Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.

BACKGROUND:Stage Ⅱ Kümmell's disease has traditionally been treated with percutaneous kyphoplasty,but this approach is associated with a high incidence of complications such as poor postoperative pain relief,suboptimal cement dispersion,and adjacent vertebral fractures.Studies have shown that cement augmentation of the injured vertebra combined with posterior spinal canal decompression and short-segment fixation has a good effect on the treatment of Kümmell's disease with neurological symptoms.OBJECTIVE:To compare the outcomes of cement-augmented short-segment percutaneous pedicle screw fixation with those of percutaneous kyphoplasty for the treatment of stage Ⅱ Kümmell's disease.METHODS:From January 2020 to January 2023,a total of 49 patients with stage Ⅱ Kümmell's disease from Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine were included in this study,with 15 males and 34 females.According to the treatment method,the patients were divided into the trial group(n=23)and the control group(n=26).The patients in the trial group received cement-augmented short-segment percutaneous pedicle screw fixation,and the patients in the control group received percutaneous kyphoplasty.The postoperative complications were recorded,and the spinal Cobb angle and the ratio of the anterior edge height of the injured vertebra were compared between the two groups at 1,6,12 weeks,6,and 12 months after surgery.The Oswestry disability index and lumbar visual analog score were compared at 1 week and 12 months after surgery.RESULTS AND CONCLUSION:(1)All patients in the two groups were followed up for more than 12 months after surgery.Five patients in the control group had adjacent vertebral fractures,three patients had severe kyphosis,and one patient in the trial group had postoperative incision complications.(2)Compared with preoperative data,the spinal Cobb angle and the ratio of the anterior edge height of the injured vertebra in both groups were significantly improved after surgery(P＜0.05).The spinal Cobb angle of the trial group was lower than that of the control group at 1,6,12 weeks,6,and 12 months after surgery(P＜0.05),and the ratio of the anterior edge height of the injured vertebra in the trial group was higher than that of the control group at 1,6,12 weeks,6,and 12 months after surgery(P＜0.05).(3)Compared with preoperative data,the Oswestry disability index and lumbar visual analog scale score of the two groups were significantly improved after surgery(P＜0.05).The Oswestry disability index and lumbar visual analog scale score of the trial group were lower than those of the control group at 1 week and 12 months after surgery(P＜0.05).(4)The results show that compared with percutaneous kyphoplasty,cement-augmented short-segment percutaneous pedicle screw fixation for stage Ⅱ Kümmell's disease can better restore the height of the affected vertebra,maintain the shape of the affected vertebra,improve spinal function,and alleviate lumbar pain.

BACKGROUND:Stage Ⅱ Kümmell's disease has traditionally been treated with percutaneous kyphoplasty,but this approach is associated with a high incidence of complications such as poor postoperative pain relief,suboptimal cement dispersion,and adjacent vertebral fractures.Studies have shown that cement augmentation of the injured vertebra combined with posterior spinal canal decompression and short-segment fixation has a good effect on the treatment of Kümmell's disease with neurological symptoms.OBJECTIVE:To compare the outcomes of cement-augmented short-segment percutaneous pedicle screw fixation with those of percutaneous kyphoplasty for the treatment of stage Ⅱ Kümmell's disease.METHODS:From January 2020 to January 2023,a total of 49 patients with stage Ⅱ Kümmell's disease from Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine were included in this study,with 15 males and 34 females.According to the treatment method,the patients were divided into the trial group(n=23)and the control group(n=26).The patients in the trial group received cement-augmented short-segment percutaneous pedicle screw fixation,and the patients in the control group received percutaneous kyphoplasty.The postoperative complications were recorded,and the spinal Cobb angle and the ratio of the anterior edge height of the injured vertebra were compared between the two groups at 1,6,12 weeks,6,and 12 months after surgery.The Oswestry disability index and lumbar visual analog score were compared at 1 week and 12 months after surgery.RESULTS AND CONCLUSION:(1)All patients in the two groups were followed up for more than 12 months after surgery.Five patients in the control group had adjacent vertebral fractures,three patients had severe kyphosis,and one patient in the trial group had postoperative incision complications.(2)Compared with preoperative data,the spinal Cobb angle and the ratio of the anterior edge height of the injured vertebra in both groups were significantly improved after surgery(P＜0.05).The spinal Cobb angle of the trial group was lower than that of the control group at 1,6,12 weeks,6,and 12 months after surgery(P＜0.05),and the ratio of the anterior edge height of the injured vertebra in the trial group was higher than that of the control group at 1,6,12 weeks,6,and 12 months after surgery(P＜0.05).(3)Compared with preoperative data,the Oswestry disability index and lumbar visual analog scale score of the two groups were significantly improved after surgery(P＜0.05).The Oswestry disability index and lumbar visual analog scale score of the trial group were lower than those of the control group at 1 week and 12 months after surgery(P＜0.05).(4)The results show that compared with percutaneous kyphoplasty,cement-augmented short-segment percutaneous pedicle screw fixation for stage Ⅱ Kümmell's disease can better restore the height of the affected vertebra,maintain the shape of the affected vertebra,improve spinal function,and alleviate lumbar pain.

