Causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional mendelian randomization study.

BACKGROUND: Epidemiological observational studies have elucidated a correlation between rheumatoid arthritis (RA) and bronchiectasis. However, the causal nature of this association remains ambiguous. To clarify this potential causal linkage, we conducted a two-sample Mendelian randomization (MR) analysis to explore the bidirectional causality between RA and bronchiectasis. METHODS: Summary statistics for RA and bronchiectasis were obtained from the IEU OpenGWAS database We employed various methods, including inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode, to explore potential causal links between RA and bronchiectasis. Additionally, a series of sensitivity studies, such as Cochran's Q test, MR Egger intercept test, and leave-one-out analysis, were conducted to assess the MR analysis's accuracy further. RESULTS: In the forward MR analysis, the primary analysis indicated that a genetic predisposition to RA correlated with an increased risk of bronchiectasis in European populations (IVW odds ratio (OR): 1.28, 95% confidence interval (CI): 1.20-1.37, p = 1.18E-13). Comparable results were noted in the East Asian subjects (IVW OR: 1.55, 95% CI: 1.30-1.34, p = 8.33E-07). The OR estimates from the other four methods were consistent with those obtained from the IVW method. Sensitivity analysis detected no evidence of horizontal pleiotropy or heterogeneity. Conversely, in the reverse MR analysis, we found no evidence to support a genetic causality between bronchiectasis and RA in either European or East Asian populations. CONCLUSION: This study indicates that genetic predisposition to RA correlates with a heightened risk of bronchiectasis in both European and East Asian populations. These results imply that routine screening for bronchiectasis in RA patients could be beneficial, and effective management of RA may contribute to a reduced risk of bronchiectasis. Future research should aim to clarify the underlying mechanisms linking these two conditions.

Investigating the effects of tilting the postural drainage lithotripsy system on cerebral blood flow, intracranial pressure, heart rate, and blood pressure.

PURPOSE: To investigate the effect of the postural drainage lithotripsy system developed by our experimental team on the vital signs of patient with urinary stones during the stone removal process. METHODS: Four groups of 15 subjects (0°, 10°, 40°, and 70°) were subjected to different angles of head-down tilt to measure middle cerebral artery blood flow velocity (MCAv), cerebrovascular conductance coefficient (CVCi), intracranial pressure (nICP), heart rate (HR), and mean arterial blood pressure (MAP). RESULTS: As the angle of HDT changed, MCAv values, nICP values, CVCi values, HR values, and MAP values changed significantly (all P ≤ 0.001), and the difference was statistically significant. During 10°HDT, despite a slight increase in nICP, the other measurements remained stable. During 40°HDT, only the MCAv values did not change significantly, whereas the rest of the measures were significantly altered. During 70°HDT, all indicators changed significantly. CONCLUSIONS: The significant alterations in cerebral blood flow, intracranial pressure, and hemodynamics induced during the treatment of renal residual fragments with postural drainage should be used with caution in individuals with cerebrovascular accidents. CHINA CLINICAL TRIALS REGISTRY: ChiCTR2300070671; Registration date: 2023-04-18.

Association between a body shape index and prostate cancer: a cross-sectional study of NHANES 2001-2018.

OBJECTIVE: Abdominal obesity, especially visceral fat, may have negative effects on the development and progression of prostate cancer (PCa). A body shape index (ABSI) can more accurately measure visceral fat accumulation. This study aimed to investigate the association between ABSI and PCa in US adults. METHODS: 11,013 participants were enrolled in the National Health and Nutrition Examination Survey from 2001 to 2018. Weighted multivariate logistic regression analyses were employed to explore the independent relationship between ABSI and PCa. Moreover, restricted cubic spline (RCS) analysis, subgroup analysis, and interaction tests were performed. RESULTS: ABSI was positively associated with the presence of PCa. When comparing the second, third, and fourth ABSI quartile to the lowest quartile, the adjusted odds ratios (95% confidence intervals) for PCa risk were 1.34 (0.77, 2.31), 1.75 (1.03, 3.00), and 1.91 (1.12, 3.27), respectively (p for trend = 0.011). The restricted cubic spline regression analysis did not reveal a non-linear correlation between ABSI and PCa (p for non-linearity = 0.076). Subgroup analysis showed a significant interaction effect in subgroups of different BMI (p for interaction = 0.01). CONCLUSIONS: Elevated ABSI is significantly associated with an increased risk of PCa, particularly among individuals who are under/normal weighted or obese.

