[Focusing on the major national demands and developing novel research models--the research progress and prospective of islet organoid].

Diabetes is a major metabolic disease and health issue worldwide that imposes a heavy burden. Research on its pathogenesis and development of effective treatments are currently our major national demands. With the advent of organoid technology, islet organoids have emerged and are attracting increasing attention as a promising model for diabetes research. The establishment of islet organoids is based on the current understanding of islet development. With addition of extra induction factors in vitro to programmatically activate or inhibit specific signaling pathways during islet development, stem cells can be induced to differentiate into three-dimensional cell cultures that possess structures and functions similar to those of natural islets. Because of their capability to mimic the development of islets in vitro, faithfully replicate islet structure, and perform islet physiological functions, islet organoids have been widely used as a valuable tool for the investigation of diabetes pathogenesis, drug screening and evaluation, and clinical transplantation, showing a great potential application. This paper reviews the current research progress, application, and challenges of islet organoids, and discusses the future directions for research on islet organoids.

Modified-Malay Eating Behavior and Pattern Questionnaire (Malay-EBPQ): translation and validation among Malaysian women.

BACKGROUND: Eating behavior primarily depends on eating patterns which are largely influenced by interactions between physiology, environment, psychology, culture and socio-economic status. This study was designed to translate and validate the Eating Behavior Pattern Questionnaire (EBPQ) among Malaysian women. METHODS: A cross-sectional study involving translation and validation of the English version of EBPQ. The original questionnaire, contained 51 items extracted into six domains was translated in Malay using forward and backward translation, pre-tested and validated among conveniently sampled female healthcare personnel. Vegetarians, pregnant ladies and women in confinement were excluded due to special daily dietary plans. Construct validity, reliability and feasibility were analyzed using Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). RESULTS: During translation, item modifications were made and subjected to field testing among 394 women. The original questionnaire was used as a reference to identify the positioning of items in constructs. Fifteen items were removed due to poor correlation with items within constructs. Seven factors were extracted using Varimax rotation with Kaiser-Meyer-Olkin (KMO) value range from 0.725-0.872 and significant Bartlett's test of Sphericity (p < 0.001). The item-loading of the items within the constructs ranged between 0.415-0.812 (explained variation = 62.7%). Cultural and lifestyle behavior was relabeled to lifestyle and behavioral eating, and snacking on sweets was relabeled as snacking pattern. Emotional eating was divided into two sub-factors as snacking behavior and emotional influence. CFA resulted with an acceptable fit with no presence of floor and ceiling effects. Intra-class correlation coefficient (ICC) for all the constructs were reported good and excellent. The overall internal consistency was reported as good. CONCLUSION: The modified 36-item Malay-EBPQ had moderate internal consistency, reliable and fit with multi-dimensional measures of eating behaviors and dietary patterns among women in the multi-racial population with cultural diversity.

The needs and experiences of critically ill patients and family members in intensive care unit of a tertiary hospital in Malaysia: a qualitative study.

BACKGROUND: Admission to an intensive care unit (ICU) is a stressful experience for patients and their family members. While the focus of management is primarily on medical care, there can be other areas which are overlooked. The purpose of this study was to investigate the needs and experiences of ICU patients and family members. METHOD: This qualitative study involved four trained researchers conducting in-depth interviews (IDI) based on a semi-structured interview guide. The participants were ICU patients and family members. All IDIs were audio-recorded and transcribed verbatim. Four researchers independently analyzed the data via thematic analysis with the aid of QDA Miner Lite®. The themes and subthemes were generated and confirmed by literature and expert opinion. RESULTS: Six IDIs were conducted with three patients and three family members, whose ages ranged from 31 to 64 years old. One pair of participants consisted of a patient and his respective family member, while the other four participants did not have a familial relationship with each other. Three main themes emerged from the analysis: (I) critical care services; (II) physical spaces; and (III) monitoring technology. Medical, psychological, physical, and social needs for critical care services were expressed by both patients and family members. Patients' needs in clinical spaces were highlighted as a conducive ICU environment with ambient temperature and controlled noise levels. In non-clinical spaces, family members expressed a need for more chairs in the waiting area. Participants expressed the need for call bells as well as patients' negative perceptions of medical equipment alarms in the ICU when it pertained to monitoring technology. CONCLUSION: This study provides an in-depth view at the needs and experiences of ICU patients and family members who have a variety of unmet needs. This understanding is critical for guiding ICU personnel and stakeholders in their efforts to humanize ICU care.

