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 investigate the benefits of using a stapler tractor in the treatment of segmental bronchus during lung segmentectomy through detailed video replay analysis of surgical procedures. Methods We collected data from patients who underwent segmentectomy performed by the same surgical team in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2020 to August 2023. After excluding data that lacked analysis parameters, the remaining patients were divided into four groups based on the methods used for dissociating segmental bronchus: a stapler tractor group (group A), a stapler with bronchial stretching group (group B), a stapler only group (group C), and a silk ligature group (group D). Then, we compared baseline data and videotaped surgical details across all groups. Surgical details included the success rate of one-time segmental bronchus dissociation and severance, the time taken for successful one-time dissociation and severance of the segmental bronchus, the incidence of bleeding during bronchus dissociation, the conversion rate to thoracotomy during surgery, and surgical outcomes such as total operative time, postoperative hospitalization days, postoperative thoracic drainage volume, and pulmonary air leakage rate. Results The study included 325 patients (203 in the group A, 62 in the group B, 29 in the group C, and 31 in the group D). There was no statistically significant difference in baseline data among the four groups. However, significant differences were found in terms of total operation time, postoperative hospitalization days, intraoperative blood loss, segmental bronchial stump length, postoperative air leakage rate, hemorrhage rate during segmental bronchial dissociation, and conversion to thoracotomy rate among the four groups (P<0.05). Conclusion Using a stapler tractor for dissociating segmental bronchus in lung segmentectomy results in shorter operative time, less risk of intraoperative bleeding, and less surgical complications. This study provides valuable evaluation methodologies through the analysis of video replay surgical details, contributing to the improvement of lung segmentectomy quality.

ObjectiveThe study of the treatment of hypertriglyceridemia with scutellaria baicalensis stem-leaf total flavonoid (SSTF) are rarely reported.The objective of this study is to investigate the effects of SSTF on lipid metabolism and oxidative stress in rats with hypertriglyceridemia.Methods60 SD rats were randomly divided into normal group, model group, fenofibrate group (100 mg·kg-1), SSTF groups with low, medium and high doses (50,100,200 mg·kg-1, respectively). All rats, except those of the normal group, were fed with high-fat diet and given corresponding drug intervention for 6 weeks. Then the body masses at the 2nd, 4th and 6th weeks as well as wet weight of the liver at the end of 6th week were recorded, and liver index was calculated. The serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected. The levels of TG, TC, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver tissue were determined, and liver histopathological changes were observed by hematoxylin-eosin (HE) staining.ResultsIn the model group, compared with the normal group, the body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week were increased, the serum levels of TG, TC and LDL-C got increased with decreased HDL-C level, and the levels of TG[（1.603±0.146）mmol/L], TC[（3.474±0.356）mmol/L] and MDA[（10.288±1.979）nmol/mg] in liver tissue were increased with decreased levels of SOD[（106.840±24.014）U/mg] and GSH-PX[（9.278±2.079）U/mg]. Compared with the model group,the fenofibrate group and all SSTF groups showed decreased body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week, decreased serum levels of TG, TC and LDL-C with increased level of HDL-C, and decreased levels of TG, TC and MDA with increased levels of SOD and GSH-PX in liver tissue. The comparsion between the fenofibrate group and the high-dose SSTF group revealed that the body masses at the 4th and 6th weeks and liver index at the end of 6th week were decreased, the serum levels of TG, TC and LDL-C were decreased with increased level of HDL-C, and the levels of TG[（0.718±0.135）mmol/L] and MDA[（5.071±1.305）nmol/mg] in liver tissue got decreased with increased levels of SOD[（172.210±30.214）U/mg] and GSH-PX[（14.623±2.418）U/mg] in the latter group. All the above-mentioned differences were statistically significant (all P<0.05).ConclusionSSTF can regulate lipid metabolism and improve pathological injury of liver in hypertriglyceridemia rats, which may be related with inhibition of lipid peroxidation and reduction of oxidative stress.

