Clinical progression of asynchronous cutaneous lesions in a patient with locally acquired mpox infection.

We present one of the earliest domestic mpox cases in Taiwan, highlighting the asynchronous and atypical progression of cutaneous lesions which could pose significant diagnostic challenges for clinicians.

Rhabdomyolysis in Pediatric Patients with SARS-CoV-2 Infection.

BACKGROUND: Rhabdomyolysis is a rare but severe complication in adult patients with Coronavirus disease 2019 (COVID-19), which can result in acute kidney injury and death; however, it is rarely reported in pediatric patients. METHODS: In this study, we retrospectively reviewed the clinical features and outcomes of rhabdomyolysis in pediatric patients aged 0-18 years with COVID-19 who were hospitalized at Taipei Tzu Chi Hospital, an epicenter of COVID-19 in northern Taiwan. RESULTS: We treated eight patients with rhabdomyolysis during the omicron variant-Severe acute respiratory syndrome coronavirus 2 (omicron variant-SARS-CoV-2) community outbreak and none during the alpha variant endemic. These eight patients shared stereotypical presentations, including the presence of bilateral calf pain after defervescence. The creatinine kinase (CK) levels were between 1346 and 6937 U/L on admission, and clinical course was uneventful after aggressive saline hydration. CONCLUSION: Rhabdomyolysis is not a rare complication in pediatric patients with the omicron-SARS-CoV-2 infection, and reassurance of a good prognosis is important to alleviate family anxiety.

Effectiveness of Booster and Influenza Vaccines against COVID-19 among Healthcare Workers, Taiwan.

Among previously uninfected healthcare workers in Taiwan, mRNA COVID-19 booster vaccine was associated with lower odds of COVID-19 after primary recombinant vaccine. Symptom-triggered testing revealed that tetravalent influenza vaccine was associated with higher odds of SARS-CoV-2 infection. COVID-19 vaccination continues to be most effective against SARS-CoV-2.

Characteristics, contacts, and relative risk of SARS-CoV-2 infection among children during school closures.

BACKGROUND: Characteristics of children with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Taiwanese households is nascent. We sought to characterize SARS-CoV-2 infection, and estimate the relative risk of infection among children within households during school closures in Taipei and New Taipei City. METHODS: We reviewed consecutive children below 18 years presenting to our emergency department from May 18, 2021 to July 12, 2021 who underwent real-time reverse-transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 from respiratory swabs. Demographics, symptoms, and contacts were captured from medical records. Household contact was defined as an individual with confirmed COVID-19 living in the same residence as the child. RESULTS: Among 56 children with SARS-CoV-2, twenty-five (45%) were male with mean age of 7.9 years. Symptoms were nonspecific, with 29% having fever, 32% having cough, and 48% were asymptomatic. The median cycle threshold (Ct) value of SARS-CoV-2 rRT-PCR was 25 (range 11-38). All 56 children reported 94 contacts with a COVID-19 patient, of which 99% were household contacts. The relative risk of infection was 8.5 (95% CI 5.0-14.7) for children whose parent(s) were COVID-19 patients, and 7.3 (95% CI 4.9-11.0) for children whose household grandparent(s) were patients, as compared to children without respective contacts. Children without COVID-19 contacts were all tested negative. CONCLUSIONS: During school closures in Taipei and New Taipei City, children with SARS-CoV-2 infection in our cohort had one or more COVID-19 contacts, mostly within their households. While diagnosing pediatric COVID-19 is challenging as children were often asymptomatic, those without contacts were likely uninfected.

Desaturation and heme elevation during COVID-19 infection: A potential prognostic factor of heme oxygenase-1.

Increased heme levels, anemia, and desaturation occur during infection. We aimed to compare the levels of heme, heme oxygenase-1 (HO-1), ferritin, and bilirubin in coronavirus disease 2019 (COVID-19) patients at different saturation levels. Heme and HO-1 enzyme levels significantly increased in the low SpO2 group, but further studies are required.

Characterization of the structure-function relationship of a novel salt-resistant antimicrobial peptide, RR12.

