BACKGROUNDAfter the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute ...neurological sequelae, known as "long COVID" - even those without specific neurological manifestations in the acute phase.METHODSDynamic brain changes are crucial for a better understanding and early prevention of "long COVID." Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge.RESULTSOverall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases.CONCLUSIONOur study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of "long COVID" and early clinical guidance toward complete recovery.FUNDINGNational Natural Science Foundation of China.
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible airflow limitation. The current medications show limited effects on the decline of pulmonary ...function in COPD. Our multicenter clinical trial found that Bu-Shen-Fang-Chuan fomula (BSFCF), a Chinese herbal formula, markedly reduced the frequencies of acute exacerbation of COPD and delayed lung function decline. However, the underlying mechanisms are still unclear. In this study, we established a COPD rat model through a 6-month exposure to cigarette smoke (CS) and found that BSFCF (7.2 g/kg) effectively improved CS-induced reduction in pulmonary function and remarkably decreased the numbers of inflammatory cells in bronchoalveolar lavage fluid (BALF). Importantly, BSFCF treatment notably prevented the accumulation of T-lymphocytes (especially CD8+ T-cells) in the lung of COPD rats. RNA sequencing analysis of lung tissue demonstrated that CXCL9/CXCL10/CXCL11-CXCR3 chemokine axis in the lung of CS-exposed rats was significantly suppressed by BSFCF. Moreover, our Real-time PCR data verified that BSFCF evidently inhibited the mRNA expressions of CXCL9, CXCL10, CXCL11 and CXCR3. Conclusively, BSFCF markedly improved pulmonary function and attenuated CD8+ T-cells recruitment in the lung of CS-exposed rats, which were partially through inhibition of CXCL9/CXCL10/CXCL11-CXCR3 axis.
Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of ...secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577,
p
= 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124,
p
= 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664,
p
= 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.
Bronchiolitis is a clinical syndrome commonly encountered in practice, particularly among infants and young children. To investigate the prevalence of pathogens in hospitalized children with ...bronchiolitis and study the clinical characteristics of bronchiolitis with or without coinfections.
We investigated the respiratory specimens and clinical data of 1012 children with bronchiolitis who were treated at the Children's Hospital of Soochow University between November 2011 and December 2018. The nasopharyngeal aspirates were examined to detect viruses by direct immunofluorescence assay or polymerase chain reaction (PCR). Mycoplasma pneumoniae (MP) was tested by PCR and enzyme-linked immunosorbent assay.
Of the 1134 children less than 2 years with bronchiolitis, 122 were excluded by exclusion criteria. Causative pathogen was detected in 83.2% (842 of 1012). The majority of these (614 72.9% of 842) were single virus infection. The most common pathogens detected were respiratory syncytial virus (RSV) (44.4%), MP (15.6%), and human rhinovirus (HRV) (14.4%). Coinfection was identified in 13.5% (137 of 1012) of the patients. Coinfection included mixed virus infection and virus infection with MP infection. Children with single virus infection had a higher rate of oxygen therapy compared with single MP infection.
The most common pathogen detected in children with bronchiolitis is RSV, followed by MP and HRV. Coinfection leads to a longer period of illness, increased severity of the symptoms and increased risk of hypoxemia.
Many studies have shown that microRNAs (miRNAs) exhibit altered expression in various cancers and may play an important role as prognostic biomarkers. The present meta-analysis was undertaken to ...summarize recent studies of the use of microRNA-145 (miR-145) in the assessment of prostate cancer and to analyze the prognostic role of miR-145 for disease-free survival (DFS) outcome.
The present meta-analysis was performed by searching PubMed with the use of multiple search strategies. Data were extracted from studies examining DFS in patients with prostate cancer who showed lower expression of miR-145. Pooled hazard ratios of miR-145 and 95% confidence intervals were calculated. Four studies with a total of 211 patients were included in this meta-analysis.
For overall DFS, the pooled hazard ratio of lower miR-145 expression in prostate cancer was 0.74 (95% confidence interval: 0.23–2.34, P = 0.001). Thus, lower miR-145 expression was found to significantly predict poorer outcomes.
The present findings suggest that downregulation of the expression of miR-145 might predict poor prognosis in patients with prostate cancer.
Small bowel obstruction is a common surgical emergency abdominal condition in clinical practice. Fecalith is one of the rare causative factors, especially phytobezoars.
We report the case of a ...66-year-old man admitted with "abdominal pain with vomiting for 1 day." Enhanced CT of the abdomen suggested incomplete small bowel obstruction. The symptomatic treatment with fasting, fluid replacement, gastrointestinal decompression, and antibiotics was conducted after the patient was admitted to the hospital. After 2 days of treatment, the patient's abdominal pain was not significantly relieved, so a decision was made to perform laparoscopic examination surgery. During surgery, a columnar foreign body was found embedded in the lumen of the small intestine about 10 cm away from the ileocecal region. Combined with the patient's preoperative history of consuming a large number of persimmons, the primary diagnosis of small intestinal fecalith obstruction was considered. We performed an enterotomy to remove the foreign body, and the procedure was uneventful. On postoperative day 7, the patient was successfully discharged.
When we encounter a patient with intestinal obstruction without a history of surgery in our clinical work, we should take a careful history, especially about the consumption of foods that can cause phytoliths. When a patient has consumed a large amount of food that can cause phytobezoars before the abdominal pain, we should diagnostically consider it as phytobezoars intestinal obstruction, which helps to reduce the incidence of misdiagnosis and allows the patient to receive treatment timely and effectively.
Anthocyanins contribute to most colors of plants and play protective roles in response to abiotic stresses.
