Ethics committee in hospitals aims to protect the rights of human subjects and patients,and provide ethical evaluation and justification for guaranteeing the quality of medical research and treatment.Based on experiences in recent years,this paper suggests the following methods in order to manage the activities of ethics committees and push its further development,such as to draft the ethics system,establish the criteria of ethics,implement the process administration and provide ethics training.

Altitude ; Altitude Sickness ; prevention & control ; Health Services Administration ; Humans

Objective To analyze the serum related proteomic fingerprints when Lost Goodwill Target (LGT) proteomic fingerprints drifting from negative to positive in the advanced lung adenocarcinoma patients. Methods The serum proteomic fingerprints of 31 advanced lung adenocarcinoma patients whose LGT fingerprints drifted from negative to positive were detected by SELDI and CM10 protein chip. More than 10 % cluster and M/Z values from 11,000+H to 12,000+H was regarded as LGT positive, otherwise as negative. Different fingerprints were screened by Biomarker Wizard 3.1 and Biomarker Wizard software and the decision tree model was established. Results There were 16 statistically different protein peaks when LGT fingerprints drifting from negative to positive, including 10 up-regulation proteomic fingerprints (M/Z:11531, 11483, 11686, 11394, 11822, 11323, 11911, 12450, 5811 and 5709) and 6 down regulation proteomic fingerprints( M/Z: 4126, 13927, 13784, 7001, 1959 and 2741). Conclusion By SELDI and CM10 protein chip detection, up-regulating fingerprints of M/Z 11531, 11483, 11686, 11394, 11822 and 11323 were regarded as the subtype of LGT when it drifting from negative to positive, while up-regulation of M/Z 11911,12450, 5811 and 5709 and down-regulating of M/Z 4126, 13927, 13784, 7001 and 1959 were regarded as the related fingerprints when LGT drifting from negative to positive. The above different fingerprints are constituted of the fingerprints library when LGT fingerprints drifting from negative to positive and it will provide a platform for studying the LGT proteins.

Objectives To provide prenatal diagnosis and genetic counseling for four athigh-risk pregnant women with a suspected family or personal history of fragile X syndrome (FXS) by genetic screening of fragile X mental retardation (FMR1) gene.Methods This study was conducted on four pregnant women (No.l to 4) who received outpatient treatment in Peking University First Hospital from August 2014 to June 2016.Genomic DNA was extracted from peripheral blood samples of the pregnant women and six of their family members,four of which were suspected or confirmed FXS and the other two were FMR1 gene carriers.Amplide X kits were used to detect CGG repeat size in FMR1 gene.Two amniocytes and one chorionic villi samples were collected from three pregnant women to extract DNAs for FMR1 gene and karyotyping analyses.Results There were patients diagnosed with FXS in all the families by detecting CGG repeat numbers in FMR1 gene.The pregnant woman No.1 was a permutation carrier;No.2 carried normal FMR1 alleles while her brother had a mutation with over 20 CGG repeats in FMRI gene at chromosome X.No.3 and 4 were full mutation carriers with over 200 CGG repeats in FMR1 gene.After genetic counseling,No.3 decided to terminate the pregnancy due to abnormal fetal karyotype (47,XY,+21) and full mutation of FMR1 alleles.No.1 and 4 continued to pregnancy as their fetuses were normal in FMR1 alleles and karyotype.No.2 continued to pregnancy as her fetus was free of FXS risk.Conclusions Prenatal diagnosis and genetic counseling should be conducted on women at highrisk for FXS to avoid birth defects.People with a family history of FXS should be tested for FMR1 gene carrier status.

Objective:To summarize the characteristics of genetic variation and prenatal diagnosis in pedigrees with X-linked adrenoleukodystrophy (X-ALD) and elucidate the value of prenatal diagnosis in preventing the birth of children with X-ALD.Methods:Twenty pedigrees, clinically diagnosed with X-ALD in Peking University First Hospital from November 2012 and March 2019, were included in this retrospective study. Genomic DNA was extracted from peripheral blood and amniotic fluid or chorionic villi samples of probands and their families for detecting variants in ATP-binding cassette subfamily D member 1 ( ABCD1) gene using polymerase chain reaction (PCR)-Sanger sequencing. Linkage analysis was also performed on five microsatellite markers near ABCD1 gene to exclude maternal contamination. Characteristics of ABCD1 gene variants and prenatal diagnosis of X-ALD pedigrees were summarized by descriptive statistics. Results:Twenty ABCD1 gene variants were identified in the 20 pedigrees. The variants in three probands that were not detected by next-generation sequencing were identified by PCR-Sanger sequencing. Among the mothers of the 20 probands, 17 carried ABCD1 variants and three did not. We performed 24 prenatal diagnoses on 20 pregnancies (24 fetuses) and identified eight fetuses with variants who were finally terminated. The 16 cases without variants were born alive. The validation results obtained after termination or delivery were consistent with those performed prenatally. Conclusions:No hotspot variants in ABCD1 gene are detected in these X-ALD patients and most variants are maternally inherited. PCR-Sanger sequencing is an effective method for detecting ABCD1 variants. Prenatal diagnosis for mothers who had a body with X-ALD could prevent another one from birth.

