Application of Non-Invasive Ventilator in Treatment of Severe COVID-19 Patients.

BACKGROUND: Since December 2019, there has been a global outbreak of COVID-19. As of the end of July 2020, more than 600,000 deaths had been reported globally. The purpose of this paper is to further explore the application of non-invasive ventilation in severe COVID-19 patients. METHODS: A retrospective study was conducted to included 57 confirmed COVID-19 patients, among which 36 cases were severe. According to different oxygen inhalation methods, they were divided into non-invasive ventilator assisted ventilation group with 21 cases (group A) and 15 cases of nasal catheter oxygen inhalation group (group B). The data of respiration (RR), heart rate (HR), partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygenation index (OI) before the treatment of noninvasive ventilator assisted ventilation or nasal catheter oxygen treatment at 24, 48, and 72 hours of treatment of the 2 groups were collected and analyzed to determine whether the above indicators were statistically different in each time period. RESULTS: After 24 hours of treatment with noninvasive ventilator assisted ventilation in group A, RR gradually decreased, PaO2 and OI were significantly higher than before treatment, while after 24 hours of treatment, PaO2, RR, HR and other indexes in group B showed no significant improvement, and OI increased gradually after 48 hours of treatment, with statistically significant difference compared with that before treatment. CONCLUSIONS: Early adoption of non-invasive ventilation can effectively improve the hypoxic state of patients with severe COVID-19. The combination of underlying diseases will not prolong the use of non-invasive ventilation.

Comparative study of hematological and radiological feature of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia.

OBJECTIVES: This study aimed to explore clinical indexes for management of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia by comparing hematological and radiological characteristics. METHODS: Severe/critically ill patients with COVID-19, H7N9, and H1N1 pneumonia were retrospectively enrolled. The demographic data, clinical manifestations, hematological parameters, and radiological characteristics were compared. RESULTS: In this study, 16 cases of COVID-19, 10 cases of H7N9, and 13 cases of H1N1 who met severe/critically ill criteria were included. Compared with COVID-19, H7N9 and H1N1 groups had more chronic diseases (80% and 92.3% vs. 25%, p < 0.05), higher APACHE Ⅱ scores (16.00 ± 8.63 and 15.08 ± 6.24, vs. 5.50 ± 2.58, p < 0.05), higher mortality rates (40% and 46.2% vs. 0%, p < 0.05), significant lymphocytopenia (0.59 ± 0.31 × 109 /L and 0.56 ± 0.35 × 109 /L vs. 0.97 ± 0.33 × 109 /L, p < 0.05), and elevated neutrophil-to-lymphocyte ratio (NLR; 14.67 ± 6.10 and 14.64 ± 10.36 vs. 6.29 ± 3.72, p < 0.05). Compared with the H7N9 group, ground-glass opacity (GGO) on chest CT was common in the COVID-19 group (p = 0.028), while pleural effusion was rare (p = 0.001). CONCLUSIONS: The NLR can be used as a clinical parameter for the predication of risk stratification and outcome in COVID-19 and influenza A pneumonia. Manifestations of pleural effusion or GGO in chest CT may be helpful for the identification of different viral pneumonia.

Improved production of GTKO/hCD55/hCD59 triple-gene-modified Diannan miniature pigs for xenotransplantation by recloning.

Multiple genetic modification is necessary for successful xenotransplantation from pigs. However, multiple-genetically modified cells usually suffer from various drug selections and long-term in vitro culture, which have a poor performance for somatic cell nuclear transfer (SCNT) to produce genetically modified pigs. We used to generate GTKO/hCD55/hCD59 triple-gene modified pigs by using drug-selective cell lines for SCNT, but the majority of cloned pigs were transgenic-negative individuals. In this study, to improve the production efficiency of multiple genetically modified pigs, we performed the recloning process by using transgenic porcine fetal fibroblast cells. As a result, two fetuses expressing hCD55 and hCD59 were obtained from 12 live-cloned fetuses, and one carrying high transgene expression was selected as a source of donor cells for recloning. Then we obtained 12 cloned piglets, all GTKO and carrying hCD55 and hCD59. Both hCD55 and hCD59 were expressed in fibroblast cells, but the expression levels of hCD55 and hCD59 were different among these piglets. Furthermore, piglet P5# had the highest expression of hCD55 and hCD59 in fibroblast cells than other piglets. Correspondingly, fibroblast cells of piglet P5# had significantly higher resistance against human serum-mediated cytolysis than those of piglet P11#. In conclusion, our results firstly provide support for improving efficiency of generating multiple genetically modified pig by recloning.

