Protocol for the development of the Expert consensus on sedation and analgesia for neurocritical care patients (2023) / 中华危重病急救医学

To further standardize the sedation and analgesia treatment for neurocritical care patients, the National Center for Healthcare Quality Management in Neurological Diseases and Chinese Society of Critical Care Medicine organized national experts in this fields to form Working group of the Expert consensus on sedation and analgesia for neurocritical care patients in order to update the Expert consensus on sedation and analgesia for patients with severe brain injury (2013) based on evidence-based medicine. This update aims to provide scientific guidance for the clinical diagnosis and treatment of neurocritical care patients. The working group followed the definition of clinical practice guidelines by the Institution of Medicine (IOM) and the World Health Organization guidelines development handbook and Guidelines for the formulation/revision of clinical guidelines in China (2022) to register and draft the Expert consensus on sedation and analgesia for neurocritical care patients. The working group will strictly adhere to the consensus development process to formulate and publish the Expert consensus on sedation and analgesia for neurocritical care patients (2023). This protocol primarily introduces the development methodology and process of the Expert consensus on sedation and analgesia for neurocritical care patients (2023), including the purpose of the update, the target population, the composition of the consensus development working group, the presentation and collection of clinical questions, evidence evaluation and summarization, and the generation of recommended opinions. This will make the consensus development process more standardized and transparent.

Clinical feature and genetic analysis of a patient with Idiopathic hypogonadotropic hypogonadism due to a novel variant of CHD7 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene.@*METHODS@#A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4).@*CONCLUSION@#The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.

Clinical characteristics and genetic analysis of an ethnic Han Chinese child with Keppen-Lubinsky syndrome due to a de novo KCNJ6 mutation / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS).@*METHODS@#Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel.@*CONCLUSION@#The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.

Quality assessment of clinical practice guidelines or consensus for pancreatic diseases in China from 2016 to 2021 / 中华胰腺病杂志

Objective:To evaluate the methodological quality and reporting quality of clinical practice guidelines or consensuses in the field of Chinese pancreatic diseases from 2016 to 2021, and provide reference for formulating clinical practice guidelines and consensuses in this field.Methods:VIP, Wanfang , CNKI and CBM databases were searched for articles published from January 2016 to March 2021. The main index terms were " pancreas" , " guideline" , " consensus" , and the supplementary index terms were " pancreatitis" , " pancreatic cancer" , " pancreatic head cancer" . Two researchers independently selected the literature. The appraisal of guidelines for research and evaluation (AGREE-China) was utilized to assess the methodological quality of the guidelines or consensuses, and the reporting items for practice guidelines in healthcare (RIGHT) tool was used to assess the reporting quality.Results:A total of 14 literature were included, including 7 literature on pancreatic cancer, 3 literature on acute pancreatitis, 1 literature on chronic pancreatitis and 3 literature on others. The results of the assessment by the AGREE-China tool showed that there were no document with a total score greater than or equal to 60.0 points, two with 40.0 to 59.9 points, eleven with 20.0 to 39.9 points, and one with less than 20.0 points. Among the results of RIGHT list, basic information was reported the highest(72.62%) and funding and declaration was the lowest(0).Conclusions:The methodological and reporting quality of the guidelines or consensuses on pancreatic disease in China from 2016 to 2021 are generally not high. In the process of developing domestic guidelines or consensuses on pancreatic diseases, the guideline developer should refer to AGREE-China and RIGHT to improve the quality of clinical practice guidelines or consensuses.

Expressions of miRNA-146a in peripheral mononuclear cells of children with systemic juvenile idiopathic arthritis and its clinical significance / 中华实用儿科临床杂志

