A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections.

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir (Paxlovid) therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30, 2022, were recruited. Laboratory parameters and chest CT (computed tomography) imaging were analyzed. The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days, whereas the control group included seven patients who received basic treatment. No serious adverse reactions or safety events were recorded. Four control patients progressed to moderate disease, and none in the treatment group showed progression of chest CT findings (P < 0.05). Paxlovid therapy tended toward early viral clearance and low viral load on Day 8. Moreover, 83.3% of the patients in the treatment group and 57.1% of the patients in the control group turned negative within 22 days. In the Paxlovid treatment group, we found significantly increased levels of lymphocytes (P=0.03) and eosinophils (P=0.02) and decreased levels of D-dimer on Day 8 compared with those on Day 1. Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients. The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

Platelet-albumin-bilirubin score and neutrophil-to-lymphocyte ratio predict intensive care unit admission in patients with end-stage kidney disease infected with the Omicron variant of COVID-19: a single-center prospective cohort study.

OBJECTIVES: The objective of this study was to develop clinical scores to predict the risk of intensive care unit (ICU) admission in patients with COVID-19 and end stage kidney disease (ESKD). METHODS: This was a prospective study in which 100 patients with ESKD were enrolled and divided into two groups: the ICU group and the non-ICU group. We utilized univariate logistic regression and nonparametric statistics to analyze the clinical characteristics and liver function changes of both groups. By plotting receiver operating characteristic curves, we identified clinical scores that could predict the risk of ICU admission. RESULTS: Out of the 100 patients with Omicron infection, 12 patients were transferred to the ICU due to disease aggravation, with an average of 9.08 days from hospitalization to ICU transfer. Patients transferred to the ICU more commonly experienced shortness of breath, orthopnea, and gastrointestinal bleeding. The peak liver function and changes from baseline in the ICU group were significantly higher, with p values <.05. We found that the baseline platelet-albumin-bilirubin score (PALBI) and neutrophil-to-lymphocyte ratio (NLR) were good predictors of ICU admission risk, with area under curve values of 0.713 and 0.770, respectively. These scores were comparable to the classic Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (p > .05). CONCLUSION: Patients with ESKD and Omicron infection who are transferred to the ICU are more likely to have abnormal liver function. The baseline PALBI and NLR scores can better predict the risk of clinical deterioration and early transfer to the ICU for treatment.

An intelligent intestinal bleeding diagnosis and treatment capsule system based on color recognition.

To our best knowledge, there are no non-invasive and painless means for the diagnosis and treatment of intestinal bleeding as of now, especially the segment of intestine that cannot be reached by endoscopy. We proposed an intelligent intestinal bleeding diagnosis and treatment capsule (IBDTC) system for the first time to diagnose and treat intestinal bleeding with low power consumption, estimated to be about 2.16mW. A hue-saturation-light (HSL) color space method was applied to diagnose bleeding according to H (hue) values of the film dyed by blood. A MEMS-based micro-igniter works as the critical component of the micro-thruster that houses the propellant (74.6% potassium nitrate, 11.9% sulfur, 13.5% charcoal) and the detonating agent (dinitrodiazophenol), to help release drug. Bleeding detection and ignition tests were performed to justify its feasibility and reliability. Results demonstrated that the bleeding diagnosis module of the IBDTC can effectively detect bleeding and the micro-igniter can successfully ignite the propellant. Owing to its simplicity and intelligence, the IBDTC system will pave a way for future accurate treatment of small intestinal bleeding with no injury, no pain, no complicated supporting equipment, no need for in vitro operation and positioning.

Serum uric acid variability increases the risk of postoperative chronic kidney disease in patients with renal cell carcinoma after radical nephrectomy.

