Table of Content

05 September 2024, Volume 44 Issue 9

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Special Issues:Organoids and Chips

Organoids and chips: biomedical and drug′s new models

LIU Yuqin

2024, 44(9):  1201-1201.  doi:10.16352/j.issn.1001-6325.2024.09.1201

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Organ-on-a-chip: a more promising in vitro model

YANG Zhenli, XIA Yujia, LIU Yuqin

2024, 44(9):  1202-1207.  doi:10.16352/j.issn.1001-6325.2024.09.1202

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Traditional in vitro models have inevitable limitations and there are significant differences in assessing drug efficacy and side effects as compared to human trials. Organ-on-a-chip technology simulates human organs in a physiological environment and functional chip with a high fidelity physiological or pathophysiological level, offering great innovative prospects for drug development. This paper mainly introduces the research progress and application of organ chip from the perspective of various systems in vivo. At the same time, the limitations of the current development process of organ chip and the future development direction are proposed.

Research progress of brain organoids in drug development

WANG Liang, XIA Longkuo, ZHANG Jianmin

2024, 44(9):  1208-1213.  doi:10.16352/j.issn.1001-6325.2024.09.1208

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In recent years, with rapid development of technology of regenerative medicine and tissue engineering, brain organoids, as an innovative in vitro model system, have become a hot spot in neuroscience research and drug development. Brain organoids simulate the complex structure and function of the human brain in terms of reproducing key processes of brain development in vitro, providing an unprecedented platform for understanding the mechanisms of neurological diseases and of evaluating drug efficacy and toxicity. This review summarizes the latest research progress in brain organoid technology, particularly its application in drug development and in exploring challenges and orientation of future development.

Preclinical translational research and application of tumor organoids

XIA Yujia, YANG Zhenli, LIU Yuqin

2024, 44(9):  1214-1218.  doi:10.16352/j.issn.1001-6325.2024.09.1214

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More and more in-depth tumor mechanism research and clinical precision treatment have put forward higher requirements for the technology for the establishment of tumor models.More and more tumor organoids have been applied. This model is able to reproduce the genomic, transcriptome, proteome and other omics features of parental tumors without heterogeneity found in cell line models. Based on these characteristics, tumor organoids have gradually become a representative preclinical model, facilitating the translation of new research results and precision treatment of patients. This article summarizes the latest progress of tumor organoids on R&D of technology and application, focusing on the current methods of establishing tumor organoids, opportunities and challenges in clinical and research application.

Progress of gastric cancer organoids in basic research and clinical application

LIU Baoqing, HUANG Rong, LU Yan, LI Kai, ZHANG Ning, LIU Changzheng, SONG Wei

2024, 44(9):  1219-1222.  doi:10.16352/j.issn.1001-6325.2024.09.1219

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Gastric cancer ranks fifth in global cancer mortality, which is highly aggressive and heterogeneous. However, the research and treatment of gastric cancer is hindered by short of research models that may characterize the developmental properties of gastric cancer. Gastric cancer organoid is a multicellular three-dimensional structure developed in vitro, which can mimic the structure and function of native gastric cancer. Gastric cancer organoids have great application potential and development prospects in establishing gastric cancer research models, mimicking the tumor microenvironment, high-throughput screening of drugs, discovering new therapeutic targets, predicting clinical therapeutic responses, and guiding individualized treatment. In this paper, the progress of gastric cancer organoids in basic research and clinical application is reviewed aiming for promoting the progress of preclinical research and supporting the clinical treatment of gastric cancer.

Culture and characterization of breast cancer organoids

XIA Yujia, YANG Zhenli, DAI Di, LIU Yuqin

2024, 44(9):  1223-1228.  doi:10.16352/j.issn.1001-6325.2024.09.1223

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Objective To establish breast cancer organoids for a long time and to characterize their molecular expression and test their sensitivity to chemotherapy drugs. Methods Breast cancer specimens were digested with collagenase to release cancer cells for organoid culture. The organoids were characterized by morphology and ER,PR,HER-2,CK expression by technology of histoimmunofluorescence. Among them, three were tested for paclitaxel, doxorubicin and cisplatin sensitivity. Results A total of 44 cases of breast cancer organoids were established, all of which showed dense spherical-like growth and ER,PR,HER-2,CK, matching their clinical counterpart. Breast cancer organoids were sensitive to chemotherapy drugs paclitaxel, doxorubicin and cisplatin. Conclusions Organoid model, as a new in vitro may reproduce the pathophysiology features with heterogeneity.