Objective:To investigate the role of miR-146a in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA) and its clinical significance.Methods:This article is a prospective clinical cohort study.Twenty-six patients with sJIA (14 cases of initial active group and 12 cases of stable group), 15 patients with multijoint juvenile idiopathic arthritis (JIA) and 15 patients with oligojoint JIA diagnosed in the Department of Rheumatology and Immunology of Anhui Provincial Children′s Hospital from June 2018 to December 2020 were enrolled.Twenty healthy controls from the out-patient clinic were also recruited.The expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) of research objects was detected by real-time fluorescence quantitative polymerase reaction (qPCR), and the serum levels of interleukin (IL) - 6, tumor necrosis factor (TNF) - α and IL-1β in sJIA patients and healthy controls were detected by enzyme-linked immunosorbent assay.The expression levels of miR-146a in PBMCs and cytokines among different groups were compared by analysis of variance. Pearson correlation analysis was used to analyze the correlation of the relative expression level of miR-146a in PBMCs with clinical inflammatory indexes and serum cytokines in sJIA patients. Results:(1) The expression level of miR-146a in PBMCs of early sJIA patients was significantly higher than that in the multijoint JIA group and oligojoint JIA group (8.77±3.15 vs.4.40±1.59, 2.55±1.15, t=6.27, 14.23; all P<0.05). The expression level of miR-146a in PBMCs of sJIA active patients was significantly higher than that in sJIA stable patients (8.77±3.15 vs.3.63±1.37, t=10.27, P<0.05). There was no significant difference in the expression level of miR-146a between the sJIA stable group and healthy control group ( P>0.05). (2) The expression levels of IL-1β, IL-6 and TNF-α were significantly higher in sJIA active patients group than those in sJIA stable group[(58.56±17.47) ng/L vs.(26.32±10.54) ng/L, (73.72±11.16) ng/L vs.(23.20±9.12) ng/L, (70.93±19.97) ng/L vs.(24.25±9.49) ng/L, all P<0.05]. There was no significant difference in the expression levels of IL-1β, IL-6 and TNF-α between the sJIA stable group and healthy control group(all P>0.05). (3)The expression of miR-146a in PBMCs of sJIA patients was positively correlated with serum ferritin levels, platelets, erythrocyte sedimentation rates, C-reactive proteins, IL-1β, IL-6 and TNF-α( r=0.542, 0.433, 0.329, 0.306, 0.333, 0.342, 0.319, all P<0.05). Conclusions:miR-146a may be involved in the inflammatory process of sJIA disease.miR-146a can well distinguish sJIA from multijoint JIA and oligojoint JIA.TNF-α, IL-1β and IL-6 are involved in sJIA inflammatory responses.

Clinical Characteristics and Treatment of Blau Syndrome in Chinese Children-a National Multicenter Study / 罕见病研究

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Clinical and prognostic features of hypertriglyceridemic pancreatitis during pregnancy / 临床肝胆病杂志

ObjectiveTo investigate the clinical and prognostic features of hypertriglyceridemic pancreatitis (HTGP) during pregnancy. MethodsA total of 77 patients with acute pancreatitis in pregnancy who were admitted to The Affiliated Hospital of Southwest Medical University from January 2013 to June 2020 were enrolled as subjects, and according to the presence or absence of HTGP, they were divided into HTGP group with 38 patients and non-HTGP group with 39 patients. The two groups were compared in terms of the clinical features including age, pregnancy, laboratory markers, complication, and prognostic indices. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of ranked data between two groups. According to the trimester of pregnancy, the patients were divided into early pregnancy group with 4 patients, middle pregnancy group with 14 patients, and late pregnancy with 59 patients, and blood lipid levels were compared between groups; the Kruskal-Wallis H test was used for comparison between two groups or within each group. ResultsCompared with the non-HTGP group, the HTGP group had significantly higher mean age (t=-3.000, P=0.004) and proportion of patients with diabetes (χ2=8.867, P=0.003). Compared with the non-HTGP group, the HTGP group had a significantly higher proportion of patients with disease onset in the third trimester (P＜0.001) and a significantly lower serum level of sodium (Z=-6.328, P＜0.001). Compared with the non-HTGP group, the HTGP group had significantly higher incidence rates of acute peripancreatic fluid collection (76.3% vs 33.3%, χ2=14.342, P＜0.001) and systemic inflammatory response syndrome (81.6% vs 410%, χ2=13.310, P＜0.001). There were significant differences between the two groups in the length of hospital stay, the rate of admission to the intensive care unit, and hospital costs (Z=-2.077, χ2=11.537, Z=-3.525, all P＜0.05). The levels of total cholesterol and triglyceride in the third trimester were significantly higher than those in middle pregnancy (both P＜0.05). ConclusionCompared with the non-HTGP group, the HTGP group has a higher proportion of patients with disease onset in the third trimester of pregnancy, a higher risk of complications, a longer length of hospital stay, and higher hospital costs.

