A high-throughput three-dimensional (3D) hepatocyte culture model is constructed in this study. It is capable of replicating the 3D in vivo environment and offers the advantages of high throughput, enhanced reproducibility, low cost, and simplified operation, rendering a valuable tool for hepatotoxicity screening of traditional Chinese medicine (TCM). First, we constructed the 3D high throughput liver chip model using collagen hydrogel. The precision and its difference with traditional cell culture plates were assessed using acetaminophen, Tripterygium hypoglaucum, and Qili San as the references. The feasibility of this model was also investigated by comparing the hepatotoxicity among four batches of T. hypoglaucum and Qili San. The methodology verification shows that the 3D hepatocyte model is better than traditional two-dimensional (2D) cell culture model in precision and feasibility. Subsequently, we compared the hepatotoxicity of different samples over a period of three or seven days and found that the hepatotoxicity of TCM extracts increased over time. Finally, we compared the hepatotoxicity of T. hypoglaucum and its compound formula Kunxian capsule under equivalent concentration. The results showed that the compound Kunxian capsule could significantly reduce hepatotoxicity of T. hypoglaucum. Generally, we constructed a high-throughput, robust 3D liver-on-a-chip model with the potential of rapid assessing TCM-induced liver toxicity.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To study influence of Status-Background-Assessment-Recommendation(SBAR)communi-cation mode intervention on patients with heart failure(HF).Methods:According to intervention method,a total of 187 HF patients treated in our hospital were divided into routine intervention group(n=96,received routine in-tervention based on routine treatment)and SBAR group(n=91,received SBAR communication mode intervention based on routine treatment).Both groups were intervened for six months.General clinical data,LVEF,left ven-tricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),scores of Morisky medi-cation compliance scale and the medical outcomes study 36-item short-form heath survey(SF-36),patients'satis-faction and incidence rate of major adverse cardiovascular events(MACE)within six-month follow-up were com-pared between two groups.Results:Compared with routine intervention group,after intervention,there were sig-nificant rise in LVEF[(53.44±2.11)%vs.(57.72±1.80)%],scores of Morisky medication compliance scale[(2.00±0.77)scores vs.(3.63±1.07)scores]and SF-36[(68.83±7.62)scores vs.(76.81±9.68)scores],and significant reductions in LVEDV[(132.63±5.59)ml vs.(119.15±6.89)ml]and LVESV[(64.36±5.82)ml vs.(56.62±4.21)ml]in SBAR group(P=0.001 all).Patients'satisfaction of SBAR group was significantly higher than that of routine intervention group(89.01%vs.73.96%,χ2=6.958,P=0.008),and incidence rate MACE during follow-up was significantly lower than the latter(5.49%vs.15.63%,LogRankχ2=5.043,P= 0.025).Conclusion:SBAR communication mode intervention can significantly improve heart function,medication compliance and quality of life in patients with heart failure,with high patients'satisfaction.

Objectives:To systematically analyze the framework and contents of World Health Organization (WHO) policy and action strategies on rehabilitation using the theory of WHO health service components, to explore the theoretical bases, methodology, framework and core elements of WHO's international rehabilitation policy. Methods:WHO has launched rehabilitation-related policy documents, mainly including Rehabilitation in Health Systems, Rehabilitation in Health Systems: Guide for Action, Rehabilitation Indicator Menu: a tool accompanying the Framework for Rehabilitation Monitoring and Evaluation (FRAME), Template for Rehabilitation Information Collection (TRIC): a tool accompanying the Systematic Assessment of Rehabilitation Situation (STARS), and established systems of international rehabilitation policy architecture system. Using content analysis, this study analyzed in detail the theoretical basis and methodology of international rehabilitation policy, the policy framework, and the core elements of the action strategy and priority areas of rehabilitation service development in perspective of WHO six building blocks of health system, namely leadership and governance, financing, human resources for health, service delivery, medical technology, and health information systems. Results:WHO rehabilitation policy is developed based on WHO's theories of person-centered health services, social determinants of health, and functioning, disability and health of International Classification of Functioning, Disability and Health. WHO rehabilitation policy recognized that the development of rehabilitation was an important pathway achieving United Nations 2030 Sustainable Development Goals 3, ensure healthy lives and promote well-being for all at all ages, i.e. Unlversal Health Coverage. This paper systematically analyzed WHO's international policy framework, action strategies, and development areas, content and priorities in six major areas: leadership and governance, financing, human resources for health, service delivery, medicine and technology, and health information systems. WHO rehabilitation policies advocates to develop national rehabilitation plans, to establish and improve rehabilitation leaderships and the development of mechanism and capacity of rehabilitation governance, to develop multiple approaches of rehabilitation financing, to integrate rehabilitation into health service system, provides different levels of rehabilitation services in the health service continuum, and to build networks of service delivery, to train professionals, to foster rehabilitation information system within health system, to enhance service quality and service coverage, to focus on key areas and priority programs to meet the diverse needs of different populations, and achieve universal health coverage; to include assistive technology into the rehabilitation service system as a field of medicine and technology; and to collect information on functioning and rehabilitation needs, outcomes and impacts of rehabilitation services in the health information system, and conduct evidence-based researches on rehabilitation systems. Conclusion:The framework and contents of WHO's international rehabilitation policies have systematically reviewed at the macro, meso, and micro levels with the perspective of WHO six building blocks of the health system. The goal of rehabilitation development is to achieve universal rehabilitation coverage. The conceptual theories of rehabilitation are based on the theories of people-centered health services and social determinants of health. Rehabilitation is an important initiative to achieve the United Nations 2030 Sustainable Development Goals. The international rehabilitation health policy system is built on six major areas of rehabilitation: leadership and governance, rehabilitation financing, rehabilitation human resources, rehabilitation service delivery, rehabilitation-related medicine and technology, and rehabilitation and health information system. The policy and action strategies for rehabilitation development, as well as specific implementation paths and methods, at macro, meso and micro levels: theory and policy, policy action, and implementation methods and tools have been reviewed and discussed. The implementation of the WHO rehabilitation policies advocates to take the following actions: strengthening the leadership, governance, planning and coordination capacity of rehabilitation services; constructing a reasonable rehabilitation financing mechanism and raising necessary funds for rehabilitation; improving the training and guarantee mechanism of rehabilitation human resources; enhancing the professional capacity of rehabilitation personnel, improving the capacity of rehabilitation service delivery and improving service quality; improving the quality and accessibility of assistive products and assistive technology services; establishing health information system covering functioning, disability and rehabilitation, and conducting scientific researches on rehabilitation.

