Multisite spontaneous hematomas and bleeding in critically ill Chinese patients with COVID-19: two case reports and a literature review.

BACKGROUND: Anticoagulation is recommended as a standardized therapy for COVID-19 patients according to the WHO guidelines. However, bleeding events have also been reported. Hemorrhage or hematoma was observed in sites including the retroperitoneum, brain, alimentary tract, muscles, and soft tissues. Reduction or suspension of anticoagulants is a common intervention. Transfusion, endoscopic hemostasis, and vascular interventional therapy have been used to improve the condition. CASE PRESENTATION: In this article, we present two cases of concurrent multisite hematomas and bleeding at other sites in patients with SARS-CoV-2 infection. Both patients were treated with heparins and experienced bleeding after the anticoagulation therapy. Both patients were older with more than two comorbidities, and critical COVID-19. Laboratory tests revealed a considerable decrease in hemoglobin levels and alterations in the coagulation system. In the first patient, the main intervention was embolization using angiography. However, we only adjusted the anticoagulation strategy in the second case. The first patient recovered and was discharged; however, the second died of other causes. This study provides a retrospective review of typical hemorrhagic cases during anticoagulation in COVID-19 patients over the course of four years. A relatively comprehensive search was performed in Pubmed by constructing MeSH subject terms on limiting the search period and specific contents. It summarizes and synthesizes the research related to heparins and other novel anticoagulants in the context of COVID-19 from the onset of the pandemic to the present disseminated phase. This study aimed to offer valuable insights and reference points for developing anticoagulation treatment strategies for patients with COVID-19. CONCLUSIONS: Anticoagulation is a crucial treatment option for patients with COVID-19. The difference in anticoagulant effects is related to the severity of COVID-19. Nafamostat can reduce thrombosis in the extracorporeal circuits in critically ill patients with COVID-19. The efficacy and safety of novel anticoagulants require further clinical data. Routine bedside assessments and real-time laboratory monitoring are essential for early identification of bleeding events during anticoagulant therapy and administering intervention.

LncRNA NR2F1-AS1 Inhibits the Malignant Properties of Cervical Cancer Cells via Targeting miR-642a-3p/NR2F1 Axis.

Background: Cervical cancer (CC), as a serious menace to the health of women, has long been one of the most lethal gynecologic neoplasms throughout the world. Long non-coding RNA (LncRNA) NR2F1-AS1 has been documented to exert crucial functions in many malignant tumors. Nonetheless, the function and molecular mechanism of NR2F1-AS1 in CC remain completely unknown. Objectives: This study aimed to explore the function and molecular mechanism of NR2F1-AS1 in CC. Methods: The expression levels of NR2F1-AS1, miR-642a-3p, NR2F1 in CC tissues, and cell lines were examined by reverse transcription real-time quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation and Transwell assays. The protein levels of epithelial-mesenchymal transition markers and NR2F1 in CC cells were assessed by Western blot analysis. The correlations among NR2F1-AS1, miR-642a-3p, and NR2F1 were estimated through luciferase reporter and RNA immunoprecipitation assays. Results: NR2F1-AS1 expression was clearly downregulated in CC tissues and cell lines. Molecular mechanistic experiments showed that NR2F1-AS1 overexpression upregulated NR2F1 expression in CC cells by directly binding to miR-642a-3p, and inhibiting by this way cell viability, proliferation, migration, and invasion in CC. Rescue assays showed that NR2F1 knockdown or miR-642a-3p overexpression offset NR2F1-AS1 upregulation-induced inhibition on CC cell malignant phenotypes. Conclusions: These findings revealed that NR2F1-AS1 played a tumor suppressor role in CC by mediating the miR-642a-3p/NR2F1 axis.

