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

BACKGROUND:In the process of intervening in the development of osteoarthritis,platelet-rich plasma plays an important role by intervening in autophagy,apoptotic cytokines and signal transduction pathways.OBJECTIVE:To summarize the structure of cytokines and signaling pathways involved in the diagnosis of osteoarthritis by platelet-rich plasma in recent years,as well as its correlation with chondrocyte apoptosis and autophagy,in order to provide effective targets for the future treatment of osteoarthritis.METHODS:Literature search was conducted in CNKI,WanFang Data,VIP,PubMed,Web of Science,and Medline databases using "platelet-rich plasma,chondrocyte,apoptosis,autophagy,osteoarthritis,cytokines,signaling pathway" as Chinese and English search terms.A systematic summary and induction were made for the 66 included articles.RESULTS AND CONCLUSION:Current research has shown that platelet-rich plasma can promote cartilage repair and assist bone tissue healing through various pathways,mainly divided into three aspects:(1) Platelet-rich plasma regulates the extension,closure,and maturation of microautophagosomes,promotes chondrocyte megaautophagy and molecular chaperone-mediated cell autophagy under specific conditions,enhances the expression of autophagy-related factors such as LC3Ⅱ/Ⅰ and Beclin1,inhibits the expression of P62/SQSTM1.Currently,there is no clear research directly exploring the specific effect of platelet-rich plasma on heat shock proteins,and further research is needed in this field in the future.(2) The various growth factors released by platelet-rich plasma inhibit the expression of pro-apoptotic factors Caspase,interleukin-1β,and tumor necrosis factor alpha,promote the expression of anti-apoptotic factor Bcl-2,and prevent chondrocyte apoptosis and degeneration.(3) By activating the PI3K/AKT/mTOR signaling pathway,NF-κB signal transduction pathway,death receptor pathway,mitochondrial stress pathway and other pathways,platelet-rich plasma inhibits the expression of Bax and Caspase,and prevents the release of cytochrome c,thereby inhibiting the death and necrotic apoptosis of chondrocytes.In general,platelet-rich plasma promotes cartilage repair,supports cartilage regeneration,and plays an anti-inflammatory role,and its biological effect in chondrocytes usually depends on the regulation of autophagy and apoptosis-related cytokines and signaling pathways.

Objective To compare the effects of remimazolam and propofol on postoperative nausea and vomiting(PONV)after pancreatic extracorporeal shock wave lithotripsy(P-ESWL),with the aim of optimizing the anesthesia regimen for this procedure.Methods Clinical data were retrospectively collected from patients who underwent P-ESWL for pancreatic stones under general anesthesia at The First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to December 2024.A total of 307 patients were recruited,with 103 in the remimazolam group and 204 in the propofol group.Inverse probability of treatment weighting(IPTW)based on propensity scores was used to balance baseline characteristics and confounding factors between the two groups.The incidence of PONV and anesthesia recovery time were compared between the two groups.Results Before IPTW,there were statistically significant differences between the remimazolam and propofol groups in gender[male/female:51/52 vs.155/49],smoking history(27.2％vs.42.6％),intraoperative sufentanil use[25(10)μg vs.30(10)μg],remifentanil use[429.00(177)μg vs.480.50(209)μg],rocuronium use[36(6)mg vs.38(7)mg],and intraoperative dexamethasone use(62.1％vs.49.0％)(all P＜0.05).After IPTW,the baseline characteristics and confounding factors were balanced and comparable between the two groups(P＞0.05).Before IPTW,the incidence of PONV was higher in the remimazolam group than in the propofol group(24.3％vs.14.7％,P=0.039).After IPTW,the two groups did not significantly differ in the incidence of PONV(21.5％vs.17.5％,P=0.215),and the anesthesia recovery time was significantly shorter in the remimazolam group than in the propofol group[3(3)min vs.9(4)min,P＜0.001].Conclusion Compared to propofol anesthesia,remimazolam does not increase the incidence of PONV in patients undergoing P-ESWL for pancreatic stones and can effectively reduce anesthesia recovery time.

The patient,a 56-year-old male,was admitted to the emergency department due to confusion and elevated body temperature persisting for 1 d.He presented with multiple organ dysfunction,including coagulation dysfunction,respiratory failure,abnormal liver and kidney function,and gastrointestinal disorders.After excluding other potential causes,a diagnosis of heatstroke was made.Additionally,the patient exhibited myocardial injury and Brugada phenocopy,as evidenced by ST-segment elevation and Brugada wave on electrocardiogram.These findings may be related to several mechanisms such as myocardial thermal injury,systemic inflammatory response after heat stress,and abnormal function of temperator-sensitive ion channels.It is necessary to strengthen the understanding of heatstroke-related myocardial injury and Brugada phenotypy to help improve the treatment and prognosis of heatstroke.

