Effect of esketamine on cerebral ischemia-reperfusion injury and association with mitochondrial stress in mice / 中华麻醉学杂志

Objective:To evaluate the effect of esketamine on cerebral ischemia-reperfusion (I/R) injury and the association with mitochondrial stress in mice.Methods:The experiment was performed in two parts. Part Ⅰ Eighteen SPF male C57BL/6 mice, aged 8-12 weeks, with body mass index of 28-30 g, were divided into 3 groups ( n=6 each) by a random number table method: sham operation group (S group), cerebral I/R group (IR group), and esketamine plus cerebral I/R group (E+ IR group). Cerebral I/R was produced by occlusion of middle cerebral artery for 1 h followed by 24-h reperfusion in anesthetized mice.Esketamine 10 mg/kg was intraperitoneally injected at 20 min before developing the model in E group. Neurological function was evaluated using the Zea Longa score and balance beam test (Feeney score). The cerebral infarct size was determined by TTC staining. Part Ⅱ Primary cortical neurons were isolated and cultured and then divided into 3 groups ( n=42 each) using a random number table method: control group (group C), oxygen-glucose deprivation-reoxygenation (OGD/R) group, and esketamine plus OGD/R group (group E+ OGD/R). Cells were subjected to O 2-glucose deprivation for 1 h followed by restoration of O 2-glucose supply for 24 h. The cells were treated with 25 μmol/L esketamine for 40 min before preparing the model in E+ OGD/R group. The neuronal viability was measured by the CCK-8 assay. The ultrastructure of neurons was observed with a transmission electron microscope. The levels of reactive oxygen species (ROS), glutathione peroxidase (GSH-px) and malondialdehyde (MDA) were determined, and the mitochondrial membrane potential was determined by JC-1 kit. The neuronal apoptosis was detected by TUNEL staining, and the apoptosis rate of neurons was calculated. The expression of Bax, cytochrome C (CytC), cleaved-caspase-9, caspase-3 and cleaved-caspase-3 was detected by Western blot. Results:Part Ⅰ Compared with S group, the Zea Longa score, Feeney score and cerebral infarct size were significantly increased in IR group ( P<0.01). Compared with IR group, the Zea Longa score, Feeney score and cerebral infarct size were significantly decreased in E+ IR group ( P<0.01). Part Ⅱ Compared with C group, the cell viability and activity of GSH-px were significantly decreased, the apoptosis rate of neurons, levels of ROS and MDA, mitochondrial membrane potential, and cleaved-caspase-3/caspase-3 ratio were increased, and the expression of Bax, Cyt C and cleaved-caspase-9 was up-regulated in OGD/R group ( P<0.01). Compared with OGD/R group, the cell viability and activity of GSH-px were significantly increased, the apoptosis rate of neurons, levels of ROS and MDA, mitochondrial membrane potential, and cleaved-caspase-3/caspase-3 ratio were decreased, and the expression of Bax, Cyt C and cleaved-caspase-9 was down-regulated in E+ OGD/R group ( P<0.01). Conclusions:Esketamine can alleviate cerebral I/R injury in mice, and the mechanism may be related to inhibition of mitochondrial stress in neurons, improvement in mitochondrial function, and inhibition of mitochondria-dependent apoptosis in neurons.

Role of autophagy in morphine preconditioning-induced reduction of OGD/R injury in primary cortical neurons of mice and the relationship with JNK / 中华麻醉学杂志

