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Introduction Neuromuscular blockade suppresses transcranial electrical motor evoked potential (TceMEP) amplitude and is usually avoided during TceMEP monitoring. In this randomized controlled trial, we investigated whether rocuronium-induced suppression of TceMEP amplitude could be reversed by sugammadex in patients undergoing spine surgery. Methods Seventy-six patients undergoing spinal surgery were randomly allocated into sugammadex and control groups. In the sugammadex group, a rocuronium infusion was titrated to maintain moderate neuromuscular blockade (2 twitches on train-of-four) until dural opening when the rocuronium infusion was discontinued and 2 mg/kg sugammadex administered. In the control group, no neuromuscular blockade was administered after induction of anesthesia. The primary outcome was a comparison between sugammadex and control groups of mean TceMEP amplitudes in the abductor pollicis brevis muscles of both upper extremities 5 minutes after dural. Secondary outcomes included TceMEP amplitudes at 10, 20, 30, and 60 minutes after dural opening. Results Sixty-six patients were included in the analysis. TceMEP amplitudes were significantly greater in the sugammadex group (629 μV, interquartile range: 987 μV) than in the control group (502 μV, interquartile range: 577 μV; P=0.033) at 5 minutes after dural opening. TceMEP amplitudes were also greater in the sugammadex group at 10 minutes (P=0.0010), 20 minutes (P=0.003), 30 minutes (P=0.001), and 60 minutes (P=0.003) after dural opening. Conclusions Moderate neuromuscular blockade induced by continuous infusion of rocuronium was effectively reversed by sugammadex. This suggests that sugammadex could be used to enhance TceMEP waveform monitoring during spine surgery requiring muscle relaxation.

The residual antibiotics in different environmental media pose a serious threat to human health and the ecosystem. The high-efficient elimination of antibiotics is one of the foremost works. In this study, chloramphenicol (CAP) was eliminated efficiently by electrocatalytic advanced oxidation process with carbon nanotubes/agarose/indium tin oxide (CNTs/AG/ITO) electrode. The influences of different experimental parameters on the degradation efficiency were systematically studied. Under the optimal conditions (4 V potential, 10 wt% CNTs dosage, and pH = 10), the maximum degradation efficiency of CAP (20 mg L− 1) achieved 88% within 180 min. Besides, the electrocatalytic degradation pathway and mechanism for CAP were also investigated, •O2− played a major role in the process of electrocatalytic degradation. Based on the QSAR (quantitative structure-activity relationship) model, the toxicities of CAP and identified intermediates were analyzed. Compared with the parent compound, the maximal chronic toxicity of intermediate ((E)-3-(4-nitrophenyl)prop-1-ene-1,3-diol) for daphnid increased 197-fold. Besides, the hybrid toxicity of the degradation system was further confirmed via disk agar biocidal tests with Escherichia coli ATCC25922, which changed slightly during the degradation process. Based on the above results, it is worth noting that the degradation pathway and toxicity assessment should be paid more attention to the treatment of antibiotic wastewater.

Background Arteriovenous fistulae (AVF) are the preferred mode of vascular access for hemodialysis. Before use, AVF remodel by thickening and dilating to achieve a functional conduit via an adaptive process characterized by expression of molecular markers characteristic of both venous and arterial identity. Although signaling via EphB4, a determinant of venous identity, mediates AVF maturation, the role of its counterpart EphrinB2, a determinant of arterial identity, remains unclear. We hypothesize that EphrinB2 signaling is active during AVF maturation and may be a mechanism of venous remodeling. Methods Aortocaval fistulae were created or sham laparotomy was performed in C57Bl/6 mice, and specimens were examined on Days 7 or 21. EphrinB2 reverse signaling was activated with EphB4-Fc applied periadventitially in vivo and in endothelial cell culture medium in vitro. Downstream signaling was assessed using immunoblotting and immunofluorescence. Results Venous remodeling during AVF maturation was characterized by increased expression of EphrinB2 as well as Akt1, extracellular signal-regulated kinases 1/2 (ERK1/2), and p38. Activation of EphrinB2 with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and was associated with increased diameter and wall thickness in the AVF. Both mouse and human endothelial cells treated with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and increased endothelial cell tube formation and migration. Conclusions Activation of EphrinB2 signaling by EphB4-Fc was associated with adaptive venous remodeling in vivo while activating endothelial cell function in vitro. Regulation of EphrinB2 signaling may be a new strategy to improve AVF maturation and patency.

