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

Restless legs syndrome （RLS） is a common neurological sensory-motor disorder， and the diagnosis of RLS mainly rely on the subjective clinical symptoms described by the patient， with a lack of specific auxiliary examinations or biomarkers. The diagnosis of this disease is still challenging for atypical cases. Various other diseases may have similar clinical symptoms as RLS， such as leg discomfort， leg pain and abnormal leg movement. This article summarizes the RLS mimics that might be confused with RLS symptoms， including the neurogenic， vascular， and musculoskeletal factors that might cause leg discomfort and pain， as well as the differential diagnosis of sleep-related movement disorders with symptoms overlapped with RLS， so as to help clinicians recognize RLS phenotype and provide a reference for the diagnosis of diseases that might be confused with RLS.

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Objective: To evaluate the clinical value of combining low-dose energy spectrum CT with virtual un-enhanced(VUE) scanning and deep-learning image reconstruction(DLIR) in aortic CT angiography(CTA). Methods : In a prospective study, 94 patients scheduled for aortic CTA were randomized into two groups: a low-dose energy spectrum group and a standard 100 kVp enhancement group, with 47 patients in each. All patients initially underwent a true un-enhanced(TUE) scan at 120 kVp using adaptive statistical iterative reconstruction-V(ASIR-V) at 40% for image reconstruction. The low-dose group received enhanced scans using gemstone spectral imaging(GSI) mode with DLIR-H, producing 60 keV virtual monoenergetic images(VMIs) and VUE images. The standard group was scanned at 100 kVp, with images reconstructed using ASIR-V at 50%. Parameters were measured including CT values, noise(SD), signal-to-noise ratio(SNR), and contrast-to-noise ratio(CNR) for key vascular and muscular areas, alongside the effective radiation dose(ED). Two radiologists evaluated the image quality using a 5-point scale. Results : The low-dose group exhibited significantly higher SNR and CNR values in the ascending aorta, descending aorta, abdominal aorta, and common iliac artery compared to the standard group(P<0.05), with comparable subjective quality scores. The VUE images also demonstrated superior SNR values in the abdominal aorta, common iliac artery, and psoas major muscle, and CNR value in the ascending aorta compared to TUE images, with similar subjective quality. Importantly, the ED in the low-dose group was about 40% lower than that of the standard group. Conclusion Low-dose energy spectrum CT with DLIR in aortic CTA can significantly enhance SNR and CNR, while approximating the image quality of traditional TUE scans, thereby substantially reducing radiation exposure.

Objective The purpose of this study was to provide a more effective method for researching the prevention and treatment of Graves'disease by comparing the effects of two plasmid vectors expressing the human thyrotropin receptor(TSHR)A subunit gene in inducing an animal model of Graves'disease via electroporation.Methods Plasmids pcDNA3.1-THSR A,and pTriEx1.1-THSR A expressing the TSHR A subunit were constructed and used to induce Graves'disease by intramuscular injection with immediate electroporation once every 3 weeks for a total of 4 times.Mice in the control group were injected with PBS.One week after the second electroporation,blood was collected to measure serum thyrotropin receptor antibody(TRAb).Three weeks following the last electroporation,echocardiography was performed on the mice.Mice were sacrificed 4 weeks after the last electroporation;blood,thyroid,and orbital tissues were collected;serum total thyroxine(TT4)was measured;and histological examination was performed.Results The average concentrations of serum TRAb in the pcDNA3.1-TSHR A group(n=15)and the pTriEx1.1-TSHR A group(n=13)were(6.9±2.0)U/L and(7.5±2.2)U/L,respectively.The latter was significantly higher than that in the control group(4.9±0.5)U/L(P=0.033).The average concentrations of serum TT4 in the pcDNA3.1-TSHR A group and pTriEx1.1-TSHR A group were(41.4±23.8)ng/mL and(63.2±53.7)ng/mL,respectively,both higher than that in the control group:(20.2±4.0)ng/mL(P＜0.01).Thyroid pathology showed thyroid follicular epithelial hyperplasia with T-cell infiltration in the model group.Echocardiography showed that the left ventricle mass in the pTriEx1.1-TSHR A group was higher than those in the control group(P=0.007)and pcDNA3.1-TSHR A group(P=0.012).Orbital pathology showed fibrotic changes in the extraocular muscles of mice in the model groups.Conclusions Both pcDNA3.1 and pTriEx1.1 expressing the TSHR A subunit were able to induce Graves'disease in mice by electroporation,and the efficiency of the two plasmids in inducing hyperthyroidism and Graves'ophthalmopathy was similar.The efficiency of pTriEx 1.1-TSHR A in inducing thyrotoxic heart disease was better than that of pcDNA3.1-TSHR A.