A case of SIFD syndrome caused by novel compound heterozygous variants of TRNT1 gene / 中华医学遗传学杂志

OBJECTIVE@#To detect variant of TRNT1 gene in a child featuring sideroblastic anemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD).@*METHODS@#The proband and his parents were analyzed through trio-whole exome sequencing. Sanger sequencing and bioinformatic analysis were carried out to verify the candidate variant sites associated with the clinical phenotype.@*RESULTS@#Genetic testing showed that the proband has carried compound heterozygous variants of the TRNT1 gene, namely c.88A>G(p.Met30Val) and c.363G>T(p.Glu121Asp). Sanger sequencing confirmed that the variants were respectively inherited from his father and mother. The variants were unreported previously. By bioinformatic analysis, both variants were predicted to affect the stability of binding of the TRNT1 protein with tRNA. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.88A>G and c.363G>T variants of TRNT1 gene were predicted to be uncertain significance (PM2+PP3+PP4) and likely pathogenic (PM1+PM2+PP3+PP4), respectively.@*CONCLUSION@#The c.88A>G (p.Met30Val) and c.363G>T(p.Glu121Asp) compound heterozygous variants of the TRNT1 gene probably underlay the disease in this patient. Above finding has enriched the spectrum of TRNT1 gene variants.

Prospects and developments in the technologies of high frequency oscillatory ventilation / 生物医学工程学杂志

The high frequency oscillatory ventilation (HFOV) is characterized with low tidal volume and low mean airway pressure, and can well support the breathing of the patients with respiratory diseases. Since the HFOV was proposed, it has been widely concerned by medical and scientific researchers. About the HFOV, this paper discussed its current research status and prospected its future development in technologies. The research status of ventilation model, mechanisms and ventilation mode were introduced in detail. In the next years, the technologies in developing HFOV will be focused on: to develop the branched high-order nonlinear or volume-depended resistance-inertance-compliance (RIC) ventilation model, to fully understand the mechanisms of HFOV and to achieve the noninvasive HFOV. The development in technologies of HFOV will be beneficial to the patients with respiratory diseases who failed with conventional mechanical ventilation as one of considerable ventilation methods.

Value of controlled low central venous pressure in laparoscopic hepatectomy within an ERAS programme / 中华麻醉学杂志

Objective:To evaluate the value of controlled low central venous pressure (CLCVP) in laparoscopic hepatectomy within an enhanced recovery after surgery (ERAS) programme.Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, of liver function Child-Pugh grade A, with New York Heart Association classⅠor Ⅱ, scheduled for elective laparoscopic hepatectomy with an expected surgery time 3-5 h, were divided into 2 groups ( n=30 each) using a random number table method: CLCVP-ERAS group (group CE) and routine ERAS group (group E). In group CE, the central venous pressure was maintained less than 5 cmH 2O through using restricted fluid replacement, adjusting the position, giving the vasodilator and etc.In group E, the central venous pressure was maintained at 5-12 cmH 2O.Arterial blood samples were then collected before operation and at 1 and 4 days after operation for determination of parameters of hepatic and renal functions.The volume of fluid infused before and after liver resection, total volume of intraoperative fluid infused, blood loss, blood transfusion, duration of surgery, postoperative time to first flatus, off-bed time, length of hospitalization and total cost of hospitalization were recorded. Results:Compared with group E, the volume of fluid infused before liver resection, total volume of intraoperative fluid infused, blood loss, and blood transfusion were significantly decreased, the volume of fluid infused after liver resection was increased, the duration of surgery, time to first flatus after operation, off-bed time and length of hospitalization were shortened, and the total cost of hospitalization was reduced ( P<0.05), and no significant change was found in the parameters of hepatic and renal functions in group CE ( P>0.05). Conclusion:CLCVP is helpful for the rapid recovery of patients without obvious adverse reactions when used for laparoscopic hepatectomy within an ERAS programme.

