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 current status and changing trends of the disease burden of traumatic brain injury (TBI) in China from 1990 to 2023, and to quantitatively assess the impact of different influencing factors on this disease burden, thereby providing references for the prevention of TBI. METHODS: Based on the 2023 Global Burden of Disease Study (GBD), indicators including incidence and years lived with disability (YLDs) were used to analyze the status and changing trends of TBI disease burden in China from 1990 to 2023. Additionally, the decomposition method established by Gupta was adopted to quantify the effects of population growth, population aging, age-specific incidence rate, and disease severity on YLDs. RESULTS: From 1990 to 2023, the age-standardized incidence rate and YLDs rate of TBI in China showed an overall upward trend, with a significant downward trend between 2015 and 2020, followed by a resumption of upward trend after 2020. The disease burden of TBI in males was higher than that in females, with a larger increase amplitude. The elderly population had higher TBI incidence rate and YLDs rate, also with a larger upward amplitude. Falls were the main cause of TBI in China, and the changing trend of the disease burden caused by falls was consistent with the overall trend of TBI disease burden; meanwhile, the elderly population bore a relatively high disease burden from falls. Taking 1990 as the baseline, the growth rates of YLDs in males and females in 2023 were 101.54% and 101.40%, respectively. For males, the proportions of YLDs growth attributed to population growth, population aging, age-specific incidence rate, and disease severity were 26.91%, 49.62%, 37.74%, and -12.73%, respectively; for females, the corresponding proportions were 28.85%, 57.69%, 27.65%, and -12.79%. CONCLUSION From 1990 to 2023, population aging had a significant impact on the disease burden of TBI in China. Strengthening the prevention and control of falls and paying close attention to males and the elderly population should be the key focuses of TBI prevention and control work in China in the future.
Humans ; Brain Injuries, Traumatic/epidemiology* ; China/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Aged ; Adult ; Cost of Illness ; Adolescent ; Young Adult ; Persons with Disabilities/statistics & numerical data* ; Child ; Global Burden of Disease ; Disability-Adjusted Life Years ; Child, Preschool ; Infant ; Aged, 80 and over

Objective To investigate the effect of blood flow restriction combined with low-intensity plyometric jump training(LI-PJT+BFR)on lower limb dynamic postural control of functional ankle instability(FAI)in college students. Methods From March to May,2023,40 FAI college students were recruited from Xi'an Physical Education University,and randomly divided into high-intensity plyometric jump training(HI-PJT,n = 14)group,low-intensity plyomet-ric jump training(LI-PJT,n = 13)group and LI-PJT+BFR group(n = 13).All the groups finished the six-week corresponding training.The maximum voluntary isometric contraction(MVIC)of tibialis anterior,peroneus lon-gus,lateral head of gastrocnemius,gluteus maximus,vastus lateralis,biceps femoris and semitendinosus were measured,and the root mean square(RMS)of electromyography of these muscles was measured during the sin-gle-leg landing(SLL),using wireless surface electromyography before and after intervention.Moreover,they were assessed with Y-balance test and Cumberland Ankle Instability Tool(CAIT). Results MVIC and RMS of the target muscles improved after intervention in all the groups(t>2.218,P<0.05),except MVIC and RMS of peroneus longus,gluteus maximus,biceps femoris and semitendinosus in LI-PJT group,and RMS of peroneus longus in LI-PJT+BFR group;and MVIC and RMS of the target muscles were the least in LI-PJT group(F>3.262,P<0.05),except those of peroneus longus.The extension scores of Y-balance test and the total score improved after intervention(t>2.485,P<0.05),and they were the least in LI-PJT group(F>5.042,P<0.05).The CAIT score improved after intervention(t>5.227,P<0.001),and it was the least in LI-PJT group(F = 4.640,P<0.05). Conclusion LI-PJT+BFR could improve lower limb dynamic postural control of FAI college students,which is similar to HI-PJT.

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.

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.

ObjectiveTo explore the effect of hip neuromuscular training on reducing the risk of anterior cruciate ligament (ACL) injury in female soccer players. MethodsFrom March to May, 2022, 39 female soccer players from Xi'an Physical Education University were randomly divided into control group (n = 19) and experimental group (n = 20). On the basis of daily training, the control group received sham intervention, and the experimental group received hip neuromuscular training, for six weeks. Before and after training, they were measured dynamic knee valgus (DKV) angle and assessed with Landing Error Score System (LESS); while they were also measured the maximal voluntary isometric contraction (MVIC) and root mean square (RMS) of electromyography as single leg landing of gluteus medius and gluteus maximus. ResultsAll the indexes varied little after training in the control group (|t| < 1.178, P > 0.05), while the indexes improved in the experimental group (|t| > 2.288, P < 0.05), except sagittal score of LESS; and all the indexes improved more in the experimental group than in the control group (|t| > 2.609, P < 0.05), except sagittal score of LESS and MVIC of gluteus maximus. ConclusionHip neuromuscular training can reduce the risk of ACL injury in female soccer players.

