Table of Content

05 October 2024, Volume 44 Issue 10

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Special Issues:Rare Tumors

Research advances and experience sharing in rare tumors

2024, 44(10):  1341-1341.  doi:10.16352/j.issn.1001-6325.2024.10.1341

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Targeted therapy and immunotherapy for malignant mesothelioma

2024, 44(10):  1342-1349.  doi:10.16352/j.issn.1001-6325.2024.10.1342

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Malignant mesothelioma (MMe) is a malignant tumor originating from mesothelial tissues, occurring mostly in locations like pleura, pericardium and peritoneum. The extensive research on its treatment has been carried on as tackling to the challenge of poor prognosis of the disease. Conventional treatment modalities including surgery, chemotherapy and radiotherapy all exhibit limited efficacy, resulting in persistently low survival rates. Hence, exploring novel therapeutic approaches is paramount for improving the prognosis of mesothelioma patients. Targeted therapy and immunotherapy, as emerging cancer treatment modalities, exert their effects by targeting specific molecular markers on tumor cells or immune cells, thus inhibiting tumor growth and metastasis, thereby offering new hope for mesothelioma treatment. This article provides a comprehensive review of recent research progress in targeted therapy and immunotherapy for mesothelioma.

Drug therapy for intracranial germ cell tumor

2024, 44(10):  1350-1356.  doi:10.16352/j.issn.1001-6325.2024.10.1350

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Intracranial germ cell tumor (IGCT) is an uncommon brain tumor, which is mostly found in male adolescents. The histology of IGCT can be divided into germinoma, mature teratoma, immature teratoma, teratoma with somatic-type malignancy, embryonic carcinoma, yolk sac tumor, choriocarcinoma and mixed intracranial germ cell tumor. Since classic high-dose radiotherapy can lead to a variety of long-term adverse effects including neurocognitive disorders and hormone secretion disorders, affecting the quality of life, chemotherapy with anti-tumor drugs is gradually increasing and clinicians have faced to more choices in the field of drug selection.

Diagnosis and treatment of tuberous sclerosis complex with TSC2 mosaic mutation and multiple angiomyolipomas:a case report

2024, 44(10):  1357-1362.  doi:10.16352/j.issn.1001-6325.2024.10.1357

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Objective To evaluate and explore the diagnosis, treatment, and clinical course of tuberous sclerosis complex(TSC)-associated hepatic angiomyolipoma (AML) and renal AML, emphasizing the limitations of genetic diagnostics and the significance of a multidisciplinary approach. Methods Utilizing comprehensive clinical data and multidisciplinary consultations, we thoroughly analyzed multiple genetic test results throughout the disease course. Following the confirmation of diagnosis, appropriate pharmacological treatment was administered, and its efficacy was evaluated.The patient was a 31-year-old male with a 12-year history of multiple atypical AMLs in the liver and kidneys. Multi-system manifestations included angiofibromas on the nose and perioral region, shagreen patches on the buttocks and cortical dysplasia found by head MRI. A history of dental enamel defects had been observing. Over theyears, the primary therapeutic approach has been performed as repeated surgical resections of AMLs. To further delineate the patient's genetic mutation profile and achieve a definitive diagnosis, we conducted a comprehensive genetic analysis. Results Through genetic analysis, a TSC2 c.2353C＞T(p.Gln785*) mutation with allele frequencies of 4.04% was identified in peripheral blood and 10.38% in tumor tissue, suggesting potential germline mosaicism originating during embryonic development. The patient was diagnosed with AML associated with TSC. Treatment with the mTOR inhibitor everolimus over one year resulted in a significant reduction in RAML lesions achieving partial remission. Conclusions It is imperative to consider the possibility of TSC in patients with AML. When TSC is diagnosed, meticulous scrutiny of low-frequency germline mutations is essential. mTOR inhibitors can be a treatment option for patients with TSC-AML.

