METTL3 Modulates Ctsk+ Lineage Supporting Cranial Osteogenesis via Hedgehog.

N6-methyladenosine (m6A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m6A modification in regulating Ctsk+ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk+ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk+ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk+ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufufl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk+ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.

[Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center].

Objective: This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects. Methods: A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments. Results: Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively (P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively (P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% (P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion: Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

Enhancing routine HIV and STI testing among young men who have sex with men: primary outcomes of the get connected clinical randomized trial (ATN 139).

BACKGROUND: Regular HIV and STI testing remain a cornerstone of comprehensive sexual health care. In this study, we examine the efficacy of Get Connected, a WebApp that combines test locators with personalized educational resources, in motivating young men who have sex with men (YMSM) to undergo regular HIV and STI testing. METHODS: Participants were randomly placed in one of two conditions. The first condition included the full version of GC (GC-PLUS), which included content tailored to users' psychosocial characteristics (e.g., age, race/ethnicity, relationship status, HIV/STI testing history). The second condition served as our attention-control and only included the testing locator (GC-TLO) for HIV/STI testing services. Participants were recruited from three cities (Houston, Philadelphia, and Atlanta) characterized by high HIV incidence. Assessments were collected at 1, 3-, 6-, 9- and 12-month follow-ups. RESULTS: Both versions of GC were acceptable and efficacious in increasing routine HIV and STI testing over a 12-month period. 40% of the sample reported testing at least twice, with no main effects observed across the two intervention arms (OR = 1.11; 95% CI: 0.69, 1.80), p =.66). Greater intervention effects were observed among YMSM who engaged more frequently with the intervention, with regional differences observed. CONCLUSIONS: Our findings underscore the need to cater to the diverse needs of YMSM through multilevel approaches. Broadly, mHealth HIV/STI testing interventions, such as Get Connected, would benefit from matching technologies to the local context to have the greatest impact. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT03132415).

[Clinical characteristics of 11 patients with Vibrio vulnificus infection and the establishment of a rapid diagnosis procedure for this disease].

