[Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway].

OBJECTIVE: To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. METHODS: We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2, 4, 6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. RESULTS: The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P < 0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P < 0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P < 0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P < 0.05). CONCLUSION: KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.

[Clinical features of peripheral neuropathy with livedo reticularis: an analysis of seven cases].

The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.

[Application of electrical impedance tomography in pulmonary rehabilitation].

Pulmonary rehabilitation is a comprehensive and individualized intervention for patients suffering from respiratory dysfunction due to various diseases. This approach has been highly valued and implemented by clinical medical professionals. However, the lack of equipment and real-time monitoring of ventilatory lung function during pulmonary rehabilitation treatment is a challenge. In addition, there is a need for improved methods that can directly guide physiotherapists to provide precise treatment. Electrical impedance tomography (EIT) is a novel medical imaging technology that allows real-time monitoring of lung ventilation status. It is currently being translated from basic research into clinical applications and is widely used in respiratory disease, particularly in critical care respiratory management. However, there is a lack of reports on pulmonary rehabilitation guidance and outcome evaluation. This article aimed to provide a comprehensive review of this field, with the aim of generating more ideas for clinical research and further improving individualized treatment in the field of pulmonary rehabilitation.

[High expression of MYH9 inhibits apoptosis of non-small cell lung cancer cells through activating the AKT/c-Myc pathway].

OBJECTIVE: To investigate the role of myosin heavy chain 9 (MYH9) in regulation of cell proliferation, apoptosis, and cisplatin sensitivity of non-small cell lung cancer (NSCLC). METHODS: Six NSCLC cell lines (A549, H1299, H1975, SPCA1, H322, and H460) and a normal bronchial epithelial cell line (16HBE) were examined for MYH9 expression using Western blotting. Immunohistochemical staining was used to detect MYH9 expression in a tissue microarray containing 49 NSCLC and 43 adjacent tissue specimens. MYH9 knockout cell models were established in H1299 and H1975 cells using CRISPR/Cas9 technology, and the changes in cell proliferation cell were assessed using cell counting kit-8 (CCK8) and clone formation assays; Western blotting and flow cytometry were used to detect apoptosis of the cell models, and cisplatin sensitivity of the cells was evaluated using IC50 assay. The growth of tumor xenografts derived from NSCLC with or without MYH9 knockout was observed in nude mice. RESULTS: MYH9 expression was significantly upregulated in NSCLC (P < 0.001), and the patients with high MYH9 expression had a significantly shorter survival time (P=0.023). In cultured NSCLC cells, MYH9 knockout obviously inhibited cell proliferation (P < 0.001), promoted cell apoptosis (P < 0.05), and increased their chemosensitivity of cisplatin. In the tumor-bearing mouse models, the NSCLC cells with MYH9 knockout showed a significantly lower growth rate (P < 0.05). Western blotting showed that MYH9 knockout inactivated the AKT/c- Myc axis (P < 0.05) to inhibit the expression of BCL2- like protein 1 (P < 0.05), promoted the expression of BH3- interacting domain death agonist and the apoptosis regulator BAX (P < 0.05), and activated apoptosis-related proteins caspase-3 and caspase-9 (P < 0.05). CONCLUSION: High expression of MYH9 contributes to NSCLC progression by inhibiting cell apoptosis via activating the AKT/c-Myc axis.

[Burden of non-communicable diseases attributable to population aging in China, 1990‒2050].

Objective: The direction and intensity of population aging on the burden of non-communicable diseases (NCDs) in China from 1990 to 2019 were analyzed, and the burden of NCDs in 2050 was predicted. Methods: The disease-specific disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) in the Chinese population from 1990 to 2019 were obtained from the Global Burden of Disease Study.The differences in indicators from 1990 to 2019 were attributed to the contribution of age structure, population size, and all other causes. The Bayesian age-time-cohort models were used to predict DALYs from NCDs to 2050. Results: The absolute level of DALYs caused by NCDs increased by 7.460 million from 1990 to 2019, and the age structure contributed 186.0% (95% Uncertainty Intervals (UIs): 178.4%-193.6%), population size contributed 77.0% (95% UIs: 69.5%-80.8%), all other causes contributed -163.0% (95% UIs:-163.1%- -159.3%). DALYs caused by NCDs consist of 2.527 million YLLs and 4.934 million YLDs, in which the contribution of age structure to YLLs and YLDs was 414.6% (95% UIs: 396.2%-432.5%) and 69.1% (95% UIs: 66.7%-71.4%), respectively. From 2019 to 2050, the diseases with increased DALYs due to changes in age structure are cardiovascular diseases, neoplasms, chronic respiratory diseases, neurological disorders, sense organ diseases, diabetes and kidney diseases, musculoskeletal disorders, digestive diseases, mental disorders, and skin and subcutaneous diseases in descending order. Conclusions: From 1990 to 2019, except for skin and subcutaneous diseases, the burden of other NCDs attributable to population aging increased, mainly due to disability. By 2050, the burden of NCDsattributable to population aging will continue to rise.

