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.

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 summarize the effectiveness of orthopedic surgery for patients with moderate and severe hallux valgus and analyze its related influencing factors. METHODS: A clinical data of 247 patients (287 feet) with moderate and severe hallux valgus, who were admitted between January 2013 and October 2024 and met the selection criteria, was retrospectively analyzed. There were 39 males and 208 females, with a median age of 57 years (range, 19-89 years). There were 207 cases of single-foot involvement and 40 cases of double-foot involvement; 159 feet were moderate hallux valgus and 128 feet were severe hallux valgus. The disease duration ranged from 3 months to 25 years, with a median of 5 years and 8 months. The hallux valgus angle (HVA), the intermetatarsal angle (IMA), proximal articular set angle (PASA), and the American Orthopaedic Foot and Ankle Society (AOFAS) scores were measured before operation and at 6 months after operation, and the differences (change values) between pre- and post-operation were calculated. All patients were grouped according to the degree of preoperative hallux valgus deformity and age, and the patients with severe hallux valgus according to different surgical procedures, and the change values of HVA, IMA, and AOFAS scores were compared between groups. All patients were grouped according to postoperative HVA, then the postoperative AOFAS scores were compared between groups. RESULTS: All patients successfully completed the operations and were followed up 6 months to 11 years and 3 months, with an average of 4 years and 6 months. The HVA, IMA, PASA, and AOFAS scores at 6 months after operation showed significant improvement compared to preoperative levels, and the differences were significant ( P<0.05). The patients with severe hallux valgus had the higher change values of HVA, IMA, and AOFAS scores than the patients with moderate hallux valgus ( P<0.05). The elderly patients had the highest change values of HVA and AOFAS scores than the young and middle-aged patients ( P<0.05). The patients with postoperative HVA ranging from 0° to 5° had the highest AOFAS scores than the other patients at 6 months after operation ( P<0.05). Among different surgical procedures for severe hallux valgus, the metatarsophalangeal joint fusion had the highest change value of HVA, the Scarf osteotomy had the highest performance in correcting the IMA, and the first metatarsal base osteotomy had the highest improvement in the postoperative AOFAS score, and the differences were significant ( P<0.05). CONCLUSION Elderly patients show the better improvement in HVA and foot function after operation. The first metatarsal base osteotomy show the better improvement in foot function than other surgical procedures. A certain HVA is allowed to remain after hallux valgus correction, and the postoperative AOFAS score is higher when the corrected HVA is in the range of 0°-5°.
Humans ; Hallux Valgus/diagnostic imaging* ; Middle Aged ; Male ; Female ; Aged ; Retrospective Studies ; Adult ; Aged, 80 and over ; Treatment Outcome ; Osteotomy/methods* ; Severity of Illness Index ; Orthopedic Procedures/methods* ; Metatarsophalangeal Joint/surgery* ; Young Adult ; Metatarsal Bones/surgery*

