Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.

Objective To establish a scientific training program that takes into account both anaerobic and aerobic training for pilots,and to explore the appropriate ratio of aerobic and anaerobic training.Methods According to the physical examination standards for pilots,a total of 16 healthy subjects aged 18-24 were selected from two batches.The two batches of subjects were trained with different aerobic and anaerobic ratios.Training period was 3 months.The changes in cardiopulmonary function of the subjects before and after training were evaluated using the cardiopulmonary function exercise testing system(CPET),and the changes in anaerobic capacity were evaluated using changes in strength as an indicator.Results After training,the weight load of the subjects in the two training programs,including barbell squats,leg flexion and hard pull,and barbell under 10RM and 3RM,was significantly increased(P<0.001),and there was no statistically significant difference in anaerobic strength growth between the two groups.The results of CPET showed that the maximum load,maximum heart rate,and respiratory quotient in the two groups were significantly increased after than before the training(P<0.01).The maximum load(Experiment group 1:29.12±19.69,Experiment group 2:72.00±46.24)and respiratory quotient(Experiment grouop 1:0.11±0.09,Experiment group 2:0.28±0.16)of the subjects in experiment group 2 before and after training were greater than those in experiment group 1.The difference was statistically significant(P<0.05).Conclusion The anaerobic and aerobic capacities of the subjects in the experiment group 2 are effectively improved,indicating that ratio of aerobic and anaerobic of the training scheme is better.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC₅₀ values of 34.89 and 19.88 μmol·L^-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC₅₀ values of 32.67, 79.38, and 16.74 μmol·L^-1, respectively.
Flavonoids/chemistry* ; SARS-CoV-2 ; Rhizome ; COVID-19 ; Peptide Hydrolases ; Antiviral Agents/chemistry*

Objective:To investigate the radiosensitization effect of low-dose sulfasalazine (SAS) on colorectal cancer (CRC) cells.Methods:Proliferation inhibition effect of SAS on CRC cells was detected by CCK-8 assay, and the concentration of SAS in vitro assays was based on its IC10 value. CRC cells were treated with SAS alone or combined with inhibitors of apoptosis, autophagy, ferroptosis and necroptosis, then cell viability was detected by CCK-8 assay. Trypan blue staining, clone formation assay and cell growth curves were used to verify the radiosensitization effect of SAS on CRC cells in vitro. CRC cells were treated with SAS and radiotherapy, then the intracellular contents of lipid peroxidation and the protein levels of GPX4, PTGS2, cleaved PARP and active caspase 3 were evaluated, respectively. Subcutaneous xenograft tumor mouse model was established to further verify the radiosensitization effect of SAS in vivo. Results:High dose (lethal dose) of SAS could induce apoptosis and ferroptosis in CRC cells. Low dose (non-lethal dose) of SAS enhanced the radiosensitivity of CRC cells in vitro, and the radiosensitivity effect of SAS could only be abolished by ferroptosis inhibitor (Fer-1). Low dose of SAS combined with radiotherapy significantly down-regulated the expression of GPX4, whereas increased the intracellular lipid peroxidation levels and the expression of PTGS2. SAS also showed significant radiosensitization effect in subcutaneous xenograft tumor model. Conclusion:Our findings suggest that low-dose SAS could increase the radiosensitivity of CRC cells by promoting ferroptosis.

