Objective:To investigate the influences of asiaticoside(AS)on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis(MsPGN)by regulating the rat sarcoma(Ras)/extracellular signal regulated kinase(ERK)/mitogen activated protein kinase(MAPK)signaling pathway.Methods:Sixty SPF SD rats were randomly divided into sham operation group(Sham group),MsPGN model group(Model group),low-dose AS group(AS-L group,40 mg/kg),high-dose AS group(AS-H group,80 mg/kg),high-dose AS+Ras/ERK/MAPK signaling pathway activator group(AS-H+anisomycin group,80 mg/kg AS+10 mg/kg anisomycin),with 12 rats in each group.Rat model of MsPGN was established by modified serum immunization.The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method.HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group.TUNEL staining was used to detect apoptosis of rat glomerular cells in each group.Levels of serum creatinine(Scr),superoxide dismutase(SOD),blood urea nitrogen(BUN),malondialdehyde(MDA),and levels of IL-18,IL-1β,TNF-α,SOD and MDA in renal tissues were measured by ELISA.Protein levels of Ras,p-ERK1/2,ERK1/2,MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot.Results:①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats.Compared with Sham group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in model group were significantly increased(P<0.05),while SOD level in serum and renal tissue was significantly decreased(P<0.05).HE staining showed that the glomerulus of rats had severe mesangial hyperplasia,a large amount of matrix deposition,and the basement membrane was significantly thickened.Compared with model group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in AS-H group rats were significantly decreased(P<0.05),while SOD level in serum and renal tissue was significantly increased(P<0.05),HE staining showed alleviated mesangial hyperplasia injury.②AS downregulated the Ras/ERK/MAPK signaling pathway.Compared with Sham group,expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased(P<0.05);compared with Model group,expression of Ras protein,phosphory-lation level of ERK1/2 and MAPK in AS-H group were significantly decreased(P<0.05),and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats(P<0.05).Conclusion:AS may reduce the inflammatory re-action and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway.

Objective:To investigate the influences of asiaticoside(AS)on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis(MsPGN)by regulating the rat sarcoma(Ras)/extracellular signal regulated kinase(ERK)/mitogen activated protein kinase(MAPK)signaling pathway.Methods:Sixty SPF SD rats were randomly divided into sham operation group(Sham group),MsPGN model group(Model group),low-dose AS group(AS-L group,40 mg/kg),high-dose AS group(AS-H group,80 mg/kg),high-dose AS+Ras/ERK/MAPK signaling pathway activator group(AS-H+anisomycin group,80 mg/kg AS+10 mg/kg anisomycin),with 12 rats in each group.Rat model of MsPGN was established by modified serum immunization.The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method.HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group.TUNEL staining was used to detect apoptosis of rat glomerular cells in each group.Levels of serum creatinine(Scr),superoxide dismutase(SOD),blood urea nitrogen(BUN),malondialdehyde(MDA),and levels of IL-18,IL-1β,TNF-α,SOD and MDA in renal tissues were measured by ELISA.Protein levels of Ras,p-ERK1/2,ERK1/2,MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot.Results:①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats.Compared with Sham group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in model group were significantly increased(P<0.05),while SOD level in serum and renal tissue was significantly decreased(P<0.05).HE staining showed that the glomerulus of rats had severe mesangial hyperplasia,a large amount of matrix deposition,and the basement membrane was significantly thickened.Compared with model group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in AS-H group rats were significantly decreased(P<0.05),while SOD level in serum and renal tissue was significantly increased(P<0.05),HE staining showed alleviated mesangial hyperplasia injury.②AS downregulated the Ras/ERK/MAPK signaling pathway.Compared with Sham group,expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased(P<0.05);compared with Model group,expression of Ras protein,phosphory-lation level of ERK1/2 and MAPK in AS-H group were significantly decreased(P<0.05),and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats(P<0.05).Conclusion:AS may reduce the inflammatory re-action and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway.