Background Perioperative stroke is a rare but devastating complication. The risk factors for massive cerebral stroke in surgical patients include older age, male sex, prior cerebrovascular disease, hypertension, renal failure, smoking, diabetes mellitus, and atrial fibrillation. Case summary We describe two cases of perioperative massive cerebral stroke following thoracic surgery and one case following bronchoscopy. Neurologic symptoms, including changes in mental status and hemiplegia, occurred within 10 h after surgery in the three patients. All three patients died after the surgery. Conclusion Perioperative massive cerebral stroke may be more likely to occur in thoracic surgical patients if there are pre-existing factors including previous stroke, hypotension, and hypoxemia. Sufficient pain control after surgery and timely neurology consultation and management are helpful for the diagnosis and control of stroke in high-risk patients.

AIM: To assess the effect of age at diabetes onset and uncontrollable high HbA1c levels on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. METHODS: This was a cross-sectional survey of diabetic patients in Subei district, China. Data covering physical measurements, fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1c), blood lipid, urinary albumin/creatinine ratio (UACR), ocular fundus examination, and diabetes treatment records were collected. An independent sample t-test were used to analyze differences. A Logistic regression analysis was applied to study the independent risk factors of DR. RESULTS: A total of 1282 patients with type 2 DM were enrolled, and 191 cases had DR (14.9%). The age at diabetes onset, education level, alcohol consumption, HbA1c level, UACR level, and hypoglycemic drugs were independent influencing factors for DR. The older the onset of diabetes, the less likely to develop DR (OR: 0.958, 95%CI: 0.942-0.975, P=0.000). Patients were then divided in terms of age at diabetes onset as follows

Occasionally, the drainage tube could not be removed because it was inadvertently sutured during the closure of the wound, which presents a dilemma for surgeons. Here, we share a simple and convenient solution: using endoscopic punching forceps to remove the sutured tube, providing a relatively simple and convenient option for surgeons.

Objectives The aim of this study was to explore the genomic content of a blaKPC-2- and mcr-1-harbouring Escherichia coli strain and to clarify the molecular mechanism for the transmission of multidrug resistance. Methods Antimicrobial susceptibility testing was conducted by the broth microdilution method to determine the resistance profile. Filter-mating conjugation assays were performed to confirm the plasmid transfer ability. Whole-genome sequence data were acquired by a combination of Illumina paired-end reads and Nanopore long-read sequencing. Results Escherichia coli strain QE11−421 was an mcr-1-positive colistin-resistant isolate that co-harboured the blaKPC-2 gene conferring carbapenem resistance. Genome sequence data confirmed QE11−421 as a sequence type 48 (ST48) E. coli that harboured five large conjugative plasmids encoding several multidrug resistance genes. The blaKPC-2 gene was located on a Tn3–Tn4401 composite transposon, which is part of a 65-kb multidrug-resistant IncN plasmid. The mcr-1 gene was harboured on another 33-kb IncX4 plasmid that was more conserved and presented few antimicrobial resistance determinants. No copies of insertion sequence ISApl1 were found flanking the mcr-1 gene, decreasing the mobility of mcr-1 based on its original Tn6330 transposon. Conclusions Horizontal transfer of multidrug resistance plasmids or resistance-related transposon units was responsible for the emergence of this notorious superbug. The coexistence of blaKPC-2–IncN and mcr-1–IncX4 plasmids in a ST48 E. coli strain in humans poses a great threat.

Background Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, is highly contagious. Global medical systems have been heavily impacted by the COVID-19 pandemic. Although the majority of patients with intracranial disease require time-sensitive surgery, how to conduct neurosurgery and prevent and control nosocomial infection during a pandemic is challenging. Materials and methods We retrospectively reviewed the clinical data of patients undergoing neurosurgical and neurointerventional procedures at Beijing Tiantan Hospital, China during the early stages of the COVID-19 pandemic between January 21 and July 31, 2020. A 3-level system of COVID-19 risk was established based on medical conditions, epidemiologic, and symptom inquiry and the results of triage. A transitional unit was established for patients in whom COVID-19 had not been ruled out on admission to hospital. Results A total of 4025 patients underwent neurosurgery during the study period, including 768 emergent and 3257 nonemergent procedures. Of these patients, 3722 were low-risk for COVID-19, 303 were moderate-risk, and none were high-risk. In addition, 1419 patients underwent neurointerventional procedures, including 114 emergent and 1305 nonemergent interventions, of which 1339 were low-risk patients, 80 were moderate-risk and none were high-risk. A total of 895 patients (neurosurgical and neurointerventional) were admitted to the transitional unit. Forty-five patients were diagnosed with COVID-19 and transferred to the COVID-19 designated hospital. There were no cases of COVID-19 nosocomial infections among surgical patients or health care workers. Conclusion On the basis of our single-center experience, developing a full screening protocol for COVID-19, establishing a risk level, and using a transitional unit for those with unknown COVID-19 status are effective measures to provide a safe environment for patients and health care workers.

