Objective To analyze molecular evolution of carbapenemase KPC-12 and its binding free energies with β-lactams.Methods Class A beta-lactamases were divided into 2 clusters:those with carbapenemase activities and those without.Minimum Evolution method in MEGA4.1 software was used to analyze molecular evolution of class A beta-lactamases with carbapenemase activity,including KPC-2 to KPC-13,SFC-1,SME-1,IMI-1,NMC-A,and class A beta-lactamases without carbapenemase activity,including TEM-1,SHV-1.Then,tertiary structure of KPC-12 was predicted by homology modeling as reported in SWISS-MODEL database depending on tertiary structure of KPC-2.Moreover,DOCK module in ArgusLab 4.1 software was used to perform molecular docking of KPC-12 to 10 kinds of beta-lactams substrates,and the binding free energies (△ G) were calculated.Results Molecular evolution between KPC-12 and KPC-2 was the closest.The top three decline in binding free energies of β-lactams were penicillin G sodium salt (△G =-8.45149 kcal/mol),ertapenem (△G =-8.36383 kcal/mol) and ampicillin (△G =-8.19326 kcal/mol),while the last two decline in binding free energies of β-lactams were aztreonam (△G =-6.50614 kca]/mol) and clavulanic acid (△G =-6.88533 kcal/mol).Conclusion Carbapenemase KPC-12 has high catalytic activities to penicillin G sodium salt,ertapenem and ampicillin,while has low catalytic activities to aztreonam and clavulanic acid.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective:To investigate the clinical effectiveness of super pulsed carbon dioxide fractional laser debridement surgery on the treatment of chronic wounds.Methods:From December 2018 to May 2019, 37 patients with chronic wounds who met the inclusion criteria were admitted to the Affiliated Hospital of Southwest Medical University for a prospective randomized controlled study. Using the random number table, the patients were divided into surgical debridement group (19 patients, 4 males and 15 females, aged (58±16) years, 25 wounds) and laser debridement group (18 patients, 9 males and 9 females, aged (58±10) years, 23 wounds). In patients of surgical debridement group, oedematous and aging granulation tissue was scraped from the wound by scalpel handle or curet, and the residual necrotic tissue was removed by sharp surgical instruments. In patients of laser debridement group, oedematous and aging granulation tissue and necrotic tissue was removed by super pulsed carbon dioxide fractional laser therapeutic machine, laser gasification debridement was performed repeatedly till fresh normal tissue layer observed. In patients of the two groups, according to the wound in the first 3 d after the first debridement, debridement dressing was performed twice at least as before, then wound debridement dressing was performed once every 1 to 4 days as before according to the wound conditions. The wound healing rates on 7, 14, 21, and 28 d after the first debridement were calculated. The positive rates of bacterial culture of wounds before and after the first debridement were calculated. The color and texture of the wound granulation tissue before the first debridement and on 7, 14, and 28 d after the first debridement were observed and scored. The pain scores before every debridement, during every debridement, and after every debridement dressing change were evaluated by visual analogue scale. The times of debridement dressing change were recorded. Data were statistically analyzed with two independent sample t test, analysis of variance for repeated measurement, Fisher′s exact probability test, Mann-Whitney U test, and Bonferroni correction. Results:(1) On 7, 14, 21, and 28 d after the first debridement, the wound healing rates of patients in laser debridement group (29.5% (24.1%, 36.0%), 47.1% (42.7%, 62.4%), 71.4% (62.2%, 76.8%), and 88.6% (79.2%, 96.3%) were significantly higher than those of surgical debridement group (1.6% (1.0%, 12.8%), 12.7% (2.0%, 16.6%), 24.5% (8.9%, 45.5%), 43.9% (23.2%, 70.8%), Z=3.477, 3.553, 2.721, 2.193, P<0.05 or P<0.01). (2) Before the first debridement, the positive rates of bacterial culture of wounds in patients of laser debridement group and surgical debridement group were 92% (23/25) and 91% (21/23), respectively, which were similar ( P>0.05). After the first debridement, the positive rate of bacterial culture of wounds of patients in surgical debridement group was 64% (16/25), which was significantly higher than 13% (3/23) of laser debridement group ( P<0.01). (3) On 7, 14, and 28 d after the first debridement, the scores of color and texture of wound granulation tissue of patients in laser debridement group were significantly higher than those of surgical debridement group ( Z=3.420, 5.682, 6.142, 4.461, 5.337, 4.458, P<0.01). (4) The pain scores during every debridement and after every debridement dressing change in patients of laser debridement group were significantly lower than those of surgical debridement group ( t=2.847, 5.046, P<0.05 or P<0.01). (5) The time of debridement dressing change in laser debridement group was 8.0 (7.0, 10.0) times, which was significantly less than 10.0 (9.5, 12.5) times in surgical debridement group ( Z=2.261, P<0.05). Conclusions:Compared with traditional surgical debridement method, super pulsed carbon dioxide fractional laser debridement surgery is more effective in treating patients with chronic wounds. Laser debridement makes the wound healing more efficiently with reduced pain and better infection control; significantly reduces the number of dressing changes, and is especially suitable for the wound treatment in outpatients.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.