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OBJECTIVE@#Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro.@*METHODS@#The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining.@*RESULTS@#The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism.@*CONCLUSION@#Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.
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Objective:To summarize the clinical characteristics and genetic etiology of infants with D-bifunctional protein deficiency (DBPD).Methods:This study involved two DBPD newborns who were hospitalized in the Second Affiliated Hospital of Wenzhou Medical University in August 2020 and November 2020. Clinical data including manifestations, radiographic findings and genetic testing results were retrospectively analyzed. Relevant articles up to November 2022 were retrieved from various databases including CNKI, Wanfang, CQVIP, Online Mendelian Inheritance in Man and PubMed using the terms of "D-bifunctional protein deficiency" and " HSD17B4" in both Chinese and English. Clinical data of the cases diagnosed with DBPD by genetic testing within two years of age were collected. Clinical features and genetic etiology of the children with DBPD were summarized by descriptive statistical analysis. Results:Both neonates in this report presented with dyspnea, hypotonia, intractable epilepsy, poor response, absence of primitive reflexes, and craniofacial malformation. Whole-exome sequencing revealed that patient 1 carried heterozygous variations of c.972+1G>T and c.727T>A (p.W243R) in the HSD17B4 gene, which were inherited from his father and mother, respectively. A homozygous variation of c.1333+4A>G in the HSD17B4 gene was identified in patient 2. All these mutations were pathogenic. Thirteen papers (12 in English and one in Chinese) involving 19 patients from 16 pedigrees were retrieved. Altogether 21 patients (eight males and 13 females) were included, and among them, four from two pedigrees were born to consanguineous parents. There were 21 patients with hypotonia, 20 with epileptic seizures (17 presenting with epileptic seizures within 5 d after birth) and 12 with craniofacial deformities including high forehead, long philtrum and high palatine arches. Genetic tests showed that 13 patients carried compound heterozygous variations in the HSD17B4 gene and eight patients had homozygous variations. Twenty-six variations in the HSD17B4 gene were detected, including 16 missense mutations, seven splicing mutations, two nonsense mutations and one frameshift mutation. Conclusion:DBPD should be considered and genetic tests should be given when newborns have dystonia and intractable epilepsy complicated by appearance deformity.
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Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.
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Objective:To investigate the current situation and correlation between organizational climate perception, professional identity, self-disclosure and transformation impact of new nurses in oncology department, and explore the chain mediating effect between organizational climate perception and professional identity between self-disclosure and transformation shock, so as to provide basis for further formulating the intervention plan of transformation impact.Methods:This study was a cross-sectional survey. From August 2021 to April 2022, a total of 252 newly graduated nurses in oncology department from nine Class ⅢGrade A hospitals in Henan Province were selected as the research objects by the convenient sampling method. General Information Questionnaire, Transformation of New Nurses Impact Evaluation Questionnaire, Distress Disclosure Index, Nursing Organization Climate Perception Scale, Professional Identity Scale were used for survey. Pearson correlation analysis was performed, and AMOS26.0 software was used to build a chain intermediary model, and the model was tested by Bootstrap method.Results:The total score of the transformation impact of new nurses in the oncology department was (96.51 ± 13.04); the total score of the Distress Disclosure Index was (33.84 ± 7.18); the total score of Nursing Organizational Climate Perception Scale was (99.16 ± 12.97); the total score of the Professional Identity Scale was (91.23 ± 19.92). Self-disclosure, organizational climate perception and professional identity were negatively correlated with transformation impact ( r = - 0.743, - 0.684, -0.631, all P<0.05). The indirect effect of self-disclosure on transformation impact was true, and the total indirect effect was 0.435. The specific mediating effect of nursing organizational climate perception accounted for 51.5% (22.4/43.5) of the total indirect effect and that of professional identity 15.9%(6.9/43.5) of the total indirect effect. The organizational climate and professional identity accounted for 32.4%(14.1/43.5) of the total indirect effects. Conclusions:Self-disclosure, organizational climate perception and professional identity of new nurses in oncology department was negatively correlated with transformation impact. Self-disclosure is positively correlated with organizational climate perception and professional identity, organizational climate perception and professional identity play a chain mediating effect between self-disclosure and transformation impact. It is suggested that managers should adopt positive and effective self-disclosure intervention programs and develop relevant training programs to improve the organizational climate perception and professional identity level of new nurses in oncology department, so as to reduce their transformation impact.