Antimicrobial peptides (AMPs) are potential candidates in designing new anti-infective agents. However, many AMPs show poor bactericidal activities in physical salt and serum solutions. Here, we disclosed the structure-function relationships of a novel salt-resistant antimicrobial peptide, RR12, which could further explain its mode of action and show its applicability in developing new antibacterial agents.

Recommendations and guidelines for the treatment of pneumonia in Taiwan.

Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia.

Adolescent onset of vertically transmitted untreated AIDS: A report of one case.

A 12-year-old adolescent girl with intractable pneumonia and desaturation was sent to our hospital. An immunocompromised state was highly suspected because of an oral thrush persisting for a year and pneumonia of unusual severity. Laboratory tests confirmed she had human immunodeficiency virus (HIV) infection and full-blown AIDS. She lived with her adopted parents and reported no history of sexual abuse, drug abuse, or blood transfusion. We contacted the Center of Disease Control and discovered that her mother had HIV and had passed away a few years ago, thus confirming that she was a case of vertically transmitted HIV patient who had only developed AIDS recently. Even though her mother had HIV, our public health department failed to follow her as a potential HIV victim, probably because routine HIV examinations for pregnant women only started in 2005, 4 years after she was born.

Effects and mechanism of moderate aerobic exercise on impaired fasting glucose improvement.

BACKGROUND: Exercise is beneficial for blood glucose metabolism. However, whether moderate aerobic exercise could improve impaired fasting glucose is unknown. And the mechanism is also needed to investigate. METHODS: A cross-sectional research was performed and 120 participants with impaired fasting glucose (IFG) were randomly assigned into active and controlled groups. Briefly, participants in active group were required to take moderate aerobic exercise at least 30 min for five times per week, whereas in controlled group, participants were also advised to take exercise but not mandatorily required the same degree as that of active group. At baseline and 3 month's follow-up, laboratory and demographic variables were compared. RESULTS: At baseline, no significant between-group differences were observed. Generally, leukocyte ROCK2 activity in the active and controlled groups were 58.7 ± 6.0 mg/mL and 60.2 ± 7.3 mg/mL, and daily average exercise time at baseline in both groups was extremely little, with 5.2 ± 3.8 min and 5.9 ± 3.5 min, respectively. After 3 months' follow-up, 52 and 56 participants in the active and controlled groups completed the whole program. Compared to baseline, leukocyte ROCK2 activity and daily average exercise time were improved in both groups. Nonetheless, compared to the controlled group, leukocyte ROCK2 activity was reduced more profoundly and the daily average exercise time was longer in the active group (37.5 ± 6.3 min versus 18.3 ± 7.2 min, p < 0.05). Moreover, the percentage of IFG in the active group was decreased more prominently than the controlled group (76.9% versus 82.1%, p < 0.05). Multivariate regression analyses revealed that exercise time and leukocyte ROCK2 activity was significantly associated with IFG, with OR of 0.836 (active group versus controlled group, 95% CI 0.825-0.852, p < 0.05) in exercise time, and 1.043 (controlled group versus active group, 95% CI 1.021-1.069, p < 0.05) in leukocyte ROCK2 activity. In addition, exercise time was significantly associated with leukocyte ROCK2 activity, with OR of 0.822 (active group versus controlled group, 95% CI 0.818-0.843, p < 0.05). CONCLUSION: In subjects with IFG, increased daily average exercise time is beneficial for improving fasting blood glucose metabolism, and the mechanism may be associated with its effects on attenuating leukocyte ROCK2 activity.

Blood pH in coronary artery microthrombosis of rats.

