Objective To investigate the effect of melatonin(MT)on tau hyperphosphorylation in hippocampus of mice with exposure to lead(Pb)at early development stage and its possible mechanism.Methods Healthy C57BL/6 mice were randomly divided into four groups:control group(received normal water),lead exposure group(exposed to 0.2% Pb acetate from postnatal day 1(PND 1)to PND 21 through drinking water),MT group(received 50 mg/mL MT through drinking water since 12-month-old for 3 months)and MT combined with lead exposure group(exposed to 0.2% Pb acetate from PND 1 to PND 21 and then given 50 mg/mL MT since 12-month-old for 3 months through drinking water).The Pb levels in the blood and hippocampus were determined by graphite furnace atomic absorption spectrometry.Morris water maze was used to detect the spatial learning and memory.The phosphorylation level of tau and the protein level of GRP78 and CHOP in hippocampus were detected by Western blotting.Results Compared with the control group,the Pb levels in the blood and hippocampus were significantly increased in lead exposure group(P<0.05),while MT treatment did not affect the Pb levels both in the blood and hippocampus.In the lead exposure group,the phosphorylation level of tau in the hippocampus was significantly increased compared with control group(P<0.01),and after treatment with MT,the phosphorylation level of tau in MT combined with lead exposure group was significantly decreased compared with the lead exposure group(P<0.05).Furthermore,the expression of GRP78 and CHOP in the hippocampus was significantly higher in lead exposure group than in control group(P<0.05),and after treatment with MT,the expression levels of GRP78 and CHOP were lower than those of the control group.Conclusion MT can ameliorate the phosphorylation level of tau in the hippocampus and defects of learning and memory in C57BL/6 mice with exposure to lead at early development stage,and this may be related with the modulation of endoplasmic reticulum stress.

Background and purpose:Duffy blood group(DBG)system contains genotype system and phenotype system.DBG phenotype system is embodied by the protein carrying blood group antigens on the surface of red blood cells.Epidemiological evidence has shown that different races had definitely different DBG phenotype disuribution and there is a variation of morbidity and mortality of breast cancer among different race populations.Therefore,this study was to investigate whether DBG phenotype affects breast cancer occurrence and malignancy.Methods:We investigated DBG phenotypes of 253 female cases with breast diseases who were consecutively hospitalized in the Shanghai Cancer Hospital and analysis was done on its relationship with clinical pathological diagnosis.DBG phenotypes were examined by indirect antiglobulin-test with anti-Fya and anti-Fyb reagents,and were classified into Fya+Fyb-,Fya-Fyb+,Fya+Fyb+,Fya-Fyb-according agglutination.Results:Neither DBG phenotypes distribution difference existed in breast disease patients nor in breast cancer patients as observed in the general Chinese Han population.Fya-Fyb-and Fya-Fyb+ demonstrated more susceptibility to breast cancer than Fya+Fyb-and Fya+Fyb+,but there was no statistical significant difference.Fya-group(57.14%)had more malignant incidence than that of Fya+ group(39.02%),but there was also no statistical significance(P=0.28).No significant differences have been observed in ER,PR,Her-2 status and P53,PCNA,PS2,nm23,P450 status between every DBG phenotypes,nor in tumor grades in various DBG phenotypes.More patients were involved in axillary lymph nodes metastasis in Fya-than that in Fya+ group and reached statistical significance(100% and 39.13% respectively,P

Objective To evaluate the therapeutic effect of abdominal multiple visceral organ transplantation for hepatic cirrhosis combined with diabetes by using donation after cardiac death (DCD).Methods Two patients suffering from hepatitis B-related liver cirrhosis,hepatocellular carcinoma combined with insulin dependent type 2 diabetes mellitus were given multiple visceral organ transplantation from May to June 2012.The transplanted organs including the liver,pancreas and duodenum were obtained from two donors after cardiac death which accorded with C-Ⅲ criteria.The donor internal and external iliac arteries were anastomosed to celiac axis and superior mesenteric artery and then the donor arteria iliaca communis was anastomosed to recipient abdominal aorta.The portal vein reconstruction was performed by end-to-side anastomosis between the donor and recipient portal vein.The pancreatic juice drainage was achieved by side to side anastomosis between donor duodenum and recipient jejunum.The pancreases of recipients were retained.Results The alanine aminotransferase,aspartate aminotransferase and total bilirubin of two patients were recovered to normal level at 2nd week after operation.The blood glucose and serum amylase returned to normal levels at 7th d and 4th d respectively.The fasting serum C-peptide and insulin were also at normal level at 2nd week.One patient with local intestinal anastomotic fistula was given percutaneous puncture drainage for four weeks and recovered.One patient recovered smoothly one month after transplantation without surgical complications.Conclusion Abdominal multiple visceral organ transplantation is an effective treatment for hepatic cirrhosis combined with diabetes by using DCD donor.

