[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

[Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure].

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

[Study on the features of Clostridioides difficile infection among diarrhea patients in Kunming from 2018 to 2020].

Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.

[Ruxolitinib as an effective treatment for panniculitis associated hemophagocytic syndrome: A report of 2 cases and literature review].

Hemophagocytic syndrome (HPS) is a severe disease characterized by excessive release of inflammatory cytokines caused by abnormal activation of lymphocytes and macrophages, which can cause multiple organ damage and even death. Panniculitis is a disease characterized by inflammation of subcutaneous adipose tissue. We effectively treated 2 patients with panniculitis-associated HPS with ruxolitinib. Case 1: A 70-year-old male started with intermittent plantar swelling and pain, and then developed leukocytosis, mild anemia, multiple red maculopapules with painless subcutaneous nodules on the forehead, neck and bilateral lower legs. The patient was treated with prednisone and leflunomide for improvement. After that, repeated fever and rash occurred again. After admission to our hospital, we found his leukocyte and hemoglobin decreased, ferritin raised, fibrinogen and natural killer (NK) cell activity decreased, and hemophagocytic cells were found in bone marrow aspiration. The skin pathology was consistent with non-suppurative nodular panniculitis. He was diagnosed with nodular panniculitis associa-ted HPS. He was treated with glucocorticoid, cyclosporine, etoposide and gamma globule, but the disease was not completely controlled. After adjusting etoposide to ruxolitinib, his symptoms and abnormal laboratory findings returned to normal. After 2 months he stopped using ruxolitinib due to repeated infections. During the follow-up, though the prednisone dose was tapered, his condition was stable. Case 2: A 46-year-old female patient developed from intermittent fever, erythematous nodular rash with tenderness, leukopenia, and abnormal liver function. antibiotic therapy was ineffective. She improved after glucocorticoid treatment, and relapsed after glucocorticoid reduction. There were fever, limb nodules, erythema with ulcerative necrosis, intermittent abdominal pain when she came to our hospital. Blood examination showed that her white blood cells, red blood cells and platelets were decreased, fibrinogen was decreased, triglyceride was increased, ferritin and soluble interleukin-2 receptor(SIL-2R/sCD25) were significantly raised, and hemophagocytic cells were found in bone marrow aspiration. It was found that Epstein-Barr virus DNA was transiently positive, skin Staphylococcus aureus infection, and pulmonary Aspergillus flavus infection, but C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were normal, and no evidence of tumor and other infection was found. Skin pathology was considered panniculitis. The diagnosis was panniculitis, HPS and complicated infection. Antibiotic therapy and symptomatic blood transfusion were given first, but the disease was not controlled. Later, dexamethasone was given, and the condition improved, but the disease recurred after reducing the dose of dexamethasone. Due to the combination of multiple infections, the application of etoposide had a high risk of infection spread. Ruxolitinib, dexamethasone, and anti-infective therapy were given, and her condition remained stable after dexamethasone withdrawal. After 2 months of medication, she stopped using ruxolitinib. One week after stopping using ruxolitinib, she developed fever and died after 2 weeks of antibiotic therapy treatment in a local hospital. In conclusion, panniculitis and HPS are related in etiology, pathogenic mechanism and clinical manifestations. Abnormal activation of Janus-kinase and signal transduction activator of transcription pathway and abnormal release of inflammatory factors play an important role in the pathogenesis of the two diseases. The report suggests that ruxolitinib is effective and has broad prospects in the treatment of panniculitis associated HPS.

[Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis].

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

[A study on longitudinal changes in white matter microstructure of parents who have lost their only child based on diffusion tensor imaging and its relationship with symptoms of posttraumatic stress disorder].