Original Articles

Scutellarin inhibits proliferation and migration of human prostate cancer cell line PC-3

XIAO Yanhong, JIANG Mingdong, LIN Yeyuan, RAN Can, LIANG Bo

2024, 44(9):  1229-1235.  doi:10.16352/j.issn.1001-6325.2024.09.1229

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Objective To investigate the effect of scutellarin(STR) on the proliferation and migration of human prostate cancer cell line (PC-3) and its underlying mechanism. Methods PC-3 cells were divided into low-dose STR group, medium-dose STR group, high-dose STR group, colivelin (STAT3 activator) group, high-dose STR+colivelin group and control group. CCK-8 assay and colony formation experiments were applied to detect cell proliferation; Scratch experiment was applied to detect cell migration; Transmission electron microscopy was applied to observe the mitochondrial ultrastructure of PC-3 cells. The intracellular free Fe²⁺, malondialdehyde (MDA) content and reactive oxygen species (ROS) levels were detected by colorimetric method; RT-qPCR was applied to detect the mRNA expression of member 11 of solute vector family (SLC7A11), proliferating cell nuclear antigen(PCNA) and matrix metalloproteinase-9 (MMP-9) in cells; Western blot was used to detected p-STAT3 and GPX4 proteins in cells. Results Compared to control group, the mitochondrial structure of PC-3 cells in the low-dose STR group, medium-dose STR group and high-dose STR group was significantly disrupted. The A₄₅₀ value, colony formation rate, scratch healing rate, PCNA, SLC7A11, MMP-9 mRNA expression, and p-STAT3, GPX4 protein all reduced. While Fe²⁺, MDA content, and that ROS level increased with dose-dependent way(P＜0.05). Compared with control group, the destruction of mitochondrial structure in cells from colivelin group improved; The A₄₅₀ value, colony formation rate, scratch healing rate, PCNA, SLC7A11, MMP-9 mRNA expression and p-STAT3, GPX4 protein all increased, while Fe²⁺ MDA content, and ROS level decreased (P＜0.05). Compared with high-dose STR group, the damage of mitochondrial structure in PC-3 cells in the high-dose STR+colivelin group was reduced. The A₄₅₀ value, colony formation rate, scratch healing rate, PCNA, SLC7A11, MMP-9 mRNA expression, and p-STAT3, GPX4 protein increased, while Fe²⁺, MDA content and ROS level decreased (P＜0.05). Conclusions The mechanism by of STR reducing proliferation and migration of prostate cancer cells is potentially related to the inhibition of STAT3/GPX4 pathway.

Fluid shear promotes apoptosis of glomerular endothelial cells by activation of Piezo 1

LUO Menglin, ZHENG Feng, JI Xinyao, QI Caihong, XIAO Yuheng, NIU Changchun

2024, 44(9):  1236-1242.  doi:10.16352/j.issn.1001-6325.2024.09.1236

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Objective To investigate the effect of fluid shear(FS) on apoptosis of glomerular epithelial cells (GECs) and the role of Piezo 1 protein in it. Methods GECs (glomerular epithelial cells) of SD rat were cultured. Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer. Apoptosis level was detected by flow cytometry. The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining. The activating of Piezo 1 channels by fluid shear was observed using Ca²⁺ indicator (Cal-590 AM). The effect of Piezo 1 on apoptosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activator Yoda1, the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1. Results Compared with the blank controlgroup, apoptosis increased in the fluid shear group (P＜0.05). The rate of apoptosis increased with the enhancing of fluid shear strength; Piezo 1 was commonly expressed in GECs. Fluid shear activated Piezo 1 channel and enhanced expression of Piezo 1. The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear. Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P＜0.05). Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.

Remimazolam alleviates myocardial injury of rats with myocardial ischemia-reperfusion

