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: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Objective To investigate the current awareness of pharmaceutical service fees among pharmacists in hospitals of Shaanxi province to provide a theoretical basis and decision-making framework for establishing such fees in hospitals of various provinces and cities in the future.Methods A questionnaire survey was conducted among 47 representative hospitals and 53 pharmacists within these hospitals in Shaanxi province.The results were analyzed using differential analysis.Results In most hospitals of Shaanxi province,pharmaceutical services are not provided or not charged for,indicating a lack of practical experience in the establishment of pharmaceutical service fees.Among hospitals that provide and charge for pharmaceutical services,there remains a need for uniformity in specific service content and fee standards,clear regulatory policy support,and a unified evaluation system.Significant differences exist among hospitals of different levels and types in terms of their capacity to provide pharmaceutical services and the forms in which they are offered.There is inconsistency among pharmacists within hospitals regarding crucial aspects of establishing pharmaceutical service fees,and further enhancement is needed in their awareness of relevant policies and the latest guidelines.Conclusions There is considerable room for improvement in establishing pharmaceutical service fees in hospitals of Shaanxi province.Stakeholders should promptly establish and standardize the fee establishment model,differentiate the fee standards for various services,enhance the publicity and dissemination of relevant document requirements to support the smooth implementation of pharmaceutical service fee policies.

Objective:To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods:From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results:Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples ( χ2=5.72, P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum ( χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions:From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.

Objective To investigate the feasibility of granzyme B(GB)promoter-controlled ferritin heavy chain(FTH1)reporter gene expression for monitoring the activation status of chimeric antigen receptor T cells(CAR-T)by magnetic resonance imaging(MRI).Methods Cytotoxic T lymphocytes(CTLs)were screened by Ficoll density gradient centrifugation and flow sorting.The GB promoter and FTH1 gene were ligated together with disialoganglioside 2(GD2)CAR,and lentiviral vectors were transfected into CTLs to construct GD2-CAR-T/pGB-FTH1 cells.GD2-CAR-T/pCMV-FTH1,GD2-CAR-T,and T cells served as control cells.CytoTox96@non-radioactive cytotoxicity was used to detect the killing effect of each group of cells after co-culture with human neuroblastoma cells(SK-N-SH).ELISA was employed to detect the coincubation factor as well as the amount of GB secretion.Western blotting,Prussian blue staining and cellular MRI were applied to detect the expression of the FTH1 gene after co-culture.Results CTLs were successfully obtained,and then GD2-CAR-T/pGB-FTH1,GD2-CAR-T/pCMV-FTH1 and GD2-CAR-T cells were constructed.The killing effect,co-incubation factor and GB secretion of the above 3 groups of cells were significantly higher than those of the T cells,and the level of GB expression was highest at day 1,and then decreased in order at day 3 and day 7 after co-culturing with SK-N-SH cells.The relative expression of FTH1 and iron content of the GD2-CAR-T/pGB-FTH1 cells showed the same trend as GB expression,and the MRI signals were gradually increased.There were no significant differences in the relative expression of FTH1,iron content and MRI signals in the GD2-CAR-T/pCMV-FTH1 cells at all time points.No FTH1 expression or iron aggregation was observed in the GD2-CAR-T and T cells groups.Conclusion MRI based on the FTH1 reporter gene driven by the granzyme B promoter can reflect the GB expression level and tumor killing effect of CAR-T cells,which provides a potential real-time visual means to monitor the cell activation status for CAR-T therapy.

Objective:To investigate the association of serum fibroblast growth factor 23(FGF23) level with insulin resistance(IR) and sex hormone levels in patients with polycystic ovary syndrome(PCOS).Methods:A retrospective study was performed in eighty-seven patients with PCOS, fifty-seven patients with simple IR, and sixty-one healthy women who were admitted to Affiliated Hospital of Zunyi Medical University during October 2021 and November 2022. According to the homeostasis model assessment-IR index, all subjects were divided into normal control group( n=61), IR group( n=57), PCOS without IR group(PCOS group, n=15), and PCOS+ IR group( n=72). The levels of serum FGF23, adiponectin, and sex hormones in all groups were compared, and their correlations with glucose and lipid metabolism indicators were analyzed. Results:The FGF23 level was significantly elevated in the IR group, while markedly reduced in the PCOS group and PCOS+ IR group, with the PCOS group showing a significantly lower concentration. The adiponectin levels were significantly decreased in the IR group, PCOS group, and PCOS+ IR group(all P<0.05). The correlation analysis showed that FGF23 level was positively correlated with adiponectin and sex hormone binding globulin, and negatively correlated with luteinizing hormone, luteinizing hormone/follicle stimulating hormone, and free testosterone index(all P<0.05). Logistic regression results indicated that both FGF23 and adiponectin could be used as good indicators for the diagnosis of PCOS and PCOS with IR(all P<0.05). Conclusion:FGF23 is closely related to IR and androgen as well, and under certain conditions, it can reflect the severity of IR and hyperandrogenemia in PCOS patients. The cutoff value of FGF23 obtained in this study can provide a good reference for the diagnosis of PCOS diseases.