Objective To observe the therapeutic efficacy of balance cupping plusYang He decoction in treating granulomatous mastitis (GM).Method Eighty GM patients were randomized into a treatment group and a control group according to the last digit of registered number, odd or even, 40 cases each. The control group was treated withYang He decoction; the treatment group was intervened by balance cupping in addition to the treatment given to the control group. They were treated for 6 months in total. The size of lump, swollen size and infection size by the ultrasound B-scanning were observed before and after the treatment, and the clinical efficacies were compared between the two groups.Result The total effective rate was 82.5％ in the treatment group versus 60.0％ in the control group, and the between-group difference was statistically significant (P<0.05). There was a significant difference in comparing the clinical efficacy between the two groups (P<0.05). The size of lump, swollen area and infection size by the ultrasound B-scanning were significantly changed in the two groups after the treatment (P<0.05); the between-group comparisons showed significant differences after the treatment (P<0.05).Conclusion Balance cupping plusYang He decoction can produce a certain efficacy in treating GM.

Compound Yizhihao, consists of Radix isatidis, Folium isatidis, Artemisia rupestris, has a significant therapeutic effect on the treatment of influenza and fever. However, the mechanism of its action is still unclear. In this investigation, we collected the key target molecule of influenza disease and the chemical constituents of Compound Yizhihao, and developed Naïve Bayesian classification models based on the input molecular fingerprints and molecule descriptors. The built models were further applied to construct classifiers for predicting the effective constituents. We used the professional network-building software to build the constituent-target network and target-pathway network, which revealed the network pharmacology of the effective constituents in Compound Yizhihao. It will contribute to the further research of mechanism of Compound Yizhihao.

BACKGROUNDCyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia, hypoxia, and others lead to infant morbidity and mortality more than acyanotic heart disease does. Despite the great effort of medical research, their genetic link and underlying microRNAs molecular mechanisms remain obscure. In this study, we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.

METHODSCyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding. Four weeks later, hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals. We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization. Furthermore, we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.

RESULTSAfter surgical procedure 4 weeks later, the cyanotic model produced lower arterial oxygen tension, arterial oxygen saturation, and higher arterial carbon dioxide tension, hematocrit and hemoglobin concentration than controls (all P < 0.05). In 1273 miRNAs expressed in the immature piglets lungs, 2 most abundant microRNAs (miR-370 and miR-320) demonstrated significant difference between cyanotic and control group (all P < 0.05).

CONCLUSIONOur results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.

Animals ; Chronic Disease ; Cyanosis ; genetics ; physiopathology ; Gene Expression Profiling ; Heart Atria ; surgery ; MicroRNAs ; analysis ; physiology ; Pulmonary Artery ; surgery ; Pulmonary Circulation ; Real-Time Polymerase Chain Reaction ; Swine ; Swine, Miniature

OBJECTIVETo evaluate and compare the antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) response and the influent factors of revaccination of 4 kinds of hepatitis B vaccine (HepB) among firstly low-response adults.