OBJECTIVE: Serum uric acid (SUA) level is associated with the progression of chronic kidney disease (CKD). However, little is known about the predictive value of SUA variability for postoperative CKD in patients with renal cell carcinoma after radical nephrectomy. We aimed to investigate the association of SUA variability with postoperative CKD in this population. METHOD: 85 patients with preoperative estimated glomerular filtration rate (eGFR)≥60 ml/min/1.73 m2 were enrolled in this single-center retrospective study and followed up for at least 6 months. Intra-individual SUA variability was defined as the standard deviation (SD) of SUA and the patients were stratified into three groups according to the tertiles of SUA SD (the lower, middle and upper tertile). The association of SUA variability with postoperative CKD, defined as an eGFR<60 ml/min/1.73m2, was analyzed by Cox proportional hazard models and Kaplan-Meier analyses. RESULTS: After a median follow-up time of 24(10-43) months, 44(51.7%) patients developed postoperative CKD. Kaplan-Meier curves showed that patients in the lower tertile had a longer CKD-free survival time [median CKD-free survival time 74(52.2-95.8) months] than those in the middle tertile [38(19.2-56.8) months] and upper tertile [21(17.9-24.1) months] (overall generalized Wilcoxon test: P=0.001; lower vs middle tertile: P=0.001; lower vs upper tertile: P<0.001). Adjusted Cox analyses indicated that increasing SUA SD tertiles were associated with a higher risk of postoperative CKD independent of baseline SUA, mean SUA during follow-up and other confounding variables. Compared with patients in the lower tertile, the risk for developing CKD increased by 4.6-fold for patients in the middle tertile and 7.9-fold in the upper tertile, respectively. CONCLUSION: Increasing SUA variability was associated with an increased risk of postoperative CKD in patients with renal cell carcinoma after radical nephrectomy.

Validation of the soft-embalmed Thiel cadaver as a high-fidelity simulator of pressure during targeted nerve injection.

INTRODUCTION: Although administration of regional anesthesia nerve blocks has increased during the COVID-19 pandemic, training opportunities in regional anesthesia have reduced. Simulation training may enhance skills, but simulators must be accurate enough for trainees to engage in a realistic way-for example, detection of excessive injection pressure. The soft-embalmed Thiel cadaver is a life-like, durable simulator that is used for dedicated practice and mastery learning training in regional anesthesia. We hypothesized that injection opening pressure in perineural tissue, at epineurium and in subepineurium were similar to opening pressures measured in experimental animals, fresh frozen cadavers, glycol soft-fix cadavers and patients. METHODS: We systematically reviewed historical data, then conducted three validation studies delivering a 0.5 mL hydrolocation bolus of embalming fluid and recording injection pressure. First, we delivered the bolus at 12 mL/min at epimysium, perineural tissue, epineurium and in subepineurium at 48 peripheral nerve sites on three cadavers. Second, we delivered the bolus at using three infusion rates: 1 mL/min, 6 mL/min and 12 mL/min on epineurium at 70 peripheral nerve sites on five cadavers. Third, we repeated three injections (12 mL/min) at 24 epineural sites over the median and sciatic nerves of three cadavers. RESULTS: Mean (95%) injection pressure was greater at epineurium compared with subepineurium (geometric ratio 1.2 (95% CI: 0.9 to 1.6)), p=0.04, and perineural tissue (geometric ratio 5.1 (95% CI: 3.7 to 7.0)), p<0.0001. Mean (95%) injection pressure was greater at 12 mL/min compared with 1 mL/min (geometric ratio 1.6 (95% CI: 1.2 to 2.1), p=0.005). Pressure measurements were similar in study 3 (p>0.05 for all comparisons). DISCUSSION: We conclude that the soft-embalmed Thiel cadaver is a realistic simulator of injection opening pressure.

Facile access to evodiakine enabled by aerobic copper-catalyzed oxidative rearrangement.

Oxidation as a fundamentally important method for the synthesis of complex structures is difficult to achieve in a selective manner. Evodiakine, a complex natural product possessing an unprecedented ring system (6/5/5/7/6), has a high oxidation state without a practical solution. Herein, we report the first synthesis of evodiakine via aerobic copper-catalyzed late-stage functionalization of evodiamine.