Efficacy of peripheral nerve blocks for pain management in patients with rib fractures: A systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to assess the efficacy of different peripheral nerve blocks, compared to conventional methods (analgesics and epidural block), for pain relief in rib fracture patients. MATERIALS AND METHODS: PubMed, Embase, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched. The review included studies that were either randomized controlled trials (RCTs) or observational in design with propensity matching. The primary outcome of interest was patient's reported pain scores, both at rest and on coughing/movement. The secondary outcomes were length of hospital stay, length of stay at intensive care unit (ICU), need for rescue analgesic, arterial blood gas values and parameters of lung function test. STATA was used for statistical analysis. RESULTS: The meta-analysis was conducted with 12 studies. Compared to conventional methods, peripheral nerve block was associated with better pain control at rest 12 hours (SMD -4.89, 95% CI: -5.91, -3.86) and 24 hours (SMD -2.58, 95% CI: -4.40, -0.76) after institution of block. At 24 hours after block, the pooled findings indicate better pain control on movement/coughing for the peripheral nerve block group (SMD -0.78, 95% CI: -1.48, -0.09). There were no significant differences in the patient's reported pain scores at rest and on movement/coughing at 24 hours post-block. There were no differences in the overall risk of any complications (RR 0.48, 95% CI: 0.20, 1.18), pulmonary complication (RR 0.71, 95% CI: 0.35, 1.41) and in-hospital mortality (RR 0.62, 95% CI: 0.20, 1.90) between the two groups. Peripheral nerve block was also associated with a relatively lower need for rescue analgesic (SMD -0.31, 95% CI: -0.54, -0.07). There were no differences in the length of ICU and hospital stay, risk of complications, arterial blood gas values or functional lung parameters, i.e., PaO2 and forced vital capacity between the two management strategies. CONCLUSIONS: Peripheral nerve blocks may be better than conventional pain management strategies for immediate pain control (within 24 hours of initiation of block) in patients with fractured ribs. This method also reduces the need for rescue analgesic. The skills and experience of the health personnel, facilities for care available and the cost involved should guide the decision on which management strategy to utilize.

[Health-adjusted life expectancy in residents in Guangzhou, 2010-2019].

Objective: To analyze the spatiotemporal distribution of life expectancy (LE) and health-adjusted life expectancy (HALE) in Guangzhou from 2010 to 2019, and quantize the comprehensive impact of different causes and sequelae on health. Methods: The LE, HALE, and cause-excluded health adjusted life expectancy (CEHALE) were estimated using cause-of-death surveillance datasets from Guangzhou Municipal Center for Disease Control and Prevention from 2010 to 2019 and open data from the Global Burden of Disease Study. Joinpoint log-linear regression model was used to analyze the temporal trend and described spatial distribution. Results: In 2019, the LE in residents in Guangzhou was 82.9 years (80.1 years in men and 85.9 years in women), and the HALE was 75.6 years (74.0 years in men and 77.3 years in women). Compared with the urban fringe, the central urban area had higher LE and HALE, and the differences between LE and HALE were small. The LE and HALE in Guangzhou showed an increasing trend from 2010 to 2019. The LE increased by 2.8 years (AAPC=0.4, 95%CI: 0.3-0.4), with the increase of 2.8 years in men and 2.9 years in women. The HALE increased by 2.4 years (AAPC=0.3, 95%CI: 0.3-0.4), with the increase of 2.5 years in men and 2.2 years in women. The median healthy life lost due to communicable, maternal, neonatal, and nutritional diseases was 6.2 years (AAPC=-4.2, 95%CI: -5.3--3.1), while the median healthy life lost due to non-communicable diseases was 14.7 years (AAPC=1.6, 95%CI: 0.9-2.3), the median healthy life expectancy reduced by injury was 6.3 years (AAPC=-3.5, 95%CI: -4.5--2.6). Musculoskeletal disorders, skin and subcutaneous diseases, cardiovascular diseases, nutritional deficiencies, diabetes and kidney diseases were the top five diseases causing healthy life expectancy loss. Conclusion: The LE and HALE in residents in Guangzhou increased steadily from 2010 to 2019, but the quality of life in the urban fringe was lower than that of the central urban area. Non-communicable diseases were the leading causes of healthy life expectancy loss. Health policies and prevention measures should be developed according to area specific characteristics, and social medical resources should be rationally allocated to key diseases to reduce their disease burden.