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease and poses a global major public health burden. The preparation of Tripterygium wilfordii Hook F (TwHF) is widely applied for treating patients with Immunoglobulin A nephropathy in China, while the molecular mechanisms remain unclear. This study aimed to verify the therapeutic mechanism of TwHF on IgAN by undertaking a holistic network pharmacology strategy in combination with in vitro and in vivo experiments. Methods: TwHF active ingredients and their targets were obtained via the Traditional Chinese Medicine Systems Pharmacology Database. The collection of IgAN-related target genes was collected from GeneCards and OMIM. TwHF-IgAN common targets were integrated and visualized by Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the predominant molecular mechanisms and pathways of TwHF on the treatment of IgAN. The protein-protein interaction network was constructed by the STRING online search tool, and hub genes were identified using R software. The expression of hub gene and related signaling were evaluated in TwHF-treated mice through immunohistochemistry and western blot and further validated in human mesangial cells (HMCs). In addition, Cell counting kit 8 (CCK8) and flow cytometry were used to detect the effects of TwHF on cell proliferation and cell cycle of mesangial cells. Results: A total of 51 active ingredients were screened from TwHF and 61 overlapping targets related to IgAN were considered potential therapeutic targets, GO functions and KEGG analyses demonstrated that these genes were primarily associated with DNA-binding transcription factor binding, lipid and atherosclerosis pathway. Genes with higher degrees including AKT1, CXCL8, MMP9, PTGS2, CASP3, JUN are hub genes of TwHF against IgAN. Verification of hub gene JUN both in vitro and in vivo showed that TwHF significantly attenuated JUN phosphorylation in the kidneys of IgAN mice and aIgA1-activated HMCs, meanwhile suppressing HMCs proliferation and arresting G1-S cell cycle progression. Conclusion: Our research strengthened the mechanisms of TwHF in treating IgAN, inhibition of JUN activation may play a pivotal role in TwHF in alleviating IgAN renal injury.

Background: Undernutrition in early life may have a lifelong effect on adult health. The associations between undernutrition and obesity parameters and dyslipidemia were inconsistent. The present study aimed to investigate the individual and combined effects of famine exposure and obesity parameters on dyslipidemia in middle-aged and older Chinese.Method: Data were selected from the China Health and Retirement Longitudinal Study Wave2011. The analytic sample included 9427 subjects aged 45 to 90. The present study analyzed data from 9427 middle-aged and older Chinese selected from the China Health and Retirement Longitudinal Study (CHARLS Wave2011). Differences between baseline characteristics and famine exposure/BMI levels/WC levels were evaluated using the Chi-square test, t-test, and F-test. Then, the difference in the prevalence of dyslipidemia between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined associations of famine exposure and obesity parameters with odds of prevalence of dyslipidemia.Results: Among the 9427 participants, 1097(11.64%) participants had been exposed to the Chinese famine during the fetal stage, whereas 3763(39.92%) participants and 3251(34.49%) participants had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with BMI measurements,2771(29.39%) were overweight and 1105(11.72%) were obese, whereas 3955(41.95%) of the participants with WC measurements were obese, respectively. Furthermore, 1899(43.23%) reported having dyslipidemia in males and 1860(36.95%) in females. In multivariable-adjusted model, famine exposure and obesity parameters were associated with prevalence of dyslipidemia independently in total populations[(1) Model three c, famine exposure with prevalence of dyslipidemia: the fatal exposed vs no exposed group, 1.32 (95% CI 1.12, 1.56); childhood-exposed vs no exposed group, 1.49 (95% CI 1.30, 1.70); the adolescence/adult-exposed vs no exposed group, 1.49 (95%CI 1.30, 1.71) ; P for trend=0.000; (2) Model three e, famine exposure with prevalence of dyslipidemia: the fatal exposed vs no exposed group, 1.29 (95% CI 1 .09, 1.52); childhood-exposed vs no exposed group, 1.39 (95% CI 1.22, 1.59); the adolescence/adult-exposed vs no exposed group, 1.27 (95%CI 1.11, 1.46) ; P for trend=0.002; (3) Model three g, BMI levels with prevalence of dyslipidemia: overweight vs normal, 2.06 (95%CI 1.86, 2.27); obesity vs normal, 2.82(95% CI 2.42, 3.27); P for trend=0.000; (4) WC levels with prevalence of dyslipidemia: overweight vs normal, 2.24 (95% CI 2.05, 2.45)]. When stratified by sex, the results in females were mostly similar to those in the total population. In a multivariable logistic regression model three c, associations between famine exposure and dyslipidemia were not observed [fatal exposed group vs non-exposed group: 0.98 (95% CI 0.75, 1.28); childhood-exposed group vs non-exposed group: 0.96 (95% CI 0.78, 1.19); adolescence/adult exposed group vs non-exposed group: 0.86 (95% CI 0.69, 1.07)] independently of BMI only (P for trend =0.110). However, in a multivariable logistic regression model three e, associations between famine exposure and dyslipidemia in male were partly observed [fatal exposed group vs non-exposed group: 0.97 (95% CI 0.74, 1.26); childhood-exposed group vs non-exposed group: 0.91 (95% CI 0.74, 1.13); adolescence/adult exposed group vs non-exposed group: 0.73 (95% CI 0.59, 0.91)] independently of BMI only (P for trend =0.001). In general, the significant synergism between famine exposure and obesity parameters in lowering the prevalence of dyslipidemia was observed in males while the significant synergism in increasing prevalence of dyslipidemia was observed in females (P-interaction =0.000).Conclusion: Individual and combined associations of obesity parameters and famine exposure with the prevalence of dyslipidemia were observed in middle-aged and elderly Chinese.

