Objective:To investigate the effect of roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with diabetic kidney disease (DKD), and its effects on iron metabolism, microinflammation status and microvascular complications.Methods:The clinical data of 89 hemodialysis renal anemia patients with DKD from January 2020 to October 2021 in Beijing Geriatric Hospital were retrospectively analyzed. Among them, 44 patients (control group)were treated with recombinant human erythropoietin and levocarnitine for renal anemia, and 45 patients (study group) were treated with recombinant human erythropoietin, levocarnitine and roxadustat for renal anemia. Both groups were treated for 3 months. The efficacy was compared between two groups. The laboratory indexes were measured before treatment and after 1, 3 months of treatment, including anemia related indexes such as hemoglobin, red blood cell count and mean corpuscular volume (MCV); iron metabolism indexes such as serum iron, ferritin and transferrin saturation (TSAT); inflammatory indexes such as interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). The adverse reactions were recorded. The patients were followed up for 1 year after treatment, the incidence of diabetic microvascular complications, including diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR), was recorded.Results:The total effective rate in study group was significantly higher than that in control group: 93.33% (42/45) vs. 77.27% (34/44), and there was statistical difference ( χ2 = 4.60, P<0.05). There were no statistical differences in the laboratory indexes before treatment between two groups ( P<0.05); the hemoglobin, red blood cell count, MCV, serum iron, ferritin and TSAT after 1 and 3 months of treatment in study group were significantly higher than those in control group, the IL-8, CRP and TNF-α were significantly lower than those in control group, and there were statistical differences ( P<0.01 or <0.05). There was no significant difference in the incidence of adverse reactions between two groups ( P>0.05). After 1 year follow-up, 2 cases were lost in study group and 3 cases in the control group. The incidence of DR and DPN in study group were significantly lower than those in control group: 0 vs. 14.63% (6/41) and 2.33% (1/43) vs. 19.51% (8/41), and there were statistical differences ( χ2 = 4.75 and 4.81, P<0.05). Conclusions:Roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with DKD is reliable and safe, and can effectively relieve anemia symptoms, improve iron metabolism, reduce inflammatory response, and reduce the risk of diabetic microvascular complications.

Objective:To explore the intervention effect of preventive nursing combined with function training on bladder function recovery in patients after transurethral resection of prostate.Methods:A non-randomized historical control study was used, 29 patients who received benign prostatic hyperplasia surgery and postoperative bladder function training in Lu′an Traditional Chinese Medicine Hospital from January 2021 to July 2022 were classified as control group, and 31 patients with benign prostatic hyperplasia surgery who received postoperative preventive nursing based on summary of influencing factors combined with bladder function training from August 2022 to February 2024 were included in combined group. Bladder function [bladder compliance (BC), maximum bladder storage capacity (VM-CC), maximum urine flow (Qmax), post-void residual urine volume (PVR)], incidence rate of bladder spasm, number of indewelling catheter days,comfort [Kolcaba comfort status scale (GCQ)] and quality of life [benign prostatic hyperplasia quality of life scale (BPHQLS)] were compared between groups at 3 months after surgery.Results:The age of the control group was (71.97 ± 3.99) years, (71.77 ± 2.92) years in the combined group, the baseline data were balanced.Conclusions:Preventive nursing combined with bladder function training can effectively improve the postoperative bladder function, reduce the risk of bladder spasm, and enhance the comfort and quality of life in patients with benign prostatic hyperplasia surgery, and it has application value.