Objective:To explore the features of levels of lung cancer biomarkers in peripheral blood of adults in Beijing and surrounding areas, and establish personalized reference intervals for these biomarkers.Methods:A cross sectional study was conducted. The lung cancer biomarker data, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neuron specific enolase (NSE), progastrin-releasing peptide (ProGRP), and squamous cell carcinoma antigen (SCC-Ag), collected from adults who underwent cancer prevention examinations at the Cancer Hospital of the Chinese Academy of Medical Sciences from July 2021 to July 2022 were retrospectively analyzed. The interquartile range method was used to eliminate outliers, and the P95 value was calculated. Upper limit of 5 lung cancer biomarkers in different gender and age groups were obtained by referring to the reference intervals of quantitative analytes in the clinical laboratory (WS/T 402-2024). By analyzing the data of 208 adults who underwent cancer prevention physical examinations at the same center in June 2021 and 140 patients with benign lung masses confirmed by surgical resection pathology from January 2016 to June 2022, the established reference intervals for biomarkers were validated. Results:Two thousand six hundred and twenty-six cases of apparently healthy physical examiners were included for constructing reference intervals, including 1 456 males (55.4%) and 1 170 females (44.6%); the age range was 20-88 years old. The serum levels [ M ( Q1, Q3)] of CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 in 2 626 cases were 1.63 (1.07, 2.43) ng/ml, 13.08 (11.44, 14.77) ng/ml, 34.93 (29.02, 42.19) pg/ml, 0.80 (0.60, 1.00) ng/ml and 1.96 (1.48, 2.63) ng/ml, respectively. The serum levels of CEA [1.88 (1.22, 2.76) ng/ml vs. 1.41 (0.93, 2.02) ng/ml], NSE [13.31 (11.87, 15.00) ng/ml vs. 12.69 (10.96, 14.53) ng/ml], SCC-Ag [0.9 (0.7, 1.1) ng/ml vs. 0.7 (0.6, 0.9) ng/ml], and CYFRA21-1 [2.02 (1.53, 2.71) ng/ml vs. 1.87 (1.40, 2.51) ng/ml] in males were higher than those in females, and ProGRP [34.00 (28.25, 41.55) pg/ml vs. 36.12 (29.97, 42.98) pg/ml] was lower than that in females, and the differences were statistically significant (all P < 0.001). There were statistically significant differences in serum CEA levels between the groups of ≤ 40 years old (458 cases), >40-50 years old (827 cases), >50-60 years old (783 cases), >60-70 years old (412 cases), and >70 years old (146 cases) in pairwise comparison (all P < 0.05). Except for the age groups of ≤ 40 years old and >40-50 years old and the age groups of >60-70 years old and >70 years old, there were statistically significant differences in serum NSE levels among the other age groups in pairwise comparison (all P < 0.05). There were statistically significant differences in serum ProGRP levels between the 5 age groups (all P < 0.05). There were statistically significant differences when comparing the serum SCC-Ag level in the >40-50 age group, >50-60 age group and >60-70 age group with that in the ≤40 age group and >70 age group, respectively (all P < 0.05). However, there was no statistically significant difference between the other age groups in pairwise comparison (all P > 0.05). There were statistically significant differences in serum CYFRA21-1 levels between the 5 age groups (all P < 0.05). When gender and age were not distinguished, the P95 values of serum CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 levels were 4.44 ng/ml, 16.61 ng/ml, 57.65 pg/ml, 1.50 ng/ml, and 4.21 ng/ml, respectively. Considering gender and age, except for the >70 age group with no statistically significant difference in the P95 value of serum CEA level between males and females ( P > 0.05), the P95 value of serum CEA level in males was higher than that in females in all other age groups (all P < 0.001); the P95 values of serum CEA level in both males and females increased with age, but showed a decreasing trend in males over the age of 70. The P95 value of serum NSE level in males was higher than that in females in the age groups of ≤ 40 years and >40-50 years (both P < 0.05), while there was no statistically significant difference in the P95 value of serum NSE level between males and females in other age groups (all P > 0.05). The P95 values of serum NSE level in both males and females decreased firstly and increased later with age, reaching their highest levels at the age of >70. The P95 values of serum ProGRP level in females aged ≤ 40 and >50-60 were higher than those in males (both P < 0.05), while there was no statistically significant difference in the P95 value of serum ProGRP level between genders in other age groups (all P > 0.05); the P95 values of serum ProGRP level in both males and females increased with age. There was no statistically significant difference in the P95 value of serum SCC-Ag level between males and females in the ≤ 40 age group ( P > 0.05), while the P95 value of serum SCC-Ag level in males was higher than that in females in all other age groups (all P < 0.05). The P95 values of serum SCC-Ag level in males increased with age, while they were stable in females. There was no statistically significant difference in the P95 value of serum CYFRA21-1 level between males and females in the >60-70 age group ( P > 0.05), while the P95 value of serum CYFRA21-1 level in males was higher than those in females in all other age groups (all P < 0.05); the P95 values of serum CYFRA21-1 level in both males and females increased with age. Based on data from 2 626 apparently healthy physical examiners, reference intervals for the levels of 5 lung cancer biomarkers were constructed in different age groups of different genders. Validation was conducted on 208 physical examiners and 140 patients with benign lung lesions, and it was found that the compliance rate of using newly created reference intervals for different gender and age groups to interpret detection results was >90%, and the validation was passed. Conclusions:There are gender and age differences in the reference intervals of CEA, CYFRA21-1, NSE, ProGRP, and SCC-Ag in peripheral blood of adults in Beijing and surrounding areas. The constructed reference intervals of gender and age for biomarkers have been validated and shown good results, providing reference for optimizing the clinical application of lung cancer-related biomarkers.