Expression profiling of planarians shed light on a dual role of programmed cell death during the regeneration.

Most animals hold the ability to regenerate damaged cells, tissues, and even any lost part of their bodies. To date, there is little known about the precise regulatory mechanism of regeneration and many fundamental questions remain unanswered. To further understand the precise regulatory mechanism of regeneration, we used planarian Dugesia japonica as a model and sequenced the transcriptomes of their regenerated tissues at different regeneration stages. Through de novo assembly and expression profiling, we found that Heat shock protein and MAPK pathway were involved into early response of regeneration in D. japonica. In addition, immune response, cell proliferation, and migration were activated during regeneration. Of notes, our results revealed a specific functional role of programmed cell death (PCD) in regeneration of D. japonica. PCD may not only remove the damaged and superfluous tissues for further patterning with regenerated tissues, but also provide signals to trigger neoblasts proliferation and differentiation directly. Together, our results revealed Heat shock protein and MAPK pathway mediated early response of regeneration and found a dual role of PCD in regeneration D. japonica. Meanwhile, we constructed regulatory networks of apoptosis, autophagy, and related signaling pathways and proposed a schematic model, which provided a global landscape of regeneration.

The role of klotho in chronic kidney disease.

Chronic kidney disease (CKD) is an inherently systemic disease that refers to a long-term loss of kidney function. The progression of CKD has repercussions for other organs, leading to many kinds of extrarenal complications. Intensive studies are now being undertaken to reveal the risk factors and pathophysiological mechanism of this disease. During the past 20 years, increasing evidence from clinical and basic studies has indicated that klotho, which was initially known as an anti-aging gene and is mainly expressed in the kidney, is significantly correlated with the development and progression of CKD and its complications. Here, we discuss in detail the role and pathophysiological implications of klotho in ion disorders, the inflammation response, vascular calcification, mineral bone disorders, and renal fibrosis in CKD. Based on the pathogenic mechanism of klotho deficiency and klotho decline in urine early in CKD stage 2 and even earlier in CKD stage 1, it is not difficult to understand that soluble klotho can serve as an early and sensitive marker of CKD. Moreover, the prevention of klotho decline by several mechanisms can attenuate renal injuries, retard CKD progression, ameliorate extrarenal complications, and improve renal function. In this review, we focus on the functions and pathophysiological implications of klotho in CKD and its extrarenal complications as well as its potential applications as a diagnostic and/or prognostic biomarker for CKD and as a novel treatment strategy to improve and decrease the burden of comorbidity in CKD.

High-throughput LC-MS method for the rapid characterization of multiple chemical constituents and metabolites of Da-Bu-Yin-Wan.

Traditional Chinese medicine is the clinical experience accumulated by Chinese people against diseases. Da-Bu-Yin-Wan is a famous traditional Chinese medicine formula consisting of Phellodendri amurensis Rupr., Anemarrhenae asphodeloides Bge., Radix Rehmanniae Preparata and Chinemys reevesii. In this study, ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight high-definition mass spectrometry with the control software of Masslynx (V4.1) was established for comprehensive screening and identification of the chemical constituents and serum metabolites of Da-Bu-Yin-Wan in vivo and in vitro. Consequently, 70 peaks in the methanol extract from Da-Bu-Yin-Wan and 38 peaks absorbed into rat blood were characterized. The 70 constituents in vitro included alkaloids, flavonoids, polysaccharide, limonoids, flavonoid, etc. And the 38 constituents consist of 22 absorbed prototypes and 16 metabolites of Da-Bu-Yin-Wan absorbed in vivo. We fully clarified the chemical constituents of Da-Bu-Yin-Wan and provided a scientific strategy for the screening and characterization of the chemical constituents and metabolites of traditional Chinese medicine in vitro and in vivo.

