Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Background and purpose:Primary adrenal intravascular large B-cell lymphoma(IVLBCL)is rare and highly aggressive.Unfortunately,comprehensive and sufficient understanding of the disease is lacking.This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL.Methods:Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology,Fudan University Shanghai Cancer Center.The clinical and histopathological features,immunophenotype,treatment and prognosis were analyzed.The molecular genetic characteristics were detected using next-generation sequencing(NGS).This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:050432-4-2307E).Results:All of the 5 patients were male,with median age 52 years(ranged 50-82 years).Two cases had low-grade fever,1 case had abdominal pain,1 case was found by physical examination,and the information of the remaining one was unknown.Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases.On initial diagnosis,imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose(FDG)uptake.Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case.Morphologically,large atypical lymphocytes were confined to blood vessels,and fibrinous necrosis was observed in some cases.Immunohistochemical study revealed that CD20 was positive in all cases.Ki-67 proliferation index was high,all above 80%.80%(4/5)of the cases were of non-germinal-center B-cell-like(non-GCB)phenotype,100%(4/4)of the cases had MYC/BCL2 double expression.Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases.Follow-up data were available in 3 patients.One patient who underwent only surgical resection died 5 months after diagnosis,one achieved complete remission after surgery plus R-CHOP,and the other diagnosed by biopsy achieved a partial remission after R-CHOP.The 1-year overall survival rate was 66.7%,and overall survival was 5-87 months.NGS testing in 1 case showed missense mutations in MYD88 V217F,TP53,CDH1,ARID1B,MSH3,MLH3,PTPRK,CD22 and FLCN.Conclusion:Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male.The majority of our patients were non-GCB phenotype,often accompanied by MYC/BCL2 double expression,and MYD88 non-L265P mutation was detected.Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity.It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease,which might not only help with early diagnosis,timely treatment and improvement of prognosis,but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.

Objective:To explore the short-term clinical efficacy, safety and patients' prognostic influencing factors of CyberKnife for the treatment of brain metastases in non-small cell lung cancer (NSCLC).Methods:A retrospective case series study was conducted. The clinical data of 58 NSCLC patients who received CyberKnife treatment for brain metastases at Jilin Cancer Hospital from July 2020 to January 2022 were retrospectively analyzed. At 3 months after CyberKnife treatment for brain metastases, and the efficacy of radiotherapy was evaluated on the basis of changes of brain metastases detected by contrast-enhanced magnetic resonance imaging (MRI) of the head. Overall survival (OS) and local recurrence-free survival (LRRFS) were analyzed in 58 patients by using the Kaplan-Meier method; the efficacy of cumulative brain metastasis volume for determining the survival of CyberKnife-treated NSCLC patients with brain metastases was analyzed by using the receiver operating characteristic (ROC) curve with the survival status of patients during the follow-up period as the gold standard, and the optimal cut-off value of cumulative brain metastasis volume was obtained; the clinical factors affecting OS and LRRFS of CyberKnife-treated NSCLC patients with brain metastases were analyzed by univariate and multivariate Cox proportional hazards models, and the adverse reactions associated with CyberKnife treatment were evaluated.Results:Among the 58 patients, 26 (44.8%) were male and 32 (55.2%) were female, with a median age [ M ( Q1, Q3)] of 64 years old (56 years old, 70 years old); there were 1-7 brain metastatic lesions in each patient, and there were 98 