Tetracyclic triterpenes and steroids are pharmacologically important molecules, and acetylation could improve their bioactivities. In this study, a highly regio- and stereo-specific acetyltransferase, AmAT19, was discovered from Astragalus membranaceus. AmAT19 could selectively catalyze the 6α-OH acetylation of four tetracyclic triterpenes and steroids. The strict selectivity is associated with different orientations of the 6α/β-OH as indicated by molecular docking. Acetylated products 1a, 3a and 4a remarkably increased the inhibitory activity against the 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2, compared to 1, 3, and 4. AmAT19 could be a promising catalyst for specific 6α-OH acetylation to expand the molecular diversity of triterpenes and steroids.

Overweight employees are viewed as lazy, slow, inactive, and even incapable. Even if such attributes are false, this perspective can seriously undermine others' evaluation of their work performance. The current study explores a broader phenomenon of weight bias that has an effect on weight change. In a longitudinal study with a time lag of 6 months, we surveyed 226 supervisor-employee dyads. We found supervisor perceptions of employee weight change notably altered their evaluation of the employee performance from Time 1, especially following low vs. high Time-1 performance evaluation. Meanwhile, the moderating effects among different levels of supervisor anti-fat bias functioned as boundary conditions for such performance evaluation alteration. In particular, the interaction between the Time-1 performance evaluation and the impact of supervisor perception of employee weight change on the Time-2 performance evaluation was significant only if supervisors held a stronger anti-fat bias.

Wear between balls and races has significant effects on the dynamic characteristics of bearing, which is the main reason to cause bearing failure. Some existing contact stiffness models were established to study the dynamic characteristics of bearing. However, the wear of bearing has been rarely investigated due to the complexities of contact load and wear mechanism. This paper presents a new dynamic wear simulation model of angular contact ball bearings mounted in pairs to solve this problem. A final contact stiffness model is established based on the wear model. The effects of running distance, horizontal load, preload, initial contact angle, number and diameter of balls on wear performances are analyzed. A generalized time-varying and piecewise-nonlinear dynamic model of angular contact ball bearings is established to perform an accurate investigation on its dynamic characteristics, especially considering the coupling effects of wear and rolling contact. The effects of wear on the contact stiffness and nonlinear dynamic characteristics are analyzed according to the dynamic model. Additionally, the variations of the contact stiffnesses and frequency responses with different preloads are discussed and the results indicate that parameter selection has significant effects on the wear and nonlinear response.

Aim This study was conducted to investigate the chronic injury of peritoneal glucose injection on the peritoneum and intestine and the protective effects of omega‐3 polyunsaturated fatty acid (ω‐3PUFA) during peritoneal dialysis (PD). Methods Peritoneal dialysis animal models were established by intraperitoneal injection of 4.25% glucose for 28 days. Protein expression in ileum and peritoneum was measured by immunofloresence and immunohistochemistry. Protein expression in macrophages was measured by Western blot. Fibrosis was analyzed by Masson staining. Results Peritoneal dialysis significantly increased the structural injury and decreased junction‐related protein ZO‐1 and occludin expression in ileum, the expression of proteins relating to the activation of M2 (Erg2, IRF4), but not M1 (CD38, IRF5) macrophages. PD significantly increased the expression of TGF‐β1, VEGF and ALK5 protein in peritoneal tissues. PD significantly increased fibrosis (Masson staining) and the expression of fibroblast marker α‐SMA in peritoneal tissues. Injection of macrophage clean reagent and ω‐3PUFA significantly inhibited M2 activation, and decreased Masson staining, α‐SMA, TGF‐β1, VEGF and ALK5 protein expression in peritoneal tissues in PD treated rats. ω‐3PUFA injection significantly decreased PD‐induced injury in ileum and normalized the expression of ZO‐1 and occludin in the ileum of PD rats. Conclusion Omega‐3 fatty acids can provide a protective role on PD‐induced peritoneal fibrosis and injury of the intestine., SUMMARY AT A GLANCE This study demonstrated that omega‐3 fatty acids inhibited peritoneal fibrosis through inhibiting activation of fibroblasts and M2 microphages and subsequently TGF‐ß1‐VEGF‐ALK5 signaling in rats that received peritoneal dialysis with 4.25% glucose. Omega‐3 fatty acids may provide a protective role on peritoneal dialysis‐induced peritoneal fibrosis.