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Background Occupational stress has been shown to be an important factor affecting the mental health of workers. The role of affective commitment to the organization and overcommitment to work cannot be ignored. However, there is a lack of research on this topic in China. Objective To explore a potential mediating effect of affective commitment on how occupational stress affects the mental health of medical staff and a potential moderating effect of overcommitment on the mediating effect of affective commitment. Methods A total of 1372 health care workers in a tertiary Grade A hospital in Lanzhou City were selected as study subjects for a cross-sectional survey. The occupational stress, emotional commitment, and psychological distress of the subjects were evaluated by the Effort-Reward Imbalance Scale, Affective Commitment Scale, and Kessler 10 Scale. SPSS 26.0 was used for correlation analysis, mediation analysis, and moderated mediation analysis. Common method bias wasevaluated by Harman one-factor test. Results A total of 1372 questionnaires were distributed, of which 1277 valid questionnaires were returned, with a valid recovery rate of 93.08%. The mean occupational stress score was 1.14±0.23, the mean overcommitment score was 20.26±3.21, the mean affective commitment score was 20.25±3.34, and the mean psychological distress score was 26.26±7.90. The Spearman correlation analysis results showed that occupational stress among medical staff was positively correlated with overcommitment and psychological distress (r=0.153, 0.410, P＜0.01) and negatively correlated with affective commitment (r=−0.341, P＜0.01); overcommitment was negatively related to affective commitment and positively related to psychological distress (r=−0.107, 0.312, P＜0.01); affective commitment was negatively related to psychological distress (r=−0.464, P＜0.01). The positive effect of occupational stress on psychological distress of medical staff was significant (b=0.41, t=15.42, P<0.001); affective commitment presented a partial mediating effect on the relationship between occupational stress and psychological distress (effect value=0.13), accounting for 31.71% of the total effect; overcommitment moderated the process of occupational stress-affective commitment-psychological distress (P＜0.01). Conclusion Affective commitment of medical staff has a partial mediating effect on the relationship between occupational stress and psychological distress, and overcommitment plays a significant role in moderating the process of occupational stress-affective commitment-psychological distress.
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ObjectiveTo investigate the prevalence of overweight or obesity in community patients with schizophrenia in Shanghai and to explore the related factors. MethodsStratified cluster sampling method was used and the general condition， physical examination and laboratory examination data of patients with schizophrenia who voluntarily participated in 2020 free health examination of National Basic Public Health Service were analyzed. ResultsA total of 3 200 patients were included into the study ，and the prevalence of overweight and obesity was 36.75% and 17.19%， respectively. Multivariate logistic regression analysis indicated that age between 40 and 60 （OR=1.333， 95%CI： 1.030‒1.724）， intake of first-generation antipsychotics （OR=1.413， 95%CI： 1.112‒1.796）， intake of second-generation antipsychotics （OR=1.573， 95%CI： 1.288‒1.921）， high-normal blood pressure （OR=1.549， 95%CI： 1.245‒1.927）， high-abnormal blood pressure （OR=2.824， 95%CI： 2.204‒3.619）， elevated ALT （OR=1.874， 95%CI： 1.386‒2.535）， elevated FBG （OR=1.270， 95%CI： 1.066‒1.513）， and elevated TG （OR=1.652， 95%CI： 1.335‒2.044） were the related factors that associated overweight or obesity in patients with schizophrenia. ConclusionOverweight and obesity are highly prevalent among community patients with schizophrenia in Shanghai. Age between 40 and 60， taking first-generation and second-generation antipsychotics， blood pressure higher than 120/80 mmHg， elevated ALT， elevated FBG， and elevated TG are associated with overweight or obesity in patients with schizophrenia. To provide personalized health guidance， medical staff in primary health care institutions should pay more attention to high-risk groups of overweight and obesity in schizophrenia patients at annual physical examination.
