BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery，in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate，surgery related complications，postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months，the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy，little impact on urinary control and sexual function recovery，and few postoperative complications，which can be used as one of the treatment options for these patients.

Transcatheter aortic valve replacement (TAVR) has emerged as the first-line treatment for aortic valve stenosis. Coronary obstruction is a severe complication of TAVR, with mortality rates exceeding 30%. Coronary obstruction can be classified as acute or delayed based on the timing of the onset, and as direct or indirect obstruction according to the underlying mechanism. Risk factors for predicting coronary obstruction include a small sinus of Valsalva diameter, excessively long native leaflets, low coronary height, and small sinotubular junction height and diameter. Accurate preoperative assessment of these anatomical parameters using CT is crucial for selecting the appropriate valve type, size, and implantation depth. Preventive technical strategies for coronary obstruction include intraoperative interventional treatments (such as the "Chimney" stenting technique), leaflet modification (such as the BASILICA technique), and alignment of the annulus and coronaries. These techniques have demonstrated significant efficacy in reducing the incidence of coronary obstruction and associated mortality. This paper reviews the epidemiology, classification, and mechanisms of coronary obstruction, with a particular focus on the identification, prevention, and treatment of high-risk patients. The aim is to highlight the importance of recognizing and managing coronary risks during TAVR and to provide actionable recommendations for the prevention and treatment of coronary obstruction in clinical practice.
Humans ; Transcatheter Aortic Valve Replacement/methods* ; Risk Factors ; Aortic Valve Stenosis/surgery* ; Postoperative Complications/prevention & control* ; Coronary Occlusion/etiology*

BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.

Objective:To analyze the clinical features and immunotherapy responsiveness of patients with myelin oligodendrocyte glycoprotein immunoglobulin G-antibody associated disease (MOGAD) with epilepsy, and display the risk factors of epilepsy in MOGAD.Methods:Eighty-nine patients with MOGAD diagnosed at the First Affiliated Hospital of Zhengzhou University between October 2019 and May 2023 were enrolled and classified into 2 groups upon MOGAD with ( n=29) or without epilepsy ( n=60). The Expanded Disability Status Scale (EDSS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used for evaluation of severity, and EDSS or CASE scores on the 30th day after first-line immunotherapy initiation lower than that on admission were defined as well treatment responsiveness. The differences of general data, clinical manifestations, cerebrospinal fluid (CSF) and peripheral blood biochemical examination results, and immunotherapy reactivity between the 2 groups were thoroughly explicated. In addition, the risk factors of epilepsy in MOGAD were analyzed by univariate and multivariate Logistic regression analysis. Results:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy were characterized by lower age of onset [24.5(10.3, 34.0) years vs 11.0(6.5, 20.0) years, Z=-2.348, P=0.019], higher percentage of male patients [43.3%(26/60) vs 75.9%(22/29), χ 2=8.326, P=0.004], higher virus infection rate [28.3%(17/60) vs 51.7%(15/29), χ 2=4.645, P=0.031], higher incidence of prodromal symptoms [11.7%(7/60) vs 34.5%(10/29), χ 2=6.586, P=0.010], higher blood-brain barrier breakdown rate [35.0%(21/60) vs 58.6%(17/29), χ 2=4.458, P=0.035], higher percentage of CSF albumin level>450 mg/L [48.3%(29/60) vs 75.9%(22/29), χ 2=6.056, P=0.014] and higher creatine kinase level [45.50(28.50, 69.75) U/L vs 57.50(41.75, 97.25) U/L, Z=-2.349, P=0.019]; more epilepsy [0(0) vs 29/29 (100.0%), χ 2=89.000, P<0.001] and disturbance of consciousness [0(0) vs 6/29(20.7%), χ 2=10.224, P=0.001] as clinical manifestations, and more cerebral cortex lesions [30/60(50.0%) vs 25/29(86.2%), χ 2=10.856, P=0.001] on magnetic resonance imaging. Nevertheless, the patients with MOGAD without epilepsy were featured with more visual impairment [23/60(38.3%) vs 3/29(10.3%), χ 2=7.406, P=0.007], limb weakness [18/60(30.0%) vs 1/29(3.4%), χ 2=8.209, P=0.004], sensory disturbance [15/60(25.0%) vs 0(0), Fisher exact probability test, P=0.002] and more cervical cord lesions [22/60(36.7%) vs 4/29(13.8%), χ 2=4.946, P=0.026] on magnetic resonance imaging. Immunotherapy responsiveness was relatively poor in the MOGAD with epilepsy group [EDSS score lower than that on admission: 15/29(51.7%) vs 46/60(76.7%), χ 2=5.641, P=0.018; CASE score lower than that on admission: 16/29(55.2%) vs 47/60(78.3%), χ 2=5.072, P=0.024] compared with the MOGAD without epilepsy group. Male was the independent risk factor of epilepsy in MOGAD ( OR=7.078, 95% CI 1.709-29.326, P=0.007). Conclusions:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy reported more male patients, lower age of onset and higher incidence of prodromal symptoms, blood-brain barrier dysfunction rate, virus infection rate, CSF albumin level and creatine kinase level; clinical phenotypes were mainly meningoencephalitis and more cerebral cortex lesions were shown on magnetic resonance imaging. MOGAD with epilepsy was closely related to poor immunotherapy responsiveness, and gender was found to be the independent risk factor for epilepsy in MOGAD.