Objective:To investigate the clinical value of different doses of paricalcitol combined with cinacalcet in the treatment of secondary hyperparathyroidism (SHPT) in patients with maintenance hemodialysis (MHD).Methods:The clinical data of 90 patients with MHD combined with SHPT from December 2020 to December 2022 in Beijing Geriatric Hospital were retrospectively analyzed. Among them, 30 patients were treated with cinacalcet (control group), 30 patients were treated with fixed dose paricalcitol combined with cinacalcet (experimental group A), and 30 patients were treated with adjusting dose of paricalcitol based on the level of intact parathyroid hormone (iPTH) combined with cinacalcet (experimental group B). All patients were continuously treated for 8 weeks. The blood calcium, blood phosphorus, iPTH, osteoprotegerin, osteocalcin, type Ⅰ collagen carboxy terminal peptide cross-linking (β-CTX), N-terminal medium molecule fragment of calcium (N-MID), fibroblast growth factor-23 (FGF-23) and Klotho protein before treatment and after 4 and 8 weeks of treatment were detected; coronary artery calcification (CAC) score and abdominal aortic calcification (AAC) score were evaluated. The adverse reactions were recorded.Results:There were no statistical differences in the indexes before treatment among three groups ( P>0.05). There were no statistical differences in blood calcium and blood phosphorus after 4 and 8 weeks of treatment among three groups ( P>0.05). After 4 and 8 weeks of treatment, the iPTH, β-CTX, osteoprotegerin, N-MID, osteocalcin and FGF-23 in experimental group A and experimental group B were significantly lower than those in control group, after 4 weeks of treatment: (936.99 ± 202.36) and (635.74 ± 135.44) ng/L vs. (1 028.56 ± 11.39) ng/L, (1.85 ± 0.32) and (1.50 ± 0.27) μg/L vs. (2.27 ± 0.69) μg/L, (71.18 ± 6.98) and (64.33 ± 7.87) ng/L vs. (80.15 ± 10.85) ng/L, (106.36 ± 14.42) and (92.64 ± 11.32) μg/L vs. (135.19 ± 15.18) μg/L, (66.17 ± 8.52) and (60.21 ± 7.85) μg/L vs. (73.15 ± 9.44) μg/L, (109.17 ± 11.24) and (98.50 ± 10.36) ng/L vs. (126.18 ± 15.64) ng/L; after 8 weeks of treatment: (632.17 ± 154.98) and (526.85 ± 98.45) ng/L vs. (819.85 ± 169.78) ng/L, (1.33 ± 0.15) and (1.15 ± 0.20) μg/L vs. (1.78 ± 0.27) μg/L, (65.78 ± 9.74) and (52.77 ± 7.18) ng/L vs. (74.26 ± 11.58) ng/L, (85.64 ± 11.62) and (70.25 ± 8.59) μg/L vs. (105.92 ± 19.17) μg/L, (48.17 ± 5.99) and (41.15 ± 6.44) μg/L vs. (59.24 ± 6.87) μg/L, (90.15 ± 11.25) and (82.58 ± 9.74) ng/L vs. (105.26 ± 14.35) ng/L, the indexes in experimental group B were significantly lower than those in experimental group A, and there were statistical differences ( P<0.05). After 4 and 8 weeks of treatment, the Klotho protein in experimental group A and experimental group B was significantly higher than that in control group, after 4 weeks of treatment: (124.25 ± 14.85) and (146.31 ± 16.85) U/L vs. (107.26 ± 11.36) U/L, after 8 weeks of treatment: (135.62 ± 16.87) and (150.24 ± 17.43) U/L vs. (115.56 ± 15.48) U/L, the Klotho protein in experimental group B was significantly higher than that in experimental group A, and there were statistical differences ( P<0.05). After 4 and 8 weeks of treatment, the CAC score and AAC score in experimental group A and experimental group B were significantly lower than those in control group, the indexes in experimental group B were significantly lower than those in experimental group A, and there were statistical differences ( P<0.05). There was no statistical difference in the incidence of adverse reactions among three groups ( P>0.05). Conclusions:Compared with the fixed dose of paricalcitol combined with cinacalcet therapy, the adjusting the dosage of paricalcitol combined with cinacalcet therapy based on iPTH level has more definite therapeutic effects in patients with MHD combined with SHPT, which can improve bone metabolism and reduce vascular calcification.

Plasma protein products, essential drugs for various clinical diseases, are therapeutic biological products extracted from healthy human plasma. The research and development of new plasma protein products, led by United States and European, has been widely deepened and enhanced. Therefore, accelerating the development of new plasma protein products in China is of great significance. This review summarizes the research and development of plasma protein products that have been marketed abroad but have not produced in China, as well as analyzes the difficulties and prospects of the development of plasma protein products in China.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:To investigate the expression of costimulatory molecule OX40 in peripheral CD4 +CD25 +CD127 low regulatory T (Treg) cells and its clinical significance in patients with acute cerebral infarction (ACI). Methods:Seventy-five patients with first-onset ACI, admitted to our hospital from April 2019 to December 2019, and 36 age- and gender-matched volunteers (control group) were selected in this study. OX40 expression on CD4 +CD25 +CD127 low Treg cells in peripheral blood samples in the two groups were analyzed by immunofluorescent labeling and flow cytometry. Correlations of OX40 +Treg cell percentage with National Institute of Health stroke scale (NIHSS) scores, ischemic penumbra volume, core infarct volume, and infarct volume in the patient group were analyzed. The changes of OX40 +Treg cell percentage in the patient group before and after endovascular treatment or intravenous thrombolysis were compared. Results:As compared with that in the control group, the Treg cell percentage in peripheral blood samples of the patient group was significantly decreased, while OX40 +Treg cell percentage was significantly increased ( P<0.05). OX40 +Treg cell percentage was positively correlated with NIHSS scores in ACI patients ( r s=0.271, P=0.018). Meanwhile, OX40 +Treg percentage was significantly correlated with ischemic penumbra volume, core infarct volume, and infarct volume in the patient group ( r s=0.435, P=0.000; r s=0.343, P=0.003; r s=0.245, P=0.034). OX40 +Treg cell percentage in ACI patients 7 d after endovascular treatment was significantly decreased as compared with that before treatment ( P<0.05); OX40 +Treg percentage in ACI patients 3 and 7 d after intravenous thrombolysis was significantly decreased as compared with that before treatment ( P<0.05). Conclusion:OX40 is abnormally expressed on peripheral Treg cells in ACI patients, and is closely correlated with neurological deficits, imaging features and reperfusion therapy.