Advances in pharmacotherapy for angiosarcoma

2024, 44(10):  1363-1367.  doi:10.16352/j.issn.1001-6325.2024.10.1363

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Angiosarcoma (AS) is a rare soft tissue sarcoma originating from vascular or lymphatic endothelial cells, accounting for less than 1% of soft tissue sarcomas. It is most common in skin and surface of soft tissue. The diagnosis of AS is based on pathology, and the expression of CD31, ERG and CD34 is commonly positive in immuno-histochemistry. Staging is performed according to the American Joint Committee on Cancer (AJCC)criteria for soft tissue sarcoma. Radical surgery is the primary therapy for locally confined disease. For un-resectable or metastatic angiosarcoma, chemotherapy is the main treatment method. Targeted therapy and immunotherapy have developed rapidly in recent years, and the combined therapy of different types of chemotherapy drug has been the focus of optimization in the future.

Original Articles

Ropivacaine alleviates LPS-induced apoptosis of ulcerative colitis cell line NCM-460

2024, 44(10):  1368-1375.  doi:10.16352/j.issn.1001-6325.2024.10.1368

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Objective To investigate the impact of ropivacaine on apoptosis of lippolysaccharide(LPS) -induced ulcerative colitis cell line NCM-460 and on activity of nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammatome.Methods Human colon epithelial cell line NCM-460 was cultured in vitro and divided into control group (no intervention), model group (10 μg/mL LPS treatment), low/medium/high concentration ropivacaine group (10 μg/mL LPS and 0.5, 1, 1.5 mmol/L ropivacaine co-treatment, respectivoly). Cell viability was determined by cell counting kit 8 (CCK-8) and the appropriate concentration was selected. The cells were then divided into control group, model group, ropivacaine group (10 μg/mL LPS and 1.5 mmol/L ropivacaine treatment) and ropivacaine + inhibitor group (10 μg/mL LPS, 1.5 mmol/L ropivacaine and 1 μmol/L NF-κB pathway inhibitor BAY 11-7082 treatment), inhibitor group (10 μg/mL LPS+1 μmol/L NF-κB pathway inhibitor BAY 11-7082 treatment) and ropivacaine + activator group (10 μg/mL LPS, 1.5 mmol/L ropivacaine and 1 μmol/L NF-κB pathway activator Prostratin), all groups were treated for 24 h. The level of IL-6, IL-8 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). The proliferation rate was detected by EdU incorporation. Hoechst 33258 staining microscopy was used to detect the apoptosis rate. Level of cyclinD1, caspase-3, NLRP3 and NF-κB pathway-related proteins were detected by Western blot. Results Compared with the control group, the cell viability of the model group was significantly decreased and the cell viability of high-concentration experimental group was increased after adding ropivacaine (P＜0.05). So, 1.5 mmol/L ropivacaine was selected for the follow-up experiment. Compared with the control group, the concentration of inflammatory cytokines IL-6, IL-8, TNF-α, apoptosis rate and the protein expression of caspase-3, NLRP3 and phosphorylated p-NF-κB in model group were all significantly increased (P＜0.05), while the proliferation rate and cycilnD1 protein expression were decreased (P＜0.05). Compared with model group, the concentrations of IL-6, IL-8, TNF-α, apoptosis rate and the expression of caspase-3, NLRP3 and p-NF-κB protein in ropivacaine group and inhibitor group were significantly decreased (P＜0.05), while the proliferation and cycilnD1 protein expression were increased(P＜0.05). Compared with ropivacaine group, the trend of the above indexes in ropivacaine + inhibitor group was more significant(P＜0.05), and the trend of these indexes in ropivacaine + agonist group was significantly reversed(P＜0.05). Conclusions Ropivacaine can inhibit the activation of NLRP3 inflammasome and block the signal transduction of NF-κB pathway, further inhibit LPS-induced apoptosis of NCM-460 cells and promote proliferation.

Expression of m⁶A-modified methyltransferase-like 14 in the hippocampus of depression-like mice

2024, 44(10):  1376-1382.  doi:10.16352/j.issn.1001-6325.2024.10.1376

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Objective To investigate the expression of m⁶A methyltransferase-like protein 14(METTL14) in the hippocampus of depression-like mice, and to provide a theoretical basis for further study of the molecular mechanism of depression and new drug targets. Methods 1)Twenty-four male C57BL/6J mice were divided into control group and depression model group. The control group was fed normally, and the model group was kept in single animal cage for 4 months and added with Chronic Unpredictable Animal Stress (CUMS) to establish the depression-like model. 2)After modeling, depression-like behaviors in model group were tested using forced swimming test (FST), sucrose preference test (SPT)and tail suspension test (TST).3)Twenty-four hours after completion of behavioral test, the hippocampus tissues of mice were collected, and the expression of m⁶A methyltransferase-like protein METTL14 in the hippocampus of mice was detected by molecular biology experiments. Results 1)The mice in the model group showed significant depression-like behavior; 2)The expression of METTL14 in the hippocampus of the model group showed an increased mRNA expression with the increased m⁶A modification. 3)In the model group, the expression of METTL14 in hippocampal CA1, CA3 and DG districts increased and there was neuronal damage found. Conclusions m⁶A methylation function has been proved to be more active in the hippocampus of depressed mice.

