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 expression and prognostic value of microRNA-145-5p(miR-145-5p)and fascin actin-bundling protein-1(FSCN1)in gastric cancer tissues.Methods The study participants were selected from 103 gastric cancer patients treated at The First Hospital of Handan from August 2019 to August 2021.The expression levels of miR-145-5p and FSCN1 mRNA in the cancer tissues and adjacent non-cancerous tissues of gastric cancer patients were measured.Pearson correlation analysis was used to assess the relationship between the expression of miR-145-5p and FSCN1 mRNA.The area under curve(AUC)was used to evaluate the prognostic value of miR-145-5p and FSCN1 mRNA for gastric cancer patients.The Cox proportional hazards regression model was used to analyze factors influencing adverse prognosis,and Kaplan-Meier method was employed for survival analysis.Results The expression level of miR-145-5p was lower in cancer tissues compared to adjacent tissues(P<0.05),while the expression level of FSCN1 mRNA was higher in cancer tissues compared to adjacent tissues(P<0.05).The expression level of miR-145-5p was lower in cancer tissues of the patients with moderate-to-poor differentiation,tumor stage Ⅲ +Ⅳ,invasion depth T3-T4,lymph node metastasis,or maximum tumor diameter≥5 cm,compared to those with high differentiation,tumor stage Ⅰ+Ⅱ,invasion depth T1-T2,no lymph node metastasis,or maximum tumor diameter<5 cm,whereas the expression level of FSCN1 mRNA was higher(P<0.05).Pearson analysis revealed a negative correlation between miR-145-5p and FSCN1 mRNA expression in cancer tissues(r=-0.617,P=0.000).COX multivariate regression analysis indicated that moderate-to-poor differentiation,tumor stage Ⅲ +Ⅳ,maximum tumor diameter≥5 cm,invasion depth T3-T4,low miR-145-5p expression,high FSCN1 mRNA expression,and lymph node metastasis were risk factors for poor prognosis in gastric cancer(P<0.05).Kaplan-Meier survival curves demonstrated a statistically significant difference in the 3-year overall survival rate between the low and high miR-145-5p expression groups(P<0.05).Similarly,a statistically significant difference was observed between the low and high FSCN1 mRNA expression groups(P<0.05).ROC curve analysis showed that the combined detection of miR-145-5p and FSCN1 mRNA yielded an AUC of 0.947 and a sensitivity of 92.3％,both of which were significantly higher than those of individual indicators(P<0.05).Conclusion MiR-145-5p and FSCN1 are closely related to the clinical pathological characteristics of gastric cancer patients and are effective prognostic indicators for survival.

Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093

The incidence rate of abdominal trauma is increasing year by year in pediatric trauma， and traumatic pancreatic injury should be taken seriously by clinicians. The pancreas is located behind the peritoneum， and it is difficult to make an early diagnosis of pancreatic injury， especially in children with grade ‍Ⅰ‍/Ⅱ injury. Through a literature review， this article analyzes the application value of endocrine indices and abdominal ultrasound in the early diagnosis of pediatric pancreatic injury， so as to improve the rate of early diagnosis and avoid the onset of related complications. Changes of the endocrine indices such as serum insulin and C Peptide have certain advantages in diagnosing and evaluating the degree of pediatric pancreatic injury and can thus be used as early warning indices for pediatric pancreatic injury. Ultrasound elastography provides a new method for the diagnosis and differentiation of pancreatic injury； contrast-enhanced ultrasound， which has no radioactive damage， has relatively high specificity and sensitivity in identifying pediatric pancreatic injury， and therefore， it is expected to become an alternative to CT examination.

Background The substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. Objective To calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. Methods Using a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. Results Overall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). Conclusion Heat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.

Objective:To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure.Methods:This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded.Results:CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions:CCM has better short-term safety and efficacy in patients with heart failure.