Investigating the mechanism of the high frequency ventilation for the oscillation airflow between left and right lungs / 生物医学工程学杂志

Traditionally, adequate tidal volume is considered to be a necessary condition to support respiratory patient breathing. But the high frequency ventilation (HFV) with a small tidal volume can still support the respiratory patient breathing well. In order to further explore the mechanisms of HFV, the pendelluft ventilation between left and right lungs was proposed in this paper. And a test platform by using two fresh sheep lungs was developed for investigating the pendelluft ventilation between the left and right lungs. Furthermore, considering the viscous resistance ( ), inertance ( ) and lung compliance ( ) in the lung, a second-order lung ventilation model was designed to inspect and evaluate the pendelluft ventilation between left lung and right lungs. On referring to both results of experiments in practice and simulation in MATLAB Simulink, between the left and right lungs, the phase difference in their airflow happens during HFV at some frequencies. And the pendelluft ventilation between the left and right lungs is resulted by the phase difference, even if the total airflow entering a whole lung is 0. Under HFV, the pendelluft ventilation between left and right lungs will benefit the lungs being more adequately ventilated, and will be improve the utilization rate of oxygen in the lungs.

Exploring the innovative " post-payment" for medical service in Hangzhou / 中华医院管理杂志

Post-payment for patients can minimize their errands and improve their medical experience. Since February 2019, Hangzhou Municipal Health Commission began to try the " post-payment" service. This mode is integrated into the municipal credit system, and the patients can obtain the corresponding credit line according to their credit rating. Within such line, the patient can pay only once for all their medical services received per visit. The mode covers all Hangzhou residents with credit rating and has served nearly 20 million outpatient and emergency patients with expedient services. Thanks to the reform, the number of payment for patients to see a doctor reduced from an average of 2 to 3 times to only 1 time. It is proved that the credit system can realize payment after medical service and it is controllable.

Effect of SALL4 on radiosensitivity of leukemia cell line HL-60 / 中华放射肿瘤学杂志

Objective@#To evaluate the effect of down-regulating SALL4 on the radiosensitivity of leukemia cells, aiming to provide new ideas for improving radiosensitivity of leukemia patients.@*Methods@#Human acute myeloid leukemia cell line HL-60 infected with shRNA SALL4 and shRNA control lentivirus was classified into the Lv-shSALL4 group and Lv-shNC group. The levels of SALL4 mRNA and protein in cells were detected by RT-PCR and Western blot. The infected cells treated with 8 Gy dose irradiation were assigned into the Lv-shSALL4+ radiation and Lv-shNC+ radiation groups. The cell apoptosis was detected by flow cytometry. The levels of cleaved Caspase-3, cleaved Caspase-9 and Bax proteins in cells were determined by Western blot. The cells in the Lv-shSALL4 and Lv-shNC groups were exposed to 0, 2, 4, 6 and 8 Gy irradiation. The radiosensitivity ratio was determined by cell clone test.@*Results@#The level of SALL4 in the Lv-shSALL4 group was significantly lower than that in the Lv-shNC group (P<0.05). The cell apoptosis rate was significantly increased, the levels of cleaved Caspase-3, cleaved Caspase-9 and Bax proteins were remarkably up-regulated in cells compared with those in the Lv-shNC group (all P<0.05). The cell proliferation ability in the Lv-shSALL4+ radiation was significantly reduced, the cell apoptosis rate was considerably increased, the levels of cleaved Caspase-3, cleaved Caspase-9 and Bax proteins were significantly up-regulated compared with those in the Lv-shSALL4 and Lv-shNC+ radiation groups (all P<0.05). The cell radiosensitization ratio in the Lv-shSALL4 group was 1.323.@*Conclusion@#Down-regulating SALL4 can increase the radiosensitivity of leukemic cells, inhibit the cell proliferation and induce the apoptosis of leukemic cells.

Clinical significance of procalcitonin in early diagnosis of acute left heart failure complicated with pulmonary infection in the elderly / 中华老年医学杂志

