Quality problems in clinical practice guidelines and guideline appraisal studies: Should we tolerate or eradicate?

BACKGROUND: Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument have been widely used by scholars around the world to assess the methodological quality of clinical practice guidelines (CPGs). We sought to identify items or domains that are commonly scored low in the assessment, and to systematically review the issues that emerged when evaluators used the AGREE II tool for guideline quality assessment. METHODS: A systematic search was conducted to identify articles published in medically relevant databases from 2022 to 2023 regarding the use of the AGREE II tool for the assessment of CPGs. We extracted six quality domains and overall quality assessment data of CPGs included in the literature, and processed the data using descriptive statistical analysis, difference analysis, regression analysis, and correlation analysis. A seven-point Likert scale was used to assess the reporting quality of the included articles. RESULTS: 151 relevant publications were identified, including 2081 guidelines published between 1990 and 2022. The results of the regression analysis showed a statistically significant impact of all domains on overall guideline quality (p < 0.001; R2 = 0.777). Domain 1, 2, 3, 4, and 6 scores differed significantly over time (p < 0.001) and were increasing. The score was good for Domain 4 (median 78.00 [IQR: 62.75-89.00]; mean 74.34 [SD 18.85]) and Domain 1 (median 78.00 [IQR: 61.00-90.00]; mean 73.57 [SD 21.12]). Scores were generic for Domain 6 (median 58.33 [IQR: 25.00-83.33]; mean 53.98 [SD 34.13]), Domain 2 (median 53.00 [IQR: 33.30-72.10]; mean 53.30 [SD 24.52]) and Domain 3 (median 51.00 [IQR: 26.02-73.00]; mean 50.44 [SD 27.19]). The score was poor for Domain 5 (median 36.20 [IQR: 20.20-58.32]; mean 40.21 [SD 24.90]). In addition, the quality evaluation results of the included articles showed that 33.1% were evaluated as low and 11.9% as very low. CONCLUSIONS: AGREE II tools have facilitated the development of methodological quality for CPGs. Although the quality of CPGs has improved over time, some general low-quality problems still exist, and solving these problems will be an effective way for developers to upgrade the quality of guidelines. In addition, addressing critical issues in the evaluation of guidelines to present high-quality study reports would be another way to guide guideline development.

Characteristic activation pattern and network connectivity of prefrontal cortex in patients with type 2 diabetes mellitus and major depressive disorder during a verbal fluency task: A functional near-infrared spectroscopy study based on network-based statistic prediction.

INTRODUCTION: Type 2 diabetes (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction (NBS-predict) was adopted as data analysis method. RESULTS: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2MD and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: There was a distinctive activation pattern and network connectivity of the prefrontal cortex in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM.

The relationship between social support and professional identity of health professional students from a two-way social support theory perspective: chain mediating effects of achievement motivation and meaning in life.

BACKGROUND: Studies has suggested that receiving social support improves the professional identity of health professional students. According to the two-way social support theory, social support includes receiving social support and giving social support. However, the effect of the two-way social support on health professional students' professional identity has not been clarified yet. METHODS: To explore the mechanism of how two-way social support affects health professional students' professional identity, an observational, cross-sectional study was conducted among a convenience and cluster sample of 1449 health professional students from two medical schools in western China. Measures included a short version of the two-way social support scale, a health professional students' professional identity questionnaire, an achievement motivation scale, and a meaning in life scale. Data were analyzed by use of SPSS26.0 software and PROCESSv4.0 plug-in. RESULTS: Receiving social support, giving social support, achievement motivation, meaning in life, and professional identity were positively correlated with each other. Receiving and giving social support not only directly predicted health professional students' professional identity, but also indirectly predicted health professional students' professional identity through the mediating roles of achievement motivation and meaning in life, and the chain mediating roles of achievement motivation and meaning in life, respectively. The effectiveness of predicting health professional students' professional identity varied among different types of two-way social support, which could be depicted as two-way social support > mainly giving social support > mainly receiving social support > low two-way social support. CONCLUSION: In the medical education, the awareness and ability of health professional students to receive and give social support should be strengthened. More attention should be drawn on the chain mediating effect of achievement motivation and meaning in life between two-way social support and professional identity. The current results shed new light on exploring effective ways of improving health professional students' professional identity, which suggested that more attention should be paid to the positive effects of mainly giving social support and two-way social support rather than only on the effects of receiving social support.