Objective:To investigate the protective effects and mechanism of exogenous milk fat globule-epidermal growth factor 8(MFG-E8) on intestinal injury and ferroptosis in mice with acute pancreatitis (AP) and its mechanism.Methods:A total of 24 male C57 BL/6 mice were randomly divided into the normal control group, AP group, AP+ MFG-E8 group (MFG-E8 group), and AP+ MFG-E8+ cilengitide group (cilengitide group), with 6 mice in each group according to the random number table. The mice of normal control group were intraperitoneally injected with 0.9% sodium chloride solution. In the AP group, MFG-E8 group, and cilengitide group, the mice were intraperitoneally injected with 8% L-arginine twice at 1-hour intervals to induce the AP model. In the MFG-E8 group, mice were intraperitoneally injected with 20 g/kg of MFG-E8 at 2 hours after L-arginine injection. In the cilengitide group, mice were intraperitoneally injected with 20 mg/kg of cilengitide at 1 hour after the L-arginine injection, and 20 g/kg of MFG-E8 1 hour later. The mice were sacrificed and blood samples and intestinal tissues were collected at 72 hours after the first L-arginine injection. Hematoxylin-eosin staining was used to evaluate intestinal tissue injury. Myeloperoxidase (MPO) immunofluorescence staining was performed to detect neutrophils in intestinal tissues.Adenosinetriphosphate (ATP) levels were examined to detect changes in mitochondrial function. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were tested to check the level of intestinal oxidative stress. Dihydroethidium (DHE) fluorescent probe was used to label the oxygen free radicals in intestinal tissues. The expression of glutathione peroxidase 4 (GSH-Px4), solute carrier family 7 member 11 (also named xCT), and ferroptosos suppressor protein-1 (FSP-1) in intestinal tissues were detected by western blotting. Indepent-samples t-test, one-way ANOVA, and Student-Newman-Keuls test were performed for statistical analysis. Results:Intestinal tissue injury and inflammatory cell infiltration in mice were induced by intraperitoneal injection of L-arginine. Compared with those of AP model group, the intestinal pathology score, MPO fluorescence quantification and DHE fluorescence density of MFG-E8 group were significantly decreased (3.93±0.57 vs. 1.73±0.74, (26.33±4.49)/field vs. (11.00±3.27)/field, (39.67±5.79)/field vs. (12.33±3.68)/field), while the contents of ATP, MDA and SOD were increased ((77.09±8.52) μmol/g vs. (119.87±6.83) μmol/g, (0.10±0.01) μmol/g vs. (0.17±0.02) μmol/g, (105.67±6.93) U/mg vs. (144.49±18.55) U/mg), and the differences were statistically significant ( t=3.33, 3.93, 5.63, 8.77, 6.54, 4.38; all P<0.05). The results of Western blotting showed that GSH-Px4, xCT, and FSP-1 in the intestinal tissue of AP mice in the MFG-E8 group were all elevated compared with those of AP group, the relative expression levels were 1.22±0.19 vs. 0.55±0.09, 1.48±0.12 vs. 0.34±0.08, and 0.48±0.08 vs. 0.04±0.03, and the differences were statistically significant ( t=5.60, 14.39, 9.53; all P<0.05). Intraperitoneal injection of integrin αVβ3 receptor inhibitor cilengitide effectively antagonized the protective effects of MFG-E8 on intestinal injury in AP mice. Compared with MFG-E8 group, the histopathological score, MPO quantification and DHE fluorescence density of cilengitide group (3.53±0.50, (27.67±6.02)/field, and (31.33±3.86)/field, respectively) all increased, the expression of ATP, MDA and SOD were inhibited ((77.41±8.51) μmol/g, (0.19±0.04) mol/g, (100.46±8.15) U/mg); and GSH-Px4, xCT and FSP-1 all decreased, with the relative expression levels of 0.59±0.11, 0.16±0.06, and 0.10±0.03, respectively, and the differences were statistically significant ( t=3.02, 3.44, 5.04, 8.70, 4.01, 4.86, 5.05, 17.47, 8.34; all P<0.05). Conclusion:MFG-E8 alleviates intestinal oxidative stress and ferroptosis by integrin αVβ3 receptor, thereby reducing intestinal injury and inflammation in AP mice.

