Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases / 药物分析学报

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic gastric signet-ring cell carcinoma / 中华核医学与分子影像杂志

Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.

Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis / 中草药·英文版

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Scutellarin alleviates lipopolysaccharide-induced renal injury via mediating cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 expression to inhibit nuclear factor-κB signaling pathway / 中华危重病急救医学

Objective:To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI).Methods:① In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). ② In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 μmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. Results:① The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. ② The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2 -ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT) : 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2 -ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2 -ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1β mRNA (2 -ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2 -ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2 -ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. Conclusions:Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Clinicopathological characteristics and prognostic factor analysis of Siewert Ⅱ and Ⅲ adeno-carcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the clinicopathological characteristics and prognostic factors of Siewert Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospetcive cohort study was conducted. The clinicopathological data of 399 patients with AEG who were admitted to Peking University People′s Hospital from January 1998 to December 2015 were collected. There were 318 males and 81 females, aged 66(range, 19-87)years. Observation indicators: (1) clinicopathological characteristics of Siewert Ⅱ and Ⅲ AEG; (2) follow-up and survival; (3) prognostic factors analysis. Patients were followed up by telephone interview and outpatient examination to detect postoperative survival up to December 2018. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. Univariate and multivariate analyses were done using the COX proportional hazard model. Results:(1) Clinicopathological characteristics of Siewert Ⅱ and Ⅲ AEG. Of 399 patients, 198 cases were Siewert Ⅱ AEG and 201 cases were Siewert Ⅲ AEG. There were 130 cases undergoing transthoracic radical AEG surgery, 172 cases undergoing trans-abdominal proximal gastrectomy and 97 cases undergoing transabdominal total gastrectomy. The age, tumor diameter, cases with surgical method as transthoracic radical AEG surgery, transabdo-minal proximal gastrectomy and transabdominal total gastrectomy, the number of positive lymph nodes, cases in tumor TNM stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were (65±10)years, (5.1±2.4)cm, 102, 68, 28, 17(range, 12?22), 20, 57, 117, 4 for patients with Siewert Ⅱ AEG, versus (62±12)years, (6.3±3.2)cm, 28, 104, 69,18(range, 14?27), 16, 41, 134, 10 for patients with Siewert Ⅲ AEG, showing significant differ-ences betweeen them ( t=2.83, ?3.82, χ2=66.97, U=17 407.05, 17 532.00, P<0.05). (2) Follow-up and survival. All 399 patients were followed up for 34(range, 2?160)months. The 5-year overall survival rate was 29.3% for patients with Siewert Ⅱ AEG, versus 37.0% for patients with Siewert Ⅲ AEG, showing no significant difference betweeen them ( χ2=1.46, P>0.05). The median survival time and 5-year overall survival rate were 29.0 months [95% confidence interval ( CI) as 23.4?34.6 months] and 22.9% for patients undergoing transthoracic radical AEG surgery, 43.0 months(95% CI as 33.9?52.1 months) and 34.7% for patients undergoing transabdominal proximal gastrectomy, 54.0 months (95% CI as 37.6?70.4 months)and 44.3% for patients undergoing transabdominal total gastrectomy, showing a significant difference in the survival among the 3 groups ( χ2=13.81, P<0.05). Of the 198 Siewert Ⅱ AEG patients, the 5-year overall survival rate was 24.6% for the 96 patients undergoing transabdominal surgery, versus 35.4% for the 102 patients undergoing transthoracic surgery, showing no significant difference in the survival between them ( χ2=3.10, P>0.05). Of the 201 Siewert Ⅲ AEG patients, the 5-year overall survival rate was 40.0% for the 173 patients undergoing transabdominal surgery, versus 16.1% for the 28 patients undergoing transthoracic surgery, showing a significant difference between them ( χ2=11.32, P<0.05). (3) Prognostic factors analysis. Results of univariate analysis showed that surgical method, pathological N staging, patholgical M staging were related factors for prognosis of Siewert Ⅱ and Ⅲ AEG ( hazard ratio=0.68, 1.25, 2.18, 95% CI as 0.54?0.86, 1.15?1.36, 1.28?3.73, P<0.05). Results of multivariate analysis showed that transthoracic approach, pathological stage N2?N3 and pathological stage M1 were independent risk factors for prognosis of Siewert Ⅱ and Ⅲ AEG ( hazard ratio=0.64, 1.25, 2.18, 95% CI as 0.51?0.80, 1.16?1.35, 1.28?3.70, P<0.05). Conclusions:Compared with Siewert Ⅲ AEG, Siewert Ⅱ AEG has a smaller tumor diameter, less positive lymph nodes, poorer prognosis. Transthoracic approach is preffered for the Siewert Ⅱ AEG. Transthoracic approach, pathological stage N2?N3 and pathological stage M1 are independent risk factors for prognosis of Siewert Ⅱ and Ⅲ AEG.

Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Molecular epidemiological investigation on Theileria in yellow cattle from Xiangxi Autonomous Prefecture of Hunan Province / 中国血吸虫病防治杂志

Objective To investigate the prevalence and genetic variation of Theileria in yellow cattle in Xiangxi Autonomous Prefecture of Hunan Province. Methods A total of 184 blood specimens were collected from Fenghuang, Huanyuan and Baojing counties of Xiangxi Autonomous Prefecture during the period from August 2018 through August 2019, and were detect using PCR assay with the specific 18S ribosomal rRNA (18S rRNA) gene targeting Theileria. The gene sequences of positive specimens were aligned with the sequences recorded in GenBank, and a phylogenetic tree was created with Plasmodium ovale 18S rRNA as an outgroup. Results A total of 143 blood samples were positive for Theileria, with a mean detection rate of 77.7%. Theileria was prevalent in the blood samples from yellow cattle in all three counties, with detection rates of 85.0% in Fenghuang County, 88.3% in Huayuan County and 61.0% in Baojing County, respectively. There was no significant difference in the detection rate of Theileria between Xiangxi yellow cattle and normal yellow cattle (77.2% vs. 79.5%; χ2 = 0.08, P > 0.05), while the detection of Theileria was significantly lower in the housed yellow cattle than in free-range cattle (68.9% vs. 89.7%; χ2 = 22.36, P < 0.01). A total of 18 PCR positive samples were randomly selected for sequencing and analysis, and all samples showed more than 99.0% homology with T. luwenshuni isolates. Phylogenetic analysis showed that the 18 positive samples were clustered into the same branch with T. luwenshuni, but were far away from other isolates. Conclusions The prevalence of Theileria is high in yellow cattle from Xiangxi Autonomous Prefecture of Hunan Province, and T. luwenshuni may be the dominant parasite species.

Network Meta-analysis of oral Chinese patent medicine in treatment of knee osteoarthritis / 中国中药杂志

To evaluate the efficacy and safety of Chinese patent medicine in the treatment of knee osteoarthritis(KOA) with network Meta-analysis, and provide evidence-based medicine evidences for clinical practice. PubMed, Cochrane Library, EMbase, CNKI, Wanfang, VIP and CBM were used to search for clinical randomized controlled trials(RCTs) on Chinese patent medicines for treatment of knee osteoarthritis, with a time limit from the establishment of each database to March 2020. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. The network Meta-analysis was performed by Stata 14.0 software. A total of 5 788 patients in 58 RCTs were included, involving 9 kinds of Chinese patent medicines. The results of the network Meta-analysis indicated that in terms of total effective rate, the top three optimal medication regimens were Jinwu Gutong Capsules + Amino Acid Glucose(AAG), Xianling Gubao + AAG and Biqi Capsules; the top three interventions to reduce the VAS score were Panlongqi Tablets > Xianling Gubao + AAG > Xianling Gubao + non steroidal anti-inflammatory drugs(NSAIDs); the top three interventions to reduce the total score of WOMAC were Jintiange Capsules+NSAIDs> Jinwu Gutong Capsules + AAG > Biqi Capsules + NSAIDs; the top three medication schemes with better curative effect to reduce Lequesnse index were Xianling Gubao + NSAIDs > Biqi Capsules + NSAIDs > Jintiange Capsules + NSAIDs; the top three interventions to reduce TNF-α level Xianling Gubao + AAG > Jintiange Capsules > Jintiange Capsules + AAG=Jinwu Gutong Capsules + AAG. In terms of safety, the top five interventions with the least adverse reactions were Biqi Capsules > Jinwu Gutong Capsules > Biqi Capsules + NSAIDs > Xianling Gubao + NSAIDs > Jintiange Capsules. The combined application of Chinese patent medicine and NSADIs or AAG can improve the clinical treatment effect and reduce adverse reactions in KOA patients.