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The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.
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Rats , Animals , NF-kappa B/metabolism , Spleen , Gastrointestinal Microbiome , Toll-Like Receptor 4 , Polysaccharides/pharmacology , Astragalus Plant/metabolism , Immune System Diseases/drug therapy , Body WeightABSTRACT
ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified an in vivo ACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection. HighlightsO_LIVitC reduces ACE2 protein levels in a dose-dependent manner C_LIO_LIVitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2 C_LIO_LIVitC blocks the interaction between USP50 and ACE2 C_LIO_LIVitC administration lowers host ACE2 and prevents SARS-CoV-2 infection in vivo C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/499651v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@196682borg.highwire.dtl.DTLVardef@190f14dorg.highwire.dtl.DTLVardef@d22b59org.highwire.dtl.DTLVardef@1c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG The deubiquitinase USP50 controls ACE2 protein stability and levels, while Vitamin C blocks the USP50-ACE2 interaction and therefore results in ACE2 degradation, offering a flexible and efficient approach to protection of the host from SARS-CoV-2 infection.
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Objective:To study the relationship between the 1580 locus (rs1130866) gene polymorphism of pulmonary surfactant protein B (SP-B) gene and susceptibility of neonatal respiratory distress syndrome (RDS) in Uygur newborns.Methods:From June 2019 to May 2020, Uyghur premature infants admitted to the Department of Neonatology of our hospital were prospectively enrolled and assigned into RDS group and control group according to their diagnosis. The genotype and allele distribution of SP-B gene 1580 locus were examined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis technology. The genotype and allele frequency of SP-B gene 1580 locus in RDS infants among Uyghur, Mongolian and Han nationality were compared.Results:A total of 160 infants were enrolled, including 80 in the RDS group and 80 in the control group. Three genotypes (TT, TC and CC) were detected in both groups. The frequencies of the three genotypes in the RDS group were 18.8%, 53.8% and 27.4%, respectively, with T allele frequency 45.6% and C allele frequency 54.4%. The frequencies of the three genotypes in the control group were 22.5%, 52.5% and 25.0%, respectively, with T allele frequency 48.8% and C allele frequency 51.3%. No significant differences existed in genotype frequency and allele frequency distribution between the two groups ( P>0.05). The CC genotype frequency of SP-B gene 1580 locus in Uyghur was significantly different from Mongolian and Han nationality ( P<0.05). Significant difference existed in C allele frequency between Uyghur and Han nationality ( P<0.05), while no significant difference existed in allele frequency between Uyghur and Mongolian nationality ( P>0.05). Conclusions:No correlation exists between the polymorphism of SP-B gene 1580 locus (rs1130866) and RDS in Uygur premature infants. Different ethnic groups have different SP-B gene 1580 locus polymorphism.