The clinical characteristics of Chinese patients with unilateral renal agenesis.

BACKGROUND: We aimed to investigate the clinical characteristics of Chinese patients with unilateral renal agenesis. METHODS: We enrolled patients with unilateral renal agenesis diagnosed radiologically at the Department of Nephrology from January 2008 to January 2016. Patients with a solitary kidney due to nephrectomy or renal atrophy due to secondary factors were excluded. Clinical data were recorded and analyzed. RESULTS: In this study, 118 Chinese patients with unilateral renal agenesis were recruited, and the gender ratio (male/female) was 1.11:1. A total of 14 (11.9%) patients had additional abnormalities, 15 (12.7%) had a family history, and 30 (25.4%) presented with renal insufficiency. Kidney length, serum creatinine level and estimated glomerular filtration rate were significantly different between patients with and without family history (P < 0.05, respectively). Gender showed a significant difference between patients with and without other abnormalities. Kidney length and the incidence of proteinuria, hematuria, hypertension, and hyperuricemia were significantly different between patients with and without renal insufficiency. Logistic regression analysis revealed that family history was associated with severe renal failure (OR = 7.11, 95% CI 1.52-33.25). CONCLUSION: Renal insufficiency is common in patients with unilateral renal agenesis. Patients with renal insufficiency have shorter kidney lengths and a higher incidence of proteinuria, hypertension, hematuria, and hyperuricemia. Family history is considered a risk factor for severe renal failure.

Identification of 8 Novel Mutations in Nephrogenesis-Related Genes in Chinese Han Patients with Unilateral Renal Agenesis.

BACKGROUND: Few genetic studies have focused on unilateral renal agenesis (URA), which is a disorder with insidious clinical manifestations and a tendency to result in renal failure. We aimed to detect pathogenic mutations in nephrogenesis-related genes, which were identified by a literature review conducted among a large cohort of Chinese Han patients with URA. METHODS: Totally, 86 unrelated URA patients were included. All URA patients were diagnosed by employing radiological methods. Patients with a solitary kidney owing to nephrectomy or renal atrophy due to secondary factors were excluded. Nine (10.5%) patients had a family history of abnormal nephrogenesis. Fifteen (17.4%) had other malformations in the urogenital system. All coding exons and adjacent intron regions of 25 genes were analyzed using next-generation sequencing and validated by Sanger sequencing and 100 ethnically matched healthy controls. RESULTS: Ten conserved mutations (9 missense mutations and 1 deletion mutation) were identified in SALL1, EYA1, RET, HNF1B, DSTYK, WNT4, and SIX5. All mutations were novel or rare (frequency <0.1%) in the public databases and absent from the 100 healthy controls. Nine patients carried mutations in candidate genes. Most of the patients carried one single heterozygous mutation, except for 2, who respectively carried compound heterozygous mutations and 2 single heterozygous mutations. In addition, 2 patients shared the same mutation in DSTYK. CONCLUSION: A total of 10.5% of our URA cases could be explained by mutations in our candidate genes. The mutations in nephrogenesis-related genes in the Chinese Han patients with URA had a decentralized distribution without any hotspot mutations.

A Smart Capsule System for Automated Detection of Intestinal Bleeding Using HSL Color Recognition.

There are no ideal means for the diagnosis of intestinal bleeding diseases as of now, particularly in the small intestine. This study investigated an intelligent intestinal bleeding detection capsule system based on color recognition. After the capsule is swallowed, the bleeding detection module (containing a color-sensitive adsorptive film that changes color when absorbing intestinal juice,) is used to identify intestinal bleeding features. A hue-saturation-light color space method can be applied to detect bleeding according to the range of H and S values of the film color. Once bleeding features are recognized, a wireless transmission module is activated immediately to send an alarm signal to the outside; an in vitro module receives the signal and sends an alarm. The average power consumption of the entire capsule system is estimated to be about 2.1mW. Owing to its simplicity, reliability, and effectiveness, this system represents a new approach to the clinical diagnosis of intestinal bleeding diseases.

