Genotype and phenotype analysis in a case of cutis laxa type 3 / 中华内分泌代谢杂志

Objective:To report the clinical and genetic characteristics of autosomal dominant cutis laxa type 3 caused by ALDH18A1 mutation, and therefore to further understand this rare disease.Methods:High-precision full-exon sequencing was performed for the patient from the Department of Endocrinology and Genetic Metabolism, Children′s Hospital of Chongqing Medical University and genotype-phenotype correlation was summarized. Relevant literature was also reviewed.Results:A 9-month-old boy was admitted with complaint of " development retardation for 9 months, cough for 3 days" , accompanied by skin laxity, special features, skeletal malformation, tracheal bronchus, inguinal hernia, gastroesophageal reflux, and abnormal creases on palms. The heterozygous variation of ALDH18A1 c. 274C>G(p.Leu92Val) on chromosome 10 was revealed using high-precision full-exon sequencing. Together with imaging and metabolomics results, the diagnosis of cutis laxa type 3 was determined. The clinical presentations of this disease are variable, encompassing skin, bone, joint, and neuromuscular system.Conclusion:For suspected pediatric case, it is very important to evaluate the clinical manifestations and metabolic index at regular intervals, and to identify the molecular basis of the disease with gene sequencing early on.

Efficacy and Safety of PEG-rhG-CSF in HSC Mobilization in 71 Normal Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in hematopoietic stem cell mobilization in 71 normal healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#From March 2018 to July 2019, 71 patients received allo-HSCT in The General Hospital of Western Theater Command were enrolled in the study, a single dose of PEG-rhG-CSF was injected subcutaneously at 12 mg to all the stem cell donors. After injection for 4 days, CD34@*RESULTS@#Seventy-one healthy stem cell donors included 39 males and 32 females with a median age of 38 (16-58) years old. The median number of CD34@*CONCLUSION@#For allo-HSCT donor mobilization, PEG-rh-G-CSF is effective, safe, and convenient, providing more options for HSC mobilization.

Mechanism of Therapeutic Methods for Activating Blood and Removing Blood Stasis in Treatment of Cerebral Hemorrhage / 中国实验方剂学杂志

Intracerebral hemorrhage (ICH) refers to the primary non-traumatic parenchymal hemorrhage, which is one of the common cerebrovascular diseases, with a high incidence, rapid development, slow recovery and high disabling rate. After intracerebral hemorrhage, a series of pathological changes occur in the brain tissue, such as local hematoma and its space occupying effect, secondary cerebral edema, death of brain cells and destruction of blood-brain barrier, which may lead to brain injury and neurological defects, seriously affect the quality of life of patients, and even endanger the life. Therefore, it is great medical value to find effective therapeutic methods and drugs, explore the mechanisms and targets for improving neurological function, reduce sequelae and improve the quality of life of patients. According to the theory of traditional Chinese medicine (TCM), cerebral hemorrhage belongs to " abnormal flow of the blood" , which equals to blood stasis. In recent years, scholars conducted extensive research on drugs for promoting blood circulation to remove blood stasis with modern scientific methods, and made in-depth discussion for the mechanism, and found that therapies for activating blood and removing blood stasis, plays a key role in intervening a series of physiological and pathological changes after cerebral hemorrhage, with significant curative effects in removing hematoma, improving the microcirculation and reducing the mortality and morbidity. This article summarized drugs for promoting blood circulation to remove blood stasis (Notoginseng Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Hirudo), formulas (Buyang Huanwu Tang, Didangtang, Naoxueshu oral liquid, Tongqiao Huoxuetang) and compound injections (Danhong injection) for the treatment of cerebral hemorrhage targets, and discussed the experimental research progress TCM for promoting blood circulation to remove blood stasis in treatment of cerebral hemorrhage in terms of promoting hematoma absorption, reducing brain edema and apoptosis, promoting angiogenesis, inhibiting the inflammatory response, and promoting the repair and regeneration of nerve tissue in nearly five years, and summarized the therapeutic mechanism, so as to provide scientific basis for clinical application of the therapeutic methods for activating blood and removing stasis to treat cerebral hemorrhage and the modern scientific research.