Objective: To investigate the longitudinal changes of white matter microstructural based on diffusion tensor imaging in parents who lost their only child without psychiatric disorders and its relationship with symptoms of posttraumatic stress disorder (PTSD). Methods: Parents who had who lost their only child and without psychiatric disorders in Jiangsu Province, from September 2016 to March 2017, were retrospectively collected (TENP group, 32). MRI scans were performed at baseline and at the end of 5-year follow-up, and the Clinician Administered PTSD Scales (CAPS) were used for assessing the severity of symptoms. Additionally, sex, age and education level matched healthy subjects were recruited as healthy controls (control group, 27) and underwent MRI scanning using the same protocol. The differences of fractional anisotropy (FA) values between TENP group and control group at baseline were analyzed by using Tract-based spatial statistics method, and the brain areas of lateral differences were used as the regions of interest for longitudinal follow-up analysis of TENP group. Partial correlation analysis was used to evaluate the relationship between FA values changes in longitudinal differences in brain regions and CAPS scores. Results: Compared with the control group, FA values of the right cingulate gyrus, Uncinate fasciculus, superior longitudinal fasciculus, corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major in TENP group were decreased at baseline ((0.613±0.032) vs (0.631±0.034), (0.539±0.048) vs (0.563±0.045), (0.534±0.033) vs (0.558±0.039), (0.560±0.038) vs (0.580±0.030), (0.519±0.023) vs(0.549±0.024), (0.489±0.038) vs (0.518±0.027), (0.499±0.027) vs (0.533±0.032); all P<0.05). From baseline to follow-up, scores of trauma reexperience symptoms and avoidance/numbness symptoms were decreased ((5.2±2.8) vs (8.1±4.9), (4.0±3.2) vs (6.6±5.4); all P<0.05); FA values of the right corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major were decreased ((0.523±0.049) vs (0.537±0.049), (0.568±0.052) vs (0.590±0.050), (0.540±0.063) vs (0.559±0.059), (0.520±0.059) vs (0.547±0.059); all P<0.05); The decrease of FA values of the right Inferior fronto-occipital fasciculus and right Inferior longitudinal fasciculus was negatively correlated with the decrease of avoidance/numbness symptoms scores (r=-0.458, -0.374, respectively, all P<0.05). Conclusions: The trauma of parents who lost their only child can result in impaired microstructural integrity of white matter. As the post-traumatic time goes by, parents who have lost their only child do not develop to PTSD and other psychiatric disorders, and the clinical symptoms are alleviated, the damage of the white matter microstructure continued to progress.

[Application and safety of hydroxychloroquine in chronic disease among children].

Objective: To analyze the disease spectrum among children who were using hydroxychloroquine (HCQ), and evaluate the drug's safety and compliance. Methods: From January 2008 to December 2019, children from Children's Hospital of Fudan University who used HCQ were selected as subjects, the disease spectrum of HCQ was analyzed, and the drug safety and compliance were evaluated for the patients who were followed up for more than 6 months. Demographic information, diagnosis, initial dose, time of continuous use, cumulative dosage and related adverse reactions report, project and the results of eye test were collected. Results: A total of 528 cases used HCQ during the 12 years, with 156 male cases and 372 female cases, and age at initial medication was (10.5±3.2) years. Among them, 514 cases (97.3%) had rheumatic disease, 5 had pulmonary interstitial lesions and 9 had other system diseases. The top three of the rheumatic diseases were systemic lupus erythematosus (SLE) in 316 cases (316/514,61.5%), juvenile idiopathic arthritis in 69 cases (69/514,13.4%), and juvenile dermatomyositis in 56 cases (56/514,10.9%). During the same period, 397 cases were diagnosed with SLE, and the utilization rate was 79.6% (316/397), which was the highest compared with other diseases and increased year by year. Pulmonary interstitial lesions included 4 cases with SFTPC gene defect related interstitial lung disease. Of the 528 ceses who were treated with HCQ, 397 cases were included for evaluating HCQ's safety and compliance, the initial dose was (4.2±1.0) mg/kg, duration was 29.6 (14.9, 48.8) months, the longest usage time was 127 months, the largest cumulative dosage was 566.8 g. The continuous usage duration (Z=-3.191, P=0.001) of SLE was significantly higher than those of other diseases, as well as cumulative dosage (Z=-5.355, P=0.001). All cases received comprehensive eye exams before medication, 354 cases (354/397, 89.2%) were followed up in the ophthalmological department, and 65.5% (232/354) of them could be reviewed regularly at least 1 time per year. One case suffered from severe skin adverse reactions when the drug was used for 32.7 months, and no other serious adverse reactions were reported. HCQ related retinopathy was not seen during the follow-up period. There were 5 cases stopped HCQ on their own. Conclusions: HCQ was widely used in rheumatic disease in children, especially in those with SLE. It was safe for long-time usage in children, and the medication compliance and the ophthalmic follow-up was good.

