOR agonist + XYSKD (10 mg·kg-1+8 mg·kg-1), mTOR inhibitor (2 mg·kg-1), and mTOR inhibitor + XYSKD (2 mg·kg-1+8 mg·kg-1). The rat model of SPID was constructed by starvation, fatigue, and ascending Escherichia coli infection. After 14 days of drug intervention, the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus, fallopian tube, and ovary was observed by laparotomy. The levels of interleukin-1β (IL-1β), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay (ELISA). The expression of myeloperoxidase (MPO) and citrullinated histone 3 (H3) in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR) were employed to determine the relative protein and mRNA levels, respectively, of neutrophil elastase (NE), intercellular adhesion molecule-1 (CD54), α-smooth muscle actin (α-SMA), H3, PI3K, and Akt. ResultsCompared with the blank group, the model group presented a large number of collagen fibers in bundles, numerous cytoplasmic folds of fibroblasts, reduced or absent mitochondrial cristae, and disordered and expanded endoplasmic reticulum. By laparotomy, extensive pelvic congestion, connective tissue hyperplasia, thickening and hardening of the tubal end near the uterus, and tubal and ovarian adhesion or cyst were observed in the model group. In addition, the model group showed raised levels of IL-1β, IL-17, and TNF-α in the peritoneal flushing fluid (P<0.01), increased average fluorescence intensities of MPO and H3 (P<0.01), and up-regulated protein and mRNA levels of NE, H3, CD54, PI3K, and Akt (P<0.01). Compared with the model group, the mTOR agonist group showed increased fibroblasts and cytoplasmic folds, absence of mitochondrial cristae, endoplasmic reticulum dilation, and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine, fallopian tube, and ovarian tissues. The levels of IL-1β, IL-17, and TNF-α in the peritoneal lavage fluid elevated (P<0.01) and the average fluorescence intensities of MPO and H3 enhanced (P<0.01) in the mTOR agonist group. In contrast, the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers, alleviated mitochondrial crista loss and endoplasmic reticulum dilation, improved morphology and appearance of the uterine, fallopian tube, and ovarian tissues, lowered levels of IL-1β, IL-17, and TNF-α in the peritoneal lavage fluid (P<0.01), decreased average fluorescence intensities of MPO and H3 (P<0.01), and down-regulated protein and mRNA levels of NE, H3, CD54, PI3K, and Akt (P<0.05). Compared with the mTOR agonist group, the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue, declined levels of IL-1β, IL-17, and TNF-α (P<0.01), decreased average fluorescence intensities of MPO and H3 (P<0.01), and down-regulated protein levels of NE, H3, CD54, α-SMA, p-PI3K/PI3K, and p-Akt/Akt (P<0.01) and mRNA levels of NE, H3, CD54, α-SMA, PI3K, and Akt (P<0.01). Compared with the mTOR inhibitor group, the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue, reduced levels of IL-1β, IL-17, and TNF-α (P<0.01), decreased average fluorescence intensities of MPO and H3 (P<0.01), and down-regulated protein and mRNA levels of NE and CD54 (P<0.05). ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue, thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β, IL-17, and TNF-α and down-regulating the expression of NE, H3, CD54, α-SMA, PI3K, and Akt in the pelvic adhesion tissue.