Objective To investigate the potential mechanism of circRNA SAMD8(circ-SAMD8) in development of pancreatic ductal adenocarcinoma (PDAC). Methods The expression profile of circRNAs in PDAC tissues was analyzed based on Microarray data (GSE79634). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of circ-SAMD8 (hsa_circ_0006148) in PDAC tissues and cells (CFPAC-1 and PANC-1).The target microRNA (miRNA) of circ-SAMD8 and its downstream mRNA were predicted by bioinformatics analysis, and identified by double luciferase reporter gene assay. The proliferation ability of PDAC cells was detected by MTT assay and colony formation assay. The expression levels of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax were detected by Western blot. The percentage of apoptotic cells was detected by flow cytometry. Results The expression levels of circ-SAMD8 in PDAC tissues and cells were significantly lower than those in paracancer tissues and normal cells (P < 0.05). Overexpression of circ-SAMD8 could effectively promote apoptosis of PDAC cells and inhibited proliferation of PDAC cells.Dual luciferase reporter gene experiments showed that miR-223-3p was a potential interacting molecule of circ-SAMD8, and the downstream mRNA target of miR-223-3p was RHOB. The miR-223-3p was abnormally overexpressed in PDAC tissues and cells, accompanied by low RHOB expression. In PDAC cells transfected with miR-223-3p mimics or sh-circ-SAMD8, RHOB expression was significantly decreased, proliferation ability was enhanced, and apoptosis rate was decreased. Conclusion Circ-SAMD8 regulates the expression of RHOB downstream by sponging miR-223-3p, and effectively inhibits the occurrence and development of PDAC.

Sarcopenia is an age-related degenerative disease.Type 2 diabetes mellitus(T2DM)is a senile disease.These two diseases often coexist.Early identification and intervention of T2DM combined with sarcopenia can improve the quality of life to a certain extent.This article reviews the research progress of T2DM combined with sarcopenia.

A 51-year-old patient with yolk sac tumor received BEP regimen [intramuscular injection of bleomycin 30 mg, on day 2, 9, and 16), IV infusions of etoposide 100 mg/(m 2· d) and cisplatin 20 mg/m 2 on day 1 to 5] after comprehensive staging surgery for ovarian cancer, 21 days was a cycle. No interstitial changes in her lungs were found on chest CT before operation and before each chemotherapy cycle. On the 12th day of the 4th treatment cycle, the patient developed cough, expectoration. Laboratory tests showed white blood cell count 0.63×10 9/L, neutrophil count 0.16×10 9/L, hemoglobin 82 g/L, platelet count 42×10 9/L. Chest CT showed a little grid shadow in both lungs. The patient was diagnosed with myelosuppression (grade Ⅳ) and pulmonary infection. Bleomycin treatment in the 3rd week of the 4th cycle was stopped. Granulocyte colony stimulating factor, thrombopoietin, meropenem, bromhexine, blood transfusion, fluid infusion, and other symptomatic and supportive treatment were given. Bone marrow suppression was relieved, but cough and expectoration were aggravated. Chest CT showed a little grid shadow in both lungs. Glucocorticoid and amphotericin B were added, and non-invasive ventilator assisted ventilation and other symptomatic support treatments were given, but the patient′s condition worsened, and respiratory failure and death occurred 45 days after the 4th cycle of chemotherapy.

A 51-year-old patient with yolk sac tumor received BEP regimen [intramuscular injection of bleomycin 30 mg, on day 2, 9, and 16), IV infusions of etoposide 100 mg/(m 2· d) and cisplatin 20 mg/m 2 on day 1 to 5] after comprehensive staging surgery for ovarian cancer, 21 days was a cycle. No interstitial changes in her lungs were found on chest CT before operation and before each chemotherapy cycle. On the 12th day of the 4th treatment cycle, the patient developed cough, expectoration. Laboratory tests showed white blood cell count 0.63×10 9/L, neutrophil count 0.16×10 9/L, hemoglobin 82 g/L, platelet count 42×10 9/L. Chest CT showed a little grid shadow in both lungs. The patient was diagnosed with myelosuppression (grade Ⅳ) and pulmonary infection. Bleomycin treatment in the 3rd week of the 4th cycle was stopped. Granulocyte colony stimulating factor, thrombopoietin, meropenem, bromhexine, blood transfusion, fluid infusion, and other symptomatic and supportive treatment were given. Bone marrow suppression was relieved, but cough and expectoration were aggravated. Chest CT showed a little grid shadow in both lungs. Glucocorticoid and amphotericin B were added, and non-invasive ventilator assisted ventilation and other symptomatic support treatments were given, but the patient′s condition worsened, and respiratory failure and death occurred 45 days after the 4th cycle of chemotherapy.