Objective: To investigate the salvage strategy and efficacy for patients with locally recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy. Methods: A total of 126 patients who met the inclusion criteria were enrolled in this study and divided into the salvage surgery, salvage radiochemotherapy and best supportive care. Results: Fifty-eight of 126 patients received salvage esophagectomy, 52 underwent salvage radiochemotherapy and the remaining 16 patients received best supportive care. The 1-, 3-, 5-year overall survival rates of patients receiving salvage therapy were 51%, 16% and 4% for the three groups, whereas all patients in the best supportive care group died within 12.0 months (P<0.001). The 1-, 3-, 5-year survival rates in the salvage surgery and salvage radiochemotherapy groups were 48%, 20% and 7%, and 51%, 11% and 3%, respectively (P=0.473). Multivariate analysis by Cox proportional hazard model showed that T staging of recurrent tumors and salvage regimen were the independent prognostic factors in patients with locally recurrent esophageal cancer (both P<0.001). Postoperative infection occurred in 16% of the patients in the salvage surgery group, and the incidence of esophagotracheal fistula and mediastinoesophageal fistula was 10% and 6% in the salvage radiochemotherapy group. Conclusions A survival benefit can be elicited by salvage surgery or salvage radiochemotherapy in patients with locally recurrent esophageal cancer after definitive radiochemotherapy. Nevertheless, extensive attention should be paid to the management of postoperative complications in clinical practice.

Objective: To explore the epidemiological distribution characteristics of glucose-6-phosphate dehydrogenase (G6PD) activity, incidence of G6PD deficiency in neonates and the cut-off values. Methods: About 1.44 million newborns in 10 districts of Zhejiang province from March 2015 to September 2017 were included in this study. Fluorescence analysis was used to determine the G6PD activity in dried blood spots. Those with initial screening positive results were recalled and confirmed by direct ratio of G6PD to 6PGD (6-phosphogluconate dehydrogenase) to confirm the diagnosis. The results were analyzed by using nonparametric and chi-square tests. Results: Significant differences of G6PD levels were found among the groups of different genders, gestational age, birth weight, blood sampling age, blood sampling season and districts (P＜0.01). The male incidence of G6PD deficiency was significantly higher than female incidence. In different regions of Zhejiang province, the highest prevalence was in Lishui (0.38%) and the lowest was in Zhoushan (0.11%), The trend of high prevalence in the south and low prevalence in the north was basically showed. When the cut-off value of G6PD activity ranged from 2.60 to 2.80 U/g Hb, the sensitivity of G6PD deficiency screening for male and female newborns was 100% and the Youden index was the highest (about 0.99). Conclusion The level of G6PD activity may be relevant to the factors of population group and period. The incidence of G6PD deficiency may be affected by different genders and different regions. The cut-off values for screening may initially set at 2.60 U/g Hb and 2.80 U/g Hb for male and female respectively.

Objective To understand the health literacy status,influencing factors and demand carrying out the health education based on the mobile terminal among college students to provide a new idea for formulating and implementing the health literacy promotion plan for university students.Methods The multi-stage stratified cluster random sampling method was adopted to extract 1 949 students from partial universities in Nanjing City and conduct the investigation by adopting the Rapid Estimate System of Health Literacy and Health Education Demand Based on the Mobile Terminal Questionnaire of College Students.The influence factors were analyzed by using the univariate analysis and ordinal multi-classification Logistic regression analy sis.Results The university students with high,marginal and low health literacy level accounted for 31.3％,48.9％ and 19.8％ respectively.The proportions of the students with high health literacy in the four dimensions,including health knowledge,health behaviors,health skill and health status,were 57.9％,18.3％,61.0％ and 44.5％ respectively.The ordinal multi-classification Logistic regression analysis showed that the major influence factors affecting the health literacy of university students were gender,education background of mothers,majors,grades,electively taking the health education course.81.2 ％ of university students wanted to or urgently wanted to understand the health literacy knowledge.The main route getting the health literacy knowledge by the university students was network(83.8％).91.8％ of students were willing to learn the health literacy knowledge through mobile terminal.87.1％ of students believed that the WeChat was suitable to learn the health knowledge,81.3％ of students hoped to use the WeChat platform for learning the health knowledge,73.8％ of students hoped the Wechat to push the health knowledge with the modes of words combined with images and video.It was recommended that the health knowledge pushing for 1-3 times per week was suitable.Conclusion The health literacy of university students is at the marginal level.The health behaviors literacy is most lacking and the demand for the health education based on the mobile terminal is stronger.The health literacy intervention of university students should sufficiently apply the new media platform superiority and the emphasis should be placed on the populations of males,low education background mothers,non-medicine major,low grade and without electively taking the health education course.