MiR-506 alleviates myocardial ischemia-reperfusion injury via targeting PI3K/AKT.

OBJECTIVE: The aim of this study was to explore the effects of micro ribonucleic acid (miR)-506 and phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) pathway on myocardial ischemia-reperfusion injury (MIRI) in rats. MATERIALS AND METHODS: A total of 90 healthy rats weighing 260-300 g were selected as research subjects, and divided into three groups, including: Control group (n=30), IR group (n=30), and miRNA treatment group (IR + miR-506 group, n=30). The model was successfully established via threading the coronary artery. The structural differences in myocardial tissues were observed via hematoxylin-eosin (HE) staining in each group. The mRNA expressions of miR-506 and PI3K in myocardial tissues were detected using fluorescence quantitative Polymerase Chain Reaction (qPCR). Meanwhile, AKT protein phosphorylation activity in myocardial tissues was detected as well. The apoptosis of myocardial tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardial tissues were compared in each group. RESULTS: In Control group, no structural abnormalities were found in myocardial tissues, and no inflammatory cells were observed. In IR group, myocardial tissues were arranged disorderly, and inflammatory cell infiltration was found. In IR + miR-506 group, myocardial tissue lesions were milder than those in the IR group. qPCR results indicated that the mRNA expressions of miR-506 and PI3K in myocardial tissues were statistically different among groups (p<0.05), with the lowest in the IR group. The expression of miR-506 was evidently higher in IR + miR-506 group than that in the Control group (p<0.05). However, the mRNA expression of PI3K was significantly higher in the Control group than IR + miR-506 group (p<0.05). There was a significant positive correlation between the expressions of miR-506 and PI3K in each group (p<0.05). The phosphorylation activity of AKT protein in IR + miR-506 group was markedly higher than the other two groups (p<0.05). In addition, TUNEL staining demonstrated that the apoptosis rate in Control group, IR group and IR + miR-506 group was only 1.3%, 20.3%, and 9.8%, respectively. SOD activity was remarkably stronger in the Control group (62.7 U/mg pro) than the other two groups (p<0.05). In addition, MDA content was remarkably higher in IR group (0.747 nmol/mg pro) than that in the other two groups (p<0.05). CONCLUSIONS: MiR-506 is associated with myocardial injury in rats, which can alleviate myocardial injury through the PI3K/AKT signaling pathway.

[Intranuclear cytoplasmic autophagosomes cause specific nucleolysis and cell death of liver cancer cells and liver cells].

The structure and performance of nuclear cytoplasmic autophagosomes was explored. Seventeen cases of hepatocellular carcinoma and liver cells with other diseases from liver tissues were selected. The nuclear cytoplasm were isolated and degraded by the nuclear membrane. Damaged cytoplasm had damaged its own membrane and the surrounding nuclear tissues other than the nuclear membrane, leading to specific nucleolysis and cell death of liver cancer cells and liver cells.

[Epidemiological characteristics of scarlet fever in Hubei Province from 2009 to 2018].