Association of seven antibody levels in lung cancer with chemotherapy effect and prognosis in patients with NSCLC

2024, 44(10):  1383-1387.  doi:10.16352/j.issn.1001-6325.2024.10.1383

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Objective To study the relationship between seven antibody of lung cancer and the chemotherapy effect and prognosis of patients with non-small cell lung cancer (NSCLC). Methods A total of 42 patients with NSCLC admitted to Taihe County People's Hospital from June 2022 to December 2023 were selected. All subjects underwent 4 cycles of chemotherapy. They were divided into effective group (n=25) and non-effective group (n=17) according to the outcome of chemotherapy. The seven antibody of lung cancer were titrated and compared and the efficacy in evaluating chemotherapy was analyzed by receiver operating characteristic (ROC) curve. In addition, the subjects were divided into a good prognosis group (n=21) and a poor prognosis group (n=21) according to the difference in clinical outcomes. The seven antibody of lung cancer were titrated and compared between the two groups, and the relationship between the antibody level and the prognosis of NSCLC patients was determined by multivariate Logistic regression analysis. Results The antibody level in effective group was lower than that in the non-effective group (P＜0.05). ROC curve analysis confirmed that the level of CAGE,GAGE7, GBU4-5, P53,PGP95, SOX2 and MAGEA1 is significantly related to better efficacy of chemotherapy and the areas under the curve were 0.861, 0.769, 0.778, 0.786, 0.793, 0.842 and 0.833, respectively. The antibody level of lung cancer in poor prognosis group was higher than those in good prognosis group (P＜0.05). Multiple Logistic regression analysis confirmed that the seven antibody levels were the risk factors for poor prognosis in NSCLC patients(all OR value＞1, P＜0.05). Conclusions The level of seven antibody of lung cancer are negatively related to the chemotherapy effect and prognosis of NSCLC patients. With increase of the seven antibody level of lung cancer, prognosis of patients resulted from chemotherapy is worse.

The efficacy of various interventions to the extracranial stenosis on reperfusion in anterior tandem lesions receiving mechanical thrombectomy

2024, 44(10):  1388-1393.  doi:10.16352/j.issn.1001-6325.2024.10.1388

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Objective To evaluate the efficacy of different interventions to the extra cranial lesions in acute ischemic stroke (AIS) due to anterior tandem lesions (TL) on reperfusion. Methods As a multi-center, cross-sectional study, AIS due to anterior TL receiving mechanical thrombectomy (MT) were retrospectively collected. Interventions to the extra-cranial stenosis were recorded. Post-procedural reperfusion was assessed using the modified thrombolysis in cerebral infarction (mTICI) score. Complete revascularization was defined as mTICI 3 and good revascularization was defined as mTICI 2b/3. The relationship between different extra-cranial intervention regimens and rate of re-vascularization was compared. Results Totally 117 patients were included with 92.3% reaching good recanalization and 63.2% reaching complete re-canalization. There was no significant difference in good re-canalization rates among various extra-cranial intervention regimens. The rate of complete re-canalization was significantly higher in patients receiving endovascular therapy(P＜0.05) and there was significant difference among various endovascular treatment regimens(P＜0.01): acute balloon angioplasty only group presented the highest rate of complete re-canalization (100.0%), followed by acute stenting only group (80%), acute stenting + balloon angioplasty group (73.7%) and conservative treatment group (54.3%). Conclusions Endovascular intervention to extra-cranial stenosis contributes to complete re-canalization in AIS due to anterior TL receiving MT, and acute balloon angioplasty seems to be quite effective than acute stenting.

