Targeted therapies for lupus nephritis: Current perspectives and future directions.

ABSTRACT: Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Clinicopathological characteristics and outcomes of lupus nephritis patients with scanty immune depositions in kidney biopsies.

BACKGROUND: The clinicopathological features, outcomes, and pathogenesis of lupus nephritis with scanty immune deposits in the kidney biopsy remain unclear. METHODS: Four hundred ninety-eight biopsy-proven lupus nephritis patients were included, and clinical and pathological data were collected. The primary endpoint was mortality, while the secondary endpoint was doubling baseline serum creatinine or end-stage renal disease. Associations between scanty immune deposits lupus nephritis and adverse outcomes were analyzed by Cox regression models. RESULTS: Among 498 lupus nephritis patients, 81 were diagnosed with scanty immune deposits. Patients with scanty immune deposits had significantly higher serum albumin and serum complement C4 than those with immune complex deposits. The proportion of anti-neutrophil cytoplasmic antibodies was similar between the two groups. In addition, patients with scanty immune deposits showed less proliferative features at kidney biopsy and lower activity index score, accompanied by milder mesangial cell and matrix hyperplasia, endothelial cell hyperplasia, nuclear fragmentation, and glomerular leukocyte infiltration. Patients in this group also had a milder degree of foot process fusion. Overall, renal survival and patient survival showed no significant difference between the two groups. 24-h proteinuria and chronicity index were significant risk factors for renal survival, and 24-h proteinuria and positive anti-neutrophil cytoplasmic antibodies were risk factors for patient survival in scanty immune deposits lupus nephritis patients. CONCLUSIONS: Compared with other lupus nephritis patients, scanty immune deposits lupus nephritis patients had significantly lower activity features on kidney biopsy, but have similar outcomes. Positive anti-neutrophil cytoplasmic antibodies may be a risk factor for patient survival in scanty immune deposits lupus nephritis patients.

Comparison of 2 Ear Molding Systems for Nonsurgical Management of Newborn Auricular Deformities.

BACKGROUND: Congenital auricular deformities are common diseases in newborn infants. We compared the efficacy of 2 ear molding systems in the nonsurgical management of newborn auricular deformities in Chinese infants. METHODS: A total of 462 newborns with auricular deformities were treated with either the EarWell or the LiangEar ear molding systems. The posttreatment outcome was graded as excellent, fair, and poor. The differences in effectiveness between the 2 ear molding systems and factors that may affect the posttreatment outcome were analyzed. RESULTS: Both ear molding systems showed substantial efficacy in the treatment of newborn auricular deformities. The effective rate was comparable between the EarWell and the LiangEar systems for 4 types of auricular deformities (cryptotia, prominent ear, helical rim abnormality, and cup ear), while the costs for the LiangEar systems were half as much as that for the EarWell systems. Multivariate regression analysis showed that earlier time points at treatment initiation, less severe auricular deformities, treatment duration, and breastfeeding were the most significant predictive factors for a better outcome. CONCLUSION: Our findings demonstrate that using the EarWell and the LiangEar systems are both optimal nonsurgical approaches for treatment of most newborn auricular deformities.

[Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data].

Objective:The etiology and pathophysiologic mechanism of sudden sensorineural hearing loss are undefined. We will use artificial intelligence and big data methods to explore the correlation between sudden sensorineural hearing loss and serum indices. Method:A total of 1218 patients with sudden deafness admitted to Sun Yat-sen Memorial Hospital were selected as the experimental group, 95 861 healthy subjects were randomly selected as the control group at the same period. Serum biochemical indexes in two groups were collected and analyzed by TreeNet and CART machine learning algorithms, to screen out highly correlated indicators with sudden sensorineural hearing loss and dig out a set of clinical features for people with high risk of sudden sensorineural hearing loss. Result:It was found that high prevalence rate of sudden sensorineural hearing loss is related to eosinophils, reticulocyte and fibrinogen. The areas under the receiver operator characteristic curves（ROC-AUC） were exploited to evaluate the prediction performance of TreeNet model. Overall the TreeNet model has provided high predictive ability by ROC curve, achieving AUC of 0.99, both recall and accuracy rate of 99.90%. Conclusion:There is significant difference between sudden deadness and normal people in serum biochemical indexes. Eosinophil is the first important indicator to distinguish sudden sensorineural hearing loss. Treenet model has important referenced significance for the screening and diagnosis of sudden sensorineural hearing loss.