Cerebellin-2 promotes endothelial-mesenchymal transition in hypoxic pulmonary hypertension rats by activating NF-κB/HIF-1α/Twist1 pathway.

AIMS: Endothelial-mesenchymal transition (EndMT) is one of the critical factors leading to vascular remodeling in pulmonary hypertension (PH). Recent studies found that the expression of Cerebellin-2 (CBLN2) is significantly increased in the lung tissue of patients with PH, suggesting that CBLN2 may be closely related to the development of PH. This study aims to investigate the role and potential mechanism of CBLN2 in the hypoxia-induced EndMT of PH rats. MATERIAL AND METHODS: Hypoxia-induced PH rat model or EndMT cell model was constructed to investigate the role of CBLN2 in the process of endothelial mesenchymal transition during PH. The effects of CBLN2 siRNA, KC7F2 (HIF-1α inhibitor), and PDTC (NF-κB inhibitor) on hypoxia-induced EndMT were observed to evaluate the potential mechanism of CBLN2 in promoting EndMT. KEY FINDINGS: The right ventricular systolic pressure and pulmonary vascular remodeling index in hypoxia-treated rats were significantly increased. The transformation of endothelial cells (marked by CD31) to mesenchymal cells (marked by α-SMA) can be observed in the pulmonary vessels of PH rats, and the expression of CBLN2 in the intima was also significantly up-regulated. In the hypoxia-induced HPAECs, endothelial cell markers such as VE-cadherin and CD31 expression were significantly down-regulated, while mesenchymal-like cell markers such as α-SMA and vimentin were increased considerably, along with the increased expressions of CBLN2, p-p65, HIF-1α, and Twist1; CBLN2 siRNA, PDTC, and KC7F2 could inhibit those phenomena. SIGNIFICANCE: CBLN2 can promote EndMT by activating NF-κB/HIF-1α/Twist1 pathway. Therefore, CBLN2 may be a new therapeutic target for PH.

Burnout Among Critical Care Personnel In Intensive Care Unit During COVID-19 Pandemic In A Malaysian Tertiary Hospital

@#Introduction: During the early phase of Coronavirus disease (COVID-19), there were various uncertainties, which had a detrimental impact on the prevalence of burnout among critical care personnel worldwide. This study aims to investigate the prevalence of burnout and its associated factors in critical care personnel involved in the COVID-19 pandemic. Methods: This is a single-center, cross-sectional study with 81 critical care personnel for a survey using Copenhagen Burnout Inventory. Binary logistic regression analysis was conducted to identify factors associated with personal burnout. Results: More than half of the respondents were female (60.5%) over the age of 30 (61.7%), and 54.3% were medical doctors. A large number (72.8%) of the respondents experienced personal burnout, with twothirds of them experiencing work-related (65.4%) and client-related burnout (59.3%). Personal burnout was found to be associated with those who had children [OR: 11.31 (1.90, 67.37), p = 0.008], stayed with family, relatives, or friends [OR: 9.40 (1.27, 69.46), p = 0.028], were medical doctors [OR: 26.52 (2.79, 252.22), p = 0.004], worked more than 45 hours per week [OR: 8.68 (1.45, 58.09), p = 0.018], and previously never had COVID-19 viral test [OR: 6.93 (1.17, 40.89), p = 0.033]. Conclusion: Overall, more than half of the critical care personnel experienced burnout. There were possible associations between personal burnout with social characteristics such as having children and living with family, relatives, or friends, and occupational characteristics such as being a medical doctor, long working hours, and previously never had COVID-19 viral test.