Objective:To investigate the possible role of long non-coding RNA (LncRNA) 00602 in promoting browning in adipocytes induced by adenovirus type 36 (Ad36).Methods:According to Ad36 infection, adipose tissue samples of obese patients were divided into Ad36-negative group and Ad36-infected group. Realtime fluorescent quantitative PCR (qRT-PCR) was used to detect the changes in the expression of LncRNA00602 mRNA in omental adipose tissue of the two groups, and analyze the differences between the two groups. The correlation between waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triacylglyceride and other indicators of the patients in the group with LncRNA00602 mRNA expression were analyzed. HE staining was used to detect the size of adipocytes in the omental adipose tissue of the Ad36 negative group and the Ad36 infection group. qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels of uncoupling protein 1 (UCP1) and PR domain containing 16 (PRDM16) in omental adipose tissue of two groups of patients. Human adipose-derived stem cells (hADSC) were isolated and cultured, using Ad36 to induce differentiation, and divided into control group and LncRNA00602 knockdown group. On 0, 2, and 4 days after LncRNA00602 knockdown, fluoroboron dipyrrole (BODIPY) and mitochondrial red fluorescence (Mito-Tracker Red) were used to stain intracellular lipid droplets and mitochondria. At the same time, qRT-PCR and Western blotting were used to detect changes in the expression of UCP1 and PRDM16.Results:The expression of LncRNA00602 gene in the Ad36 infection group was higher than that in the Ad36 negative group (all P<0.05). The expression of LncRNA00602 in the Ad36 negative group was not significantly different from the above clinical indicators, while the expression of LncRNA00602 was negatively correlated with serum fasting blood glucose and triacylglyceride ( r=-0.522, -0.486, P<0.05) in the Ad36 infection group; HE staining showed that the average adipocyte area of the Ad36 infection group was smaller than that of the Ad36 negative group. At the same time, UCP1 and PRDM16 gene expression were higher than the negative group (all P<0.05). At the cellular level, on the 2nd and 4th days after knockdown of LncRNA00602, the lipid droplet area of adipocytes in the LncRNA00602 knockdown group was larger than that of the control group, the number of mitochondria decreased compared with the control group, and difference was statistically significant ( P<0.05 or P<0.01); Compared with the control group, there was significantly lower expression of the browning marker genes UCP1, PRDM16, and protein in the adipocytes in the LncRNA00602 knockdown group (all P<0.05). Conclusion:In Ad36-induced adipocyte differentiation, LncRNA00602 may positively regulate the expression of UCP1, PRDM16 and lipid droplet metabolism, and promote the browning of adipocytes.

Objective To investigate the effect of flash glucose monitoring (FGM) on ambulatory glucose profile of only oral antidiabetic drugs treated patients with type 2 diabetes mellitus. Methods Twenty-eight type 2 diabetic mellitus patients with only oral antidiabetic drugs treatment from August 2017 to January 2018 were enrolled. All the patients were exposed to FGM for 14 d without changing the original treatment and encouraged to manage self-behavior by adjusting diet and activity based on the blood glucose data obtained from the real-time scanning. The changes in glucose profile during the FGM period were observed, including estimated glycated hemoglobin (HbA1c), standard deviation of blood glucose, variable coefficient of blood glucose, mean amplitude of glycemic excursions, time in range (blood glucose 3.9 to 10.0 mmol/L), area under the curve hyperglycemia (blood glucose> 10.0 mmol/L) and area under the curve hypoglycemia (blood glucose<3.9 mmol/L). The blood glucose levels on second day and thirteenth day were used as baseline and end point respectively. Results All of the 28 patients did not change their anti-diabetic drug therapy and there were no adverse events occurred. The estimated HbA1c was significantly lower than the baseline HbA1c: (6.90 ± 1.48)% vs. (7.57 ± 1.35)%, and there was statistical difference (P = 0.004). The standard deviation of blood glucose, variable coefficient of blood glucose, mean amplitude of glycemic excursions, area under the curve hyperglycemia and area under the curve hypoglycemia at end were significantly lower than those at baseline: (2.07 ± 0.86) mmol/L vs. (2.44 ± 0.86) mmol/L, 0.26 ± 0.11 vs. 0.30 ± 0.11, (5.32 ± 2.75) mmol/L vs. (6.76 ± 3.06) mmol/L, 265 (0, 1 310) vs. 351 (107, 2 177) and 0 (0, 0) vs. 0 (0, 19), the time in range at end was significantly higher than that at baseline: (1 069 ± 386) min vs. (921 ± 449) min, and there were statistical differences (P＜0.05 or＜0.01). The rate of scanning was (12.92 ± 4.87) times/d. Conclusions FGM could be applied by type 2 diabetic mellitus patients to make self-glycemic management without changing therapy, reduce the estimated HbA1c,and hypoglycemia, and improve the glucose fluctuations, which may result from real-time scanning to find abnormal glycemia and adjust daily behavior.