The interaction effects of risk factors for hypertension in adults: a cross-sectional survey in Guilin, China.

BACKGROUND: The prevalence of hypertension in adults is increasing each year and has become a main public health issue worldwide. We must consider the impact of both individual factors and interactions among these factors on hypertension in adults. This study was designed to elucidate the clinical and metabolic characteristics of the prevalence of hypertension in adults and to explore the risk factors and interactions among these factors in adults with hypertension. METHODS: We used overall random sampling to conduct a cross-sectional survey of 6660 individuals undergoing a health check from July to November 2012, the subjects were aged 20 to 89 years, including 3480 men and 3180 women. The survey content included a questionnaire, anthropometry, laboratory measurements, and liver Doppler ultrasonography. The clinical and metabolic characteristics were compared between the cases (adult hypertensive patients) and the controls (normotensives). The classification tree model and the non-conditional logistic regression were used to analyze the interactions of risk factors for hypertension in adults. RESULTS: In total, 1623 adult hypertensive patients (940 men and 683 women) were detected. The results showed that adult hypertensive patients were older and had higher levels of systolic blood pressure, diastolic blood pressure, body mass index, fasting plasma glucose, uric acid, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and prevalence of non-alcoholic fatty liver disease (P < 0.001). The classification tree model comprising 5 layers, 39 nodes, and 20 terminal nodes showed that two variables, age and BMI, were closely related to hypertension in adults. The area under the receiver operating characteristic curve for classification tree model was 81.6 % (95 % CI: 80.6 % ~ 82.5 %). Both univariate and multivariate logistic regression analyses revealed that advanced age and high BMI had a significant positive interaction in terms of hypertension in adults. After controlling for confounding factors, the percentage of attributed interaction was 47.62 %. CONCLUSIONS: This study showed that age, BMI, UA, TG, and TC were closely associated with the risk of hypertension in adults, and the positive interaction effect between advanced age and high BMI was an important risk factor for the prevalence of hypertension in adults.

Rapid discovery of absorbed constituents and metabolites in rat plasma after the oral administration of Zi Shen Wan using high-throughput UHPLC-MS with a multivariate analysis approach.

Zi Shen Wan is a typical formula consisting of three herbs, Phellodendri Amurensis Cortex, Rhizoma Anemarrhenae, and Cortex Cinnamomi, and has been widely used for treating prostatitis and infection diseases. However, it lacks in-depth research of the constituents of Zi Shen Wan in vivo and in vitro. In this work, ultra high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and MassLynx software was established to characterize the chemical compositions of Zi Shen Wan in vivo and in vitro. In total, 92 peaks were characterized in vitro and 33 peaks were characterized in vivo based on mass spectrometry and tandem mass spectrometry data. Among the 33 compounds characterized in rat plasma, 22 prototype components absorbed in rat serum and 11 metabolites were identified in vivo. This work was fully reports the chemical constituents of traditional Chinese formula of Zi Shen Wan, it demonstrated that ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry coupled to MassLynx software and multivariate data processing approach could be successfully applied for rapid screening and comprehensive analysis of chemical constituents in vitro and prototype components or metabolites in vivo of traditional Chinese medicine.

Identification and characterization of the chemical constituents of Simiao Wan by ultra high performance liquid chromatography with mass spectrometry coupled to an automated multiple data processing method.

The chemical constituents of Simiao Wan (SW), a traditional Chinese medicine preparation, are difficult to determine and remain unclear. To more efficiently detect ions, a multiple data processing approach has been used in the characterization of the compounds. In this study, a rapid and sensitive method based on ultra high performance liquid chromatography with mass spectrometry and the multiple data processing approach was established to characterize the chemical constituents of SW. Ultra high performance liquid chromatography with mass spectrometry coupled with the multiple data processing approach could efficiently remove nonrelated ion signals from accurate mass data. We report the application of the multiple data processing approach for comprehensive detection and rapid identification of chemical constituents of SW. Of note, the total analysis time for separation was less than 20 min without losing any resolution. In the variable, importance in projection plot of orthogonal projection to latent structure-discriminant analysis, a total of 72 ions of interest (37 ions in positive mode, 38 ions in negative mode and three ions in both mode) were extracted or tentatively characterized based on their retention times, exact mass measurement for each molecular ion and subsequent fragment ions. In summary, the methodology proposed in this study could be valuable for the structural characterization and identification of the multiple constituents in the traditional Chinese medicine formula SW.