Introduction Tumours are more likely to metastasize after the development of resistance to EGFR-TKIs. CD146 is a multifunctional molecule and is implicated in tumour invasion and metastasis; however, its role in lung cancer has not been clearly established. Objective Here, we aimed to explore the relationship between CD146 pathway and stem cell phenotype after EGFR-TKI resistance in lung cancer. Methods EGFR-TKI-resistant cell lines were established by exposing parental cells to erlotinib/gefitinib. The CD146 level was measured by a western blot, RT-PCR and immunocytochemistry fluorescent. Cell migration was examined by the transwell assay and the scratch assay. Stemness phenotype genes were evaluated by RT-PCR and stem cell phenotype was observed by the microsphere formation assay. Results CD146 and stemness phenotype genes increased while β-catenin decreased in acquired EGFR-TKI-resistant cell lines. CD146's over-expression induced the up-regulation of stemness-related genes and was inversely correlated with the β-catenin expression, which further increased the migration capability of resistant cancer cells. CD146's knockdown suppressed cell migration and stemness phenotype. Conclusions CD146 molecule contributes to the stemness phenotype and migration in EGFR-TKI-resistant cells. CD146 might be a potential therapeutic target for EGFR-TKI-resistant lung cancer or metastasis prevention.

Consciousness is supported by rich neuronal dynamics to orchestrate behaviors and conscious processing can be disrupted by general anesthetics. Previous studies suggested that dynamic reconfiguration of large-scale functional network is critical for learning and higher-order cognitive function. During altered states of consciousness, how brain functional networks are dynamically changed and reconfigured at the whole-brain level is still unclear. To fill this gap, using multilayer network approach and functional magnetic resonance imaging (fMRI) data of 21 healthy subjects, we investigated the dynamic network reconfiguration in three different states of consciousness: wakefulness, dexmedetomidine-induced sedation, and recovery. Applying time-varying community detection algorithm, we constructed multilayer modularity networks to track and quantify dynamic interactions among brain areas that span time and space. We compared four high-level network features (i.e., switching, promiscuity, integration, and recruitment) derived from multilayer modularity across the three conditions. We found that sedation state is primarily characterized by increased switching rates as well as decreased integration, representing a whole-brain pattern with higher modular dynamics and more fragmented communication; such alteration can be mostly reversed after the recovery of consciousness. Thus, our work can provide additional insights to understand the modular network reconfiguration across different states of consciousness and may provide some clinical implications for disorders of consciousness.

Summary A crescentic lesion in renal biopsy could be segmental or circumferential, but the distribution and clinical implication of the circumferential crescents in immunoglobulin A nephropathy (IgAN) remains unknown. A total of 384 crescentic IgAN patients between 2011 and 2019 were included. The subjects were classified as the circumferential crescent who have at least one crescent involving ≥50% circumference of Bowman’s capsule, otherwise as to the segmental crescent. Clinical, pathological, and prognostic relationships were analyzed. The primary endpoint was a 30% decline in eGFR, and the secondary endpoint was more than 3.5 g/d proteinuria during follow-up. Of the 384 patients, 72 (18.8%) patients had more than one circumferential crescent. 52 (17.6%) Oxford C1 patients have circumferential crescent. During a mean follow-up of 32.3 months, both the primary and secondary endpoints have occurred more in the circumferential crescent patients. Kaplan–Meier analysis showed the patient with the circumferential crescent had significantly lower renal survival than those without. In multivariable Cox analyses, having the circumferential crescents in at least one-fifth of glomeruli was independently associated with primary endpoint (hazard ratio:3.60, 95% CI:1.46–8.83), after adjusting for Oxford-score, eGFR, systolic blood pressure, and proteinuria. Furthermore, those patients who scored C1 in Oxford and presenting with circumferential crescents, had better renal survival if they received the other immunosuppressants therapy. The circumferential crescents lesion was associated with adverse outcomes in IgAN, and more than one-fifth of glomeruli circumferential crescents is an independent predictor of 30% eGFR decline after adjusting for clinical and histological parameters.

Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of miR-214-3p in the renal cortex of IgAN mice by miRNA sequencing. In situ hybridization analysis showed that miR-214-3p expression was obviously elevated in MCs in the renal cortex in IgAN. Functionally, knockdown of miR-214-3p alleviated mesangial hypercellularity and renal lesions in IgAN mice. In vitro, the inhibition of miR-214-3p suppressed MC proliferation and arrested G1-S cell cycle pSrogression in IgAN. Mechanistically, a luciferase reporter assay verified PTEN as a direct target of miR-214-3p. Downregulation of miR-214-3p increased PTEN expression and reduced p-JNK and p-c-Jun levels, thereby inhibiting MC proliferation and ameliorating renal lesions in IgAN. Moreover, these changes could be attenuated by co-transfection with PTEN siRNA. Collectively, these results illustrated that miR-214-3p accelerated MC proliferation in IgAN by directly targeting PTEN to modulate JNK/c-Jun signaling. Therefore, miR-214-3p may represent a novel therapeutic target for IgAN.

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s13577-021-00499-y.

Assessment of lung and heart states is of critical importance for patients with pneumonia. In this study, we present a small-sized and ultrasensitive accelerometer for continuous monitoring of lung and heart sounds to evaluate the lung and heart states of patients. Based on two-stage amplification, which consists of an asymmetric gapped cantilever and a charge amplifier, our accelerometer exhibited an extremely high ratio of sensitivity to noise compared with conventional structures. Our sensor achieves a high sensitivity of 9.2 V/g at frequencies less than 1000 Hz, making it suitable to use to monitor weak physiological signals, including heart and lung sounds. For the first time, lung injury, heart injury, and both lung and heart injuries in discharged pneumonia patients were revealed by our sensor device. Our sound sensor also successfully tracked the recovery course of the discharged pneumonia patients. Over time, the lung and heart states of the patients gradually improved after discharge. Our observations were in good agreement with clinical reports. Compared with conventional medical instruments, our sensor device provides rapid and highly sensitive detection of lung and heart sounds, which greatly helps in the evaluation of lung and heart states of pneumonia patients. This sensor provides a cost-effective alternative approach to the diagnosis and prognosis of pneumonia and has the potential for clinical and home-use health monitoring.

A rapid, highly sensitive, and robust diagnostic technique for point-of-care (PoC) testing can be developed using the combination of the nanoparticle-based lateral flow biosensors (LFB) and isothermal nucleic acid amplification technology. Here, we developed a polymerase spiral reaction (PSR) containing FITC-labeled DNA probes coupled with the nanoparticle-based LFB assay (PSR-LFB) to detect the amplified products to detect HBV visually. Under the optimized conditions, the PSR assay involved incubation of the reaction mixture for 20 min at 63°C, followed by visual detection of positive amplicons using LFB, which would generate a red test line based on the biotin/streptavidin interaction and immunoreactions, within 5 min. A cross-reactivity test revealed that the developed PSR-LFB assay showed good specificity for HBV and could distinguish HBV from other pathogenic microorganisms. For the analytical sensitivity, the limit of detection (LoD) of PSR-LFB assay was recorded as 5.4 copies/mL of HBV genomic DNA, which was ten-times more sensitive than qPCR and loop-mediated isothermal amplification (LAMP). Additionally, all the HBV-positive (29/82) samples, identified using ELISA, were also successfully detected by the PSR-LFB assay. We found that the true positive rate of the PSR-LFB assay was higher than that of qPCR (100 vs. 89.66%, respectively), as well as the LAMP assay (100 vs. 96.55%, respectively). Furthermore, the integrated procedure could be completed in 60 min, including the processing of the blood samples (30 min), an isothermal reaction (20 min), and result visualization (5 min). Thus, this PSR-LFB assay could be a potentially useful technique for PoC diagnosis of HBV in resource-limited countries.

Antibiotic resistance in environmental matrices becomes urgently significant for public health and has been considered as an emerging environmental contaminant. In this work, the ampicillin-resistant Escherichia coli (AR E. coli) and corresponding resistance genes (blaTEM-1) were effectively eliminated by the electrocatalytic process, and the dissemination risk of antibiotic resistance was also investigated. All the AR E. coli (∼8 log) was inactivated and 8.17 log blaTEM-1 was degraded by the carbon nanotubes/agarose/titanium (CNTs/AG/Ti) electrode within 30 min. AR E. coli was inactivated mainly attributing to the damage of cell membrane, which was attacked by reactive oxygen species and subsequent leakage of intracellular cytoplasm. The blaTEM-1 was degraded owing to the strand breaking in the process of electrocatalytic degradation. Furthermore, the dissemination risk of antibiotic resistance was effectively controlled after being electrocatalytic treatment. This study provided an effective electrocatalytic technology for the inactivation of antibiotic resistant bacteria and control of antibiotic resistance dissemination risk in the aqueous environment.