The aim of this paper was to study the specific mechanism of Fangji Huangqi Decoction(FHT) in decreasing uric acid and improving renal function in mice with hyperuricemia(HUA) induced by potassium oxonate, so as to provide theoretical basis for the research and development of drugs for clinical prevention and treatment of HUA and the modernization of traditional Chinese medicine. Sixty Kunming male mice were randomly divided into 6 groups, with 10 mice in each group, namely normal group, model group(250 mg·kg~(-1) potassium oxonate), FHT high, medium and low-dose groups(10 920, 5 460, and 2 730 mg·kg~(-1)) and positive drug allopurinol group(5 mg·kg~(-1)). Drug administration was given once a day for 7 days. On the 6 th day, mice of each group were kept in metabolic cages, and their urine was collected for 24 hours for determination of uric acid, creatinine, and β2-microglobulin(β2-MG) levels. After 7 days, the animals were sacrificed to determine serum uric acid, creatinine β2-MG and interleukin-1β(IL-1β) levels, and their liver and kidney tissues were collected. The liver tissues were used for subsequent determination of xanthine oxidase(XOD) activity, and the kidney tissues were used for subsequent determination of IL-1β levels, pathological tests and related Western blot experiments. In the cell transfection experiment, the cells were divided into blank group, model group(4.8 mmol·L~(-1) uric acid treatment), FHT administration group(4.8 mmol·L~(-1) uric acid+200 μg·mL~(-1) FHT), leucine-rich repeat kinase 1(LRRK1)-small interfering RNA(siRNA) group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection) and LRRK1-siRNA+FHT group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection+200 μg·mL~(-1) FHT). After 24 h incubation, the level of IL-1β in the cell supernatant was detected, and the cellular proteins were extracted and used to determine LRRK1, epidermal growth factor receptor(EGFR), PDZ kinase 1(PDZK1) and nuclear factor-kappa B(NF-κB) protein expression levels. The results showed that, FHT could significantly reduce the uric acid, creatinine and β2-MG levels in serum and β2-MG levels in urine, increase the uric acid and creatinine levels in urine, and improve the renal pathological results of the HUA mice, but showed no effect on liver XOD activity; at the same time, we found that the expression level of IL-1β in serum and kidney, NF-κB, LRRK1 and EGFR protein levels in kidney of HUA mice were significantly increased, and the expression level of PDZK1 protein was significantly decreased, while FHT could significantly improve the abnormal expression of these proteins, and FHT increased protein expression of renal organic anion transporter 1(OAT1), OAT3 and ATP bin-ding transporter G2(ABCG2) in HUA mice, but FHT had no effect on the expression of urate transporter 1(URAT1). In the cell transfection experiment, after transfection of LRRK1-siRNA, the levels of IL-1β, EGFR and NF-κB in supernatant were significantly reduced, and the expression of PDZK1 protein was significantly increased. As compared with the LRRK1-siRNA group, the levels of IL-1β, EGFR, PDZK1 and NF-κB did not change significantly with the additional FHT. This study showed that FHT may regulate the renal uric acid transport system through LRRK1 gene, improve the capacity of uric acid excretion, so as to reduce the level of serum uric acid. At the same time, FHT can not only protect the kidney directly, but also in an indirect manner by reducing the level of uric acid.
Animals ; Drugs, Chinese Herbal ; Hyperuricemia/drug therapy* ; Kidney ; Male ; Mice ; Uric Acid

Objective:To compare the changes of cerebral blood flow (CBF) in bipolar disorder type Ⅱ patients with and without suicidal ideation.Methods:Pseudo-continuous arterial spin labelling (pCASL) was examined with resting-state functional magnetic resonance imaging(rs-fMRI) on all subjects, CBF images of bipolar disorder type Ⅱ depression with suicidal ideation ( n=48), Bipolar Disorder type Ⅱ without suicidal ideation ( n=41), healthy controls ( n=62) at rest were collected. One-way ANOVA and Gaussian random field (GRF) were used to compare the CBF values between the groups to locate the regions with significant change. Results:Compared with the control group, CBF of left superior temporal gyrus (extending to the temporal pole) ( t=3.87, P<0.01; t=4.44, P<0.01) and left putamen ( t=4.04, P<0.01; t=3.19, P<0.01) increased in bipolar disorder type Ⅱ patients with and without suicidal ideation, and CBF of the right posterior cingulate gyrus (extending to the calcarine gyrus) decreased in bipolar disorder type Ⅱ patients with suicidal ideation( t=-4.66, P<0.01). Conclusions:There were abnormal CBF in left superior temporal gyrus and left putamen in bipolar disorder type Ⅱ patients with suicidal ideation and bipolar disorder type Ⅱ patients without suicidal ideation, while the decreased CBF in right posterior cingulate gyrus may be the specific brain change in bipolar disorder type Ⅱ patients with suicidal ideation.

Objective:To investigate the changes of white matter fiber bundles in patients with bipolar disorder depressive epoch.Methods:Forty-two patients with unmedicated bipolar disorder (BD) depression and 59 age-, sex- and handedness-matched healthy controls who underwent DTI were recruited in the study. According to the Johns Hopkins University human white matter fiber bundle map, the white matter tissue of the brain was segmented into 20 acknowledged large fiber bundles. The PANDA software was used to calculate the four average diffusion properties of each white matter fiber bundle for each subject. Nonparametric substitution test was used to detect the difference of diffusion index between the two groups on these 20 white matter fiber bundles. Pearson correlation analysis was performed between FA values and RD values extracted from significantly different white matter fiber bundles and clinical indices.Results:In comparison to the normal controls, BD patients had a significant decreased fractional anisotropy (FA) values in the left uncinate fasciculus (0.40±0.01 vs. 0.41±0.01, P=0.001) and the forceps minor (0.36±0.02 vs. 0.38±0.02, P<0.001). Additionally, the radial diffusivity values increased in the left uncinate fasciculus (6.57×10 -4±2.41×10 -5vs. 6.40×10 -4±2.42×10 -5, P=0.001 7). Pearson correlation analysis showed that there were no significant correlations among the clinical indices the FA values and AD values in the left uncinate fasciculus and forceps minor. Conclusions:The patients with bipolar disorder in depression possibly have abnormal left uncinate fasciculus and the forceps minor.