OBJECTIVE: To study the mechanism and significance of pH change in the coronary artery microthrombosis of rats. METHODS: After the sodium laurate-induced model of coronary artery microthrombosis of rats was constructed, the vascular endothelial cells were separated and then cultured in the mediums with different pH values for 24 h. Enzyme linked immunosorbent assay was used to detect the content of von Willebrand factor (vWF) in the medium; while the real-time PCR and western blot assay were used to detect the expression of fibrinogen-like protein 2 (FGL2) at the mRNA and protein level. The comprehensive evaluation was performed to discuss the effect of pH change on the coronary artery microthrombosis of rats. RESULTS: The expression level of vWF detected by enzyme linked immunosorbent assay was 336.67 ± 24.95, 311.33 ± 14.98, 359.67 ± 39.63, 354.67 ± 49.01 and 332.00 ± 33.42 (pg/mL) respectively; while the expression of vWF in the model group was 570.00 ± 57.94, 524.67 ± 57.94, 437.00 ± 95.38, 415.33 ± 44.38 and 444.67 ± 74.31 respectively. Being cultured under the different pH values, the relative expression level of FGL2 mRNA in the model group was 7.93 ± 0.93, 6.70 ± 0.70, 5.03 ± 0.32, 5.13 ± 0.40 and 5.57 ± 0.83 respectively. CONCLUSIONS: The coronary artery microthrombosis of rats can cause the high expression and secretion of vWF. Meanwhile, FGL2 is also up-regulated in the thrombosis and such up-regulation is more significant in the condition with low pH, which indicates that the low pH condition may be one of factors that contribute to the cardiovascular diseases.

Pediatric round pneumonia.

"Round pneumonia" or "spherical pneumonia" is a well-characterized clinical entity that seems to be less addressed by pediatricians in Taiwan. We herein report the case of a 7-year-old boy who presented with prolonged fever, cough, and chest X-rays showing a well-demarcated round mass measuring 5.9 × 5.6 × 4.3 cm in the left lower lung field, findings which were typical for round pneumonia. The urinary pneumococcal antigen test was positive, and serum anti-Mycoplasma pneumoniae antibody titer measurement using a microparticle agglutination method was 1:160 (+). After oral administration of antibiotics including azithromycin and amoxicillin/clavulanate, which was subsequently replaced by ceftibuten due to moderate diarrhea, the fever subsided 2 days later and the round patch had completely resolved on the 18th day after the diagnosis. Recent evidence suggests treating classical round pneumonia with antibiotics first and waiving unwarranted advanced imaging studies, while alternative etiologies such as abscesses, tuberculosis, nonbacterial infections, congenital malformations, or neoplasms should still be considered in patients with atypical features or poor treatment response.

Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway.

Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against pulmonary fibrosis. However, the mechanisms by which ACE2 and Ang-(1-7) attenuate pulmonary fibrosis remain unclear. We hypothesized that up-regulation of the ACE2/Ang-(1-7)/Mas axis protects against bleomycin (BLM)-induced pulmonary fibrosis by inhibiting the mitogen-activated protein kinase (MAPK)/NF-κB pathway. In vivo, Ang-(1-7) was continuously infused into Wistar rats that had received BLM or AngII. In vitro, human fetal lung-1 cells were pretreated with compounds that block the activities of AT1R, Mas (A-779), and MAPKs before exposure to AngII or Ang-(1-7). The human fetal lung-1 cells were infected with lentivirus-mediated ACE2 before exposure to AngII. In vivo, Ang-(1-7) prevented BLM-induced lung fibrosis and AngII-induced lung inflammation by inhibiting the MAPK phosphorylation and NF-κB signaling cascades. However, exogenous Ang-(1-7) alone clearly promoted lung inflammation. In vitro, Ang-(1-7) and lentivirus-mediated ACE2 inhibited the AngII-induced MAPK/NF-κB pathway, thereby attenuating inflammation and α-collagen I production, which could be reversed by the Mas inhibitor, A-779. Ang-(1-7) inhibited AngII-induced lung fibroblast apoptotic resistance via inhibition of the MAPK/NF-κB pathway and activation of the BCL-2-associated X protein/caspase-dependent mitochondrial apoptotic pathway. Ang-(1-7) alone markedly stimulated extracellular signal-regulated protein kinase 1/2 phosphorylation and the NF-κB cascade. Up-regulation of the ACE2/Ang-(1-7)/Mas axis protected against pulmonary fibrosis by inhibiting the MAPK/NF-κB pathway. However, close attention should be paid to the proinflammatory effects of Ang-(1-7).