Technology-enhanced higher education: Text mining and bibliometrics.

Objectives: Research on technology-enhanced higher education (TEHE) has been active and influential in educational technology. The study had three objectives: (1) to recognize the tendencies in the field and the contributing countries/regions/institutions, (2) to visualize scientific collaborations, and (3) to reveal important research topics, their developmental tendencies, correlations, and distributions across contributing countries/regions/institutions. Methods: We collected 609 papers in relation to TEHE from 2004 to 2022 and analyzed them using text mining and bibliometric methods. Specifically, we focused on determining article trends, identifying contributing institutions/countries/regions, visualizing scientific collaborations through social network analysis, and revealing the important topics and their conceptual evolutions over time using topic models, Mann-Kendall trend test, hierarchical clustering, and Sankey visualization. Results: Regarding the first objective, TEHE articles have grown consistently and will continue to expand. This growth was due to the contributions of Spanish universities and institutions from other countries/regions such as the USA, the UK, Australia, Germany, China, and Turkey. Regarding the second objective, the exploration of regional and institutional collaborations through social networks revealed that geographically adjacent institutions tended to foster close collaborations, particularly among those sharing similar research interests. Nevertheless, more cross-regional collaborations are needed to advance TEHE research. Regarding the third objective, the analysis of topics highlighted research hotspots and emerging themes such as Massive Online Open Courses, AI and big data in education, Gamification and engagement, Learning effectiveness and strategies, Social networks and discussion forums, COVID-19 and online learning, and Plagiarism detection and learning analytics. Conclusions: This bibliometric study comprehensively analyzed the research landscape of TEHE research regarding contributors, collaborations, and research topics, and offers a glimpse into what the future may hold. It can be used as a guide for contributors to the field to identify the current research hotspots and emerging themes.

Meta-analysis of traditional Chinese medicine on chronic kidney disease.

OBJECTIVE: To explore the effect of traditional Chinese medicine (TCM) on the treatment of chronic kidney disease (CKD). METHODS: Databases were used for literature research until 16 December 2022, including PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Embase. After full-text screening, data were extracted by two researchers independently. The Cochrane ROB tool was applied for quality assessment. The heterogeneity was tested using the Chi-squared-based Q statistic test and the I2 statistic. RESULTS: The findings revealed that the use of TCM significantly improved the total effective rate (pooled odds ratio (OR) = 1.35, 95% confidence interval (CI) = [1.15, 1.57]), reduced the serum creatinine (SCr) level (pooled mean difference (MD) = -0.11, 95% CI = [-0.20, -0.03]), and increased the estimated glomerular filtration rate (eGFR, pooled MD = 3.76, 95% CI = [2.66, 4.87]) in patients with CKD, compared with non-TCM treatment. Meanwhile, TCM performed better effect on 24-h proteinuria (pooled MD = 0.17, 95% CI = [0.04, 0.31]) than non-TCM. No significant difference in the incidence of adverse events was found between TCM and non-TCM treatment (pooled OR = 0.63, 95% CI = [0.32, 1.24]). Sensitivity analysis demonstrated the stability of the pooled estimates. CONCLUSION: TCM has the advantage over non-TCM treatment and is worth popularizing and applying in the prevention and cure of CKD. PROSPERO REGISTRATION NUMBER: CRD42021279281.

Alleviation of metal stress in rape seedlings (Brassica napus L.) using the antimony-resistant plant growth-promoting rhizobacteria Cupriavidus sp. S-8-2.