Objective:To investigate the effect of integrated psychological and behavioral intervention on cognitive function and P300 in children with attention-deficit/hyperactivity disorder (ADHD).Methods:A randomized controlled study was conducted on 112 children with ADHD admitted to the Shaoxing 7 th People's Hospital from March 2022 to September 2023. These children were randomly divided into two groups: Group A ( n = 56) and Group B ( n = 56), using a random number table method. Group A received conventional drug treatment, whereas Group B received conventional drug treatment and an integrated psychological and behavioral intervention. The treatment lasted for 3 months. Before and after treatment, the levels of norepinephrine (NE) and dopamine (DA), scores on the Integrated Visual and Auditory Continuous Performance Test, electroencephalogram θ/β ratio, and P300 (latency and amplitude) were determined in each group. The clinical efficacy of the treatment was evaluated in both groups. Results:After treatment, the NE and DA levels in Group B were (340.83 ± 43.22) ng/L and (1.12 ± 0.25) ng/L, respectively. These levels were significantly lower than those in Group A [(416.15 ± 48.37) ng/L, (1.30 ± 0.31) ng/L, t = 8.69, 3.38, both P < 0.05]. The full scale attention quotient and full scale response control quotient in Group B were (82.52 ± 14.15) points and (96.34 ± 13.95) points, respectively. These values were significantly higher than those in Group A [(75.20 ± 13.83) points, (90.62 ± 15.16) points, t = -2.77, -2.08, both P < 0.05). The electroencephalogram θ/β ratio was significantly lower in Group B than in Group A ( t = 3.22, P < 0.05). The latencies of P300 in the Cz and Fz regions in Group B were (346.21 ± 40.52) ms and (344.65 ± 39.52) ms, respectively. The latencies were significantly shorter than those in Group A [(376.16 ± 43.04) ms, (369.35 ± 42.16) ms, t = 3.79, 3.20, both P < 0.05]. Similarly, the amplitudes of P300 in the Cz and Fz regions were significantly greater in Group B [(7.73 ± 1.80) μV, (7.22 ± 1.73) μV] than in Group A [(5.90 ± 1.15) μV and (5.76 ± 1.12) μV] ( t = -6.41, -5.30, both P < 0.05). The total response rate in Group B was significantly higher than that in Group A [94.6% (53/56) vs. 82.1% (46/56), χ2 = 4.26, P < 0.05]. Conclusion:The integrated psychological and behavioral intervention in children with ADHD is good. It can reduce NE and DA levels, improve cognitive function, decrease electroencephalogram θ/β , and improve P300.

Objective:To explore the relationship between personality characteristics, social psychology and satisfactory rate in people undergoing facial cosmetic surgery.Methods:People undergoing facial cosmetic surgery who were admitted to the First Affiliated Hospital of Naval Medical University from February 2021 to February 2022 were seclected. They were asked to fill out the Big Five Inventory (abbreviated version), social psychological factors questionnaire before surgery, and the surgical satisfaction scale 2 weeks after surgery. According to the results of surgical satisfaction, they were divided into satisfied group and dissatisfied group. The distribution of personality characteristics and social psychological factors was analyzed, univariate analysis and logistic multiple regression were used to analyze the personality characteristics and social psychological factors affecting the satisfaction result.Results:There were 217 cases, including 9 males and 208 females, aged 18-45 years old with an average age of 26 years old. According to the operation satisfaction survey, 174 cases were satisfied and 43 cases were dissatisfied. Among the personality characteristics of 217 cases, low agreeableness, high responsibility, high extraversion, low openness, and high neuroticism accounted for the majority; there were statistically significant differences in agreeableness, extraversion, openness, and neuroticism between the satisfied group and the dissatisfied group( P<0.05); but in the comparison of responsibility, there was no statistically significant difference between the two groups ( P>0.05). Among the psychosocial factors of 217 cases, female, aged 18-28 years, with a bachelor’s degree or above, a vocational student or employee, urban registered residence, with a medium income, with a history of plastic surgery, following the doctor’s advice, moderate expectation, surgery suggestion with family members account for the majority; the results of univariate analysis show that the satisfied group and the dissatisfied group were compared in terms of age, education level, monthly income, surgical cost, previous plastic surgery history, and expected effect, the difference was statistically significant ( P<0.05); however, there was no statistically significant difference in gender, marital status, occupation, nature of household registration, choice of surgery, surgery recommended by family members, and consultation in multiple hospitals ( P>0.05). The results of logistic regression analysis showed that low agreeableness, low extraversion, high neuroticism, low age, high education level, and high expectation were independent risk factors affecting the surgical satisfaction( P<0.05). Conclusion:Personality characteristics (low agreeableness, low extraversion, high neuroticism) and social psychological factors (low age, high education level, high expectation) are independent risk factors of surgical satisfaction in people undergoing facial cosmetic surgery.