Bacillus subtilis is recognized as a generally-regarded-as-safe strain, and has been widely used in the biosynthesis of high value-added products, including N-acetylneuraminic acid (NeuAc) which is widely used as a nutraceutical and a pharmaceutical intermediate. Biosensors responding to target products are widely used in dynamic regulation and high-throughput screening in metabolic engineering to improve the efficiency of biosynthesis. However, B. subtilis lacks biosensors that can efficiently respond to NeuAc. This study first tested and optimized the transport capacity of NeuAc transporters, and obtained a series of strains with different transport capacities for testing NeuAc-responsive biosensors. Subsequently, the binding site sequence of Bbr_NanR responding to NeuAc was inserted into different sites of the constitutive promoter of B. subtilis, and active hybrid promoters were obtained. Next, by introducing and optimizing the expression of Bbr_NanR in B. subtilis with NeuAc transport capacity, we obtained an NeuAc-responsive biosensor with wide dynamic range and higher activation fold. Among them, P535-N2 can sensitively respond to changes in intracellular NeuAc concentration, with the largest dynamic range (180-20 245) AU/OD. P566-N2 shows a 122-fold of activation, which is 2 times of the reported NeuAc-responsive biosensor in B. subtilis. The NeuAc-responsive biosensor developed in this study can be used to screen enzyme mutants and B. subtilis strains with high NeuAc production efficiency, providing an efficient and sensitive analysis and regulation tool for biosynthesis of NeuAc in B. subtilis.
N-Acetylneuraminic Acid/metabolism* ; Bacillus subtilis/metabolism* ; Promoter Regions, Genetic/genetics* ; Binding Sites ; Biosensing Techniques

Objective:To analyze the clinical features of tuberculous peritonitis (TBP).Methods:The clinical data of 252 TBP patients admitted to three hospitals in Wuhu area from January 2014 to June 2020 were retrospectively analyzed, and the clinical characteristics of TBP patients of different genders and ages were compared. SPSS 26.0 software was used to analyze the data.Results:Among 252 TBP patients, 130 were males (51.6%) and 122 were females (48.4%). History of abdominal surgery, abdominal masses, reproductive disorders, genital tuberculosis, and delay in diagnosis were more common in female patients (all P<0.01); while fever, cough/sputum expectoration, intestinal tuberculosis and active tuberculosis were more common in male patients (all P<0.01). The proportion of adenosine deaminase in ascites (ADA) ≥35 U/L, strong positive tuberculin test or T-cell spot test in middle-aged and elderly patients was lower than that in young patients ( P<0.01), but there was no significant difference between different genders. Compared with young patients, middle-aged and elderly patients had a low complete response rate, a high proportion of irregular medications, a high incidence of gastrointestinal reactions, liver damage and overall adverse reactions (all P<0.05). Conclusion:Female patients with TBP have fewer symptoms of systemic tuberculosis and high rate of delay in diagnosis, and are prone to complicated with reproductive tuberculosis. In middle-aged and elderly patients with TBP, the sensitivity of ADA and tuberculosis tests is decreased, and the anti-tuberculosis therapy is less effective. The study indicates that the clinical diagnosis and treatment of TBP should be optimized based on the gender and age of patients.

Objective:To investigate the status of frailty and activities of daily living (ADL) in maintenance hemodialysis (MHD) patients, and to explore the effect of frailty phenotype on ADL.Methods:The patients who underwent MHD in Kidney Disease Center of the First Affiliated Hospital from March 2019 to March 2020 were enrolled in this study. The demographic and laboratorial data were collected by cross-sectional survey method. Fried frailty phenotype scale and ADL scale were used to evaluate the frailty and ADL, respectively. The differences of basic data and different frailty phenotypes between the normal function group and the function decline group were compared in terms of ADL, physical self-maintenance ability and instrumental ADL ability. Pearson correlation analysis was used to analyze the correlation between frailty and ADL, and binary logistic regression analysis was used to analyze the influencing factors of ADL.Results:A total of 676 MHD patients were included in this study, including 434 males (64.2%) and 242 females (35.8%). The age was (59.2±19.4) years old, and the median dialysis age was 59.0 (25.3, 110.0) months. There were 159 frailty patients (23.5%), 230 pre-frailty patients (34.0%), and 287 non-frailty patients (42.5%). The ADL was decreased in 163 patients (24.1%), including 131 patients (19.4%) with decreased physical self-maintenance ability and 161 patients (23.8%) with decreased instrumental ADL ability. Pearson correlation analysis showed that the frailty score was positively correlated with total ADL score ( r=0.728, P<0.001), physical self-maintenance ability score ( r=0.669, P<0.001) and instrumental ADL ability score ( r=0.729, P<0.001). Binary logistic regression analysis results showed that older age and lower physical activity, fatigue, slowed steps and lower grip strength in the frailty phenotypes were the independent influencing factors of ADL, physical self-maintenance ability and instrumental ADL ability (all P<0.05). Conclusions:The prevalence of frailty is 23.5% in MHD patients, and 24.1% of MHD patients have decreased ADL. Elder age and lower physical activity, fatigue, reduced step counts, and lower grip strength in frailty phenotypes are the independent influencing factors for poor ADL, poor physical self-maintenance ability and poor instrumental ADL ability.