Objective:To evaluate the role of autophagy in morphine preconditioning-induced reduction of oxygen-glucose deprivation and restoration (OGD/R) injury in primary cortical neurons of mice and the relationship with c-Jun N-terminal kinase (JNK).Methods:Primary cortical neurons extracted from C57BL/6 neonatal mice within 24 h after birth were divided into 9 groups ( n=24 each) using a random number table method: control group (C group), OGD/R group, morphine preconditioning group (M group), autophagy inhibitor 3-methyladenine (3-MA) group (3-MA group), 3-MA+ morphine preconditioning group (3-MA+ M group), autophagy inhibitor chloroquine group (Ch group), chloroquine + morphine preconditioning group (Ch+ M group), JNK inhibitor SP600125 group (SP group) and SP600125 + morphine preconditioning group (SP+ M group). Morphine preconditioning: morphine was added at a final concentration of 3 μmol/L before OGD/R, and the cells were incubated for 2 h in OGD/R group. In 3-MA, Ch and SP groups, 3-MA 5 mmol/L, chloroquine 50 μmol/L and SP600125 25 μmol/L were added, respectively, and the cells were incubated for 150 min. In 3-MA+ M, Ch+ M and SP+ M groups, 3-MA 5 mmol/L, chloroquine 50 μmol/L and SP600125 25 μmol/L were added, respectively, at 30 min before morphine preconditioning. Then the cells were subjected to oxygen-glucose deprivation for 1 h followed by restoration of oxygen-glucose supply for 24 h. CCK-8 assay was used to detect the neuronal viability. The expression of JNK, phosphorylated JNK (p-JNK), microtubule-associated protein 1 light chain 3 (LC3), p62, Beclin1, caspase-3, and cleaved-caspase-3 was determined by Western blot. The autophagosomes and autolysosomes were counted using LC3-double fluorescent adenovirus transfection, and the neuronal apoptosis rate was determined by TUNEL staining. Results:Compared with C group, the neuronal viability was significantly decreased, the expression of Beclin1 was up-regulated, the expression of p62 was down-regulated, and the LC3Ⅱ/LC3Ⅰ ratio, p-JNK/JNK ratio, the number of autophagosomes and autolysosomes, cleaved-caspase-3/caspase-3 ratio and neuronal apoptosis rate were increased in OGD/R group ( P<0.001). Compared with OGD/R group, the neuronal viability, p-JNK/JNK ratio, LC3Ⅱ/LC3Ⅰ ratio and the number of autophagosomes and autolysosomes were significantly increased, the expression of Beclin1 was up-regulated, and the expression of p62 was down-regulated in M group, the LC3Ⅱ/LC3Ⅰ ratio was significantly decreased, and the expression of p62 was down-regulated in 3-MA group, the LC3Ⅱ/LC3Ⅰ ratio was significantly increased, and the expression of p62 was up-regulated in Ch group ( P<0.001), and no significant change was found in the parameters mentioned above in SP600125 group ( P>0.05). Compared with M group, the neuronal viability was significantly decreased, the LC3Ⅱ/LC3Ⅰ ratio was decreased, and the expression of p62 was up-regulated in M+ 3-MA group, the neuronal viability was significantly decreased, the LC3Ⅱ/LC3Ⅰ ratio was increased, and the expression of p62 was up-regulated in M+ Ch group, and the neuronal viability, LC3Ⅱ/LC3Ⅰ ratio and p-JNK/JNK ratio were significantly decreased, the expression of p62 was up-regulated, the number of autophagosomes and autolysosomes was decreased, the expression of Beclin1 was down-regulated, and the cleaved-caspase-3/caspase-3 ratio and neuronal apoptosis rate were increased in M+ SP group ( P<0.001). Conclusions:Morphine preconditioning can attenuate OGD/R injury by activating JNK, enhancing autophagy and inhibiting apoptosis in primary cortical neurons of mice.

IgD multiple myeloma: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

nPKCepsilon and NMDA receptors participate in neuroprotection induced by morphine pretreatment.

