Objective To evaluate the value of rs61330082 and rs4730153 polymorphisms of Visfatin locus for the diagnosis of type 2 diabetes mellitus(T2DM)in a high-risk population.Methods SNPscanTM high-throughput single nucleotide polymorphism typing technique was used to genotype Visfatin gene loci rs61330082 and rs4730153 in 346 T2DM patients(T2DM group)and 1426 normal controls(NC group).Logistic regression analysis was used to analyze T2DM risk factors.ROC curves were used to analyze the optimal cut-off values of Visfatin gene rs61330082 and rs4730153 for the diagnosis of T2DM.Results The proportion of women,age,obesity,smoking,hypertension,FPG,HbA1c and TG were higher in T2DM group than those in NC group(P<0.01)and HDL-C was lower than in NC group(P<0.01).The frequency of G allele and GG genotype was higher in T2DM group compared with NC group(P<0.05).Logistic regression analysis showed that age,female,obesity,hypertension,TG,and GG genotype at rs4730153 locus were risk factors for T2DM,HDL-C was a protective factor for T2DM.The area under the ROC curve of GG genotype at Visfatin rs4730153 mutation for diagnosis of T2DM was 0.668 and the optimal cut-off point for predicting T2DM was 20.04%,with sensitivity 60.1%and specificity 66.1%,respectively.Conclusion The GG genotype of Visfatin gene rs4730153 locus is associated with the risk of T2DM and can beused as a candidate gene for predicting phenotype of T2DM.

Objective To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. Methods Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO₂ mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. Results A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). Conclusions The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.

Objective:To explore the chain mediating effect of anxiety and flow experience on perceived stress and mobile phone addiction in nursing college students.Methods:In December 2021, a cross-sectional design survey was conducted on 4 179 freshmen and sophomores in a nursing college in Heilongjiang Province. The Chinese perceived stress scale, generalized anxiety disorder-7, flow state scale, and mobile phone addiction tendency scale were selected separately to assess perceived stress, anxiety symptoms, flow experience and mobile phone addiction. SPSS 26.0 software was used for descriptive analysis, independent sample t-test, Spearman correlation analysis, and AMOS 24.0 software was used for mediating effect test. Results:(1) Among the 3 050 nursing students, there were 714(23.41%) students who were addicted to mobile phones. (2) Spearman correlation analysis indicated that perceived stress(27.31±9.56) was positively correlated with anxiety(7.00(1.00, 10.00), r=0.441, P<0.05), flow experience((12.00±3.40), r=0.517, P<0.05), and mobile phone addiction((42.42±13.05), r=0.476, P<0.05).Anxiety was positively correlated with flow experience ( r=0.430, P<0.01) and mobile phone addiction ( r=0.538, P<0.01).Flow experience was positively correlated with mobile phone addiction ( r=0.490, P<0.01). (3) Anxiety and flow experience played seperate mediating and chain mediating roles between perceived stress and mobile phone addiction, accounting for 26.06%(0.165/0.633), 23.54%(0.149/0.633) and 3.48%(0.022/0.633) of the total effect. Conclusion:Perceived stress not only directly affects the mobile phone addiction of nursing students, but also indirectly affects mobile phone addiction through the independent and chain mediating effects of anxiety and flow experience.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1^G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1^G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).
Humans ; NF-kappa B/metabolism* ; Ginsenosides/pharmacology* ; Amyotrophic Lateral Sclerosis/genetics* ; Culture Media, Conditioned/pharmacology* ; Superoxide Dismutase-1 ; Neurodegenerative Diseases ; Neurons/metabolism* ; Apoptosis

Objective:The hemodynamic parameters of elderly patients with septic shock were measured simultaneously with pulse index continuous cardiac output(PiCCO)and thoracic electrical bioimpedance(TEB)to evaluate the accuracy of TEB and to provide empirical evidence for its clinical use.Methods:A total of 24 elderly patients with septic shock admitted to the intensive care unit of our hospital between July 2021 and December 2021 were retrospectively recruited.TEB and PiCCO hemodynamic monitoring were performed continuously in all patients, and hemodynamic data were collected for statistical analysis.Results:Cardiac output, cardiac index, stroke volume, stroke index and systemic vascular resistance measured by the two methods had no significant difference( P>0.05). The 95% confidence intervals in the Bland-Altman plots for cardiac output, CI, stroke volume, stroke index, and systemic vascular resistance were(-1.18, 1.25), (-0.65, 0.71), (-24.23, 37.00), (-12.93, 19.26)and(397.11, 425.83). In the Bland-Altman plots for cardiac output, cardiac index, stroke volume and systemic vascular resistance, 4.17% of the points(1/24)fell outside of the 95% confidence interval, and in the Bland-Altman plots for stroke index, 8.33% of the points(2/24)fell outside of the 95% confidence interval. Conclusions:TEB and PiCCO have good consistency in evaluating the hemodynamics of elderly patients with septic shock.Therefore, TEB can be recommended for community hospitals and used in elderly patients.

Objective:To explore the effect of a new teaching mode, which includes bridge-in, outcome, pre-test, participation, post-test and summary (BOPPPS), on the online teaching of radiobiology related knowledge for cancer radiotherapy practitioners.Methods:Taking the cell survival curve, cell cycle and radiosensitivity as examples, the radiotherapy practitioners in multiple university-affiliated hospitals were organized to carry out a multicenter prospective randomized control study. All practitioners were randomly divided into BOPPPS group and control group. The courses for BOPPPS group were designed as an online classroom, consisting of pre-class preparation, online teaching and post-class stages. The online teaching stage included video viewing, basic knowledge learning, literature discussion, group discussion and others. The control group employed the traditional teaching mode. The χ2 test was used to compare the consistency of general conditions between the two groups, and nonparametric test was used to compare the differences in scores between two or more groups. Results:The score of the pre-class test was 58.56 ± 0.99. Post-class average score for BOPPPS group was 85.48±0.85 and for control group 77.79±1.10, with the former being higher 7.69 ( Z=5.31, P<0.001) than the latter. The average answer time was (296.62±15.40) s for BOPPPS group and (386.41±21.27) s for control group, with the former being shorter 89.79 s ( Z=3.34, P=0.001) than latter. Subgroup analysis shown that the scores of BOPPPS group were significantly rising, regardless of whether or not the students had studied radiobiology courses. Among the students who have not studied these courses, the scores were rising greatly. Moreover, From the analysis of different positions, it was found that both the scores of BOPPPS group and control group have risen, especially for doctors, deputy chief doctors, physicists and technicians. There were also statistically differences between different degrees, with significantly rise in scores for undergraduate and doctoral students ( Z=3.64, 4.18, P<0.001). Conclusions:The flexible application of BOPPPS teaching mode to the online education of such boring disciplines, like radiobiology, is of great significance to raise the theoretical basis of radiotherapy practitioners.

Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10⁶ bone marrow cells with 8×10⁶ spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4⁺ T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ²=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.

Objective: To analyze the significance of serum free light chain (sFLC) for the prognosis of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 621 NDMM patients in Changzheng Hospital from June 2010 to December 2016 was retrospectively analyzed. The serum free light chain levels were measured and the ratios of κ/λ chains were calculated. The significance of serum free light chain ratio (sFLCR) for the prognosis of NDMM patients was analyzed. Results: Among the 621 NDMM patients, 42 patients (6.8%) were in the normal free light chain ratio group (0.26≤sFLCR≤1.65), 247 patients (39.8%) were in the low free light chain ratio group (0.01＜sFLCR＜0.26 or 1.65＜sFLCR＜100), and 332 patients (53.5%) were in the high free light chain ratio group (sFLCR≤0.01 or sFLCR≥100). Compared with normal sFLCR group, the abnormal sFLCR group showed low level of hemoglobin; elevated levels of bone marrow plasma cells, serum creatinine and β 2 -MG, and more patients were in DS stage Ⅲ and ISS stage Ⅲ with high risks of cytogenetics(all P＜0.05). The overall survival (OS) in the normal sFLCR group was significantly better than the abnormol sFLCR groups (not reached vs 58.7 months, P=0.043). Compared with the patients with both high sFLCR and low risks of cytogenetics, the patients with high sFLCR and high risks of cytogenetics showed shorter overall survival time (median OS time was 41.6 months vs 61.4 months, P=0.015). Conclusion The NDMM patients with significantly abnormal sFLCR may indicate more tumor load and higher aggressive progression. sFLCR should be an independent prognostic indicator for the outcome of multiple myeloma. The patients with high sFLCR and cytogenetic abnormalities, have worse prognosis than the others.