Objective To investigate clinical significance of procalcitonin (PCT)in the early diagnosis of acute left heart failure complicated with pulmonary infection in the elderly.Methods A total of 113 patients with acute left heart failure or acute left heart failure complicated with pulmonary infection who were admitted into our emergency department from August 2012 to February 2018 were retrospectively analyzed.Data of serum concentration of PCT were collected on the first and third days after admission.The diagnostic values of serum PCT and C-reaction protein(CRP)were evaluated based on the patient's diagnostic data.ROC curves were plotted for PCT,and its cut-off value was calculated.Results Serum levels of PCT on the first and third days after admission were higher in pulmonary infection group than in left heart failure group[(2.45±0.42) μg/L vs.(0.54±0.03) μg/L,(1.25±0.17) μg/L vs.(0.43±0.03) μg/L,t =34.27 and 35.78,P=0.000 and 0.000].The diagnostic specificity,positive predictive value,and negative predictive value of PCT were better than those of CRP(x2 =4.97,4.76 and 4.17,P =0.030,0.030 and 0.040).There was no significant difference in the diagnostic sensitivity between PCT and CRP (x2 =3.05,P =0.080).The best diagnostic cut-off value of PCT was 0.597 μg/L in which the sensitivity of diagnosis of heart failure complicated with pneumonia was 91.07％ and the specificity was 90.77％.Conclusions Serum PCT test can assist the early diagnosis of acute left heart failure complicated with pulmonary infection in elderly patients with high sensitivity and specificity.The best diagnostic cut-off value of PCT is 0.597 μg/L.Based on serum PCT test,early rational use of antibiotics for controlling acute left heart failure complicated with pulmonary infection in elderly patients is worthy of generalization.

Effect of SALL4 on radiosensitivity of leukemia cell line HL-60 / 中华放射肿瘤学杂志

Objective To evaluate the effect of down-regulating SALL4 on the radiosensitivity of leukemia cells,aiming to provide new ideas for improving radiosensitivity of leukemia patients.Methods Human acute myeloid leukemia cell line HL-60 infected with shRNA SALL4 and shRNA control lentivirus was classified into the Lv-shSALL4 group and Lv-shNC group.The levels of SALL4 mRNA and protein in cells were detected by RT-PCR and Western blot.The infected cells treated with 8 Gy dose irradiation were assigned into the Lv-shSALL4 + radiation and Lv-shNC+radiation groups.The cell apoptosis was detected by flow cytometry.The levels of cleaved Caspase-3,cleaved Caspase-9 and Bax proteins in cells were determined by Western blot.The cells in the Lv-shSALL4 and Lv-shNC groups were exposed to 0,2,4,6 and 8 Gy irradiation.The radiosensitivity ratio was determined by cell clone test.Results The level of SALL4 in the Lv-shSALL4 group was significantly lower than that in the Lv-shNC group (P＜0.05).The cell apoptosis rate was significantly increased,the levels of cleaved Caspase-3,cleaved Caspase-9 and Bax proteins were remarkably up-regulated in cells compared with those in the Lv-shNC group (all P＜ 0.05).The cell proliferation ability in the Lv-shSALL4 + radiation was significantly reduced,the cell apoptosis rate was considerably increased,the levels of cleaved Caspase-3,cleaved Caspase-9 and Bax proteins were significantly up-regulated compared with those in the Lv-shSALL4 and Lv-shNC+ radiation groups (all P＜0.05).The cell radiosensitization ratio in the Lv-shSALL4 group was 1.323.Conclusion Down-regulating SALL4 can increase the radiosensitivity of leukemic cells,inhibit the cell proliferation and induce the apoptosis of leukemic cells.

Study on risk factors of urinary stone formation in primary gout patients / 中华风湿病学杂志

Objective To explore the risk factors of urinary stone formation in primary gout patients by urinary chemical,serum and urinary biochemical features analysis.Methods All the patients diagnosed as primary gout at Peking University First Hospital from 2009 to 2015 were included in the study.All patients were diagnosed with or without urolithiasis by ultrasound or computed tomography.Their clinical features,baseline urinary metabolic panels and stone composition were analyzed and compared between the two group of patients.Moreover,the risk factors of uric acid stone formation were determined by comparing different composition of stone formation group.Analysis of variance,t-test,chi-square test,spearman's test and logistic regression were used for statistical analysis.Results One hundred and forty-four male gout patients were enrolled in the study among these patients,48 were with urolithiasis and 96 patients were without urolithiasis.Most (136,94.4％) patients were under excretion of uric acid.Among 48 gout patients with uric acid urolithiasis,30 (62.5％) patients who had pure uric acid stones,and 18 (37.5％) had stones composed of mixed uric acid and oxalic acid.Compared with mixed stone group,the mean age was significantly lower in pure uric acid stone group [(46±13) years vs (60±15) years,t=4.1,P＜0.05];and disease duration was shorter [(42±11)months vs (71±22) months,t=-0.2,P＜0.01].The 24-hour urinary uric acid were significantly higher in the uric acid stone group [(5 205±3 524) μmol/d vs (2 132±1 326) μmol/d,t=3.6,P＜0.05].Also,the mean of both Ccr and Cua were higher [(119±61) ml/min vs (75±39) ml/min,t=3.6,P＜0.05;(6.3±3.6) ml/min vs (3.2±2.0)ml/min,t=l.4,P＜0.05].Urinary pH was negatively correlated with uric acid stone in primary gouty patients (r=-0.212,P＜0.01);The total excretion of urinary uric acid was positively correlated with uric acid stones formation (r=0.633,P＜0.05).High urinary uric acid excretion and Ccr were independent risk factors for uric acid stone formation in primary gout patients.Conclusion Urine pH is negatively correlated with uric acid stone formation.Urinary analysis of 24-hour uric acid and Ccr are risk factors for pure uric acid urolithiasis in primary gout patients.