Objective To investigate the effect of midazolam on inflammatory response in patients with moderate and severe craniocerebral injury and its protective effect on the brain and mechanism.Methods A prospective study was conducted.One hundred and twenty patients with moderate and severe craniocerebral injury admitted to the Intensive Care Unit (ICU) of Jiangsu Subei Peoples' Hospital from April 2013 to July 2016 were enrolled,and they were divided into a conventional treatment group (58 cases) and a midazolam group (62 cases) according to the random number table method.Both groups were given conventional western medicine treatment,and in cases with surgical indications,operations were performed;in midazolam group,additionally intravenous injection of midazolam 2-3 mg was given firstly,and then continuous intravenous infusion of the drug 0.05-0.10 mg· kg-1· h-1 was applied by a pump,and in operative patients,the above management was given 3 hours after operation.The mean arterial pressure (MAP),heart rate (HR),Riker sedation agitation score (SAS) and electroencephalogram bispectral index (BIS) were measured before and after treatment for 24,48 and 72 hours,respectively.The levels of interleukin-6 (IL-6) and soluble nerve chemotactic protein (sFkn) in plasm and cerebrospinal fluid (CSF) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA) at each time point;the incidence of epilepsy and 28-day mortality were recorded.Results Before and after treatment,the MAP and HR in the two groups of patients were stable,the difference being not statistically significant (both P ＞ 0.05).Compared with those before treatment,after treatment the SAS score and BIS in two groups of patients were gradually decreased,and at 72 hours reached the lowest levels (SAS score:conventional treatment group was 3.8 ± 1.0 vs.5.7 ± 2.0,midazolam group was 3.6 ± 0.9 vs.5.8 ± 1.7;BIS:conventional treatment group was 69± 12 vs.82± 12,midazolam group was 72± 15 vs.82± 12,all P ＜ 0.05),but there were no significant differences between the two groups (all P ＞ 0.05),suggesting that the two groups had achieved the desired goal of sedation.ELISA results showed:compared with those before treatment,after treatment for 24 hours,the CSF IL-6,sFkn and plasm sFkn levels were temporarily increased in short term,and then showed a tendency of gradually decreasing,and the plasm IL-6 presented persistently descending in the conventional treatment group,while in the midazolam group,since 24 hours after treatment,each index showed a trend of decrease and continued to 72 hours.After treatment at each time point,the CSF and plasm levels of IL-6 and sFkn were significantly lower in midazolam group than those of the conventional treatment group,and reached to the minimal levels at 72 hours [CSF:IL-6 (ng/L) was 251.6 ± 145.7 vs.347.3 ± 146.4,sFkn (ng/L):289.7 ± 79.3 vs.423.6 ± 132.8;plasm:IL-6 (ng/L) was 54.4± 27.3 vs.85.6 ± 41.8,SFkn (ng/L):919.9±426.3 vs.1 199.4 ± 414.8,all P ＜ 0.05].The incidence of epilepsy in the midazolam group was obviously lower than that in the conventional treatment group [1.61％ (1/62) vs.10.34％ (6/58),P ＜ 0.05],but there was no significant difference between midazolam group and the conventional treatment group in the 28-day mortality [11.29％ (7/62) vs.10.34％ (6/58),P ＞ 0.05].Conclusion Midazolam can reduce the incidence of epilepsy in patients with moderate and severe traumatic brain injury,and its brain protective effect may be related to the decrease of CSF and plasm IL-6 and sFkn levels.

To investigate the effects of different fluid resuscitation on renal function and glycocalyx in septic shock rats. The septic shock SD rats (induced by lipopolysaccharide) were randomly divided into control group, normal saline resuscitation group, Lactate Ringer′s solution resuscitation group and succinyl gelatin resuscitation group ( n=6 each). The mean arterial pressure, heart rate, serum creatinine (Scr), urea nitrogen (BUN), renal blood flow, renal tissue pathology, serum interleukin-6, tumor necrosis factor α and glycocalyx were measured at baseline, the development of septic shock, 0 hour and 8 hours after resuscitation. When shock was established, the renal blood flow significantly decreased ( P<0.05) and recovered to normal at 0 hour and 8 hours after resuscitation. Compared with normal saline group and succinyl gelatin group, the levels of Scr, BUN and glycocalyx components (heparan sulfate, syndecan-1) were significant lower in Lactate Ringer′s solution group ( P<0.05). The pathology of kidney tissue suggested that the microscopic ischemic damage with Lactate Ringer′s solution were minor than the other two groups. Compared with normal saline and succinyl gelatin, Lactate Ringer′s solution can reduce the damage of renal function and glycocalyx in septic shock rats.

ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.

