Objective To systematically evaluate toxicities of nifedipine in pregnant women with hypertension, and provide references for nifedipine’s clinical safety application. Methods Study was conducted with data from US food and drug administration adverse event reporting system（FARES） database from January 1, 2015, to March 31, 2021. Information component （IC） and reporting odds ratio（ROR）methods were applied for signal mining. Results Finally, a total of 539278 records of pregnant women with hypertension were selected for analysis, and 70 positive adverse drug event signals were detected. Premature delivery （IC₀₂₅=2.87，ROR₀₂₅=9.52）, pre-eclampsia （IC₀₂₅=1.82，ROR₀₂₅=3.82） and fetal growth restriction （IC₀₂₅=2.37，ROR₀₂₅=5.69）were positive adverse events with higher frequency. Polydactyly（IC₀₂₅=3.13， ROR₀₂₅=10.05）, fetal death（IC₀₂₅=2.93，ROR₀₂₅=8.57）and premature delivery（IC₀₂₅=2.87，ROR₀₂₅=9.52）were positive adverse events with higher intensity. Vascular resistance systemic increased, small for dates baby and fetal death corresponded to higher death rates. Conclusion Nifedipine-associated drug toxicities were detected in pregnant women with hypertension, and some adverse events with high frequency and high death rate were deserved further attention by medical staffs.

Objective To analyze the deep venous thrombosis(DVT)after plasma infusion in a patient with congenital dysfibrinogene-mia(CD),and explore the relationship between the CD and DVT.Methods The clinical data were collected and the pedigree was investigated(3 subjects of 2 generations in total).The relevant indexes of coagulation factors of the patient and her family members were detected.The genomic DNA of peripheral blood was extracted for PCR amplification.All the exons,flanking sequences,5'and 3'untranslated regions of FGA,FGB and FGG genes of fibrinogen(Fg)of the patient were analyzed by direct sequencing.The corre-sponding mutation site was subjected to sequence in the other members of this family.The PyMol software was used to construct the pro-tein model before and after gene mutation.Results The patient was admitted to hospital for hysteromyomectomy.DVT appeared in 3 days after surgery.The prothrombin time(PT),thrombin time(TT),Fg activity(Fg∶C)and Fg antigen(Fg∶Ag)of the patient was 14.9 s,33.3 s,0.94 g/L and 2.10 g/L,respectively.The above four indicators in her mother were 14.7 s,32.8 s,0.97 g/L and 2.35 g/L,respectively.Gene sequencing revealed that both the patient and her mother had a heterozygous missense mutation c.2185G＞A(p.Glu729Lys)in exon 6 of the FGA gene.The protein model analysis demonstrated that p.Glu729Lys mutation changed the amino acid side chain and reduced the number of hydrogen bonds originally formed with Arg854.Conclusion A heterozygous missense mutation c.2185G＞A(NM_000508)in exon 6 of the FGA gene should be responsible for the low fibrinogen level in this pedigree,which might be the main reason for DVT after plasma infusion in this patient.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

