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.

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 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*

Hepatolenticular degeneration （HLD），also known as Wilson disease (WD) is an uncommon hereditary disorder of the nervous system， characterized by hepatic impairment， extrapyramidal manifestations， psychiatric symptoms， and renal dysfunction， while impaired vision is a rare comorbidity. This article conducts a retrospective analysis of visual acuity changes， treatment， and prognosis of a female patient， aged 22 years， who were diagnosed with HLD complicated by bilateral neuritis in an affiliated hospital of Anhui University of Chinese Medicine in 2022， and a literature review was performed. The findings suggest that impaired vision is a rare manifestation of HLD. Ophthalmologists should consider the possibility of HLD in patients with optic atrophy and optic neuritis， and early intravenous administration of methylprednisolone may help to improve prognosis.

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 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.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.