This study investigated an effective strategy for remediating antimony (Sb)-contaminated soil using the bacterial strain screened from Sb-contaminated fern rhizospheres due to its superior growth-promoting, heavy-metal(loid) resistant, and antibiotic-tolerant characteristics. The strain that belongs to Cupriavidus sp. was determined by 16S rRNA sequencing and showed no morphological changes when grown with high concentrations of Sb (608.8 mg/L). The strain showed prominent indole acetic acid (IAA), phosphate-solubilizing abilities, and ACC deaminase activity under Sb stress. Moreover, IAA and soluble phosphate levels increased in the presence of 608.8 mg/L Sb. Inoculation of rape seedlings with Cupriavidus sp. S-8-2 enhanced several morphological and biochemical growth features compared to untreated seedlings grown under Sb stress. Inoculation of Cupriavidus sp. S-8-2 increased root weight by more than four-fold for fresh weight and over two-fold for dry weight, despite high environmental Sb. The strain also reduced Sb-mediated oxidative stress and malondialdehyde contents by reducing Sb absorption, thus alleviating Sb-induced toxicity. Environmental Scanning Electron Microscope (ESEM) imaging and dilution plating technique revealed Cupriavidus sp. S-8-2 is localized on the surface of roots. Identifying the Sb-resistant plant growth-promoting bacterium suggested its usefulness in the remediation of contaminated agricultural soil and for the promotion of crop growth. We highly recommend the strain for further implementation in field experiments.

Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression.

KRAS is the most commonly mutated oncogene in human cancer, and mutant KRAS is responsible for over 90% of pancreatic ductal adenocarcinoma (PDAC), the most lethal cancer. Here, we show that RNA polymerase II-associated factor 1 complex (PAF1C) is specifically required for survival of PDAC but not normal adult pancreatic cells. We show that PAF1C maintains cancer cell genomic stability by restraining overaccumulation of enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) driven by mutant Kras. Loss of PAF1C leads to cancer-specific lengthening and accumulation of pervasive transcripts on chromatin and concomitant aberrant R-loop formation and DNA damage, which, in turn, trigger cell death. We go on to demonstrate that the global transcriptional hyperactivation driven by Kras signaling during tumorigenesis underlies the specific demand for PAF1C by cancer cells. Our work provides insights into how enhancer transcription hyperactivation causes general transcription factor addiction during tumorigenesis.

Insertion of a Preserflo microshunt inside a non-valved glaucoma shunt to treat late-onset hypotony.

We present a case of advanced glaucoma with previously failed trabeculectomy who underwent a Baerveldt tube (BVT) insertion, with initial success. However, 9 months post BVT insertion he developed profound clinically significant hypotony. Two attempts at controlling this with suture exchange led to episodes of significant ocular hypertension, followed by hypotony each time. We describe a technique of using a cut segment of the novel, polystyrene-block-isobutylene-block- styrene (SIBs) based Preserflo Microshunt (Santen Inc., Miami, FL) inserted into the tip of a BVT to control late onset hypotony with success. IOP at 6 weeks was 12mmHg on two drops with complete resolution of the choroidal maculopathy.

Weight gain promotes the progression of IgA nephropathy in Asians: A protocol for systematic review and meta-analysis.

INTRODUCTION: The relationship between weight gain and progression of IgA nephropathy (IgAN) has been investigated by many researchers but remains controversial. The incidence of IgAN is significantly higher in Asia than in other regions. Therefore, we investigated the relationship between weight gain and primary IgAN in the Asian population. METHODS AND ANALYSIS: Seven databases were retrieved up to now. We stratified the included population by body mass index (BMI) and performed a meta-analysis of associated risk factors. OBJECTIVES: In this study, Asian IgAN patients with different BMI were grouped together to clarify the relationship between BMI and IgAN progression in Asian populations, so as to provide more ideas and treatment means for the prevention and treatment of IgAN in the future.

Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: A protocol for systematic review and meta-analysis.