Factors influencing the interval from isolation to diagnosis of local COVID-19 in Shaanxi Province / 西安交通大学学报(医学版)

【Objective】 To understand the epidemiological characteristics of COVID-19 in Shaanxi Province from December 9, 2021 to January 20, 2022, and analyze the factors influencing the interval from isolation to diagnosis. 【Methods】 We collected the data of local COVID-19 cases from December 9, 2021 to January 20, 2022 published on the official website of Health Commission of Shaanxi Province. Descriptive statistical method was used to analyze the epidemiological characteristics of COVID-19 in Shaanxi Province. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the differences between groups. The unconditional Logistic regression model was applied to analyze the factors influencing the interval between isolation and diagnosis. 【Results】 The outbreak of COVID-19 in Shaanxi Province started on December 9, 2021 and ended on January 20, 2022. The overall change trend of the outbreak showed an "inverted V" shape. A total of 2,080 confirmed local cases were reported, and the main type of disease was mild, with an incidence rate of 5.26/100,000. Xi’an had the most cases, accounting for 98.69% of the total. The reported cases were mainly concentrated in people aged 21 to 55 years old, with a male-to-female sex ratio of 1.19∶1. The median interval from isolation to diagnosis was 3 days, the shortest interval being 0 day and the longest interval being 21 days. Unconditional Logistic regression model analysis showed that the way of finding cases was the factor influencing the interval from isolation to diagnosis. Compared with the way of isolation of the key population, the way of the nucleic acid screening could reduce the risk of late detection of confirmed cases by 89% (OR=0.11, 95% CI: 0.07-0.16). 【Conclusion】 The way of finding cases is the factor influencing the interval from isolation to diagnosis. In the face of the recent intensification of the spread of Omicron variant in mainland China, accurate and rapid identification and detection of confirmed cases can not only reduce the risk of the spread of the epidemic, but also endeavor more time and initiative for the treatment of patients, which is the key to curbing the spread of the epidemic.

Towards increased accuracy and reproducibility in SARS-CoV-2 next generation sequence analysis for public health surveillance

During the COVID-19 pandemic, SARS-CoV-2 surveillance efforts integrated genome sequencing of clinical samples to identify emergent viral variants and to support rapid experimental examination of genome-informed vaccine and therapeutic designs. Given the broad range of methods applied to generate new viral genomes, it is critical that consensus and variant calling tools yield consistent results across disparate pipelines. Here we examine the impact of sequencing technologies (Illumina and Oxford Nanopore) and 7 different downstream bioinformatic protocols on SARS-CoV-2 variant calling as part of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Tracking Resistance and Coronavirus Evolution (TRACE) initiative, a public-private partnership established to address the COVID-19 outbreak. Our results indicate that bioinformatic workflows can yield consensus genomes with different single nucleotide polymorphisms, insertions, and/or deletions even when using the same raw sequence input datasets. We introduce the use of a specific suite of parameters and protocols that greatly improves the agreement among pipelines developed by diverse organizations. Such consistency among bioinformatic pipelines is fundamental to SARS-CoV-2 and future pathogen surveillance efforts. The application of analysis standards is necessary to more accurately document phylogenomic trends and support data-driven public health responses.

Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells.

Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway.

Health-related quality of life of Malaysian patients with chronic non-malignant pain and its associated factors: a cross-sectional study.

BACKGROUND: Chronic pain has a major impact on a patient's quality of life, affecting physical and psychological functioning. It has debilitating consequences on social and economic aspects too. This study aimed to explore the status of health-related quality of life (HRQoL) of Malaysian patients suffering from chronic non-malignant pain. METHODS: Four hospitals offering pain clinic services were involved in this multicentre cross-sectional study conducted between June and September 2020. Adult patients who had been diagnosed with non-malignant chronic pain lasting for at least three months and able to communicate in English or Malay language were recruited in this study. Participants were informed about the study and were made aware that their participation was entirely voluntary. A battery of questionnaires consists of the EuroQol-5 dimensions-5 levels questionnaire (EQ-5D-5L) and the EuroQol visual analogue scale (EQ VAS), the Pain Self-Efficacy questionnaire (PSEQ) and the Pain Catastrophizing Scale (PCS) were self-administered by the patients. Besides, a structured questionnaire was used to collect their socio-demographic information, pain condition, sleep quality and working status. Participants' usage of pain medications was quantified using the Quantitative Analgesic Questionnaire (QAQ). RESULTS: A total of 255 patients participated in this study. A median EQ-5D index value of 0.669 (IQR: 0.475, 0.799) and a median EQ VAS score of 60.0 (IQR: 50.0, 80.0) were recorded. Malay ethnicity (Adj. B: 0.77; 95% CI: 0.029, 0.126; p = 0.002) and a higher level of self-efficacy (Adj. B: 0.008; 95% CI: 0.006, 0.011; p < 0.001) were predictors of a better HRQoL, while suffering from pain in the back and lower limb region (Adj. B: -0.089; 95% CI: - 0.142, - 0.036; p = 0.001), the use of a larger amount of pain medications (Adj. B: -0.013; 95% CI: - 0.019, - 0.006; p < 0.001), and a higher degree of pain magnification (Adj. B: -0.015; 95% CI: - 0.023, - 0.008; p < 0.001) were associated with a poorer HRQoL. CONCLUSIONS: These findings suggested that Malay ethnicity and a higher level of self-efficacy were predictors of a better HRQoL in patients with chronic pain, whereas pain-related factors such as higher usage of medication, specific pain site and pain magnification style were predictors of poorer HRQoL.