ZHEN Lei, ZHANG Yilan, WANG Xiaona, ZHANG Xiaoqiong

2024, 44(9):  1243-1248.  doi:10.16352/j.issn.1001-6325.2024.09.1243

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Objective To investigate the effect of remimazolam (RE) on myocardial injury in myocardial ischemia-reperfusion (MI/R) rats and its mechanism. Methods The MI/R rat model was constructed and divided into sham group, MI/R model group, RE low, medium, high dose group (RE-L, RE-M, RE-H group)and Yes associated protein(YAP) inhibitor verteporfin group. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening(LVFS) were recorded in each group and commercially available kit was applied to detect the level of myocardial injury marker like LDH, c-TnI and CK-MB. The size of myocardial infarction was evaluated by TTC staining. Pathological changes in myocardial tissue was microscopied by HE staining.The apoptosis of myocardial cell was observed by TUNEL method. Expression of Hippo/YAP signaling pathway proteins in myocardial tissue was detected by Western blot. Results Compared to the sham surgery group, the myocardial structure of rats in the model group was disrupted,myocardial cells were reduced, the LVFS and LVEF were decreased, the expression of YAP was greatly reduced. The level of serum LDH, CK-MB, cTnI, myocardial infarction area, myocardial cell apoptosis rate, p-MST1/MST1, p-LATS1/LATS1 and p-YAP expression were all significantly increased(P＜0.05); As compared to model group, the pathological change in myocardial tissue of rats in the low, medium, and high-dose RE groups was greatly reduced. The LVFS and LVEF were increased. The expression of YAP was significantly increased. The serum level of LDH, CK-MB, cTnI, the myocardial infarction area, myocardial cell apoptosis rate, p-MST1/MST1, p-LATS1/LATS1 and p-YAP expression were evidently reduced (P＜0.05). The YAP inhibitor verteporfin reversed the improvement effect of RE on myocardial injury in MI/R rats. Conclusions RE may improve cardiac function in MI/R rats, alleviate myocardial infarction and myocardial cell apoptosis and inhibit myocardial injury by regulating the Hippo/YAP signaling pathway.

Tauroursodeoxycholic acid attenuates severe acute pancreatitis-induced liver injury in rat models

YIN Qiang, WANG Lei, LI Tonghao

2024, 44(9):  1249-1255.  doi:10.16352/j.issn.1001-6325.2024.09.1249

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Objective To investigate the effect and mechanism of tauroursodeoxycholic acid (TUDCA) on severe acute pancreatitis (SAP)-induced liver injury in rat model. Methods Thirty SD rats were randomly divided into three groups(10 in each ):shame operation group(SO group),severe acute pancreatitis group(SAP group) and tauroursodeoxycholic acid group(TUDCA group).The SAP model was established by retrogradely injecting 5% sodium taurocholate (STC) solution (1 mL/kg) into pancreaticobiliary duct. The TUDCA group rats were intraperi- toneally injected with TUDCA(400 mg/kg·d^-1) for three days continuously fore establishing models and the SAP and SO group rats were intraperitoneally injected with the same volume of saline. Rats were sacrificed 12 hrs after modeling, and then peripheral blood and part of pancreatic and liver tissues were collected. The level of amylase(AMY), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) was detected by automatic biochemical analyzer. The expression of interleukin-6(IL-6) was detected by enzyme-linked immunosorbent assay (ELISA).The histo-pathological profile of pancreas and liver was examined by hematoxylin-eosin (HE) staining microscopy and liver apoptosis was observed by in situ terminal deoxynucleotide transferase labeling (TUNEL). The expression level of glucose-regulating protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), nuclear factor-κB p65(NF-κB p65) and caspase-3 protein was determined by Western blot. Results Compared with SO group, the expression level of AMY,AST, ALT and IL-6 was increased in SAP group(P＜0.05); pancreas and liver necrosis and hepatocyte apoptosis were found to be more significant and the level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein increased (P＜0.05). Compared with SAP group, the expression of AMY, AST, ALT and IL-6 was reduced in TUDCA group and pancreas and liver necrosis and hepatocyte apoptosis were less severe. The level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein significantly decreased(P＜0.05). Conclusions TUDCA may have a protective mechanism to alleviate pancreatitis-induced severe and acute liver injury in rats by reducing the occurrence of endoplasmic reticulum stree(ERS), alleviating the inflammation and apoptosis as well as inhibiting PERK signaling pathway.