INTRODUCTION: Ophiocordyceps sinensis(O. sinensis), a genus of ascomycete fungi, has been intensively studied in various disease models, which is a rich source of various bioactive compounds and used in the treatment for end-stage renal disease patients. This systematic review highlights the therapeutic roles of O. sinensis as adjuvant treatment for dialysis patients with clinical evidence. METHODS AND ANALYSIS: The systematic review will be performed according to the Cochrane Handbook for Systematic Reviews of Interventions. The protocol is being reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Statement. An literature search strategy will be developed and adapted for 9 databases. Searches will be run from the database inception until the date of the search implementation and be updated before the review is completed. Randomized controlled trials that investigate the effects of O. sinensis for dialysis patients (peritoneal dialysis and hemodialysis) will be included. We will focus on outcomes recommended by the core outcome measures in effectiveness trials, including mortality, cardiovascular disease, infection, vascular access problems, dialysis adequacy, hyperkalaemia, life participation. Two researchers will independently screen the studies, extract data and evaluate study quality using the Risk of Bias 2 tool. Subgroup analysis will be performed according to peritoneal dialysis and hemodialysis. Sensitivity analyses will be conducted based on the Leave-1-Out Method. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to rate the quality of the evidence. Meta analysis will be performed using Review Manager 5.3 and R packages. OBJECTIVES: Studies have reported positive results of O. sinensis as adjuvant treatment for patients with dialysis. This review will synthesis current evidence on how O. sinensis can improve dialysis. Thus, it is expected that robust and conclusive evidence of the effects of O. sinensis during or after treatment can be obtained. These findings can inform future research and the selection of O. sinensis to promote quality of life for people with dialysis.

Efficacy of Traditional Chinese Medicine on Animal Model of IgA Nephropathy: A Systematic Review and Meta-Analysis.

Objective: Traditional Chinese medicine (TCM) has a long history in the treatment of Immunoglobulin A nephropathy (IgAN). A large number of animal experiments focused on the TCM treatment of IgAN are conducted every year. The evidence for these preclinical studies is not clear. This study summarized and evaluated the results of animal experiments on TCM treatment for IgAN. Methods: We systematically searched animal studies from 6 databases from inception to August 30, 2022. We included Chinese studies from the key magazine of China technology. The quality of the included studies was evaluated with the SYRCLE animal experimental bias risk assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Out of 832 records identified in the initial search, 30 studies were selected. The results indicated that, compared with the control group, the TCM treatment group improved 24 h urine protein (24 h-UP) level (standardized mean difference (SMD) 3.57, 95% confidence interval (CI) 4.48 to 2.66, P < 0.001), urine red blood cell (U-RBC) (SMD 13.66, 95% CI 17.99 to 9.32, P < 0.001), serum creatinine (Scr) (mean difference (MD) 10.89, 95% CI 17.00 to 4.77, P < 0.001), blood urea nitrogen (BUN) (MD 2.44, 95% CI 3.42 to 1.47, P < 0.001), tumor necrosis factor-α (TNF-α) (MD 171.28 to 95% CI 323.68 to 18.88, P=0.03), transforming growth factor-ß1 (TGF-ß) (SMD 4.02, 95% CI 7.26 to 0.77, P=0.02), matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1(MMP-9/TIMP-1) (MD 0.03, 95% CI 0.00 to 0.06, P=0.02), nephrin mRNA (SMD 3.39, 95% CI 2.59 to 4.18, P < 0.001). However, there is no difference in albumin level (MD 1.10, 95% CI 0.06 to 2.26, P=0.06) and interleukin-6 (IL-6) (MD 170.77, 95% CI 365.3 to 23.75, P=0.09). Conclusions: TCM can improve 24 h-UP, U-RBC, Scr, BUN, MMP-9/TIMP-1, TNF-α, TGF-ß, and nephrin mRNA of IgAN animal models. Moreover, there is a need for rigorous reporting of preclinical research methodology, which is essential to support the quality of preclinical research. Registration. This review was registered with a systematic review record CRD42020171404 in the PROSPERO database.

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders.