Molecular profiling of gene fusions in soft tissue sarcomas by Ion AmpliSeqTM: a study of 35 cases.

Background: The accurate diagnosis of sarcoma can be difficult as there are over 70 different subtypes. While molecular profiling in soft tissue sarcoma (STS) has gradually been incorporated into routine diagnostics, conventional methods such as fluorescence in situ hybridization (FISH), reverse transcriptase-PCR (RT-PCR), and Sanger sequencing have several drawbacks. By allowing simultaneous analysis of multiple targets and increasing sequencing depth to achieve ultra-sensitivity, next-generation sequencing (NGS) can not only detect common genetic abnormalities without prior assumptions but also identify uncommon or even new variants. Methods: In this study, the applicability of NGS in assessing STS using the Ion Torrent Proton was evaluated and compared with other methods. A cohort of 35 tissue specimens from STS patients, including alveolar soft-part sarcoma (ASPS), Ewing's sarcoma (ES), synovial sarcoma (SS), dermatofibrosarcoma protuberans (DFSP), and myxoid liposarcoma (MLPS) patients, were subjected to NGS by an Ion AmpliSeqTM Custom panel. Results: A proportion of 97.14% (34/35) were successfully conducted to detect gene fusion positive events and met all criteria for good quality. The concordance between NGS and conventional techniques was 94.12% (32/34). NGS also showed superior results, as Sanger sequencing and FISH in two cases were false negatives, demonstrating the excellent diagnostic utility of NGS for translocation detection in STS. Conclusions: The results in this study show the potential for NGS to aid in diagnosis and clinical monitoring of STS and warrant additional studies in larger cohorts.

The landscape of antibiotic usage among COVID-19 patients in the early phase of pandemic: a Malaysian national perspective.

BACKGROUND: During the early phase of the COVID-19 pandemic, antibiotic usage among COVID-19 patients was noted to be high in many countries. The objective of this study was to determine the prevalence of antibiotic usage and factors affecting antibiotic usage among COVID-19 patients during the early phase of the COVID-19 pandemic in Malaysia. METHODS: This was a cross-sectional study that involved reviewing medical records of COVID-19 Malaysian patients aged 12 and above who were diagnosed with COVID-19 and received treatment in 18 COVID-19 hospitals from February to April 2020. A minimum sample of 375 patients was required. A binary logistic regression analysis was performed to determine factors associated with antibiotic usage. Variables with p < 0.05 were considered statistically significant. RESULTS: A total of 4043 cases were included for analysis. The majority of the patients (87.6%) were non-smokers, male (65.0%), and had at least one comorbidity (37.0%). The median age was 35 years (IQR: 38). The prevalence of antibiotic usage was 17.1%, with 5.5% of them being prescribed with two or more types of antibiotics. The most frequent antibiotics prescribed were amoxicillin/clavulanic acid (37.8%), ceftriaxone (12.3%), piperacillin/tazobactam (13.3%), azithromycin (8.3%), and meropenem (7.0%). Male patients (adjusted OR 1.53), who had a comorbidity (adjusted OR 1.36), associated with more severe stage of COVID-19 (adjusted OR 6.50-37.06), out-of-normal range inflammatory blood parameters for neutrophils, lymphocytes, and C-reactive protein (adjusted OR 2.04-3.93), corticosteroid use (adjusted OR 3.05), and ICU/HDU admission (adjusted OR 2.73) had higher odds of antibiotic use. CONCLUSIONS: The prevalence of antibiotic usage in the early phase of the COVID-19 pandemic was low, with amoxicillin/clavulanic acid as the most common antibiotic of choice. The study showed that clinicians rationalized antibiotic usage based on clinical assessment, supported by relevant laboratory parameters.