TET2 Is Downregulated in Early Esophageal Squamous Cell Carcinoma and Promotes Esophageal Squamous Cell Malignant Behaviors.

OBJECTIVE: To explore the expression of the ten eleven translocation (TET) 2 protein in early esophageal squamous cell carcinoma (EESCC), precancerous lesions, and cell lines and to evaluate the effect of TET2 on the functional behavior of EC109 esophageal cancer cells. METHODS: Thirty-one samples of EESCC and precancerous lesions collected via endoscopic submucosal dissection at Taihe Hospital, Shiyan, from February 1, 2017, to February 1, 2019, were analyzed. The study involved evaluating TET2 expression levels in lesion tissue and adjacent normal epithelium, correlating these with clinical pathological features. Techniques including 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide, cell scratch assays, flow cytometry for propidium iodide (PI) staining, Hoechst 333258/PI double staining, and nude mouse tumorigenesis experiments were employed to assess the effect of TET2 on the proliferation, migration, cell cycle, apoptosis, and tumorigenic ability of esophageal cancer cells. RESULTS: TET2 expression was notably reduced in early esophageal cancer tissue and correlated with tumor invasion depth (P < 0.05). Overexpression of TET2 enhanced the proliferation and migration of esophageal cancer cells, increased the cell population in the G0 phase, decreased it in the S phase, and intensified cell necrosis (P < 0.05). There was a partial increase in tumorigenic ability (P = 0.087). CONCLUSION: TET2 downregulation in ESCC potentially influences the necrosis, cell cycle, and tumorigenic ability of esophageal cancer cells, suggesting a role in the onset and progression of esophageal cancer.

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies.

Background: Depression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression. Method: Electronic databases were searched using the search terms "depression," "emotion recognition," and "neuroimaging" from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis. Results: We retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001). Conclusion: Among depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution. Systematic review registration: https://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057.

Attention bias modification for depression: A systematic review and meta-analysis.

Background: Depression is a mental health disorder characterized by affective, somatic, and cognitive symptoms. Attention bias modification (ABM) has been widely used to treat depression. However, the results seem inconsistent. We conducted a systematic review and meta-analysis to investigate the efficacy of ABM for depression and to explore the optimal protocol of ABM. Methods: Seven databases were systematically searched from their inceptions to 5 October 2022 to include randomized controlled trials (RCTs) of ABM for depression. Two independent reviewers selected the eligible articles, extracted data, and evaluated the risk of bias using version 2 of the Cochrane risk-of-bias tool (ROB 2.0) for randomized trials. The primary outcome was the evaluation of depressive symptoms using widely accepted and validated scales. The secondary outcomes included rumination and attentional control. Meta-analysis was conducted by using RevMan (version 5.4) and Stata (version 12.0). Subgroup analyses and meta-regressions were performed to identify the source of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 19 trials involving 20 datasets (1,262 participants) were included. The overall risk of bias in one study was rated as low risk of bias, three studies were considered as high, and the remaining studies were some concerns. Compared with attention control training (ACT), ABM had a greater effect in the improvement of depression (SMD = -0.48, 95% CI -0.80 to -0.17, I2 = 82%) and rumination (MD = -3.46, 95% CI -6.06 to -0.87, I2 = 0%). No significant differences were observed in the attentional control outcome between ABM and ACT (MD = 3.07, 95% CI -0.52 to 6.65, I 2 = 0%). Subgroup analysis demonstrated that adults exhibited a greater decrease in depression scores than adolescents. ABM using the dot-probe task, training target stimulus presented by face, and training directions by left-right were associated with better antidepressant effects. ABM training delivered in the laboratory tended to yield a better effect than those conducted at home. Sensitivity analysis indicated that the results were robust. The certainty of the evidence for all outcomes was low or very low, and publication bias may exist. Conclusion: Due to high heterogeneity and limited studies, not enough current evidence supported that ABM could be an effective intervention to relieve depressive symptoms. More rigorous RCTs are required to verify the benefits and to explore the optimal protocol of ABM training for depression.Systematic Review Registration: [PROSPERO], identifier [No. CRD42021279163].