Computer-aided diagnosis of laryngeal cancer via deep learning based on laryngoscopic images.

OBJECTIVE: To develop a deep convolutional neural network (DCNN) that can automatically detect laryngeal cancer (LCA) in laryngoscopic images. METHODS: A DCNN-based diagnostic system was constructed and trained using 13,721 laryngoscopic images of LCA, precancerous laryngeal lesions (PRELCA), benign laryngeal tumors (BLT) and normal tissues (NORM) from 2 tertiary hospitals in China, including 2293 from 206 LCA subjects, 1807 from 203 PRELCA subjects, 6448 from 774 BLT subjects and 3191 from 633 NORM subjects. An independent test set of 1176 laryngoscopic images from other 3 tertiary hospitals in China, including 132 from 44 LCA subjects, 129 from 43 PRELCA subjects, 504 from 168 BLT subjects and 411 from 137 NORM subjects, was applied to the constructed DCNN to evaluate its performance against experienced endoscopists. RESULTS: The DCCN achieved a sensitivity of 0.731, a specificity of 0.922, an AUC of 0.922, and the overall accuracy of 0.867 for detecting LCA and PRELCA among all lesions and normal tissues. When compared to human experts in an independent test set, the DCCN' s performance on detection of LCA and PRELCA achieved a sensitivity of 0.720, a specificity of 0.948, an AUC of 0.953, and the overall accuracy of 0.897, which was comparable to that of an experienced human expert with 10-20 years of work experience. Moreover, the overall accuracy of DCNN for detection of LCA was 0.773, which was also comparable to that of an experienced human expert with 10-20 years of work experience and exceeded the experts with less than 10 years of work experience. CONCLUSIONS: The DCNN has high sensitivity and specificity for automated detection of LCA and PRELCA from BLT and NORM in laryngoscopic images. This novel and effective approach facilitates earlier diagnosis of early LCA, resulting in improved clinical outcomes and reducing the burden of endoscopists.

Synthesis, Characterization, and Sensitivity of a CL-20/PNCB Spherical Composite for Security.

Highly energetic materials have received significant attention, particularly 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). However, the application of this material was limited due to its high sensitivity. It is well known that the shape, size, and structure of energetic materials (EMs) significantly influence their sensitivity. At present, there are several ways to reduce the sensitivity of CL-20, such as spheroidization, ultrafine processing, and composite technology. However, only one or two of the abovementioned methods have been reported in the literature, and the obtained sensitivity effect was unsatisfactory. Thus, we tried to further reduce the sensitivity of CL-20 by combining the above three methods. The as-prepared composite was precipitated from the interface between two solutions of water and ethyl acetate, and the composite was insensitive compared with other reported CL-20-based EMs. The H50 value for the composite ranged up to 63 cm. This approach opens new prospects for greatly reducing the sensitivity of high Ems.

[Determination of immunoglobulin G in mare colostrum by high-performance gel permeation chromatography].

A direct high-performance gel permeation chromatographic (HPGPC) method for the determination of immunoglobulin G in mare colostrum was established. HPGPC separation was performed on a TOSOH TSK-G4000PW(XL) column (300 mm x 7.8 mm, 5 microm) with 0.05 mol/L phosphate buffer solution (pH 6.9) as the mobile phase at a flow rate of 0.8 mL/min, and the column temperature was maintained at 25 degrees C. The injection volume was 20 microL. At the detection wavelength of 280 nm, the linear range was from 0.2 to 3.0 g/L (r2 = 0.999 5) with a detection limit of 0.08 mg/L (S/N = 10). The recovery was 97.47% with a relative standard deviation (RSD) of 1.22%. The RSDs of the peak area of stability, accuracy and reproducibility for the established method were 2.86%, 1.62% and 1.82%, respectively. Mare milk was collected from Zhaosu (China), a complete collection was stored in an ice box, then sent to a laboratory and stored in a low temperature refrigerator. The whey milk was prepared by centrifugation two times at 12 000 r/min and 4 degrees C for 30 min. The whey protein was obtained from the middle layer. A 2 mL volume of the whey milk was mixed with 23 mL of mobile phase. The average contents of IgG were from 35.0 g/L to 50.0 g/L at the first lactation (2 h), and the average contents of IgG were from 2.0 g/L to 4.0 g/L after 72 h. The relatively simple analytical method was proved to be accurate and precise in its application to mare colostrum.