The patient,a 56-year-old male,was admitted to the emergency department due to confusion and elevated body temperature persisting for 1 d.He presented with multiple organ dysfunction,including coagulation dysfunction,respiratory failure,abnormal liver and kidney function,and gastrointestinal disorders.After excluding other potential causes,a diagnosis of heatstroke was made.Additionally,the patient exhibited myocardial injury and Brugada phenocopy,as evidenced by ST-segment elevation and Brugada wave on electrocardiogram.These findings may be related to several mechanisms such as myocardial thermal injury,systemic inflammatory response after heat stress,and abnormal function of temperator-sensitive ion channels.It is necessary to strengthen the understanding of heatstroke-related myocardial injury and Brugada phenotypy to help improve the treatment and prognosis of heatstroke.

Objective To compare the effects of remimazolam and propofol on postoperative nausea and vomiting(PONV)after pancreatic extracorporeal shock wave lithotripsy(P-ESWL),with the aim of optimizing the anesthesia regimen for this procedure.Methods Clinical data were retrospectively collected from patients who underwent P-ESWL for pancreatic stones under general anesthesia at The First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to December 2024.A total of 307 patients were recruited,with 103 in the remimazolam group and 204 in the propofol group.Inverse probability of treatment weighting(IPTW)based on propensity scores was used to balance baseline characteristics and confounding factors between the two groups.The incidence of PONV and anesthesia recovery time were compared between the two groups.Results Before IPTW,there were statistically significant differences between the remimazolam and propofol groups in gender[male/female:51/52 vs.155/49],smoking history(27.2％vs.42.6％),intraoperative sufentanil use[25(10)μg vs.30(10)μg],remifentanil use[429.00(177)μg vs.480.50(209)μg],rocuronium use[36(6)mg vs.38(7)mg],and intraoperative dexamethasone use(62.1％vs.49.0％)(all P＜0.05).After IPTW,the baseline characteristics and confounding factors were balanced and comparable between the two groups(P＞0.05).Before IPTW,the incidence of PONV was higher in the remimazolam group than in the propofol group(24.3％vs.14.7％,P=0.039).After IPTW,the two groups did not significantly differ in the incidence of PONV(21.5％vs.17.5％,P=0.215),and the anesthesia recovery time was significantly shorter in the remimazolam group than in the propofol group[3(3)min vs.9(4)min,P＜0.001].Conclusion Compared to propofol anesthesia,remimazolam does not increase the incidence of PONV in patients undergoing P-ESWL for pancreatic stones and can effectively reduce anesthesia recovery time.

BACKGROUND:In the process of intervening in the development of osteoarthritis,platelet-rich plasma plays an important role by intervening in autophagy,apoptotic cytokines and signal transduction pathways.OBJECTIVE:To summarize the structure of cytokines and signaling pathways involved in the diagnosis of osteoarthritis by platelet-rich plasma in recent years,as well as its correlation with chondrocyte apoptosis and autophagy,in order to provide effective targets for the future treatment of osteoarthritis.METHODS:Literature search was conducted in CNKI,WanFang Data,VIP,PubMed,Web of Science,and Medline databases using "platelet-rich plasma,chondrocyte,apoptosis,autophagy,osteoarthritis,cytokines,signaling pathway" as Chinese and English search terms.A systematic summary and induction were made for the 66 included articles.RESULTS AND CONCLUSION:Current research has shown that platelet-rich plasma can promote cartilage repair and assist bone tissue healing through various pathways,mainly divided into three aspects:(1) Platelet-rich plasma regulates the extension,closure,and maturation of microautophagosomes,promotes chondrocyte megaautophagy and molecular chaperone-mediated cell autophagy under specific conditions,enhances the expression of autophagy-related factors such as LC3Ⅱ/Ⅰ and Beclin1,inhibits the expression of P62/SQSTM1.Currently,there is no clear research directly exploring the specific effect of platelet-rich plasma on heat shock proteins,and further research is needed in this field in the future.(2) The various growth factors released by platelet-rich plasma inhibit the expression of pro-apoptotic factors Caspase,interleukin-1β,and tumor necrosis factor alpha,promote the expression of anti-apoptotic factor Bcl-2,and prevent chondrocyte apoptosis and degeneration.(3) By activating the PI3K/AKT/mTOR signaling pathway,NF-κB signal transduction pathway,death receptor pathway,mitochondrial stress pathway and other pathways,platelet-rich plasma inhibits the expression of Bax and Caspase,and prevents the release of cytochrome c,thereby inhibiting the death and necrotic apoptosis of chondrocytes.In general,platelet-rich plasma promotes cartilage repair,supports cartilage regeneration,and plays an anti-inflammatory role,and its biological effect in chondrocytes usually depends on the regulation of autophagy and apoptosis-related cytokines and signaling pathways.