The Effect of Consultation-Liaison Psychiatry on Postoperative Delirium in Elderly Hip Fracture Patients in the General Hospital.

OBJECTIVE: The low recognition rate of postoperative delirium has gradually aroused clinical attention in China. The present study was to investigate the impact of consultation-liaison psychiatry on postoperative delirium in elderly hip fracture patients. METHODS: From March 2012 to September 2013, 89 patients with hip fractures hospitalized in Wuhan Mental Health Center were included in this prospective study as the consultation-liaison group. A total of 81 patients selected from August 2010 to February 2012 were defined as the conventional group. The delirium was evaluated using the confusion assessment method (CAM) recommended by the American Psychiatric Association guidelines. RESULTS: There was no difference of sex, age, trauma, surgical methods, and anesthesia between two groups (p > 0.05). The consultation rate of consultation-liaison group was significantly higher than that of conventional group (37.07% vs 17.28%, p < 0.05). After the consultation, there were 26 cases (78%) and nine cases (64%) of delirium in the consultation-liaison and conventional group, respectively (p > 0.05). In the consultation-liaison group, three patients (9.09%) were diagnosed with anxiety and three patients (9.09%) were diagnosed with depression, while in the conventional group, three patients (21.42%) were diagnosed with communication and one patient (7.14%) was diagnosed with depression. In addition, this study showed the incidence of delirium in consultation-liaison group was significantly higher than that of conventional group (29.21% vs 11.11%, p < 0.05). The average hospital stay in consultation-liaison group was significantly lower than that of conventional group (11.42 ± 2.63 vs. 15.17 ± 2.38 days, p < 0.01). CONCLUSION: Consultation-liaison psychiatry could improve the recognition rate of postoperative delirium in elderly hip fracture patients, shorten hospitalization time. The training of mental health knowledge for non-psychiatrists could improve the ability of early identification and treatment of delirium.

Self-made wire loop snare successfully treats gastric persimmon stone under endoscopy.

BACKGROUND: Large gastric persimmon stones are generally resistant to standard endoscopic treatments. We applied an alternative endoscopic method using a hand-made snare for the treatment of large gastric phytobezoars. AIM: To explore the clinical efficacy of a self-made wire loop snare to treat giant gastric persimmon stones. METHODS: A retrospective study evaluated the clinical data of 38 patients with gastroliths admitted to Taihe Hospital in Shiyan City, Hubei Province, China, between March 2015 and October 2020. The patients were divided into observation (n = 23) and control (n = 15) groups. Patients in the observation group were treated with self-made wire loop snares for lithotripsy, and patients in the control group were treated with traditional foreign body forceps, snares, injection needles, and other tools. Successful stone removal, treatment time, and hospital stay were compared. RESULTS: The average operating time was significantly shorter (P < 0.001) in the observation group (53.4 min) than that in the control group (172.8 min). The average hospital stay of the observation group (5.4 d) was significantly shorter (P < 0.001) than that in the control group (10.3 d). Successful one-time treatment was significantly more frequent (P < 0.001) in the observation group (87%) than in the control group (7%). CONCLUSION: Self-made guidewire loop snares were successfully used to treat gastrolithiasis, and were significantly more effective than foreign body forceps, snares, and other traditional methods.

Clinical practice guidelines and expert consensus statements on rehabilitation for patients with COVID-19: protocol for a systematic review.