METHODSA total of 11 590 adults who were 18 - 49 years old, never received HepB vaccination, without HBV infection history, HBs-Ag negative, and had been living at 3 towns of Zhangqiu county in Shandong province Ji'nan city for more than half a year, were selected in the study in July, 2009. Self-designed questionnaire was used to select the basic information of the subjects. The subjects were divided into 4 groups by cluster sampling, and were vaccinated according to the "0-1-6" immune procedure with 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Saccharomyces Cerevisiae (HepB-SC), 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), 20 µg HepB-SC and 20 µg HepB made by recombinant deoxyribonucleic acid techniques in Chinese hamster ovary cell (HepB-CHO), 3 doses respectively. The adults who were low-response to the primary hepatitis B vaccination (10 mU/ml ≤ anti-HBs < 100 mU/ml) were divided into four groups by cluster sampling. These groups were revaccinated with one-dose of above-mentioned four kinds of HepB respectively. Blood samples were drawn from each person one month after the revaccination. Anti-HBs was detected by chemiluminescence microparticle immunoassay and compared by the vaccine type. The influence factors about antibody response were also analyzed.

RESULTSOut of the 11 590 subjects, 8592 adults had accepted the primary vaccination of hepatitis B and been collected the blood samples; among whom, 1306 subjects showed low-response, at the rate of 15.20%. A total of 1034 low-response subjects accepted secondary strengthened vaccination and were collected blood samples; 55.13% of them showed anti-HBs seroconversion (anti-HBs ≥ 100 mU/ml); while the seroconversion rate in each group was 44.54% (106/238) in 10 µg HepB-SC group, 57.14% (156/273) in 10 µg HepB-HP group, 56.08% (143/255) in 20 µg HepB-SC group and 61.57% (165/268) in 20 µg HepB-CHO group, respectively. There was significant difference among the groups (χ² = 17.14, P < 0.01). The rates of anti-HBs seroconversion were significantly higher in 10 µg HepB-HP and 20 µg HepB-CHO groups than it in 10 µg HepB-SC group (χ² were 8.09 and 14.70 respectively, P < 0.01). The geometric mean concentration (GMC) of anti-HBs was 178.24 mU/ml among the low-responders after one dose of revaccination. The GMC was 109.77, 243.50, 144.98 and 242.83 mU/ml in 10 µg HepB-SC group, 10 µg HepB-HP group, 20 µg HepB-SC group and 20 µg HepB-CHO group, respectively. There was significant difference among groups (F = 9.52, P < 0.01).

CONCLUSIONAnti-HBs response could be strengthened effectively after one-dose of HepB revaccination among the low-response adults. Many factors like the vaccine types could effect the immune effects to HepB. A better response could be achieved if the 20 µg HepB-CHO or 10 µg HepB-HP was used for revaccination.

Adolescent ; Adult ; Antibody Formation ; immunology ; Female ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Vaccines ; immunology ; Humans ; Immunization, Secondary ; Male ; Middle Aged ; Young Adult

BACKGROUNDCyanotic patients have potential growth retardation and malnutrition due to hypoxemia and other reasons. Ghrelin is a novel endogenous growth hormone secretagogue that has effects on growth and cardiovascular activities. The aim of this study was to evaluate the plasma level and myocardial expression of ghrelin and insulin-like growth factor-1 (IGF-1) using an immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow.

METHODSTwelve weanling Chinese piglets underwent procedures of main pulmonary artery-left atrium shunt with pulmonary artery banding or sham operation as control. Four weeks later, hemodynamic parameters were measured. Enzyme-linked immunosorbent assay for plasma ghrelin and IGF-1 level measurement were performed. Ventricular ghrelin and IGF-1 mRNA expressions were measured by quantitative real-time polymerase chain reaction.

RESULTSFour weeks after surgical procedure, the cyanotic model produced lower arterial oxygen tension ((68.73 ± 15.09) mmHg), arterial oxygen saturation ((82.35 ± 8.63)%), and higher arterial carbon dioxide tension ((51.83 ± 6.12) mmHg), hematocrit ((42.67 ± 3.83)%) and hemoglobin concentration ((138.17 ± 16.73) g/L) than the control piglets ((194.08 ± 98.79) mmHg, (96.43 ± 7.91)%, (36.9 ± 4.73) mmHg, (31.17 ± 3.71)%, (109.83 ± 13.75) g/L) (all P < 0.05). Plasma ghrelin level was significantly higher in the cyanotic model group in comparison to the control (P = 0.004), and the plasma IGF-1 level was significantly lower than control (P = 0.030). Compared with control animals, the expression of ghrelin mRNAs in the ventricular myocardium was significantly decreased in the cyanotic model group (P = 0.000), and the expression of IGF-1 mRNAs was elevated (P = 0.001).

CONCLUSIONSChronic cyanotic congenital heart defects model was successfully established. Plasma ghrelin level and myocardial IGF-1 mRNA expression were significantly up-regulated, while plasma IGF-1 level and myocardial ghrelin mRNA expression were down-regulated in the chronic cyanotic immature piglets. The ghrelin system may be an important part of the network regulating cardiac performance.

Animals ; Cyanosis ; blood ; metabolism ; physiopathology ; Female ; Ghrelin ; blood ; metabolism ; Heart Defects, Congenital ; blood ; metabolism ; physiopathology ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Pulmonary Circulation ; physiology ; Swine