Clinical characteristics and prognosis of acute B-lymphoblastic leukemia complicated with chemotherapy-induced peripheral neuropathy in children

2024, 44(10):  1394-1399.  doi:10.16352/j.issn.1001-6325.2024.10.1394

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Objective To summarize the characteristics of chemotherapy-induced peripheral neuropathy (CIPN) in children with acute B-lymphoblast leukemia (B-ALL) and to identify the influencing factors and prognosis of CIPN. Methods The clinical data of 60 children with B-ALL admitted to the 29th Ward of the Department of Hematology and Oncology, Children's Hospital Affiliated to Soochow University from June 2020 to December 2023 who received chemotherapy and had finished chemotherapy for 6 months were retrospectively reviewed. Results There were 37 cases of B-ALL combined with CIPN; the incidence of CIPN was 61.7%. Increasing age of onset was a risk factor for CIPN in children[OR= 1.209, 95% CI(1.023-1.428), P=0.026] with the highest incidence of sensory nerve dysfunction (78.4%). Electromyography indicated that B-ALL combined with CIPN was multiple peripheral neurogenic lesions with certain reversibility. In the induction stage of chemotherapy, 13 cases (35.1%) showed CIPN, accounting for the highest proportion. The CIPN improvement rate 6 months after chemotherapy was 67.6%, the age of onset[OR=2.418, 95% CI(0.212-2.106), P=0.018] and the severity of CIPN[OR=203.394, 95% CI(2.29-18 065.04). P=0.02] were risk factors for poor prognosis of children with CIPN. The older the age of onset was, the higher the severity of CIPN and worse prognosis were found. Conclusions Children with B-ALL complicated with CIPN are reversible multiple peripheral nerve lesions, and the occurrence and outcome of CIPN is potentially related to individual differences of children.

Roflumilast alleviates lung injury in rats with pneumococcal pneumonia

2024, 44(10):  1400-1406.  doi:10.16352/j.issn.1001-6325.2024.10.1400

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Objective To investigate the effect of roflumilast on pulmonary injury induced by Streptococcus pneumonia (SP) in rat model. Methods Rats were randomly divided into control group, pneumonia model group, roflumilast low dose group, high dose group and roflumilast high dose plus Colivelin (STAT3 activator) intervention group. The level of PaO₂, PaCO₂, IL-1β, IL-8, IL-10 and TNF-α were detected. Lung tissue wet/dry ratio (W/D), MDA content, MPO and SOD activity were examined. HE staining microscopy was used to observe the pathological injury of lung tissue. Apoptosis, cleaved caspase-3, IL-6, and p-STAT3/STAT3 protein expression were detected. Results Compared with the control group, the lung tissue of animals in the model group showed obvious damage; blood PaO₂, oxygenation index(OI), lung tissue IL-10 level, and SOD activity were all significantly reduced; the level of blood PaCO₂, lung tissue IL-1β, IL-8, TNF-α and W/D values, MDA content, MPO activity, cell apoptosis rate, cleaved caspase-3, IL-6, and p-STAT3/STAT3 protein expression were significantly increased(P＜0.05). Compared with the model group, the lung tissue damage of rats in the low and high dose groups of roflumilast was obviously reduced; the level of blood PaO₂, OI and, lung tissue IL-10, and SOD activity were obviously increased, the level of blood PaCO₂, lung tissue IL-1β, IL-8, TNF-α and, W/D values, MDA content, MPO activity, cell apoptosis rate, cleaved caspase-3, IL-6, and p-STAT3/STAT3 protein expression were significantly reduced(P＜0.05); Colivelin was able to partially reverse the improvement effect of roflumilast on lung injury in rats with SP pneumonia (P＜0.05). Conclusions Roflumilast may inhibit inflammatory response, oxidative damage and apoptosis of SP-induced pneumonia in rats resulting in an improvement of lung function.