INTRODUCTION: COVID-19 is a highly infectious disease, characterised by respiratory, physical and psychological dysfunctions. Rehabilitation could effectively alleviate the symptoms and promote recovery of the physical and mental health of patients with COVID-19. Recently, rehabilitation medical institutions have issued clinical practice guidelines (CPGs) and expert consensus statements involving recommendations for rehabilitation assessments and rehabilitation therapies for COVID-19. This systematic review aims to assess the methodological quality and reporting quality of the guidance documents, evaluate the heterogeneity of the recommendations and summarise the recommendations with respect to rehabilitation assessments and rehabilitation therapies for COVID-19 to provide a quick reference for front-line clinicians, therapists and patients as well as reasonable suggestions for future guidelines. METHODS AND ANALYSIS: The electronic databases including PubMed, Embase, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Wanfang Database and China National Knowledge Infrastructure (CNKI) and websites of governments or organisations (eg, National Guideline Clearinghouse, Guidelines International Network, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network and WHO) will be searched for eligible CPGs and expert consensus statements from inception to August 2022. CPGs and expert consensus statements published in Chinese or English and presenting recommendations for modern functional rehabilitation techniques and/or traditional Chinese medicine rehabilitation techniques for COVID-19 will be included. Reviews, interpretations, old versions of CPGs and expert consensus statements and those for the management of other diseases during the pandemic will be excluded. Two reviewers will independently review each article, extract data, appraise the methodological quality following the Appraisal of Guidelines for Research & Evaluation II tool and assess the reporting quality with the Reporting Items for Practice Guidelines in Healthcare statement. The Measurement Scale of Rate of Agreement will be used to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements. Agreement between reviewers will be calculated using the intraclass correlation coefficient. We will also summarise the recommendations for rehabilitation in patients with COVID-19. The results will be narratively described and presented as tables or figures. ETHICS AND DISSEMINATION: Ethics approval is not needed for this systematic review because information from published documents will be used. The findings will be submitted for publication in a peer-reviewed journal and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PROSPERO REGISTRATION NUMBER: CRD42020190761.

Intermittent lipid nanoparticle mRNA administration prevents cortical dysmyelination associated with arginase deficiency.

Arginase deficiency is associated with prominent neuromotor features, including spastic diplegia, clonus, and hyperreflexia; intellectual disability and progressive neurological decline are other signs. In a constitutive murine model, we recently described leukodystrophy as a significant component of the central nervous system features of arginase deficiency. In the present studies, we sought to examine if the administration of a lipid nanoparticle carrying human ARG1 mRNA to constitutive knockout mice could prevent abnormalities in myelination associated with arginase deficiency. Imaging of the cingulum, striatum, and cervical segments of the corticospinal tract revealed a drastic reduction of myelinated axons; signs of degenerating axons were also present with thin myelin layers. Lipid nanoparticle/ARG1 mRNA administration resulted in both light and electron microscopic evidence of a dramatic recovery of myelin density compared with age-matched controls; oligodendrocytes were seen to be extending processes to wrap many axons. Abnormally thin myelin layers, when myelination was present, were resolved with intermittent mRNA administration, indicative of not only a greater density of myelinated axons but also an increase in the thickness of the myelin sheath. In conclusion, lipid nanoparticle/ARG1 mRNA administration in arginase deficiency prevents the associated leukodystrophy and restores normal oligodendrocyte function.

Dataset-based assessment of heavy metal contamination in freshwater fishes and their health risks.

The ecological risks and health hazards of heavy metals pollution in Taihu Lake have received widespread concern. This study has developed a species-pollution dataset which includes a large amount of data on heavy metal pollution in Taihu fish. The heavy metal contamination poses a significant threat to human consumption, but no studies have been conducted to assess the risk of exposure to consumption of these fish and to make recommendations for their consumption. In this study, we systematically integrated the relevant data in the dataset, analyzed its contamination level using PI (single pollution index) and MPI (metal pollution index) models, and assessed health hazards of fish consumption using THQ (target hazard quotient) and ILCR (incremental lifetime cancer risk) models. Results showed that the contamination levels of heavy metals in fish varied in a feeding habit and living habit dependent manner. The risk of non-cancer health is the highest from consuming omnivorous fish, then from carnivorous and herbivorous fish. The ILCR model predicted that the long-term Taihu consumption of omnivorous fish may pose a potential carcinogenic risk, especially for children. In all, our study provided a comprehensive understanding on the risk of heavy metals in Taihu. Accordingly, it is recommended that children should try to choose herbivorous fish when consuming fish from Taihu Lake while avoiding long-term consumption of omnivorous fish.