Effect of Qingkailing on Expression of Toll-like Receptor 4, gp91phox and Zonula Occludens-1 in Cerebrovascular Endothelial Cells Induced by Hypoxia Activating Microglias / 中国康复理论与实践

Objetive To investigate the effect of Qingkailing injection on the expression of Toll-like receptor 4 (TLR4), gp91phox and zonula occludens-1 (ZO-1) in cerebrovascular endothelial cells induced by hypoxia activation of microglias. Methods:BV2 microglia cells were divided into six groups. They were cultured in serum-free DMEM, while the Qingkailing groups of low, middle and high dosages were cultured with 0.0625%, 0.125% and 0.25% Qingkailing injection, respectively, and minocycline group with minocycline of 200 nmol/L. The groups other than control group underwent hypoxia for 24 hours and reoxygenation for 24 hours. Then, the medium of microglia was put into the medium of Balb/c endothelial cells for 24 hours. The cell viability of endothelial cells was measured with CCK-8, the concentration of nitric oxide (NO) was detected with colorimetry, and the experission of TLR4, gp91phox and ZO-1 was detected with Western blotting. Results:Compared with the control group, the cell viability and the expression of ZO-1 decreased in the model group (P < 0.01), while the concentration of NO and the expression of TLR4 and gp91phox increased (P < 0.05). Compared with the model group, the cell viability and the expression of ZO-1 increased in the Qingkailing groups and the minocycline group (P < 0.05), while the concentration of NO and the expression of TLR4 and gp91phox decreased (P < 0.05). Conclusion:Qingkailing injection may enhance the survival and function of cerebrovascular endothelial cells by inhibiting the hypoxia activation of microglias, reducing the expression of TLR4 and gp91phox, and increasing the expression of ZO-1.

Fear Network Model in Panic Disorder: The Past and the Future

The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.

Promising Neuroimaging Biomarkers in Depression

The neuroimaging has been applied in the study of pathophysiology in major depressive disorder (MDD). In this review article, several kinds of methodologies of neuroimaging would be discussed to summarize the promising biomarkers in MDD. For the magnetic resonance imaging (MRI) and magnetoencephalography field, the literature review showed the potentially promising roles of frontal lobes, such as anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). In addition, the limbic regions, such as hippocampus and amygdala, might be the potentially promising biomarkers for MDD. The structures and functions of ACC, DLPFC, OFC, amygdala and hippocampus might be confirmed as the biomarkers for the prediction of antidepressant treatment responses and for the pathophysiology of MDD. The functions of cognitive control and emotion regulation of these regions might be crucial for the establishment of biomarkers. The near-infrared spectroscopy studies demonstrated that blood flow in the frontal lobe, such as the DLPFC and OFC, might be the biomarkers for the field of near-infrared spectroscopy. The electroencephalography also supported the promising role of frontal regions, such as the ACC, DLPFC and OFC in the biomarker exploration, especially for the sleep electroencephalogram to detect biomarkers in MDD. The positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in MDD demonstrated the promising biomarkers for the frontal and limbic regions, such as ACC, DLPFC and amygdala. However, additional findings in brainstem and midbrain were also found in PET and SPECT. The promising neuroimaging biomarkers of MDD seemed focused in the fronto-limbic regions.

Supervision System on Drug Post-marketing Research in America and Its Enlightenments to China / 中国药房

OBJECTIVE:To put forward suggestions for improving the supervision of phase Ⅳ clinical trials in China. METH-ODS:According to summarizing the post-marketing research in America,FDA's supervision(including key elements,supervision flow,auxiliary supervision system and enforcement measures)for drug post-marketing research in America was analyzed,and sug-gestions for the supervision of phaseⅣclinical trials in China was put forward. RESULTS&CONCLUSIONS:The drug post-mar-keting research in America included post-marketing commitment research(PMR)and post-marketing requirement research(PMC). The key elements included supervision subjects(dealt by Office of New Drugs affiliated to Drug Evaluation and Research Center), key document (including the documents helping FDA and applicants reached a research agreement,and documents for process tracking and supervision in identified studies)and important time node. The supervision flow included developing drafts and review-ing reports. FDA had established PMC/PMR database,which was used as auxiliary supervision system,and relevant enforcement measures were respectively developed for PMC and PMR. Relevant supervision departments in China should converse the supervi-sion ideas,give full play to the government's guidance and supervision,enhance the connection of supervision between pre- and post-marketing,specially develop phase Ⅳ clinical program,establish system for phase Ⅳ clinical trial data,enhance whole pro-cess supervision,draw lessons from"pre-process plan,dynamic tracking in the process,and post-process decision according to law"of FDA to improve the supervision of phaseⅣclinical trials in China.