Therapeutic effect of evodiamine on atopic dermatitis in rat models

JIANG Su, LYU Xinxiang, CUI Yanhong, LYU Liting, LI Dongxia

2024, 44(9):  1256-1262.  doi:10.16352/j.issn.1001-6325.2024.09.1256

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Objective To evaluate the therapeutic effect of evodiamine (Evo) on atopic dermatitis (AD) in rat models by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway. Methods A rat model of AD was established by administration of multiple doses of 2,4-dinitrochlorobenzene (DNCB).The animals were randomly divided into AD group, Evo-low-dose (Evo-L, 5 mg/kg) group, Evo-high-dose (Evo-H, 10 mg/kg) group, Evo-H+H-89 (5 mg/kg) group and dexamethasone (0.1 mg/kg) group. Normal rats were used as the control group and then the degree of skin damage of rats in each group was scored. Abdominal blood was taken to detect the levels of interleukin-4 (IL-4), cAMP, and tumor necrosis factor-α(TNF-α) in serum; Skin lesion tissue was collected to detect pathological change, counting of mast cells, PKA/CREB related protein expression and expression of IL-4 and TNF-α mRNA in the tissue. Results Compared with control group, the level of cAMP in serum, the expression of p-PKA/PKA, and p-CREB/CREB in skin lesions of AD group were reduced, the severity score of skin lesions, level of IL-4 and TNF-α, epidermal thickness, number of mast cells and mRNA expression of IL-4 and TNF-α in skin lesion tissues were all significantly increased (P＜0.05). Compared with AD group, the level of cAMP in serum, the expression of p-PKA/PKA, and p-CREB/CREB in skin lesions in Evo-L group, Evo-H group, and dexamethasone group were increased, the severity score of skin lesions, level of IL-4 and TNF-α, epidermal thickness, number of mast cells, and mRNA expression of IL-4 and TNF-α in skin lesion tissues all reduced (P＜0.05). Compared with the Evo-H group, the level of cAMP in serum, the expression of p-PKA/PKA, and p-CREB/CREB in skin lesions in Evo-H+H-89 group was reduced and the severity score of skin lesion, level of IL-4 and TNF-α, epidermal thickness, number of mast cells, and mRNA expression of IL-4 and TNF-α in skin lesion tissues significantly increased(P＜0.05). Conclusions Evo inhibits inflammatory response and pathological damage through regulation of cAMP/PKA/CREB signaling pathway in AD rat models.

Polysaccharides from Atractylodes macrocephala koidz. inhibit inflammatory response in rat model of severe pneumonia

MENG Dequan, QIN Xin, CHEN Ling, QIN Jun

2024, 44(9):  1263-1268.  doi:10.16352/j.issn.1001-6325.2024.09.1263

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Objective To investigate the molecular mechanism of polysaccharides from Atractylodes macrocephala koidz.(PAM) to treat severe pneumonia. Methods Sixty male SD rats were randomly divided into control group, model group (inoculation of Klebsiella pneumonia by tracheal puncture), positive control group (levofloxacin, 18 mg/kg), PAM low-dose group (50 mg/kg) and PAM high-dose group (200 mg/kg) with 12 in each. After occurrence of severe pneumonia, the rats were orally administered the medicine once daily for 7 day. The lung tissue underwent histopathological examination using HE staining microscopy to find the pathological alterations and evaluate the extent of injury. Wet/dry ratio of lung tissue was measured by weighing method. The leukocytes and neutrophils counts in peripheral blood were determined by hematology analyzer. The level of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and IL-6 in serum and bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay. The expression of proteins related to the Toll-like receptor 4 (TLR4) / myeloid differentiation factor 88 (MyD88)/nuclear factor-κB(NF-κB) signaling pathway in lung tissues was detected using Western blot analysis. Results Compared with the control group, lung injury score and wet/dry ratio, the number of leukocytes and neutrophils in peripheral blood, the level of TNF-α, IL-1β and IL-6 in serum and in BALF,protein expression of TLR4 and MyD88 and the phosphorylation level of NF-κB p56 in lung tissues from model group were all significantly increased(P＜0.05). The lung injury of rats in each levofloxacin treatment group exhibited significant improvement compared to the model group. Among them, the number of leukocytes and neutrophils in peripheral blood of rats in PAM high-dose group decreased significantly(P＜0.05); The level of TNF-α, IL-1β and IL-6 in serum and BALF, the protein expression of TLR4 and MyD88 and the phosphorylation level of NF-κB p56 in lung tissue were significantly decreased(P＜0.05). Conclusions The administration of PAM exerts a specific protective effect against Klebsiella pneumoniae-induced pneumonia in rats, potentially suppress inflammatory response through modulation of the TLR4/MyD88/NF-κB signaling pathway.

Marein alleviates high glucose-induced damage of rat myocardial cell line H9c2

Zulipiya·ABULA, ZHAO Qiang, ZHANG Taimin, LI Tian

2024, 44(9):  1269-1273.  doi:10.16352/j.issn.1001-6325.2024.09.1269

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Objective To study the effect of marein on the damage of rat myocardial cell line (H9c2) induced by high glucose. Methods H9c2 cells were divided into Ctrl group, high glucose (30 mmol/L) injury model group and marein (25, 50, 100 μmol/L) intervention group. The viability of H9c2 cells was detected by MTT method. Western blot was used to detect the protein expression level of LC-3Ⅱ/Ⅰ,p62 and mTOR. Results Compared with the Ctrl group, the viability of H9c2 cells in the model group was decreased (P＜ 0.01) and the viability of H9c2 cells in the marein group was significantly increased (P＜ 0.01). The protein expression of LC-3Ⅱ/Ⅰ in model group was decreased (P＜ 0.05) and the level of p62 and mTOR was increased (P＜ 0.01). The level of LC-3Ⅱ/Ⅰ in the marein group was increased, while the level of p62 and mTOR was decreased (P＜ 0.01). The protein expression was more obvious with the increase of concentration. Conclusions Marein can affect the expression of autophagy associated proteins in cardiomyocyte injury induced by high glucose.