Comparison between frontalis suspension and levator resection in treatment of blepharoptosis: a meta-analysis / 中华医学美学美容杂志

Objective:To compare the postoperative efficacy and complications of frontalis suspension and levator resection in the treatment of blepharoptosis.Methods:According to the Cochrane systematic review method, we searched PubMed, Medline, Cochrane Library, Wanfang database, VIP Database, and China Knowledge Network database. The randomized and non-randomized controlled trials for comparing frontalis suspension and levator resection in the treatment of blepharoptosis were included. Revman 5.3 Meta analysis software was used.Results:A total of 13 clinical trials were involved in this study, including 1308 patients. Frontalis suspension was performed in the experimental group and levator resection was performed in the control group. The OR value of postoperative efficacy between the 2 groups was 2.91, 95% CI (1.57-5.39), P<0.01, the difference was statistically significant. Postoperative lagophthalmos after frontalis suspension was better [ MD=-1.05, 95% CI (-1.43--0.68), P<0.01], the difference was statistically significant. The OR value of undercorrection between the 2 groups was 0.24, 95% CI(0.16-0.36), P<0.01, the difference was statistically significant. Conclusions:The postoperative efficacy after frontalis suspension is higher. Postoperative complications after frontalis suspension are less.

Current situation and influencing factors of blood glucose management in diabetic patients aged 15 and above in Gansu / 公共卫生与预防医学

Objective To analyze the relationship between follow-up service, personal characteristics, lifestyle and blood sugar management of diabetic patients in Gansu Province, and put forward scientific suggestions on influencing blood sugar management of diabetic patients. Methods Based on the data of the 6th National Health Service Questionnaire, 273 subjects were included. Chi-square test and unconditional logistic regression were used to analyze the blood glucose control and its influencing factors of diabetic patients. Results A total of 39.56% patients' blood sugar status was well controlled. 76.92% patients signed up for family doctor service, and 77.66% patients took hypoglycemic drugs according to the law of doctor's advice. There were significant differences in blood sugar control among patients in different regions, educational levels and occupational types (P <0.05) , logistic regression analysis showed that Hui patients (OR=0.21), doctors without family contract (OR=2.86) and patients taking hypoglycemic drugs intermittently (OR = 6.58). Conclusion The blood sugar control rate of diabetic patients in Gansu is low, and the nationality, contracted family doctors and medication plan affect the blood sugar control level of patients. In order to ensure the high efficiency of follow-up treatment, the related follow-up services provided by primary medical institutions, it is necessary to provide self-management programs that meet the individual characteristics and meet the needs of the disease.

Construction and practice of standardized workflow and informatization platform for centralized volume-based procurement / 中国药房

OBJECTIVE To sum marize the pro cedure and informatization construction of centralized volume-based procurement（VBP）in our hospital ，in order to give references for normal development of centralized VBP. METHODS The standardized workflow system was established ，including using flow chart method to establish standardized workflow ，carrying out procedure training and inspection of procedure implementation ， and continuously conducting procedure optimization. The information system was developed for the task links that needed a lot of calculation to improve the automation level of information processing. RESULTS & CONCLUSIONS Eight specific work procedures were established in our hospital ，including the work procedures of submitting the demand data of centralized VBP and the implementation of centralized VBP ，and has taken measures such as procedure training ，establishing supervision and inspection system and using auxiliary means to promote the implementation of the procedure ，so as to optimize the procedure and work form. An informatization platform for the clinical task allocation of the agreed purchase quantity of centralized VBP and a supervision platform for the daily use of VBP were also established in our hospital，then the two tasks with a large amount of calculation could be finished. Standardized workflow system and informatization platform construction has improved the operation and supervision efficiency of centralized VBP in our hospital ，ensured the completion of centralized purchase tasks and saved human resources ，which has a certain promotion value.