Establishment of high-resolution bioassay profiling platform to screen α-glucosidase inhibitors from Malus hupehensis / 药学学报

italic>α-Glucosidase inhibitors play an important role in the treatment of diabetes. This study established a high-resolution bioassay profiling platform for rapidly screening α-glucosidase inhibitors in natural product extracts. Five α-glucosidase inhibitors were identified from Malus hupehensis, namely, 3-hydroxyphloridzin, quercetin-3-O-β-D-glucopyranoside, phloridzin, avicularin and quercitrin. The establishment and successful application of this platform provides a powerful tool for the efficient discovery of anti-diabetic active ingredients in complex systems.

Expression and Prognostic Value of Metabolism-related Genes in Pediatric Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression and prognostic value of metabolism-related genes in pediatric acute lymphoblastic leukemia (ALL), and explore the potential prognostic biomarkers or therapeutic targets.@*METHODS@#Transcriptome data from 84 children with B-cell ALL at the time of diagnosis and prior to any treatment were used to analyze the differential gene expression. A prognostic scoring system based on the expression of the metabolism-related genes was constructed using Cox and Lasso regression methods. The prognostic value of the scoring system was further assessed by multivariate Cox regression analysis. Gene set enrichment analysis was carried out by using GSEA software.@*RESULTS@#Among the 933 metabolism-related genes, 14 up-regulated genes and 17 down-regulated genes were identified as differentially expressed genes. In addition, 8 up-regulated genes (ASS1, CKM, PTGES, ADCY5, HNMT, PHGDH, CYP4F3, AADAT) and 4 down-regulated genes (GDA, DHRS9, IDO2, UGT2B4) were selected to establish a novel prognostic scoring system. Patients in the high-risk group showed poorer survival significantly than patients in the low-risk group (P<0.05). The prognostic scoring system was still shown to be an independent prognostic factor for the survival of children with ALL after the clinical characteristics, such as gender, age, white blood cell count at initial diagnosis, cytogenetics and molecular genetics were included (HR=8.906, 95%CI: 3.114-25.470). GSEA results showed that 6 metabolism-related pathways (amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, glyoxylate and dicarboxylate metabolism, pyrimidine metabolism, selenoamino acid metabolism) were enriched in the high-risk group.@*CONCLUSION@#The abnormal metabolism-related gene expression is associated with the clinical outcome of children with ALL, and these results provide potential novel prognostic biomarkers and treatment targets for pediatric ALL.

Naringenin protects ischemia-reperfusion-induced acute kidney injury by nuclear factor κB / 中华肾脏病杂志

Objective:To explore the effect and involved mechanism of naringenin on acute kidney injury (AKI) induced by ischemia-reperfusion (IR).Methods:The IR-AKI rat model was constructed using the classic bilateral renal pedicle clamping method, then renal function and pathological change were assessed, as well as inflammation-associated genes were detected by quantitative real-time PCR. The hub genes were selected through differential gene analysis and protein-protein interaction network analysis, and their transcription factors were predicted, which constructed a protein library together. The proteins binding to naringenin were selected by reverse molecular docking analysis and further their binding patterns were predicted to explore the mechanism of naringenin. Finally, the results of bioinformatics were verified by experimental methods.Results:Compared with the AKI group, the kidney pathology of the rats in the naringenin pretreatment group was significantly improved, and the renal tubular injury score was reduced ( P<0.01); meanwhile the serum creatinine level and the mRNA expression of the kidney injury molecule 1 (KIM-1) were significantly decreased (both P<0.05). Compared to sham group, IR-AKI increased the level of nuclear factor κB (NF-κB), tumor necrosis factor-α and interleukin-1β (all P<0.05), which reversed by naringenin indicated that naringenin inhibited inflammation in IR-AKI. Differential gene analysis was performed on the GSE98622 data set, and 359 differential genes were obtained. In reverse molecular docking, the proteins with smallest binding energy including NFKBIA, BCL3, NFKB2 and RELA were considered to be related to the preventive effect of naringenin, which were mainly enriched in NF-κB-related inflammation pathways. Domain functional analysis of NF-κB-related genes showed that naringenin could stably bind to its key domain. According to quantitative real-time PCR results, naringenin increased BCL3 level after AKI ( P<0.05), and further decreased the expression level of RELA and NFKB2 (both P<0.05). Conclusion:Naringenin protects IR-AKI by alleviating inflammation, and its mechanism is related to increasing BCL3 and thereby inhibiting the NF-κB pathway.