Interleukin-33 increases type 2 innate lymphoid cell count and their activation in eosinophilic asthma.

BACKGROUND: Interleukin-33 (IL-33) exacerbates asthma probably through type 2 innate lymphoid cells (ILC2s). Nevertheless, the association between eosinophilic asthma (EA) and ILC2s remains obscure, and the mechanisms by which IL-33 affects ILC2s are yet to be clarified. METHODS: ILC2s were evaluated in peripheral blood mononuclear cells, induced sputum, and bronchoalveolar lavage fluid obtained from patients with EA. Confocal microscopy was performed to locate ILC2s in lung tissue and the mRNA expression of ILC2-related genes was also evaluated in the EA model. The proliferation of ILC2s isolated from humans and mice was assessed following IL-33 or anti-IL-33 stimulation. RESULTS: The counts, activation, and mRNA expression of relevant genes in ILC2s were higher in PBMCs and airways of patients with EA. In addition, ILC2 cell counts correlated with Asthma control test, blood eosinophil count, Fractional exhaled nitric oxide level, and predicted eosinophilic airway inflammation. IL-33 induced stronger proliferation of ILC2s and increased their density around blood vessels in the lungs of mice with EA. Moreover, IL-33 treatment increased the counts and activation of ILC2s and lung inflammatory scores, whereas anti-IL-33 antibody significantly reversed these effects in EA mice. Finally, IL-33 enhanced PI3K and AKT protein expression in ILC2s, whereas inhibition of the PI3K/AKT pathway decreased IL-5 and IL-13 production by ILC2s in EA. CONCLUSIONS: ILC2s, especially activated ILC2s, might be critical markers of EA. IL-33 can induce and activate ILC2s in the lungs via the PI3K/AKT pathway in EA. Thus, using anti-IL-33 antibody could be a part of an effective treatment strategy for EA.

Ultrasonographic manifestations and the effective diagnosis of epididymal leiomyosarcoma: Case report and systematic literature review.

Background: Epididymal leiomyosarcoma is an extremely rare tumor. In this study, we describe the sonographic features of this uncommon tumor. Methods: A case of epididymal leiomyosarcoma diagnosed at our institute was retrospectively analyzed. Ultrasonic images, noted clinical manifestations, treatment procedures, and pathology results were collected for this patient. The same information was collected from a systematic literature search on epididymal leiomyosarcoma, including the PUBMED, Web of Science and Google Scholar databases. Results: The literature search resulted in 12 articles; we were able to extract data from 13 cases of epididymal leiomyosarcomatosis. The median patient age was 66 (35-78) years, and the average tumor diameter was 2-7 cm. All patients had unilateral epididymal involvement. The lesions were all solid, irregular-shaped in almost half of the cases, featured clear borders in six cases, and had unclear borders in four cases. The internal echogenicity was heterogeneous in the majority of lesions: six cases were hypoechoic (7/11) and three cases moderately echoic (3/10). Information on blood flow within the mass was provided in four cases, but all were noted with significant vascularity. Surrounding tissue invasion was discussed in 11 cases, with 4 featuring peripheral invasion or metastasis. Conclusion: Epididymal Leiomyosarcoma demonstrates sonographic characteristics common to many malignant tumors, such as increased density, irregular shape, heterogeneous internal echogenicity, and hypervascular. Ultrasonography is helpful to differentiate benign epididymal lesions, and can provide some reference for clinical diagnosis and treatment. However, compared with other malignant tumors of the epididymis, it has no characteristic sonographic features,and pathological confirmation is required.

Quantitative CT Metrics for the Prediction of Therapeutic Effect in Asthma.