Application of "secret room escape" game teaching combined with situational case teaching mode in the teaching of standardized training of neurological nursing / 中华医学教育探索杂志

Objective:To explore the application effect of "secret room escape" game teaching combined with situational cases on the teaching of standardized training of neurological nursing.Methods:A total of 102 nurses who underwent the standardized training in the Department of Neurology of Xinjiang Uygur Autonomous Region People's Hospital from January 2019 to September 2020 were divided into control group ( n=51) and observation group ( n=51). The control group used situational case teaching, and the observation group used "secret room escape" game teaching combined with situational case teaching. The scores of critical thinking and learning engagement of the two groups were evaluated, and the theoretical assessment scores, clinical comprehensive ability scores and teaching satisfaction of the two groups were compared. SPSS 22.0 was performed for chi-square test and t test. Results:Before teaching, there was no significant difference in the scores and total scores of truth seeking, mind opening, analytical ability, systematic ability, self-confidence of critical thinking, thirst for knowledge and cognitive maturity between the two groups. After teaching, the scores and total scores of the observation group in above aspects were higher than those of the control group ( P<0.05). There was no significant difference in the scores and total scores of behavioral engagement, cognitive engagement and emotional engagement between the two groups before teaching; after teaching, the scores and total scores of these aspects in the observation group were higher than those in the control group ( P<0.05). The scores of theoretical examination [(82.02±3.27) vs. (79.66±3.45)] and clinical comprehensive ability [(83.30±3.54) vs. (80.82±3.73)] in the observation group were higher than those in the control group. The teaching satisfaction of the observation group was 98.04% (50/51), higher than 82.35% (42/51) of the control group. Conclusion:The "secret room escape" game teaching combined with situational cases can improve the critical thinking ability of standardized training nurses, stimulate them to participate in learning, improve their theoretical examination results and clinical comprehensive ability, and improve their satisfaction with teaching and the recognition rate of teaching effect.

The Challenges and Strategies in Managing Intensive Care Unit for COVID-19 Pandemic in Malaysia

@#The number of patients requiring intensive care has surged since the outbreak of the SARS-CoV-2 virus. This had rendered the intensive care unit (ICU) a huge challenge not only to provide care for the existing patients but also to support the COVID-19 patients. The ICU was restructured to ensure strict adherence to the infection control guidelines. The aspects of change in the ICU had been ranging from the clinical operation, medication equipment and facilities, medications supply, and staffing. Strategies required upon implementation of change include having contingency plans, being innovative, getting the collaboration from other ICUs, exchanging information, getting support from the health policymakers, and ensuring the safety of the healthcare workers. This article aimed to share the experience of challenges and strategies in managing an ICU for the COVID-19 pandemic in Malaysia.

Coronary Revascularization and Out-of-hospital Cardiac Arrest: Past, Present and Future.

Cardiologists and the cardiac catheter laboratory have key roles to play in the management of patients after out-of-hospital cardiac arrest (OHCA). Although immediate catheter laboratory activation is the standard of care in cardiogenic shock and ST elevation myocardial infarction, the majority of patients will present without these features and with an uncertain diagnosis. Even in the latter, early assessment and invasive management may be beneficial, but this is counterbalanced by significant resource utilization, potential to cause harm and the possibility that any diagnostic or therapeutic gains are offset by a poor neurological outcome. Past consensus on the management of the OHCA patient without ST elevation or cardiogenic shock is being challenged by emerging results from new trials in this field. Further randomized trials are ongoing, and are expected to deliver robust data from over 4,000 patients, allowing us to further refine the optimal management strategy in this challenging cohort. This article describes the benefits and pitfalls of a strategy of immediate coronary angiography in these patients, examines the recently published COACT and TOMAHAWK trials in detail, and describes a framework with which to approach the patient after resuscitated OHCA, based on the available evidence to date.