Brassica napus
is widely cultivated worldwide as both an oilseed and a vegetable. However, ...only several high anthocyanin-containing cultivars have been reported, and the mechanisms of anthocyanin accumulation have not been well-elucidated in
B. napus
. Here, the phenotype, comparative whole-genome identification, and gene expression analysis were performed to investigate the dynamic change of the anthocyanin content and the gene expression patterns of anthocyanin biosynthetic genes (ABGs) in
B. napus
. A total of 152 ABGs were identified in the
B. napus
reference genome. To screen out the critical genes involved in anthocyanin biosynthesis and accumulation, the RNA-seq of young leaves of two
B. napus
lines with purple leaves (PL) or green leaves (GL), and their F
1
progeny at 41, 91, and 101 days were performed to identify the differentially expressed genes. The comparative expression analysis of these ABGs indicated that the upregulation of
TT8
together with its target genes (such as
DFR
,
ANS
,
UFGT
, and
TT19
) might promote the anthocyanin accumulation in PL at the early developmental stage (41–91 days). While the downregulation of those ABGs and anthocyanin degradation at the late developmental stage (91–101 days) might result in the decrease in anthocyanin accumulation. Our results would enhance the understanding of the regulatory network of anthocyanin dynamic accumulation in
B. napus
.
The safety and efficacy of dapoxetine for the treatment of premature ejaculation (PE) is still controversial. Thus, we decided to conduct a meta-analysis using trial sequential analysis (TSA) to ...determine the sufficiency of conclusions.
Evaluate the efficacy and safety of dapoxetine in the treatment of patients with PE and assess the reliability of the findings.
Meta-analysis of randomized controlled trials (RCTs).
Electronic databases including PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang data were reviewed up to July 2017. RCTs evaluating the efficacy of dapoxetine in patients with PE and reporting intravaginal ejaculatory latency time (IELT), patient global impression of change (PGIC) and/or adverse events (AEs) were included.
Mean differences between trials in efficacy for IELT, and risk ratios for PGIC and treatment-emergent AEs.
8 RCTs.
For IELT and PGIC, significant effects were found for all doses of dapoxetine versus placebo, and similar results were obtained in subgroups of the 30-mg dose versus 60-mg dose. There were also statistically different dose-related effects on AEs. Trial sequential analysis showed that the result of our meta-analysis was confirmed and further trials are unnecessary.
The evidence suggests that dapoxetine may be a safe and effective drug for patients with PE.
Not registered, no published protocol.
No relationship with manufacturer of drug.
Abstract
Background
Various factors have been found to be associated with high levels of death anxiety experienced by oncology nurses. The aim of this study was to use a person-oriented approach to ...examine the death anxiety patterns of Chinese oncology nurses and to analyze the differences in anxiety characteristics and their associated influencing factors.
Methods
A cross-sectional survey regarding palliative care among registered oncology nurses was conducted in Jiangsu Province, China.Latent class analyses was applied to identify their patterns of death anxiety. The score of PCQN-C (The Chinese version of the Palliative Care Quiz for Nursing) and FATCOD-B-C (The Chinese version of the Frommelt Attitude Toward Care of the Dying scale), the demographic and working characteristics were further analyzed through covariance analysis (ANCOVA) and multivariate (or logistic) regression across the subgroups.
Results
A two-potential-category model was selected based on the fit index. The results showed that 79% of oncology nurses belonged to the high pressure and pain group and 21% belonged to the low death anxiety group. The high pressure and pain group had significantly higher scores in the dimensions of emotion, stress and pain, time awareness, and cognition compared to the low death anxiety group. Factors influencing the high pressure and pain group included shorter working years, non-national or provincial oncology nursing specialists, non-national palliative care specialists, never discussing the topic of death with patients or family members, no palliative care related training, and PCQN and FATCOD scores.
Conclusions
Our study suggests that oncology nurses’ death anxiety can be divided into two categories: low death anxiety and high stress pain, and certain factors, such as being female, having a short work experience, and lacking palliative care-related training, increase the likelihood of death anxiety.
Juglone is a natural pigment, which has cytotoxic effect against various human tumor cells. However, its cytotoxicity to glioma cells, especially to tumor stem-like cells (TSCs) has not been ...demonstrated.
TSCs of glioma were enriched from U87 and two primary cells (SHG62, and SHG66) using serum-free medium supplemented with growth factors, including bFGF, EGF and B27. After treatment of juglone with gradient concentrations (0, 10, 20, and 40 μM), the viability and apoptosis of TSCs were evaluated by WST-8 assay and flow cytometry. Reactive oxygen species (ROS) was labeled by the cell-permeable fluorescent probe and detected with flow cytometry. ROS scavenger (NAC) and p38-MAPK inhibitor (SB203580) were applied to resist the cytotoxic effect. Caspase 9 cleavage and p38 phosphorylation (P-p38) were quantified by western blot. Juglone as well as temozolomide (TMZ) were administrated in intracranial xenografts and MR scan was performed every week to evaluate the anti-tumor effect in vivo.
Juglone could obviously inhibit the proliferation of TSCs in glioma by decreasing cell viability (P < 0.01) and inducing apoptosis (P < 0.01), which was accompanied by increased caspase 9 cleavage in a dose-dependent manner (P < 0.01). In the meantime, juglone could generate ROS significantly and increase p38 phosphorylation (P < 0.01). In addition, pretreatment with ROS scavenger or p38-MAPK inhibitor could reverse juglone-induced cytotoxicity (P < 0.01). More importantly, juglone could also suppress tumor growth in vivo and improve the survival of U87-bearing mice compared with control (P < 0.05), although TMZ seemed to have better effect.
Juglone could inhibit the growth of TSCs in gliomas through the activation of ROS-p38-MAPK pathway in vitro, and the anti-glioma effect was validated in vivo, which offers a potential therapeutic agent to gliomas.
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