Objective To study the effect of light sedation and traditional sedation (moderate sedation with daily sedation interruption) on hemodynamic indexes and prognosis in critically ill patients after cardiac surgery. Methods A total of 134 patients who were ventilated delay after heart surgery in our hospital from January to June 2017 were enrolled in this study. The patients were randomly divided into light sedation group (RASS score-1-1, n=65) and traditional sedation group (RASS score -3--2, n=69). All patients received sufentanil for postoperative analgesia. The light sedation group received propofol and/or dexmedetomidine as sedative drugs after operation, and the conventional sedation group used midazolam for postoperative sedation. The hemodynamic indexes, the first time of weaning off the ventilator, the duration of mechanical ventilation and ICU stay were compared between the two groups. Patients with low cardiac output syndrome after surgery were analyzed in subgroups. Results (1) There were no significant differences in heart function, operative complications and other indicators between the two groups after surgery (all P＞0.05). The low cardiac output syndrome was found in 12 patients in the light sedation group and 10 cases in the traditional sedation group. (2) Hemodynamic monitoring results displayed that the sedation/central venous oxygen saturation (SvO2/ScvO2) and cardiac index (CI) were higher after sedation than before sedation in both groups (all P＜0.05), but there was no significant difference between the two groups (all P＞0.05). Subgroup analysis showed that the SvO2/ScvO2index was higher in patients with low cardiac output syndrome in the traditional sedative group than that in the light sedation group (P＜0.05). There was no difference in the SvO2/ScvO2 index in patients with non-low cardiac output syndrome between two groups. (3) Compared with the traditional sedation group, the first off-line time, the total mechanical ventilation after surgery and the ICU stay time were significantly shortened, and the incidence of postoperative delirium was decreased in the light sedation group (all P＜0.05). Subgroup analysis showed that in patients with non-low cardiac output syndrome, the first off-line time, total postoperative mechanical ventilation time and total ICU stay were significantly shorter in the light sedation group than those in the traditional sedation group (all P＜0.05). There was no significant difference in patients with low cardiac output syndrome between the two groups (P＞0.05). Conclusion Patients with non-low cardiac output syndrome after cardiac surgery benefit significantly from the superficial sedative strategy, and the postoperative mechanical ventilation time and ICU residence time are reduced. The moderate sedation may contribute to the early cardiac function recovery in patients with low cardiac output syndrome.

Interleukin-1 receptor antagonist (IL-1ra), a member of IL-1 family, is a naturally occurring IL-1 inhibitor as "receptor antagonist", which blocks biological responses mediated by IL-1. Recombinant human IL-1ra (rhIL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 to approximately 2002, rhIL-1 ra was approved by the US Food and Drug Administration and the European Agency for the Evaluation of Medicine Procedure. Unfortunately, 10,000 to 100,000-fold excess amounts of IL-1ra are needed to relieve disease because minimal IL-1 can induce complete biological responses, and the dosage of 100 to approximately 150mg/day in a RA patient is so big that it greatly influence patients' physical, psychological and economical situation. In this study, IL-1ra mutants were established by site-specific mutagenesis to improve its stability. The sites of mutagenesis included R6 K7-AA,R93 K94-AA and K97 R98-AA. IL-1ra and its mutants were expressed in E. coli BL21 (DE3) using pTIG-Trx expressing system with the induction of IPTG. The recombinant proteins were purified by Ni2+ chelate chromatography and Sephadex G75 gel filtration chromatography. The activity of mutants is as high as IL-1ra. We characterized the pharmacokinetic profile of IL-1ra and its mutants. The third mutant's half life is 2.26 times than wt IL-1ra. The study has provided some approaches and experience for further research to improve the metabolism stability of IL-1ra.
Animals ; Escherichia coli ; genetics ; metabolism ; Female ; Humans ; Interleukin 1 Receptor Antagonist Protein ; biosynthesis ; genetics ; pharmacokinetics ; Mutagenesis, Site-Directed ; methods ; Mutant Proteins ; biosynthesis ; pharmacokinetics ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacokinetics

Using the latency of paw withdrawal (PWL) from a noxious thermal stimulus as a measure of hyperalgesia, the effects of i.p. injection of meptazinol and its isomers, 112824 and 112825, on carrageenan-induced thermal hyperalgesia were studied in awaked carrageenan-inflamed rats. Peripheral inflammation was induced by intraplantar (i.pl.) injection of carrageenan (2 mg/100 microl) into one hindpaw in rats. Carrageenan produced marked inflammation (edema and erythema) and thermal hyperalgesia in the injected paws, which peaked at 3 h after injection and showed little change in magnitude for another 3 h. Injection of 0.1 mg/kg meptazinol (i.p.) at 3 h after carrageenan had no effect on the PWLs of either inflamed or non-inflamed hindpaw during the next 100 min (P>0.05, n=8). At the dosage of 1 and 10 mg/kg, meptazinol produced marked anti-nociception and anti-hyperalgesia in non-inflamed and inflamed hindpaw, respectively (P<0.05, n=8-11). The prolonging effect of meptazinol on PWL in inflamed hindpaw was more potent than that in non-inflamed hindpaw. Pre-administration of 1.5 mg/kg naloxone significantly antagonized meptazinol-induced anti-nociception and anti-hyperalgesia. Intraperitoneal injection of an isomer of meptazinol, 112825 (1.5 mg/kg), but not 112824 (1 mg/kg), markedly increased the PWL of the non-inflamed hindpaw. Nevertheless, both the isomers produced similar anti-hyperalgesic effect to that of meptazinol (P<0.05, n=8), which was completely reversed by naloxone (1.5 mg/mg). The results suggest that meptazinol and its isomers have anti-nociceptive and anti-hyperalgesic properties with the former more potent. The effects are mainly mediated by mu opioid receptors. This study provides an important clue for extending clinical utilization of meptazinol and its isomers.
Analgesics, Opioid ; pharmacology ; Animals ; Carrageenan ; Hyperalgesia ; chemically induced ; physiopathology ; Inflammation ; chemically induced ; Isomerism ; Male ; Meptazinol ; pharmacology ; Nociceptors ; drug effects ; Pain ; physiopathology ; Pain Measurement ; methods ; Rats ; Rats, Sprague-Dawley

Bisphosphonate-related osteonecrosis of the jaw (BRONJ),as one serious side-effect of bisphosphonate therapy,has been known for more than ten years since it was first reported in 2003.In the majority of the cases,BRONJ occurs more commonly in the mandible.Those involving the maxilla are relatively few.This paper reported a case that a patient with multiple myeloma developed bilateral maxillary BRONJ after tooth extraction.The patient had used bisphosphonates for more than three years,meanwhile with uncontrolled diabetes mellitus.The patient recovered completely after surgical treatment,in combination with diabetes disease control and antibiotics application.Two key factors to ensure the success of surgical treatment are as follows:sufficient removal of infected and necrotic tissue,and good blood-supply for the local flap to help completely close the wound.The literature was reviewed to analyze the reasons why bone necrosis related to bisphosphonates was most likely to occur in the jaw,especially in the mandible,according to the pathogenesis of this disease.Furthermore,the related risk factors of BRONJ presented in this case were discussed,such as tooth extraction,oral infection and diabetes mellitus,etc.We summarized adjuvant prophylaxes for prevention of BRONJ after tooth extraction,for example,drug holiday that could be used in the dental clinic.This case report reminds us that it's of great importance to establish the awareness that the osteonecrosis of the jaw may be related to the use of some bone-stabilizers.As for patients with a history of exposure to antiresorptive or antiangiogenic agents,dentists are supposed to be cautious.It's recommended to take appropriate measures in perioperative period of oral surgical treatment to prevent BRONJ.

Objective To investigate the current prevailing status of endemic fluorosis in the Yellow River basin of Shandong Province and to provide the scientific evidence for making strategies in prevention and control.Methods Nine counties were chosen to carry out the epidemiological investigation.The content of fluoride in drinking water was determined by F-ion selective electrode and dental fluorosis of children aged 8～12 years old was diagnosed by Deans method.Results Water fluoride content was determined in 1761 fluorosis villages,among which 606 villages had water fluoride content≤1.00 mg/L,accounting for 34.41%(606/1761);1155 villages had water fluoride content＞1.00 mg/L,which accounted for 65.59%(1155/1761).The highest water fluoride content was 11.33 mg/L.Water fluoride content of 618 water-improving and defluoridation projects had been determined,among which 449 projects had water fluoride content≤1.00 mg/L and accounted for 72.65%(449/618),169 projects had water fluoride content＞1.00 mg/L and accounted for 27.35%(169/618),the highest water fluoride content was 5.85 mg/L.The total rate of dental fluorosis of children aged 8～12 years old was 45.03%(25 579/56 804) and the index of dental fluorosis was 0.80. Conclusions In the Yellow River basin in Shandong Province,up to 50.00%in the villages the water fluoride content exceeds the county standard(≤1.00 mg/L).The prevalence of endemic fluorosis in the basin hasn't been effectively controlled.So the counterrneasures for endemic fluorosis should be carried out as soon as possible.