[Comparative analysis on prevalence of tobacco and e-cigarettes uses in junior middle school students in Shanghai, 2013 and 2019].

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ2 test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.

[A survey on clinical practice of tracheostomy decannulation in medical institutions at all levels across the country].

Objective: A questionnaire survey was conducted on the clinical practice of tracheostomy decannulation among medical staff in medical institutions at all levels across the country. Methods: The questionnaire was determined by literature review and expert consultation to investigate the clinical practice of tracheostomy decannulation among medical staff in comprehensive and rehabilitation hospitals of different levels across the country and the factors considered when deciding to decannulate. Statistical methods used χ² test and one-way ANOVA. Results: A total of 570 questionnaires were collected from all over the country, with 463 valid questionnaires. The survey results showed that the most important factors in clinical practice to determine the decannulation of the tracheostomy tube were upper airway patency, cough effectiveness, level of consciousness and oxygenation. Before decannulation, 220 (47.50%) would choose to change to metal cannula, and 384 (82.90%) would routinely occlude the tube. 294 (63.50%) thought that re-intubation within 24 hours after decannulation of the tracheostomy tube was failure of decannulation. The decannulation failure rate was mostly 2%-5%. Conclusions: Upper airway patency, cough effectiveness, level of consciousness and oxygenation were important factors when considering decannulation. Reintubation within 24 hours of decannulation was defined as failure by the majority of respondents.

Prenatal diagnosis of ductal origin of distal pulmonary artery: presentation of three cases and literature review.

Ductal origin of distal pulmonary artery (DODPA) is a rare congenital cardiovascular anomaly, with an incidence of approximately 1 in 200 000 people. It involves the proximal interruption of one pulmonary artery branch, with the distal part arising from the base of the brachiocephalic artery, via the ipsilateral ductus arteriosus (DA) and the intrapulmonary branch of the pulmonary artery is usually intact. If timely treatment is not provided after birth, it is very likely that, due to DA closure, severe hypoplasia will occur in the lung supplied by the abnormal pulmonary artery. Hence, prenatal diagnosis of DODPA is important to enable initiation of prostaglandin treatment and early rehabilitation of the affected lung. Herein, we report three cases of fetal DODPA diagnosed via two-dimensional (2D) ultrasonography combined with four-dimensional (4D) spatiotemporal image correlation. We also present a literature review, and explore the ultrasonographic findings and the importance of 2D and 4D ultrasonography in obtaining an accurate prenatal diagnosis of DODPA. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

[The predictive value of ureteral wall area for impacted ureteral stones].

Objective: To investigate the clinical indicators for preoperative prediction of impacted ureteral stones and analyze the predictive value of ureteral wall area(UWA). Methods: A total of 197 patients who underwent ureteroscopic lithotripsy due to ureteral stones at our institution from January to December 2020 were retrospectively analyzed. Preoperative patient age, gender, body mass index (BMI), history of hypertension, diabetes mellitus, side of stone, location of stone, maximum diameter of stone, CT value of stone, C-reactive protein (CRP), creatinine, renal pelvis diameter, ureteral wall thickness and UWA were collected. Patients were divided into impacted and non-impacted groups according to whether the stones were impacted intraoperatively. Univariate analysis was used to compare the differences in each clinical indicator between the two groups, and multivariate logistic regression was performed to analyze the independent predictors of impacted stones for those with differences. The receiver operating characteristic (ROC) curve was used to analyze the predictive power of each independent predictor, and the Delong test was used to analyze whether the difference in the area under the curve (AUC) of each independent predictor was statistically significant. Results: All 197 patients successfully completed the operation, aged 51 (36, 56) years; 137 males and 60 females. According to the results of ureteroscopy, they were divided into 82 cases of impacted ureteral stones and 115 cases of non-impacted ureteral stones. Univariate analysis showed that there were significant differences in maximum stone diameter, stone CT value, renal pelvis diameter, ureteral wall thickness and ureteral wall area between the two groups (P<0.05); There was no significant difference in age, gender, BMI, history of hypertension, diabetes, stone side, location of stone, CRP and creatinine (P>0.05). Multivariate logistic regression analysis showed that stone CT value (P<0.01), ureteral wall thickness (P<0.001) and ureteral wall area were independent predictors of impacted ureteral stones (P<0.001). The ROC curve was used to compare the predictive efficacy of independent predictors of stone CT value, ureteral wall thickness and ureteral wall area. The area under the ureteral wall area curve was the largest (AUC = 0.901, 95%CI: 0.859-0.943, P<0.001), followed by ureteral wall thickness (AUC = 0.799, 95%CI: 0.736-0.862, P<0.001) and stone CT value (AUC = 0.700, 95%CI: 0.626-0.775, P<0.001). By Delong test, there were significant differences in AUC between ureteral wall area and stone CT value (Z=4.527, P<0.001) and ureteral wall thickness (Z=3.407, P<0.001). The best predictive value of ureteral wall area was 79.6 mm2. The sensitivity and specificity of this critical value for predicting ureteral incarcerated calculi were 80.1% and 89.5%. Conclusions: The UWA, ureteral wall thickness as well as the CT value of stones were all independent predictors of impacted ureteral stones, and UWA had a better predictive value.