3.The expression of CRIP1 and STUB1 in cancer tissues of patients with hepatocellular carcinoma and their clinical prognostic significance
Jing ZHANG ; Chen SHEN ; Pengfei MA ; Youwei ZHENG
International Journal of Laboratory Medicine 2024;45(3):266-271
Objective To investigate the expression of cysteine-rich intestinal protein 1(CRIP1),STIP1 ho-mology and U-box protein 1(STUB1)in cancer tissues of patients with hepatocellular carcinoma and their clinical prognostic significance.Methods From February 2018 to February 2020,112 patients with hepatocel-lular carcinoma were selected as the study objects.The expression of CRIP1 and STUB1 in cancer tissues and adjacent tissues of patients with hepatocellular carcinoma was detected by immunohistochemistry.To analyze the relationship between the expression of CRIP1 and STUB1 and their clinicopathological features in hepato-cellular carcinoma patients.Kaplan-Meier survival analysis of the effects of CRIP1 and STUB1 expression on the prognosis of patients with hepatocellular carcinoma.COX regression analysis was performed to analyze the prognostic factors of hepatocellular carcinoma.Results The positive rate of CRIP1 in cancer tissues of pa-tients with hepatocellular carcinoma was 62.50%(70/112),which was significantly higher than that in adja-cent tissues[7.14%(8/112)],the difference was statistically significant(x2=76.652,P<0.05).The positive rate of STUB1 in cancer tissues of patients with hepatocellular carcinoma was 26.23%(32/112),significantly lower than that in adjacent tissues[82.14%(92/112)],and the difference was statistically significant(x2=73.284,P<0.05).The expression of CRIP1 was negatively correlated with STUB1 in cancer tissues(r=-0.678,P<0.001).There were significant differences in the positive rates of CRIP1 and STUB1 in hepato-cellular carcinoma patients with different TNM stages,histological grades and maximum tumor diameter(P<0.05).The 3-year cumulative survival rate of CRIP1 positive group was significantly lower than that of CRIP1 negative group,with statistical significance(Log-rank x2=29.601,P<0.001).The 3-year cumulative survival rate of STUB1 negative group was significantly lower than that of STUB1 positive group,with statistical sig-nificance(Log-rank x2=13.590,P<0.001).TNM stage Ⅱ-Ⅲ,histological grade Ⅲ,maximum tumor diam-eter>5 cm,CRIP1 positive and STUB1 negative were independent risk factors for prognosis of hepatocellular carcinoma patients.Conclusion CRIP1 expression is up-regulated and STUB1 expression is down-regulated in hepatocellular carcinoma tissues.The prognosis of patients with hepatocellular carcinoma can be evaluated clinically based on the expression of CRIP1 and STUB1 in hepatocellular carcinoma tissues.
4.Selection of inner ear fenestration strategy and surgical effect of patients with oval window atresia accompanied by facial nerve aberration
Zhongrui CHEN ; Ruowei TANG ; Jing XIE ; Jingying GUO ; Pengfei ZHAO ; Zijing YANG ; Guopeng WANG ; Shusheng GONG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(9):902-908
Objective:To summarize the clinical features and postoperative efficacy of patients with oval window atresia accompanied by facial nerve aberration.Methods:The clinical data of patients with congenital middle ear malformation with facial nerve aberration admitted to our hospital from January 2015 to March 2023 were retrospectively analyzed. There were 97 cases (133 ears) in total. Among them, 39 patients (44 ears) had complete follow-up data, including 27 male patients and 12 females, aged 7-48 years old, with an average age of 17.8 years old. Of these, 14 cases (16 ears) were patients combined with facial nerve aberration, and 25 cases (28 ears) were without facial nerve aberration. The results of imaging examination, pure-tone audiometry, selection of surgical strategy, intraoperative findings and postoperative hearing improvement were summarized and analyzed. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Prism 9 software was used to statistically analyze the mean bone conductance and air-bone gap of patients before and after surgery.Results:All the 14 patients (16 ears) with middle ear malformation accompanied by facial nerve aberration and oval window atresia showed poor hearing and no facial palsy since childhood. High resolution CT (HRCT) examination of temporal bone, pure tone audiometry and Gelle test were performed before surgery. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Preoperative high-resolution CT (HRCT) examination of temporal bone found 12 ears with 4 or more deformities, accounting for 75.00%, in the group of patients with facial nerve malformation. The preoperative average bone conductive threshold was (15.3±10.4) dB and the average air-bone gap was (46.3±10.6) dB in pure-tone audiometry (0.5, 1, 2, 4kHz). According to the different degrees of facial nerve and ossicle malformation, we performed three different hearing reconstruction strategies for the 14 patients (16 ears) with facial nerve aberration and oval window atresia, including 7 ears of incus bypass artificial stape implantation, 7 ears of Malleostapedotomy (MS) and 2 ears of Malleus-cochlear-prothesis (MCP). After 3 months to 18 months of follow-up, all patients showed no facial paralysis. The postoperative mean bone conductive threshold was (15.7±7.9) dB and air-bone gap was (19.8±8.5) dB. There were significant differences in mean air-bone gap before and after operation ( t=7.766, P<0.05), and there was no significant difference between the mean bone conductive threshold before and after surgery ( t=0.225, P=0.824). There was no significant difference of mean reduction of air-bone gap between patients with and without facial nerve aberration ( t=1.412, P=0.165). There was no significant difference between the three hearing reconstruction strategies. There was no significant displacement of the Piston examined by U-HRCT. Conclusion:For patients of middle ear malformation whose facial nerve cover the oval window partially, incus bypass artificial stape implantation or Malleostapedotomy (MS) can be selected according to the specific condition of auditory ossis malformation, and for patients whose facial nerve completely covers the oval window area, Malleus-cochlear-prothesis (MCP) can be selected. Three types of stapes surgery are safe and reliable for patients with oval window atresia accompanied by facial nerve aberration. There was no significant difference in efficacy between them. Preoperative HRCT assessment of middle ear malformation is effective. There is no significant difference of surgical effect with or without facial nerve aberration. The U-HRCT can be used to evaluate the middle ear malformation before surgery and the Piston implantation status after surgery. Due to the risks of surgery, those who do not want to undergo surgery can choose artificial hearing AIDS, such as hearing aid, vibrating soundbridge, bone bridge or bone-anchored hearing aid.
5.Impact of ERCC1 C8092A gene polymorphism on the efficacy of platinum-based chemotherapy for lung cancer
LI Yixuan ; WANG Yiwei ; FU Yihui ; MENG Chong ; KUANG Shicheng ; LYU Pengfei ; ZHOU jing ; XU Qiongjun ; HUANG Hairong ; XIAO Sha
China Tropical Medicine 2024;24(1):65-
Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.
6.Research on Construction of Test Environment for Assessment of RF-Induced Heating Effects of Implants
Yonghua LI ; Lingfeng LU ; Jing WANG ; Chengling LI ; Pengfei YANG ; Zhichao WANG ; Dajing WU ; Xun LIU ; Sheng HU
Chinese Journal of Medical Instrumentation 2024;48(3):281-284,297
In magnetic resonance examination,the interaction between implants and the radio frequency(RF)fields induces heating in human tissue and may cause tissue damage.To assess the RF-induced heating of implants,three steps should be executed,including electromagnetic model construction,electromagnetic model validation,and virtual human body simulations.The crucial step of assessing RF-induced heating involves the construction of a test environment for electromagnetic model validation.In this study,a hardware environment,comprised of a RF generation system,electromagnetic field measurement system,and a robotic arm positioning system,was established.Furthermore,an automated control software environment was developed using a Python-based software development platform to enable the creation of a high-precision automated integrated test environment.The results indicate that the electric field generated in this test environment aligns well with the simulated electric field,making it suitable for assessing the RF-induced heating effects of implants.
7.Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder
ZHENG WEIHAO ; ZHANG QIN ; ZHAO ZIYANG ; ZHANG PENGFEI ; ZHAO LEILEI ; WANG XIAOMIN ; YANG SONGYU ; ZHANG JING ; YAO ZHIJUN ; HU BIN
Journal of Zhejiang University. Science. B 2024;25(10):857-877,中插1-中插11
Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper-connectivity,among individuals with major depressive disorder(MDD).However,the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear.Hence,we analyzed dynamic FC(dFC)between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls(HCs)to investigate time-varying changes in thalamocortical FC in patients with MDD.Moreover,dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time.Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated.We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks,compared with the HCs.In addition,MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration.The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort.Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms.Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients.The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.