LncRNA NR2F1-AS1 Inhibits the Malignant Properties of Cervical Cancer Cells via Targeting miR-642a-3p/NR2F1 Axis

ABSTRACT Background: Cervical cancer (CC), as a serious menace to the health of women, has long been one of the most lethal gynecologic neoplasms throughout the world. Long non-coding RNA (LncRNA) NR2F1-AS1 has been documented to exert crucial functions in many malignant tumors. Nonetheless, the function and molecular mechanism of NR2F1-AS1 in CC remain completely unknown. Objective: This study aimed to explore the function and molecular mechanism of NR2F1-AS1 in CC. Methods: The expression levels of NR2F1-AS1, miR-642a-3p, NR2F1 in CC tissues, and cell lines were examined by reverse transcription real-time quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation and Transwell assays. The protein levels of epithelial-mesenchymal transition markers and NR2F1 in CC cells were assessed by Western blot analysis. The correlations among NR2F1-AS1, miR-642a-3p, and NR2F1 were estimated through luciferase reporter and RNA immunoprecipitation assays. Results: NR2F1-AS1 expression was clearly downregulated in CC tissues and cell lines. Molecular mechanistic experiments showed that NR2F1-AS1 overexpression upregulated NR2F1 expression in CC cells by directly binding to miR-642a-3p, and inhibiting by this way cell viability, proliferation, migration, and invasion in CC. Rescue assays showed that NR2F1 knockdown or miR-642a-3p overexpression offset NR2F1-AS1 upregulation-induced inhibition on CC cell malignant phenotypes. Conclusion: These findings revealed that NR2F1-AS1 played a tumor suppressor role in CC by mediating the miR-642a-3p/NR2F1 axis.

Treatment Strategy in Atrial Tachycardia Originating From the Atrial Appendage.

Background: Atrial appendage tachycardia (AAT) originating from the atrial appendage (AA) is extremely difficult to eliminate using radiofrequency catheter ablation (RFCA). The optimal management strategy for AAT refractory to RFCA remains unclear. Objective: This study aims to investigate the long-term result of ablative therapy and the optimal alternative management for AAT refractory to RFCA. Methods: A total of 51 patients with AAT originating from the AA undergoing RFCA were recruited. Video-assisted atrial appendectomy and oral ivabradine were performed on those with AATs refractory to RFCA, and this study aimed to evaluate their safety and long-term efficacy. Results: We included 51 patients (51/586, 8.7%) with AATs confirmed by activation mapping and contrast venography. Among them, there were 28 (54.9%) AATs originating from the distal AA. In total, 14 (27.4%) AATs were refractory to RFCA, including 13 originating from the distal AA and one arising from the proximal AA. Ten of 11 (90.9%) AATs originating from the distal AA were eliminated after an atrial appendectomy, and the other three AATs were suppressed using oral ivabradine. Origins from the distal AA refractory to RFCA and early age of AAT onset ≤26.5 years indicated the need for atrial appendectomy. No major complications occurred, and nine patients with tachycardia-induced cardiomyopathy fully recovered. Long-term success was achieved in 98.0% of patients with multiple treatment managements. Conclusion: AATs originating from the distal AA were more refractory to RFCA. RFCA was the cornerstone of AAT catheter ablation. Video-assisted thoracoscopic atrial appendectomy was an effective strategy for those origins at the distal AA and the age of AAT onset ≤26.5 years. Ivabradine represents a promising treatment for AAT temporarily in pediatric and young adult patients.

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box-Behnken Experimental Design.

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box-Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF's was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0-t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.

Effects of salt concentration, pH, and their interaction on plant growth, nutrient uptake, and photochemistry of alfalfa (Medicago sativa) leaves.

In order to explore the main limiting factors affecting the growth and physiological function of alfalfa under salt and alkali stress, the effect of the salt and alkali stress on the growth and physiological function of alfalfa was studied. The results showed that effects of the excessive salt concentration (100 and 200 mM) on the growth and physiological characteristics were significantly greater than that of pH (7.0 and 9.0). Under 100 mM salt stress, there was no significant difference in the growth and photosynthetic function between pH 9.0 and pH 7.0. Under the 200 mM salt concentration the absorption of Na+ by alfalfa treated at the pH 9.0 did not increase significantly compared with absorption at the pH 7.0. However, the higher pH directly reduced the root activity, leaf's water content, and N-P-K content also decreased significantly. The PSII and PSI activities decreased with increasing the salt concentration, especially the damage degree of PSI. Although the photoinhibition of PSII was not significant, PSII donor and electron transfer from the QA to QB of the PSII receptor sides was inhibited. In a word, alfalfa showed relatively strong salt tolerance capacity, at the 100 mM salt concentration, even when the pH reached 9.0. Thus, the effect on the growth and photosynthetic function was not significant. However, at 200 mM salt concentration, pH 9.0 treatment caused damage to root system and the photosynthetic function in leaves of alfalfa was seriously injured.