Clinical Sciences

Malnutrition is associated with dysphagia in patients with Parkinsonism

WANG Rui, FU Jin, LI Rui, ZHANG Yuping, WANG Han, LIU Yanping

2024, 44(9):  1274-1278.  doi:10.16352/j.issn.1001-6325.2024.09.1274

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Objective To identify the characteristics of nutritional problems in patients with Parkinsonism who participated in multi-disciplinary team (MDT) and to investigate the correlation between nutritional status and dysphagia in these patients. The predictive value of video fluoroscopic swallowing study (VFSS) and EAT-10 scale for malnutrition was compared. Methods Subjects were patients with Parkinsonism participated in joint MDT consultation project in Peking Union Medical College Hospital from November 2020 to January 2023. Subjective and objective dysphagia were evaluated by EAT-10 scale score and VFSS dysphagia score. Nutritional status of the patients was evaluated by geriatric nutrition risk index (GNRI), albumin, prealbumin, serum folic acid, vitamin B12 and temporal muscle thickness. Results A total of 30 participants met the criteria and were included in the study. The age was 45-82 (66.1±9.0) years old. Six (20%) were at risk of malnutrition shown b a comprehensive nutritional status assessment using GNRI. The areas under receiver operating characteristic(ROC) curves(AUC) of VFSS dysphagia score and EAT-10 score to predict malnutrition were 0.781 (0.568-0.995) and 0.927 (0.827-1.000), respectively. EAT-10 score was correlated with GNRI(r=-0.524, P＜0.01), BMI(r=-0.618, P＜0.001), prealbumin (r=-0.616, P＜0.001). The VFSS dysphagia score was only correlated with BMI (r=-0.446, P＜0.05) and prealbumin(r=-0.387, P＜0.05). Conclusions Patients with Parkinsonism requiring MDT often have multiple micronutrient imbalance. Patients′ subjective perception of dysphagia has a greater impact on their nutritional status than objective assessment of dysphagia.

Epidemiological characteristics and pathogenic analysis of hand, foot, and mouth disease in Hebei province

LIU Zehao, WANG Le, CAO Yanyan, YAN Xiaotong, ZHAO Xin, LI Wenhui, GE Shengwang

2024, 44(9):  1279-1283.  doi:10.16352/j.issn.1001-6325.2024.09.1279

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Objective To identify epidemiological characteristics and pathogen distribution of hand, foot, and mouth disease (HFMD) in Hebei Children′s Hospital in order to support prevention and treatment of HFMD. Methods A total of 1 698 cases throat swab samples from children diagnosed as HFMD from 2016 to 2023 were collected. Real-time PCR was used to detect the specific classification of HFMD. Statistical analysis was performed according to the year, season, age, and sex and enterovirus type of HFMD in the children. Results From 2016 to 2023, the ratio of male to female patients among the 1 698 children admitted to Hebei Children′s Hospital was 1.72∶1. Among them, the highest incidence rate in summer was 778 cases, accounting for 45.8% of all cases, followed by autumn, with a total of 614 cases, accounting for 36.2% of cases. The highest incidence was recorded in age group of 1-3 years, with a total of 1 032 cases (60.8%). The lowest incidence was 38 cases in age group ＞6 years old (2.2%); There were 988 cases of HFM (58.2%) caused by different strains of enterovirus undefined(EVU) except enterovirus 71(EV71) and coxsackievirus A16(CA16). Conclusions HFMD found in Hebei Children′s Hospital from 2016 to 2023 are mainly caused by enteroviruses except EV 71 and coxsackievirus A16. High morbidity is found in children aged 1-3 years, and summer and autumn are the main epidemic seasons. This result may facilitate and support decision making and strategy development in disease prevention and control as well as to strengthen public health resources.

Association of serum KLF5 and actinin-4 levels with prognosis of TACE treatment for hepatocellular carcinoma