Moderated Online Data-Collection for Developmental Research: Methods and Replications.

Online data collection methods are expanding the ease and access of developmental research for researchers and participants alike. While its popularity among developmental scientists has soared during the COVID-19 pandemic, its potential goes beyond just a means for safe, socially distanced data collection. In particular, advances in video conferencing software has enabled researchers to engage in face-to-face interactions with participants from nearly any location at any time. Due to the novelty of these methods, however, many researchers still remain uncertain about the differences in available approaches as well as the validity of online methods more broadly. In this article, we aim to address both issues with a focus on moderated (synchronous) data collected using video-conferencing software (e.g., Zoom). First, we review existing approaches for designing and executing moderated online studies with young children. We also present concrete examples of studies that implemented choice and verbal measures (Studies 1 and 2) and looking time (Studies 3 and 4) across both in-person and online moderated data collection methods. Direct comparison of the two methods within each study as well as a meta-analysis of all studies suggest that the results from the two methods are comparable, providing empirical support for the validity of moderated online data collection. Finally, we discuss current limitations of online data collection and possible solutions, as well as its potential to increase the accessibility, diversity, and replicability of developmental science.

[The mechanisms of the translation of polymerase from HBV pregenomic RNA].

Hepatitis B virus (HBV) is an important pathogen that causes different liver diseases such as viral hepatitis and liver cirrhosis. HBV pregenomic RNA (pgRNA) plays a crucial role in HBV life cycle, which is not only the translation template of core (C) and polymerase (P), but also the template of reverse transcription. The ratio of P protein to core protein is tightly regulated. Since P and core are both translated by pgRNA and the open reading frame (ORF) of P is located downstream of the ORF of core, how to initiate P protein translation is a key scientific question. Previous studies suggest that P can be translated through different mechanisms, such as leaky scanning and reinitiation. In this review, we summarized the proposed mechanisms relevant to the translation of polymerase from HBV pgRNA through literature review and derivation.

Impact of age and menopausal stage on serum anti-Müllerian hormone levels in middle-aged women.

OBJECTIVE: This study aimed to evaluate the association between age, menopausal stage and serum anti-Müllerian hormone (AMH) levels in middle-aged women. METHODS: In this cross-sectional study, the serum AMH levels of 288 healthy women aged 40-55 years (divided into age groups: 40-44, 45-49 and 50-55 years) were evaluated. Stages of Reproductive Aging Workshop + 10 criteria were used to categorize these women into menopausal stages: late reproductive, menopausal transition and early postmenopausal stages. The impact of age, menopausal stage and hormone replacement therapy on serum AMH levels was analyzed using multi-factor analysis of variance. Effects of body mass index, smoking status and oral contraceptive use were simultaneously considered. RESULTS: The median AMH level was 0.140 ng/ml. Log-AMH levels varied according to age group (variance = 20.113, F = 88.538, p < 0.001) and menopausal stage (variance = 5.543, F = 24.501, p < 0.001). An exponential model defined as AMH = 227,421.757 × e(-0.301 × age) was fit to describe the decline in AMH level with age. The 5th-95th percentiles of the AMH levels ranged from less than 0.020 to 3.150, less than 0.020 to 1.944 and less than 0.020 to 0.030 ng/ml in the aforementioned menopausal stages, respectively. CONCLUSION: Age and menopausal stage were associated with AMH levels; age had a greater impact on AMH than menopausal stage in middle-aged women.

Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations.

