1.Establishment and in vivo imaging observation of a nude mouse model of type 2 diabetes mellitus and pancreatic cancer
Yongning XU ; Xuehuan HUANG ; Zhipan TANG ; Ruohan LI ; Wen QIN
Journal of Clinical Hepatology 2024;40(6):1231-1239
Objective To establish a nude mouse model of type 2 diabetes mellitus(T2DM)and pancreatic cancer that allows dynamic observation of tumor formation process and facilitates in vivo research.Methods At first,human pancreatic cancer PANC-1 cells were transfected with lentiviral vector GV260 to construct the pancreatic cancer cell line PANC-1-Luc with stable expression of firefly luciferase.Then,36 specific pathogen-free nude mice were randomly divided into control group with 12 mice and model group with 24 mice(nude mice with T2DM and pancreatic cancer).The mice in the control group were fed with breeding diet and were then given ectopic subcutaneous implantation of PANC-1-Luc cells,and those in the model group were first given high-fat diet and intraperitoneal injection of 1%STZ,followed by ectopic subcutaneous implantation of PANC-1-Luc cells.The fluorescence in vivo imaging system and the manual measurement method were used for simultaneous and dynamic monitoring of the growth of pancreatic cancer in nude mice in the two groups,and the tumor growth curve was plotted to investigate the correlation between fluorescence value and tumor volume.Subcutaneous tumors and pancreatic islets were observed under a microscope to verify whether the model was successfully established,and immunohistochemistry was used to measure the expression of Ki-67 in tumor tissue to investigate the influence of hyperglycemia on the growth of pancreatic cancer in nude mice.The independent-samples t test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups.Results The optimal virus titer was determined as 5×107 TU/mL for the stable transfection of lentiviral vector in PANC-1 cells,and the optimal concentration selected with puromycin was 20 μg/mL,with an optimal selection time of 9 days.The fluorescence value of PANC-1-Luc cells was linearly and positively correlated with the number of cells,with the linear equation of y=42.56x-42 504(r=0.977,P=0.004).The blood glucose value of T2DM nude mice was 23.05(19.25-26.40)mmol/L,with a blood glucose level of>11.1 mmol/L in each nude mouse,and there was a significant difference in blood glucose value between the T2DM nude mice and the control nude[6.15(5.20-7.30)mmol/L](Z=-8.45,P<0.001).Compared with the control group,the model group had reductions in the number and volume of pancreatic islets,with irregular shapes and unclear boundaries,and pathological examination confirmed that the xenograft tumor was pancreatic cancer tissue,which showed that the model was established successfully.In the model group,there was a linear positive correlation between subcutaneous tumor size and fluorescence values,with the linear equation of y=232 348 691x-8 258 608(r=0.911,P=0.031).The model group had a significantly higher positive rate of Ki-67 than the control group(50.333%±7.808%vs 15.917%±4.055%,t=13.55,P<0.001),suggesting rapid tumor proliferation in the model group.Conclusion The T2DM nude mouse model of pancreatic cancer established in this study can simulate the pathological process of the development and progression of pancreatic cancer in the context of T2DM and dynamically observe the influence of hyperglycemia on the growth of pancreatic cancer cells in vivo,thereby providing a new experimental vector for the in vivo study of the development and progression of pancreatic cancer in the context of T2DM.