LI Shunle, LI Rong, TIAN Yaya, RAN Xiaoli, ZHAO Yanpei, XU Meng

2024, 44(9):  1284-1289.  doi:10.16352/j.issn.1001-6325.2024.09.1284

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Objective To explore the relationship between serum Krüppel-like factor 5(KLF5) and actinin-4 with prognosis of hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). Methods From March 2015 to March 2020, 130 HCC patients admitted into the Second Affiliated Hospital were collected as study subjects and divided into HCC group and 86 patients with liver cirrhosis were collected as control group. After 3 years of postoperative follow-up, HCC patients were sub-divided into survival group (n=38) and mortality group (n=92) based on their survival outcomes. ELISA was applied to detect the level of serum KLF5 and actinin-4 in each group and analyzed the correlation between serum KLF5 and actinin-4 levels. Cox regression was applied to analyze the risk factors affecting the prognostic mortality of HCC patients; Receiver operating characteristic curve(ROC) was plotted to evaluate the predictive value of serum KLF5 and actinin-4 levels for the prognostic mortality of HCC patients. Results The serum level of KLF5 and actinin-4 in the mortality group was significantly higher than those in the survival group(P＜0.05); There was a positive correlation between serum level of KLF5 and actinin-4 in HCC patients(P＜0.001); Low differentiation, staging (CNLC) stage IIIa of China liver cancer staging (CNLC), vascular invasion and elevated level of KLF5 and actinin-4 were risk factors for prognostic mortality in HCC patients(P＜0.05); The area under the curve (AUC) of serum KLF5 and actinin-4 alone and in combination for predicting mortality in HCC patients was 0.835, 0.866, and 0.936, respectively, showing a high level of combined predicting function (Zcombination-KLF5=2.792, P=0.005, Zcombination-actinin-4=2.014, P=0.044). Conclusions Serum level of KLF5 and actinin-4 l found in HCC patients has a high predictive value for prognosis.

Clinical outcomes and risk factors of COVID-19 patients with adrenal insufficiency

ZHOU Xiang, XU Yijing, LIU Yiwen, ZHU Huijuan, LU Lin

2024, 44(9):  1290-1297.  doi:10.16352/j.issn.1001-6325.2024.09.1290

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Objective To summarize the clinical characteristics and outcomes of corona virus disease 2019(COVID-19) in patients with adrenal insufficiency (AI), and analyze the risk factors of outcomes. Methods The clinical data of COVID-19 patients with AI in Peking Union Medical College Hospital in December 2022 were analyzed retrospectively and the patients were followed up to collect outcomes of their diseases. Results Among 28 COVID-19 patients with AI, 20 cases (71.4%) received basal corticosteroid replacement. Among the 18 patients with community-acquired COVID-19, 11 cases (61.1%) increased the corticosteroid dosage proactively at home. The most common symptoms of COVID-19 were fever (96.4%), gastrointestinal symptoms (82.1%) and consciousness disturbance (78.6%). Occurrence of severe consciousness disturbance was associated with older age and lower basal corticosteroid replacement dose(P＜0.05). Adrenal crisis(AC) occurred in 20 patients(71.4%), which was associated with lower basal corticosteroid replacement dose, hypochloremia, lower eosinophil, lower platelet, and longer activated partial thromboplastin time(APTT)(P＜0.05). 2 patients died during hospitalization.26.3 % (5/19) of surviving patient′s recovered consciousness longer than 48 hours. Delayed recovery of consciousness was associated with lower systolic pressure, higher blood creatinine, and higher fibrinogen(P＜0.05). Long COVID-19 symptoms such as fatigue and poor appetite occurred in 48.0 % (12/25) of patients. Among patients with increased corticosteroid dosage, 50.0 % (12/24) had their dose reduced to baseline within 3 weeks. Conclusions COVID-19 patients with AI have a high frequency of consciousness disturbance and AC. AI patients are lack of awareness of adjusting corticosteroid dosage proactively in case of infection stress, thus education of “sick day rules” for AI patients should be strengthened in clinical practice.

Mini Reviews

Advances in the treatment of dental stem cells for Parkinson′s disease

YU Manshu, ZHAO Xiaomin, QIU Mingyue, LIU Chunran, NA Risu

2024, 44(9):  1298-1302.  doi:10.16352/j.issn.1001-6325.2024.09.1298

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Parkinson′s disease (PD) is the second most common neurodegenerative disease, mainly due to the loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in motor dysfunction. Dental stem cells (DSCs) are derived from the cranial neural crest which can be easily harvested. DSCs coming from the cranial neural crest have excellent proliferation and differentiation ability, and can promote nerve repair and regeneration. DSCs can secrete new dopamine neurons and secrete a large number of neurotrophic factors(NTFs) to improve the neural function, and also inhibit the neuroinflammatory response through immune modulation. DSCs can effectively alleviate the motor dysfunction in rats with PD and play an important role in R&D of regenerative medicine.

Impact of chronic stress on the development of breast cancer

SU Lingfeng, WANG Huxia, WANG Yanfeng, SONG Zhangjun

2024, 44(9):  1303-1307.  doi:10.16352/j.issn.1001-6325.2024.09.1303

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Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women. Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development. Stress leads to dysfunctions of cells, molecules and neural circuits, thus promoting depression. Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients.