Zinc finger protein A20-targeting siRNA promotes pyroptosis of human rheumatoid arthritis fibroblast-like synoviocytes

2024, 44(10):  1407-1413.  doi:10.16352/j.issn.1001-6325.2024.10.1407

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Objective To investigate the regulatory effect of small interfering RNA (siRNA) silencing zinc finger protein A20 on pyroptosis of rheumatoid arthritis(RA) fibroblast-like synoviocytes (HFLS-RA). Methods Human FLS-RA cell line MH7A cells were cultivated, A20 siRNA silencing group was synthesized for knocking down the human A20 gene, and then specific A20 gene siRNA and siRNA-NC(negative control)were transfected into MH7A cells using liposome method. RT-qPCR was applied to detect the expression of NLRP3 and Caspase-1 mRNA in cells.The protein expression of NLRP3 and Caspase-1 was detected by Western blot, and IL-1β and IL-18 in cell culture medium were detected by ELISA method. Transmission electron microscopy (TEM) was used to detect pyroptosis. Results After A20 knockdown, the mRNA and expression of NLRP3 and Caspase-1 in MH7A cells in the siRNA-A20 group were significantly increased as compared with the siRNA-NC group(P＜0.01). The concentration of IL-1β and IL-18 in the cell culture supernatant of the siRNA-A20 group was significantly increased compared with the siRNA-NC group (P＜0.01). Compared with the siRNA-NC group, some cells in the siRNA-A20 group showed swollen and ruptured. The integrity of the cell membrane was also lost, and a large area of edema was present in the cell. In addition, a blurred depression of the local nuclear membrane was noted, while an increase in heterochromatin pyknosis was accompanied by their uneven distribution as well as their aggregation around the nuclear membrane. Conclusions Silencing of A20 gene with siRNA might promote NLRP3/Caspase-1 mediated pyroptosis in HFLS-RA, which lays an experimental foundation for new clinical treatment methods of RA.

Efficacy of ketorolac versus tramadol for analgesia during percutaneous vertebroplasty

2024, 44(10):  1414-1418.  doi:10.16352/j.issn.1001-6325.2024.10.1414

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Objective To evaluate the efficacy of ketorolac versus tramadol used in analgesia during percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fracture(OVCF). Methods This retrospective study selected 126 patients who underwent PVP for treatment of osteoporotic vertebral compression fracture. Among them, there were 35 males and 91 females, with an age range of 60-82 years and an average age of 71.2±6.5 years old. The patients were divided into two groups: ketorolac group and tramadol group. Operation time and analgesic consumption of the two groups were recorded and compared; The mean artery pressure (MAP) and heart rate (HR) were recorded at following times point: entering operation room (T0), beginning of surgery (T1), injection of bone cement into the vertebral body (T2), ending of surgery (T3); pain visual analogue scale (VAS) were recorded at admission, after analgesic medication, intraoperative maximum, at discharge and 1 year after surgery; Oswestry disability index (ODI) 1 year after surgery, satisfaction scores of patient, adverse events happened intraoperatively and postoperatively were also collected for comparison. Results There was no difference in general data between the two groups. The values of HR and MAP at T1, T2 and T3 were significantly lower in the ketorolac group compared to tramadol group (P＜0.05); No difference in VAS scores between the two groups of patients was observed at admission, discharge, and follow-up. Ketorolac group showed significantly lower VAS scores than tramadol group after analgesic medication and during surgery (P＜0.05); There was no difference in the treatment course of preoperative analgesics between the two groups. The dosage of intraoperative analgesics in ketorolac group was significantly lower than that in tramadol group, and the difference was statistically significant (P＜0.05). The operation time in the ketorolac group was significantly shorter than that in tramadol group, and patient satisfaction was significantly higher than that in tramadol group(P＜0.001). There was no difference in pre-operative and post-operative ODI scores between the two groups. The incidence of post-operative nausea was significantly lower in ketorolac group than in the tramadol group(P＜0.05). Conclusions Ketorolac can effectively shorten operation time, reduce the pain intensity of patients with osteoporotic vertebral compression fracture, and can decrease the occurrence of postoperative nausea and improve patient satisfaction.