Effects and evaluation of different processing and drying methods on components in Paeoniae Radix Alba / 中国中药杂志

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-β-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.

Comparison and correlation analysis of sleep parameters between watch-type sleep monitor (Actiwatch) and polysomnography / 北京大学学报(医学版)

OBJECTIVE@#With the rapid development of sleep medicine, there are various methods for detecting sleep diseases. This study compared the correlation between the lightweight watch-type sleep monitor (Actiwatch) and the "gold standard" polysomnography (PSG) in the Chinese population, in order to provide a basis for clinical application.@*METHODS@#From August 2018 to December 2019, 121 subjects who simultaneously performed sleep breathing monitoring (PSG) and wearing a watch-type sleep monitor (Actiwatch) in the Sleep Center of Peking University People's Hospital were enrolled. All subjects received PSG and Actiwatch at the same time, and filled out the sleep diary next morning. Monitoring indicators were collected for linear correlation analysis and paired t test to compare the differences.@*RESULTS@#Under low sensitivity conditions, the correlation coefficient of total sleep time (TST) between PSG and Actiwatch was 0.53 (P < 0.05). Paired t test analysis showed that there was no significant difference between the TSTs of Actiwatch and PSG (t=-0.890, P=0.36). According to age stratification, the smaller the age, the stronger the correlation between the TSTs of Actiwatch and PSG, and the coefficient could be up to 0.92 (P < 0.05). Paired t test showed that there was no significant difference between them (t=-1.057, P=0.35). According to the stratification by diagnosis, the correlation coefficient between the TSTs of Actiwatch and PSG in normal PSG group could be as high as 0.79 (P < 0.05), the results of paired t test showed that there was no significant difference between the TSTs of Actiwatch and PSG in normal PSG group (t=-0.784, P=0.44).@*CONCLUSION@#As a wearable home recorder, when the analysis parameters of Actiwatch were set as low sensitivity, PSG and Actiwatch had the highest TST correlation. The younger the age, the stronger correlation between the TSTs of Actiwatch and PSG. The PSG and Actiwatch subjects with normal PSG presentation had a higher TST correlation.

Identification of metabolites of Zhali Nusi Prescription in rat plasma, bile, urine and feces after oral administration / 中国中药杂志

This study was designed to determine the metabolites of Zhali Nusi Prescription(ZLNSP) in rats. The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric(UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques were applied to analyze the metabolites of ZLNSP in rat plasma, bile, urine and feces. The biological samples were analyzed by ACQUITY UPLC BEH T_3 column(2.1 mm×100 mm,1.7 μm), with 0.1% formic acid water(A)-acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). An analytical method for biological samples of rats was established, and 8 prototype components and 36 metabolites were identified. The results showed that the metabolic pathways of the main components of ZLNSP in rats included methylation, glucuronidation, sulfation and so on. It provi-ded information for the therapeutic effect of ZLNSP in vivo.

Clinical Study on Safety and Efficacy of MicrowaveAblation for Primary Hyperparathyroidism