Strategies for the prevention and treatment of endometrial injury

LI Jiaming, YANG Chao, MA Li

2024, 44(9):  1308-1313.  doi:10.16352/j.issn.1001-6325.2024.09.1308

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Endometrial injury is the main fact leading to the damage of endometrial basal layer. It is usually caused by traumatic treatment, inflammatory injury, radiation, chemical drug-related injury, and delivery-related diverticulum. The use of hyaluronic acid, decellularized matrix, amniotic membrane, platelet-rich plasma, mesenchymal stem cells (especially scaffold-based therapeutic delivery) has been proved to reduce post-injury scar formation and promote endometrial growth and repair, which provides a new therapeutic strategy for repairing the damaged endometrium with improved tolerability and fertility outcomes.

Effects of endotracheal tube and laryngeal mask airway on postoperative pulmonary complications in general anesthesia

PENG Yu, YI Jie

2024, 44(9):  1314-1319.  doi:10.16352/j.issn.1001-6325.2024.09.1314

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Postoperative pulmonary complications (PPCs) after general anesthesia surgery significantly affect patient prognosis. However, there′s insufficient evidence to confirm if different airway management tools influence PPCs. Airway management tools used in general anesthesia surgery can be divided into two categories: supraglottic and subglottic. Among them, the laryngeal mask airway (LMA) and endotracheal tube (ETT) are typical representatives and are the two most widely used airway management tools in general anesthesia surgery. Therefore, it is necessary to review and evaluated the effects of these two mainstream airway management tools in general anesthesia surgery on PPCs, thus providing a theoretical basis for the selection of airway management tools during general anesthesia surgery in clinical practice.

Medical Education

Practice of neurosurgery professional degree education based on the exemplary demonstration course of “Basic Neurosurgery Operations and Surgical Approaches”

WANG Dan, WANG Li′ao, MA Shunchang, JIA Wang, LI Deling

2024, 44(9):  1320-1323.  doi:10.16352/j.issn.1001-6325.2024.09.1320

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Objective To explore the role of the exemplary demonstration course “Basic Neurosurgery Operations and Surgical Approaches” in improving the teaching quality of standardized training of neurosurgery. Methods A total of 42 graduate students who participated in the course from September 2021 to December 2023 were selected, matched 1:1 with their counterparts who did not participate in the course. All trainees were required to complete a same questionnaire survey. The basic data, questionnaire scores of the two groups were compared, and statistical descriptions of the satisfaction and course evaluation of the participating students were performed. Statistical tests including t-test, Mann-Whitney test, Dunn′s multiple comparison tests and Chi-square test were applied using Graphpad Prism 10.0. Results There were no significant differences in educational background and age distribution between the two groups indicating comparability. The questionnaire scores of the students who participated in the course[7.0(6.0-9.0) points] were significantly higher than those of the students who did not participate in the course[3.5(2.0-5.0) points] (P＜0.000 1). This score advantage applied to students who participated in the course in the school year from 2021 to 2023, and there was no statistical difference in questionnaire scores among students who participated in the course across the three years. Additionally, 88.1% of the students who participated in the course expressed a high satisfaction and 90.5% of them considered the course was very practical for training of clinical skills. Conclusions The exemplary demonstration course “Basic Neurosurgery Operations and Surgical Approaches”may improve learning outcomes of surgical approaches and support the clinical training of neurosurgery graduates.

Optimization of medical education question bank construction based on a flipped classroom model

WANG Qiang, ZHOU Yaxuan, WU Dong

2024, 44(9):  1324-1327.  doi:10.16352/j.issn.1001-6325.2024.09.1324

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The importance of question bank construction in medical education has been well proved. However, there are still some weaknesses in the clinical teaching assessment question bank, including the inconsistency between assessment and clinical practice, the lack of coherence in question bank updates, and the mismatch between proposition and student learning stage. To address these issues, this article explores a teaching model which connects flipped classroom with student independent proposition and analyzes the advantages of applying flipped classroom to question bank construction. The connection between the two effectively established a regular updating mechanism for question banks, thus improve the construction of question banks in current medical education. It may support the capacity building of students′ self-oriented and regulated learning and improve the quality of teaching assessment.