We detected the seroprevalence of Toxoplasma gondii (T.gondii) in the wild birds in northeast China.The wild bird's blood was collected from the cutaneous ulnar vein and the serum was isolated and used for detection of anti T.gondii antibody by modified agglutination test (MAT).Results showed that totally 179 birds' serum samples were collected.Twenty serum samples (11.17％) were positive with T.gondii antibody,which belonged to 9 orders,17 families and 31 species.The seroprevalence against T.gondii was about 5.26％ (1/19) in Columbiformes,9.09％ (9/99) in Passeriformes,14.29％ (3/21) in Falconiformes,15.00％ (5/22) in Piciformes,16.67％ (1/6) in Coraciiformes,and 25.00％ (1/4) in Anseriformes.Based on their feeding behavior,the seroprevalence was 12.00％ (3/25) in carnivorous wild birds,10.60％ (15/141) in omnivorous wild birds,and 15.38％ (2/13) in the wild birds feeding on aquatic animals or plants.These wild birds also can be sorted as migratory and sedentary (non-migratory) according to their migration habits,and the serum positivity was 11.67％ (14/120),and 10.71％ (6/59) respectively.The seroprevalence against Toxoplasma gondii in wild birds in northeast China is about 11.17％,which indicates a common infection of Toxoplasma gondii in wild birds.

Objective: To investigate the efficacy and safety of micafungin (MCF) for pulmonary invasive fungal disease (PIFD) in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation. Method: Twenty-five neutropenic PIFD children with acute leukemia or post hematopoietic stem cells transplantation in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were selected from January 2012 to June 2015, including 12 males and 13 females, age range 2-15 (average 6.2±2.0) years. There were 12 cases of acute leukemia (AL) after chemotherapy, 4 cases of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 9 cases of β-thalassemia major after allo-HSCT. All children received MCM for the treatment of PIFD, the dosage of MCM was 3-4 mg/ (kg·d) , once a day. The children received 2 to 6 courses of treatment, individually with a course of 7 days. 1, 3-β-D glucan assay (G test), galactomannan antigen test (GM test), high-resolution CT and the biochemical indexes for organ functions were closely monitored. Result: Twenty-five cases were diagnosed as PIFD, including 2 patients diagnosed as proven, 6 as probable and 17 as possible. Of the 25 cases, 1 was confirmed aspergillus by biopsy pathology and 1 was candida albicans by blood culture. The G and GM test with positive results was 5 and 2 respectively. Chest CT scans of the 25 cases had obvious lesions: air crescent sign and cavitation in 4 cases, diffuse ground glass change in 9 cases, double lung scattered patchy, small nodules and cord like high density shadow in 7 cases, unilateral or bilateral chest wall wedge-shaped consolidation edge in 5 cases and pleural effusion in 5 patients. The effective rate of MCF in treatment of PIFD was 68% (17/25), including 13 cases cured, 4 cases improved, 4 cases were improved clinically and in 4 cases the treatment was ineffective. Eight cases were effective in MCF monotherapy group (12 cases) and nine were effective in MCF combined therapy group(13 cases), respectively. Side-effects including allergies, gastrointestinal side effects, electrolyte disturbances, impairment of liver and kidney function, and myelosuppression were not found in those children treated with MCF. Conclusion Micafungin is effective and safe in the treatment of pulmonary invasive fungal disease in pediatric patients with acute leukemia or post hematopoietic stem cell transplantation.

OBJECTIVETo evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD).

METHODSA retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B.

RESULTSOverall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects.

CONCLUSIONFor IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.

Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Hematologic Diseases ; microbiology ; Humans ; Mycoses ; drug therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome