AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P<0.05).CONCLUSION: The optimal concentrations for IHC staining in different proteins of mouse RP models were as follows: the concentrations of endoplasmic reticulum stress-related protein antibodies were 1:1000 in IRE1, 1:500 and 1:1000 in ATF6, 1:1500 in PERK, 1:200 in GRP78, and 1:100 in Caspase-12.

Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.
Humans ; Central Venous Pressure ; Respiration ; ROC Curve

Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

OBJECTIVE: To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl₂), which mimics mangnism. METHODS: Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H₂O intragastrically (ig), MnCl₂ group received 15 mg/kg MnCl₂(Mn²⁺ 6.48 mg/kg) intraperitoneally plus dd H₂O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl₂+ CUR1 group received 15 mg/kg MnCl₂ intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl₂+ CUR2 group received 15 mg/kg MnCl₂ intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum. RESULTS: After exposure to MnCl₂ for four weeks, MnCl₂-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH⁺ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl₂ group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl₂ group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl₂ group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl₂+ CUR2 group were significantly improved compared with MnCl₂ group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl₂+ CUR2 group compared with MnCl₂ group. Further, compared with MnCl₂ group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl₂+ CUR2 group (P < 0.05). CONCLUSION Curcumin alleviated the MnCl₂-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.
Animals ; Autophagy ; Chromatin ; Curcumin/pharmacology* ; Male ; Mammals ; Manganese/toxicity* ; Rats ; Rats, Sprague-Dawley ; Saline Solution/pharmacology* ; TOR Serine-Threonine Kinases

The Second Affiliated Hospital of Shandong First Medical University treated a patient with oral sulfur mixture poisoning on January 14, 2020. The patient presented with cyanosis and disturbance of consciousness as the first manifestations, accompanied by metabolic acidosis, shock, hypercalcemia and severe liver function and myocardial damage. The patient was given active treatment, including gastric lavage, blood purification, methylene blue application, correction of shock, organ support and other therapies. However the treatment was poor. Finally, the patient's family chose to give up and requested to be discharged from the hospital, and the patient died on the same day after follow-up.
Calcium Compounds ; Humans ; Poisoning/therapy* ; Sulfides

Objective:To explore the relationship between the selection of different P2Y 12 inhibitors and the long-term prognosis of acute coronary syndrome (ACS) patients with and without CYP2C19 defect gene. Method:289 consecutive ACS patients who underwent percutaneous coronary intervention (PCI) at Tianjin Third Central Hospital from March 2016 to October 2016 were selected for CYP2C19 gene polymorphism detection. According to the detection results, the patients were divided into group A (with CYP2C19 loss-of-function gene, 199 cases) and group B (without CYP2C19 loss-of-function gene, 90 cases). After PCI, different P2Y 12 inhibitors were selected. The patients were followed up for 3 years, and 23 cases were lost to follow-up. Finally, 182 cases were enrolled in group A and 84 cases were enrolled in group B. According to whether there were major adverse cardiovascular events (MACE) within 3 years, the patients in groups A and B were divided into MACE subgroups (58 cases, 32 cases) and non-MACE subgroups (124 cases, 52 cases). The single factor analysis of the two subgroups in groups A and B was carried out based on the patient's clinical data, coronary artery disease and intervention status, and postoperative drug treatment plan. Risk factors with statistical significance ( P<0.05) were selected, and multivariate logistic regression analysis was performed on groups A and B to compare the effects of different P2Y 12 inhibitors on the prognosis of the two groups. Results:The differences in platelet volume, fasting blood glucose, HbA1c, left ventricular end-diastolic diameter, proportion of single-branch lesions, proportion of intervention for left main lesions, and dual antiplatelet therapy were statistically significant between the two subgroups in group A (all P<0.05). The differences in low-density lipoprotein (LDL), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, proportion of two-branch lesions, proportion of three-branch lesions, and proportion of using tirofeben were statistically significant between the two subgroups in group B (all P<0.05). In the group A, the choice of different P2Y 12 inhibitors was the independent risk factor for the long-term prognosis. Compared with patients treated with Ticagrelor, the probability of long-term MACE was 11.971 times larger ( OR=12.971, 95% CI: 5.028~33.464, P<0.001) among patients treated with Clopidogrel 75 mg/day, and 5.029 times larger ( OR=6.029, 95%CI: 2.278~15.958) among patients treated with Clopidogrel 100 mg/day. No significant correlation was witnessed between different P2Y 12 inhibitors and long-term prognosis in group B. In the group B, different P2Y 12 inhibitors have no significant correlation with their long-term prognosis of patients( P>0.05). Conclusions:For ACS patients with CYP2C19 loss-of-function gene, the choice of P2Y 12 inhibitors is associated with their long-term MACE events after PCI. Ticagrelor therapy brings the lowest risk of long-term MACE. For those without CYP2C19 loss-of-function gene, the correlation between the choice of different P2Y 12 inhibitors and their prognosis is not significant.

Adult ; Cytogenetics ; Genes, p53 ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Tumor Suppressor Protein p53/genetics*

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.
Consolidation Chemotherapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Remission Induction

Objective? To anaLyze the infLuencing factors of stress hypergLycemia in patients undergoing surgery for non-diabetic Standard Type A aortic dissection and to expLore the methods of its monitoring and management. Methods? TotaLLy 100 patients with non-diabetic Standard Type A aortic dissection admitted in the Department of Cardiac Surgery, Zhongshan HospitaL were retrospectiveLy incLuded. Their generaL information incLuding age, gender, body mass index (BMI), pain score, operation time and time of circuLatory arrest as weLL as morning fasting bLood-gLucose (FBG) before operation, before extracorporeaL circuLation, before and after circuLatory arrest, after rewarming, after machine haLt, at ICU admission and on 1 - 6 day postoperativeLy was coLLected. Univariate anaLysis and Logistic regression anaLysis were used to expLore the factors affecting the peak bLood-gLucose perioperativeLy. ResuLts? The area under the ROC curve for perioperative bLood-gLucose and overaLL adverse outcome was 0.646 (95%CI 0.528-0.763,P=0.021), and the comparativeLy good cutoff vaLue of perioperative peak bLood-gLucose for the disease was 14.35. The patients' bLood-gLucose started to rise after extracorporeaL circuLation, and the tendency to rise was more significant after rewarming. Their bLood-gLucose remained at a reLativeLy high LeveL at ICU admission. It tended to decrease since 24 h postoperativeLy, and it returned to normaL LeveLs at 6 d post operation. Univariate anaLysis showed that there was statisticaL difference in BMI, white bLood ceLL, C-reactive protein (CRP), time of extracorporeaL circuLation, Acute PhysioLogy and Chronic HeaLth EvaLuation Scoring System (APACHEⅡ) and whether emergency surgery received between the patients with ≥14.35 mmoL/L or ＜14.35mmoL/L bLood-gLucose perioperativeLy (P＜0.05). According to Logistic regression anaLysis, BMI, CRP and time of extracorporeaL circuLation were independent risk factors of stress hypergLycemia in patients undergoing surgery for non-diabetic Standard Type A aortic dissection (OR＞1). ConcLusions? Severe infLammatory response and high BMI preoperativeLy indicate that stress hypergLycemia may occur in patients undergoing surgery for non-diabetic Standard Type A aortic dissection during the perioperative period. Perioperative hypergLycemia can be reduced by reducing the time of extracorporeaL circuLation. MedicaL and nursing workers need to enhance gLycemic monitoring in the process of extracorporeaL circuLation, after rewarming and post operation and deveLop targeted gLycemic management protocoLs for the patients.