The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca's area cluster,Wernicke's area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding clus-ter or BA.The findings of the present study could provide explanations for the functional connec-tions between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These pro-teomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.

Objective　To investigate the prevalence of anxiety and depression in epilepsy patients in rural areas,and to explore the influencing factors.Methods　The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to evaluate depression and anxiety of 388 epilepsy patients in rural areas From March 2020 to March 2021.Univariate analysis was performed on factors that may cause comorbid anxiety and depression of epilepsy patients,and logistic regression was used to analyze the possible influencing factors.Results　Among the 388 rural epilepsy patients,there were 198 (51.03%) patients comorbid with anxiety,159 (40.98%) comorbid with depression,and 130 (33.51%) comorbid with both anxiety and depression.Multivariate logistic regression analysis showed that patients，educational level,age of onset,seizure frequency,the cost of treatment and compliance were the influencing factors of anxiety.The seizure frequency,the cost of treatment and compliance of patients were the influencing factors of epilepsy comorbid depression.Conclusion　Epilepsy patients in rural areas have a higher prevalence of anxiety and depression.Low education level and age of onset between 21 and 30 years old are risk factors for comorbid anxiety in epilepsy patients.The seizure frequency,treatment cost and poor compliance are risk factors for comorbid anxiety and depression.Targeted interventions should be carried out for the epilepsy patients in rural areas.

【Objective】 To investigate the effect and mechanism of inhibiting Yes-associated protein1 (YAP1) expression by verteporfin on proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) exposed to hypoxia environment and the possible mechanisms that further affect placental angiogenesis in preeclampsia. 【Methods】 MTT method was used to detect the cell viability of HUVECs at different concentrations (0, 4, 8, 12 and 16 μg/mL) after 12 h and 24 h treatment with verteporfin under hypoxia and calculate the IC50 value to select the subsequent experimental drug concentration. Flow cytometry was made to analyze verteporfin’s effect on HUVEC apoptosis in hypoxic environment. The wound healing assay and Transwell invasion assay were used to determine the effect of verteporfin on HUVEC cell migration and invasion abilities under hypoxic environment. Angiogenesis test was used to detect the effect of verteporfin on the angiogenesis of HUVECs under hypoxic environment. The effects of verteporfin on the expression levels of YAP1 and TEAD1 in Hippo signaling pathway under normoxia and hypoxia were determined by Western blotting. 【Results】 Under hypoxic environment, verteporfin could inhibit the proliferation of HUVECs by calculating the IC50 value, the subsequent experimental group selected 16 μg/mL verteporfin to treat cells. Flow cytometry showed that verteporfin induced the apoptosis rate of HUVECs under hypoxia (P<0.01). The results of wound healing, Transwell invasion and the angiogenesis experiments confirmed that compared with the control group, verteporfin could inhibit the migration, invasion and angiogenesis of HUVECs in hypoxic environment (P<0.05). Western blotting assay indicated that under normoxia and hypoxia, the expressions of YAP1 and TEAD1 were reduced (P<0.01). 【Conclusion】 In hypoxic environment, verteporfin inhibits the proliferation of HUVECs by inhibiting the expressions of YAP1 and TEAD1, and reduces the migration, invasion and angiogenesis of HUVECs. It is confirmed that the Hippo-YAP1 signaling pathway may affect the placental angiogenesis of preeclampsia and participate in the occurrence of preeclampsia by regulating the proliferation and invasion of vascular endothelial cells.

BACKGROUND: If high-intensity resistance training is used as a rehabilitation measure after musculoskeletal injury, it may be aggravated by factors such as pain. The blood flow restriction training can achieve high-intensity resistance training through low-intensity resistance training, which can accelerate the recovery of patients. OBJECTIVE: To elaborate the current situation of blood flow restriction training as a new way to accelerate musculoskeletal rehabilitation at home and abroad. METHODS: The first author searched the related studies on the musculoskeletal rehabilitation of blood flow restriction training included in PubMed, Cochrane Library and CNKI from January 2002 to October 2018. The keywords were "blood flow restriction training; Kaatsu training; low intensity resistance training; safety; musculoskeletal rehabilitation; knee osteoarthritis; patellofemoral pain; knee joint injury; ankle joint injury; quantitative difference" in English and Chinese. RESULTS AND CONCLUSION: Blood flow restriction training, as a new treatment method, can reduce the training load and achieve the effect similar to the high-intensity resistance training by designing an individualized and precise rehabilitation scheme. Additionally, it can make the resistance training happen in advance due to its unique advantage, thus contribute to rapid rehabilitation. However, this method is mostly applied to lower limb injuries, and its feasibility for other parts still needs a further investigation.