Morphine pretreatment induces ischemic tolerance in neurons, but it remains uncertain whether novel protein kinase C epsilon isoform (nPKCepsilon) and N-methyl-D-aspartate (NMDA) receptors are involved in this neuroprotection. The present study examined this issue. Hippocampal slices from adult BALB/C mice were incubated with morphine at 0.1-10.0 muM in the presence or absence of various antagonists for 30 minutes and then kept in morphine- and antagonist-free buffer for 30 minutes before being subjected to oxygen-glucose deprivation for 20 minutes. After recovery in oxygenated artificial fluid for 5 hours, assessment of slice injury was done by determination of the intensity of slice stain after they were incubated with 2% 2,3,5-triphenyltetrazolium chloride for 30 minutes and extracted by organic solvent for 24 hours. At designated periods, slices were preserved for immunoblot analysis to observe effects of morphine pretreatment on membrane translocation and total protein expression of nPKCepsilon and phosphorylation of NR1 subunits of NMDA receptors. The neuroprotection induced by morphine pretreatment was partially blocked by chelerythrine (a nonselective PKC blocker), epsilonv(1-2) (a selective nPKCepsilon antagonist), MK-801 (a noncompetitive NMDA receptor blocker), chelerythrine combined with MK-801, and epsilonv(1-2) with MK-801. Morphine pretreatment significantly inhibited nPKCepsilon membrane translocation and phosphorylation of NR1 subunits of NMDA receptors during reperfusion injury. However, epsilonv(1-2) blocked these effects induced by morphine pretreatment. These findings suggested that nPKCepsilon and NMDA receptors might participate in neuroprotection induced by morphine pretreatment, and NMDA receptors might be downstream targets of nPKCepsilon.

Effect of immunophenotyping on prognosis of multiple myeloma patients treated with bortezomib as main treatment / 白血病·淋巴瘤

Objective@#To investigate the effect of immunophenotyping on prognosis of multiple myeloma (MM) patients treated with bortezomib regimen as main treatment.@*Methods@#Seventy-six MM patients in the Department of Hematology in the Affiliated Hospital of Qingdao University from January 2012 to January 2017 were retrospectively analyzed. The effects of the expressions of CD45, CD56 and other factors on progression free survival (PFS) and overall survival (OS) in MM patients treated with bortezomib-containing regimen were also analyzed.@*Results@#Univariate analysis showed that statistical differences of the median PFS (12 months vs. 19 months, P < 0.001) and median OS (19 months vs. 23 months, P= 0.001) were significant in the group of CD45 positive and negative of MM patients; the median PFS (14 months vs. 21 months, P= 0.014) and median OS (16 months vs. 25 months, P= 0.026) for MM patients with hemoglobin (Hb) < 100 g/L and Hb ≥ 100 g/L were statistically significant; the median PFS (13 months vs. 18 months, P= 0.004) and median OS (14 months vs. 24 months, P= 0.008) for MM patients with albumin (ALB) < 35 g/L and ALB ≥ 35 g/L were statistically significant. The median PFS time and the median OS time in female MM patients were shorter than those in male MM patients (13 months vs. 19 months, P= 0.008; 16 months vs. 25 months, P= 0.008). Multivariate analysis showed that female and CD45 positive were the independent poor prognostic factors for PFS and OS in MM patients (P < 0.05).@*Conclusion@#CD45 positive and female are important prognostic factors for MM patients treated with bortezomib regimen as main treatment.

Prognostic analysis of 71 patients with primary central nervous system diffuse large B-cell lymphoma / 中华放射肿瘤学杂志

Objective To investigate prognostic factors in patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLCBL).Methods The clinical data of 71 patients with PCNS-DLCBL confirmed by pathology and clinical tests, who were admitted to our hospital from 1991 to 2015, were retrospectively analyzed.All patients received chemotherapy, mainly with high-dose methotrexate (HD-MTX, 66/71), and 59 patients received radiotherapy, mainly with whole brain radiotherapy (WBRT)±local boost.The Kaplan-Meier method was used to calculate survival rates, the log-rank test was used for survival comparison and univariate prognostic analysis, and the Cox model was used for multivariate prognostic analysis.Results Fifty-eight patients achieved a complete response (CR), ten achieved a partial response (PR), and three had progressive disease (PD).The 5-year overall survival (OS) rate was 43%, and the 5-year progression-free survival (PFS) rate was 34%.The univariate analysis showed that the factors associated with OS included the following:age of onset, Karnofsky Performance Scale (KPS) score, single or multiple lesions, whether to receive radiotherapy, evaluation results after radiotherapy and chemotherapy, and the presence or absence of recurrence (P=0.000-0.047);the multivariate analysis showed that the three factors that affected OS were age of onset, KPS score, and the presence or absence of recurrence (P=0.000-0.022).The univariate analysis revealed that chemotherapy regimen, whether to receive radiotherapy, total radiotherapy dose, WBRT dose, evaluation results after radiotherapy and chemotherapy, and the presence or absence of recurrence were the factors associated with PFS (P=0.000-0.028);the multivariate analysis revealed that KPS score and the presence or absence of recurrence were associated with PFS (P=0.000-0.011).Conclusions Among patients with PCNS-DLCBL, younger age, higher KPS score, and no recurrence are associated with better OS, and single lesion, radiotherapy, and better evaluation results after radiotherapy and chemotherapy may be associated with better OS;higher KPS score, better evaluation results after radiotherapy and chemotherapy, and no recurrence are the factors associated with better PFS, and HD-MTX chemotherapy, radiotherapy, higher total radiotherapy dose, and higher WBRT dose may be associated with better PFS.Whether to receive radiotherapy after achieving a CR with chemotherapy and the target area and dose of radiotherapy need to be further studied.

Combination of red and blue light therapy with acne film coating in treatment of moderate and severe acne / 中华全科医师杂志

Objective To evaluate the efficacy of combined red and blue light therapy with acne film coating in treatment of moderate and severe acne.Methods Totally 547 patients with moderate or severe acne were enrolled in the study from March 2012 to July 2014.Using open control,according to the cycle of time sequence will patients were divided into three groups:183 patients (study group) were received alternatively red and blue light therapy twice a week,and acre film coating was applied once a day;182 patients in control group 1 received film coating alone and another 182 patients (control group 2) received light therapy alone.The treatment lasted for 6 weeks in all three groups.The numbers of skin lesions were recorded before and 2,4,6 w after treatment,and the curative effect was evaluated 10 w after treatment.Results The number of skin lesion were significantly reduced 6w after treatment in all three groups,that for study group was most markedly.For patients with moderate acne,the total effective rates in study group and in control groups 1 and 2 were 84.6％ (110/130),58.5％ (76/130) and 51.9％ (67/129),respectively (x2 =21.836,and 31.955,P ＜0.01).For patients with severe acne the total effective rates in study group and in control groups 1 and 2 were 84.9％ (45/53),57.7％ (30/52) and 56.6％ (30/53),respectively (x2 =9.525 and 10.258,P ＜0.01).There are 20 cases in observation group therapy for different degree of erythema,itching,burning,tingling,incidence of side effects was 10.9％ (20/183),control group 1 and 2 were 7.1％ (14/182),12.1％ (22/182),are tolerated.Conclusion The combination of red/blue light therapy with acne film coating is more effective than the application of single method alone for patients with moderate or severe acne.

The effect of rosuvastatin calcium on vascular endothelial function, tumor necrosis factor-α and interleukin-1 in hyperlipidemia patients / 中国医师进修杂志