Objective: To analyze the clinical characteristics of patients with Vibrio vulnificus infection, share diagnosis and treatment experience, and establish a rapid diagnosis procedure for this disease. Methods: This study was a retrospective case series study. From January 2009 to November 2022, 11 patients with Vibrio vulnificus infection who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. The gender, age, time of onset of illness, time of admission, time of diagnosis, route of infection, underlying diseases, affected limbs, clinical manifestations and signs on admission, white blood cell count, hemoglobin, platelet count, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, procalcitonin, albumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and blood sodium levels on admission, culture results and metagenomic next-generation sequencing (mNGS) results of pathogenic bacteria and the Vibrio vulnificus drug susceptibility test results during hospitalization, treatment methods, length of hospital stay, and outcomes of all patients were recorded. Comparative analysis was conducted on the admission time and diagnosis time of patients with and without a history of exposure to seawater/marine products, as well as the fatality ratio and amputation of limbs/digits ratio of patients with and without early adequate antibiotic treatment. For the survived patients with hand involvement, the hand function was assessed using Brunnstrom staging at the last follow-up. Based on patients' clinical characteristics and treatment conditions, a rapid diagnosis procedure for Vibrio vulnificus infection was established. Results: There were 7 males and 4 females among the patients, aged (56±17) years. Most of the patients developed symptoms in summer and autumn. The admission time was 3.00 (1.00, 4.00) d after the onset of illness, and the diagnosis time was 4.00 (2.00, 8.00) d after the onset of illness. There were 7 and 4 patients with and without a history of contact with seawater/marine products, respectively, and the admission time of these two types of patients was similar (P>0.05). The diagnosis time of patients with a history of contact with seawater/marine products was 2.00 (2.00, 5.00) d after the onset of illness, which was significantly shorter than 9.00 (4.25, 13.00) d after the onset of illness for patients without a history of contact with seawater/marine products (Z=-2.01, P<0.05). Totally 10 patients had underlying diseases. The affected limbs were right-hand in 8 cases, left-hand in 1 case, and lower limb in 2 cases. On admission, a total of 9 patients had fever; 11 patients had pain at the infected site, and redness and swelling of the affected limb, and 9 patients each had ecchymosis/necrosis and blisters/blood blisters; 6 patients suffered from shock, and 2 patients developed multiple organ dysfunction syndrome. On admission, there were 8 patients with abnormal white blood cell count, hemoglobin, and albumin levels, 10 patients with abnormal CRP, procalcitonin, and NT-proBNP levels, 5 patients with abnormal creatinine and blood sodium levels, and fewer patients with abnormal platelet count, ALT, and AST levels. During hospitalization, 4 of the 11 wound tissue/exudation samples had positive pathogenic bacterial culture results, and the result reporting time was 5.00 (5.00, 5.00) d; 4 of the 9 blood specimens had positive pathogenic bacterial culture results, and the result reporting time was 3.50 (1.25, 5.00) d; the mNGS results of 7 wound tissue/exudation or blood samples were all positive, and the result reporting time was 1.00 (1.00, 2.00) d. The three strains of Vibrio vulnificus detected were sensitive to 10 commonly used clinical antibiotics, including ciprofloxacin, levofloxacin, and amikacin, etc. A total of 10 patients received surgical treatment, 4 of whom had amputation of limbs/digits; all patients received anti-infection treatment. The length of hospital stay of 11 patients was (26±11) d, of whom 9 patients were cured and 2 patients died. Compared with that of the 6 patients who did not receive early adequate antibiotic treatment, the 5 patients who received early adequate antibiotic treatment had no significant changes in the fatality ratio or amputation of limbs/digits ratio (P>0.05). In 3 months to 2 years after surgery, the hand function of 8 patients was assessed, with results showing 4 cases of disabled hands, 2 cases of incompletely disabled hands, and 2 cases of recovered hands. When a patient had clinical symptoms of limb redness and swelling and a history of contact with seawater/marine products or a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection. Conclusions: Vibrio vulnificus infection occurs most frequently in summer and autumn, with clinical manifestations and laboratory test results showing obvious infection characteristics, and may be accompanied by damage to multiple organ functions. Both the fatality and disability ratios are high and have a great impact on the function of the affected limbs. Early diagnosis is difficult and treatment is easily delayed, but mNGS could facilitate rapid detection. For patients with red and swollen limbs accompanied by a history of contact with seawater/marine products or with a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection.

Modified 2-stage IPAA has similar postoperative complication rates and functional outcomes compared to 3-stage IPAA.

INTRODUCTION: Reconstructive ileal-pouch anal anastomosis (IPAA) for ulcerative colitis (UC) is often created in 3-stages: colectomy â€‹+ â€‹ileostomy, proctectomy â€‹+ â€‹pouch creation with diverting loop ileostomy, then subsequent ileostomy closure. Modified 2-stage IPAA is without pouch diversion, thus avoiding a third operation. This study compares perioperative complications, quality of life (QOL) and functional outcomes of 3- versus modified 2-stage IPAA. METHODS: Charts were reviewed for adult UC patients undergoing IPAA between 2010 and 2020. QOL and function were assessed with EQ-5D-3L Quality of Life and Pouch Functional Score questionnaires. RESULTS: 152 patients were identified. 43 modified 2-stage and 109 3-stage IPAA were similar for anastomotic leak (9.3% vs. 1.8%, p â€‹= â€‹0.06), SSI (34.9% vs. 29.7%, p â€‹= â€‹0.51) and ileus (32.6% vs. 33%, p â€‹= â€‹0.96). Modified 2-stage had less bowel obstruction than 3-stage IPAA (7.0% vs. 30.1%, p â€‹= â€‹0.006). 92 patients returned questionnaires with similar QOL and pouch function. CONCLUSIONS: Perioperative complications, QOL and function are similar for 3-stage IPAA and modified 2-stage IPAA. Modified 2-stage IPAA in select patients is safe and has less postoperative bowel obstruction than 3-stage IPAA.