Objective: To observe whether an Xingnaojing 醒脑静 injection could improve the prognosis of patients, by increasing rifampicin penetration through the blood-brain barrier. Methods: Patients with severe tuberculous meningitis were enrolled in this study. The concentrations of Xingnaojing in cerebrospinal fluid and blood in patients treated with Xingnaojing and control were determined by high performance liquid chromatography. The changes in cerebrospinal fluid and the improvement of clinical symptoms and signs, were evaluated two weeks after admission. The long-term prognosis of the patients in the two groups were evaluated by the Glasgow Outcome Scale (GOS). Results: The concentration of rifampicin in cerebrospinal fluid was significantly higher in the Xingnaojing group (1.77±0.17 μg/mL), than in the control group (1.27±0.16 μg/mL, p<0.05). The difference in concentration of rifampicin in the blood was not significant (P>0.05). The short-term effective rate of the Xingnaojing group was 92.5% (37/40), which was significantly higher than that of the control group (80%, 32/40, p<0.05). After 6 months, 75% (30/40) of the Xingnaojing group had good prognosis according to the GOS score, whereas that of the control group was 50% (20/40) showing significantly better long-term treatment effect of the Xingnaojing group compared to the control group (P<0.05). Conclusion: Xingnaojing injection improved rifampicin penetration into the central nervous system. The increase in rifampicin concentration in cerebrospinal fluid improved outcomes in patients with severe tuberculous meningitis.

Animals ; Bacterial Infections/metabolism* ; Glucose/metabolism* ; Homeostasis ; Insulin Secretion ; Mice ; Mice, Knockout ; Sirtuins/metabolism*

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective To explore the expressions of costimulatory molecules OX40 and OX40L in peripheral blood (PB) samples of multiple sclerosis (MS) patients,and reveal their clinical significance.Methods PB samples of 39 MS patients and 37 health control subjects (HC) were collected from June 2013 to October 2018.OX40 expressions on CD4+ T cells,OX40L expressions on CD14+ monocytes and CD19+ B cells were detected by immunofluorescent labeling and flow cytometer.The correlations between expanded disability status scale (EDSS) scores and OX40 and OX40L expressions were analyzed,and the influences of different clinical typing and gender in OX40 and OX40L expressions were analyzed.The changes of OX40 and OX40L expressions before and after methylprednisolone shock therapy in 8 patients with recurrent MS were observed.Results (1) As compared with those in the HC group,the expressions of CD4+OX40+ and CD 14+OX40L+ in the peripheral blood of patients in the MS group were significantly increased (P＜0.05).(2) The OX40 expression on the surface of CD4+ T cells was positively correlated with EDSS scores of MS patients (r=0.684,P=0.000).(3) As compared with that in the MS patients at remission phase,the OX40 expression in the CD4+ T cells of MS patients at recurrence phase was significantly increased (P＜0.05);there were no significant differences in the expressions of OX40 and OX40L between male and female MS patients (P＞0.05).(4) EDSS scores of 8 patients with relapsed MS after intravenous infusion of methylprednisolone were significantly lower than those before treatment (P＜0.05);the OX40 expression on the surface of CD4+ T cells after intravenous infusion of methylprednisolone was significantly decreased as compared with that before treatment (P＜0.05).Conclusion Abnormal OX40 expression is closely correlated to neurologic impairment and clinical characteristics,and distinctly responded to corticosteroid therapy in MS patients,which suggests that OX40 may be a promising biomarker and is involved in the pathogenesis of MS.