Magnolol attenuates right ventricular hypertrophy and fibrosis in hypoxia-induced pulmonary arterial hypertensive rats through inhibition of the JAK2/STAT3 signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol is a com?pound isolated from Magnolia officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. METHODS ① Male SD rats (220 g) were randomly divided into 5 groups (n=10): the normoxia group, the hypoxia group, the hypoxia plus Magnolol (10 and 20 mg·kg-1·d-1) group, and the vehicle group. Rats in the normoxia group were kept in a normoxia environment for 4 weeks, while rats in the hypoxia group were kept in a hypoxic chamber (10％ O2). The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg-1 (ip) once a day for 4 weeks. At the end of 4 weeks, the heart function was assessed by Doppler echocardiography, and then the rats were anesthetized with sodium pentobarbital (30 mg·kg-1, ip). The RVSP was measured by the right heart catheterization method. The heart tissues were collected and dissected to calculate the index of RV remodeling (RV/LV+IVS, RV/tibial length, or RV/body weight). Part of the RV samples was fixed with 4％paraformaldehyde for morphological analysis, while other samples were frozen at-80℃for molecular studies (measurements of ANP, BNP,α-SMA, and col?lagen Ⅰ/Ⅲ mRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels). ② To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis, H9c2 or cardiac fibroblasts were divided into 7 groups: the control group, cells were cultured under normal conditions; the hypoxia group, cells were cultured under hypoxic condition (3％ O2);the hypoxia plus magnolol 10 mg·kg-1 group, magnolol10μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg-1 group, magnolol 20μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group, TG-101348 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group, JSI-124 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group, an equal volume of vehicle (DMSO) was added to the culture medium before the hypoxia treatment. At the end of the experiments, the cells were collected for morphological and molecular analysis. RESULTS In vivo, male Sprang-Daley rats were exposed to 10％ O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of RV remodeling index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3％ O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagenⅠ, collagenⅢandα-SMA). Administration of mag?nolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.

Bioinformatic analysis revealing mitotic spindle assembly regulated NDC80 and MAD2L1 as prognostic biomarkers in non-small cell lung cancer development.

BACKGROUND: Lung cancer has been the leading cause of tumor related death, and 80% ~ 85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. METHODS: Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. RESULTS: Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. CONCLUSIONS: Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.

Optimization of the Formulation of Polygala japonica Cream by Central Composite Design-response Surface Methodology Based on AHP-CRITIC Analysis and Its Quality Evaluation / 中国药房

OBJECTIVE：To optimize the formul ation of Polygala japonica cream，and to evaluate the quality of prepared cream. METHODS ：With centrifugal stability ，heat resistance stability and viscosity as evaluation indexes ，the weight coefficient was determined by analytic hierarchy process （AHP），criteria importance through intercriteria correlation （CRITIC）method and mixed weighted AHP-CRITIC ，and the comprehensive score was calculated. The amount of octadecyl alcohol ，hexadecanol and mixed emulsifier （polysorbate 60 mixed with glycerin monostearate at the mass ratio of 2.82）in the formulation of P. japonica cream were screened by central composite design-response surface methodology. The optimized formulation was validated. P. japonica cream prepared by the optimal preparation was evaluated in terms of apperance ，particle，pH，stability and rheological characteristics. RESULTS ：The weight coefficients of centrifugal stability ，heat resistance stability and viscosity were 0.428 5， 0.415 6 and 0.155 9 respectively，according to the mixed weighted AHP-CRITIC. The optimal formulations were 1.96 g of hexadecyl alcohol ，5.17 g of octadecyl alcohol ，2.48 g of mixed emulsifier ，1.83 g of polysorbate 60，0.65 g of glyceride monostearate，1 g of benzyl alcohol ，5 g of propylene glycol ，6 g of isopropyl myristate and 5 g of P. japonica extract，and then added water to 100 g. Prepared cream was a light yellow fluid paste with particle size of 0.5-2.5 μm and pH value of 6.5；the results of centrifugal test ，heat resistance test and cold resistance stability test showed that the cream had no oil-water separation or thickened paste. The prepared cream was shear-thinning non-Newtonian fluid. CONCLUSIONS ：P. japonica cream is prepared successfully，which shows good apperance ，particle，acidity and stability.