In order to understand the prevalence and genetic variation of H9N2 subtype avian influ-enza virus in Shandong,a total 492 tracheal and lung tissue samples collected from chicken farms with respiratory symptoms in partial areas in Shandong were detected by H9 subtype AIV real-time RT-PCR,and the positive samples were inoculated with chicken embryos for two generations.Whole genome sequences of the positive strains by applying Illumina Miaseq platform,and genetic evolution and mutation at positions associating with viral pathogenicity and transmissibility were analyzed.The results showed that there were 72 samples were positive for H9 subtype AIV among the 492 samples,with a positive rate of 14.63％.Thirty-four strains of H9 subtype AIV were ob-tained from the positive samples after passing through chicken embryo,meanwhile,the 34 isolates were all H9N2 subtype AIV by whole genome sequencing analysis.By analyzing the evolutionary tree of HA and NA genes,HA and NA genes of the 34 H9N2 AIV strains belonged to Y280-like branch and F/98-like branch,respectively.Meanwhile,based on above branches,there were obvious time node subbranch,which one was"isolates before 2013",another one was"isolates after 2013".The HA cleavage sites of thirty-four H9N2 strains were all 325PSRSSR↓GLF333,which met the se-quence characteristics of the lowly pathogenic avian influenza virus,and the HA receptor binding site 226 amino acid was leucine,which had the characteristics of blinding to a-2,6 mammalian sialic acid receptors.Among the internal amino acid sites that are key to mammalian adaptation,all strains had an I368V mutation in the PB1 gene that enhanced viral transmissibility in mammals and the PB2 genes of some strains were mutated to enhance the mammalian adaptation of I292 V and A588 V.The above results illustrated that the H9N2 subtype AIV gene segments in Shandong have different degrees of recombination and gene variation,so it is necessary to strengthen the monito-ring of virus variation.