Extracorporeal Shock Wave Therapy on Spasticity After Upper Motor Neuron Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the effectiveness and safety of extracorporeal shock wave therapy on spasticity after upper motor neuron injury. DESIGN: Eight electronic databases were searched systematically from their inception to August 3, 2021, to provide robust evidence for the efficacy of extracorporeal shock wave therapy for spasticity and range of motion after upper motor neuron injury. Study screening, data extraction, risk of bias assessment, and evaluation of the certainty of evidence were performed independently by two independent reviewers. Data analysis was conducted using RevMan 5.3.5 and R 3.6.1 software. RESULTS: Forty-two studies with 1973 patients who met the eligibility criteria were selected from articles published from 2010 to 2021, of which 34 were included in the meta-analysis. A comparison intervention revealed that extracorporeal shock wave therapy significantly decreased the Modified Ashworth Scale score and increased the passive range of motion of a joint. Regarding the safety of extracorporeal shock wave therapy, slightly adverse effects, such as skin injury, bone distortion, muscle numbness, pain, petechiae, and weakness, were reported in five studies. CONCLUSIONS: Extracorporeal shock wave therapy may be an effective and safe treatment for spasticity after upper motor neuron injury. However, because of poor methodological qualities of the included studies and high heterogeneity, this conclusion warrants further investigation. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the impact of extracorporeal shock wave therapy on spasticity after upper motor neuron injury; (2) Describe the factors that affect the efficacy of extracorporeal shock wave therapy on spasticity; and (3) Discuss the mechanism of action of extracorporeal shock wave therapy on spasticity. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The effects of acupuncture therapy in migraine: An activation likelihood estimation meta-analysis.

Background: Previous functional magnetic resonance imaging studies indicated that acupuncture could activate the brain regions in patients with migraine. However, these studies showed inconsistent results. This activation likelihood estimation (ALE) meta-analysis aimed to investigate the consistent activated change of brain regions between pre- and post-acupuncture treatment in migraineurs. Methods: We conducted a literature search in PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang Database, and the Chinese Biomedical Literature Database from their inception to 18 August, 2022, to obtain articles assessing the functional magnetic resonance imaging changes of acupuncture for migraine. Two investigators independently performed literature selection, data extraction, and quality assessment. The methodological quality was assessed with a modified version of the checklist. The reporting quality of interventions among included studies was evaluated by the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Our meta-analysis was conducted according to the GingerALE software. The Jackknife sensitivity analysis was used to assess the robustness of the results. Results: 14 articles were finally included according to the eligible criteria. Regarding the immediate effect of acupuncture on migraine, the ALE meta-analysis demonstrated that the deactivation regions were mainly located in the superior frontal gyrus, and middle frontal gyrus (uncorrected P < 0.001). The ALE meta-analysis of the cumulative effect showed that the activation regions were the thalamus, superior frontal gyrus, posterior lobe of the cerebellum, insula, middle frontal gyrus, precentral gyrus, anterior cingulate, and the deactivation brain regions were located in the transverse temporal gyrus, postcentral gyrus, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, inferior parietal lobule, and inferior occipital gyrus (uncorrected P < 0.001). Conclusion: Acupuncture could activate multiple brain areas related with the regulation of pain conduction, processing, emotion, cognition, and other brain regions in patients with migraine. In the future, the combination of multiple imaging technologies could be a new approach to deeply investigate the central mechanism of acupuncture for migraine.

Three new andrastin derivatives from the endophytic fungus Penicillium vulpinum.