Effects of hypokalemia on transmural dispersion of ventricular repolarization in left ventricular myocardium.

OBJECTIVE: To observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit, and explore the role of hypokalemia in malignant ventricular arrhythmia (MVA). METHODS: A total of 20 rabbits were randomly divided into control group and hypokalemic group. Isolated hearts in the control group were simply perfused with modified Tyrode's solution, and were perfused with hypokalemic Tyrode's solution in hypokalemic group. Ventricular fibrillation threshold (VFT), 90% monophasic action potential repolarization duration (APD90) of subepicardial, midmyocardial and subendocardial myocardium, transmural dispersion of repolarization (TDR) and C×43 protein expression in three layers of myocardium were measured in both groups. RESULTS: VFT in the control group and the hypokalemic group were (13.40 ± 2.95) V, and (7.00 ± 1.49) V, respectively. There was a significant difference between two groups (P<0.01). APD90 of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group (P<0.01). ΔAPD90 in the hypokalemic group and the control group were (38.10 ± 10.29) ms and (23.70 ± 5.68) ms, and TDR were (52.90 ± 14.55) ms and (36.10 ± 12.44) ms, respectively. ΔAPD90 and TDR in the hypokalemic group were significantly higher than those in the control group (P<0.05), and the increase in APD90 of midmyocardium was more significant in the hypokalemic group. Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group (P<0.01), and ΔCx43 was significantly increased (P<0.05). Reduction of Cx43 protein expression was more significant in the midmyocardium. CONCLUSIONS: Hypokalemic can increase transmural heterogeneity of C×43 expression and repolarization in left ventricular myocardium of rabbit, and decrease VFT and can induce MVA more easily.

Characteristics of directly observed treatment short-course workers in Taiwan.

BACKGROUND: Little is known about the characteristics of health workers. The objective of this study was to figure out the characteristics of different types of health workers involved in Directly Observed Treatment Short-course (DOTS) work. METHODS: The study comprised of 444 community health workers and 822 potential DOTS workers; the participants attended the training course and completed structured questionnaires. The questionnaires were then analyzed to investigate the knowledge, stigmatization, and accountability of community health partnerships (ACHPs) in tuberculosis (TB) control. RESULTS: Our study results found statistically significant differences in TB knowledge scores (p < 0.001) and ACHPs scores (p < 0.001), but not in stigmatization scores (p = 0.541) among the participants. Analysis of variance of stigmatization factors 2 and 3 differed significantly among participants (p < 0.001 for both factors). Level of education (Odds ratio, OR = 1.69) and stigmatization factor 3 [avoidance (OR = 1.25)] were found to be negative factors, whereas knowing a patient with TB (OR = 0.75), having TB knowledge (OR = 0.78), and high scores in stigmatization factor 1 [attribution (OR = 0.87)] were found to be positive factors. CONCLUSION: The main factor explaining why DOTS workers did not enter into a contract was avoidance, and that main reason why they chose to become employed was sympathy. Potential DOTS workers who know a patient with TB, have high TB knowledge, and have high attribution concerns are more likely to remain under contract.

Epidemiology and clinical manifestations of children with macrolide-resistant Mycoplasma pneumoniae pneumonia in Taiwan.

Mycoplasma pneumoniae accounts for 10-30% of community-acquired pneumonia (CAP) in children. This study reveals the epidemiology and clinical manifestations of children with macrolide-resistant (ML(r) ) M. pneumoniae pneumonia in Taiwan. Respiratory tract specimens were collected from children hospitalized with CAP for evaluation via PCR followed by DNA sequencing for several point mutations related to the ML(r) character. Of the 412 specimens collected during the study period, 60 (15%) were positive for M. pneumoniae, 14 (23%) of which presented point mutation (all A2063G) in 23S rRNA. Clinical symptoms and chest X-ray findings between the ML(s) and ML(r) groups were not significantly different. However, the ML(r) group had longer mean duration of fever after azithromycin treatment (3.2 days vs. 1.6 days, P = 0.02) and significantly higher percentage of changing antibiotics for suspected ML(r) strain (42% vs. 13%, P = 0.04). Although 58% of children in the ML(r) group did not receive effective antibiotics, all children were discharged without sequelae. In conclusion, 15% of CAP in children is caused by M. pneumoniae and the macrolide-resistance rate is 23% in Taiwan. Despite ineffective antibiotics, children with ML(r) M. pneumoniae pneumonia recover completely.