Objective:To explore the relationship between personality characteristics, social psychology and satisfactory rate in people undergoing facial cosmetic surgery.Methods:People undergoing facial cosmetic surgery who were admitted to the First Affiliated Hospital of Naval Medical University from February 2021 to February 2022 were seclected. They were asked to fill out the Big Five Inventory (abbreviated version), social psychological factors questionnaire before surgery, and the surgical satisfaction scale 2 weeks after surgery. According to the results of surgical satisfaction, they were divided into satisfied group and dissatisfied group. The distribution of personality characteristics and social psychological factors was analyzed, univariate analysis and logistic multiple regression were used to analyze the personality characteristics and social psychological factors affecting the satisfaction result.Results:There were 217 cases, including 9 males and 208 females, aged 18-45 years old with an average age of 26 years old. According to the operation satisfaction survey, 174 cases were satisfied and 43 cases were dissatisfied. Among the personality characteristics of 217 cases, low agreeableness, high responsibility, high extraversion, low openness, and high neuroticism accounted for the majority; there were statistically significant differences in agreeableness, extraversion, openness, and neuroticism between the satisfied group and the dissatisfied group( P<0.05); but in the comparison of responsibility, there was no statistically significant difference between the two groups ( P>0.05). Among the psychosocial factors of 217 cases, female, aged 18-28 years, with a bachelor’s degree or above, a vocational student or employee, urban registered residence, with a medium income, with a history of plastic surgery, following the doctor’s advice, moderate expectation, surgery suggestion with family members account for the majority; the results of univariate analysis show that the satisfied group and the dissatisfied group were compared in terms of age, education level, monthly income, surgical cost, previous plastic surgery history, and expected effect, the difference was statistically significant ( P<0.05); however, there was no statistically significant difference in gender, marital status, occupation, nature of household registration, choice of surgery, surgery recommended by family members, and consultation in multiple hospitals ( P>0.05). The results of logistic regression analysis showed that low agreeableness, low extraversion, high neuroticism, low age, high education level, and high expectation were independent risk factors affecting the surgical satisfaction( P<0.05). Conclusion:Personality characteristics (low agreeableness, low extraversion, high neuroticism) and social psychological factors (low age, high education level, high expectation) are independent risk factors of surgical satisfaction in people undergoing facial cosmetic surgery.

Objective:To explore the application effect of progressive case teaching method based on core competency in standardized nursing training.Methods:A total of 63 nursing students rotated in department of neurosurgery from June 2020 to June 2022 were selected as the research objects and randomized into experimental group ( n=31) and control group ( n=32). The experimental group adopted the progressive case teaching method based on core competency, and the control group adopted the conventional teaching mode. The data was analyzed using SPSS 26.0 to conduct t-test or non-parametric test based on the data normality for comparing the theory results, objective structure clinical examination (OSCE) scores, core competency, self-directed learning ability scores, teaching satisfaction and nursing satisfaction of patients in two wards between the two groups. Results:The theoretical results ( t=4.74, P<0.001) and OSCE scores ( t=3.81, P<0.001) of the experimental group were better than those of the control group. The scores of core competency and autonomous learning ability ( t=4.32, P<0.001) of the experimental group were better than those of the control group. The teaching satisfaction score ( t=2.21, P=0.044) and patient satisfaction score ( t=2.92, P=0.011) of the observation group were better than those of the control group. Conclusion:The progressive case teaching method based on core competency can improve the post competency of nurses, and also improve the teaching satisfaction rate and patient satisfaction rate, which is worthy of being carried out in the subsequent teaching activities.