Major depressive disorder (MDD) is a common and complex mental disorder, that adversely impacts an individual's quality of life, but its diagnosis and treatment are not accurately executed and a symptom-based approach is utilized in most cases, due to the lack of precise knowledge regarding the pathophysiology. So far, the first-line treatments are still based on monoamine neurotransmitters. Even though there is a lot of progress in this field, the mechanisms seem to get more and more confusing, and the treatment is also getting more and more controversial. In this study, we try to review the broad advances of monoamine neurotransmitters in the field of MDD, and update its effects in many advanced neuroscience studies. We still propose the monoamine hypothesis but paid special attention to their effects on the new pathways for MDD, such as inflammation, oxidative stress, neurotrophins, and neurogenesis, especially in the glial cells, which have recently been found to play an important role in many neurodegenerative disorders, including MDD. In addition, we will extend the monoamine hypothesis to basic emotions; as suggested in our previous reports, the three monoamine neurotransmitters play different roles in emotions: dopamine-joy, norepinephrine-fear (anger), serotonins-disgust (sadness). Above all, this paper tries to give a full picture of the relationship between the MDD and the monoamine neurotransmitters such as DA, NE, and 5-HT, as well as their contributions to the Three Primary Color Model of Basic Emotions (joy, fear, and disgust). This is done by explaining the contribution of the monoamine from many sides for MDD, such the digestive tract, astrocytes, microglial, and others, and very briefly addressing the potential of monoamine neurotransmitters as a therapeutic approach for MDD patients and also the reasons for its limited clinical efficacy, side effects, and delayed onset of action. We hope this review might offer new pharmacological management of MDD.

Inhibition of FOXO1­mediated autophagy promotes paclitaxel­induced apoptosis of MDA­MB­231 cells.

Triple­negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it often becomes resistant to paclitaxel (PTX) therapy. Autophagy plays an important cytoprotective role in PTX­induced tumor cell death, and targeting autophagy has been promising for improving the efficacy of tumor chemotherapy in recent years. The aim of the present study was to clarify the mechanism of PTX inducing autophagy in TNBC cells to provide a potential clinical chemotherapy strategy of PTX for TNBC. The present study reported that PTX induced both apoptosis and autophagy in MDA­MB­231 cells and that inhibition of autophagy promoted apoptotic cell death. Furthermore, it was found that forkhead box transcription factor O1 (FOXO1) enhanced PTX­induced autophagy through a transcriptional activation pattern in MDA­MB­231 cells, which was associated with the downstream target genes autophagy related 5, class III phosphoinositide 3­kinase vacuolar protein sorting 34, autophagy related 4B cysteine peptidase, beclin 1 and microtubule associated protein 1 light chain 3ß. Knocking down FOXO1 attenuated the survival of MDA­MB­231 cells in response to PTX treatment. These findings may be beneficial for improving the treatment efficacy of PTX and to develop autophagic targeted therapy for TNBC.

Risk Factors for Radiological Progression Within Admissive One Week in the Hospitalized COVID-19 Omicron Variant-Infected Patients.

Purpose: Recently, the SARS-CoV-2 Omicron variant was identified as responsible for a novel wave of COVID-19 worldwide. We perform a retrospective study to identify potential risk factors contributing to radiological progression in the COVID-19 patients due to the Omicron variant infection. These findings would provide guiding information for making clinical decisions that could improve the Omicron infection prognosis and reduce disease-related death. Methods: This is a retrospective cohort study from a single center in China. According to the radiological change within admissive one week, enrolled cases were divided into two groups: the progressive (1w-PD) and the stable or improved disease (1w-non-PD). Separate analyses were performed on patients stratified into subgroups using the Mann-Whitney U-test, the Fisher exact test, or the Chi-squared test and a multivariable logistic regression analysis. Results: Both the 1w-non-PD and 1w-PD cohorts displayed comparable asymptomatic infection, have similar underlying disease, impairment in respiratory function, coagulation dysfunction, tissue injury, SARS-CoV-2 viral load, and disease severity. However, the 1w-PD cohort was more inclined to cluster in populations presented with age between 41 and 65, higher CURB-65 scores, undetectable SARS-CoV-2 IgG, and lung affection. Based on the multiple logistic regression analysis, complicated bilateral and ground-glass opacities (GGOs) like pneumonia at admission were independent risk factors to radiological progression within admissive one week. Conclusion: This study provided preliminary data regarding disease progression in Omicron-infected patients that indicated the development of pneumonia in the context of Omicron infection was worthy of potential risk factors.