Objective To observe the effect of rosuvastatin calcium on lipid,vascular endothelial growth factor (VEGF),nitric oxide (NO),tumor necrosis factor (TNF)-α and interleukin (IL)-1 in hyperlipidemia patients.Methods One hundred and twenty-seven hyperlipidemia patients were randomly divided into two groups.Patients in the study group included 72 patients which were given rosuvastatin calcium 10 mg and enteric-coated aspirin 100 mg,orally,once a day for 8 weeks.The control group included 55 patients which were only given enteric-coated aspirin 100 mg,orally,once a day for 8 weeks.The change of lipid,VEGF,NO,TNF-α and IL-1 was observed before and after treatment.Results Before treatment,the level of total cholesterol(TC),triglyceride (TG),low density lipoprotein-cholesterol (LDL-C),high density lipoprotein-cholesterol (HDL-C),VEGF,NO,TNF-α and IL-1 in two groups had no significant difference (P ＞ 0.05).After treatment,the level of TC,TG,LDL-C,TNF-α and IL-1 in study group were significantly lower than those in control group [(4.410 ± 0.688) mmol/L vs.(6.491 ± 0.744) mmol/L,(1.762 ± 0.834) mmol/L vs.(2.632 ± 0.792) mmol/L,(2.256 ± 0.347) mmol/L vs.(4.544 ± 0.493) mmol/L,(41.14 ± 5.41) ng/L vs.(71.34 ± 6.76) ng/L,(0.22 ± 0.18) μ g/L vs.(0.42 ± 0.23) μ g/L] (P ＜ 0.05).The level of HDL-C,VEGF and NO in study group were significantly higer than those in control group [(1.807 ± 0.730) mmol/L vs.(1.432 ± 0.514) mmol/L,(564.86 ± 120.02) ng/L vs.(451.23 ± 100.72) ng/L,(42.39 ± 6.71) μ mol/L vs.(33.65 ± 6.24) μ mol/L](P＜ 0.05).No adverse reaction occurred in two groups.Conclusions Rosuvastatin calcium can obviously decrease the level of lipid,elevate the expression of VEGF and NO,and reduce the expression of TNF-α and IL-1.Rosuvastatin calcium can improve vascular endothelial function obviously in hyperlipidemia patients.

The influence of mini-invasive evacuation of hematoma for myelin basic protein and neuronspecific enolase in patients with cerebral hemorrhage / 中国医师进修杂志

ObjectiveTo observe the influence of mini-invasive evacuation of hematoma for myelin basic protein (MBP) and neuron-specific enolase (NSE) in patients with cerebral hemorrhage.Methods Eighty patients with cerebral hemorrhage were divided into group A and group B by random digits table method with 40 cases each.The patients in group A were given conservation treatment.The patients in group B were given mini-invasive evacuation of hematoma treatment.At the same time 30 cases of healthy people randomly were selected as control group.The serum MBP and NSE were determined before treatment,after treatment 1,3,7,14 d in group A and group B.ResultsThe effective rate in group B was 92.5％ (37/40),which was higher than that in group A [80.0％(32/40)],there was significant difference (P ＜ 0.05 ).The serum NSE before treatment in group A and group B was higher than that in control group [ (12.8 ± 2.9),( 13.1 ± 2.8 ) μg/L vs.( 5.3 ± 2.4) μg/L],there was significant difference(P ＜ 0.05 ).The serum NSE after treatment in group B was obviously decreased compared with group A.The serum MBP after treatment 1 d was increased,7 d was decreased,that in group B was obviously decreased compared with group A [ (5.4 ± 1.5) μ g/L vs. (6.9 ± 1.3) μ g/L,P ＜ 0.05 ].ConclusionThe method of mini-invasive evacuation of hematoma in treatment of cerebral hemorrhage patients has good effect,and can decrease the serum MBP and NSE.

Clinical study of combined prednisone with minoxidil in treatment of the androgenetic alopecia / 中国医师进修杂志

Objective To investigate the clinical effect of prednisone and zinc preparation combined with 2％ minoxidil in the androgenetic alopecia. Methods Ninety-eight patients with the androgenetic alopecia were randomly divided into two groups, each group was 49 patients. The treatment group received prednisone and zinc preparation oral solution combined with 2％ minoxidil, the control group received only prednisone and zinc preparation oral solution. The each course of treatment was 3 months, the effect was observed after 1-4 courses of treatment. Results The curative rate of the treatment group and control group were 10.2％( 5/49 ) ,36.7％ (18/49) and 6.1％ (3/49) ,22.4％ (11/49) respectively in 3 and 6 months after treatment, there were no significant difference between two groups (P ＞ 0.05 ). The curative rate of the treatment group and control group were 77.6％ (38/49), 91.8％ (45/49) and 42.9％ (21/49 ), 59.2％(29/49) respectively in 9 and 12 months after treatment, there were significant difference between two groups (P＜ 0.05). Conclusion On treating the androgenetic alopecia, prednisone and zinc preparation combined with minoxidilis effective and safe.