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

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

BACKGROUND:For thoracolumbar spine fractures with developmental stenosis of the vertebral arch,accurate nail placement is difficult using traditional fluoroscopy-assisted techniques.O-arm navigation assistance systems offer higher precision in general vertebral arch nail placement,but there is scarce literature on the application of O-arm navigation-assisted nail placement in thoracolumbar spine fractures with developmental stenosis of the vertebral arch both domestically and abroad. OBJECTIVE:To explore the accuracy of percutaneous vertebral arch nail placement assisted by O-arm navigation in patients with thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch. METHODS:A retrospective analysis was conducted on 53 patients who underwent percutaneous vertebral arch screw fixation surgery at Department of Orthopedics,General Hospital of Central Theater Command of PLA for thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch from January 2021 to March 2023.Totally 208 cases of vertebral arch developmental stenosis were found(cases with multiple vertebral arch developmental stenosis were counted separately).Based on the surgical approach,the patients were divided into two groups:O-arm navigation group(n=98)and C-arm fluoroscopy group(n=110).Postoperative imaging data were compared between the two groups,including anatomical perforation score,functional perforation score,actual vs.expected nail trajectory in the horizontal plane,and sagittal plane angle differences. RESULTS AND CONCLUSION:(1)There was no significant difference in the narrowest width of the pedicle isthmus(pow)between the two groups of patients(P>0.05).The proportions of different degrees of narrowing(mild:6 mm≤pow<7 mm,moderate:5 mm≤pow<6 mm,severe:pow<5 mm)were also not significantly different between the two groups(P>0.05).(2)The overall grade and scores of anatomical perforation and functional perforation were lower in the O-arm group compared to the C-arm group,and these differences were statistically significant(P<0.001).In terms of the angular deviation between the actual and planned screw trajectories,the O-arm group had smaller deviations,and these differences were statistically significant(P<0.05).(3)In the mild and moderate narrowing groups,the O-arm group showed significant advantages in anatomical perforation,functional perforation,and angular deviation between actual and planned screw trajectories,and these differences were statistically significant(P<0.001).(4)The O-arm group demonstrated better performance in anatomical perforation and functional perforation,especially in the T12-L2 segment,with more significant advantages.Additionally,the O-arm group had better angular deviations in actual and planned screw trajectories in all segments compared to the C-arm group.(5)Therefore,the use of O-arm navigation-assisted percutaneous screw placement for the treatment of thoracolumbar fractures with developmental pedicle isthmal narrowing provides higher accuracy and safer surgery.

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.

AIM: To systematically evaluate the efficacy and safety of low-concentrations atropine eye drops in controlling adolescent myopia.METHODS:A computer search was conducted on Wanfang Data, CNKI, VIP, PubMed, Cochrane Library, and Embase databases from January 2010 to March 2024 on clinical studies on low-concentration atropine eye drops for controlling adolescent myopia. Two researchers independently screened trials, extracted data, evaluated risk of bias and quality, and used Review Manager5.4 software to perform Meta-analysis.RESULTS:A total of 17 articles, involving 3 764 cases and 3 952 eyes, were included. The Meta-analysis showed that compared with the control group, low concentrations of atropine could effectively slow down the growth of axial length [MD=-0.15, 95% CI(-0.20, -0.10), P<0.00001], significantly controlled the changes in spherical equivalent [MD=0.39, 95% CI(0.29, 0.48), P<0.00001], and had a significant effect on pupil diameter [MD=0.80, 95% CI(0.33,1.28), P=0.0010] and amplitude of accommodation [MD=-2.54, 95%CI(-4.49, -0.60), P=0.01].CONCLUSION:Low-concentrations atropine are effective in controlling spherical equivalent and axial length of myopia in adolescents, significantly affecting pupil diameter and amplitude of accommodation, and effectively delaying the progression of myopia.