Objective To investigate the effects of remimazolam and propofol on postoperative nausea and vomiting(PONV)in patients undergoing painless prostate biopsy,so as to optimize the anesthesia protocols.Methods A retrospective analysis was conducted on the clinical data of 1217 patients who underwent painless prostate biopsy in our hospital during Jan.2023 and Jun.2024.Among them,1093 patients met the inclusion criteria and were divided into two groups:the remimazolam group(n=294)and the propofol group(n=799).After 1∶1 propensity score matching,with 267 patients in either group,a comparison was conducted regarding the incidence of PONV and anesthesia recovery time.Results Before propensity score matching,the remimazolam group had older age[66(53,83)years vs.63(49,78)years],higher body mass index(BMI)[25.30(21.83,29.23)vs.24.46(20.79,28.91)],larger intraoperative use of sufentanil[9(8,10)μg vs.7(6,9)μg],higher intraoperative use rate of ondansetron(55.4％vs.47.6％),and longer surgical duration[16(14,20)min vs.15(13,17)min],with statistically significant differences(P＜0.05).There were no statistically significant differences in the aforementioned factors between the two groups after propensity score matching(P＞0.05).Before propensity score matching,the incidence of PONV was higher in the remimazolam group than in the propofol group(17.7％vs.11.5％,P=0.007),while after propensity score matching,the incidence of PONV did not differ significantly between the two groups(12.7％vs.17.2％,P=0.146).Before and after propensity score matching,the anesthesia recovery time was significantly shorter in the remimazolam group than in the propofol group[3(2,4)min vs.7(4,10)min,P＜0.001].Conclusion Compared with propofol,remimazolam does not increase the incidence of PONV in patients undergoing painless prostate biopsy but can shorten anesthesia recovery time.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To study the clinical characteristics of patients with brucella bloodstream infection in different age groups, and provide a basis for clinicians to take targeted diagnosis and treatment measures. Methods:Demographic data and general condition (age, sex, occupation, location, onset season, source of infection, clinical stage), clinical characteristics (main clinical symptoms and complications), and laboratory test results (routine and pathogenic tests) of adult patients with brucella bloodstream infection admitted to the Affiliated Hospital of Chengde Medical College from January 2015 to January 2020 were collected. According to the age stratification standards recommended by the World Health Organization, the patients were divided into a young group (18 - 44 years old), a middle-aged group (45 - 59 years old), and an elderly group (≥60 years old), and various indicators among different age groups were compared and analyzed. Results:A total of 75 patients were included, including 15 cases (20.00%) in the young group, 37 cases (49.33%) in the middle-aged group, and 23 cases (30.67%) in the elderly group. Among them, 61 cases (81.33%) were males and 14 cases (18.67%) were females, with statistically significant differences in gender ratios among different age groups (χ 2 = 7.28, P = 0.021). The majority of patients were farmers (64 cases, 85.33%), and 92.00% (69/75) of the patients came from rural areas. The main sources of infection were infected cattle and sheep, and contaminated food (39 cases, 52.00%). The main season of onset was spring and summer (45 cases, 60.00%). The clinical staging was mainly in the acute phase (66 cases, 88.00%). In terms of clinical symptoms, the young group of patients had no symptoms of low back pain, while the incidence rates of low back pain in the middle-aged and elderly groups were 35.14% (13/37) and 30.43% (7/23), respectively. There was a statistically significant difference between the three groups (χ 2 = 6.98, P = 0.031). In terms of complications, there were no cases of concurrent spondylitis in the young group of patients. The incidence rates of spondylitis in the middle-aged and elderly groups were 32.43% (12/37) and 34.78% (8/23), respectively. There was a statistically significant difference among the three groups (χ 2 = 6.86, P = 0.032). In terms of routine laboratory examinations, there were statistically significant differences in the proportion of blood lymphocytes and albumin levels among patients of different age groups ( F = 3.41, 3.27, P = 0.038, 0.044). In terms of pathogenic examination, there was a statistically significant difference in the median alarm time for positive blood culture among patients of different age groups ( H = 9.54, P = 0.008), with the middle-aged group having the longest (66.24 h) and the elderly group having the shortest (58.80 h). Conclusions:The clinical characteristics of patients with brucella bloodstream infection vary among different age groups, middle-aged and elderly patients are prone to low back pain symptoms, accompanied by spondylitis. Clinicians should pay attention to the patient's own characteristics and provide targeted diagnosis and treatment.