Objective@#To evaluate the safety, feasibility, and efficacy of microwave ablation (MWA) for the treatment of primaryhyperparathyroidism (PHPT). @*Materials and Methods@#This study enrolled 67 PHPT patients (22 men, 45 women; mean age, 56.0 ± 16.3 years; range, 18–83 years) from January 2015 to December 2018. The laboratory data, including the serum intact parathyroid hormone (iPTH),calcium, phosphorus, and alkaline phosphatase (ALP) levels, were evaluated before MWA and again 2 hours, 1 day, 7 days, 1month, 3 months, 6 months, 12 months, 18 months, and 24 months after. @*Results@#Complete ablation was achieved with all 72 hyperplastic parathyroid glands found on the 67 patients enrolled, 64 ofwhom were treated in one session and 3 were treated over two sessions. The technical success rate was 100%. The medianfollow-up time was 13.6 months (range, 10.0–31.1 months). The clinical success rate was 89.4%. The volume reduction ratewas 79.4% at 6 months. Compared to pre-MWA, the serum iPTH, calcium, phosphorus, and ALP levels had significantlyimproved 6 months post-MWA (iPTH, 157.3 pg/mL vs. 39.2 pg/mL; calcium, 2.75 ± 0.25 mmol/L vs. 2.34 ± 0.15 mmol/L;phosphorus, 0.86 ± 0.20 mmol/L vs. 1.12 ± 0.22 mmol/L; ALP, 79 U/L vs. 54 U/L, respectively; all, p < 0.01). Hoarseness wasa major complication in 4 patients (6.0%), but it improved spontaneously within 2–3 months. @*Conclusion@#MWA is safe, feasible, and effective for the treatment of PHPT.

Distribution and Drug Sensitivity of Pathogens Causing Nosocomial Infection in Patients with Hematological Granulocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution and drug resistance of nosocomial infection pathogens in AL patients with hematological agranulocytosis, so as to provide evidence for the clinical rational use of antibiotics.@*METHODS@#Pathogenic data of 504 hospitalized patients with agranulocytosis caused by nosocomial infection in the Department of Hematology, the First Hospital of Lanzhou University from May 2015 to May 2018 were collected and retrospectively analyzed for the distribution of pathogenic bacteria and the results of drug susceptibility.@*RESULTS@#The isolated pathogenic bacteria strains amounted to 184, out of which, 168 strains (91.3%) orginated from the patients with acute leukemia, while 16 strains (8.7%) originated from the patients with non-acute leukemia. The positive samples mainly originated from blood stream, the isolated bacteria from which were 81 straims (44%); then originated from sputam and pharynx swabs, from which isolated bacteria amounted to 54 strains (29.3%) and 35 strains (19%) respectively. In the pathogenic bacteria, the Gram-negative bacteria amounted to 126 strains accounting for 68.46%, out of which the most commond bacteria strains were Klebseilla pneumoniae, cscherichia coli and Pseudomonas aeruginosa; the Gram positive bocteria amounted to 23 strains accounting for 12.5%, mainly staphy lococeus anreus, and Staphylococcus epitermidis; the fungi amounted to 35 strains accounting for 19.02%, mainly Candida albicans. The detection rates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases (ESBLs) were 40.0% and 22.2%, respectively. They were 100% sensitive to amikacin and 27.8% resistant to carbapenems. Klebsiella pneumoniae had the highest sensitivity to amikacin, 94.44% to ampicillin, 97.22% to carbapenems and 100% sensitive to ammonia. Their penicillin-resistance rate was the highest, up to 80%; Pseudomonas aeruginosa was sensitive to the antibiotics (＞80%）. Methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were detected in Gram-positive bacteria. The susceptibility rate of main Gram-positive bacteria to vancomycin and linezolid was 100%, and they were 100% resistant to penicillin.@*CONCLUSION@#Gram-negative bacteria are the main pathogens of nosocomial infection in patients with hematological agranulocytosis. Pathogens have different resistance to antimicrobial agents. It is important to know the distribution and susceptibility of common pathogens for rational selection of antimicrobial agents and control of nosocomial infection.

Research progress on mechanism of active components of Chinese materia medica in treatment of osteoporosis based on signaling pathway / 中草药

Osteoporosis is a systemic skeletal disease that causes a huge medical burden on patients and society. Drug treatment is the main intervention for anti-osteoporosis, but objectively existing adverse reactions reduce the patient's compliance and affect the effect of medication. Traditional Chinese medicine has good curative effect and safety in the prevention and treatment of osteoporosis, but its mechanism of action needs to be further studied. The pathway regulates the progress of osteoporosis and is one of the main targets for osteoporosis pathological mechanism and pharmacological research. In recent years, an increasing number of studies have been made on the regulatory mechanism of osteoporosis signaling pathways by active ingredients of Chinese materia medica. Recent research results on the active components of Chinese materia medica interfering with biological signaling pathways was reviewed in this article, in order to provide ideas for new drug development, basic research, and clinical applications for osteoporosis.