Objective To investigate the expression of cysteine rich protein 2 binding protein(CSRP2BP)mRNA and estrogen related receptors β(ESRRB)mRNA and protein in cervical cancer tissues and their correlation with epithelial mesenchymal transition(EMT)and clinical prognosis.Methods A total of 106 cervical cancer patients admitted to Yan'an Traditional Chinese Medicine Hospital from March 2018 to March 2020 were selected.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect CSRP2BP mRNA,ESRRB mRNA and EMT related indicators[E-cadherin(E-cad),N-cadherin(N-cad),snail family transcriptional repressor 1(Snail)].Immunohistochemistry was used to detect the CSRP2BP protein and ESRRB protein expression in tissues.Pearson correlation analysis was used to analyze the correlation between CSRP2BP mRNA,ESRRB mRNA and EMT related indicators.Kaplan-Meier curve and COX regression were used to analyze the effect of CSRP2BP mRNA and ESRRB mRNA expression on the prognosis of cervical cancer patients.Results CSRP2BP mRNA(3.14±0.52 vs 1.22±0.21)expression and protein positive rate(86.79%vs 9.43%),ESRRB mRNA expression(2.86±0.31 vs 1.06±0.20)and protein positive rate(92.45%vs 8.49%),N-cad mRNA(3.22±0.43 vs 1.05±0.26)and Snail mRNA(2.67±0.36 vs 0.69±0.17)expression in cancer tissues were higher than those in adjacent tissues,while E-cad mRNA(0.84±0.17 vs 2.15±0.24)expression was lower than that in adjacent tissues,and the differences were statistically significant(t/x2=34.249,127.049;50.234,149.466;44.461,51.204,45.858,all P<0.001).The expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer was positively correlated with N-cad mRNA and Snail mRNA(r=0.663,0.731;0.726,0.715,all P<0.001),and was negatively correlated with E-cad mRNA(r=-0.594,-0.669,all P<0.001).The expression of CSRP2BP mRNA(4.48±0.36,4.21±0.37,4.69±0.33)and ESRRB mRNA(4.48±0.36,4.21±0.37,4.69±0.33)in cervical cancer tissues of patients with FIGO stage Ⅰ B2～Ⅱ A,poor differentiation and lymph node metastasis was higher than that of patients with FIGO stage ⅠA～ⅠB1(2.60±0.44,2.06±0.24),medium and high differentiation(2.43±0.44,2.01±0.25)and no lymph node metastasis(2.53±0.58,2.07±0.26),and the differences were statistically significant(t=16.327,41.135;18.507,36.545;14.501,43.806,all P<0.001).The 3-year overall survival rate of patients with high expression of CSRP2BP mRNA was 66.00%(33/50),which was lower than 89.29%(50/56)in the low expression group,while the 3-year overall survival rate of the high expression group of ESRRB mRNA was 65.38%(34/52),which was lower than 90.74%(49/54)of the low expression group,and the differences were statistically significant(Log rank x2=5.401,11.400,P=0.020,0.001).Multivariate Cox regression analysis showed that,CSRP2BP mRNA high expression(HR=1.327,95%CI:1.097～1.605),ESRRB mRNA high expression(HR=1.322,95%CI:1.108～1.577),FIGO stage Ⅰ B2～Ⅱ A(HR=1.423,95%CI:1.154～1.755),lymph node metastasis(HR=1.363,95%CI:1.095～1.698)and poor differentiation(HR=1.297,95%CI:1.064～1.581)were risk factors affecting the prognosis of cervical cancer patients(all P<0.001).Conclusion The increased expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer are related to EMT related indicators and adverse clinical and pathological features,and are new tumor markers for prognostic evaluation.

"Bio-separation engineering" is a compulsory course for undergraduate students majored in bioengineering, and an important part of the "emerging engineering education" system for bioengineering. Our teaching team follows the principle of "student development as the center, innovation thinking as the core". Guided by the concept of "learning achievement", we reconstructed the teaching contents of this course, and carried out the teaching reform aiming at solving several long-standing problems. These include, for instance, the theoretical teaching is separated from the experimental practice, and students cannot internalize the theoretical knowledge into practical ability in time. Moreover, the contents of course is out-of-date and out of line with industry demand, the teaching form and assessment methods are relatively single, and the students' professional ability and quality are not effectively cultivated. In the new curriculum system, in which the "online" and "offline" teaching are both applied, we broke the boundary between theoretical and experimental courses, and made the contents keep up with the forefront of industry development through research-based teaching. In terms of teaching methods and teaching evaluation, we made full use of modern information technology to enrich classroom teaching activities, and carried out complete, dynamic and diversified assessment for students. These teaching reform measures greatly improved the students' interest in learning this course, as well as their professionalism and research ability.
Bioengineering ; Biomedical Engineering ; Curriculum ; Humans ; Learning ; Students

Objective:To investigate the clinical features of Epstein-Barr virus associated lymphoproliferative disease in children and to improve the understanding of this disease.Methods:This study included the children with Epstein-Barr virus associated lymphoproliferative disease admitted to the First Affiliated Hospital of College of Medicine of Zhejiang University from January 2014 to December 2018.Data of these children were collected, including age, clinical manifestations, laboratory results, treatment and outcome.The clinical features and therapeutic effects were analyzed.Results:A total of 114 cases(mean age 6 years, 0~17 years)were enrolled in this study, including 53 males and 61 females.There were 107 cases(93.86%) in the mild group (38 cases of EBV infection and 69 cases of infectious mononucleosis) and 7 cases in the severe group (6.14%). Six cases of the severe group were T cell or NK cell proliferation.Compared with the mild group, the load of EBV-DNA was higher in the severe group, but there was no significant difference( χ2=0.957, P>0.05). The IgM in severe group was significantly lower( Z=-2.041, P<0.05). But the differences in the level of immune function including IgA, IgG, CD4 + cell and CD8 + cell between the severe group and the mild group were not significant.The cases in the mild group had improved after antiviral treatments.Among the severe group, 3 cases survived after treatment, another 1 case was diagnosed as hydroa vacciniforme-like EBV-related proliferative disease (HV-like LPD). After antiviral treatment, the effect was not good, then after high-dose IVIG treatment and Bortezomib combined with methylprednisolone treatment, the EBV-DNA load decreased and the condition improved.While 1 case lost to follow-up, there were 2 cases with EBV-associated hemophagocytic syndrome and 1 case with EBV-associated lymphoma died after chemotherapy or transplantation. Conclusion:EBV-associated lymphoproliferative disease may manifest as a condition similar to infectious mononucleosis.High IgE, low IgM or high DNA load may indicate poor prognosis.Immune function after EBV infection may have different effects on prognosis.When the infected lymphocyte types are NK or T cells, it may indicate poor prognosis.The efficacy of transplantation and chemotherapy in severe cases is still uncertain.