Objective To investigate the correlation between the elastographic characteristics of liver and postoperative function of liver allografts.Methods Forty-eight cases of liver transplantation from The First Affiliated Hospital of Sun Yat-sen University were analyzed,Shear wave elastography (SWE) was performed before operation or at one week or one month post-operation.Liver function was evaluated by measuring alanine aminotransferase (ALT),aspartate transaminase (AST),total bilirubin (TBIL),γ-glutamine transferase (GGT),albumin (ALB),alkaline phosphatase (ALP),prothrombin time (PT),activated partial thromboplastin time (APTT),and international normalized ratio (INR).Early allograft dysfunction (EAD) was also analyzed with reference to SWE among liver transplant recipients.Results SWE at one week after transplantation was significantly correlated with TBIL (r=0.525 6,P<0.01),APTT (r=0.668 3,P<0.000 1),PT (r=0.593 7,P=0.000 1),INR (r=0.609 6,P<0.000 1) and prealbumin (r=-0.464 1,P<0.01).However,no significant correlation was observed between pre-operative SWE and parameters of post-operative liver function.SWE in EAD patients was higher than that of patients without EAD (17.60±1.09 kPa vs.13.38±0.99 kPa,P<0.01).The optimal cut-off value of SWE at one week post-operation was 14.85 kPa.Conclusion Postoperative SWE is significantly correlated with postoperative liver function tests and EAD,suggesting SWE is a potential test for evaluating the quality of liver allografts.

Objective To improve the clinical understanding of glucagonoma. Methods A total of 14 cases of glucagonoma were admitted to our hospital, and the clinical features of these cases were retrospectively analyzed. Results (1) The female/ male case ratio was 1 : 1. (2) The median age of onset was 47 years (range 33-61), while the median age at diagnosis was 50 years (range 33-64). (3) The most common initial presentation was necrolytic migratory erythema (7/ 14, 50％). (4) Hyperglycemia was the most common presentation at the time of diagnosis (14/ 14, 100％), followed by necrolytic migratory erythema (13/ 14, 92.9％). (5) The misdiagnosis rate before admission to our hospital was as high as 85.7％ (12/ 14), and the most common misdiagnosis was eczema (7/ 12, 58.3％). (6) The median time from onset of probable symptoms to diagnosis was 4 years. (7) The median plasma glucagon level at diagnosis was 798 pg/ ml (range 200-2853). (8) The median length of the longest tumor diameter of the pancreatic tumors at diagnosis was 4. 0cm ( range 2. 2-8. 0). ( 9) 57. 1％ of primary pancreatic glucagonomas localized in the tail of the pancreas. (10) 57.1％ of patients (8/ 14) had metastases at the time of diagnosis. Conclusions (1)Necrolytic migratory erythema is a relatively sensitive and specific symptom for diagnosis of glucagonoma. (2) The diagnosis for glucagonoma was often delayed, and misdiagnosis was common. ( 3) Most glucagonoma patients had metastases at the time of diagnosis.

Objective:To analyze the risk factors of poor short-term outcome in patients with autoimmune encephalitis (AE).Methods:The data were collected retrospectively from patients hospitalized in the First Affiliated Hospital of Fujian Medical University from March 2016 to January 2021. According to the Modified Rankin Scale (mRS), eighty-one patients with AE were divided into the good prognosis group (mRS≤2, n=48) and the poor prognosis group (mRS>2, n=33). The clinical data, including the basic demographic data, main clinical manifestations, cranial MRI and electroencephalogram, as well as laboratory indicators from blood and cerebrospinal fluid (CSF), were compared between two groups, and the risk factors for poor outcome were analyzed by multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to determine the cut-off value of these risk factors on predicting the poor short-term outcome for the AE patients. Results:The time of hospitalization was significantly longer in the poor prognosis group than in the good prognosis group ( P<0.05). Prevalence of severe disease course at admission, abnormal mental and behavior, δ wave and δ brush of abnormal EEG was significantly higher in the poor prognosis group than in the good prognosis group (all P<0.05). Serum leukocyte count, neutrophil count, lymphocyte count, mononuclear cell count, C-reactive protein, procalcitonin(PCT), alanine aminotransferase, aspartate transaminase, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, apoA1/B, calcium, sodium, anion gap in serum, CSF oligoclonal bands, CSF-IgG index and antibody titer were significantly different between the two groups (all P<0.05). Severity of illness at admission ( OR=1.816, 95% CI 1.250-2.639, P=0.002), PCT ( OR=1.345, 95% CI 1.008-1.794, P=0.044), antibody titer in serum ( OR=1.422, 95% CI 1.071-1.888, P=0.015), CSF-IgG index ( OR=1.802, 95% CI 1.035-3.138, P=0.037) and anionic gap ( OR=1.640, 95% CI 1.191-2.259, P=0.002) were the independent risk factors for the poor short-term prognosis of patients with AE. The AUC value of combing the above 5 indexes to predict the poor short-term prognosis in patients with AE was 0.920 (95% CI 0.834-0.971), with 83.87% sensitivity and 88.37% specificity. Conclusion:Severity of illness at admission, PCT, antibody titer in serum, CSF-IgG index and anionic gap are the independent risk factors of poor short-term prognosis in patients with AE and the combination of these 5 indexes can sufficiently predict the poor short-term prognosis in patients with AE.

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.