Donation after death is the most important ethical principle to carry out organ donation after citizens’ death. The newly-revised Regulations on Human Organ Donation and Transplantation does not define death, and avoids the key question of “whether to recognize brain death”. Certain legal risks or damages to the rights and interests of donors may exist in organ donation. Death is an inevitable part of human life. It is necessary to establish specific criteria, which is also the only approach, to define death in any era. Death criteria are established based on the view of death, and restricted by the development level of productive forces and other social factors. The determination of death criteria hugely varies between China and the West. To standardize organ donation and transplantation and promote high-quality development of organ donation, medical staff must adhere to the principle of pure motivation, take informed consents as the premise, respect the donors' and their close relatives' rights to choose their own death criteria, strictly follow the death judgment procedures and operating norms, and ensure the scientificity, accuracy and fairness of death determination.

Objective:To investigate the effect of minocycline on neuroinflammation of rats with post-traumatic stress disorder(PTSD).Methods:The rat model of PTSD was prepared by a single prolonged stress(SPS)method,and the rats were treated with minocycline(PTSD+Mino group)or normal saline(PTSD group)by gavage.The behavioral changes of rats were detected by light-dark box test.The expression of ionized calcium-binding adapter molecule 1(Iba-1)in hippocampus was detected by immunohistochemical staining.The contents of IL-1β and TNF-α in hippocampus were detected by ELISA,and the expression levels of IL-1β and TNF-α mRNA in hippocampus were detected by real-time RT-PCR(qRT-PCR).Results:After 3 days of SPS stimulation,the anxiety-like behavior of rats was obvious,the expression of Iba-1 in hippocampus was increased,and the contents of IL-1β and TNF-α in hippocampus were in-creased.Minocycline treatment significantly reduced anxiety-like behavior and decreased the expression of Iba-1 in the hippocampus of PTSD rats.Meanwhile,minocycline treatment also decreased the levels of IL-1β and TNF-α mRNA and protein in the hippocampus.Conclusion:Minocycline can improve the anxiety-like behavior of PTSD rats by inhibiting the activation of microglia.

Objective:To investigate the role of purine receptor P2X7 in cerebral ischemia-reperfusion injury(CI-RI).Methods:The CIRI model was prepared by right middle cerebral artery occlusion(MCAO).The P2X7 inhibitor bright blue G(BBG)or NLRP3 inhibitor MCC950 were injected intraperitoneally.Neurological function score was used to detect the changes of neural function in rats.The integrity of blood-brain barrier was detected by Evans blue staining.The contents of IL-1 β and IL-18 in cerebrospinal fluid(CSF)of rats were detected by ELISA,and the expressions of P2X7,CD11b,and NLRP3 in the right cerebral cortex were detected by Western Blot.Results:Treatment with BBG or MCC950 improved neural function in CIRI rats,while reducing the amount of Evans blue in brain tissue and IL-1 β and IL-18 levels in CSF.In addition,BBG can reduce the expression of CD11b and NLRP3 in the right cerebral cortex,while MCC950 can only reduce the expression of CD11b,but has no effect on P2X7 expression.Conclusion:BBG alle-viates neuroinflammation in CIRI rats by inhibiting P2X7/NLRP3 pathway.

Objective:To investigate the effect of lateral hydraulic injury(LFPI)on the integrity of blood-brain bar-rier in rats and its molecular mechanism.Methods:The rat LFPI model was prepared.Neurological impairment of rats was assessed by neurological severity score(NSS).The integrity of blood-brain barrier was assessed by dry/wet ratio test and Evans blue penetration test.The expressions of zonula occludens-1(ZO-1),occludin,and aquaporin 4(AQP4)were detected by Western Blot.Results:LFPI resulted in neurological dysfunction,increased cerebral water content,increased Evans blue permeability,decreased occludin and ZO-1 expression,and increased AQP4 expression.Conclusion:LFPI can cause cerebral edema and damage the integrity of blood-brain barrier in rats.