Objective:To investigate the changes of white matter fiber bundles in patients with bipolar disorder depressive epoch.Methods:Forty-two patients with unmedicated bipolar disorder (BD) depression and 59 age-, sex- and handedness-matched healthy controls who underwent DTI were recruited in the study. According to the Johns Hopkins University human white matter fiber bundle map, the white matter tissue of the brain was segmented into 20 acknowledged large fiber bundles. The PANDA software was used to calculate the four average diffusion properties of each white matter fiber bundle for each subject. Nonparametric substitution test was used to detect the difference of diffusion index between the two groups on these 20 white matter fiber bundles. Pearson correlation analysis was performed between FA values and RD values extracted from significantly different white matter fiber bundles and clinical indices.Results:In comparison to the normal controls, BD patients had a significant decreased fractional anisotropy (FA) values in the left uncinate fasciculus (0.40±0.01 vs. 0.41±0.01, P=0.001) and the forceps minor (0.36±0.02 vs. 0.38±0.02, P<0.001). Additionally, the radial diffusivity values increased in the left uncinate fasciculus (6.57×10 -4±2.41×10 -5vs. 6.40×10 -4±2.42×10 -5, P=0.001 7). Pearson correlation analysis showed that there were no significant correlations among the clinical indices the FA values and AD values in the left uncinate fasciculus and forceps minor. Conclusions:The patients with bipolar disorder in depression possibly have abnormal left uncinate fasciculus and the forceps minor.

Objective:To compare the changes of cerebral blood flow (CBF) in bipolar disorder type Ⅱ patients with and without suicidal ideation.Methods:Pseudo-continuous arterial spin labelling (pCASL) was examined with resting-state functional magnetic resonance imaging(rs-fMRI) on all subjects, CBF images of bipolar disorder type Ⅱ depression with suicidal ideation ( n=48), Bipolar Disorder type Ⅱ without suicidal ideation ( n=41), healthy controls ( n=62) at rest were collected. One-way ANOVA and Gaussian random field (GRF) were used to compare the CBF values between the groups to locate the regions with significant change. Results:Compared with the control group, CBF of left superior temporal gyrus (extending to the temporal pole) ( t=3.87, P<0.01; t=4.44, P<0.01) and left putamen ( t=4.04, P<0.01; t=3.19, P<0.01) increased in bipolar disorder type Ⅱ patients with and without suicidal ideation, and CBF of the right posterior cingulate gyrus (extending to the calcarine gyrus) decreased in bipolar disorder type Ⅱ patients with suicidal ideation( t=-4.66, P<0.01). Conclusions:There were abnormal CBF in left superior temporal gyrus and left putamen in bipolar disorder type Ⅱ patients with suicidal ideation and bipolar disorder type Ⅱ patients without suicidal ideation, while the decreased CBF in right posterior cingulate gyrus may be the specific brain change in bipolar disorder type Ⅱ patients with suicidal ideation.

Objective To understand the endemic situation and control effect of schistosomiasis through the surveillance in a national surveillance site of Jurong City, so as to provide the evidence for formulating the prevention and control measures. Methods According to the National Schistosomiasis Monitoring Scheme (2014 Edition), the surveillance of schistosome infection in Oncomelania hupensis snails, residents and livestock was performed in the Kongqing Village, a national surveillance site of Jurong City, from 2015 to 2017. Results The areas with snails were 0, 0, and 0.63 hm² in 2015, 2016, and 2017 respectively; the average densities of living snails were 0, 0, and 0.19 snails/0.1 m² in 2015, 2016, and 2017 respectively. No schistosome-infected snails were found. The positive rates of blood tests for schistosomiasis in the local residents were 7.72%, 7.45% and 3.45%, and the positive rates of blood tests in the floating population were 4.90%, 3.47% and 0.97% in 2015, 2016 and 2017, respectively. No positives were found in the schistosome etiology detection in the crowd and livestock. Conclusions The effect of schistosomiasis prevention and control is obvious in Jurong City, but O. hupensis snails are still of recurrence. Therefore, the monitoring and control efforts should be strengthened to consolidate the achievements of schistosomiasis prevention and control.

[ABSTRACT]OBJECTIVETo investigate the phoenix roebelenii pollen as the allergen of allergic rhinitis in Hainan Province and provide guidance for prevention and treatment of allergic rhinitits.METHODSA total of 2054 patients with allergic rhinitis were tested with the allergen of phoenix roebelenii pollen by skin prick test, and then choose 30 positive cases to give the nasal mucosa provocation test. RESULTSThe total positive rate of allergen of phoenix roebelenii pollen by skin prick test was 67.38% (1384/2054). The 30 cases with positive skin prick test were all positive in nasal mucosa provocation test and the cases in control group were all negative.CONCLUSIONPhoenix roebelenii pollen is an important allergen in Hainan Province. There is a correlation between skin prick test and nasal mucosa provocation test. The allergen skin prick test can provide clue for the patients to avoid the pathogenic allergens and for the specific immunotherapy.