Background: Few studies have explored the correlation between asthma medication and features on HRCT images. We aim to analyse the differences and temporal changes of lung function and airway resistance in asthma with diverse HRCT phenotypes in a short period after inhalation of budesonide/formoterol. Method: This observational study recruited 55 adult patients with varying severities of asthma. We performed detailed airway metrics measurements of chest CT scans, such as airway wall thickness (WT), wall area percentage (WA%), wall thickness percentage (T/OR), and airways with an inner perimeter of 10 mm (Pi10). The effect of lung structural features on asthma medication response was explored according to the WA% and T/OR twelve hours post-drug administration. Using multivariable regression models, we then assessed the influence of WA% on lung function. Results: WA% (p < 0.001) and T/OR (p < 0.001) significantly increased in asthma than in healthy control subjects. Compared to mild asthma, airway walls were further thickened (WA%, p = 0.023; T/OR: p = 0.029) and associated with lumen narrowing (Pi10, p = 0.055) in moderate to severe asthma. WA% and T/OR correlated well with lung function (FEV1, FVC, MMEF, and PEF) and airway resistance (R5, R20, Rp, and Fres). Regression analysis showed that MEF25 decreased with increasing age and WA% (R2 = 0.58, p < 0.001). Patients with thickened airway walls experienced a maximal increase in FVC, FEV1, and PEF at 2 h (p < 0.001) and a maximal decrease of R5, Z5, and Rp at 2 h (p < 0.001) in those with a thickened airway pattern. Conclusions: Asthma patients with different bronchial wall thicknesses exhibited variable lung function changes. Specifically, patients with thick airway wall patterns were more sensitive to inhaled budesonide in the short term.

[Clinical observation of transurethral holmium laser enucleation of prostate by two-way rendezvous and trenching].

OBJECTIVE: Exploring the clinical efficacy, safety, and surgical techniques of two-way rendezvous and trenching method for transurethral holmium laser prostatectomy in the treatment of benign prostatic hyperplasia. METHODS: Retrospective analysis of clinical data on preoperative, intraoperative, and postoperative follow-up of 326 patients with benign prostatic hyperplasia who underwent two-way rendezvous and trenching method of transurethral holmium laser prostatectomy at the Urology Department of Wujin People's Hospital in Changzhou City from January 2020 to January 2023. RESULTS: Compared with preoperative measures, IPSS symptom score, quality of life (QoL) score, maximum urinary flow rate (Qmax), and residual urine volume (PVR) were significantly improved at 1, 6, and 12 months postoperatively (P<0.05). Thirty two patients with normal and regular sexual life pre-operation were observed. There were no significant changes in their IIEF-5 score and Erectile Hardness Scale (EHGS) score after surgery compared with pre-operation (P<0.05). There were 9 patients (28.12%) with retrograde ejaculation after surgery. CONCLUSION: The two-way rendezvous and trenching method of transurethral holmium laser prostatectomy is a safe and effective method for treating benign prostatic hyperplasia, with precise results, high safety, minimal trauma, and fast postoperative recovery.

[Comparison of therapeutic effects between holmium laser and plasma transurethral enucleation in the treatment of benign prostatic hyperplasia].

OBJECTIVE: Comparison of clinical efficacy between transurethral holmium laser prostate enucleation (two-way rendezvous and trenching method) and transurethral plasma enucleation. METHODS: A total of 483 patients with benign prostatic hyperplasia who were admitted to our hospital from December 2019 to December 2022 were randomly divided into an observation group (245 cases) and a control group (238 cases) using a random number table method. The observation group underwent transurethral holmium laser prostatectomy, while the control group underwent transurethral plasma prostatectomy,evaluate the efficacy of two surgical methods. RESULT: The IPSS symptom score, quality of life (QOL) score, maximum urinary flow rate (Qmax), residual urine volume (PVR) and other indicators were significantly improved in both groups after 6 months of surgery compared to before (P<0.05), and there was no statistically significant difference between the two groups (P>0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (P<0.05). There was no statistically significant difference in sexual function and retrograde ejaculation between the two groups of patients(P>0.05). CONCLUSION: Both surgical methods have good surgical efficacy, but compared with prostate plasma resection, holmium laser prostatectomy can reduce intraoperative bleeding in patients with BPH, effectively shorten catheter retention time, patient hospitalization time, and postoperative bladder flushing time, resulting in higher quality of life and safety.