2.Changes of serum Klotho and fibroblast growth factor 23 levels and their relationships with growth and development of small for gestational age infants after birth
Xiaopei LI ; Xin WANG ; Chan WANG ; Yongning ZHENG ; Lei LUO ; Yaying CHENG
Journal of Jilin University(Medicine Edition) 2024;50(3):804-811
Objective:To discuss the changes of serum levels of Klotho and fibroblast growth factor 23(FGF23)in the small for gestational age(SGA)infants after birth,and to clarify their relationships with growth and development.Methods:A total of 35 SGA and 53 appropriate for the gestational age(AGA)infants were selected and divided into SGA group(n=35)and AGA group(n=53),including 51 infants in premature group,among them 20 infants in preterm SGA group and 31 infants in preterm AGA group;among them 37 infants in full-term group,15 infants in full-term SGA group and 22 infants in full-term AGA group.The clinical materials of the infants in various groups were collected.The levels of Klotho and FGF23 in serum and clinical biochemical markers of the infants on the 7th and 14th days after birth were detected.The relationships between the levels of Klotho and FGF23 in serum on the 7th and 14th days postnatally and newborn growth indicators such as body weight,body length,head circumference,chest circumference,and Kopu index,as well as their correlations with calcium and phosphorus metabolism were analyzed.Results:Compared with AGA group,the body weight,body length,head circumference,chest circumference,and Kopu index of the infants in SGA group were decreased(P<0.05).On the 7th and 14th days after birth,compared with preterm group,the serum levels of Klotho and FGF23 of the infants in full-term group were significantly increased(P<0.01).Compared with the 7th day after birth,the levels of serum Klotho of the infants in preterm and full-term groups on the 14th day were significantly increased(P<0.01),and the levels of FGF23 in serum were decreased(P<0.01).Compared with AGA group,the levels of serum Klotho and FGF23 of the infants in SGA group on the 7th and 14th days after birth were significantly decreased(P<0.05 or P<0.01).Compared with the 7th day after birth,the levels of serum Klotho of the infants in both AGA and SGA groups on the 14th days after birth were significantly increased(P<0.01),and the FGF23 levels were decreased(P<0.05 or P<0.01).Compared with preterm AGA group,the levels of Klotho and FGF23 in serum of the infants in preterm SGA group on the 7th and 14th days after birth were significantly decreased(P<0.05 or P<0.01).Compared with full-term AGA group,the levels of Klotho and FGF23 in serum of the infants in full-term SGA group on the 7th and 14th days after birth were significantly decreased(P<0.05 or P<0.01).In SGA group,the serum levels of Klotho and FGF23 on the 7th day after birth were positively correlated with the gestational age,body weight,body length,head circumference,chest circumference,and Kopu index(P<0.05 or P<0.01);there was a positive correlation between the serum level of Klotho and the serum level of FGF23(P<0.05).In terms of calcium-phosphorus metabolism,in SGA group,the serum level of Klotho on the 7th day after birth was positively correlated with serum phosphorus level(P<0.01),and the level of serum FGF23 on the 7th day after birth was positively correlated with serum calcium and phosphorus levels(P<0.05 or P<0.01).Conclusion:Klotho and FGF23 proteins are closely associated with growth and development and phosphate metabolism of the infants.The expression levels of Klotho and FGF23 in serum of the SGA infants postnatally are lower,but the secretion of Klotho is increased with the gradul improvement of each organ,and the decrease of FGF23 may be the adaptive response.
3.Surgical management of gastric cancer in the era of immunotherapy
Ziyu LI ; Yongning JIA ; Xinxing LU ; Guangmin GUAN ; Qi WANG
Chinese Journal of Surgery 2024;62(5):353-358
With the widespread application of immune checkpoint inhibitors, chemotherapy combined with immunotherapy has shown promising efficacy in the treatment of various cancers. Especially gastric cancer, this strategy is gradually expanding from first-line treatment in advanced stages to perioperative management. Compared to neoadjuvant chemotherapy alone, the combined approach not only improves pathological regression but also leads to better downstaging, which is particularly significant in gastric cancer subsets that are HER2-positive, mismatch repair deficient, PD-L1 combined positive score ≥5, or EB virus-positive. This combined treatment has made it possible to reduce the extent of gastrectomy, perform function-preserving surgeries, or even consider non-surgical strategies. Currently, exploring the optimal protocols for combining immune checkpoint inhibitors with chemotherapy, identifying potential indications for function-preserving surgery, improving surgical methods, and developing non-surgical strategies represent key issues in the surgical management of gastric cancer in the era of immunotherapy.
4.Surgical management of gastric cancer in the era of immunotherapy
Ziyu LI ; Yongning JIA ; Xinxing LU ; Guangmin GUAN ; Qi WANG
Chinese Journal of Surgery 2024;62(5):353-358
With the widespread application of immune checkpoint inhibitors, chemotherapy combined with immunotherapy has shown promising efficacy in the treatment of various cancers. Especially gastric cancer, this strategy is gradually expanding from first-line treatment in advanced stages to perioperative management. Compared to neoadjuvant chemotherapy alone, the combined approach not only improves pathological regression but also leads to better downstaging, which is particularly significant in gastric cancer subsets that are HER2-positive, mismatch repair deficient, PD-L1 combined positive score ≥5, or EB virus-positive. This combined treatment has made it possible to reduce the extent of gastrectomy, perform function-preserving surgeries, or even consider non-surgical strategies. Currently, exploring the optimal protocols for combining immune checkpoint inhibitors with chemotherapy, identifying potential indications for function-preserving surgery, improving surgical methods, and developing non-surgical strategies represent key issues in the surgical management of gastric cancer in the era of immunotherapy.