Objective:To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer.Methods:A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate.Results:Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion:For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by clonal proliferation of lymphocytes. To meet the demands of energy, tumor cells can drive metabolic reprogramming. Previous studies have shown that the transformation of metabolic patterns in CLL cells is closely related to disease progression, treatment and prognosis. This article reviews the role of metabolic reprogramming in CLL in order to help in-depth understanding of the metabolic heterogeneity of CLL cells, and provide ideas for finding feasible therapeutic targets involved in the metabolic process of CLL.

ObjectiveTo observe the effect of augmented reality training based on enriched environment on walking dysfunction after stroke. MethodsFrom January, 2021 to June, 2022, 36 stroke patients in the Affiliated Suzhou Hospital of Nanjing University Medical School were randomly divided into control group (n = 18) and experimental group (n = 18). Both groups received conventional rehabilitation treatment. The control group was supplemented with conventional walking training, and the experimental group was supplemented with augmented reality training based on enriched environment, for four weeks. They were assessed with Berg Balance Scale (BBS), Timed Up and Go Test (TUGT), 10-meter walk test (10MWT) and Barthel Index (BI) before and after treatment, and the gait parameter was compared. ResultsNo adverse event occurred during treatment. After treatment, the BBS score, TUGT time, 10MWT speed, BI, gait speed, gait frequency and the proportion of single-leg support on the affected side significantly improved in both groups (|t| > 5.161, P < 0.001). All the above indexes were better in the experimental group than in the control group (|t| > 2.106, P < 0.05), except for BI (t = 1.099, P = 0.282). ConclusionAugmented reality training based on enriched environment could improve the walking function of paitents after stroke, which is better than conventional walking training.

Objective:To analyze the distribution of different SF3B1 genotypes in patients with myelodysplastic syndromes (MDS) and its prognostic value.Methods:Totally, 377MDS patients who were initially diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to January 2022 were included in the retrospective analysis.The patients were divided into three different groups according to mutation stcote of SF3B1, including 317 patients with SF3B1 wild type (SF3B1 WT) (214 males and 103 females, 63(49, 71) years old),39 patients with SF3B1 K700E mutation(SF3B1 K700E(17 males and 22 females, 65(52, 73)years old)) and 21 patients with SF3B1 non-K700E mutation(SF3B1 non-K700E)(13 males and 8 females, 67(63, 73) years old). MDS-related 20 gene mutations were detected using targeted sequencing technology; Survival curves were constructed by the Kaplan-Meier method; Cox proportional hazards model was established to evaluate different factors at diagnosis on survival by univariate and multivariate analyses.. Results:Compared with SF3B1 non-K700E patients, SF3B1 K700E patients had a higher median absolute neutrophil count ( P=0.002) and were likely to be in the low/int-1 International Prognostic Scoring System (IPSS) categories ( P=0.023). A 20-gene targeted sequencing analysis showed that, compared with SF3B1 WT patients, SF3B1 K700E patients were associated with lower frequency of ASXL1 and U2AF1 mutations ( P=0.018 and P=0.003); while compared with SF3B1 non-K700E patients, the frequency of ASXL1 mutation was significantly lower in SF3B1 K700E cases ( P=0.029). Patients with SF3B1 K700E had better overall survival (OS) in comparison with SF3B1 WT and SF3B1 non-K700E in MDS patients ( P<0.001 and P=0.045, respectively). In comparison with SF3B1 WT patients, SF3B1 MUT patients had more favorable OS and progression-free survival (PFS) in MDS without excess blasts ( P<0.001 and P<0.001, respectively), but no significant difference was found in MDS with excess blasts ( P>0.05). Compared with SF3B1 WT patients, SF3B1 K700E patients had superior OS and PFS in the int-1 IPSS category ( P=0.010 and P=0.013, respectively). By multivariable analysis, the presence of SF3B1 K700Ewas an independent predictor of superior OS ( HR=0.461,95% CI 0.262-0.811, P=0.007). Conclusion:SF3B1 K700E and SF3B1 non-K700E patients had significantly improved OS in comparison with SF3B1 WT MDS patients. Furthermore, SF3B1 K700E patients were associated with a better OS compared with SF3B1 non-K700E MDS patients. SF3B1 mutation could not overcome the poor prognostic effect of excess blasts, which highlights the importance of the SF3B1 mutation subtype in risk assessment of MDS without excess blasts.