The impact of different doses of azithromycin maintenance treatment on expiratory flow limitation and quality of life among stable patients with non-cystic fibrosis bronchiectasis / 中国医师进修杂志

Objective To observe the benefits and safety of different maintenance doses of azithromycin for long-term treatment in adult patients with non-cystic fibrosis (CF) bronchiectasis. Methods One hundred and thirty-two indigenous outpatients (>18 years old) with stable non-CF bronchiectasis were enrolled. All patients were randomly assigned to a control group and two treatment groups. Patients in the azithromycin fixed-dose treatment group received oral azithromycin (250 mg daily) and ambroxol hydrochloride (30 mg, 3 times/d). Azithromycin progressively decreased dosage treatment group received oral azithromycin (250 mg daily for 8 weeks-250 mg 3 times/week for 8 weeks-250 mg 2 times/week for 10 weeks) and ambroxol hydrochloride (30 mg, 3 times/d). Subjects in control group only received ambroxol hydrochloride therapy. The course of treatment lasted for 26 weeks. Spirometry, exacerbations, sputum microbiology, quality of life, dyspnea scores and adverse effects were monitored after treatment for 26 weeks. Results One hundred and twenty-nine evaluable subjects completed the study. After treatment, the level of percentage of estimated value forced expiratory volume in 1 second (FEV1% Pred) in azithromycin fixed-dose treatment group and azithromycin progressively decreased dosage treatment group was significantly higher than that before treatment: (83.01 ± 5.79)% vs. (79.39 ± 3.53)%, (84.97 ± 5.10)% vs. (80.94 ± 3.46)%, P<0.05. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%- 75%) was also increased in two groups: (54.87 ± 5.72) % vs. (51.86 ± 8.16)%, (55.65 ± 3.39)% vs. (53.46 ± 5.75)% , there was significant difference (P<0.05). But the levels of above parameters between two groups after treatment had no significant differences (P >0.05). The parameters of FEV1% Pred, forced expiratory volume in 1 second (FEV1)/forced ventilatory capacity (FVC) and FEF25%-75%were lower compared to those before treatment in the control group (P <0.05). However, the scores of LRTI-VAS and FACED in control group after treatment were decreased slightly: (20.55 ± 1.76) scores vs. (21.34 ± 1.86) scores, P<0.05; (4.16 ± 0.75) scores vs. (4.36 ± 0.72) scores, P > 0.05. Seven episodes of acute exacerbation was occured during 26 weeks, 2 cases exited. The others did not interrupt azithromycin treatment during acute exacerbation. Drug-related adverse reactions were mild. Conclusions For adult stable patients with non-CF bronchiectasis, the clinical symptoms and airflow limitation are improved after long-term treatment of low-dose azithromycin. Similar effects on FACED score and LRTI-VAS score are observed in patients with progressively decreased dosage of azithomycin.

Molecular guidance cues in the development of visual pathway

70%-80% of our sensory input comes from vision. Light hit the retina at the back of our eyes and the visual information is relayed into the dorsal lateral geniculate nuclei (dLGN) and primary visual cortex (V1) thereafter, constituting the image-forming visual circuit. Molecular cues are one of the key factors to guide the wiring and refinement of the image-forming visual circuit during pre- and post-embryonic stages. Distinct molecular cues are involved in different developmental stages and nucleus, suggesting diverse guidance mechanisms. In this review, we summarize molecular guidance cues throughout the image-forming visual circuit, including chiasm determination, eye-specific segregation and refinement in the dLGN, and at last the reciprocal connections between the dLGN and V1.