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

Objective: To describe the dermoscopic features of extramammary Paget′s disease (EMPD) and chronic eczema of the vulva, and to explore the value of dermoscopy in the diagnosis and differential diagnosis of the above diseases. Methods: Dermoscopic images were collected from 20 patients with histopathologically confirmed vulvar EMPD and 16 patients with clinically confirmed chronic eczema of the vulva in Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Pekin Union Medical College from January 2017 to April 2018, and retrospectively analyzed. Fisher′s exact test was used to compare the prevalence of dermoscopic features between the two groups. Results: As dermoscopy showed, the milky red background was observed in 19 EMPD patients and in only 1 patient with chronic eczema, and there was a significant difference in the prevalence of milky red background between the two groups (P < 0.001) . White scales were the most common desquamation, and were observed in 9 EMPD patients and 13 patients with chronic eczema (P = 0.128) . Blood vessels were uniformly distributed in EMPD patients, including dotted-globular vessels in 19 and linear vessels in 14, while blood vessels were distributed in a patchy or clustered pattern in the patients with chronic eczema, including dotted-globular vessels in 16 and linear vessels in 7. There was a significant difference in the prevalence of different distribution patterns of blood vessels between the two groups (P < 0.001) . Bright white streaks, bright white structureless area and reticular structure were observed in 19, 20 and 19 EMPD patients respectively, and in 1, 1 and 1 patient with chronic eczema respectively, and there were significant differences in the prevalence of the above 3 structures between the two diseases (all P < 0.001) . Conclusion Vulvar EMPD and chronic eczema both show characteristic dermoscopic features, and dermoscopy is of great value to the diagnosis and differential diagnosis of EMPD.

Objective: To evaluate the safety and feasibility of treating de novo coronary lesions with paclitaxel-eluting balloon. Methods: This is a retrospective study, which enrolled 76 patients with 80 de novo coronary lesions treated with paclitaxel-eluting balloons(<30% residual stenosis and there was no blood flow limited dissection after pretreatment) from April 2015 to November 2016 in Guangdong general hospital. The data of basic characteristics,procedures,devices and follow-up information were retrieved and analyzed. The primary endpoint was the composite of cardiac death, recurrent myocardial infarction and target lesion revascularization. Results: (1)The age was (63.3±10.3) years. There were 68.4%(52/76) acute coronary syndrome patients, prevalence of type 2 diabetes was 36.8%(28/76), and 64.5%(49/76)patients with at least one high bleeding risk. (2)The lesion length was (17.4±7.6)mm, and the stenosis was (88.1±8.2)%.The reference vessel diameter≥2.75 mm accounted for 51.2% (41/80), and bifurcation stenosis accounted for 67.5%(54/80). (3)53.7%(43/80) lesions were pretreated with scoring balloon to optimize plaque modification. The paclitaxel-eluting balloon length and diameter were (22.3±5.5)mm and (2.74±0.52)mm.The residual stenosis was (12.3±10.3)%. Procedural success was 88.8%(71/80).Bail-out stenting rate was 5.0%(4/80). (4)The median follow-up duration was 12(6, 25) months. Primary endpoint occurred in 3 cases (3.9%), including 2 cardiac deaths(1 patient died of recurrent myocardial infarction, and 1 patient died of acute heart failure induced by severe mitral insufficiency), and one patient receivedtarget lesion revascularization. Conclusion In case of no more than 30% residual stenosis and no blood flow limited dissection after lesion pretreatment,it is safe and feasible to treat de novo coronary lesionsusing paclitaxel-eluting balloon.