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Objective:To study the clinical characteristics of purulent meningitis complicated with hydrocephalus in neonates, and to analyze the risk factors of the disease.Methods:Neonates diagnosed with purulent meningitis complicated with hydrocephalus who hospitalized in the department of neonatology of the Second Affiliated Hospital of Wenzhou Medical University from January 2002 to August 2021 were selected as the case group. Neonates with positive pathogen cultures but no hydrocephalus during the same period were assigned by random number table method as the control group. The ratio of the control group and the case group was 2 ∶1. The clinical data such as bacteria distribution, cranial imaging, therapy and prognosis were compared between the two groups. The risk factors for hydrocephalus were predicted. Statistical analysis was conducted using chi-square test and multiple logistic regression analysis.Results:There were 33 cases in the case group and 66 cases in the control group. A total of 27 cases had confirmed pathogen results, of which 20 cases (74.1%) were Gram-negative bacteria and seven cases (25.9%) were Gram-positive bacteria. The time of diagnosis for hydrocephalus were 13.0(5.5, 28.5) days after the onset. Twenty-six cases received non-surgical treatment, while seven cases received surgery. The cure rate of case group was 42.4%(14/33), which was lower than that of control group (72.7%, 48/66), and the difference was statistically significant ( χ2=8.63, P=0.003). Univariate analysis showed that the incidences of protein>3 g/L in cerebrospinal fluid, glucose<2 mmol/L in cerebrospinal fluid, convulsions, central respiratory failure, intracranial hemorrhage and encephalomalacia in the case group were all higher than those in the control group, with statistical significance ( χ2=19.72, 12.04, 19.04, 5.73, 11.85 and 17.48, respectively, all P<0.050). Multivariate logistic regression analysis showed that convulsions (odds ratio ( OR)=4.476, 95% confidence interval ( CI) 1.091 to 18.363, P=0.037), intracranial hemorrhage ( OR=8.031, 95% CI 1.894 to 34.059, P=0.005) and encephalomalacia ( OR=35.189, 95% CI 2.954 to 419.150, P=0.005) were risk factors for neonatal purulent meningitis complicated with hydrocephalus. Conclusions:Gram-negative bacteria are common pathogen of neonatal purulent meningitis complicated with hydrocephalus. Convulsions, intracranial hemorrhage and encephalomalacia are important predictors for neonatal purulent meningitis complicated with hydrocephalus.
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Background Current evidence on whether occupational sulfur dioxide (SO2) exposure affects the risk of hypertension is still limited, and the research results of the effect of environmental SO2 exposure on risk of hypertension remain inconsistent. Objective To analyze the association between self-reported occupational exposure to SO2 and the risk of hypertension, and the potential dose-response relationship between the years of exposure to SO2 and the risk of hypertension. Methods Based on the Jinchang cohort, a nested case-control study design was adopted. A total of 841 newly diagnosed hypertension patients were followed up as the case group, and the control group was selected with 1∶1 individual matching based on non-occupational factors and occupational factors, respectively. The former matching conditions included age ±2 years old, same gender, working age ±2 years, and home address in the same sub-district. The latter was limited to working in the same workshop on the basis of the former conditions. Finally, the former included 717 controls and the latter included 488 controls. A unified questionnaire was used to collect general demographic characteristics, lifestyle habits, history of diabetes, family history of hypertension, and information on occupational exposure to SO2 (self-reported history of occupational exposure to SO2 and years of exposure to SO2). Conditional logistic regression model was used to analyze the association between occupational exposure to SO2 and hypertension, and the dose-response relationship between the years of SO2 exposure and the risk of hypertension. Results In the nested case-control study matching with the non-occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO2 was 2.39 (95%CI: 1.68-3.39); while when matching with the occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO2 was 1.48 (95%CI: 1.04-2.12). The results of the dose-response relationship showed that as the SO2 exposure years increased from 1-9 years, 10-19 years, 20-29 years, and 30 years and above, in the nested case-control study matching with non-occupational factors, the ORs of hypertension were 1.85 (95%CI: 0.68-5.08), 1.46 (95%CI: 0.58-3.67), 1.64 (95%CI: 1.00-2.67), and 4.95 (95%CI: 2.63-9.31), respectively; in the nested case-control study matching with occupational factors, the ORs of hypertension were 0.98 (95%CI: 0.40-2.41), 1.84 (95%CI: 0.72-4.70), 1.37 (95%CI: 0.82-2.29), and 2.44 (95%CI: 1.37-4.35), respectively. The two dose-response relationships were positive by χ2 trend test (Ptrend<0.05). Conclusion Self-reported occupational exposure to SO2 is associated with the risk of hypertension in the study population, and the hypertension risk increases with the increase of SO2 exposure years.