Dietary habits and physical activity during the third wave of the COVID-19 pandemic: associated factors, composite outcomes in a cross-sectional telephone survey of a Chinese population, and trend analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created many challenges for Hong Kong residents attempting to maintain healthy lifestyle habits. This study aimed to measure the prevalences of unhealthy dietary habits and physical inactivity levels in Hong Kong Chinese, identify associated factors, and conduct a time trend analysis during the third wave of the COVID-19 pandemic. METHODS: A cross-sectional telephone survey was conducted in Hong Kong by simple random sampling. The survey comprised socio-demographic characteristics, clinical information, the Hong Kong Diet Score (HKDS), smoking and alcohol consumption, and a Chinese version of the International Physical Activity Questionnaire Short Form. The composite outcome was low HKDS, physical inactivity, smoking, and alcohol consumption. We used 14 Health Behaviour Survey reports from 2003 to 2019 to establish a trend analysis regarding fruit and vegetable consumption, physical activity level, smoking, and alcohol consumption. RESULTS: We performed 1500 complete telephone surveys with a response rate of 58.8%. Most participants were older adults (≥65 years, 66.7%), women (65.6%), and married (77.9%). The HKDS was significantly lower in men, single individuals, low-income participants, alcohol drinkers, and patients with diabetes mellitus or renal disease. Participants who were single, undergoing long-term management of medical diseases, or had diabetes or renal diseases exhibited greater likelihood of physical inactivity. CONCLUSION: Prevalences of unhealthy lifestyle habits were high among men, single individuals, and chronic disease patients during the third wave of the COVID-19 pandemic in Hong Kong. The adoption of physical activity habits tended to decrease in the past two decades.

Outcome and etiology of fetal pleural effusion, fetal ascites and hydrops fetalis after fetal intervention: retrospective observational cohort from a single institution.

OBJECTIVES: Non-immune hydrops fetalis (NIHF) is the pathological accumulation of fluids in fetal compartments, without maternal isoimmunization. Fetal interventions (e.g. shunting, fetal paracentesis, fetal thoracocentesis, fetal pleurodesis) are used to alleviate fluid accumulations, but the outcome is uncertain because the underlying causes of NIHF vary. We aimed to explore the etiology and long-term outcome of NIHF after fetal intervention. METHODS: This was a retrospective review of fetuses with NIHF, defined by the presence of fetal ascites, pleural or pericardial effusion, skin edema or cystic hygroma, or a combination of these features, who underwent intervention at our institution during the period 2012-2021. Clinical surveillance, genetic analysis and viral infection screening were used to define the etiology. Chart reviews and telephone interviews were conducted to assess the long-term outcomes. RESULTS: In total, 55 fetuses were enrolled and 46 cases had final follow-up data after delivery. Etiology was identified in 33 cases, including four for which the underlying causes were not identified initially using small-gene-panel tests but which were later diagnosed with monogenic disorders by whole-exome sequencing (WES). Twenty-three cases with follow-up survived, having a follow-up period of 2-11 years at the time of writing, of which 17 were healthy. All 11 cases initially presenting as congenital chylothorax survived with favorable outcome. CONCLUSIONS: The etiologies of NIHF are heterogeneous, and the long-term (spanning 2-11 years) outcome of fetal intervention varies, according to the underlying etiology, with cases caused by congenital chylothorax having the best prognosis. Genome-wide tests, such as WES, may be helpful in determining the underlying condition in cases caused by a genetic disorder, and this may affect fetal therapy approaches in the future. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy and Safety of Programmed Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) Checkpoint Inhibitors in Patients With Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Meta-analysis.