Three new andrastin derivatives, 10-formyl andrastone A (1), 10-demethylated andrastone A (2) and andrastin G (3), together with four known andrastin analogues (4-7) were isolated from an endophytic fungus Penicillium vulpinum. Their structures were determined by 1 D, 2 D NMR, and the absolute configurations were further determined by experimental and calculated ECD spectra. Compound 5 exhibited significant antibacterial activity against Bacillus paratyphosus B with an MIC value of 6.25 µg·mL-1. Compounds 2 and 6 showed remarkable inhibitory activities against Bacillus megaterium with the MIC value of 6.25 µg·mL-1, respectively.

Fusidane-Type Antibiotics from the Marine-Derived Fungus Simplicillium sp. SCSIO 41513.

Simplifusidic acids A-K (1-11), 11 new fusidane-type nortriterpenoids, were isolated from the marine-derived fungus Simplicillium sp. SCSIO 41513. Compound 1 possessed an unprecedented fusidane triterpene skeleton with a 6/6/7/5/5 polycyclic system. Their structures were elucidated by spectroscopic methods, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra, comparison of experimental ECD spectra, and single-crystal X-ray diffraction analysis. Compound 9 showed strong antibacterial activity toward Staphylococcus aureus with an MIC value of 0.078 µg/mL. Their structure-bioactivity relationship was also discussed.

Mast cells-derived exosomes worsen the development of experimental cerebral malaria.

Cerebral malaria (CM) is the most severe neurological complication caused by Plasmodium falciparum infection. The accumulating evidence demonstrated that mast cells (MCs) and its mediators played a critical role in mediating malaria severity. Earlier studies identified that exosomes were emerging as key mediators of intercellular communication and can be released from several kinds of MCs. However, the potential functions and pathological mechanisms of MCs-derived exosomes (MCs-Exo) impacting on CM pathogenesis remain largely unknown. Herein, we utilized an experimental CM (ECM) model (C57BL/6 mice infected with P. berghei ANKA strain), and then intravenously (i.v.) injected MCs-Exo into P. berghei ANKA-infected mice to unfold this mechanism and investigate the effect of MCs-Exo on ECM pathogenies. We also used an in vitro model by investigating the pathogenesis development of brain microvascular endothelial cells line (bEnd.3 cells) co-cultured with P. berghei ANKA blood-stage soluble antigen (PbAg) after MCs-Exo treatment. The higher numbers of MCs and levels of MCs degranulation were observed in skin, cervical lymph node, and brain of ECM mice than those of the uninfected mice. Exosomes were successfully isolated from culture supernatants of mouse MCs line (P815 cells) and characterized by spherical vesicles with the diameter of 30-150 nm, and expression of typical exosomal markers (e.g., CD9, CD63, and CD81). The i.v. injection of MCs-Exo dramatically elevated incidence of ECM in the P. berghei ANKA-infected mice, exacerbated liver and brain histopathological damage, promoted Th1 cytokine response, aggravated brain vascular endothelial activation and blood brain barrier breakdown in ECM mice. In addition, the treatment of MCs-Exo led to the decrease of cells viability and mRNA levels of Ang-1, ZO-1, and Claudin-5, but increase of mRNA levels of Ang-2, CCL2, CXCL1, and CXCL9 in bEnd.3 cells co-cultured with PbAg in vitro. Taken together, our data indicated that MCs-Exo could worsen pathogenesis of ECM in mice.

MicroRNA-145-5p inhibits hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes by targeting ROCK1.

There is increasing evidence that microRNAs (miRs) play critical roles in the pathological and physiological processes associated with myocardial ischemia reperfusion (I/R). miR-145 has been extensively studied in the cardiovascular system; however, the role of miR-145 in myocardial I/R remains unclear. Therefore, the present study aimed to investigate the role and mechanism of miR-145-5p in myocardial I/R by establishing a hypoxia/reoxygenation (H/R) model using H9c2 cardiomyocytes. The expression of miR-145-5p was regulated by transfection and the potential target of miR-145-5p was identified. In addition, apoptosis of the cardiomyocytes was evaluated using flow cytometry and the detection of cleaved caspase-3 by western blotting. The results revealed that miR-145-5p expression was decreased while cell apoptosis and Rho-associated coiled-coil-containing kinase 1 (ROCK1) expression were increased in H/R-stimulated H9c2 cardiomyocytes. The upregulation of miR-145-5p reduced apoptosis and the expression of ROCK1 in H/R-stimulated H9c2 cardiomyocytes. Furthermore, the overexpression of ROCK1 significantly attenuated the miR-145-5p-induced reduction of apoptosis following H/R. In conclusion, the present study indicates that the overexpression of miR-145-5p inhibits H/R-induced cardiomyocyte apoptosis by targeting ROCK1.

