The observation and nursing care of a case of fulminant type 1 diabetes mellitus related to immune checkpoint inhibitor were summarized.To improve prognosis of the disease and guarantee patients'safety,key points of nursing are as following:sufficient early liquid resuscitation to improve renal perfusion;dynamic monitoring and summary of blood glucose changes,implementing a target-oriented blood glucose management program;providing nutritional support;regularly follow-up and health education.After positive rescue and careful nursing,no serious complications occurred;blood glucose was controlled well;nutritional status was improved;the patient was in stable conditions and was discharged.Telephone follow-up of the patient for 3 months showed stable blood glucose and good condition.

Objective:To investigate the predictive value of plasma exosomal microRNA (miR)-124-3p in the risk of chronic cerebral hypoperfusion (CCH).Methods:A case-control study. Thirty patients who were diagnosed with CCH (CCH group) based on cranial artery spin labeling (ASL) in the neurology outpatient clinic of Sichuan Provincial People′s Hospital from March 2022 to June 2022 and 30 healthy volunteers (control group) were included. Age, gender, smoking history, alcohol consumption history, diabetes history, hypertension, hyperlipidemia history, uric acid, fasting blood glucose, homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups. Comparisons of categorical variables were analyzed by either χ2 test or Fisher′s exact test. If the data of continuous variables followed a normal distribution, they were expressed as mean±standard deviation (SD) and compared by t-test for two independent samples; otherwise, the data were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test for comparison between two groups. The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson′s correlation. Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH, and corresponding odds ratios ( OR) and 95% confidence intervals ( CI) were calculated. P<0.05 was considered significant. Results:There was no significant difference in age (64±8 vs. 60±8 years old), gender (33.3% vs. 30.0%), history of smoking (20.0% vs. 3.3%), alcohol consumption (20.0% vs. 6.7%), diabetes mellitus (13.3% vs. 13.3%), hypertension (53.3% vs. 30.0%), history of hyperlipidemia (46.7% vs. 36.7%), uric acid (288±60 vs.319±67 μmol/L), and fasting glucose [4.99(4.63, 5.91) vs. 5.28(5.09, 6.05) mmol/L] and homocysteine [11.35(10.18, 13.08) vs.11.00(9.78, 13.03) μmol/L] between the CCH and control groups ( P>0.05). Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group [13.08 (8.59, 21.55) vs. 2.85 (1.44, 5.10), respectively; U=169.50, P<0.001]. Pearson′s correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH ( r=-0.932, P<0.001). Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH ( OR=1.169,95% CI 1.063-1.286, P=0.001). Conclusions:The expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH. Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.

Objective:To investigate the effect of electroacupuncture (EA) on synaptic damage to hippocampal neurons in rats with sepsis-associated encephalopathy (SAE).Methods:A total of 48 healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (Sham group), SAE group, SAE+ EA group and SAE+ sham EA group (SAE+ SEA group). SAE was induced by cecal ligation and puncture in anesthetized rats.Baihui, Quchi and Zusanli acupoints were stimulated with constant voltage (2/15 Hz) and disperse-dense waves for 30 min once a day for 10 consecutive days, and the stimulation intensity was defined as less than 1.5 mA causing slight muscle contraction at 2 days before operation in group SAE+ EA.In group SAE+ SEA, stimulating electrodes were placed at the points 5 mm lateral to the corresponding acupoints, but no electrical stimulation was applied.On day 14 after operation, the rats were sacrificed, and hippocampal tissues were obtained and stained with haematoxylin and eosin for examination of the pathological changes in the hippocampal CA1 region, for determination of the expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD-95) (by Western blot), and for calculation of dendritic spine density of neurons in the hippocampal CA1 area (using Golgi staining) and pyramidal neurons counts. Results:Compared with Sham group, the expression of SYN and PSD-95 in hippocampus was significantly decreased, and the basal and apical dendrite spine density of neurons in hippocampal CA1 area was decreased in SAE group, the expression of PSD-95 was decreased, and the apical dendrite spine density of neurons in the hippocampal CA1 area was increased in SAE+ EA group, and the pyramidal neuron counts in the hippocampal CA1 area were reduced in SAE, SAE+ EA and SAE+ SEA groups ( P<0.05). Compared with group SAE, the expression of SYN and PSD-95 was significantly up-regulated, the basal and apical dendrite spine density of neurons in the hippocampal CA1 area was increased and the pyramidal neuron counts were increased in group SAE+ EA ( P<0.05), the pathological damage of hippocampal CA1 area was alleviated and no significant change was found in the parameters mentioned above in group SAE+ SEA ( P>0.05). Compared with group SAE+ EA, the expression of SYN and PSD-95 was down-regulated, the basal and apical dendrite spine density of neurons in the hippocampal CA1 area was decreased, and the pyramidal neuron counts were reduced in SAE+ SEA group ( P<0.05). Conclusion:The mechanism by which EA alleviates SAE may be related to reducing synaptic damage to hippocampal neurons in rats.