Background Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods This retrospective study included N = 291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p p = 0.008, p = 0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p = 0.012, p = 0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT ( Conclusion Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

The transmission of antibiotic resistance in surface water has attracted much attention due to its increasing threat to human health. The role of sunlight irradiation and the effect of dissolved organic matter (DOM) on the transmission of antibiotic resistance are still unclear. In this study, photo-inactivation of antibiotic resistant bacteria (ARB) was investigated using antibiotic resistant E. coli (AR E. coli) that contained the tetracycline resistance gene (Tc-ARG) as a representative. The results showed that AR E. coli underwent significant photo-inactivation due to the membrane damage induced by direct irradiation and by the generated reactive oxygen species. Simulated sunlight irradiation specifically suppressed the expression of tetracycline resistance, which is attributed to the destruction of tetracycline-specific efflux pump. Tetracycline inhibited the photo-inactivation of AR E. coli due to its selective pressure on tetracycline resistant E. coli and competitive light absorption effect. Suwannee River fulvic acid (SRFA), a representative DOM, promoted the inactivation of AR E. coli and further inhibited the expression of tetracycline resistance gene due to the generation of its excited triplet state, singlet oxygen, and hydroxyl radical. The extracellular Tc-ARG also underwent fast photodegradation under light irradiation and in the presence of SRFA, which leads to the decrease of its transformation efficiency. This study provided insight into the sunlight-induced inactivation of ARB, which is of significance for understanding the transmission of tetracycline resistance in surface water.

Background The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a looming threat to human health. Although there are numerous studies regarding porin alteration in association with the production of ESBLs and/or AmpC β-lactamase, a systematic study on the treatment-emergence of porins alteration in antibiotic resistance does not yet exist. The aim of this study was to investigate the underlying mechanism of resistance of K. pneumoniae during carbapenem treatment. Results Here, we report three strains (FK-2624, FK-2723 and FK-2820) isolated from one patient before and after imipenem treatment during hospitalization. Antibiotic susceptibility testing indicated that that the first isolate, FK-2624, was susceptible to almost all tested antimicrobials, being resistant only to fosfomycin. The subsequent isolates FK-2723 and FK-2820 were multidrug resistant (MDR). After imipenem therapy, FK-2820 was found to be carbapenem-resistant. PCR and Genome Sequencing analysis indicated that oqxA, and fosA5, were identified in all three strains. In addition, FK-2624 also harbored blaSHV-187 and blaTEM-116. The blaSHV-187 and blaTEM-116 genes were not detected in FK-2723 and FK-2820. blaDHA-1, qnrB4, aac (6′)-IIc, and blaSHV-12, EreA2, CatA2, SulI, and tetD, were identified in both FK-2723 and FK-2820. Moreover, the genes blaDHA-1, qnrB4, aac (6′)-IIc were co-harbored on a plasmid. Of the virulence factors found in this study, ybtA, ICEKp6, mrkD, entB, iroN, rmpA2–6, wzi16 and capsular serotype K57 were found in the three isolates. The results of pairwise comparisons, multi-locus sequencing typing (MLST) and pulsed-field gel electrophoresis (PFGE) revealed high homology among the isolates. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that isolate FK-2820 lacked OmpK36, with genome sequence data validating that there was a premature stop codon in the ompK36 gene and real-time RT-PCR suggesting high turnover of the ompK36 non-sense transcript in FK-2820, with the steady-state mRNA level 0.007 relative to the initial isolate. Conclusion This study in China highlight that the alteration of outer membrane porins due to the 14-day use of imipenem play a potential role in leading to clinical presentation of carbapenem-resistance. This is the first description of increased resistance developing from a carbapenem-susceptible K. pneumoniae with imipenem treatment driven by outer membrane remodeling.