Objective:To study the prevalence and association factors of depressive and anxiety disorders in the hypertensive population.Methods:Using the database obtained from the 2013 China Chronic Disease and Risk Factor Surveillance and the 2013-2015 China Mental Health Survey,4 861 hypertensive residents were used as study subjects.And using the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)as diagnostic criterion for depressive and anxiety disorders,the 12-month prevalence was calculated.Multifactorial lo-gistic regression models were used to explore the association factors of hypertension comorbid depressive and anxie-ty disorders.Results:The 12-month prevalence rates of depressive disorders and anxiety disorders were 4.1％and 5.0％in 4 861 hypertensive residents.Chinese Han[OR(95％CI):2.00(1.01-3.93)],lack of sleep[OR(95％CI):1.82(1.34-2.48)],having myocardial infarction[OR(95％CI):2.35(1.18～4.67)]and stroke in the past year[OR(95％CI):2.10(1.19-3.72)],and chronic obstructive pulmonary disease[OR(95％CI):2.11(1.11-4.05)]were risk factors of hypertension comorbid depressive disorder.Hypertensive people with controlled blood pressure[OR(95％CI):2.01(1.30-3.13)]had a higher risk of co-morbid depressive disorder than those with blood pressure above the normal range on this measurement.Chinese Han[OR(95％CI):2.51(1.32-4.80)],Southwest China[OR(95％CI):1.64(1.02-2.63)],and lack of sleep[OR(95％CI):1.45(1.09-1.93)]were risk factors of hypertension comorbid anxiety disorder.Former but current non-smoking[OR(95％CI):0.48(0.23-0.99)]was a protective factor of hypertension comorbid anxiety disorder.Conclusion:The 12-month prevalence of anxiety disorder was higher than that of depressive disorder in this hypertensive population.Both Han and sleep deprived hypertensive people had a higher risk of comorbid depressive and anxiety disorders.

Objective To study the impact of a Western diet-type feed on biological indicators and histopathology in APOE-/-mice.Methods Forty-eight female and 48 male APOE--mice,and 48 female and 48 male C57BL/6J mice were divided into eight breeding groups:APOE-/-breeding feed group,APOE-/-Western dietary feed group,C57BL/6J breeding feed group,and C57BL/6J Western dietary feed group(24 male and 24 female mice per group).Mice were fed the respective diets from 3 weeks until the end of the experiment at 20 weeks.After the experiment,serum was collected for measurement of biochemical indicators.Aortas were removed for oil red O staining and gross examination and the aorta root was paraffin sectioned and stained with hematoxylin and eosin.Results A Western diet did not significantly increase body weight in APOE-/-mice,but did significantly improve the blood lipid index and total cholesterol,low-density lipoprotein,and high-density lipoprotein levels,and promoted the formation of atherosclerotic plaques.Male mice were suitable for modeling gross aortic plaques while female mice were suitable for modeling aortic arch root plaques.Conclusions A Western diet can promote atherosclerosis in APOE-/-mice,increase the aortic plaque area ratio,shorten modeling time,and improve modeling uniformity.