Preliminary application of 3D digital technology in laparoscopic operation training in urology

DONG Dexin, WANG Wenda

2024, 44(9):  1328-1330.  doi:10.16352/j.issn.1001-6325.2024.09.1328

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Objective To evaluate the application effect of the three-dimensions(3D) technology in teaching laparoscopic surgical skills in urology. Methods Eighteen clinical interns who rotated in the urology department of Peking Union Medical College Hospital from July 2023 to March 2024 were randomly divided into a test group and a control group with 9 in each. The test group received laparoscopic operation skill training using 3D reconstruction and 3D printing technology, while the control group received laparoscopic operation skill training using conventional methods. After one month of rotating training, two groups of interns underwent laparoscopic operation skill assessment, and the training outcomes were evaluated using a survey questionnaire. Results The laparoscopic operation skill assessment scores of the test group and the control group were (94.33±2.12) and (88.11±2.39) points, respectively (P＜0.01). In terms of clinical skills, the test group showed a significant improvement in skill of clinical performance. According to the feedback from the survey questionnaire, the test group showed satisfaction from trainees and trainers as compared to the control group. Conclusions The 3D digital technology in laparoscopic operation skill training can significantly improve the outcomes of laparoscopic operation skill of interns. The satisfaction of the teaching mode is high among both trainers and trainees, so it is a potential and effective teaching method for the training of interns in department of urology.

Application of flipped classroom combined with a case-based learning in genetics courses

ZHANG Lei, JI Peili, YUE Cai, ZHAO Xiuli, LIU Yaping, CHEN Limeng

2024, 44(9):  1331-1334.  doi:10.16352/j.issn.1001-6325.2024.09.1331

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In recent years, with the development of gene testing and new drug research, the diagnosis and treatment of inherited diseases have made rapid progress, corresponding to higher requirements for genetics education. As a teacher of medical genetics, the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a “case-based learning” supported by flipped classroom in order to optimize teaching effects and learning outcomes. The result of this remodeling project proposes a new strategy to guide perspectives course design in future.

Chinese Medicine

Professor LIANG Xiaochun′s experience in the treatment of diabetic kidney disease

LI Yaoyang, WANG Shuyu, YANG Dan, WU Qunli

2024, 44(9):  1335-1340.  doi:10.16352/j.issn.1001-6325.2024.09.1335

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Objective To summarize the prescription characteristics and medication rules for the treatment of diabetic kidney disease (DKD) from professor LIANG Xiaochun and to inherit professor LIANG Xiaochun′s academic anamnesis. Methods Using the retrospective real world research (RWS) method and the electronic medical record of Peking Union Medical Union Hospital Information System (HIS),the clinical records of DKD outpatient treatment by professor LIANG Xiaochun′s from 2020 to 2022 was collected to built a database with the support of Traditional Chinese Medicine inheritance computing platform (V3.5) software. Correlation analysis, cluster analysis and other methods were used to analyze the frequency of medication performance and the medication′s four natures, five flavors, meridian tropism, and the combination of commonly used drugs in the treatment of DKD were reviewed. Results A total of 205 cases covering 193 traditional Chinese medicines were collected. The most frequent use of drugs were Cuscutae Semen,Mori Cortex,Ligustri Lucidi Fructus,Achyranthes aspera Linn,Commelinae Herba,Smilacis Glabrae Rhizoma,Radix Et Rhizoma Rumei,Ramulus Euonymi Alati and Astmgali Radix. The four natures shared by them are cold and the five flavors are mostly sweetness. The meridian tropism belongs to the liver, spleen, and kidney. The analysis of drug association showed that the core drug combination was: Cuscutae Semen-Ligustri Lucidi Fructus,Cuscutae Semen-Achyranthes aspera Linn,Ligustri Lucidi Fructus-Achyranthes aspera Linn,Achyranthes aspera Linn-Smilacis Glabrae Rhizoma,Cuscutae Semen-Smilacis Glabrae Rhizoma etc. The four core prescriptions were obtained by cluster analysis: Cuscutae Semen-Ligustri Lucidi Fructus-Mori Cortex-Achyranthes aspera Linn-Smilacis Glabrae Rhizoma-Radix Et Rhizoma Rumei,Cuscutae Semen-Commelinae Herba-Mori Cortex-Achyranthes aspera Linn-Ligustri Lucidi Fructus-Smilacis Glabrae Rhizoma,Cuscutae Semen-Ligustri Lucidi Fructus-Mori Cortex-Commelinae Herba-Achyranthes aspera Linn-Radix Et Rhizoma Rumei,Mori Cortex-Ligustri Lucidi Fructus-Cuscutae Semen-Astmgali Radix-Smilacis Glabrae Rhizoma-Commelinae Herba. Conclusions Professor LIANG Xiaochun treated DKD with the principle of tonifying the spleen and kidney, promoting blood circulation, and removing turbidity. The experience of medication embodies the academic anamnesis the combination of tonifying kidney and solidifying astringency, the combination of removing turbidity and detoxifying supplemented by activating blood and water circulation in human body.