brain metastatic lesions in the 58 patients. There were 2 deaths (3.4%) within 3 months after CyberKnife treatment. At 3 months after treatment, there were 3 cases (5.4%) in complete remission, 36 cases (64.3%) in partial remission, 13 cases (23.2%) in stable disease, and 4 cases (7.1%) in disease progression in the remaining 56 patients. ROC curve analysis showed that the area under the curve for determining the survival of CyberKnife-treated NSCLC patients with brain metastases based on the cumulative brain metastasis volume was 0.593 (95% CI: 0.423-0.763), and the optimal cut-off value of cumulative brain metastasis volume was 15 cm 3. Median follow-up time was 12.6 months (7.5 months, 17.9 months). The 6- and 12-month OS rates were 91.3% and 79.5%, respectively, and the 6- and 12-month LRRFS rates were 93.0% and 89.2%, respectively. Multivariate Cox regression analysis showed that the Karnofsky functional status score (>70 points vs. ≤70 points, HR= 0.103, 95% CI: 0.019-0.545, P = 0.007), control of extracranial tumor (controlled vs. uncontrolled, HR = 0.145, 95% CI: 0.049-0.429, P < 0.001), cumulative brain metastasis volume (≤15 cm 3vs. >15 cm 3, HR = 0.105, 95% CI: 0.028-0.399, P = 0.001) were independent influencing factors for poor OS, and the control of extracranial tumor (controlled vs. uncontrolled, HR = 0.062, 95% CI: 0.006-0.616, P = 0.018), cumulative brain metastasis volume (≤15 cm 3vs. >15 cm 3, HR = 0.440, 95% CI: 0.007-0.292, P = 0.001), and target area total bioequivalent dose (BED) (≤60 Gy vs. >60 Gy, HR = 5.299, 95% CI: 1.020-27.530, P = 0.047) were independent influencing factors for poor LRRFS. Only grade 1-2 headache [53.5% (31/58)], nausea and vomiting [36.2% (21/58)] and other adverse reactions occurred after treatment, and no ≥grade 3 adverse reactions occurred. Conclusions:CyberKnife treatment for NSCLC brain metastases has high local control rate and short-term survival rate with mild adverse effects. Karnofsky functional status score, control of extracranial tumor and cumulative brain metastasis volume may affect OS of CyberKnife-treated NSCLC patients with brain metastases, and the control of extracranial tumor, cumulative brain metastasis volume and total BED may affect local recurrence.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To evaluate the effect of image-guided with cone-beam computed tomography (CBCT) based on volumetric modulated arc therapy (VMAT)-flattening filter free (FFF) on the setup errors of stereotactic body radiotherapy (SBRT) in patients with spinal metastatic tumors.Methods:The clinical data of 15 patients with spinal metastatic tumors who underwent SBRT in Jilin Cancer Hospital from August 2020 to January 2022 were retrospectively analyzed. The radiotherapy dose of bone metastasis was 32 Gy per 4 times and CBCT scanning was performed before and after radiotherapy. Every patient received radiotherapy 4 times; all 15 patients underwent SBRT 60 times in total and 120 CBCT volume images were finally obtained and analyzed. The systematic error (Σ) and random error (σ) were calculated at different correction threshold levels. The translational setup error and rotational setup error at the left-right (X axis), head-foot (Y axis) and front-back (Z axis) directions before and after radiotherapy were compared, which were expressed as Σ ± σ.Results:The pre-SBRT and post-SBRT translational setup errors were (0.14±0.27) cm and (0.07±0.19) cm, respectively ( P<0.001) in the X direction, (-0.05±0.33) cm and (0.00±0.19) cm, respectively ( P = 0.001) in the Y direction, (-0.13±0.19) cm and (-0.02±0.14) cm, respectively ( P = 0.012) in the Z direction. The pre-SBRT and post-SBRT rotational setup errors were (-0.31±0.76)° and (-0.09±0.34)°, respectively ( P < 0.001) in the X direction, (-0.13±0.88)° and (-0.07±0.36) °, respectively ( P < 0.001) in the Y direction, (0.10±0.51)° and (0.16±0.38)°, respectively ( P < 0.001) in the Z direction. Conclusions:CBCT correction could reduce Σ and σof the translational setup and rotational setup, increase the accuracy of SBRT based on VMAT-FFF for patients with spinal metastatic tumors.