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OBJECTIVE To provide reference and ideas for optimizing the continuing education system of pharmacists in China. METHODS By introducing the continuing professional development （CPD）model of pharmacists in Japan ，the current situation and existing problems for continuing education of pharmacists in China were analyzed to puts forward some suggestions. RESULTS & CONCLUSIONS The continuing education system of CPD model for pharmacists in Japan included five continuous cycle processes ：self-assessment，making plan ，implementing plan ，learning record and result evaluation. It emphasized the autonomy and sustainability of pharmacists ’learning and promoted the sustainable development of pharmacists ’career. The education and training of pharmacists in Japan were subject to the certification system ，and a diversified implementation organization composed of industry associations ，colleges and universities and commercial education institutions had been formed. After continuous reform ，Japan had established a relatively mature and perfect sustainable career development model for pharmacists. Our country can refer to the CPD model of Japanese pharmacists ，promote the legislation of pharmacists ，explore the unified management model （the unity of hospital pharmacists and licensed pharmacists ），explore the construction of pharmacists ’ continuing education certification mechanism ，carry out refined continuing education for pharmacists in different practice fields ， improve the enthusiasm of industry associations ，and add practical content to pharmacists ’continuing education projects.
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ObjectiveTo investigate the characteristics of pelvic floor structure and electrophysiology in female patients with stroke. MethodsFrom June to December, 2020, 21 female inpatients with stroke in Zhongda Hospital, Southeast University (stroke group) were divided into urinary incontinence (UI) group (n = 6) and non-urinary incontinence (NUI) group (n = 15), and other 20 healthy subjects were as control group. They were observed with pelvic floor ultrasonography and pelvic floor surface electromyogram. ResultsAverage electromyography, integral electromyography, root mean square, mean power frequency and median frequency decreased in UI and NUI groups compared with those of the control group (P < 0.05), but there was no significant difference between UI group and NUI group (P > 0.05). Bladder neck position, bladder neck angle, bladder neck mobility, urethral rotation angle; and anteroposterior diameter, left-right diameter and area of levator ani muscle hiatus after Valsalva's action were all not different among three groups (F < 2.484, P > 0.05). ConclusionThe activities of pelvic floor muscles decrease in female patients with stroke, without obvious changes of pelvic floor supporting structures, whatever UI.
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Objective:To investigate the clinical characteristics and pathogenic gene mutation of lateral meningocele syndrome(LMS).Methods:We retrospectively collected the clinical manifestations, laboratory examination, imaging examinations, and genetic analysis of a neonate with LMS which was diagnosed at the Department of Neonatology of the Second Affiliated Hospital of Wenzhou Medical University in May 2020. Relevant literature up to February 2021, retrieved from PubMed, OMIM, CNKI, Wanfang, and CQVIP database with the terms of "lateral meningocele syndrome", " NOTCH3", were reviewed to summarize the clinical characteristics, pathogenesis, and genetic etiology of this disease. Results:A full-term male newborn was admitted to our hospital due to feeding difficulty 7 d after birth. The clinical characteristics included hypotonia, dysphagia, hypertension, lateral spinal meningocele, craniofacial anomaly, and cryptorchidism. Abnormal spinal MRI and brainstem evoked potential were also observed. Whole exome sequencing revealed a heterozygous frameshift variation c.6667_6686del(p.Ala2223Profs*12) of NOTCH3 gene located in 19p13.12, which was not detected in the parents. Only 12 English literature were retrieved, with 17 patients from 15 pedigrees. Out of the 18 patients including the index case, 10 were genetically diagnosed as LMS. The age at diagnosis ranged from 15 d to 55 years. Regarding the clinical features, multiple lateral thoracolumbar spinal meningoceles (18/18) was the most common one, followed by retrognathia and low-set ears (16/18), eyelid ptosis and down slanting palpebral fissures (15/18), hypotonia (13/18), hypertension (11/18), developmental delay (9/18), mixed or conductive hearing loss (9/18), cardiovascular dysplasia (7/18), and cryptorchidism (7/10). A total of nine NOTCH3 gene variants were detected, all were heterozygous variants, including six frameshift and three nonsense variants. Conclusions:LMS is caused by NOTCH3 gene mutation with the clinical characteristics including multiple lateral thoracolumbar spinal meningoceles, craniofacial dysmorphisms, hypotonia, hypertension, developmental delay, difficulty in feeding, cryptorchidism, etc.