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

Objective To summarize the operation experience of 1 case of ultra-long-distance single-port robotic-assisted laparoscopic renal cyst decortication using a domestic robotic system,and provide references for the development of long-distance telesurgery.Methods The procedure was performed using a domestically produced single-port robotic system.The distance between the main control end and the patient end was 2 400 km.The operation was conducted remotely via a 5G network and a 100 Mbps dedicated line provided by China Telecom.The surgeon controlled the robotic arm remotely.Results The surgery was completed smoothly within a duration of 32 min.The real-time latency was(90±20)ms.Blood loss during the operation was 10 mL,and no drainage tube was placed.The patient recovered smoothly and returned to the ward without any complications.Conclusion It is safe and feasible for the domestically produced single-port robotic system to implement ultra-long-distance telesurgery.This approach facilitates the decentralization of advanced medical resources and helps mitigate disparities in healthcare access.

Objective:To design a set of new type of surgery instrument for pectus excavatum(PE),so as to improve safety and effectiveness of minimally invasive operation in surgery for PE.Methods:The design of the new type of surgical instrument for PE adopted multifunctional orthopedic board that combined both penetrating and supporting functions.The T type handle,special sealing screw for single hole,setscrew and stator,which were convenient for operation,were equipped for the orthopedic board.The new type of surgical instrument was applied in clinical PE surgery since November,2010,and a total of 1398 PE surgeries were conducted in the 10 years,which included 1078 surgeries with single hole,and 320 surgeries with multi holes.The success rate of PE surgery with single hole mode was assessed.Results:In 1398 PE surgeries,the number of PE patients,whose ages were less or equal to 12 years old,and who all adopted single hole mode,was 887 cases,and the success rate of surgery with single hole was 100%.In addition,the number of PE patients,whose age was larger than 12 years old,was 511 cases,and the surgery with single hole was successfully applied in 191 cases of them,and the success rate of surgery with single hole was 37.4%.Conclusion:The the new type of surgical instrument for PE by surgery with single hole and multi holes has mature technique,and it is safety and effectiveness,which has higher clinical application value.

Objective:To analyze the infection status and epidemiological characteristics of respiratory pathogens in children with acute respiratory infections (ARI) at Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University from 2023 to 2024.Methods:This study enrolled the patients (aged 0-17 years) who visited the outpatient or emergency department or were hospitalized at Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University due to ARI from March 2023 to March 2024. Throat swab specimens of the patients were collected, and fluorescence quantitative PCR was used to detect influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), human rhinovirus (HRV), human adenovirus (HAdV), and Myocoplasima pneumonia ( Mp). These patients were divided into five groups by gender: <1, 1-2, 3-5, 6-11, 12-17 years. Chi-square test was used to perform statistical analysis on the detection rates of respiratory pathogens among patients of different genders and ages, and across distinct seasons. Results:A total of 46 379 children were enrolled and among them, 27 418 children tested positive for respiratory pathogens, with a positive rate of 59.12%. Among the positive cases, 5 177 (18.88%) were infected with more than one respiratory pathogen, with the co-infection of Mp and HRV being the most common type, followed by Mp and HAdV co-infection. The pathogens, ranked from the highest to the lowest detection rates, were Mp (20.74%, 9 620/46 379), RSV (12.76%, 5 920/46 379), HAdV (11.64%, 5 399/46 379), HRV (11.24%, 5 213/46 379), FluB (8.23%, 3 815/46 379), and FluA (6.80%, 3 154/46 379). There were statistically significant differences in the detection rates of RSV, HRV and Mp among children of different genders (χ 2=11.85, 15.23, 16.36; all P<0.001). The differences in the detection rates of the six pathogens among different age groups were statistically significant (all P<0.001), and the detection rates of FluA, FluB, HRV, HAdV and Mp in children aged 0-5 years showed an upward trend with age (all P<0.001). The highest detection rates of FluA, FluB, HRV and HAdV were in the 3-5 years group, while the highest detection rate of Mp was in the 6-11 years group, which was 40.15% (4 615/11 495). The detection rate of RSV showed a decreasing trend with age ( P<0.001), with the highest detection rate observed in the <1 year group (25.02%, 2 208/8 826). There were statistically significant differences in the detection rates of the six pathogens in different seasons (all P<0.001). Conclusions:The overall detection rate of respiratory pathogens in children with ARI in Xuzhou from 2023 to 2024 is high. Single-pathogen infection is the predominant pattern, and the most prevalent pathogen is Mp. There are gender differences in the detection rates of RSV, HRV, and Mp. The detection rate of RSV decreases with age, while the detection rates of FluA, FluB, HRV, HAdV, and Mp increase with age among children aged 0-5 years. The prevalence of FluA, FluB, RSV, HRV, HAdV, and Mp all exhibit seasonal patterns.