Descriptive epidemiological methods were adopted to analyze the epidemiological characteristics of scarlet fever in Hubei Province from 2009 to 2018. During this study, the epidemiological data was obtained from the Chinese Center for Disease Control and Prevention Information System. The results showed that there were 7 329 cases of scarlet fever reported in Hubei Province from 2009 to 2018 and the annual average incidence was 1.25 per 10 000. The number of cases was increased by years, and in 2018 it was the highest peak during these ten years and up to 1 758 which was account for 24% in these ten years, and the incidence was 2.98 per 10 000. The number of reported cases of male and female was 4 473 and 2 856, respectively, and both of the incidence rates were on the rise. The reported cases were distributed in 0-60 year-old group, mainly in the <15-year-old group (98.4%, 7 214/7 329). The season with the highest incidence rates were summer and winter. There were cases in all cities and prefectures, and the number of cases were the highest in Wuhan (n=2 105), Yichang (n=1 390), Jingzhou (n=954) and Enshi (n=1 090). Hence, it was very necessary to be on guard for the outbreak of scarlet fever and strengthen the surveillance in summer and winter for the people who were younger than 15 years old, especially in Wuhan, Yichang, Jingzhou and Enshi.

[A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection].

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

[Clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients].

Objective: To describe the clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients. Methods: Medical records of newly diagnosed diabetes onset with ketosis or ketoacidosis in the Third Affiliated Hospital of Sun Yat-sen University between January 2011 and August 2016 were reviewed. Patients aged 18 years or older were included, while other diseases that may cause urinary ketoacidosis and special types of diabetes were excluded. Patients were classified as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) or diabetes mellitus untyped based on discharged diagnosis, and groups were compared for differences in clinical profiles. Then the patient's medication, final diagnosis and outcome within 2 years of discharge were tracked through the inpatient and the outpatient medical record systems. Receiver operating characteristics (ROC) curves were analyzed to check the ability of clinical indicators such as onset age, body mass index (BMI) and C-peptide to discriminate T1DM from T2DM, and to find the best diagnostic cut-off points. Results: A total of 123 patients (88 males) were enrolled [with a mean age of (41.1±13.6) years old], with 37 patients (30.1%) diagnosed as T1DM, 60 patients (48.8%) diagnosed as T2DM and 26 patients (21.1%) diagnosed as Untyped. There was a statistically significant difference in onset age, BMI, blood pressure, blood gas pH and bicarbonate, blood lipids, fasting, 0.5 h and 2 h C-peptide level, any diabetic antibody and anti-glutamic acid decarboxylase antibody (GADA) positive rate, combined fatty liver ratio and family history among the three groups (all P<0.05). ROC curve analysis was performed on patients diagnosed with T1DM (n=36) and T2DM (n=87) after 2 years follow-up, and the area under the curve (AUC) of onset age, BMI, fasting C-peptide, 0.5 h and 2 h C-peptide was 0.735, 0.813, 0.855, 0.898, and 0.882, respectively. Conclusion: The ROC curve analysis indicates that C-peptide, onset age and BMI can provide effective diagnostic value, and the diagnostic value of C peptide is better than BMI and onset age.

Bioinformatics analysis of common differential genes of coronary artery disease and ischemic cardiomyopathy.

OBJECTIVE: This paper aims at screening the common differential genes of coronary atherosclerotic heart disease (CAD) and ischemic cardiomyopathy (ICM), and to conduct pathway analysis and protein-protein interaction (PPI) network analysis for the differential genes. MATERIALS AND METHODS: The CAD and ICM datasets were collected from the Gene Expression Omnibus (GEO) database for human tumors to extract data components of peripheral blood RNA of patients and normal people in GSE71226 and GSE9128 chips; "limma" package of "R" software was used to screen the differential genes, and "pheatmap" package was applied to construct heat maps for the differential genes; Cytoscape, Database for Annotation, Visualization and Integration Discovery (DAVID) and String platforms were utilized for PPI network analysis, Genome Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on the selected differential genes. RESULTS: A total of 575 differential genes were screened from GSE71226, including 350 genes with up-regulated expression and 225 with down-regulated expression, which was statistically significant (p<0.05, fold change >1). 75 differential genes were screened from GSE9128, including 47 genes with up-regulated expression and 28 with down-regulated expression. By virtue of String, DAVID and Cytoscape software, the PPI network diagram was constructed, and GO and KEGG analyses were performed successfully. CONCLUSIONS: A total of 8 common differential genes are screened, and functional annotation and pathway analysis are conducted, which is conducive to further studying the interactions between the differentially expressed genes.