[Characterization of the biological activities of lyophilized recombinant adenovirus expressing the triple mutant of hypoxia inducible factor-1α].

OBJECTIVE: To investigate the influence of lyophilization on the biological activity of recombinant adenovirus-mediated triple mutant of hypoxia inducible factor-1α (Ad-HIF-1α-564/402/803). METHODS: Ad-HIF-1α-564/402/803 was amplified from HEK293A cells and purified by ultracentrifugation in CsCl gradient solutions. The infection efficiency was observed by X-gal staining. The lyophilized adenovirus was prepared under appropriate conditions. Before and after lyophilization, the effect of Ad-HIF-1α-564/402/803 on hMVEC proliferation was evaluated by MTS assay. The recombinant adenovirus was confirmed by PCR and DNA sequence analysis before and 1 day, 6 months and 12 months after lyophilization, and hMVECs infected with Ad-HIF-1α-564/402/803 at these time points were examined for HIF-1α protein expression using Western blotting. RESULTS: No significant changes were observed in the effect of lyophilized Ad-HIF-1α-564/402/803 on hMVECs proliferation at the optimal multiplicity of infection of 100 pfu/cell (P>0.05). At the 4 time points, the recombinant adenovirus HIF-1α showed no structural alterations or significant changes in the expression level of HIF-1α protein in the transfected hMVECs (P>0.05). CONCLUSION: Lyophilized Ad-HIF-1α-564/402/803 can maintain its biological activities for a long time.

[Effect of granulocyte colony stimulating factor EPC on cardiac function in patients with heart failure after myocardial infarction].

OBJECTIVE: To study the changes of cardiac function following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. METHODS: Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 µg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPCs) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVSD, EDV, and LVEF) were evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. RESULTS: The number of EPCs was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (P<0.01). In both groups, BNP level was lowered significantly after the treatment to recover the normal level (P<0.01). The cardiac functions were improved in all the patients at 7 days and 4 months after the treatment, and the improvement was more obvious in the treatment group (P<0.05), especially in terms of LVEF at 4 months after the treatment (P<0.01). CONCLUSION: EPC mobilization by G-CSF can effectively improve the cardiac functions and lessen ventricular remodeling in patients with heart failure after myocardial infarction.

[Comparison of right atrial matrix metalloproteinase expression between patients with unstable angina and myocardial infarction].

OBJECTIVE: To compare right atrial structural remodeling and the expression of matrix metalloproteinase (MMP) and tissue inhibitors (TIMP) between patients with unstable angina (UA) and myocardial infarction (MI). METHODS: Right atrial appendages were obtained from 18 patients with UA and 22 patients with MI undergoing coronary artery bypass grafting (CABG) operations. MMP-1, -3, -7, -9 and TIMP-1 protein expressions were detected by immunohistochemistry and RT-PCR. Echocardiography was performed before CABG. RESULTS: The left and right atrial diameter, left ventricular diameter and mRNA levels of MMP-3, MMP-9 and TIMP-1 were significantly higher in MI group than those in UA group [LAD: (40.8 +/- 4.2) mm vs. (33.1 +/- 5.1) mm, P < 0.01; RAD: (44.1 +/- 6.8) mm vs. (28.8 +/- 6.0) mm, P < 0.01; LVEDD: (48.9 +/- 6.0) mm vs. (39.7 +/- 7.1) mm, P < 0.05; MMP-3: 0.39 +/- 0.18 vs. 0.28 +/- 0.07, P < 0.05; MMP-9: 0.81 +/- 0.21 vs. 0.55 +/- 0.20, P < 0.01; TIMP-1: 1.79 +/- 0.89 vs. 0.94 +/- 0.47, P < 0.01]. MMP-1, MMP-7 levels were similar between the 2 groups (MMP-1: 0.14 +/- 0.06 vs. 0.10 +/- 0.08, P > 0.05; MMP-7: 0.25 +/- 0.05 vs. 0.23 +/- 0.06, P > 0.05). CONCLUSION: Right atrial up-regulation of MMP-3, MMP-9 and TIMP-1 levels may contribute to the right atrial structural remodeling in MI patients.