Techniques and Methods

Establishment and characterization of pancreatic cancer cell strains with stable expression of Cas9 protein, fluorescent proteins and luciferase

2024, 44(10):  1419-1427.  doi:10.16352/j.issn.1001-6325.2024.10.1419

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Objective To establish human and mouse pancreatic cancer cell strains stably expressing Cas9 protein, green fluorescent protein, red fluorescent proteins, luciferase-tdTomato, and to validate the activity of luciferase and gene editing of Cas9 function for pancreatic cancer research using luciferase and CRISPR/Cas9 system. Methods In human pancreatic cancer cells (AsPC-1, CFPAC-1, HPAC, BxPC-3, HS 766T, MIA PaCa-2, PANC-1, and SW 1990), and mouse pancreatic cancer cell (Pan02), the cells were infected with Cas9-expressing plasmid pLv-EF1α-Cas9m1.1-Puro, and single-cell clones were selected for culture and expansion. After extracting the total protein, Western blot verified the expression level of Cas9; Infected with fluorescent protein expression plasmids pLv-EF1α-EGFP, pLv-EF1α-mCherry, pLv-EF1α-tdTomato, pLv-EF1α-Luc2-tdT, and selected single cell clones stably expressing fluorescent proteins were cultured and amplified under fluorescence microscope. Cas9 stable expression cell line was selected to be infected with pLv-EF1α-Luc2-tdT, and the monoclonal culture of stable expression of fluorescent proteins was selected for expansion under fluorescence microscope. One of the cell lines were selected to be infected with Lv-EF1a-mCherry, and the mCherry-positive cells were sorted out by flow cytometry, and then the guide RNA of mCherry gene was then infected by lentivirus to target the mCherry gene, and after cell expansion, mCherry knockdown was detected by fluorescence microscope observation and flow cytometry; 5 BALB/c Nude mice were subcutaneously inoculated with MIA PaCa-2-Luc2-tdT cells (1.0×10⁷/cells each), and imaged in vivo after 36 days. Results 48 human pancreatic cancer cell strains with stable Cas9 expression were screened(including 23 cells expressing Cas9m1.1, 25 cells expressing Cas9m1.1-Luc2-tdT),33 pancreatic cancer cell strains with stable expression of fluorescent proteins were screened (8 cells expressing EGFP, 7 expressing mCherry, and 9 each expressing Luc2-tdT and tdTomato). Cells expressing mCherry and Cas9 were infected with mCherry gRNA and mCherry was knocked down. In vivo imaging showed that both bioluminescence and fluorescence luminescence were present in MIA PaCa-2 cells expressing Luc2-tdT. Conclusions 33 pancreatic cancer cell strains with stable expression of fluorescent proteins are successfully established, in which the Luc2-tdT-expressing cell strains have luciferase activity; 48 pancreatic cancer cell strains with stable expression of Cas9 are successfully established, and the Cas9 protein has gene editing activity, gene editing activity varies depending on the original cell strains.

Optimization of methods for isolation and culture of primary mouse hepatocytes and establishment of a steatosis model

2024, 44(10):  1428-1435.  doi:10.16352/j.issn.1001-6325.2024.10.1428

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Objective To improve the isolation and culture methods for primary hepatocytes and to establish a hepatic steatosis cell model for enhancing experimental efficiency and model precision. Methods Improvements were made upon existing techniques for primary hepatocyte cultivation and steatosis model establishment. The technology oriented to optimize the retrograde cannulation and fixation procedures, meticulously calibrating the perfusion speed and duration for mouse liver digestion. The culture medium was supplemented with 2% fetal bovine serum (FBS) during the removal of liver capsules and filtration steps. Additionally, the induction parameters for the steatosis cell model were refined, including the selection of free fatty acid (FFA) types and optimize their concentrations, ratios, and precise induction durations. Results The optimized protocol yielded mouse primary hepatocytes with a viability exceeding 90%, demonstrating ample quantity, favorable morphology, and excellent overall condition. The steatosis cell model exhibited prominent cytoplasmic lipid droplets, impaired glucose and lipid metabolism, as well as mild inflammation and insulin resistance, closely mimicking key aspects of the disease in vivo. Conclusions The refined techniques facilitated the establishment of a stable and physiologically representative in vitro steatosis cell model, which may support further research of pathogenesis of the disease, identification of potential therapeutic targets.

Mini Reviews

Role of TERT in regulating mitochondrial oxidative stress in diseases

2024, 44(10):  1436-1441.  doi:10.16352/j.issn.1001-6325.2024.10.1436

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Oxidative stress is the result of imbalance between the formation of reactive oxygen species (ROS) and antioxidant level. Mitochondria are important organelles regulating oxidative stress. Telomerase reverse transcriptase (TERT) not only in the nucleus to maintain telomerase activity and telomere length, but also reversibly transits to mitochondria. Improving the activity of oxidative respiratory chain of mitochondria to reduce the production of mitochondrial reactive oxygen species (mtROS) and to activate GSH system as well as autophagy pathway to promote the clearance of mtROS are all important to down-regulate the level of mtROS, which will alleviate oxidative stress and damage and keep the REDOX balance of cells and the normal function of the body.