Objective:To assess the diagnostic value of anti-salivary gland protein-1(SP1)antibody combined with anti-parotid secretory protein(PSP)antibody for Sj?gren's syndrome(SS).Methods:A total of 60 patients with primary SS(pSS)who were treated in the outpatient and inpatient department of Department of Rheumatology and Immunology of the Second Hospital of Hebei Medical University from January 2020 to December 2022 were collected.Thirty patients with other autoimmune diseases accompa-nied by dry mouth and/or dry eyes were collected as disease control group.Thirty healthy subjects from the physical examination center were collected for healthy control group,serum samples were obtained from all of them.Their general features and clinical information including clinical manifestations,labora-tory examinations and other examinations were recorded.The 2016 American College of Rheumatology(ACR)/European League against Rheumatism(EULAR)classification criteria were adopted as the diag-nostic standard of pSS.Immunoglobulin G(IgG)subtype of anti-SP1 antibody and anti-PSP antibody were detected by chemiluminescence immunoassay.The receiver operating characteristic(ROC)curve was used to evaluate the accuracy of anti-SP1 antibody and anti-PSP antibody in diagnosing pSS.The cli-nical characteristics of anti-SP1 antibody and anti-PSP antibody positive patients and negative patients in pSS group were further compared.Independent samples t test,Mann-Whitney U test,variance analysis,Kruskal-Wallis test,Chi-square test or Fisher's exact test and Spearman correlation analysis were used for statistical analysis.Results:There was no significant difference in age(F=1.406,P=0.495)and gender(x2=2.105,P=0.349)among pSS group,disease control group and healthy control group.The expression levels of anti-SP1 antibody(H=16.73,P＜0.001)and anti-PSP antibody(H=26.09,P＜0.001)were statistically different among the three groups.An intergroup comparison of anti-SP1 antibody expression levels showed that there was a statistically significant difference between pSS and healthy con-trol group(P＜0.001),but no statistically significant difference between the other groups.Comparison of anti-PSP antibody expression levels between the groups showed that there were statistically significant differences between pSS and healthy control group(P＜0.001),and between disease control group and healthy control group(P=0.009),while no statistically significant differences between the other groups.The positive rate of anti-SP1 antibody in pSS group was significantly higher than that in disease control group and healthy control group(58.33％vs.40.00％vs.13.33％,P＜0.001).The positive rate of anti-PSP antibody in pSS group was significantly higher than that in disease control group and healthy control group(75.00％vs.56.17％vs.16.67％,P＜0.001).The area under the curve for anti-SP1 antibody was 0.688(P＜0.001).The sensitivity and specificity of anti-SP1 antibody were 58.33％(35/60)and 70.00％(42/60)respectively,the positive predictive value was 66.04％(35/53)and the negative predictive value was 54.55％(42/77)of anti-SP1 antibody.The area under the curve of anti-PSP antibody was 0.720(P＜0.001),with a sensitivity was 75.00％(45/60),and spe-cificity was 63.33％(38/60).The positive predictive value and negative predictive value of anti-PSP an-tibody were 67.16％(45/67)and 71.70％(38/53)respectively.All the 13 pSS patients were negative for anti-Sjogren's syndrome A(SSA,including SSA52 and SSA60)antibody and anti-Sjogren's syn-drome B(SSB)antibody.Among them,11 patients were positive for both anti-SP1 antibody and anti-PSP antibody,1 patient was positive for anti-SP1 antibody and 1 patient was positive for anti-PSP anti-body.The clinical features of anti-SP1 antibody and anti-PSP antibody positive and negative groups were compared in pSS patients.The duration of disease in anti-SP1 antibody positive group was shorter(Z=-2.277,P=0.023)when compared with the negative patients.The patients with positive anti-PSP an-tibody were younger than those in the negative group(t=2.598,P＜0.05),the positive rate of rheuma-toid factor(P=0.002)and the serum level of IgG(t=3.806,P=0.003)in anti-PSP antibody positive group were higher than in the negative group.Analysis of the correlation between anti-SP1 antibody and anti-PSP antibody in the pSS patients showed that there was significant correlation between them(r=0.801,P＜0.001).Conclusion:Both anti-SP1 antibody and anti-PSP antibody are valuable in the diag-nosis of SS,and anti-SP1 antibody is helpful for the early diagnosis of pSS.The combined detection of anti-SP1 antibody and anti-PSP antibody is helpful for the early diagnosis of pSS patients with negative anti-SSA antibody and anti-SSB antibody.

High-quality development is the primary task of building a socialist modern country in an all-round way. Organ donation and transplantation in China are evolving from high-speed growth to high-quality development, which put forward new requirements for the safe, stable and healthy operation of Organ Procurement Organization (OPO). Safety is the foundation and prerequisite for achieving the goal of high-quality development. As an independent and comprehensive department, internal audit should create new achievements in the new era. The department should include OPO and organ donation into the scope of internal audit, shift the emphasis upon the overall development of organ donation. Besides, it should fully consider the actual situation in different places, conduct all-round, objective and fair evaluation, provide evaluation and consulting services for OPO to properly implement organ donation, and give full play to the supervision and prevention role of internal audit.

OBJECTIVES: Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM). METHODS: A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups. RESULTS: The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T_1/2), area under the curve (AUC), time to reach maximum concentration (T_max). Compared with the control group, AUC was increased by 23.5%, T_max and T_1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population. CONCLUSIONS Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.
Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Metformin/therapeutic use* ; Acidosis, Lactic ; Tandem Mass Spectrometry ; Hypoxia ; Glucose

Léri-Weill dyschondrosteosis (LWD) has typical triad: short middle limbs, short stature, Madelung deformity of wrist, and increased body mass index. Short stature and high body mass index are risk factors for metabolic syndrome, type 2 diabetes, cardiovascular diseases, and autoimmune thyroid diseases. However, metabolic disorders and thyroid diseases in adult LWD patients have not been elucidated. This paper reports two adult patients with LWD presented to the Department of Endocrinology and metabolism. By introducing clinical characteristics, genetic variations, and diagnostic methods, physicians can deepen their understanding of LWD, improve diagnosis, and be aware of the comorbid metabolic diseases and thyroid disorders with a view of early prevention and treatment.