Hyperbaric oxygen inhalation downregulates the expression of BCL2-associated protein X and upregulates the expression of the B lymphoblastoma-2 gene after cerebral hemorrhage / 中华物理医学与康复杂志

Objective:To explore any effect of inhaling hyperbaric oxygen on edema resulting from cerebral hemorrhage.Methods:Cerebral hemorrhage was modeled using collagenase in 125 Wistar rats, with 5 others used as controls. The injured rats were randomly divided into a second control group without any hyperbaric oxygen intervention, and groups which inhaled hyperbaric oxygen for 40 min, 60 min, 80 min or 100 min. There were 25 rats in each group. The inhalation began 6 hours after the modeling and was administered once a day. On the 2nd, 4th, 6th, 8th and 16th day of the treatment, 5 rats from each group were sacrificed and the expression of the B lymphoblastoma-2 gene (Bcl-2) and BCL2-associated protein X (Bax) in the brain tissue around the hematoma was detected using immunohistochemical methods.Results:The average Bax expression in all of the HBO groups was significantly lower than in the second control group at each time point, but with significant differences between the HBO 60 min and HBO 40 min groups, as well as between the HBO 80 min and HBO 100 min groups. By the 4th day the average Bcl-2 expression in the HBO 40 min group was significantly different from that in the HBO 80 min group, and the same was true of the HBO 60 min and HBO 100 min groups.Conclusions:One of the mechanisms by which HBO treats intracerebral hemorrhage may be related to down-regulating the expression of Bax and increasing the expression of Bcl-2. The best everyday treatment duration is 80 min.

Efficacy of gradual dural decompression in treatment of severe traumatic brain injury / 中华创伤杂志

Objective:To explore the effect of gradual dural decompression(GDD)in preventing intraoperative encephalocele in severe traumatic brain injury (TBI).Methods:A retrospective case-control study was conducted to analyze the clinical data of 78 patients with severe TBI admitted to Affiliated Hospital of North Sichuan Medical College from January 2015 to October 2018, including 55 males and 23 females, aged 15-68 years with an average age of 38.2 years. Thirty-eight patients were treated by GDD (GDD group). During the operation, the hematoma was cleared by opening a window in the area with more hematoma, then gradually cleared in the area without opening a window. Finally, the dural "junction" was cut and the skull was closed quickly after covering the dural patch. The other 40 patients were operated by fast open dural (FOD) operation (FOD group). The incidence of intraoperative encephalocele, intracranial pressure data at the time, 24 hours, 72 hours and 7 days after operation, incidence of delayed intracranial hematoma and glasgow outcome score (GOS) at 3 months after operation were compared between the two groups.Results:All patients (except for 26 deaths) were followed up for 3-14 months, with an average of 8 months. None had intraoperative encephalocele in GDD group, compared to 8 patients in FOD group ( P<0.05). Intracranial pressure in GDD group was respective (18.4±3.6)mmHg, (20.4±4.0)mmHg, (27.7±4.6)mmHg and (28.3±4.5)mmHg at the time, 24 hours, 72 hours and 7 days after operation, showing no significant differences compared to FOD group [(19.1±3.4)mmHg, (20.9±3.9)mmHg, (27.0±3.5)mmHg, (27.6±3.4)mmHg, respectively] ( P>0.05). There was no significant difference in the incidence of delayed intracranial hematoma between the two groups [16% (6/38) in GDD group and 16% (5/32) in FOD group (except 8 cases of intraoperative encephalocele)] ( P>0.05). Three months after operation, the good rate of GOS score of GDD group was 61% (23/28) higher than that of FOD group [28% (11/40)], and the mortality rate of GDD group was 21% (8/38) lower than that of FOD group [45% (18/40)] ( P<0.05). There was no significant difference between the two groups in medium severe disability and plant survival rate ( P>0.05). Conclusions:For patients with severe TBI, compared with FOD, GDD is more effective in reducing the incidence of intraoperative encephalocele, improving the prognosis and decreasing mortality.