To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective To analyze the genetic characteristics and variations of influenza A (H3N2) viruses in Ma'anshan from 2022 to 2024, and to provide a scientific basis for local influenza prevention and control. Methods From April 2022 to March 2024, influenza-like illness (ILI) specimens were collected from three national influenza surveillance sentinel hospitals in Ma’anshan. Samples positive for influenza by real-time PCR were subjected to virus culture and identification. A total of 40 representative A/H3N2 strains with hemagglutination titers ≥8 were selected for whole-genome sequencing. Genetic evolution, homology, amino acid variations, and glycosylation sites were analyzed. Results All H3N2 representative strains from the 2022–2023 influenza season belonged to clade 3C.2a1b.2a.1a.1, while those from the 2023–2024 season fell into clade 3C.2a1b.2a.2a.3a.1. The nucleotide and amino acid sequence similarities of HA and NA between the 40 representative strains and the vaccine strain A/Darwin/6/2021 were all above 97.35%. Compared with the vaccine strain, amino acid mutations were identified in antigenic sites A, B, C, and E, as well as in receptor-binding sites of the HA protein. An I222V substitution was detected in the NA protein. The HA protein contained four additional glycosylation sites compared to the vaccine strain, while the glycosylation pattern of the NA protein remained consistent. Conclusion No antigenic drift was observed in the influenza A/H3N2 viruses in Ma'anshan City from 2022 to 2024, but genetic changes such as branching variations, key amino acid substitutions, and an increase in HA glycosylation sites were observed. These findings underscore the importance of sustained molecular surveillance of local influenza viruses.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN).Methods:This was a single-center, retrospective and single-arm study. The clinical data of AAGN patients who received RTX induction therapy at the First Affiliated Hospital of Zhejiang University School of Medicine from April 2016 to July 2021 and had a follow-up period of more than 6 months were collected. The follow-up was up to June 2022. The Birmingham Vasculitis Activity Score (BVAS) from 2003 was used to assess vasculitis activity. The treatment regimen for RTX was once every 1 to 2 weeks, with 375 mg/m 2 each time. For some patients, the dose was adjusted according to the immune status before medication. The clinical outcomes, renal remission, recurrence and safety was analyzed. Kaplan-Meier method was used to analyze the cumulative renal remission rate. Results:A total of 43 AAGN patients were included in the study, with age of (57.6±16.6) years, 19 males (44.2%) and 34 (79.1%) newly treated patients. There were 34 patients (79.1%) with positive myeloperoxidase-ANCA and 8 patients (18.6%) with positive proteinase 3-ANCA. The dosage of RTX used at the 12-month follow-up was 600 (500, 1 200) mg. At 6 months of follow-up, 32 patients (74.4%) achieved renal remission, and renal remission time was 5.0 (3.3, 5.8) months. Three patients (7.0%) progressed to end-stage renal disease, and two patients (4.7%) died. Compared with patients without renal remission, patients with renal remission had lower baseline serum creatinine ( Z=-2.853, P=0.004), serum uric acid ( t=-2.861, P=0.007), urine protein/urine creatinine ratio ( Z=-2.130, P=0.033) and proportion of methylprednisolone pulse therapy ( χ 2=5.002, P=0.025), and higher estimated glomerular filtration rate ( Z=-2.728, P=0.006). At 12 months of follow-up, 33 patients (76.7%) achieved renal remission, and the cumulative renal remission rate was 82.4%. Two patients (4.7%) had renal recurrence, 5 patients (11.6%) progressed to end-stage renal disease, and 3 patients (7.0%) died. Infection (4 patients, including 2 severe infections) was the main adverse event, all of which occurred within 6 months of RTX treatment. Conclusions:The clinical remission rate and safety of RTX in the treatment of AAGN are both relatively high.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

Objective To explore the clinical application of needle-embedding therapy for preventing and treating postoperative constipation in the patients with thoracolumbar vertebral fractures based on the theory of"preventing illness".Methods Eighty patients meeting the criteria for postoperative constipation af-ter thoracolumbar vertebral surgery in a tertiary hospital of Hangzhou City from January 2023 to February 2024 were selected as the study subjects.The patients were divided into the control group and experimental group by using the random number table method,40 cases in each group.The control group adopted the treat-ment of orally taking lactulose oral solution and the nursing such as routine postoperative food and drink and bed defecation training.The experimental group was given the needle-embedding therapy on the basis of rou-tine care.The gastrointestinal syndrome rating scale(GSRS)score,intra-abdominal pressure(IAP),abdomi-nal circumference,defecation and exhausting situation before and after intervention were performed the statis-tics and compared between the two groups.Results At 36,72 h after oeperation,the GSRS score,IAP and ab-dominal circumference in the both groups were significantly declined or decreased compared with those imme-diately after the operation,the above indicators in the experimental group were superior to those in the control group,and the differences were statistically significant(P＜0.01).The first exhausting and defecation time of the experimental group was earlier than that of the control group,and the difference was statistically signifi-cant(P＜0.01).Conclusion Under the basis of"preventing illness",the needing-embedding therapy has signif-icant therapeutic effects in preventing and treating postoperative constipation in thoracolumbar fractures,could effec-tively reduce IAP,alleviate the symptoms of constipation in the patients and improve their quality of life.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Objective:To explore the value of high resolution computed tomography（HRCT） combined with Magnetic Resonance Imaging（MRI） in the diagnosis of inner ear malformation. Methods:HRCT and MRI data of 82 patients with inner ear malformations were analyzed retrospectively. HRCT MPR and CPR reconstruction of the inner ear structure, facial nerve canal and oblique sagittal MRI reconstruction of the internal auditory canal were performed. The inner ear malformations were classified, the conditions of facial nerve canal and cochlear nerve were evaluated. The association between inner ear malformation and cochlear nerve dysplasia were analyzed by Chi-square test with continuity correction. Results:Among the 82 patients with inner ear malformations,there were 49 cases of bilateral symmetry, 11 cases of bilateral asymmetry and 22 cases of unilateral inner ear malformations. Respectively, the most prevalent types were IP-Ⅱ（42.96%）, dilatation of atrium aqueduct（18.31%） and malformations of atrium and semicircular canal 19.72%. Out of 50 cases of cochlear malformations,only 3 were isolated cochlear malformations, and the rest were accompanied by other malformations of varying degrees. In the 67 ears examined by MRI, 26（38.81%） had cochlear nerve deficiency（CND）, and the incidence of CND varied with different types of inner ear malformations. Out of 142 ears, 28（19.72%） had abnormalities of the facial nerve canal. Conclusion:HRCT combined with MRI can accurately distinguish the types of inner ear malformation and effectively evaluate the facial nerve canal and cochlear nerve, and further provides the important finger and Guide value for the clinician to formulate the reasonable treatment and the operation plan.
Humans ; Ear, Inner/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Child ; Adolescent ; Adult ; Child, Preschool ; Cochlear Nerve/diagnostic imaging* ; Facial Nerve/abnormalities* ; Cochlea/abnormalities* ; Infant ; Young Adult

Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.