[Coenzyme Q(10) treatment for one child with COQ6 gene mutation induced nephrotic syndrome and literature review].

Objective: To summarize the clinical manifestation and molecular characteristics of COQ6 mutation induced nephrotic syndrome, and to evaluate efficacy of CoQ(10) therapy. Method: Clinical data of the case with infantile nephrotic syndrome was summarized, including clinical manifestations, laboratory findings and family investigation. The patient received CoQ(10) 30 mg/(kg·d) therapy. Urine protein/creatinine ratio, serum albumin and creatinine were detected to assess the efficacy of the therapy. Result: (1) The 10 months old boy was presented with nephrotic level proteinuria and hypoalbuminemia. Extra-renal manifestations included cardiovascular abnormality, motor and mental retardation and unilateral ptosis. The patient had no consanguinity. A novel homozygous p. R360W mutation in COQ6 gene was identified and confirmed by next-generation sequencing and Sanger sequencing, respectively. Family analysis showed that homozygous p. R360W mutation in COQ6 gene was inherited from his parents. Missense p. R360W mutation was damaging by prediction online PolyPhen and SIFT software. After 2 months of CoQ(10) complementary therapy, the patient's urine protein/creatinine ratio declined from 7.2 to 1.3, and decreased further to 0.01 mg/mg with normal albumin level and renal function within 3 months. Nephropathy remission was maintained and growth retardation improved significantly during the last follow-up. Nevertheless, the patient manifested with sensorineural deafness at the age of 2 years. (2) There were 6 different mutations in coenzyme Q(10) biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping in the whole world. Each mutation was linked to early-onset SRNS with sensorineural deafness. Renal biopsy revealed FSGS in 7 cases and DMS in 1 case. Other manifestations included ataxia, seizures, facial dysmorphism, nephrolithiasis and growth retardation. Four patients received CoQ(10) supplementation and responded to the treatment. Conclusion: Renal disease caused by recessive COQ6 gene mutation was nephrotic syndrome. The patient benefited from early CoQ(10) complement and reached nephropathy remission.

Association of IL-1α gene polymorphism with susceptibility to type 1 diabetes in Chinese children.

The interleukin-1α (IL-1α) gene appears to play a role in the pathogenesis of type 1 diabetes (T1D). Therefore, the aim of this study was to investigate the contribution of the IL-1 rs1800587 gene polymorphism to susceptibility to T1D in Chinese children. This case-control study included 332 Chinese children with T1D and 332 healthy controls. Identification of genetic variants of rs1800587 in the IL-1α gene was performed by polymerase chain reaction amplification. The IL-1α rs1800587 polymorphism demonstrated a significant association with T1D risk. The allelic frequency significantly differed between the T1D and control groups [odds ratio (OR) = 0.7; 95% confidence interval (CI) = 0.52-0.86; P = 0.002]. Furthermore, significant differences were observed in the dominant model (CC/CT + TT; OR = 0.6; 95%CI = 0.46-0.85; P = 0.003). In T1D patients, the prevalence of hypertension in T allele carriers was 4.2-fold higher than that in C allele carriers, (95%CI = 2.67-6.58; P < 0.001). In conclusion, the present study found evidence of a significant association between the rs1800587 polymorphism in the IL-1α gene and T1D.