Progress in Intradermal and Transdermal Gene Therapy with Microneedles.

Gene therapy is one of the most widely studied treatments and has the potential to treat a variety of intractable diseases. The skin's limited permeability, as the body's initial protective barrier, drastically inhibits the delivery effect of gene medicine. Given the potential adverse effects and physicochemical features of the medications, improving generic drug penetration into the skin barrier and achieving an effective level of target tissues remains a challenge. Microneedles have made tremendous improvements in aided gene transfer and medication delivery as a unique method. Microneedles offer the advantage of being minimally invasive and painless, as well as the ability to distribute gene medicines straight through the stratum corneum. Microneedles have been used to penetrate skin tissue with various nucleic acids and medicines in recent years, allowing for a wide range of applications in the treatment of skin ailments. This review focuses on skin-related disorders and immunity, and it primarily discusses the progress of microneedle transdermal gene therapy in recent years. It also complements the current major vectors and related microneedle gene therapy applications.

Effects of Stone Removal via Different Approaches in the Treatment of Incarcerated Upper Ureteral Calculi: A Comparative Study.

Objective: The aim of this study is to investigate the clinical effects of percutaneous nephrolithotomy and transurethral ureteroscopic lithotripsy in the treatment of incarcerated upper ureteral calculi. Methods: This study retrospectively reviewed 400 patients with incarcerated upper ureteral calculi admitted to the hospital from January 2016 to December 2021. Among them, 200 patients treated with percutaneous nephrolithotomy were included in the percutaneous group and 200 patients treated with transurethral ureteroscopic lithotripsy were included in the transurethral group. Perioperative indicators and stone clearance rates on day 7 and 1 month after operation and the reoperation rate were compared between the two groups. The incidence of postoperative complications was recorded. Results: The operation time and postoperative hospital stay of the percutaneous group were longer than those of the transurethral group (P < 0.05). There was no significant difference in intraoperative blood loss, 24 h postoperative pain score, stone clearance rates on day 3 and day 14 after operation, or the reoperation rate between the two groups (P > 0.05). Postoperative complications in the two groups were mainly grade I and II. The total incidence of complications in the percutaneous group was significantly lower than that in the transurethral group (P < 0.05). Conclusion: Both percutaneous nephrolithotomy and transurethral ureteroscopic lithotripsy are effective in the treatment of incarcerated upper ureteral calculi. The former can reduce the incidence of postoperative complications, but the operation time and postoperative hospital stay are longer.

Antimicrobial Peptide-Loaded Gelatinase-Responsive Photothermal Nanogel for the Treatment of Staphylococcus aureus-Infected Wounds.

As the most common pathogen of community and nosocomial infection, the resistance of Staphylococcus aureus (S. aureus) to traditional antibiotics is still increasing with years. Although the potent antibacterial activity of antimicrobial peptides (AMPs) has been widely confirmed, the unpredictable cytotoxicity remains the biggest obstacle to their clinical application. The development of a targeted drug delivery system for S. aureus is a practical strategy to ameliorate the inherent limitations of AMPs. In this work, we constructed an AMP release nanogel (cypate-GNPs@Cy3-AMP, CGCA) of S. aureus infection microenvironment using gelatinase nanoparticles (GNPs) for toxicity control and bacterial clearance. Gelatinase present in the infected site degrades GNPs, thus releasing Cy3-AMP in situ to destroy bacterial cells. Cypate modified on the surface of GNPs supports CGCA to generate localized heat under near-infrared (NIR) laser irradiation, which together with AMPs could cause irreversible physical damage to bacteria. In addition, the encapsulation from GNPs not only effectively limited the toxicity of AMPs but also significantly promoted cell proliferation and migration in vitro. In the mouse infection model, CGCA also exhibited excellent effects of bacterial clearance and wound healing, providing a potential direction for the correct use of AMPs.

Separation of ofloxacin enantiomers by capillary electrophoresis with fluorescence detection using deoxyribonucleic acid oligonucleotides as chiral selectors.