Etoposide and immunotherapy can improve the outcome of severe anti-GABAB R encephalitis presenting with delta brush: A case report.

RATIONALE: Anti-gamma-aminobutyric-acid B receptor (anti-GABAB R) encephalitis is clinically characterized by seizures, cognitive disorders, and behavioral changes. Most patients are diagnosed with small-cell lung carcinoma. PATIENT CONCERNS: The patient suffered from a repeated grand mal seizure lasting for 10 minutes, intermittent speech vagueness, manic at night, and mental disorder. DIAGNOSIS: The patient was diagnosed with autoimmune encephalitis. The gamma-aminobutyric-acid B(GABAB) receptor antibody test result was positive. After a bronchoscopic biopsy, the patient was diagnosed with small-cell lung carcinoma. INTERVENTIONS: The patient was administered with intravenous immunoglobulin and Methylprednisolone. Etoposide was used after the small-cell lung carcinoma was diagnosed. OUTCOMES: After immunotherapy, following the 4 months of Etoposide and antiseizure treatment, the neurology examination revealed a remarkable improvement. MRS score reduced from 5 to 1. Electroencephalogram (EEG) recovered to normal from an extreme delta brush (EDB) electroencephalographic-pattern. CONCLUSION: Immunotherapy and Etoposide can improve the outcome of severe anti-γ-aminobutyric acid B receptor encephalitis with small-cell lung carcinoma. After immunotherapy and antineoplastic therapy, Electroencephalogram (EEG) can be recovered to normal from an extreme delta brush.

Adverse reproductive function induced by maternal BPA exposure is associated with abnormal autophagy and activating inflamation via mTOR and TLR4/NF-κB signaling pathways in female offspring rats.

Bisphenol A (BPA) can affect reproductive function, but its mechanism of reproductive toxicity is unclear, and the effect of BPA on the onset of puberty was inconsistent. The main purpose of this study is to investigate the effects of perinatal exposure to BPA on the onset of puberty and reproductive function, and its mechanism from the aspect of autophagy and inflammation in ovarian and uterus tissues of female offspring. Twenty-one pregnant SD rats were randomly divided into three groups: Control group, 1 µg/mL BPA (LBPA) and 10 µg/mL BPA group (HBPA) via drinking water from gestational day 6 to the end of lactation. After weaning, female offspring rats were fed a normal diet and drinking water for 5 weeks. The levels of E2, LH, FSH, T, and IL-6 and TNF-α, and the onset of puberty, and morphological changes in ovarian and uterine were determined in female offspring at 8 weeks. The levels of TLR4, NF-κB, PI3K/Akt/mTOR and autophagy related protein in uterine tissue were also detected. Our results indicated that perinatal exposure to BPA advanced puberty, which was associated with increased serum E2, LH and FSH levels. There was a significantly thin endometrium epithelium in HBPA group compared with control group, which may affect reproductive function. The adverse effect of perinatal BPA exposure on reproductive function maybe was associated with the activation of inflammation and abnormal autophagy via TLR4/NF-κB and mTOR signaling pathways respectively in female offspring.

Outcomes of Reinterventions for Children with Postoperative Pulmonary Venous Restenosis.

This report aims to summarize and evaluate the efficacy and experience of reintervention for children with postoperative pulmonary venous restenosis. Clinical data from 61 patients with postoperative pulmonary venous restenosis who underwent reintervention at Shanghai Children's Medical Center (SCMC) from September 2009 to June 2018 were retrospectively analyzed. The patients comprised 38 boys and 23 girls, with a mean age of 15.4 ± 12.6 months (2-83 months) and a mean weight of 8.1 ± 3.4 kg (3.7-18.5 kg). The mean pulmonary venous velocity was 2.31 ± 0.47 m/s (1.86-3.22 m/s). Primary disease included 48 cases of total anomalous pulmonary venous drainage, nine cases of partial anomalous pulmonary venous drainage, and four cases of primary pulmonary venous stenosis. The reintervention procedures included 34 cases using the sutureless technique, ten cases using bovine pericardium enlargement, three cases using blunt enlargement, four cases of balloon dilatation, one case using stent implantation and nine cases involving more than two surgical methods. The early postoperative pulmonary venous velocity was 1.16 ± 0.20 m/s. There were five in-hospital deaths, resulting in a mortality rate of 8.2%. Fifty-six survivors were followed for 52.8 ± 46.5 months (6-103 months) with no delayed deaths. Echocardiography showed pulmonary venous anastomosis and diameter growth after reintervention, exhibiting a mean growth speed of 0.026 ± 0.013 cm/month (p < 0.05) and a mean velocity of 1.24 ± 0.26 m/s; five patients experienced varying degrees of pulmonary venous obstruction (> 1.6 m/s), but did not require reoperation. Postoperative pulmonary venous restenosis is a common complication after surgery for pulmonary venous malformations. Reintervention should be performed in the early period of pulmonary venous obstruction. Growth of pulmonary venous anastomoses was observed after performing the sutureless technique, bovine pericardium enlargement and blunt enlargement. Although balloon dilatation has a good effect in the early postoperative period, its restenosis rate is high, and strict mid- to long-term follow-up is needed.

Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy.

Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. In particular, we have designed immunoadjuvant nanomedicine carriers on the basis of polydopamine (PDA) simultaneously loaded with resiquimod (R848)-a kind of toll-like receptor 7 (TLR7) agonist-and carbon dots (CDs)-a fluorescent agent. This nanomedicine is defined as PDA-PEG-R848-CD nanoparticle (NP). The multitasking PDA-PEG-R848-CD NPs can destroy 4T1 breast tumors by PTT under near-infrared laser irradiation in addition to generating tumor-associated antigens. Moreover, the PTT effect triggered the release of R848, thereby inducing a strong antitumor immune response. Meanwhile, this synergistic therapy also shows the abscopal effects by completely inhibiting the growth of untreated distant tumors by effectively triggering the tumors infiltrated by CD3/CD8. Such findings suggest that PDA-PEG-R848-CD NPs could significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.

A Randomized Controlled Study of the Yi Qi Gu Biao Pill in the Treatment of Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease (Lung and Spleen Qi Deficiency Syndrome).

OBJECTIVE: To evaluate the efficacy and safety of Yi Qi Gu Biao (YQGB) pill in treating frequent exacerbator phenotype in chronic obstructive pulmonary disease (lung and spleen qi deficiency syndrome) (FEPCOPD). METHODS: This prospective, randomized, double-blind, controlled study assessed 112 cases (64 included) of FEPCOPD treated at the outpatient department in our hospital in January-August 2016. The patients were randomly divided into YQGB and placebo (Pb) and treated for three months. Lung function, CAT, mMRC, and TCM symptom scores (TCMs) were observed. RESULTS: Compared with Pb, YQGB showed decreased wheezing symptom scores (WSs) and TCMs at one month and decreased CAT and TCMs at three months. From one to three months, CAT, cough, sputum, WSs, and TCMs in YQGB were lower than pretreatment values. But in Pb, CAT was lower than pretreatment values after one month; CAT, sputum, and TCMs were lower than pretreatment values after two months; CAT, cough, sputum, WSs, and TCMs were lower than pretreatment values after three months. CONCLUSION: Yi Qi Gu Biao pill can improve wheezing, health status, and TCMs in FEPCOPD and also can shorten the durations of cough, sputum, and wheezing. This trial is registered in the Clinical Trials Registry of China: ChiCTR-IOR-15007542 (on 8 December 2015).

Investigations on the Flat-Detector Computed Tomography-Based CBV Map Acquisition Using a Left Ventricle Contrast Media Injection Protocol.

OBJECTIVES: Cerebral blood volume (CBV) acquired with the use of flat-detector computed tomography with contrast media (CM) injected at the ascending aorta provides real-time brain functional information with minimized CM usage; however, unexpected asymmetric perfusion is observed for certain patients without cerebral circulatory disorders. This work tested the feasibility of left ventricle (LV) CM injection to achieve symmetric perfusion. METHODS: CBV maps were acquired for 10 patients without perfusion-related cerebral abnormities. Perfusion symmetry was predicted with the use of color-coded quantitative digital subtracted angiography with CM injected at ascending aorta. Time density curves were extracted at bilateral common carotid arteries with area under curves calculated. Planes were selected on CBV maps with regions of interest defined covering characteristic regions, where asymmetric perfusion most likely to appear. RESULTS: No adverse physiological changes were detected for any patient. Non-uniform CM distributions were detected for 4 patients with relative area under curves 0.66 ± 0.03, indicating asymmetric perfusion using ascending aorta injection. With LV injection, all the patients demonstrated good perfusion symmetry with relative CBV 1.03 ± 0.07. CONCLUSION: CBV maps acquisition with LV injection offered an approach to acquire immediate brain functional information for patients who are limited by asymmetric perfusion using ascending aorta injection and are sensitive to CM dose.