Collecting Protein Biomarkers in Breath Using Electret Filters: A Preliminary Method on New Technical Model and Human Study.

Biomarkers in exhaled breath are useful for respiratory disease diagnosis in human volunteers. Conventional methods that collect non-volatile biomarkers, however, necessitate an extensive dilution and sanitation processes that lowers collection efficiencies and convenience of use. Electret filter emerged in recent decade to collect virus biomarkers in exhaled breath given its simplicity and effectiveness. To investigate the capability of electret filters to collect protein biomarkers, a model that consists of an atomizer that produces protein aerosol and an electret filter that collects albumin and carcinoembryonic antigen-a typical biomarker in lung cancer development- from the atomizer is developed. A device using electret filter as the collecting medium is designed to collect human albumin from exhaled breath of 6 volunteers. Comparison of the collecting ability between the electret filter method and other 2 reported methods is finally performed based on the amounts of albumin collected from human exhaled breath. In conclusion, a decreasing collection efficiency ranging from 17.6% to 2.3% for atomized albumin aerosol and 42% to 12.5% for atomized carcinoembryonic antigen particles is found; moreover, an optimum volume of sampling human exhaled breath ranging from 100 L to 200 L is also observed; finally, the self-designed collecting device shows a significantly better performance in collecting albumin from human exhaled breath than the exhaled breath condensate method (p<0.05) but is not significantly more effective than reported 3-stage impactor method (p>0.05). In summary, electret filters are potential in collecting non-volatile biomarkers in human exhaled breath not only because it was simpler, cheaper and easier to use than traditional methods but also for its better collecting performance.

Advances in the early detection of lung cancer using analysis of volatile organic compounds: from imaging to sensors.

According to the World Health Organization (WHO), 1.37 million people died of lung cancer all around the world in 2008, occupying the first place in all cancer-related deaths. However, this number might be decreased if patients were detected earlier and treated appropriately. Unfortunately, traditional imaging techniques are not sufficiently satisfactory for early detection of lung cancer because of limitations. As one alternative, breath volatile organic compounds (VOCs) may reflect the biochemical status of the body and provide clues to some diseases including lung cancer at early stage. Early detection of lung cancer based on breath analysis is becoming more and more valued because it is non-invasive, sensitive, inexpensive and simple. In this review article, we analyze the limitations of traditional imaging techniques in the early detection of lung cancer, illustrate possible mechanisms of the production of VOCs in cancerous cells, present evidence that supports the detection of such disease using breath analysis, and summarize the advances in the study of E-noses based on gas sensitive sensors. In conclusion, the analysis of breath VOCs is a better choice for the early detection of lung cancer compared to imaging techniques. We recommend a more comprehensive technique that integrates the analysis of VOCs and non-VOCs in breath. In addition, VOCs in urine may also be a trend in research on the early detection of lung cancer.

Molecular characterization and expression analysis of the autophagic gene beclin 1 from the purse red common carp (Cyprinus carpio) exposed to cadmium.

Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, which has been linked to diverse biological processes including immunity, development, tumor suppression, lifespan extension, etc. However, the relevant study about Beclin 1 is rare in fish compared with mammals. In this study, we isolated Beclin 1 gene from the kidney tissue of common carp (Cyprinus carpio) using rapid amplification of cDNA ends (RACE). The deduced amino acid sequence of cloned Beclin 1 comprised 447 amino acids, which showed approximately 80.7% identity and 88.9% similarity to human Beclin 1. It possessed a typical Bcl-2 homology domain 3 (BH3) and an evolutionarily conserved domain (ECD). Phylogenetic analysis demonstrated that common carp Beclin 1 formed a clade with zebrafish Beclin 1. To explore the relationship between Beclin 1 and cadmium (Cd)-induced injury, a Cd exposure experiment was conducted. The result showed that Cd content was significantly increased in a dose-dependent manner in kidney after Cd exposure. Swelling and vacuolation of renal tubular epithelial cells, and glomerular hyalinization were observed. Renal leukocyte infiltration was diffusely distributed in the interstitial tissue. Real-time quantitative RT-PCR analysis revealed that the mRNA transcript level of Beclin 1 was markedly up-regulated in a dose-dependent and time-dependent manner after exposure to Cd. Similarly, Western blot analysis indicated that its protein level was significantly elevated in a dose-dependent manner after Cd treatment. All the results indicate that the common carp Beclin 1 gene may play a regulatory role against Cd toxicity.