This study used capillary electrophoresis with fluorescence detection- and a partial-filling mode-based method for chiral separation of ofloxacin. The deoxyribonucleic acid oligonucleotides with different base sequences were studied as potential chiral selectors including deoxyribonucleic acid tetrahedron, G-quadruplex, and G-riched double-strand deoxyribonucleic acid. Under the optimized conditions, all the deoxyribonucleic acid chiral selectors exhibited excellent chiral separation capabilities with a resolution higher than 1.5. The electrophoretic behavior of the ofloxacin enantiomer might result from the intermediate conjugate with different stabilities between chiral selectors and analytes by a combination of the hydrogen bond and spatial recognition structure. Moreover, satisfactory repeatability regarding run-to-run and interday repeatability was obtained, and all the relative standard deviation values of migration times and resolutions were below 4% (n = 6). Conclusively, both spatial structure and arrangement of the G bases potentiated the chiral separation capability of deoxyribonucleic acid for ofloxacin enantiomer. This work offered a stepping stone for enantioseparation using deoxyribonucleic acid as chiral selectors.

Hypersensitivity may be involved in severe COVID-19.

BACKGROUND: Deaths attributed to Coronavirus Disease 2019 (COVID-19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID-19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS). METHOD: We detected the serum level of anti-SARS-CoV-2-spike S1 protein-specific IgE (SP-IgE) and anti-SARS-CoV-2 nucleocapsid protein-specific IgE (NP-IgE) in COVID-19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID-19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation. RESULT: The levels of serum SP-IgE and NP-IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO2 /FiO2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID-19. After the application of CS in severe COVID-19, SP-IgE and NP-IgE decreased, but maintained at a high level. CONCLUSION: Hypersensitivity may be involved in severe COVID-19.

Regulatory T cell deficiency in patients with eosinophilic asthma.

BACKGROUND: There is a lack of information about regulatory T cells (Tregs) and inflammatory phenotypes in patients with asthma. In this study, we aimed to compare the characteristics of Tregs in patients with eosinophilic asthma. METHODS: Forty healthy and 120 stable asthmatic patients were recruited. Sputum and airway inflammatory phenotypes were assessed, and all patients were followed for one year. Human peripheral blood mononuclear cells (PBMCs) were collected and stimulated with phytohemagglutinin (PHA) and Dermatophagoides farina (Derp) to detect CD4+CD25+FOXP3+T cells and Foxp3 levels. Interleukin (IL)-13, IL-5, IL-17, IL-9, and interferon (IFN)-γ levels were measured. RESULTS: 38.33% of patients had eosinophilic asthma, 13.33% had neutrophilic asthma, 6.67% had mixed granulocytic asthma, and 41.67% had pauci-granulocytic asthma. The eosinophilic asthma patients had a relatively high Asthma Control Test (ACT) score, an increased prediction and improvement FEV1 (%) rate, and elevated total IgE serum levels (P < 0.05). T helper cell 2 (Th2) cytokines IL-13 and IL-5 were predominantly expressed in the eosinophilic phenotype, while the Th1 cytokine IFN-γ and Th17 cytokine were found in the neutrophilic phenotype. IL-10 was significantly lower in eosinophilic asthmatic patients compared to the controls (P < 0.05). CD4+CD25+FOXP3+T cells (%Tregs) and Foxp3 gene expression in the PHA stimulated eosinophilic asthma samples were significantly lower compared to the control samples (P < 0.05). The airway inflammation phenotypes remained stable after one-year of therapy. CONCLUSION: Asthmatic patients with the eosinophilic phenotype in this study were deficient in Tregs, as characterized by a Th2 cell-biased pattern.

A single center study that evaluates the preclinical use of a newly developed software and moving bed system to facilitate the spontaneous excretion of residual fragments after primary stone treatment (RIRS or PCNL).