Objective:To investigate the changes of brain microstructure in active Crohn's disease (CD) patients with or without anxiety by diffusion kurtosis imaging (DKI), and to explore the relationship between brain microstructure and anxiety in patients with CD.Methods:Thirty-seven patients with CD who were treated in Changzhou Second People's Hospital Affiliated to Nanjing Medical University from January 2022 to January 2023 were included as the CD group, and 20 healthy subjects were included as the healthy control group during the same period. All subjects were assessed with hospital anxiety and depression scale-anxiety (HADS-A) before magnetic resonance imaging(MRI) scan. According to the HADS-A score, CD patients were divided into the CD group with anxiety (16 cases) and the CD group without anxiety (21 cases). After MRI scan, DKI parameters were obtained by DKE software. One-way analysis of variance was used to compare DKI parameters between the two groups of CD patients and the healthy control group. Pearson correlation was used to analyze the correlation between DKI parameters in different brain areas and psychological scale scores in the two groups of CD patients.Results:The axial diffusion kurtosis(AK)values in the right insula, the left superior temporal gyrus, the right thalamus, the left middle temporal gyrus, the right inferior temporal gyrus, the left lingual gyrus and the right anterior cuneus were significantly different among the three groups ( F=3.060-9.627, all P<0.05).There were significant differences in the radial diffusion kurtosis(RK) values in the right cerebellar region 6 and the left hippocampus among the three groups ( F=4.124, 3.536, 4.200, all P<0.05). Further multiple comparison results showed that the AK values of the right insula (0.701±0.028)( P=0.019), the left superior temporal gyrus (0.764±0.016)( P=0.002) and the right thalamus (0.728±0.016)( P=0.001) in the CD group without anxiety were lower than those of the healthy control group(0.726±0.010, 0.780±0.015, 0.771±0.082), and the RK value of the right cerebellar region 6 ( P=0.021) was lower than that of the healthy control group. The AK values of the right insula ( P=0.023), the left superior temporal gyrus ( P=0.015), the right thalamus ( P=0.031), the left middle temporal gyrus ( P=0.006), the right inferior temporal gyrus ( P=0.001) and the left lingual gyrus ( P=0.007) in the CD group with anxiety were lower than those in the healthy control group. The RK values of right cerebellar region 6 ( P=0.012) and left hippocampus ( P=0.004) were lower than those of healthy control group. The AK values of the right insula ( P=0.002) and the right anterior cuneus ( P=0.017) in the group with anxiety were lower than those in the CD group without anxiety. In the CD group with anxiety, the AK value of the right insula was correlated with erythrocyte sedimentation rate(ESR)( r=-0.47, P=0.048), HADS-A score ( r=-0.68, P=0.002), SES-CD( r=-0.84, P<0.001) and duration of disease ( r=-0.61, P=0.008) were negatively correlated. AK values in the left superior temporal gyrus with anxiety CD group were negatively correlated with HADS-A score ( r=-0.51, P=0.030) and SES-CD score ( r=-0.48, P=0.046). Conclusion:The microstructure of some brain regions was damaged in CD patients with or without anxiety, which was manifested as decreased RK and AK values in DKI parameter values, which may be related to the anxiety state in active CD patients.

Objective:To investigate the expression characteristics of mucin 5B (MUC5B) protein and programmed cell death factor 4 (PDCD4) protein in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram model for prognosis prediction.Methods:Clinical data of 100 patients who underwent radical surgical resection and were diagnosed as ICC by postoperative pathology from September 2009 to September 2020 in the Third Affiliated Hospital of Wenzhou Medical University were retrospectively selected, including 46 males and 54 females, aged (56.9±12.2) years old. Immunohistochemistry was used to detect the expression of MUC5B and PDCD4 protein in 100 cases of ICC and corresponding adjacent tissues respectively, and the relationship between them and clinicopathological factors of ICC patients was analyzed. Univariate and multivariate Cox regression analysis were performed to analyze the influencing factors on postoperative prognosis of ICC patients. The nomogram model was constructed using rms package and performed internal verification.Results:The positive expression rate of MUC5B protein in ICC was 76.0% (76/100), which was higher than that in para-cancer tissues 27.0%(27/100), and the difference was statistically significant ( χ2=11.33, P=0.015). While the positive expression rate of PDCD4 protein in ICC was 21.0%(21/100), which was lower than that in normal tissues 73.0% (73/100), and the difference was statistically significant ( χ2=15.57, P=0.007). Multivariate Cox regression analysis showed that ICC patients with carbohydrate antigen 19-9>37 kU/L, tumor length>5 cm, tumor TNM stage Ⅱ/Ⅲ, tumor medium/low differentiation, MUC5B positive expression, and PDCD4 negative expression had a high risk of short survival after resection (all P<0.05). The nomogram model was constructed based on the above indicators, and the C-index was 0.801. The postoperative survival calibration curve showed that the high predictive survival fit of the nomogram model, and the area under the receiver operating characteristic curve was 0.862. Conclusions:Positive expression of MUC5B protein and negative expression of PDCD4 protein in ICC tissue suggest poor prognosis of ICC patients. The nomogram model constructed on the basis of MUC5B and PDCD4 protein is well distinguished and has ideal predictive efficacy.