AIMS: The aim of this systematic review with meta-analysis was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: We searched PubMed, Embase and Cochrane Library until 1 July 2022 for mCRPC trials testing PD-1/PD-L1 checkpoint inhibitors. We measured the efficacy and safety using overall survival, progression-free survival (PFS), overall response rates (ORR), prostate-specific antigen (PSA) response rate or treatment-related adverse events (TRAEs). When possible, data were meta-analysed. RESULTS: Thirteen studies involving 2533 participants were included in this meta-analysis. The pooled hazard ratio for overall survival was 0.81 (95% confidence interval 0.42-1.20, I2 = 80.3%, PHeterogeneity＜0.001) and for PFS was 0.65 (95% confidence interval 0.38-0.92, I2 = 72.2%, PHeterogeneity = 0.013). Furthermore, better ORR (relative risk = 2.77, 95% confidence interval 1.25-6.13, I2 = 0%, PHeterogeneity = 0.699) was found in PD-L1-expressing tumours. However, no statistical trends between PD-L1 status on PSA response rate (relative risk = 0.79, 95% confidence interval 0.5-1.25, I2 = 0%, PHeterogeneity = 0.953) and tumour mutational burden on ORR (relative risk = 2.53, 95% confidence interval 0.49-13.12, I2 = 74.5%, PHeterogeneity = 0.02) were observed. The pooled proportions of TRAEs and ≥ grade 3 TRAEs were 85.1% (95% confidence interval = 71.7-98.5%) and 31.6% (95% confidence interval = 18.9-44.4%), respectively. CONCLUSIONS: This meta-analysis showed that among selected populations of men with mCRPC, anti-PD-1/PD-L1 combination treatment may significantly increase the PFS benefits. However, overall survival in mCRPC warrants further testing.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Willingness to receive and recommend hypothetical mpox vaccination and associated factors in Chinese adults: a community-based survey in Shenzhen, China.

OBJECTIVES: China may face new threats to public health due to the increased risk of imported mpox (monkeypox) cases. However, research gaps exist in the acceptance of mpox vaccination and potential associated factors in the Chinese population. STUDY DESIGN: We conducted a cross-sectional study targeting community residents in Shenzhen, China, from August 5 to September 7 2022. METHODS: A self-administered questionnaire was used to collect information about demographic and health characteristics, mpox-related perceptions, and attitudes towards mpox vaccination. Multivariable logistic regression models were applied to detect the factors associated with willingness to receive and recommend mpox vaccination. RESULTS: A total of 2293 community residents were included in the analyses (average age: 34.03, female: 72.6%). Among the participants, 76.9% were aware of mpox, 62.1% were aware of the global mpox outbreak, but only 53.6% had a high knowledge level of mpox. Males had a higher proportion of high knowledge (56.9% vs 52.3%, P＜0.05) and a lower proportion of high worry (30.2% vs 45.4%, P＜0.05) than females. Approximately 69.1% of the participants were willing to vaccinate against mpox, and 69.6% were willing to recommend mpox vaccination to people around them, in which no gender difference was found. The obstacle reported most among people hesitant to receive vaccination was concerning the safety and side-effects, whereas it changed to be concerning the suitability due to individual health differences among people hesitant to recommend mpox vaccines. Factors associated with the willingness to receive and recommend mpox vaccination included having a history of influenza vaccination, having a history of COVID-19 vaccination, being aware of the global mpox outbreak, having a high knowledge level of mpox, and having a high level of mpox-related worry. CONCLUSIONS: This study identified a moderate willingness to receive and recommend mpox vaccination among Chinese adults. Without gender differences, willingness to receive and recommend mpox vaccination was significantly associated with mpox-related perceptions, such as awareness, knowledge, and worry. Authoritative and up-to-date information is needed to help the general population improve public confidence in mpox vaccines in China.

[Impact of COVID-19 pandemic on the management of imported malaria in China].

OBJECTIVE: To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance. METHODS: All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021). RESULTS: A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ2 = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ2 = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ2 = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ2 = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ2= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ2 = 3.95, P < 0.05). CONCLUSIONS: The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.

Ru-Based Organometallic Agents Bearing Phenyl Hydroxide: Synthesis and Antibacterial Mechanism Study against Staphylococcus aureus.