PURPOSE: We developed a Postural Drainage Lithotripsy System (PDLS) that uses the patient's computed tomography urography (CTU) data to reconstruct the three-dimensional figure of the renal pelvis, provides an individualized inversion and overturning angle and uses gravity to remove residual fragments (RFs). The purpose of this study was to investigate PDLS in the treatment of renal RFs. METHODS: A stone with a diameter of 4.0 mm was placed in the upper, middle, and lower calyx of the renal model. A total of 60 trials were applied to 20 renal models. The movement trajectory, passage rate, and postural drainage angle of calculi during the treatment of PDLS were observed. RESULTS: All of the stones in 60 trials were observed to move during treatment, and 53/60 (88%) were relocated successfully to the renal pelvis. The passage rate of the upper calyx was 14/20 (70%), that of the middle calyx was 20/20 (100%), and that of the lower calyx was 19/20 (95%). CONCLUSIONS: PDLS can provide individualized inversion and reversal angles and remove stones from the renal model. More clinical trials are needed to verify the above view and evaluate its efficacy.

Effect of different targeted calyxes on the treatment of multi-site calculi in the postural drainage lithotripsy system.

Objectives: We developed a postural drainage lithotripsy system (PDLS) that can provide an individualized inversion and overturning angle and uses gravity to remove residual fragments (RFs). This study aimed to evaluate the effect of different targeted calyces on treating multi-site stones in PDLS. Methods: A total of 20 stones with different sizes and diameters of 0-4 mm were placed in the kidney model through ureteroscopy, and 20 stones were evenly scattered in the middle calyx and the lower calyx of the model. The ventral-middle calyx, the dorsal-middle calyx, the ventral-lower calyx, and the dorsal-lower calyx were used as the targeted calyx of PDLS to treat multi-site stones. During treatment, if the stone moved from the starting position of the renal calyx to the ureteropelvic junction, it was recorded as "passing through." The clearance rate was recorded, and the efficacy of different targeted calyxes in the treatment of multiple-site calyx was compared. Each model was treated with four different targeted calyxes, and 20 models were tested 80 times. Results: When the lower calyx was the targeted calyx, the total stone clearance rate was higher than when the middle calyx was the locating calyx (94.5 vs. 64%, P = 0.000), and the result was statistically significant. Conclusions: Choosing the lower calyx as the targeted calyx, we can obtain a better stone clearance rate. However, there is no significant difference between the ventral lower calyx and the dorsal lower calyx.

One-Step Microfluidic Fabrication of Multi-Responsive Liposomes for Targeted Delivery of Doxorubicin Synergism with Photothermal Effect.

INTRODUCTION: Cancer of the bladder is one of the most common and life-threatening. Compared with traditional delivery methods, intravesical administration reduces the amount of drugs required, increases the amount of drugs reaching the lesion site, and minimizes systemic exposure to therapeutic agents. To overcome the limitations of urinary voiding, low urothelium permeability, and intermittent catheterization for large dilution and irrigation of drugs in the bladder, magnetic and photothermal-responsive folate receptor-targeted thermal liposomes (FA-TMLs) were designed for the targeted delivery of doxorubicin (DOX) to bladder cancer cells. METHODS: Through a microfluidic mixer chip, the magnetic nanoparticles (MNPs), gold nanorods (GNRs) and DOX were encapsulated in folate-modified thermosensitive liposomes to form FA-TMLs@MNPs-GNRs-DOX. DLS, TEM, DSC, and magnetic hysteresis loop were used to characterize the construction of FA-TMLs@MNPs-GNRs-DOX. RESULTS: FA-TMLs@MNPs-GNRs-DOX had a size of about 230 nm and exhibited superparamagnetic properties with the saturation magnetization of 20 emu/g. The DOX loading capacity was as high as 0.57 mg/mL. Additionally, drug release of the FA-TMLs@MNPs-GNRs-DOX could be controlled by temperature change through the photothermal effect. A 980 nm laser beam was selectively irradiated on the FA-TMLs@MNPs-GNRs-DOX to trigger the structural changes of the FA-TMLs, and an average of 95% of the drug was released after 3 hours. The results of cell uptake experiments reveal indicated that FA-TMLs@MNPs-GNRs-DOX were able to specifically bind folate-receptor-positive cells and exhibited toxicity to bladder tumor cells. CONCLUSION: The present results suggest FA-TMLs@MNPs-GNRs-DOX have a promising multifunctional response and can act as an ideal multifunctional drug delivery system (DDS) for the treatment of bladder tumors.

Hypersensitivity in the lungs is responsible for acute respiratory failure in COVID-19 patients: Case series of patients who received high-dose/short-term methylprednisolone.