Objectives Lung cancer has the highest mortality rate among the various types of cancer. Panax ginseng (C. A. Mey). is a popular anti‐cancer herbal supplement. The quality control of ginseng is crucial to ensure its clinical efficacy. This study aimed to establish new quality control methods for ginseng and to identify its main active components responsible for lung cancer treatment. Methods Ultra‐high‐performance liquid chromatography (UPLC) was used to establish fingerprints of 18 batches of ginseng. CCK‐8 test was performed to evaluate the inhibitory activity of ginseng on Lewis lung cancer (LLC) cells. The spectrum‐effect relationship analysis of ginseng was assessed by canonical correlation analysis (CCA) and bioactivity validation. Key findings Six common peaks were identified and the variation coefficients were determined. The 18 batches of ginseng inhibited the proliferation of LLC cells to different degrees, showing different half maximal inhibitory concentration (IC50) values. Spectrum‐effect relationship analysis showed that ginsenoside Ro is the main anti‐proliferative constituent of LLC cell. Conclusions Spectrum‐effect relationship is suitable for quality control of ginseng used for lung cancer. It is also effective in discovering the active ingredients related to the clinical efficacy of traditional Chinese medicine., Panax ginseng is a popular herbal supplement in lung cancer patients. We used cells viability assay and chromatographic fingerprint to establish the spectrum‐effect relationship method to evaluate the effect of 18 ginseng samples on Lewis lung cancer (LLC) cells. We found ginsenoside Ro is the main active constituents. And our work indicates that spectrum‐effect relationships is a reliable method for controlling quality and discovering the material basis related to the clinical efficacy of traditional Chinese medicine.

Summary: Background: Although the emergence of the plasmid-mediated colistin resistance gene, mcr-1, caused global concern, little is known about its clinical implications and transmission characteristics over time. We aimed to investigate the clinical relevance of infection with mcr-1-positive Escherichia coli isolates and to investigate long-term plasmid dynamics. Methods: We did a multicentre case-control study and molecular epidemiological survey of mcr-1-positive E coli infections. E coli isolates from four hospitals in China in 2008 to 2017 were collected and screened for mcr-1 by PCR and Sanger sequencing. Patients with mcr-1-positive E coli infections and matched controls with mcr-1-negative E coli infections were included in a 1:4 ratio, considering age, sex, living environment, comorbidities, antimicrobials used, and clinical sample type as potential risk factors in a regression model. 28-day mortality was also observed. The genomes of all mcr-1-positive E coli were sequenced to explore their genetic background and map IS Apl1 elements. Plasmids carrying mcr-1 were characterised by their resistance profile and incompatibility group. Findings: 29 100 isolates were collected across all hospitals and during the study period, 300 (1·03%) of which were mcr-1-positive E coli. The overall proportion of mcr-1-positive isolates significantly increased from 0·42% (1 of 240) in 2008 to 1·39% (66 of 4748; p

Aims Cancer associated fibroblasts (CAFs) play a crucial role in lung tumor development, but the underlying mechanism is still not fully understood. Main methods SCRIB expression in the CAFs of human lung cancer tissues was examined by immunohistochemistry (IHC). A coculture of mouse Lewis lung cancer cells (LLC) and fibroblasts was used to investigate SCRIB expression in cocultured fibroblasts. Proliferation, scratch wound, and transwell assays were used to examine the proliferation, migration and invasion ability of SCRIB knockdown fibroblasts and their effects on LLC. A 3D-coculture system and co-injection xenograft model were used to examine LLC invasion. RNA sequencing and transwell experiments were used to explore the molecules that may participate in LLC invasion. Key findings Herein, we found that the low expression of SCRIB in CAFs is correlated with advanced tumor stages and poor survival for human lung squamous cell carcinoma. SCRIB expression in fibroblasts is drastically downregulated by LLC cells. SCRIB knockdown fibroblasts not only enhance invasion but also facilitate LLC invasion in a 3D-coculture system and in an in vivo subcutaneous transplantation model. The upregulation of asporin in SCRIB knockdown fibroblasts is involved in LLC invasion in vitro. Significance Collectively, the results indicate that fibroblasts with low SCRIB expression promote lung cancer cell invasion, which suggests that the downregulated expression of SCRIB may represent one of the important characteristics of tumor-promoting CAFs in lung squamous cell cancer.

Anti-Mullerian hormone (Amh) plays a critical role in both early sex determination and later gonad development in vertebrate species. However, it remains unknown in northern snakehead (Channa argus), which is economically important freshwater fish with sexual dimorphism. This study aimed to identify the expression profiles and estrogenic regulation of CaAmh during gonadal sex differentiation in C. argus. The cDNA and genomic DNA sequences of CaAmh were identified by PCR and RACE techniques. The expression patterns of CaAmh were detected by qRT-PCR during the gonadal sex differentiation and after 17α-ethinyloestradiol (EE2) treatments. CaAmh is composed of seven exons and six introns, and its full-length cDNA is 2413 bp in length, with 1635 bp open reading frame (ORF) that encodes a 544 amino acid protein. Tissues expression patterns revealed that CaAmh display the highest expression in testis of XY males (40.36 folds, p