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Objective@#To analyze heavy metal health risks of direct drinking water in primary and secondary schools in Huangpi District, Wuhan, so as to provide reference basis for ensuring drinking water safety of teachers and students.@*Methods@#Cadmium (Cd), Plumbum (Pb) and arsenic (As) in water samples from primary and secondary schools were detected in accordance with the GB/T 5750-2006 "Standard Examination Methods for Drinking Water", water quality was evaluated based on the Quality Standard for Fine Drinking Water(CJ 94-2005). Health risk assessment model was used to evaluate the potential risk of heavy metals in direct drinking water in primary and secondary schools.@*Results@#The unqualified rates of Pb, Cd and As were 0.95%, 1.22% and 0 in 66 primary and secondary schools in Huangpi District, Wuhan. The risk of noncarcinogens related to the direct drinking water of heavy metals (Pb, Cd, As) were less than 1. The range of carcinogenic risks related to the direct drinking water was within the range of 1.07×10 -8 /year -5.58×10 -6 /year which were both within the acceptable level.@*Conclusion@#Concentrations of cadmium, plumbum and arsenic were not found to be significantly elevated as compared to "Quality Standard for Fine Drinking Water" in Huangpi District of Wuhan. Pb and Cd slightly exceeded the standard, with no significant health risk. Water quality and health risk assessment should be strengthened to ensure the safety of drinking water for teachers and students.
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OBJECTIVE：To provi de reference for improvin g the quality assurance system of clinical pharmaceutical talent training and promoting the development of clinical pharmaceutical education in China. METHODS ： The background of pharmaceutical education reform and accreditation in Japan was introcuded ；the development of clinical pharmaceutical professional accreditation standards in Japan and the main changes of current standards were analyzed so as to put forward the enlightenment to the development of clinical pharmaceutical education in China. RESULTS & CONCLUSIONS ：Japan officially started the six-year clinical pharmaceutical education in 2006，which stipulated that only graduates of six-year clinical pharmaceutical education can be qualified to participate in the national examination for pharmacists. Japan Accreditation Borad of Pharmaceutical Education （JABPE）is responsible for the professional accreditation of clinical pharmacy in Japan. Its accreditation standards experienced the development of three versions in 2006，2012 and 2018. The main changes in the latest accreditation standards in Japan （2018 edition）are reflected in the innovation of index system framework ，accreditation concept and training requirements. For example ， its system framework integrates 57 benchmarks and 176 viewpoints in 2012 edition of accreditation standard into 19 benchmarks and 53 viewpoints in 2018 edition of accreditation standard ，with prominent focus ，clarity and simplification. Our country should learn from the development experience of clinical pharmaceutical professional accreditation in Japan ，perfect laws and regulations to ensure the healthy and orderly development of accreditation system ；establish an independent third-party certification body ；explore the mechanism of organic connection between professional certification and professional qualification ；attach importance to the application of self-evaluation and qualitative indicators ； explore and construct a training mode of clinical pharmaceutical talents based on national conditions and in line with international standards.