OBJECTIVE：To study the effe cts of the water extract from Carpesium cernuum （AECC）on the proliferation ， metastasis and invasion of prostate cancer PC 3 cells. METHODS ：Cells were divided into control group and different concentration groups of AECC （5，10，20，40，80 μg/L），and then treated with relevant medicine or medium for different time （24，48，72 h）. The survival rates of cells were detected. Cells were divided into control group ，and AECC low ，medium and high concentration groups（20，40，80 μg/L）. After cultured for 24 h，Hoechst 33258 staining and flow cytometry were used to detect the apoptosis of cells. The number of cell metastasis and invasion were detected by Transwell assay. RT-qPCR and Western blot assay were applied to detect the mRNA and protein expression of β-catenin signaling pathway related migration and apoptosis proteins （β-catenin， MMP-7，c-Myc，caspase-3，Bcl-2 and Bax ）in AECC low and medium concentration groups. RESULTS ：With the increase of the concentration and culture time ，the survival rates of cells in AECC different concentration groups were significantly lower than control group （P＜0.05 or P＜0.01），and showed a decreasing trend. Compared with control group ，the early apoptosis rate （except the medium concentration group ）and the number of cell metastasis and invasion in AECC groups ，the mRNA and protein expression of MMP- 7，c-Myc（except for the low concentration group ）and Bcl- 2（except for mRNA of the low concentration group）in AECC low and medium concentration groups were decreased significantly （P＜0.05 or P＜0.01）. Late apoptosis rate of AECC groups ，the mRNA and protein expression of β-catenin，caspases-3（except for the low concentration group ），Bax（except for mRNA of the low concentration group ）in AECC low and medium concentration groups were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：AECC could inhibit the proliferation ，metastasis and invasion of PC 3 cells；the mechanism of which may be associated with regulating the expression of β-catenin signaling pathway related migration and apoptotic factors.

Objective:To investigate the application values of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and cytogenetic testing in newly diagnosed multiple myeloma.Methods:A total of 280 patients with multiple myeloma who were newly diagnosed in Tianjin KingMed Diagnosis Center from September 2018 to August 2019 were collected. The bone marrow biopsy was carried out according to the routine method, and bone marrow morphology, bone marrow immunohistochemistry, flow cytometry immunophenotyping, FISH and cytogenetic testing were performed. The detection results of each method were compared.Results:In 280 patients, the bone marrow immunohistochemistry results showed that the median ratio of plasma cells was higher than those of bone marrow morphology (20 cases, 0.675 vs. 0.300) and flow cytometry (47 cases, 0.650 vs. 0.147), and the differences were statistically significant ( Z = -3.883, P < 0.01; Z = -5.947, P < 0.01). Flow cytometry results showed that the positive rates of CD38, CD138, κ, λ, CD56 and CD19 were 100.0% (280/280), 100.0% (280/280), 57.5% (161/280), 42.5% (119/280), 62.1% (174/280) and 19.3% (54/280); bone marrow immunohistochemistry results showed that the positive rates of CD38, CD138, κ, λ and CD56 were 98.9% (277/280), 98.2% (275/280), 57.5% (161/280), 42.5% (119/280) and 62.1% (174/280); there was no statistical difference between the two detection methods in the detection coincidence rate of the same detection index (all P > 0.05). Among patients who underwent FISH detection, the detection rate of gene abnormalities was 69.9% (93/133); the detection rate of abnormalities by direct fluorescence in situ hybridization (D-FISH) was 42.9% (57/133); the detection rate of abnormalities by CD138 immunomagnetic sorting myeloma cells (MACS)-FISH was 82.7% (110/133). Among patients who underwent G-band karyotyping, the detection rate of abnormal karyotype was 38.5% (85/221). FSIH, especially MACS-FISH, had a higher detection rate of cytogenetic abnormalities than G-band karyotyping, and the difference was statistically significant ( χ2 = 65.697, P < 0.05). Conclusion:The comprehensive application of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, FISH (especially MACS-FISH), cytogenetic testing and other detection methods is more helpful for the diagnosis of multiple myeloma, and may be useful for prognostic judgment.

