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 value of serum soluble E-cadherin (sEC) and cyclooxygenase-2 (COX-2) levels in predicting postoperative recurrence and metastasis of breast cancer.Methods:198 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) From Mar. 2023 to Mar. 2025 were selected and followed up for 3 years. The recurrence and metastasis were counted. Patients with recurrence and metastasis were included in the poor prognosis group, and patients without recurrence and metastasis were included in the good prognosis group. The general data, preoperative serum sEC and COX-2 levels were compared between the two groups. The influencing factors of recurrence and metastasis of breast cancer after operation were analyzed. The dose-response relationship and predictive value of serum sEC and COX-2 levels with recurrence and metastasis were analyzed. Logistic regression equation (LR) model 1 was constructed according to conventional influencing factors, and LR model 2 was constructed according to conventional influencing factors combined with serum sEC and COX-2. The predictive efficacy and accuracy of the two models were analyzed by receiver operating characteristic curve (ROC) and calibration curve. According to the ratio of 7∶3, another 85 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) from May. 2023 to May. 2025 were selected for external validation (validation set) .Results:Among 198 breast cancer patients who underwent postoperative follow-up for 3 years, 3 cases were lost to follow-up, and the recurrence and metastasis rate among the 195 patients who completed the 3-year postoperative follow-up was 26.15% (51/195). In the good prognosis group, the proportion of TNM stage III was 20.14%, the proportion of lymph node metastasis was 11.81%, the preoperative serum carbohydrate antigen 153 (CA153) level was (54.19±10.84) U/mL, the carbohydrate antigen 125 (CA125) level was (46.03±10.27) U/mL, the sEC level was (1987.65±191.37) ng/mL, and the COX-2 level was (17.85±5.21) ng/mL. In the poor prognosis group, the proportion of TNM stage III was 45.10%, the proportion of lymph node metastasis was 35.29%, the preoperative serum CA153 level was (65.87±12.23) U/mL, the CA125 level was (57.76±11.51) U/mL, the sEC level was (2 295.37±261.48) ng/mL, and the COX-2 level was (10.42±3.16) ng/mL. Compared with the good prognosis group, they were increased ( t/χ 2=12.00, 14.11, 6.39, 6.79, 8.92, 12.00, P<0.05). Multivariate Logistic regression analysis showed that TNM stage III ( OR=2.078, 95%CI =1.569-2.751, P<0.05), lymph node metastasis ( OR=2.435, 95 %CI=1.843-3.216, P<0.05), serum CA153 ( OR= 1.180,95 %CI=1.026-1.357, P<0.05), CA125 ( OR=1.206,95 %CI=1.033-1.408, P<0.05), sEC ( OR=1.011,95 %CI= 1.007-1.015, P<0.05), COX-2 ( OR=1.378,95 %CI=1.128-1.683, P<0.05) were independent risk factors for postoperative recurrence and metastasis of breast cancer. Restricted cubic spline (RCS) analysis showed that serum sEC and COX-2 levels were positively correlated with the risk of recurrence and metastasis of breast cancer ( P<0.05). ROC analysis showed that serum sEC (AUC=0.762,95 %CI=0.696-0.820, P<0.05) and COX-2 (AUC=0.757,95 %CI=0.691-0.815, P<0.05) could be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. The AUC of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was 0.862 (95 %CI=0.805-0.907, P<0.05). The AUC of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 0.965 (95 %CI= 0.891-0.983, P<0.05), which was significantly larger than that of LR model 1 ( Z=2.015, P<0.05). The calibration curve analysis showed that the calibration degree of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was good, and the prediction results were in good agreement with the actual observation results. The calibration degree of LR model 2 was high, and the prediction results were in good agreement with the actual observation results. The results of external validation showed that the sensitivity of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 82.61%, the specificity was 93.55%, the accuracy was 90.59%, and the Kappa value was 0.762 (95 %CI: 0.549-0.974) . Conclusions:Preoperative serum sEC and COX-2 levels are independent risk factors for postoperative recurrence and metastasis of breast cancer. They can be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. Combined with conventional indicators, they can significantly improve the predictive efficacy.