Objective:To explore the expression of circ-KEL in patients with acute myeloid leukemia (AML) and the effect and mechanism of circ-KEL on leukemic cells.Methods:The expression of circ-KEL was detected by quantitative real-time polymerase chain reaction in bone marrow mononuclear cells collected from 116 patients with AML and 40 healthy donors. The correlation of circ-KEL expression with the clinical characteristics of patients with AML was further systematically analyzed. The modulations among circ-KEL, miR-335-5p, and LRG1 were predicted through bioinformatics analysis and validated by dual luciferase assay. Cell proliferation and apoptosis were detected using CCK8 and flow cytometry.Results:The expression of circ-KEL was significantly elevated in patients with AML compared with the healthy controls (Relative expression level, -Δct, AML: -7.117±1.831; control: -8.669±1.771, P<0.001) . Moreover, patients with high circ-KEL expression have significantly worse overall survival. The level of circ-KEL in patients with AML was downregulated after chemo-treatment. In addition, circ-KEL could serve as the sponge of miR-335-5p and regulate LRG1. Bioinformatics analysis showed that miR-335-5p correlates with good prognosis and was negatively associated with LRG1. LRG1 could promote cell proliferation and inhibit cell apoptosis. Our results also exhibited the higher expression of LRG1 in patients with AML. Moreover, circ-KEL exerted functional effects via sponging miR-335-5p and regulating LRG1. Conclusion:circ-KEL expresses highly in patients with AML and correlates with poor prognosis, suggesting its important role in the genesis and progress of AML.

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.

Objective To study the similarities and differences in brain activation under N-back and DMTS paradigms of working memory. Methods Through searching of BrainMap function database by the combination keywords,a total of 122 articles with 122 experiments ( N-back: 67 experiments,937 sub-jects,900 foci;Delayed Matched to Sample: 55 experiments,806 subjects,872 foci). Maps were analyzed using the FDR PN (P<0. 0001) method based coordinates of the Montreal Neurological Institute ( MNI) space. Results In the combine of the N-back and DMTS paradigms,these regions were activated including the bilateral inferior parietal lobe (Left: -36,-52,44; Right: 38,-52,48) and insula(Left:-34,22,0;Right:34,24,2),the superior frontal gyrus (2,16,50) and inferior frontal gyrus (-44,8,30) of the left brain,and the middle frontal ( 46,36,24) and sub-gyral ( 30,4,56) of the right brain. The N-back paradigm was similar to the above results,whereas the DMTS paradigm only activated the precentral gyrus (-50,8, 34) of the left brain and the right insula ( 34,24,4) . Conclusion The neural circuit of working memory is the frontal-parietal networks. N-back paradigm with the brain activation consists to the neural circuit of work-ing memory. However,DMTS paradigm activates less brain regions and is inconsistent to the neurons of work-ing memory.

Objective To understand the current situation of doctors and nurses perceptions on doctor-patient relationship and its main influencing factors, and to make recommendations for further healthcare improvement. Methods Based on the survey results of the third-party evaluation of the National Healthcare Improvement Initiative of 136 public tertiary hospitals, we analyzed the doctors' and nurses' perceptions on doctor-patient relationship and the influencing factors. SAS 9.4 software was used to conduct variance test of doctors' and nurses' basic information and multivariate logistic regression analysis of the influencing factors of doctors' and nurses' perceptions on doctor-patient relationship. Results The recognition of doctors and nurses on the statement of "doctor-patient relationship has been getting better", their career identity and hoping children to study medicine varied significantly (P <0.05) with hospital type,age, department, academic rank, and annual income. The main influencing factors were patients' satisfactions and medical liability insurance (OR>1, P<0.05). Another main positive influencing factor was the communication duration between the doctor and outpatient(OR>1,P<0.05). Conclusions It is imperative to protect rights of doctors and nurses by enforcing relevant laws and regulations, and improving existing medical dispute handling mechanism. Other measures to this end include higher pay for medical workers equivalent to their value and career identity;media guidance by the government,which will all help create a better medical environment and doctor-patient relationship.