Objective:To evaluate the role of heme oxygenase-1 (HO-1) in electroacupuncture (EA)-induced alleviation of cognitive dysfunction in mice with sepsis-associated encephalopathy (SAE) and the relationship with mitochondrial fusion-division balance.Methods:Thirty clean-grade male C57BL/6 mice (24 wide-type mice and 6 HO-1 knockout mice), aged 6-8 weeks, weighing 18-22 g, were studied.Twenty-four wide-type mice were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), SAE group, SAE plus EA group (group SAE+ EA), and SAE plus sham EA group (group SAE+ SEA). HO-1 knockout mice in which EA intervention was performed after establishing SAE model served as SAE plus EA plus HO-1 knockout group (group SAE + EA+ H). Sepsis was induced by intraperitoneally injecting lipopolysaccharide 15 mg/kg.EA of Zusanli and Baihui acupoints lasting 30 min was performed after intraperitoneal injection of lipopolysaccharide once a day for 5 consecutive days in SAE+ EA and SAE+ EA+ H groups.Cognitive function was assessed using Morris water maze test before stimulation every day.The mice were sacrificed, and hippocampal tissues were removed for detection of the expression of mitofusin 2 (Mfn2), optic atrophy 1 (OPA1) and mitochondrial dynamin-related protein 1 (Drp1) by Western blot. Results:Compared with group C, the expression of Mfn2 and OPA1 was significantly down-regulated, the escape latency was prolonged, and the time spent in the target quadrant was shorted in SAE, SAE+ SEA and SAE+ EA+ H groups, and the expression of Drp1 was significantly up-regulated in SAE, SAE+ EA, SAE+ SEA and SAE+ EA+ H groups ( P<0.05). Compared with group SAE, the expression of Mfn2 and OPA1 was significantly up-regulated, the expression of Drp1 was down-regulated, the escape latency was shortened, and the time spent in the target quadrant was prolonged in group SAE+ EA ( P<0.05), and no significant change was found in the parameters mentioned above in group SAE+ SEA ( P>0.05). Compared with group SAE+ EA, the expression of Mfn2 and OPA1 was significantly down-regulated, the expression of Drp1 was up-regulated, the escape latency was prolonged, and the time spent in the target quadrant was shortened in SAE+ SEA and SAE+ EA+ H groups ( P<0.05). Conclusion:HO-1 is involved in EA-induced alleviation of cognitive dysfunction in mice with SAE, and the mechanism may be related to the regulation of mitochondrial mitochondrial fusion-division balance.

Objective:To evaluate the relationship between melatonin receptors and mitochondrial fission proteins and to clarify the mechanism of melatonin alleviating lipopolysaccharide(LPS)-induced damage to type Ⅱ alveolar epithelial cells of rats.Methods:The rat type Ⅱalveolar epithelial cells were seeded in 6-well plates at a density of 2×10 5 cells/ml and divided into 5 groups ( n=10 each) using a random number table method: control group (C group), LPS group (L group), LPS plus melatonin group (LM group), LPS plus melatonin receptor blocking group (LL group), and LPS plus melatonin plus melatonin receptor blocker group (LML group). The model of LPS-induced damage to cells was established by incubating with LPS 10 μg/ml for 24 h. Melatonin 0.1 mmol/L and/or melatonin receptor blocker luzindole 0.2 μmol/L was added in LM group, LL group and LML group.The concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay after the end of incubation.The mitochondrial respiratory control rate (RCR) was measured by GENMED purified mitochondrial RCR quantitative detection kit in each group.Western blot was used to detect the expression of dynamin-related protein 1 (Drp1) and mitochondrial adaptor fission 1 (Fis1). Results:Compared with C group, the concentrations of TNF-α and IL-6 in culture medium were significantly increased, RCR was decreased, and the expression of Drp1 and Fis1 was up-regulated in L, LM, LL and LML groups ( P<0.05). Compared with L group, the concentrations of TNF-α and IL-6 in culture medium were significantly decreased, RCR was increased, and the expression of Drp1 and Fis1 was down-regulated in LM group ( P<0.05), and no significant change was found in parameters mentioned above in LL group ( P>0.05). Compared with LM group, the concentrations of TNF-α and IL-6 in culture medium were significantly increased, RCR was decreased, and the expression of Drp1 and Fis1 was up-regulated in LML group ( P<0.05). Conclusion:The mechanism by which melatonin attenuates LPS-induced damage to type Ⅱ alveolar epithelial cells is related to activating melatonin receptors and inhibiting the expression of mitochondrial fission proteins in rats.