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BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a cluster of coronavirus disease 2019 (COVID-19). We reported the clinical characteristics of COVID-19 patients with acute respiratory distress syndrome (ARDS), and further investigated the treatment and progression of ARDS in COVID-19. MethodsThis study enrolled 109 patients with COVID-19 admitted to the Central Hospital of Wuhan, a designated hospital in Wuhan, China, from January 2 to February 1, 2020. Patients were followed up to February 12, 2020. The clinical data were collected from the electronic medical records. The differences in the treatment and progression with the time and the severity of ARDS were determined. FindingsAmong 109 patients, mean age was 55 years, and 59 patients were male. With a median 15 days (range, 4 to 30 days) follow-up period, 31 patients (28.4%) died, while 78 (71.6%) survived and discharged. Of all patients, 53 (48.6%) developed ARDS. Compared to non-ARDS patients, ARDS patients were elder (mean age, 61 years vs. 49 years), and more likely to have the coexistent conditions, including diabetes (20.8% vs. 1.8%), cerebrovascular disease (11.3% vs. 0%), and chronic kidney disease (15.1% vs. 3.6%). Compared to mild ARDS patients, those with moderate and severe ARDS had higher mortality rates. No significant effect of antivirus, glucocorticoid, or immunoglobulin treatment on survival was observed in patients with ARDS. InterpretationThe mortality rate increased with the severity of ARDS in COVID-19, and the effects of current therapies on the survival for these patients were not satisfactory, which needs more attention from clinicians. FundingHealth and Family Planning Commission of Wuhan Municipality.
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Objective:To explore the efficacy and safety of open cardiac operation and interventional therapy in pregnant patients and describe the feto-neonatal and maternal outcomes.Methods:A retrospective study of 39 cases of women undergoing open cardiac operation or interventional therapy during pregnancy was conducted in Guangdong Provincial People′s Hospital from Jan. 2014 to Oct. 2019.Results:The age of 39 pregnant women with gestational heart disease was (30±6) years old (21-43 years old). Among them, 37 cases were single and 2 cases were twin pregnancy. Modified World Health Organization (mWHO) pregnancy risk classification were all level Ⅳ. There were 22 women receiving cardiac operation under cardiopulmonary bypass during pregnancy, 14 patients undergoing percutaneous balloon mitral valvuloplasty, 2 patients accepting percutaneous balloon pulmonary valvuloplasty, and 1 case receiving atrial septal defect occluder with ultrasound guidance. Three were no maternal deaths during and after the operation. One patient had an inevitable abortion. Four fetuses died in the uterine after open cardiac surgery. There patients chose termination of the pregnancy after cardiac operation. There were 31 live birth, in which 7 cases were preterm live birth and 24 patients were term live birth. The total number of newborns were 33. Two fetuses suffered neonatal intracranial hemorrhage and died after birth. Thirty-one fetuses were alive and born without any abnormity.Conclusion:For pregnant women with high risk of cardiovascular disease and classified as mWHO pregnancy risk level Ⅳ, cardiopulmonary bypass and interventional therapy during pregnancy could be used as an alternative for better materal and fetal outcomes.