[Role of matrix metalloproteinase and tissue inhibitor of metalloproteinase in atrial structural remodeling in patients with atrial fibrillation].

OBJECTIVE: To study the relationship between atrial structural remodeling and the expressions of matrix metalloproteinase (MMPs) and their tissue inhibitors (TIMPs) in atrial fibrillation (AF). METHODS: Biopsy samples of the right atrial appendages were collected from 20 patients with sinus rhythm and 30 with AF undergoing heart valve replacement surgery for rheumatic heart diseases. All the patients received echocardiographic examination preoperatively. MMP-1, -3, -7, -9 and TIMP-1, -2, -3, -4 protein expressions were detected by immunohistochemistry and RT-PCR. RESULTS: Compared with those in patients with sinus rhythm, the AF patients had significantly increased left and right atrial diameters and mRNA levels of MMP-3, -7, -9 and TIMP-1, -2, -3, -4 (P<0.01). MMP-1 expression also showed an increase in AF patients, but the difference was no statistically significant from that in patients with sinus rhythm. CONCLUSION: The expressions of MMP-1, -3, -7, -9 and TIMP-1, -2, -3, -4 increase in fibrillating atrial tissue, which may contribute to atrial structural remodeling and atrial dilatation in AF patients.

[Effects of recombinant adenovirus-mediated triple mutant of hypoxia inducible factor-1alpha in modulating angiogenesis].

OBJECTIVE: To investigate the effect of recombinant adenovirus-mediated triple mutant of hypoxia inducible factor-1alpha (Ad-HIF-1alpha-564/402/803) in modulating angiogenesis in vitro. METHODS: The recombinant adenoviruses Ad-lacZ, Ad-Null, Ad-HIF-1alpha-nature, and Ad-HIF-1alpha-564/402/803 were amplified in HEK293A cells and purified by ultracentrifugation in CsCl step gradient solutions, and the adenoviral titer was determined by end-point dilution assay. The recombinant adenovirus was confirmed by PCR and DNA sequence analysis, and the infection efficiency was observed by X-gal staining. Human microvascular endothelial cells (HMVECs) were infected with Ad- HIF-1alpha-564/402/803, Ad- HIF-1alpha-nature, or Ad-Null to compare the number of capillary-like tube structures in vitro. The effect of Ad- HIF-1alpha-564/402/803, Ad-HIF-1alpha-nature, and Ad-Null on angiogenesis was evaluated using a chick embryo chorioallantoic membrane (CAM) model. RESULTS: PCR and gene sequencing suggested the correct construction of the recombinant adenovirus HIF-1alpha, and the adenoviral titer reached 1011-1012 PFU/ml. Infection of the hMVECs with Ad-HIF-1alpha-564/402/803 at the optimal multiplicity of infection of 100 pfu/cell resulted in a significantly greater number of capillary-like tube structures than infection by Ad-HIF-1alpha-nature and Ad-Null (P=0.000). Ad-HIF-1alpha-564/402/803 group showed significantly higher microvessel density than Ad-HIF-1alpha-nature, Ad-Null, and PBS groups, with also higher angiogenesis area to CAM area ratio (P=0.01, 0.000, and 0.000, respectively). CONCLUSION: The triple mutant Ad-HIF-1alpha-564/402/803 can obviously promote the formation of capillary-like tube structures in vitro and modulate angiogenesis in the CAM model, suggesting the capacity of Ad-HIF-1alpha-564/402/803 in promoting angiogenesis under normoxic condition.