Objective:To evaluate the role of heme oxygenase-1 (HO-1)-induced endogenous protection in lipopolysaccharide (LPS)-caused apoptosis in rat alveolar macrophages and the relationship with endoplasmic reticulum stress.Methods:Alveolar macrophages of rats were randomized into 4 groups ( n=32 each) using a random number table method: control group (group C), LPS group (group L), Con siRNA group and HO-1 siRNA group. Cells were cultured normally in group C, and 10 μg/ml LPS was added to the culture medium in the other three groups. Con siRNA and HO-1 siRNA transfection was performed at 48 h before adding LPS in Con siRNA and HO-1 siRNA groups. At 24 h of treatment with LPS, MTT method was used to measure the cell viability, flow cytometry was used to determine the cell apoptosis rate, and Western blot was used to detect the expression of glucose regulatory protein 78 (GRP78), phosphorylated kinase receptor-like endoplasmic reticulum kinase (p-PERK), CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated type I endoplasmic reticulum transmembrane protein kinase (p-IRE-1), phosphorylated stress-activated protein kinase (p-JNK) and caspase-12. Results:Compared with group C, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1, GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in the other three groups ( P<0.05). Compared with group L, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1 was down-regulated, and the expression of GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in group HO-1 siRNA ( P<0.05), and no significant change was found in each parameter in group Con siRNA ( P>0.05). Compared with group Con siRNA, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1 was down-regulated, and the expression of GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in group HO-1 siRNA ( P<0.05). Conclusion:The mechanism of HO-1-induced endogenous protection is related to inhibiting endoplasmic reticulum stress and then reducing LPS-induced apoptosis in alveolar macrophages of rats.

Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h. HG-induced senescent cells showed the emergence of senescence associated heterochromatin foci, up-regulation of P16 and cyclin D1, increased senescence-associated β-galactosidase activity, and elevated expression of membrane decoy receptor 2. SKI treatment potently prevented these changes in a dose-independent manner. SKI treatment prevented HG-induced up-regulation of pro-senescence molecule mammalian target of rapamycin and p66Shc and down-regulation of anti-senescence molecules klotho, sirt1, and peroxisome proliferator-activated receptor-g in renal tubular epithelial cells. SKI may be a novel strategy for protecting against HG-induced renal tubular cell senescence in treatment of diabetic nephropathy.
Animals ; Cells, Cultured ; Cellular Senescence ; drug effects ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diabetic Nephropathies ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; metabolism ; Glucose ; Kidney Tubules, Proximal ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL

Objective: To evaluate the effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury (ALI). Methods: Thirty clean-grade healthy adult male C57BL/6 mice, weighing 20-25 g, aged 2 months, were divided into 3 groups (n=10 each) using a random number table method: control group (group C), endotoxin-induced ALI group (group LPS) and endotoxin-induced ALI plus dexmedetomidine group (group LPS+ DEX). In LPS and LPS+ DEX groups, lipopolysaccharide (LPS) 10 mg/kg was injected via the caudal vein to establish the model of endotoxin-induced ALI.In group LPS+ DEX, dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before injection of LPS, while the equal volume of normal saline was given instead in C and LPS groups.The mice were sacrificed at 6 h after LPS administration, and lung tissues were obtained for examination of the pathological changes (with a light microscope) which were scored and for determination of the level of reactive oxygen species (ROS) and expression of mitochondrial fusion proteins mitofusin 1 (Mfn1), Mfn2, optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1) and fission protein 1 (Fis1)(using Western blot). Results: Compared with group C, the lung injury scores and ROS level in lung tissues were significantly increased, the expression of Mfn1, Mfn2 and OPA1 was down-regulated, and the expression of Drp1 and Fis1 was up-regulated in LPS and LPS+ DEX groups (P<0.05). Compared with group LPS, the lung injury scores and ROS level in lung tissues were significantly decreased, the expression of Mfn1, Mfn2 and OPA1 was up-regulated, and the expression of Drp1 and Fis1 was down-regulated in group LPS+ DEX (P<0.05). Conclusion Dexmedetomidine can reduce endotoxin-induced ALI through maintaining the mitochondrial fusion-fission balance in mice.