Objective: To investigate the safety and efficacy of haploidentical hematopoietic stem cell transplantation with different intensity conditioning regimen in the treatment of childhood aplastic anemia (AA) . Methods: Thirty-seven AA patients who underwent haploidentical transplantation in BaYi Children's Hospital Affiliated to PLA Army General Hospital from January 2013 to January 2017 were enrolled. According to the dosage of conditioning regimen, 34 patients excluding 3 other conditioning regimens were divided into high-dosage group (regimen 2, 22 cases) and low-dosage group (regimen 3, 12 cases). The data of Engraftment, graft-vs-host disease (GVHD), hematopoietic reconstitution, relapse, infection, overall survival (OS) were analyzed. The comparison between the two groups was tested by χ² test. Results: A total of 35 of 37 patients achieved primary engraftment; 2 cases died of regimen-related toxicity and severe infection before the infusing of the grafts. The activation rate of CMV and EBV was 60% (21/35) . Post-transplant lymphocyte disease (PTLD) of lung occurred in one case. The cumulative incidences of acute GVHD grade Ⅰ-Ⅳ and chronic GVHD were 29% (10/35) and 34% (12/35) respectively and the incidence of extensive chronic GVHD was 6% (2/35) . The median follow-up time was 18.8 (2.9-44.1) months, the OS was 92% (34/37) .All survived patients were no longer dependent on blood transfusion and none of them had recurrence. Comparing the rates of overall survival(86%(19/22) vs.100%(12/12)) and rates of chronic GVHD(40%(8/20) vs. 17%(2/12)) in regimen 2 and regimen 3 group, there were no significant difference (χ²=1.742, 1.841, all P>0.05) . Significant difference was found at the incidence of Ⅰ-Ⅳ acute GVHD (10% (2/20) vs. 50% (6/12) ,χ²=6.200, P=0.013). Conclusions Haploidentical hematopoietic stem cell transplantation is effective and safe. It is suitable for patients who are not eligible for matched donor transplantation. Application of reduced dose preconditioning in haploid transplantation is worth exploring.

Objective To detect the role of PAR2-PKA/PKCε signaling pathway in periphery neurons in the tran-sition from acute to chronic pain,and investigate the possible approach to prevent both acute and chronic pain simultane-ously. Methods SD rats were randomly divided into control group,sham model group,model group,iPAR2-1 group and iPAR2-2 group. The hyperalgesia priming model was established by injection of carrageenan and PGE2 into the left hind-paw except control and sham model group. PGE2 was administrated at 7 days after carrageenan injection. The PAR2 inhibi-tor was administrated before and after PGE2 injection separately in the iPAR2-1 group and iPAR2-2 group. The paw with-drawal thresholds(PWTs)of rats in each group was detected before and at 5 h,3 d,6 d,7 d 0.5 h,7 d 4 h,7 d 24 h after carrageenan injection. The expression level of PAR2, PKA and PKCε proteins in the dorsal root ganglion(DRG) were detected at 24 h after carrageenan injection. Results The hyperalgesia priming model was successfully generated. When PGE2 was administrated at 7 days after carrageenan injection, the hyperalgesia induced by PGE2 was significantly prolonged. The PWTs of rats in the model group were significantly lower than that of the control and sham model groups(P<0.01),though the PWTs of sham model group had no significant difference with the control on 7 d 24 h after carrageenan injection(P>0.05). The expression level of PAR2 and PKCε in the ipsilateral DRG neurons were significantly increased on 7 d 24 h after carrageenan injection,when compared with the control and sham model groups(P<0.05). PAR2 inhibi-tor prevented the prolonged hyperalgesia induced by PGE2(P<0.05)and decreased the PKCε expression in DRG neurons whenever it was given(P<0.05). However,PAR2 inhibitor did not regulate the acute inflammatory pain of PGE2 and the expression of PKA in DRG neurons(P>0.05). Conclusions Inhibition of the expression of PAR2 can prevent the tran-sition from acute to chronic pain. This effect may be related with the inhibitory effect on the activation of PAR2-PKCε sig-naling pathway in DRG neurons. However,inhibition of PAR2 can not regulate the acute pain. These may because of that the PAR2-PKA signaling pathway does not play a role in acute pain.