The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 µg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus in vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus.

[Impact of asthma action plan-based remote joint management model on asthma control in children].

Objective: To compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ2-test or χ2-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ2=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ2=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.

Artificial intelligence aided diagnosis of pulmonary nodules segmentation and feature extraction.

AIM: To develop a high-accuracy low-dose computed tomography (LDCT) lung nodule diagnosis system by combining artificial intelligence (AI) technology with the Lung CT Screening Reporting and Data System (Lung-RADS), which can be used in the future AI-aided diagnosis of pulmonary nodules. MATERIALS AND METHODS: The study comprised the following steps: (1) the best deep-learning segmentation method for pulmonary nodules was compared and selected objectively; (2) the Image Biomarker Standardization Initiative (IBSI) was used for feature extraction and to determine the best feature reduction method; and (3) a principal component analysis (PCA) and three machine learning methods were used to analyse the extracted features, and the best method was determined. The Lung Nodule Analysis 16 dataset was applied to train and test the established system in this study. RESULTS: The competition performance metric (CPM) score of the nodule segmentation reached 0.83, the accuracy of nodule classification was 92%, the kappa coefficient with the ground truth was 0.68, and the overall diagnostic accuracy (calculated by the nodules) was 0.75. CONCLUSION: This paper summarises a more efficient AI-assisted diagnosis process of pulmonary nodules, and has better performance compared with the previous literature. In addition, this method will be validated in a future external clinical study.

[Measuring and analysis of the shoulder circumferences of 840 adults' permanent teeth crown preparations].

Objective: To measure and analyze the shoulder circumferences of adults' permanent teeth crown preparations based on data collected through the intraoral scanning, so as to provide dental anatomy data for clinical diagnosis and analysis. Methods: Intraoral scanning data of 840 complete crown preparations were collected, and were entrusted to the World Dental Laboratory Co., Ltd. in Fuzhou between March 2021 and June 2022. Except the data of the third molar, the rest data were categorized in terms of 14 tooth positions in the upper and lower jaw (each category involved 30 samples from male group and 30 samples from female group). Image measurement software was used to measure the shoulder circumferences of permanent teeth crown preparations. And analysis was conducted to reveal the difference of shoulder circumference diameters between male and female groups. And then they were grouped according to the mean value at each tooth position, on the premise that the difference between the maximum and minimum values and the mean value of the entire group was≤±1.00 mm. Analysis were further conducted to determine the differences of shoulder circumference diameters between each dental position and the differences between male and female in the same groups. Results: Bivariate analysis of variance showed that gender had no effect on the shoulder circumference of full crown preparations (F=0.55, P=1.457), while tooth position had a significant impact on the shoulder circumference of full crown preparations (F=273.15, P<0.001). The samples were classified into 5 groups according to the mean values of shoulder circumference diameters relating to each tooth position. Statistical analysis showed that Group 1, covering maxillary lateral incisor, mandibular central incisor and mandibular lateral incisor, had shoulder circumference with diameters of (16.62±2.21) mm; Group 2, consisting of maxillary central incisor, maxillary cusp, mandibular cusp, mandibular first premolar and mandibular second premolar, had diameters of (20.78±2.48) mm; Group 3, consisting of maxillary first premolar and maxillary second premolar, had diamerters of (22.09±2.72) mm; Group 4, covering maxillary first molar, maxillary second molar and mandibular first molar, had diamerters of (30.21±2.67) mm; while group 5, with mandibular second molar alone its member, had diamerters of (31.34±3.18) mm. The difference among the 5 groups was statistically significant (P<0.05). Conclusions: Significant differences of shoulder circumference diameters could be found between different tooth positions, while at the same tooth position, the differences between male and female are not significant. The 14 tooth positions could be grouped into 5 groups according to their shoulder circumference diameters. Future research could take the grouping as reference.

[Efficacy of intravenous drug information management system on the improvement of anemia in maintenance hemodialysis patients].

Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P<0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P=0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P=0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] (P=0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.