Objective To establish a predictive nomogram model for diabetic peripheral neuropathy(DPN)in elderly diabetic patients.Methods A total of 200 elderly patients with T2DM admitted to our hospital were enrolled in this study from January 2021 to October 2023.All the patients were divided into a simple T2DM group(n=160)and a T2DM combined with DPN(DPN,n=40)group.The general data and biochemical indexes were compared between the two groups.Spearman correlation analysis was used to explore the correlation between clinical indicators and the occurrence of DPN in the elderly.Logistic regression was used to analyze the influencing factors for DPN in the elderly,and a nomogram was constructed.The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the model.Results The DM duration,DR and HbA1c were higher(P<0.05),while HDL-C was lower in the DPN group than in the T2DM group(P<0.05).Spearman correlation analysis showed that elderly DPN were positively correlated with DR,DM duration and HbA1c(r=0.456,0.565,0.580,P<0.05),and negatively correlated with HDL-C(r=-0.542,P<0.05).Logistic regression analysis showed that DR(OR 1.035,95%CI 1.032～1.040),DM duration(OR 1.070,95%CI 1.045～1.080),HbA1c(OR 1.235,95%CI 1.156～1.280)and HDL-C(OR 0.895,95%CI 0.877～0.950)were both influencing factors for elderly DPN.A nomogram prediction model for elderly DPN was constructed based on DR,DM duration,HbA1c and HDL-C.ROC curve analysis showed that the area under curve of this prediction model was 0.955,with a sensitivity of 92.50%,a specificity of 95.00%,and a cutoff value of 0.251.Conclusions The established predictive diagram model involves four variables,including DR,DM duration,HbA1c and HDL-C,which can assist the clinic to make an early assessment of DPN risk.

Objective:To explore the value of serum soluble E-cadherin (sEC) and cyclooxygenase-2 (COX-2) levels in predicting postoperative recurrence and metastasis of breast cancer.Methods:198 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) From Mar. 2023 to Mar. 2025 were selected and followed up for 3 years. The recurrence and metastasis were counted. Patients with recurrence and metastasis were included in the poor prognosis group, and patients without recurrence and metastasis were included in the good prognosis group. The general data, preoperative serum sEC and COX-2 levels were compared between the two groups. The influencing factors of recurrence and metastasis of breast cancer after operation were analyzed. The dose-response relationship and predictive value of serum sEC and COX-2 levels with recurrence and metastasis were analyzed. Logistic regression equation (LR) model 1 was constructed according to conventional influencing factors, and LR model 2 was constructed according to conventional influencing factors combined with serum sEC and COX-2. The predictive efficacy and accuracy of the two models were analyzed by receiver operating characteristic curve (ROC) and calibration curve. According to the ratio of 7∶3, another 85 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) from May. 2023 to May. 2025 were selected for external validation (validation set) .Results:Among 198 breast cancer patients who underwent postoperative follow-up for 3 years, 3 cases were lost to follow-up, and the recurrence and metastasis rate among the 195 patients who completed the 3-year postoperative follow-up was 26.15% (51/195). In the good prognosis group, the proportion of TNM stage III was 20.14%, the proportion of lymph node metastasis was 11.81%, the preoperative serum carbohydrate antigen 153 (CA153) level was (54.19±10.84) U/mL, the carbohydrate antigen 125 (CA125) level was (46.03±10.27) U/mL, the sEC level was (1987.65±191.37) ng/mL, and the COX-2 level was (17.85±5.21) ng/mL. In the poor prognosis group, the proportion of TNM stage III was 45.10%, the proportion of lymph node metastasis was 35.29%, the preoperative serum CA153 level was (65.87±12.23) U/mL, the CA125 level was (57.76±11.51) U/mL, the sEC level was (2 295.37±261.48) ng/mL, and the COX-2 level was (10.42±3.16) ng/mL. Compared with the good prognosis group, they were increased ( t/χ 2=12.00, 14.11, 6.39, 6.79, 8.92, 12.00, P<0.05). Multivariate Logistic regression analysis showed that TNM stage III ( OR=2.078, 95%CI =1.569-2.751, P<0.05), lymph node metastasis ( OR=2.435, 95 %CI=1.843-3.216, P<0.05), serum CA153 ( OR= 1.180,95 %CI=1.026-1.357, P<0.05), CA125 ( OR=1.206,95 %CI=1.033-1.408, P<0.05), sEC ( OR=1.011,95 %CI= 1.007-1.015, P<0.05), COX-2 ( OR=1.378,95 %CI=1.128-1.683, P<0.05) were independent risk factors for postoperative recurrence and metastasis of breast cancer. Restricted cubic spline (RCS) analysis showed