Skeletal muscle sodium channelopathies due to SCN4A gene mutations have a broad clinical spectrum. However, each phenotype has been reported in few cases of Chinese origin. We present detailed phenotype and genotype data from a cohort of 40 cases with SCN4A gene mutations seen in neuromuscular diagnostic service in Huashan hospital, Fudan University. Cases were referred from 6 independent provinces from 2010 to 2018. A questionnaire covering demographics, precipitating factors, episodes of paralysis and myotonia was designed to collect the clinical information. Electrodiagnostic studies and muscle MRI were retrospectively analyzed. The clinical spectrum of patients included: 6 Hyperkalemic periodic paralysis (15%), 18 Hypokalemic periodic paralysis (45%), 7 sodium channel myotonia (17.5%), 4 paramyotonia congenita (10%) and 5 heterozygous asymptomatic mutation carriers (12.5%). Review of clinical information highlights a significant delay to diagnosis (median 15 years), reports of pain and myalgia in the majority of patients, male predominance, circadian rhythm and common precipitating factors. Electrodiagnostic studies revealed subclinical myotonic discharges and a positive long exercise test in asymptomatic carriers. Muscle MRI identified edema and fatty infiltration in gastrocnemius and soleus. A total of 13 reported and 2 novel SCN4A mutations were identified with most variants distributed in the transmembrane helix S4 to S6, with a hotspot mutation p.Arg675Gln accounting for 32.5% (13/40) of the cohort. Our study revealed a higher proportion of periodic paralysis in SCN4A-mutated patients compared with cohorts from England and the Netherlands. It also highlights the importance of electrodiagnostic studies in diagnosis and segregation studies.

[Analysis of a pedigree with inherited factor V deficiency caused by compound heterozygous mutation].

Objective: To explore the molecular pathogenesis of a family with hereditary factor Ⅴ (FⅤ) deficiency. Methods: All the exons, flanking sequences, 5' and 3' untranslated regions of the F5 of the proband, and the corresponding mutation sites of the family members were analyzed via direct DNA sequencing. The CAT measurement was used to detect the amount of thrombin produced. The ClustalX software was used to analyze the conservation of mutation sites. The online bioinformatics software, Mutation Taster, PolyPhen-2, PROVEAN, LRT, and SIFT were applied to predict the effects of mutation sites on protein function. The Swiss-PdbViewer software was used to analyze the changes in the protein model and intermolecular force before and after amino acid variation. Results: The proband had a heterozygous missense mutation c.1258G>T (p.Gly392Cys) in exon 8 of the F5, and a heterozygous deletion mutation c.4797delG (p.Glu1572Lys fsX19) in exon 14, which results in a frameshift and produces a truncated protein. Her grandfather and father had p.Gly392Cys heterozygous variation, whereas her maternal grandmother, mother, little aunt, and cousin all had p.Glu1572LysfsX19 heterozygous variation. The ratio of proband's thrombin generation delay to peak time was significantly increased. Conservation analysis results showed that p.Gly392 was located in a conserved region among the 10 homologous species. Five online bioinformatics software predicted that p.Gly392Cys was pathogenic, and Mutation Taster also predicted p.Glu1572Lys fsX19 as a pathogenic variant. Protein model analysis showed that the replacement of Gly392 by Cys392 can lead to the extension of the original hydrogen bond and the formation of a new steric hindrance, which affected the stability of the protein structure. Conclusion: The c.1258G>T heterozygous missense mutation in exon 8 and the c.4797delG heterozygous deletion mutation in exon 14 of the F5 may be responsible for the decrease of FⅤ levels in this family.

Curcumin decreases dibutyl phthalate-induced renal dysfunction in Kunming mice via inhibiting oxidative stress and apoptosis.

Curcumin (Cur) has been used extensively in dietary supplement with antioxidant and anti-apoptotic properties. Although dibutyl phthalate (DBP) has adverse effects on the kidney, any association between DBP exposure and the role of Cur is unclear. We tested the hypothesis that exposure to DBP has adverse consequences on renal dysfunction in mice and the potential protective role of Cur in decreasing DBP-induced renal dysfunction via inhibiting oxidative stress and apoptosis. Kidney function, oxidative stress biomarkers, and apoptosis factors as well as Bcl-2 and Bax were investigated. The results showed a marked increase of renal dysfunction, oxidative stress and apoptosis level after DBP exposure compared to the control. While administration of Cur to DBP-treated mice may reduce these adverse biochemical changes compared with DBP-alone group. Overall, these results suggest that oxidative stress and apoptosis are involved in DBP-induced renal disorder, whereas Cur plays a protective role in inhibiting these two pathways.