Objective:To understand the thyroid function of the physical examination population in Tangshan area, and analyze the effects of thyroid function on blood lipids, fasting blood glucose (FPG), and serum 25 hydroxyvitamin D [25(OH)D].Methods:A population from the Tangshan area who underwent physical examinations at the Kailuan General Hospital from June 2020 to June 2021 was selected as the study subjects and the levels of their thyroid serological indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (TT3), and thyroid hormone (TT4)] were tested. According to thyroid function, they were divided into normal group, hyperthyroidism group, hypothyroidism group, subclinical hyperthyroidism group, and subclinical hypothyroidism group. We compared the blood lipid indicators [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], FPG, and 25(OH)D levels in different subgroups, and the Pearson correlation analysis was used to investigate the correlation between TSH levels and blood lipids, FPG, and 25(OH)D levels.Results:In this study, 2 884 subjects were selected from the physical examination population in Tangshan area. The proportion of people with abnormal thyroid function was 12.03%(347/2 884), among which the proportion of subclinical thyroid function abnormal population in the total thyroid function abnormal population was 80.69%(280/347). As men age, the proportion of thyroid dysfunction in the age groups of 21-<30 years old, 30-<40 years old, 40-<50 years old, and ≥50 years old was 5.06%(4/79), 7.52%(33/439), 8.91%(53/595), and 9.95%(66/663), respectively. The proportion of thyroid dysfunction in the above age group of women was 14.02%(15/107), 15.06%(61/405), 15.47%(67/433), and 29.45%(48/163). The serum TG, TC, LDL-C, and 25(OH)D levels in the hyperthyroidism group were lower than those in the normal group, while HDL-C and FPG levels were higher than those in the normal group, with statistically significant differences (all P<0.05). The serum TG and TC in the hypothyroidism group were higher than those in the normal group, while FPG and 25(OH)D were lower than those in the normal group, with statistically significant differences (all P<0.05). TSH levels were positively correlated with TC and LDL-C, while negatively correlated with FPG and 25(OH)D (all P<0.05). Conclusions:Subclinical thyroid dysfunction is the main cause of thyroid dysfunction in the Tangshan area, and TSH levels are correlated with blood lipids, fasting blood glucose, and serum 25(OH)D levels.

Objective:To investigate the association between split foot and electrophysiology in patients with amyotrophic lateral sclerosis (ALS).Methods:The clinically definite or clinically probable ALS patients hospitalized in the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from April 2021 to December 2022 were prospectively collected. From April 2021 to December 2022, patients who visited the Chinese People′s Liberation Army General Hospital for other reasons without abnormal electrophysiological examination were collected as the control group. The incidence of split leg [the limb whose modified Medical Research Council Muscle Strength Scale (mMRC) score of ankle dorsiflexors was lower than that of ankle plantarflexors] in ALS patients was calculated, and the incidence of split foot (the limb whose mMRC score of hallux dorsiflexors was lower than that of hallux plantarflexors) in ALS patients was calculated. The amplitude of compound muscle action potential (CMAP) of common peroneal nerve and tibial nerve was detected to observe the involvement of motor neurons innervating ankle dorsiflexors and ankle plantarflexors. The characteristics of split leg and split foot in ALS patients were analyzed from the perspective of muscle strength, and the characteristics of split foot in ALS patients were analyzed from the perspective of electrophysiology. Receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of peroneal nerve/tibial nerve CMAP amplitude ratio in distinguishing ALS patients from controls.Results:A total of 101 ALS patients with lower limb involvement and 110 controls with normal lower limb muscle strength were collected. Among the 101 ALS patients with lower limb involvement, strength of ankle plantarflexors was greater than that of ankle dorsiflexors in 35.64% (36/101) patients, strength of ankle dorsiflexors was greater than that of ankle plantarflexors in 5.94% (6/101) patients, and strength of ankle plantarflexors and ankle dorsiflexors was equal in 58.42% (59/101) patients. Strength of hallux dorsiflexors was lower than that of hallux plantarflexors in 53.47% (54/101) patients, strength of hallux dorsiflexors was greater than that of hallux plantarflexors in 1.98% (2/101) patients, and the strength of hallux dorsiflexors and hallux plantarflexors was equal in 44.55% (45/101) patients. The incidence of split leg was negatively correlated with age ( OR=0.25, 95% CI 0.16-0.40, P<0.05), course of disease ( OR=0.52, 95% CI 0.38-0.80 P<0.05) and ALS functional revised scores ( OR=0.29, 95% CI 0.12-0.67, P<0.05). The incidence of split foot was negatively correlated with the onset time of lower limb symptoms ( OR=0.96, 95% CI 0.93-0.99, P<0.05). Compared with the control group, the differences of the decrease of CMAP amplitude in the common peroneal nerve and tibial nerve [the common peroneal nerve (6.45±2.56) mV vs (3.63±1.83) mV, tibial nerve (12.87±4.72) mV vs (9.18±6.22) mV] were statistically significant ( t=-4.65, t=-3.44, both P<0.001) and the differences of the peroneal nerve/tibial nerve CMAP amplitude ratio (0.54±0.24 vs 0.36±0.18) decrease was statistically significant ( t=-4.31, P<0.001) in patients with split foot. ROC curve analysis showed that the area under the ROC curve of CMAP amplitude ratio of common peroneal nerve/tibial nerve in ALS patients with split foot was 0.70, indicating that the accuracy of CMAP amplitude of common peroneal nerve/tibial nerve in distinguishing ALS patients from controls was low. Conclusions:In ALS patients with lower limb involvement, strength of ankle dorsiflexors is weaker than that of ankle plantarflexors, and strength of hallux dorsiflexors is weaker than that of hallux plantarflexors. At the diagnostic level, the CMAP amplitude ratio of common peroneal nerve/tibial nerve in ALS patients with split foot has a lower accuracy in the diagnosis of ALS.