Integrin ß6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy.

It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin αvß6 can contribute to malignant behavior of colon cancer. We have found that integrin αvß6 and eIF4E were co-expressed and positively correlated in colon cancer tissues. Recently, deregulation of the protein synthesis apparatus has begun to gain attention as a major participant in cancer development and progression. However, the regulation of integrin ß6 expression at translational level has never been investigated before. In present study, gene-silencing technique for eIF4E by small interfering RNA (siRNA) was used in all the subsequent experiments, in order to investigate whether eIF4E could translationally regulate expression of integrin ß6 in colon cancer SW480 and HT-29 cell lines. Additionally, the subsequent effects of eIF4E knockdown on cellular malignant behavior were observed. siRNA in SW480 and HT-29 transfectants. Subsequently, protein expression of ß6 was markedly suppressed, while mRNA expression of ß6 showed no significant variation before and after eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate the expression of ß6, without effect on ß6 mRNA expression. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT-29 and ß6-transfected SW480 as well as their survival to 5-FU was decreased distinctly. Expression of integrin ß6 could be translationally regulated by eIF4E, which subsequently contributed to tumor malignancy through enhancing cellular migration, survival, anti-apoptosis, and chemoresistance of colon cancer in vitro. Thus, targeting eIF4E in integrin αvß6 expressing tumors can be a potential therapeutic strategy for patients with colon cancer.

[Structure and biological functions of plant FKBP family].

FK506-binding proteins (FKBPs) are well known as both the receptor for the immunosuppressant drug FK506 and the prolyl isomerase (PPIase) enzyme. FKBPs are widely and constitutively expressed, and highly conserved during evolution. In higher plants, FKBPs usually form a relative large and diverse family compared with that in other eukaryotes, and serve as important molecular chaperones that interact with specific protein partners to regulate a diversity of cellular processes which mainly influence the plant development and stress responding. More recently, studies discovered a series of new interacting partners of FKBPs, which implicate FKBPs in gene expression regulation and photosynthetic adaptation. This review mainly focuses on the structural characteristics, classification, and the latest discoveries in the physiological functions of FKBPs in higher plants.

(E)-2-(2-Furylmethyl-idene)-2,3-dihydro-1H-pyrrolizin-1-one.

The title compound, C(12)H(9)NO(2), was prepared by an Aldol reaction of furfuraldehyde with 2,3-dihydro-1H-pyrrolizin-1-one. The mol-ecule is almost planar, with an r.m.s. deviation of 0.045 Å, excluding the methyl-ene H atoms. In the crystal structure, mol-ecules are linked via weak inter-molecular C-H⋯O hydrogen bonding and aromatic π-π stacking [centroid-centroid distance = 3.6151 (9) Å].

Potential cost-effectiveness of a rotavirus immunization program in rural China.

BACKGROUND: To assess the incidence and economic burden of rotavirus diarrhea and the potential cost-effectiveness of a rotavirus immunization program in rural Zhengding County in Hebei Province, China. METHODS: Population-based surveillance was conducted during the peak season for diarrhea among children who were <5 years of age in Zhengding County from 14 October 2004 through 19 January 2005. The cost of illness was measured from the perspectives of both patient and society. A decision-analytic model was applied to the cost-effectiveness analysis using real data derived from surveillance and from a cost-of-illness study. RESULTS: During the surveillance period, 500 episodes of diarrhea were registered. Of these 500 episodes, 125 (25%) occurred in patients who were positive for rotavirus. Of these 125 episodes, 63 (50%) occurred in patients who were hospitalized. The overall incidence rate of rotavirus infection was 61.4 cases per 1000 children per year during the 14-week epidemic season. For a Chinese cohort of 5000 newborns, a universal rotavirus immunization program would prevent 1764 cases of rotavirus diarrhea, averting 882 hospitalizations of patients