5.Study of labor analgesia on primipara pelvic floor muscle function, pelvic floor muscle status and pain
Zhi JIA ; Li LI ; Haiyan LIU ; Liming WANG ; Qun LIU ; Jingjing CAO ; Yongning ZHU
Chinese Journal of Postgraduates of Medicine 2024;47(8):742-746
Objective:To explore the protective effect of labor analgesia on pelvic floor muscle function of primipara after vaginal delivery.Methods:A total of 140 cases of primipara with vaginal delivery admitted to the Affiliated Hospital of Jining Medical College from March to August 2022 were selected retrospectively, and they were divided into control group (routine delivery) and observation group (painless delivery) according to the intention of delivery, each group with 70 cases. Labor pain, pelvic floor muscle function score and pelvic floor muscle status at 6 weeks postpartum, Female Sexual Function Scale (FSFI) score at 3 months postpartum and reported postpartum symptoms were compared between the two groups.Results:The scores of Visual Analogue Scale (VAS) at immediately after gastric antral empting, after drinking carbohydrates (5, 30, 60, 120 min) and at full opening of uterine orifice in the observation group were lower than those in control group, there were statistical differences ( P<0.05). At 6 weeks postpartum, the maximum muscle voltage of pelvic floor muscle and the average muscle voltage of continuous contraction of pelvic floor muscle for 60 s in the observation group were higher than those in control group: (20.97 ± 2.64) μV vs. (17.31 ± 2.48) μV, (17.33 ± 3.01) μV vs. (13.42 ± 2.77) μV; the mobility of bladder neck and the hiatus area of levator anal muscle in resting state in the observation group were lower than those in the control group: (27.15 ± 3.55) mm vs. (31.05 ± 4.75) mm, (9.97 ± 2.12)cm 2 vs. (11.57 ± 2.84) cm 2, there were statistical differences ( P<0.05). At 6 weeks postpartum, the scores of static pre-stage, static post-stage, type Ⅰ muscle fiber, type Ⅱ muscle fiber and total scores in the observation group were higher than those in the control group: (67.21 ± 12.54) scores vs. (54.17 ± 10.84) scores, (69.12 ± 14.11) scores vs. (56.47 ± 11.24) scores, (63.54 ± 11.45) scores vs. (50.97 ± 10.74) scores, (57.15 ± 8.15) scores vs. (49.76 ± 6.44) scores, (64.25 ± 12.14) scores vs. (57.84 ± 20.57) scores, there were statistical differences ( P<0.05). At 6 weeks postpartum, the scores of FSFI in the observation group were higher than those in the control group ( P<0.05). The rate of urine leakage, fever and mattress sweat reported in the observation group were lower than those in the control group: 22.86%(16/70) vs. 40.00%(28/70), 15.71%(11/70) vs. 30.00%(21/70), 30.00%(21/70) vs. 47.14%(33/70), there were statistical differences ( χ2 = 4.77, 4.05, 4.34, P<0.05). Conclusions:Labor analgesia can effectively shorten labor process, relieve labor pain and protect pelvic floor muscle function during vaginal labor in primipara.
6.Inhibition of Gpx4-mediated ferroptosis by curcumin attenuates acute lung injury in rats with sepsis
Lei WANG ; Xin KUAI ; Qingsong LI ; Yongning LI
Chinese Journal of Immunology 2024;40(10):2116-2120
Objective:To investigate the involvement of ferroptosis mediated by glutathione peroxidase 4(Gpx4)in acute lung injury in rats with sepsis,as well as the intervention mechanism of curcumin(Cur).Methods:Twenty-four rats were randomly divided into three groups,with 8 rats in each group:Sham group,Sepsis group and Cur group.The rat model of acute lung injury in sepsis was established by cecal ligation and puncture(CLP).The Sham group only underwent laparotomy and closure.Both Sepsis group and Cur group underwent CLP,Cur group was injected with curcumin(200 mg/kg)intraperitoneally 1 hour after modeling,and the administra-tion was repeated 24 hours later.The lung tissues of the rats were sampled 48 hours after surgery,and the wet/dry weight of lung tissue ratio(W/D)of lung tissues in each group was measured.Morphological changes of lung tissues were observed by HE staining.The con-tents of GSH,MDA,and Fe2+and the levels of inflammatory factors including TNF-α,IL-6,and IL-1β in the lung tissues were mea-sured using test kits.Western blot was used to detect the expressions of nuclear factor E2-related factor 2(Nrf2)and the key regulatory protein of ferroptosis Gpx4.Apoptosis of alveolar epithelial cells was detected by TUNEL method.Ultrastructural changes of alveolar