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OBJECTIVE： To establish the prediction model of steady-state dose of warfarin in patients with renal insufficiency on the basis of CYP2C9＊3（1075A＞C） and VKORC1-1639G＞A gene polymorphism. METHODS： The clinical data of 103 patients with renal dysfunction （involving primary glomerulonephritis， chronic pyelonephritis， hypertensive renal arteriosclerosis， diabetic nephropathy， secondary glomerulonephritis， tubulointerstitial lesions， hereditary kidney diseases） who took warfarin and whose INR was stable at 1.5-3.0 were collected from nephrology department of the First Affiliated Hospital of Xi’an Jiaotong University during Jun. 2016 to Jun. 2019. The CYP2C9＊3（1075A＞C） and VKORC1-1639G＞A genotypes were detected by fluorescence staining in-situ hybridization. The relationship of genotype， gender， age， body mass index （BMI） and glomerular filtration rate （eGFR） with steady-state dose of warfarin were analyzed. The multiple linear regression method was used to establish the prediction model for steady-state dose of warfarin in patients with renal insufficiency. Other 25 patients were involved in validation. RESULTS： The frequencies of CYP2C9＊3（1075A＞C） and VKORC1-1639G＞A genes in 103 patients were in accordance with Hardy-Weinberg equilibrium. The average steady-state dose （3.20±0.88） mg/d of warfarin in CYP2C9＊3 （1075A＞C） AA genotype was significantly higher than that （2.17±0.13） mg/d in CYP2C9＊3 （1075A＞C） AC genotype （P＜0.05）； average steady-state dose （2.89±0.08） mg/d of warfarin in VKORC1-1639G＞A AA genotype was significantly lower than that （4.01±0.17） mg/d in VKORC1-1639G＞A GA genotype （P＜0.05）； steady-state dose of warfarin in male patients （3.16±0.11） mg/d was higher than that in female patients （3.07±0.13） mg/d （P＞0.05）. Age was negatively correlated with steady-state dose of warfarin （P＜0.05）； eGFR was positively correlated with steady-state dose of warfarin （P＜0.05）. BMI had no significant correlation with steady-state dose of warfarin （P＞0.05）. The prediction model for steady-state dose of warfarin included steady-state dose of warfarin＝3.057－0.73* VKORC1-1639G＞A+0.08*eGFR－0.013* age+0.565* CYP2C9＊3（1075A＞C） [VKORC1-1639G＞A：AA＝1，GA＝0，GG＝0；CYP2C9＊3（1075A＞C）：AA＝1，AC＝0；the age was years old； the unit of eGFR was mL/（min·1.73 m2）] （R2＝0.502）. There was no statistical significance between the dose （3.12±0.56） mg/d of prediction model and actual steady-state dose （3.06±0.93） mg/d in 25 validation patients （P＞0.05）. CONCLUSIONS： There are significant differences in steady-state dose of warfarin among different genotype patients with CYP2C9＊3（1075A＞C） AA and VKORC1-1639G＞A. The prediction model of warfarin steady-state dose in patients with renal insufficiency is established successfully.
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Objective To evaluate the effects of selective brain hypothermia on the expression of miR-484 during cerebral ischemia-reperfusion ( I/R) in rats. Methods A total of 120 clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=30 each) using a random number table method: sham operation group ( group S) , cerebral I/R group ( group I/R) , hypothermia group ( group H) and normothermia group ( group N) . Blood vessels were only separa-ted and ligated without blockade in group S. In the other three groups, cerebral I/R was induced by inser-ting a nylon thread with rounded tip into the right internal carotid artery, and the middle cerebral artery was occluded for 2 h followed by reperfusion. In group H, 4℃ normal saline was infused for 15 min at a rate of 80 ml·kg-1 ·h-1 through the internal carotid artery immediately after removing the nylon thread. In group N, 37 ℃ normal saline was infused in the same way. Neurological deficit scores were evaluated at 6, 24 and 48 h after reperfusion. Animals were then sacrificed, the cerebral cortex of the ischemic penumbra was removed for determination of nerve cell apoptosis ( by TUNEL method) , expression of mitochondrial fission protein 1 ( Fis1) ( by Western blot) and expression of miR-484 ( quantitative real-time polymerase chain re-action) . The apoptotic rate was calculated. Results Compared with group S, the neurological deficit score and apoptotic rate of nerve cells were significantly increased, and the expression of Fis1 was up-regulated at each time point in the other three groups, the expression of miR-484 was significantly down-regulated in I/R and N groups, and the expression of miR-484 was significantly up-regulated in group H ( P＜0. 05 or 0. 01) . Compared with group I/R and group N, the neurological deficit score and apoptotic rate of nerve cells were significantly decreased, and the expression of Fis1 was down-regulated, and the expression of miR-484 was up-regulated at each time point in group H ( P＜0. 05 or 0. 01) . Conclusion The mechanism by which se-lective cerebral hypothermia attenuates cerebral I/R injury is associated with up-regulating miR-484 expres-sion and thus down-regulating Fis1 expression in rats.