Understanding the psychiatric symptoms of COVID-19: a meta-analysis of studies assessing psychiatric symptoms in Chinese patients with and survivors of COVID-19 and SARS by using the Symptom Checklist-90-Revised.

Understanding the psychiatric symptoms of COVID-19 could facilitate the clinical management of COVID-19 patients. However, the profile of psychiatric symptoms among COVID-19 patients has been understudied. We performed a meta-analysis of studies assessing psychiatric symptoms of COVID-19 and SARS patients and survivors by using the Symptom Checklist-90-Revised (SCL-90-R), an instrument covering a wide spectrum of psychiatric symptoms. Studies reporting SCL-90-R subscale scores among patients with and survivors of COVID-19 and SARS were retrieved from major English and Chinese literature databases. Patients' pooled SCL-90-R subscale scores were compared to the Chinese normative SCL-90-R data, and Cohen's d values were calculated to indicate the severity of psychiatric symptoms. The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess the quality of the included studies. The search yielded 25 Chinese studies with 1675 acute COVID-19 and 964 acute SARS patients, 30 COVID-19 and 552 SARS survivors during very early recovery (up to 1 month since discharge), 291 SARS survivors during early recovery (1-6 months after discharge), and 48 SARS survivors during late recovery (12 months after discharge). None of the included studies were rated as good quality. The ten SCL-90-R-defined psychiatric symptoms, which were of medium-to-severe severity (d = 0.68-3.01), were all exhibited in acute COVID-19 patients, and the severity of these symptoms decreased to mild-to-medium during very early recovery (d = 0.17-0.73). SARS patients presented eight psychiatric symptoms with mild-to-severe severity during the acute stage (d =0.43-1.88), and thereafter, the severity of symptoms decreased over the follow-up period. However, somatization (d = 0.30) and anxiety (d = 0.28) remained at mild levels during late recovery. A wide variety of severe psychiatric symptoms have been reported by acute COVID-19 patients, and these symptoms, despite decreasing in severity, persist in very early recovery. The changing trajectory observed with SARS suggests that psychiatric symptoms of COVID-19 may persist for a long time after discharge, and therefore, periodic monitoring of psychiatric symptoms, psychosocial support, and psychiatric treatment (when necessary) may be necessary for COVID-19 patients from the acute to convalescent stages.

Effects of different statins application methods on plaques in patients with coronary atherosclerosis.

BACKGROUND: Discontinued application of statins may be related to adverse cardiovascular events. However, it is unclear whether different statins administration methods have effects on coronary artery plaques. AIM: To evaluate the effects of different statins application methods on plaques in patients with coronary atherosclerosis. METHODS: A total of 100 patients diagnosed with atherosclerotic plaque by coronary artery computed tomography were continuously selected and divided into three groups according to different statins administration methods (discontinued application group, n = 32; intermittent application group, n = 39; sustained application group, n = 29). The effects of the different statins application methods on coronary atherosclerotic plaque were assessed. RESULTS: The volume change and rate of change of the most severe plaques were significantly reduced in the sustained application group (P ≤ 0.001). The volume change of the most severe plaques correlated positively with low-density lipoprotein (LDL-C) levels only in the sustained application group (R = 0.362, P = 0.013). There were no changes in plaques or LDL-C levels in the intermittent and discontinued application groups. CONCLUSION: Continuous application of statins is effective for controlling plaque progression, whereas discontinued or intermittent administration of statins is not conducive to controlling plaques. Only with continuous statins administration can a reduction in LDL-C levels result in plaque volume shrinkage.