The Relief Effects of Ramelteon on Refractory Chronic Migraine: A Case Report

The selective melatonin receptor agonism effect of ramelteon is useful for insomnia. Here we wanted to present a refractory chronic migraine case, who had significant improvements in migraine after using ramelteon. The possible mechanism for the ramelteon in the migraine relief might be related to melatonin effects.

The Accompanying Changes in Brain Structure of a Remitted Depression Patient with the Bupropion Treatment

The impacts from the bupropion on the brain structures have seldom been mentioned in the literature. The bupropion is a kind of antidepressant with dual action in the norepinephrine and dopamine receptors. Here we have a case to share about the bupropion-related effects in the brain structure.

Study on HLA-DRB1 shared epitope in patients with IgA mesangial proliferative glomerulonephritis / 中国免疫学杂志

Objective:To explore the clinical correlation of HLA-DRB1 shared epitope with IgA mesangial proliferative glomer-ulonephritis( IgA MsPGN).Methods:The renal function were examined routinely,and HLA-DRB1 shared epitope were determined by PCR in a total of 164 patients with IgA MsPGN and 164 healthy subjects.The renal function and HLA-DRB1 shared epitope were compared in patients with IgA MsPGN and healthy subjects,and clinical correlation of HLA-DRB1 shared epitope and renal function were analyzed.Results:(1)24 h proteinuria,serum creatinine and serum urea nitrogen were significantly different in patients with IgA MsPGN and healthy subjects(P<0.01);(2)The high-frequency gene of HLA-DRB1 in patients with IgA MsPGN were DRB1*04, DRB1*07,DRB1*09,DRB1*11,DRB1*14 and DRB1*15;(3) The distribution frequency of DRB1*09 and DRB1*11 in patients with IgA MsPGN increased significantly(P<0.01 or P<0.05);(4)24 h proteinuria,serum creatinine and serum urea nitrogen in patients with IgA MsPGN with DRB1*09 and DRB1*11 were significantly different compared with those in patients with IgA MsPGN with other HLA-DRB1 shared epitope(P<0.01).Conclusion:HLA-DRB1 shared epitope is related to IgA MsPGN,DRB1*09 and DRB1*11 can increase the risk of IgA MsPGN,and related to the severity of glomerulonephritis.

Late-onset Quetiapine-related Tardive Dyskinesia Side Effects in a Patient with Psychotic Depression

The atypical antipsychotics were believed to induce less extrapyramidal syndrome, including tardive dyskinesia (TD). Since the introduction of the quetiapine, it is also reported with less TD side effects. It even can relieve the symptoms of severe TD and reduce the risk of TD. The quetiapine's low affinity and fast dissociation from postsynaptic dopamine D2 receptors should give the least risk of producing the symptoms of TD. The quetiapine even can reduce the TD side effects related to clozapine, which has the lowest risk for TD. However, since the first case report of TD side effects related to quetiapine published on 1999, the safety of quetiapine in TD aspect has been questioned. Therefore, we want to share this case report, which was written to describe the severe late-onset TD side effects after long-term use of quetiapine in a patient with psychotic depression. The patient had no significant findings after concurrent comprehensive neurological examinations, magnetic resonance imaging of brain and electroencephalogram since the onset of TD.

Death causes and risk factors of uremia patients / 中华肾脏病杂志

Objective To investigate the death causes and risk factors of uremia patients in order to improve the prognosis of uremia patients.Methods Clinical data of 247 uremia inpatients and outpatients from 2001 to 2011 in our hospital were retrospectively analyzed.Dead patients were served as death group (n=124) and survival patients as control group (n=123).Death causes and primary disease were studied.Frequency of hemodialysis,prealbumin,albumin,natremia and pulmonary infection were compared between two groups.Results Age and gender were not associated with the death of uremia patients.The most common cause of death was cardiovascular disease followed by respiratory failure,uremic encephalopathy,cerebral hemorrhage,gastrointestinal hemorrhage,etc.Hemodialysis frequency,prealbumin,albumin and natremia of dead patients were obviously lower than those of control group.More patients in death group suffered from pulmonary infection.Logistic multivariate analysis revealed that death risk increased by 40.7％ when reducing 1 time per week of hemodialysis; death risk increased by 53.4％ when reducing 50 mg/L of prealbumin; death risk increased by 14.6％ when reducing 5 mmol/L of blood sodium; death risk of patients with pulmonary infection increased by 15.06 times of patients without pulmonary infection;death risk of diabetes mellitus increased by 4.26 times of patients without diabetes mellitus.Conclusions Cardiovascular disease,respiratory failure,uremic encephalopathy,cerebral hemorrhage,and gastrointestinal hemorrhage are common causes of death in uremia patients.Hemodialysis frequency,prealbumin,hyponatremia,pulmonary infection and diabetes can be regarded as risk factors for death of uremia patients.