epithelial cells were observed by transmission electron microscopy.Results:Compared with the Sham group,lung tissues in the Sepsis group showed an increased W/D(P<0.05),significantly higher levels of inflammatory factors TNF-α,IL-6,and IL-1β and contents of MDA and Fe2+(P<0.05),decreased content of GSH,up-regulated expression of Nrf2,and down-regulated expression of Gpx4(P<0.05),the type Ⅱ alveolar epithelial cells were seen to be edematous,congested,and infiltrated with inflammatory cells via light microscopy,and ferroptosis signs such as mitochondrial crinkling,thickened bilayer membrane density,and reduced or broken cristae were seen via transmission electron microscopy.Compared with Sepsis group,lung tissues in the Cur group showed decreased W/D(P<0.05),lower levels of TNF-α,IL-6 and IL-1β,lower contents of MDA and Fe2+,increased content of GSH,down-regulated expression of Nrf2,and up-regulated expression of Gpx4(P<0.05),the pathological changes of lung tissues were significantly reduced.Conclusion:Curcumin reduces sepsis-induced acute lung injury in rats,and the mechanism is related to inhibiting inflamma-tory response and GPX4-mediated ferroptosis.
7.Magnetic Resonance Imaging-Related Anatomic and Functional Parameters for the Diagnosis and Prognosis of Chiari Malformation Type I: A Systematic Review and Meta-analysis
Zairan WANG ; Zhimin LI ; Shiyuan HAN ; Xianghui HU ; Siyuan PANG ; Yongning LI ; Jun GAO
Neurospine 2024;21(2):510-524
Objective:
Imaging parameters of Chiari malformation type I (CMI) development are not well established. This study aimed to collect evidence of general or specific imaging measurements in patients with CMI, analyze indicators that may assist in determining the severity of CMI, and guide its diagnosis and treatment.
Methods:
A comprehensive search was conducted across various databases including the Cochrane Library, PubMed, MEDLINE, Scopus, and Embase, covering the period from January 2002 to October 2023, following predefined inclusion criteria. Meta-analyses were performed using RevMan (ver. 5.4). We performed a quantitative summary and systematic analysis of the included studies. This study was registered in the PROSPERO (International Prospective Register of Systematic Reviews) prior to initiation (CRD42023415454).
Results:
Thirty-three studies met our inclusion criteria. The findings indicated that out of the 14 parameters examined, 6 (clivus length, basal angle, Boogard’s angle, supraocciput lengths, posterior cranial fossa [PCF] height, and volume) exhibited significant differences between the CMI group and the control group. Furthermore, apart from certain anatomical parameters that hold prognostic value for CMI, functional parameters like tonsillar movement, obex displacement, and cerebrospinal fluid dynamics serve as valuable indicators for guiding the clinical management of the disease.
Conclusion
We collated and established a set of linear, angular, and area measurements deemed essential for diagnosing CMI. However, more indicators can only be analyzed descriptively for various reasons, particularly in prognostic prediction. We posit that the systematic assessment of patients’ PCF morphology, volume, and other parameters at a 3-dimensional level holds promising clinical application prospects.
8.Magnetic Resonance Imaging-Related Anatomic and Functional Parameters for the Diagnosis and Prognosis of Chiari Malformation Type I: A Systematic Review and Meta-analysis
Zairan WANG ; Zhimin LI ; Shiyuan HAN ; Xianghui HU ; Siyuan PANG ; Yongning LI ; Jun GAO
Neurospine 2024;21(2):510-524
Objective:
Imaging parameters of Chiari malformation type I (CMI) development are not well established. This study aimed to collect evidence of general or specific imaging measurements in patients with CMI, analyze indicators that may assist in determining the severity of CMI, and guide its diagnosis and treatment.
Methods:
A comprehensive search was conducted across various databases including the Cochrane Library, PubMed, MEDLINE, Scopus, and Embase, covering the period from January 2002 to October 2023, following predefined inclusion criteria. Meta-analyses were performed using RevMan (ver. 5.4). We performed a quantitative summary and systematic analysis of the included studies. This study was registered in the PROSPERO (International Prospective Register of Systematic Reviews) prior to initiation (CRD42023415454).