Role of neutrophils and NETs in osteosarcoma and soft tissue sarcoma

2024, 44(10):  1442-1446.  doi:10.16352/j.issn.1001-6325.2024.10.1442

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Neutrophils are one of the important components of the tumor microenvironment. Neutrophil extra cellular traps (NETs) are a network structure released by neutrophils, and their formation process is called neutrophil inflammatory apoptosis (NETosis). Neutrophils in the tumor microenvironment, also known as tumor associated neutrophils (TANs). TANs including N1 phenotype and N2 phenotype have a bidirectional regulatory effect on tumors. While N1 phenotype inhibits tumor growth, and N2 phenotype promotes tumor growth, and N1 and N2 types undergo mutual transformation due to the influence of the tumor microenvironment. Neutrophils and NETs also play important roles in bone and osteosarcoma tissue sarcoma, which can affect tumor progression and predict patient prognosis. Blocking the formation of NETs may be a potential therapeutic target.

Progress of research on the mechanism of GPSM2 in tumor development

2024, 44(10):  1447-1450.  doi:10.16352/j.issn.1001-6325.2024.10.1447

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G-protein signaling modulator 2 (GPSM2) is a negative regulator of G protein coupled receptor signaling pathway, which plays an important role in cell growth. In recent years, it has been found that GPSM2 is abnormally expressed in a variety of malignant tumors and is related to many clinical symptoms of tumors. Based on the structure and function of GPSM2, this paper discusses its role and mechanism in tumor development, so as to identify new targets for tumor diagnosis and treatment.

Research progress of Apelin in female reproductive health

2024, 44(10):  1451-1454.  doi:10.16352/j.issn.1001-6325.2024.10.1451

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Apelin is an adipokine family which includes Apelin-13, Apelin-36 and other isoforms and regulates physiological functions by immunomodulation, oxidative stress, glycolipid metabolism, and apoptosis and so on. Apelin is closely related to polycystic ovary syndrome, ovarian cancer and other diseases of the female reproductive system so it is expected to be new target molecules and may orient the development of research and clinical treatment.

Role of zinc transporter family in pancreatic cancer

2024, 44(10):  1455-1459.  doi:10.16352/j.issn.1001-6325.2024.10.1455

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As an essential trace element in organisms, Zn²⁺ is involved in the formation of protein structure and as a coenzyme factor affects cell homeostasis. The imbalance of Zn²⁺ homeostasis is closely related to the occurrence and metastasis of pancreatic cancer. Zn²⁺ homeostasis is regulated by two zinc transporter families, ZIP and ZnT, which mediate the processes of cell proliferation, differentiation and death. The ZIP protein family is mainly involved in DNA damage repair, cellular immunity, exosome secretion, and epithelial-mesenchymal transition (EMT) processes through RAS/RREB1 and cAMP/JAK/STAT signaling pathways, thereby affecting pancreatic cancer. The ZnT protein family mainly promotes the occurrence and development of pancreatic cancer through ERK, p38MAPK, NF-κB, and mTOR pathways. This review aims to provide some theoretical basis for the prevention, diagnosis, treatment and prognosis of pancreatic cancer.

Role of Ghrelin in gastric cancer

2024, 44(10):  1460-1464.  doi:10.16352/j.issn.1001-6325.2024.10.1460

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Ghrelin is a newly discovered gastrointestinal peptide that is involved in regulating the body's growth, development and energy balance, and plays a key role in the occurrence and progression of malignant tumors, such as cell proliferation, migration, invasion, apoptosis, inflammatory response and vascular disease. Generate immune cell infiltration and so on. Ghrelin affects the progression of gastric cancer by activating NF-κB/p65 and AMPK and other signaling pathways. Ghrelin not only assist in early screening of gastric cancer, but also function a new marker for predicting the prognosis and survival of gastric cancer patients. Ghrelin and its analogs have clinical application value in the treatment of gastric cancer-related syndromes such as cachexia or sarcopenia.