Establish predictive model of colorectal cancer by using surface enhanced laser desorption/ionization-time of flight-mass spectrometry / 中华外科杂志

<p><b>OBJECTIVE</b>To establish serum proteome fingerprinting predictive models and search for proteins associated with colorectal cancer.</p><p><b>METHODS</b>Thirty-six randomly selected colorectal cancer patients and 36 cases with hernia or gall bladder diseases scheduled for elective operation were enrolled as cancer group and control group respectively. Peripheral venous blood samples were collected before the operations. Special serum protein or peptide fingerprint was investigated by using surface enhanced laser desorption/ ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after blood sample had been treated with weak cation exchange protein chip (CM10) for each case. The obtained data were analyzed by Biomarker Wizard software to screen serum proteome tumor markers and set up diagnosis predictive model for colorectal cancer. Blind validation of the model with 44 healthy controls and 88 colorectal cancer patients were carried out by using Biomarker Patterns Software.</p><p><b>RESULTS</b>In comparing colorectal cancer group with control group, 5 specific protein peaks (P < 0.05) were found. The predictive model had a sensitivity of 100% and a specificity of 97.2%. A sensitivity of 71.6% and a specificity of 72.7% was got with the blind validation. The specific protein peaks with a mass-to-charge ratio (m/z) of 8908 and 13,707 showed in all the results and it showed their strong relationship with colorectal cancer.</p><p><b>CONCLUSIONS</b>The predictive models built by the differences of serum proteome fingerprint could be a very useful diagnostic tool in colorectal cancer. Proteins with m/z of 8908 and 13,707 would possibly be the tumor markers of colorectal cancer.</p>

Application of SELDI-TOF-MS in detection of liver metastasis from colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a serum protein fingerprint model for prediction of liver metastasis from colorectal cancer by SELDI-TOF-MS analysis, and to determine the differentiatial proteins associated with the metastatic liver cancers.</p><p><b>METHODS</b>Data were collected from the Department of General Surgery in Zhongshan Hospital. A group of patients with colorectal cancer (CRC) without liver metastasis (n = 36) and another group with liver metastasis (n = 36) were included in this study. Serum samples were collected from peripheral venous blood before operation. Special serum protein or peptide fingerprint was determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The obtained data were analyzed by Biomarker Wizard software to screen the serum protein markers discriminating colorectal cancer patients with and without liver metastasis. A serum protein fingerprint model was established. This model was blindly verified in of CRC patients with and 44 cases without liver metastasis.</p><p><b>RESULTS</b>Comparing the characteristic proteins in those two groups of patients, 10 specific protein peaks were identified with statistical significance (P < 0.05). According to m/z growing from small to large, they were: 2398, 2814, 4084, 4289, 4465, 6422, 6619, 11 482, 11 649 and 13 714. The predictive model had a sensitivity of 91.7% and a specificity of 97.2%. The validation showed a sensitivity of 75.0% and a specificity of 81.8%.</p><p><b>CONCLUSION</b>A predictive model based on differentiatial serum protein fingerprint with high sensitivity and specificity has been successfully established. It should be a very useful tool in detection and diagnosis of liver metastasis in colorectal cancer patients.</p>

Therapeutic effects of hepatic resection in liver metastasis of colorectal cancer / 中华外科杂志