Objective:To study the epidemiological and spatio-temporal distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Hangzhou City, providing a scientific basis for prevention and control of HFRS.Methods:Data of HFRS cases reported in Hangzhou City from January 1, 2010 to December 31, 2022 were collected through the Infectious Disease Surveillance and Reporting Information System of China Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the prevalence and three-distribution characteristics of HFRS in Hangzhou City. Joinpoint regression was used to analyze the trend of HFRS incidence in Hangzhou City from 2010 to 2022. Global and local spatial autocorrelation were used to analyze the spatial distribution pattern of HFRS and the hotspots of incidence in Hangzhou City. And spatio-temporal scanning was used to analyze the spatio-temporal aggregation areas of HFRS in Hangzhou City.Results:From 2010 to 2022, a total of 224 HFRS cases were reported in Hangzhou City, with an average annual incidence of 0.18/100 000. The distribution of cases showed obvious seasonality, with peak incidence in spring (March to May) and autumn (September to November), accounting for 30.80% (69/224) and 26.34% (59/224), respectively. HFRS cases were reported in all districts (counties, cities) of the city, among which Xiaoshan District (66 cases, 29.46%), Chun'an County (41 cases, 18.30%) and Jiande City (25 cases, 11.16%) ranked the top three. The majority of the cases were individuals aged 31 to 60 (65.18%, 146/224), males (74.55%, 167/224), and farmers (46.43%, 104/224). Joinpoint regression analysis indicated that the overall incidence of HFRS in Hangzhou City was in downward trend from 2010 to 2022 [average annual percent change (AAPC) = - 5.01%, 95% confidence intervals ( CI): - 9.46% to - 0.34%, t = - 2.10, P = 0.036]. Global spatial autocorrelation analysis showed that there was a positive spatial correlation in the incidence of HFRS among various streets (townships) in Hangzhou City from 2011 to 2014, 2018, and 2020 (Moran's I > 0, Z > 1.96, P < 0.05). Local spatial autocorrelation analysis showed that from 2010 to 2022, the number of streets (towns) in hot areas (high-high) in Hangzhou City was 0, 2, 3, 3, 3, 3, 0, 0, 4, 0, 1, 0, and 1, respectively, and was relatively fixed in the southwest districts (counties, cities). Spatio-temporal scan analysis identified three clusters: Cluster I was from August 2011 to January 2015, centered on Fenkou Town in Chun'an County, involving 5 townships in Chun'an County; Cluster Ⅱ-1 was from August 2012 to March 2016, centered on Puyang Town in Xiaoshan District, involving 5 townships in Xiaoshan District; Cluster Ⅱ-2 was from June 2019 to June 2020, centered on Xiaya Town in Jiande City, not involving other streets (townships). Conclusions:From 2010 to 2022, the majority of HFRS cases in Hangzhou City are middle-aged male farmers. The overall trend of HFRS epidemic is decreasing, mainly concentrated in the southwest districts (counties, cities) of Hangzhou City. In the future, precise prevention and control measures should be implemented in key areas and among key populations.

Objective:To evaluate the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion for thoracolumbar burst fractures with severe disc injury.Methods:A retrospective study was conducted to analyze the clinical data of 22 patients who had been treated for thoracolumbar burst fractures with severe disc injury at Department of Orthopaedic, General Hospital of Central Theater Command from June 2016 to June 2021. There were 15 males and 7 females, aged 43.50 (29.75, 52.25) years. By the AO classification, there were 12 cases of type B2, 10 cases of type C3. All the patients were treated by the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion. The visual analogue scale (VAS), Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), vertebral wedge angle (VWA) and spinal canal encroachment rate (SCER) were compared between pre-surgery, 1 week post-surgery, 3 months post-surgery and the last follow-up. Their neurological function was graded according to the American Spinal Injury Association (ASIA) impairment scale and interbody fusion evaluated according to their 3D CT at the last follow-up.Results:All the 22 patients were followed up for (26.1±1.3) months. In all patients, the VAS and ODI were significantly lower at 1 week post-surgery than the pre-surgery ones ( P<0.05), and then decreased significantly at 3 months post-surgery and at the last follow-up compared with the values at 1 week post-surgery ( P<0.05). For all patients, there were significant improvements in AVHR, KCA, VWA and SCER at 1 week post-surgery, 3 months post-surgery and the last follow-up compared with the pre-surgery values ( P<0.05), and the SCER at the last follow-up was significantly decreased compared with that at 1 week post-surgery ( P<0.05). All patients experienced improved neurological function in different degrees at the last follow-up, and all intervertebral spaces achieved solid bony fusion. Conclusion:In the treatment of thoracolumbar burst fractures with severe disc injury, the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion can lead to satisfactory long-term therapeutic efficacy, because this strategy can effectively reduce spinal canal encroachment, restore the height of the injured vertebra, reconstruct the curvature of the fracture area and ensure reliable intervertebral fusion.