Long non-coding RNA and diseases

2024, 44(10):  1465-1469.  doi:10.16352/j.issn.1001-6325.2024.10.1465

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Long non-coding RNA (lncRNA) is a class of endogenous non-coding RNA with a length of more than 200 nt. Due to lack of open reading frame (ORF), they lack the ability to directly encode proteins, but they play a crucial role in gene regulation. They are widely involved in epigenetics, transcription, translation, modification and degradation, thereby affecting the life activities of the body, and their expression imbalance is closely related to the occurrence and development of diseases. Therefore, analyzing the inherent characteristics of lncRNA and revealing its intrinsic role can not only deepen our understanding of human physiological and pathological processes, but also provide new ideas and potential solutions for the diagnosis, prevention and treatment of diseases. So as to provide references for the related research of lncRNAs.

CKAP2 and malignant tumors

2024, 44(10):  1470-1473.  doi:10.16352/j.issn.1001-6325.2024.10.1470

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Cytoskeleton-associated protein 2 (CKAP2) gene is located on human chromosome 13q14.3 and encodes cytoskeleton associated protein 2, which is involved in regulating the separation of mitotic chromosomes. CKAP2 has been confirmed in multiple studies to be an oncogenic gene that can regulate JAK2/STAT3, FAK-ERK2, and NF-κB signaling pathway affects the biological behaviors of tumor cells such as proliferation, apoptosis, and invasion, alters the tumor microenvironment, and regulates tumor immunity. CKAP2 is also closely related to the formation of spindle bodies during mitosis, and dysregulation of CKAP2 can lead to incorrect chromosome separation, promoting tumor development. In addition, CKAP2 is closely related to chemotherapy resistance in tumors, and the underlying mechanisms are not yet clear.CKAP2 may become a novel tumor marker and effective therapeutic target, playing an important role in the diagnosis and treatment of tumors.

Medical Education

Application and effect evaluation of MOOC combined with flipped classroom in the teaching of urology courses

2024, 44(10):  1474-1477.  doi:10.16352/j.issn.1001-6325.2024.10.1474

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Objective To develope and evaluate the outcomes of combining “Curriculum Ideological and Political Education” with interactive teaching in ultrasonic practice class. Methods Fifty-one sophomores in the medical engineering cross experimental class of Beihang University who participated in the ultrasonic course in 2022 were selected as research objects. They were divided into two groups: one group adopted the classic teaching mode, the another group adopted the “Curriculum Ideological and Political Education”interactive teaching mode. After the training, a questionnaire survey and a written examination of basic knowledge were conducted. The test scores of the two groups and the feedback from questionnaires for teaching effect were compared. Results There was no significant difference in the theoretical exam achievement rate between the two groups of students. The students′ learning initiative and understanding of doctors′ profession after the application of this new training method were significantly improved as compared with the classic lecture group, with a statistical difference. Student feedback showed that more ideological and political elements needed to be integrated into the ultrasound medicine classroom. Conclusions It is a good teaching method to integrate the interactive teaching of “Curriculum Ideological and Political Education” with learning of ultrasonic specialized courses.

Application and effect evaluation of MOOC combined with flipped classroom in the teaching of urology courses

2024, 44(10):  1478-1480.  doi:10.16352/j.issn.1001-6325.2024.10.1478

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Objective To evaluate the efficacy of MOOC combined with flipped classroom teaching in clinical training of urology. Methods A total of 100 clinical medical students from Peking Union Medical College were randomly assigned to either an experimental group or a control group. The experimental group adopted the teaching mode of MOOC combined with flipped classroom, while the control group adopted classic teaching method. The two groups were compared in terms of their theoretical exam scores, case analysis skills and teaching satisfaction level. Results There were no significant difference in theoretical examination scores between experimental group and control group (the mean value of scores are 45.12 and 44.50, respectively). However, the interview scores from experimental group was significant higher than that of control group (the mean value of scores are 42.28 and 40.10, respectively, P＜0.001). The MOOC combined with flipped classroom mode significantly improved students′capacity building of clinical reasoning for diagnosis and communication skills. Students were more willing to continue receiving this teaching mode. Conclusions The integration of MOOC with the flipped classroom model significantly enhances the quality and efficacy of urology teaching.