Objective:To explore the clinical effectiveness of high-frequency color Doppler ultrasound (HFCDU) assisted harvest of radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap to repair soft tissue defect below the elbow.Methods:A retrospective study was conducted on the clinical data of patients who underwent repair of soft tissue defects below the elbow using the radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap at the Second Hospital of Tangshan from January 2016 to June 2021. Prior to the surgery, HFCDU was utilized to identify and measure the course of the lateral forearm cutaneous nerve and the perforating branch of the radial artery surrounding the wound. Subsequently, the flap rotation point, axis, and area were meticulously designed. During the surgical procedure, the skin flap was harvested either through a subcutaneous tunnel or by direct transfer, while the nerve stump at the defect site was anastomosed end-to-end with the lateral cutaneous nerve of the forearm contained in the skin flap. After reducing the wound at the donor site, it was either directly sutured or repaired using a medium-thick skin graft harvested from the thigh. After surgery, the survival of the skin flap, wound healing at the donor site, and the survival of the skin graft were observed. At the last follow-up, the static two-point discrimination of the flap was measured, and patient satisfaction with the appearance of the flap was assessed using the Michigan hand outcomes questionnaire(MHQ). This questionnaire categorized satisfaction into five levels: very dissatisfied (1 point), dissatisfied (2 points), fair (3 points), satisfied (4 points), and very satisfied (5 points). The scar condition of the donor site was evaluated according to the Vancouver scar scale (VSS), which scored from 0 to 15 points, with higher scores indicating more severe scarring. Descriptive analysis of the data was performed using SPSS 27.0 software.Results:A total of 33 patients were included in the study, comprising 20 males and 13 females, with an average age of (41.0±11.7) years (range, 23-65 years). The defect locations included 6 forearms, 9 wrists, and 18 hands, with all patients having exposed bones and (or) tendons. The defect area ranged from 3.0 cm × 2.5 cm to 12.0 cm × 5.0 cm. The detection result of cutaneous nerves and perforating blood vessels using HFCDU were consistent with the actual findings during surgery, showing no discrepancies. The area of the skin flaps ranged from 3.5 cm × 3.0 cm to 13.0 cm × 6.0 cm. All 33 skin flaps survived postoperatively, with good blood supply and no infections reported; the wounds at the donor site healed primarily, and all grafted skin survived. The duration of postoperative follow-up was (15.6±2.9) months (range, 10-24 months), and the patients’ static two-point discrimination of the flap was measured at (12.5±3.3) mm (range, 8-20 mm). The result of the MHQ indicated that 23 patients were very satisfied with the appearance of the flap (5 points), while 10 patients were satisfied (4 points). The VSS score for the donor site was (4.3±0.9) points (range, 3-6 points), indicating that the scar at the donor site was mild.Conclusion:HFCDU can accurately identify the lateral forearm cutaneous nerve and the perforating branch of the radial artery.The radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap can provide a reliable blood supply, good appearance, sense and patient satisfaction, which is suitable for repairing soft tissue defects below the elbow.