High-risk factors of premenstrual acne / 中华健康管理学杂志

Objective To investigate the high-risk factors of premenstrual acne to provide evidence for disease prevention and treatment.MethodsA total of 660 patients with premenstrual acne during February 2006 and October 2009 were retrospectively reviewed.Pillshbury method was used for diagnose and classification of premenstrual acne.Six hundred and sixty complete questionnaires were received for statistic analysis.Results Age and season showed no effect on moderate to sever premenstrual acne.However,spicy and fried food(x2=5.68),mental stress(x2=14.58),gastrointestinal disorders(x2=8.07),family history(x2=12.79),longer hairs around areolas(X2=11.88),and thyroid gland,adrenal gland or adnexal cysts(x2=9.72)had significantimpact on moderate to severpremenstrual acne(all P＜0.05).In addition.inflammatory papules on frontal partress were found in 67.4% of moderate premenstmal acne.ConclusionFood intake,mental health,gastrointestinal disorders,family history,longer hair around areolas,and thyroid gland,adrenal gland,adnexal cysts may be high-risk factors of premenstrual acne.

Factors affecting the protective effect of morphine preconditioning on murine hippocampal neurons against anoxia-reoxygenation injury / 中华麻醉学杂志

Objective To investigate the factors affecting the protective effects of morphine preconditioning on murine hippocampal neurons against anoxia/reoxygenation (A/R) injury and the underlying mechanisms.Methods Hippocampal slices (400 μm thick) were prepared using hippocampi isolated from decapitated mice. A/R injury was simulated in vitro using artificial cerebral spinal fluid (ACSF) deprived of O_2 and glucose for 20 min followed by reoxygenation and glucose supply for 2 h. The experiment was performed in 4 parts: I .The slices were incubated with 5 different concentrations of morphine (0.1, 0.3, 0.5, 1.0, 3.0, 10.0 /μmol/L) for 30 min at 30 min before A/R; Ⅱ. The slices were incubated with morphine 3.0 /μmol/L for 5 different periods of time (5, 15, 30, 45, 60 min) at 30 min before A/R; Ⅲ. The slices were incubated with morphine 3.0 μmol/L for 30 min followed by A/R at 6 different intervals (0, 5, 15,30,60, 120 min); Ⅳ. The slices were incubated with (a) chelerythrine (a non-selective PKC antagonist) 10 /μmol/L or (b) εVl-2 (a selective nPKCe isoform antagonist) 2 μmol/L or (c) AIP 2 μmol/L (a selective CaMK Ⅱ antagonist) or (d) MK-801 10 μmol/L (a non-competitive NMDA receptor blocker) for 30 min and then for another 30 min together with morphine 3.0 μmol/L before A/R at 30 min interval. The survival rates of the hippocampal neurons were assessed by TTC staining. Results Neuronal survival rates were significantly higher in morphine preconditioning groups which preconditioned with morphine (0.5-10.0 μmol/L) for 15-60 min at an interval of 0-60 min before A/R than in A/R group. Increase in neuronal survival rate induced by morphine preconditioning was partially blocked by chelerythrine or εV1-2 or AIP or MK-801. Conclusion Preconditioning with appropriate concentrations of morphine (0.5-10.0 μmol/L) for appropriate period of time (15-60 min) at appropriate interval (within 60 min) before A/R can protect hippocampal neurons against A/R injury through activation of nPKCε, NMDA receptor and CaMKⅡ.