Results:
Thirty-three studies met our inclusion criteria. The findings indicated that out of the 14 parameters examined, 6 (clivus length, basal angle, Boogard’s angle, supraocciput lengths, posterior cranial fossa [PCF] height, and volume) exhibited significant differences between the CMI group and the control group. Furthermore, apart from certain anatomical parameters that hold prognostic value for CMI, functional parameters like tonsillar movement, obex displacement, and cerebrospinal fluid dynamics serve as valuable indicators for guiding the clinical management of the disease.
Conclusion
We collated and established a set of linear, angular, and area measurements deemed essential for diagnosing CMI. However, more indicators can only be analyzed descriptively for various reasons, particularly in prognostic prediction. We posit that the systematic assessment of patients’ PCF morphology, volume, and other parameters at a 3-dimensional level holds promising clinical application prospects.
9.Magnetic Resonance Imaging-Related Anatomic and Functional Parameters for the Diagnosis and Prognosis of Chiari Malformation Type I: A Systematic Review and Meta-analysis
Zairan WANG ; Zhimin LI ; Shiyuan HAN ; Xianghui HU ; Siyuan PANG ; Yongning LI ; Jun GAO
Neurospine 2024;21(2):510-524
Objective:
Imaging parameters of Chiari malformation type I (CMI) development are not well established. This study aimed to collect evidence of general or specific imaging measurements in patients with CMI, analyze indicators that may assist in determining the severity of CMI, and guide its diagnosis and treatment.
Methods:
A comprehensive search was conducted across various databases including the Cochrane Library, PubMed, MEDLINE, Scopus, and Embase, covering the period from January 2002 to October 2023, following predefined inclusion criteria. Meta-analyses were performed using RevMan (ver. 5.4). We performed a quantitative summary and systematic analysis of the included studies. This study was registered in the PROSPERO (International Prospective Register of Systematic Reviews) prior to initiation (CRD42023415454).
Results:
Thirty-three studies met our inclusion criteria. The findings indicated that out of the 14 parameters examined, 6 (clivus length, basal angle, Boogard’s angle, supraocciput lengths, posterior cranial fossa [PCF] height, and volume) exhibited significant differences between the CMI group and the control group. Furthermore, apart from certain anatomical parameters that hold prognostic value for CMI, functional parameters like tonsillar movement, obex displacement, and cerebrospinal fluid dynamics serve as valuable indicators for guiding the clinical management of the disease.
Conclusion
We collated and established a set of linear, angular, and area measurements deemed essential for diagnosing CMI. However, more indicators can only be analyzed descriptively for various reasons, particularly in prognostic prediction. We posit that the systematic assessment of patients’ PCF morphology, volume, and other parameters at a 3-dimensional level holds promising clinical application prospects.
10.Magnetic Resonance Imaging-Related Anatomic and Functional Parameters for the Diagnosis and Prognosis of Chiari Malformation Type I: A Systematic Review and Meta-analysis
Zairan WANG ; Zhimin LI ; Shiyuan HAN ; Xianghui HU ; Siyuan PANG ; Yongning LI ; Jun GAO
Neurospine 2024;21(2):510-524
Objective:
Imaging parameters of Chiari malformation type I (CMI) development are not well established. This study aimed to collect evidence of general or specific imaging measurements in patients with CMI, analyze indicators that may assist in determining the severity of CMI, and guide its diagnosis and treatment.
Methods:
A comprehensive search was conducted across various databases including the Cochrane Library, PubMed, MEDLINE, Scopus, and Embase, covering the period from January 2002 to October 2023, following predefined inclusion criteria. Meta-analyses were performed using RevMan (ver. 5.4). We performed a quantitative summary and systematic analysis of the included studies. This study was registered in the PROSPERO (International Prospective Register of Systematic Reviews) prior to initiation (CRD42023415454).
Results:
Thirty-three studies met our inclusion criteria. The findings indicated that out of the 14 parameters examined, 6 (clivus length, basal angle, Boogard’s angle, supraocciput lengths, posterior cranial fossa [PCF] height, and volume) exhibited significant differences between the CMI group and the control group. Furthermore, apart from certain anatomical parameters that hold prognostic value for CMI, functional parameters like tonsillar movement, obex displacement, and cerebrospinal fluid dynamics serve as valuable indicators for guiding the clinical management of the disease.
Conclusion
We collated and established a set of linear, angular, and area measurements deemed essential for diagnosing CMI. However, more indicators can only be analyzed descriptively for various reasons, particularly in prognostic prediction. We posit that the systematic assessment of patients’ PCF morphology, volume, and other parameters at a 3-dimensional level holds promising clinical application prospects.

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