BACKGROUND: COVID-19 is a highly contagious respiratory disease caused by the SARS-CoV-2 virus. Patients with severe disease have a high fatality rate and face a huge medical burden due to the need for invasive mechanical ventilation. Hypoxic respiratory failure is the major cause of death in these patients. There are currently no specific anti-SARS-CoV-2 drugs, and the effect of corticosteroids is still controversial. METHODS: The clinical data of 102 COVID-19 patients, including 27 patients with severe disease, were analyzed. The serum levels of total IgE and anti-SARS-CoV-2 specific IgE were compared in healthy controls and COVID-19 patients, changes in the level of anti-SARS-CoV-2 specific IgE and clinical response to methylprednisolone (MP) treatment were analyzed, and the effect of high-dose/short-term MP therapy for patients with critical illness and respiratory failure was determined. RESULTS: COVID-19 patients had elevated serum levels of anti-SARS-CoV-2 specific IgE, and patients with severe disease, especially critical illness, had even higher levels. Application of short-term/high-dose MP significantly reduced the level of these IgE antibodies and also blocked the progression of hypoxic respiratory failure. Hypoxic respiratory failure in patients with COVID-19 is related to pulmonary hypersensitivity. CONCLUSIONS: Hypersensitivity in the lungs is responsible for acute respiratory failure in COVID-19 patients. Application of high-dose/short-term MP appears to be an effective life-saving method for COVID-19 patients who have hypoxic respiratory failure.

Parabronema skrjabini (Nematoda: Habronematidae) infection and development in the intermediate host-Haematobia irritans (Linnaeus, 1758) in Inner Mongolia, China.

Parabronemosis is a disease that severely threatens camel health, causing huge economic losses to industries involved in camel husbandry. Previous studies have reported that horn flies (Haematobia irritans) act as intermediate hosts of Parabronema skrjabini; however, the infection and developmental processes of P. skrjabini in horn flies remain unclear. In the present study, the infection rates of P. skrjabini were determined in morphologically and molecularly identified horn flies collected from Bactrian camels (Camelus bactrianus) producing regions in Inner Mongolia, China that have high P. skrjabini infection rates. The horn flies were dissected to obtain the nematode larvae at various instar stages. The P. skrjabini found in the different instar stages of horn fly instars were counted and identified to assess the infection and developmental status. Nematode larvae at different developmental stages were obtained from the horn fly instars for further molecular analysis. Sequencing results confirmed that the nematode larvae were P. skrjabini. Furthermore, we found that the mean growth rate of the nematode larva increased as the horn fly instars develops. The results suggested that P. skrjabini infected the horn flies at the larval instar stage, and that the nematode larvae developed simultaneously with the horn fly instars stages. Our findings provide useful information into the elucidation of P. skrjabini infection and life history by studying horn fly development.

Development and validation of a VHL-associated immune prognostic signature for clear cell renal cell carcinoma.

BACKGROUND: VHL mutation is the most common mutation in clear cell renal cell carcinoma (ccRCC). Here, we developed and validated an immune-related signature to predict the prognosis of ccRCC with VHL mutations. METHODS: VHL mutation status and RNA expression were analysed in the TCGA datasets and our cohort. LASSO Cox analysis was performed to develop an immune-related signature. Candidate genes for the immune-related signature were differentially expressed between VHLwt and VHLmut ccRCC patients. RESULTS: VHL mutations resulted in the downregulation of the immune response in ccRCC. To develop an immune-related signature, LASSO Cox analysis was constructed by immune-related genes that were differentially expressed between VHLwt (WHL wild type) and VHLmut (VHL mutation) ccRCC patients. The signature was developed and validated in the TCGA and our own cohort to classify patients into groups based on having a low or high risk of poor survival. Functional enrichment analysis showed that the immune-related pathway represented the major function and pathway. In addition, patients in the high-risk group had a positive correlation with low fractions of CD4 + T cells and dendritic cells and presented a lower expression of CTLA-4 and PD-1 than the low-risk group. CONCLUSION: In this study, we proposed a novel immune-related signature, which is a feasible biomarker for predicting the overall survival in VHLmut patients with ccRCC.