Objective:Charcot-Marie-Tooth disease (CMT) comprises a group of clinically and genetically heterogeneous inherited neuropathies with an estimated prevalence of 1 in 2500. This study aimed to analyze the clinical and mutational characteristics of Chinese CMT patients with MFN2, BSCL2 and LRSAM1 variants.Methods:In this study, genetic analysis was performed in 206 Chinese patients at Chinese PLA General Hospital from December 2012 to March 2020 with clinical diagnosis of CMT, and reported variants of MFN2, BSCL2 and LRSAM1 related to CMT2.Results:We reported ten MFN2 mutations in ten unrelated patients (7 male, 3 female), two of whom had positive family history. Three novel mutations were detected including c.475-2A>G (splicing); c.687dupA (p.E230Rfs*16) and c.558dupT (p.S186fs). We reported three BSCL2 mutations of four unrelated patients, including c.461C>G (p.S154W), c.461C>T(p.S154L), and novel variants of c.1309G>C (p.A437P) and c.845C>T (p.A282V). Furthermore, two novel variants of LRSAM1, including c.1930G>T (p.G644C) and c.1178T>A (p.L393Q) were detected in two unrelated patients.Conclusion:Mutational spectrum of MFN2-, BSCL2-and LRSAM1-related CMT disease is expanded with the identification of novel variants in Chinese patients.

Objective:To investigate the correlation between serum thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) cconcentrations and arteriosclerosis development in middle-aged and older adult patients with depression.Methods:A total of 200 middle-aged and older adult patients with depression who received treatment in the Third People's Hospital of Huzhou from January 2018 to October 2019 were included in this study. They were divided into four groups ( n = 50/group) according to TG-Ab and TPO-Ab test results: TG-Ab-positive (group 1), TPO-Ab-positive (group 2), TG-Ab-positive and TPO-Ab-positive (group 3), TG-Ab-negative and TPO-Ab-negative (control group). Serum thyroid hormone level, ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity, and the incidences of intima-media thickening and plaque formation in the lower extremity arteries were compared between groups. Results:Total thyroxine concentration in the control group, groups 1, 2 and 3 was (89.96 ± 2.45) nmol/L, (101.29 ± 3.35) nmol/L, (90.09 ± 2.70) nmol/L, (97.55 ± 2.57) nmol/L, respectively. There was a significant difference in total thyroxine concentration between groups ( F = 3.85, P < 0.05). Brachial-ankle pulse wave velocity in the control group, groups 1, 2, and 3 was (1 327.55 ± 67.78) cm/s, (1 510.36 ± 83.05) cm/s, (1 422.71 ± 71.40) cm/s, (1 533.95 ± 87.01) cm/s, respectively. There was a significant difference in brachial-ankle pulse wave velocity between groups ( F = 65.12, P < 0.05). The incidence of intima-media thickening in the control group, groups 1, 2, and 3 was 18% (9/50), 50% (25/50), 32% (16/50), 60% (30/50), respectively. The incidence of plaque formation in the control group, groups 1, 2, and 3 was 22% (11/50), 56% (28/50), 40% (20/50), 70% (35/50), respectively. There were significant differences in intima-media thickening and plaque formation between groups ( χ2 = 21.83, 25.77, all P < 0.001). Logistic multivariate regression analysis showed that age ( OR = 0.953) and TG-Ab ( OR = 1.116) were independent risk factors for developing arteriosclerosis in middle-aged and older adult patients with depression ( P < 0.05). Conclusion:TG-Ab-positive results are an independent risk factor for developing arteriosclerosis in middle-aged and older adult patients with depression. TPO-Ab-positive results have a synergistic effect on the occurrence and development of arteriosclerosis in middle-aged and older adult patients with depression. Monitoring serum TG-Ab and TPO-Ab concentrations is of great clinical significance for the prevention and treatment of arteriosclerosis in middle-aged and older adult patients with depression.

Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.