A smart capsule system of gastric occult blood detection.

Prior research indicated that occult blood screening can be used to detect early gastric cancer. Based on capsule endoscopy and occult blood detection theory, an automatic detection capsule system for gastric occult blood (GOB) was proposed. This paper designed the detecting sensor, image acquisition system and wireless transmitter module respectively based on collaurum immune theory, the image sensor and radio frequency chip. In vitro experiments were conducted to testify the system, and the detecting result image information was acquired by the image acquisition (IMAQ) system and transmitted to the outside of the body through the wireless transmitter module. The receiver module received and displayed the information on the computer, from which doctors could diagnose whether there was occult blood (OB) or not. Therefore, this paper provides a new idea for the screening of early-stage gastric cancer with reliability and simplicity.

Cadmium induces liver cell apoptosis through caspase-3A activation in purse red common carp (Cyprinus carpio).

Caspase-3, the essential effector caspase, plays a pivotal role during caspase-dependent apoptosis. In this study, we isolated and characterized caspase-3A gene from common carp. The common carp caspase-3A comprising 273 amino acids showed 71.8% sequence similarity and 59.3% sequence identity to human caspase-3. It exhibited an evolutionarily conserved structure of mammalian caspase-3 genes, including a pro-domain, a large subunit, a small subunit and other motifs such as the pentapeptide active-site motif (QACRG) and the putative cleavage sites at the aspartic acids. Phylogenetic analysis demonstrated that common carp caspase-3A formed a clade with cyprinid fish caspase-3. To assess whether caspase-3A is involved in cadmium (Cd)-induced cell apoptosis in common carp, a Cd exposure experiment was performed. TUNEL analysis showed that Cd triggered liver cell apoptosis; caspase-3A activity was markedly increased; its proenzyme level was significantly decreased, and the levels of its cleaved forms were markedly increased. However, real-time quantitative PCR analysis revealed that the mRNA transcript level of caspase-3A was not significantly elevated. Immunoreactivities were observed in the cytoplasm of hepatocytes by immunohistochemical detection. The findings indicates that Cd can trigger liver cell apoptosis through the activation of caspase-3A. Caspase-3A may play an essential role in Cd-induced apoptosis.

Study on the application of an ultra-high-frequency fractal antenna to partial discharge detection in switchgears.

The ultra-high-frequency (UHF) method is used to analyze the insulation condition of electric equipment by detecting the UHF electromagnetic (EM) waves excited by partial discharge (PD). As part of the UHF detection system, the UHF sensor determines the detection system performance in signal extraction and recognition. In this paper, a UHF antenna sensor with the fractal structure for PD detection in switchgears was designed by means of modeling, simulation and optimization. This sensor, with a flat-plate structure, had two resonance frequencies of 583 MHz and 732 MHz. In the laboratory, four kinds of insulation defect models were positioned in the testing switchgear for typical PD tests. The results show that the sensor could reproduce the electromagnetic waves well. Furthermore, to optimize the installation position of the inner sensor for achieving best detection performance, the precise simulation model of switchgear was developed to study the propagation characteristics of UHF signals in switchgear by finite-difference time-domain (FDTD) method. According to the results of simulation and verification test, the sensor should be positioned at the right side of bottom plate in the front cabinet. This research established the foundation for the further study on the application of UHF technique in switchgear PD online detection.