<p><b>OBJECTIVES</b>To evaluate therapeutic effects of hepatic resection in liver metastasis of colorectal cancer (LMCC).</p><p><b>METHODS</b>The clinical data of 133 cases of LMCC received hepatic resection from January 1, 2000 to December 31, 2005 in Zhongshan Hospital were analyzed retrospectively. The relationship between hepatic resection and survival rate was also concerned.</p><p><b>RESULTS</b>One hundred and thirty-three cases received curative hepatic resection in all 470 LMCC cases, of which 30 cases from synchronous liver metastasis (SLM) group (totaled 196 cases) and 103 cases from metachronous liver metastasis (MLM) group (totaled 274 cases). Mortality rate during operation was 3.3% in SLM and 1.9% in MLM (P < 0.05). All patients were followed-up till June 31, 2006, the 1, 3, 5 year survival rates and median survival time of SLM were similar to those of MLM, but its recurrence rate was higher (36.7% vs 20.4%, P = 0.030). The 1, 3, 5 year survival rate in the 49 patients who were operable but received non-operation treatment were significantly lower than those in operated patients (P = 0.003). In 30 SLM cases, 22 received I stage resection of their primary and liver metastasis tumor and 8 received liver metastasis resection after the primary surgery (II stage operation), 1, 2, 3 year survival and the median survival time were similar in the two groups. With COX multivariate analysis, incision margin > or = 1 cm (P = 0.036) and reoperation after recurrence (P = 0.041) were protective survival factors, and post-operation recurrence (P = 0.023) was survival risk factor.</p><p><b>CONCLUSIONS</b>Curative hepatic resection is the first choice of therapy in liver metastasis of colorectal cancer and it can improve survival.</p>

Evaluation of cyclooxygenase-2 in the prediction of liver metastasis of colorectal carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of cyclooxygenase-2 (COX-2) in colorectal carcinoma and its correlation with liver metastasis of colorectal carcinoma.</p><p><b>METHODS</b>The expression of COX-2 was detected using immunohistochemical methods in 30 colorectal carcinoma tissues without liver metastasis, 30 with preoperative liver metastasis, 30 with postoperative liver metastasis and 30 surrounding normal colorectal tissues. And its correlation with gender, age, Dukes stages was analyzed too.</p><p><b>RESULTS</b>The expression of COX-2 in colorectal carcinoma was significantly higher than that in surrounding normal colorectal tissue (P < 0.05), and meanwhile, its level in colorectal carcinoma without liver metastasis was significantly lower than those in tissues with preoperative or postoperative liver metastasis (P < 0.05). The COX-2 level had no correlation with gender, age, histological type, histological grade or the preoperative serum CEA and CA 19-9 levels in colorectal carcinoma (P > 0.05), but it was related to Dukes stages and lymph node metastasis.</p><p><b>CONCLUSIONS</b>COX-2 plays a role in the course of generation, development and metastasis of colorectal carcinoma. The high expression of COX-2 in colorectal carcinoma tissues may be considered as an indicator for liver metastasis.</p>

Bladder cancer and arsenic exposure: differences in the two populations enrolled in a study in southwest Taiwan / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 microg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis. As the continuous analysis presentation had been used by both the NRC and the EPA to assess the carcinogenic risk from arsenic ingestion, an explanation of the discontinuity was sought.</p><p><b>METHODS</b>Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so. Underlying data for the Morales et al. study were obtained from the appendix to the NRC report. Bladder cancer mortality rates were calculated from case counts and person-years of observation for each study village. Villages were categorized by water source according to the descriptions from the underlying study. Graphic and regression analyses were conducted of the bladder cancer mortality rates using exposure as a continuous variable and simultaneously stratifying by water source.</p><p><b>RESULTS</b>The median village well arsenic levels ranged from 350 to 934 microg/L for villages solely dependent on artesian well water and from 10 to 717 microg/L for villages not solely dependent on artesian well water. Bladder cancer mortality rates were found to be dependent upon the arsenic level only for those villages that were solely dependent on artesian well water for their water source. Bladder cancer mortality rates were found to be independent of arsenic level for villages with non-artesian well water sources.</p><p><b>CONCLUSIONS</b>The data indicate that arsenic exposure levels do not explain the bladder cancer mortality risk in SW Taiwan among villages not dependent upon artesian well water. The association for villages dependent upon artesian well water may be explained either by arsenic acting as a high-dose carcinogen or in artesian well water as a co-carcinogen with some other aspect of artesian well water (possibly humic acid). Arsenic exposure level alone appears to be an insufficient exposure measure to describe the risk of bladder cancer mortality in the BFD-endemic area. Risk analyses that fail to take water source into account are likely to misrepresent the risk characterization, particularly at low arsenic levels.</p>