that serum sEC and COX-2 levels were positively correlated with the risk of recurrence and metastasis of breast cancer ( P<0.05). ROC analysis showed that serum sEC (AUC=0.762,95 %CI=0.696-0.820, P<0.05) and COX-2 (AUC=0.757,95 %CI=0.691-0.815, P<0.05) could be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. The AUC of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was 0.862 (95 %CI=0.805-0.907, P<0.05). The AUC of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 0.965 (95 %CI= 0.891-0.983, P<0.05), which was significantly larger than that of LR model 1 ( Z=2.015, P<0.05). The calibration curve analysis showed that the calibration degree of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was good, and the prediction results were in good agreement with the actual observation results. The calibration degree of LR model 2 was high, and the prediction results were in good agreement with the actual observation results. The results of external validation showed that the sensitivity of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 82.61%, the specificity was 93.55%, the accuracy was 90.59%, and the Kappa value was 0.762 (95 %CI: 0.549-0.974) . Conclusions:Preoperative serum sEC and COX-2 levels are independent risk factors for postoperative recurrence and metastasis of breast cancer. They can be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. Combined with conventional indicators, they can significantly improve the predictive efficacy.

Objective To establish a predictive nomogram model for diabetic peripheral neuropathy(DPN)in elderly diabetic patients.Methods A total of 200 elderly patients with T2DM admitted to our hospital were enrolled in this study from January 2021 to October 2023.All the patients were divided into a simple T2DM group(n=160)and a T2DM combined with DPN(DPN,n=40)group.The general data and biochemical indexes were compared between the two groups.Spearman correlation analysis was used to explore the correlation between clinical indicators and the occurrence of DPN in the elderly.Logistic regression was used to analyze the influencing factors for DPN in the elderly,and a nomogram was constructed.The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the model.Results The DM duration,DR and HbA1c were higher(P<0.05),while HDL-C was lower in the DPN group than in the T2DM group(P<0.05).Spearman correlation analysis showed that elderly DPN were positively correlated with DR,DM duration and HbA1c(r=0.456,0.565,0.580,P<0.05),and negatively correlated with HDL-C(r=-0.542,P<0.05).Logistic regression analysis showed that DR(OR 1.035,95%CI 1.032～1.040),DM duration(OR 1.070,95%CI 1.045～1.080),HbA1c(OR 1.235,95%CI 1.156～1.280)and HDL-C(OR 0.895,95%CI 0.877～0.950)were both influencing factors for elderly DPN.A nomogram prediction model for elderly DPN was constructed based on DR,DM duration,HbA1c and HDL-C.ROC curve analysis showed that the area under curve of this prediction model was 0.955,with a sensitivity of 92.50%,a specificity of 95.00%,and a cutoff value of 0.251.Conclusions The established predictive diagram model involves four variables,including DR,DM duration,HbA1c and HDL-C,which can assist the clinic to make an early assessment of DPN risk.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Objective To evaluate the effect of photo-activated disinfection(PAD)as a kind of adjuvant treatment on moderate to severe chronic periodontitis.Methods 21 patients with the chronic periodontitis(totally 218 selected sites)were randomly enrolled and divided into group A(minocycline hydrochloride),group B(PAD),group C(PAD + minocycline hydrochloride),and group D(no adjunctive therapy)for the adjunctive treatment after receiving the scaling and root planing(SRP).Periodontal indexs as probing depth(PD),bleeding on probing(BOP)and clinical attachment loss(CAL)were examined at the baseline,6 and 12 weeks after the treatment.Meanwhile,periodontal pathogens as Porphyromonas gingivalis(Pg)and Tannerella forsythia(Tf)from subgingival plaque of group A,B and C were detected by Real-time PCR.Results Compared with the baseline,the periodontal inflammations of all groups were improved signiffcantly at 6 and 12 weeks after the treatment(P<0.001),and group A,group B and group C were better than group D(P<0.001),group C was better than group A(P<0.001);Furthermore,the concentration of Pg and Tf was decreased significantly(P<0.001),and there was no difference among the three groups with adjunctive therapy.Conclussion As the adjunctive treatment of SRP,PAD could achieve the same and even better effect than minocycline hydrochloride ointment.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.