Role of Hes1 in malignant transformation of human bronchial epithelial cells induced by tobacco / 中国病理生理杂志

AIM: To investigate the role of transcription factor hairy and enhancer of split 1 (Hes1) in the malignant transformation of human bronchial epithelial cell line BEP2D induced by tobacco.METHODS: The BEP2D cells were chronically exposed to cigarette smoke condensate (CSC) at 1 cigarette per L until the 70th generation.The phenotype of malignant transformation of the cells induced by CSC was detected by soft agar clony formation assay.RT-PCR and Western blot were used to determined the expression of Hes1 at mRNA and protein levels in each generation of the cells.The proliferation and apoptosis of the BEP2D cells exposed to CSC were analyzed with the methods of MTT assay, flow cytometry and cell colony formation assay after treatment with Notch pathway bloker DAPT or liposome transfection with Hes1-siRNA.The expression of Hes1 in the peripheral small airway tissues of the smoking rats was evaluated by immunohistochemical staining.The expression of Hes1 in non-small-cell lung cancer and normal airway tissues was also detected by the methods of immunohistochemistry and RT-PCR.RESULTS: The BEP2D cells in the 70th generation had a malignant transformation phenotype.The expression of Hes1 in the BEP2D cells exposed to CSC for different time showed an increa-sing trend.DAPT and liposome transfection with Hes1-siRNA down-regulated the expression of Hes1, inhibited the cell proliferation and induced cell apoptosis.The expression of Hes1 in the airway mucosa of the rats exposed to cigarette smoke for 1 month and 6 months was significantly higher than that in control group.Cigarette smoking induced the expression of Hes1 in lung cancer and normal airway tissues.CONCLUSION: Hes1 may be involved in smoking-induced lung cancer by promoting the imbalance between apoptosis and proliferation.

Allogeneic hematopoietic stem cell transplantation for intermediate cytogenetic risk acute myeloid leukemia / 中国组织工程研究

BACKGROUND: Previous studies have shown that HLA-identical sibling allogeneic peripheral blood hematopoietic stemcelltransplantation (allo-HSCT) provides higher disease-free and overall survival rates for patients with intermediatecytogenetic risk acute myeloid leukemia (AML) in complete remission (CR). But prognosis factors have not been fullydefined.OBJECTIVE: To evaluate the outcome of patients with intermediate cytogenetic risk AML undergoing HLA-matchedallo-HSCT in CR, and to analyze the prognostic factors.METHODS: Fifty cases of intermediate cytogenetic risk AML in CR receiving HLA-matched allo-HSCT from January2009 to January 2015 were retrospectively analyzed. Primary outcome measures of the study included overall survival(OS), relapse rate and non-relapse mortality.RESULTS AND CONCLUSION: The 4-year OS of the study population reached to 64%, and the relapse rate and NRMreached to 18% and 20% respectively. Incidence of acute graft-versus-host disease was 26%. Different prognosis wasobserved between female donor/male recipient (FDMR) combination transplant and control (4-year OS: 50% vs. 71.9%,P=0.041), between patients requiring more than one course of induction chemotherapy to achieve CR and control(4-year OS: 40% vs. 70%, P=0.038), between older age (≥ 40 years) and control (4-year OS: 44.4% vs. 68.3%,P=0.056). The 4-year OS for matched sibling donor and matched unrelated donor was 63.2% and 66.7% (P=0.427),respectively. Further analysis revealed significantly high non-relapse mortality in FDMR combination transplant (P=0.024)and older age (≥ 40 years; P=0.043). Multivariate analysis revealed three negative prognostic factors: FDMRcombination (P=0.031, RR=1.38, 95% CI: 1.03-1.95), requiring more than one course of induction chemotherapy toachieve CR (P=0.016, RR=1.46, 95% CI: 1.10-1.98) and older age (≥ 40 years; P=0.024, RR=1.63, 95% CI: 1.32-2.12).To conclude, HLA-matched allo-HSCT is a choice for the intermediate cytogenetic risk AML case in CR. FDMRcombination, requiring more than one course of induction chemotherapy to achieve CR and older age (≥ 40 years) areconfirmed as risk factors of poor prognosis for HLA-matched allo-HSCT patients with intermediate cytogenetic risk AMLin CR. To these cases, the donor-recipient sex combination is more important than the donor type in donor selection.