8.Application of Non-Contrast-Enhanced Whole-Heart Coronary Magnetic Resonance Angiography in Coronary Artery Lesions of Kawasaki Disease in Children
Juan LIANG ; Yurong MA ; Na HAN ; Fangzhou GUO ; Pengfei WANG ; Kai AI ; Jing ZHANG
Chinese Journal of Medical Imaging 2024;32(2):136-141
Purpose To demonstrate the advantages of non-contrast-enhanced whole-heart coronary magnetic resonance angiography(NCE-CMRA)in evaluating coronary arteries by comparing ultrasonography(US),and to explore the clinical value of NCE-CMRA in the diagnosis of coronary artery lesions of Kawasaki disease(KD)in children.Materials and Methods NCE-CMRA and US imaging data of 41 children with KD from June 2017 to June 2021 who were diagnosed clinically in Lanzhou University Second Hospital were analyzed retrospectively.The display ability of US and NCE-CMRA in coronary arteries were compared.At the same time,the imaging characteristics of NCE-CMRA were analyzed,and the imaging characteristics such as the range and degree of coronary artery lesions displayed by NCE-CMRA were summarized.Results The overall segment display rate of NCE-CMRA in 41 children with KD was 75.6%;the overall segment display rate of US was 46.3%,with statistical difference between the two techniques(χ2=59.04,P<0.001).Regarding the display of the middle and distal segments of coronary arteries,NCE-CMRA had a clear imaging advantage over US(χ2=57.98 and 161.47,P<0.001).In all cases,25 patients(200 segments)had coronary artery lesions,and 94 segments of coronary artery showed different degrees of dilatation,including 8 segments(8.6%)of giant coronary artery aneurysm,35 segments(37.2%)of medium coronary artery aneurysm,and 51 segments(54.2%)of small coronary artery aneurysm or coronary artery dilation.Conclusion NCE-CMRA technology can objectively and accurately display coronary artery in children,and it can specifically evaluate the degree of damage caused by KD.It has important clinical significance in the diagnosis and evaluation of coronary artery lesions in children with KD.
9.Development of the Spleen Deficiency Evidence Scale for County Residentsand Test of Reliability and Validity
Meng ZHU ; Lingjuan JIA ; Fuzhen PAN ; Huiqing CHEN ; Jing XIAO ; Pengfei SHAO ; Yuxuan GONG ; Weifang ZHENG ; Yongsheng ZHANG ; Xiaqiu WU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(7):1939-1945
Objective This study was to develop a"Spleen Deficiency Certificate Scale for County Residents"and test its reliability.It was then developed as an objective tool for Chinese medicine evidence and symptoms for the prevention and control of chronic diseases among county residents.Methods The scale was compiled based on the team's previous foundation.The reliability of the scale was evaluated using internal consistency reliability and split-half reliability,while its validity was evaluated using structural validity,content validity,calibration validity,and discriminant validity.Results The study included 213 adults from Lanxi,of whom 155 were tested for intestinal flora.Seven scale entries were identified:Fatigue,fear of cold,bland mouth,loss of appetite,diarrhea,weak bowel movements,and tooth-marked tongue.In the reliability test,Cronbach's alpha coefficient was 0.828 and McDonald's ω coefficient was 0.825.The"stomach pain"and"bloating"entries did not meet the inclusion requirements and were recommended to be deleted.The Spearman-Brown coefficient was 0.839.The exploratory factor analysis of the two common factors explained 61.6%of the cumulative variance.The calibration validity indicated that the ratio of salivary amylase activity before and after acid stimulation was 0.826±0.253 in the group with spleen deficiency.Significant differences(P<0.05)in the genera Dialister,Shigella,Leuconostoc,Photobacterium,Trabulsiella,and Parvimonas between the spleen deficiency group and the non-spleen deficiency group.Conclusion The Spleen Deficiency Scale for County Residents demonstrates good reliability and validity.
10.Formation Mechanism of magnetic resonance equipment artifacts and maintenance of fault cases
Sai JING ; Yan WANG ; Xiaochen ZHAO ; Pengfei WANG
China Medical Equipment 2024;21(7):192-195
To explore the formation mechanism of static magnetic field artifacts,motion artifacts,chemical shift artifacts and folding artifacts in magnetic resonance imaging(MRI)equipment,and to propose for different artifact failures and common faults using multiple maintenance methods.The artifacts were mainly related to the anomaly of the magnetic field strength,the unoptimized sequence,and the physical limits.The occurrence of static magnetic field artifacts was reduced by using plane avoidance sequence excitation technology,the motion artifacts were eliminated by propeller imaging technology,the occurrence rate of motion artifacts was reduced by reducing hydrogen proton signal interference,and the fold artifacts were suppressed by expanding the scanning field of view,in order to obtain a good resonance image effect and reduce the probability of MRI artifacts,improve the accuracy of medical detection.

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