MiR-577 inhibits pancreatic ß-cell function and survival by targeting fibroblast growth factor 21 (FGF-21) in pediatric diabetes.

Pancreatic ß-cell dysfunction is a central component of the pathogenesis of pediatric diabetes. MicroRNA (miRNA) have become one of the most encouraging and fruitful fields in biological research, and have been implicated as new players in the pathogenesis of diabetes and diabetes-associated complications. The role of miRNA in diabetes begins with the development of pancreatic islets. Fibroblast growth factor (FGF)-21 enhances glucose uptake in adipocytes, protecting transgenic animals from diet-induced obesity when overexpressed, and lowers blood glucose and triglyceride levels in diabetic animals (when administered); therefore, it is a good way to treat diabetes. However, the mechanism of miRNA in regulation of FGF21 is not known. In this study, FGF-21 was predicted to be the target of miR-577. Therefore, we investigated the effects of miR-577 on ß-cell function and survival by targeting FGF-21. We demonstrated that, although FGF-21 does not acutely stimulate insulin secretion in isolated islets from normal rats, it increases insulin secretion and insulin content in diabetic islets and protects ß-cells from apoptosis via the activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways.

The dissemination mode of drug-resistant genes in Enterobacter cloacae.

BACKGROUND: Enterobacter cloacae (E. cloacae) infection has the highest mortality rate among Enterobacter infections. This study aimed to determine the prevalence and the transmission route of the class I integron, qnr genes, and CTX-M ESBLs genes in clinical isolates and to analyse the association between the prevalence of MDR genes and the antibiotic resistance of E. cloacae. MATERIALS AND METHODS: The antibiotic susceptibility was tested the agar dilution method. The class I integron, qnr genes, and CTX-M ESBLs genes were detected by polymerase chain reaction (PCR). The prevalence data were analysed with the Chi-square test. RESULTS: In the 100 clinical isolates, the class I integron-positive rate was 65%, with 12% on chromosome, 15% on plasmids and 38% on both. The positive rate of qnr genes was 37% with plasmid location. The positive rates for qnrA, qnrB and qnrS were 6%, 23% and 8%, respectively. The CTX-M ESBLs-positive rate was 34%. For CTX-M-1 ESBLs, 15% were on chromosome, 6% on plasmids and 4% on both; for CTX-M-9 ESBLs, 1% was on chromosome and 7% on plasmid; for CTX-M-25 ESBLs, 3% were on chromosome and 1% on plasmid. CONCLUSION: Antibiotic resistance genes may be horizontally and vertically disseminated among E. cloacae, which helps multidrug-resistant (MDR) strains of E. cloacae to be successful nosocomial agents.

Effect of transcription factor ZBTB20 on mouse pituitary development.

Pituitary, a critical component in the neuroendocrine system, plays an indispensable role in the regulation of body growth. The transcriptional factor ZBTB20 is widely expressed in brain tissues and participates in hippocampal development; however, the detailed molecular mechanism remains unknown. Therefore, the aim of this study was to investigate the effect of ZBTB20 on mouse pituitary development and related mechanisms in ZBTB20 gene knockout mice. The expressional profiles of ZBTB20 in various neuroendocrinal cells during the different developmental stages (from E10 to P0) were described by immunofluorescence staining. A ZBTB20 gene knockout mouse model was then generated. Real-time polymerase chain reaction and western blotting assays were used to detect the levels of five hormones: growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). ZBTB20 protein expression was identified from E14 until birth. A majority of the pituitary endocrinal cells were ZBTB20-positive. In ZBTB20 knockout mice, the level of GH decreased by half and PRL expression was eliminated. No significant change was observed in the other three hormones (LH, FSH, and TSH). ZBTB20, an important transcriptional factor in pituitary development, is mainly responsible for the terminal differentiation of prolactin-secreting cells, thereby regulating the secretion of the pituitary hormones.