Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Objective:To explore the predictive value of qualitative and quantitative parameters of dual-layer spectral detector CT plain scan on the invasiveness of pure ground-glass pulmonary nodules (pGGNs).Methods:Clinical and imaging data of 113 patients (119 pGGNs) with pathology-proven lung adenocarcinoma who underwent preoperative dual-layer spectral detector CT plain scan in Tianjin Medical University Cancer Institute and Hospital from November 2019 to December 2020 were retrospectively analyzed. According to invasiveness, pGGNs were divided into non-invasive adenocarcinoma (non-IA) group ( n=66) and IA group ( n=53). The non-IA group included atypical adenomatous hyperplasia ( n=10), adenocarcinoma in situ ( n=26) and minimally invasive adenocarcinoma ( n=30). The qualitative parameters were nodule shape, lung-tumor interface, lobulation, spiculation, pleural retraction, bubblelike lucency, air bronchogram and vascular abnormality. The quantitative parameters included nodule size, effective atomic number (Z eff), CT value on 120 kVp images (CT 120 kVp) and virtual monoenergetic images from 40 keV to 200 keV (CT 40 keV-CT 200 keV), and slope of energy spectrum curve (λHU). The χ 2 test, Mann-Whitney U test and independent sample t test were used to analyze the parameter differences between non-IA group and IA group. Multivariate logistic regression analysis was performed to screen out independent predictors. Receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of single predictor and combined independent factors for the invasiveness of pGGN. Results:Significant differences were found in nodule shape, lobulation, air bronchogram, vascular abnormality, nodules size, Z eff, CT 120 kVp and CT 40 keV-CT 200 keV between non-IA and IA groups ( P<0.05). The maltivariate logistic regression analysis showed that nodule size [odds ratio 9.269, 95% confidence interval (CI) 1.640-52.395, P=0.012] CT 200 keV (odds ratio 1.012, 95%CI 1.006-1.019, P<0.001) as well as vascular abnormality sign (odds ratio 4.940, 95%CI 1.358-17.969, P=0.015) were independent predictors of pGGN invasiveness. ROC curve analysis of a single independent predictor and a combination of the three factors showed that the area under the curve (AUC) of the combination of three factors predicting the invasiveness of pGGN was significantly higher than the AUC of vascular abnormality sign ( Z=4.01, P<0.001) and CT 200 keV ( Z=3.25, P=0.001), while there was no significant difference in AUC between the combination of the three factors and nodule size ( Z=1.94, P=0.052). The AUC of the combination of the three independent predictors was 0.909, and the sensitivity and specificity for predicting pGGN invasion were 81.1% and 86.4%, respectively, using a threshold of 0.505. Conclusion:The combination of qualitative and quantitative parameters of dual-layer spectral detector CT plain scan shows a high predictive value for the invasiveness of pGGNs.

Objective:To investigate the expression at protein level and diagnostic value of histone acetyltransferase MYST2 in pancreatic cancer.Methods:From December 1st, 2017 to June 30th, 2020, at Peking Union Medical College Hospital, a total of 54 cases of pancreatic cancer tissues and corresponding paracancerous pancreatic tissues (>5 cm from the surgical margin) resected and confirmed by pathology were collected. ASPC1 and BXPC3 pancreatic cancer cell lines were knocked down (ASPC1 and BXPC3 knockdown group), CFPAC1 and SW1990 pancreatic cancer cell lines were overexpressed (CFPAC1 and SW1990 overexpression group), the untreated ASPC1, BXPC3, CFPAC1 and SW1990 were set as blank vector control group. The expression at protein level of MYST2 was detected by Western blotting in patients with different degrees of pathological differentiation, human normal pancreatic duct epithelial cell line HPDE, human pancreatic cancer cell lines ASPC1, BXPC3, CFPAC1 and SW1990, knockdown group, overexpression group and blank vector control group. The cell proliferation, migration, invasion and colony formation ability of the knockdown group, overexpression group and blank vector control group were determined by real-time cellular analysis, Transwell migration and invasion test, and plate colony formation assay. MYST2 immunohistochemical scoring was performed on pancreatic cancer tissues and para cancer tissues. Receiver operating characteristic curve was drawn to analyze the value of different MYST2 protein expression levels in the diagnosis of pancreatic cancer. Independent sample t test and variance analysis were used for statistical analysis. Results:Among the pathological slides of 54 cases of pancreatic cancer, 13 cases were highly differentiated, 24 cases were moderately differentiated, 15 cases were poorly differentiated and 2 cases were undifferentiated, the MYST2 expression at protein level in pancreatic cancer cells was 3.12±1.67, 2.87±1.59, 2.12±1.03 and 1.08±0.34, respectively, and the difference was statistically significant ( F=1.241, P<0.05). The MYST2 expression levels of ASPC1, BXPC3, CFPAC1 and SW1990 were all higher than that of normal pancreatic ductal epithelial cell lines HPDE (1.41±0.47, 1.40±0.93, 1.13±0.62 and 1.71±0.46 vs. 0.82±0.25), and the differences were statistically significant( t=1.625, 1.577, 1.319 and 1.832, all P<0.05). The MYST2 expression level of BXPC3 knockdown group was lower than that of BXPC3 blank vector control group (0.39±0.12 vs. 0.75±0.34); that of ASPC1 knockdown group was lower than that of ASPC1 blank vector control group (0.43±0.22 vs. 0.82±0.48); that of CFPAC1 overexpression group was higher than that of CFPAC1 blank vector control group (1.38±0.45 vs. 0.82±0.37); that of SW1990 overexpression group was higher than that of SW1990 blank vector control group (1.34±0.65 vs. 0.51±0.22), and the differences were statistically significant ( t=1.414, 1.378, 1.319 and 1.934, all P<0.05). The cell proliferation of ASPC1 knockdown group was slower than that of ASPC1 blank vector control group, and the proliferation peak at 80 h was lower than that of blank vector control group (1.02±0.77 vs. 4.31±2.45); the cell proliferation of BXPC3 knockdown group was slower than that of BXPC3 blank vector control group, and the proliferation peak at 80 h was lower than that of blank vector control group (0.91±0.24 vs. 2.84±0.53); the proliferation of pancreatic cancer cells in SW1990 overexpression group was faster than that of SW1990 blank vector control group, and the proliferation peak at 80 h was higher than that of blank vector control group (3.10±0.67 vs. 1.04±0.17); the proliferation of pancreatic cancer cells in CFPAC1 overexpression group was faster than that that of CFPAC1 blank vector control group, and the proliferation peak at 80 h was higher than that of blank vector control group (5.45±1.13 vs. 1.01±0.29), and the differences were statistically significant ( t=1.427, 1.316, 1.292 and 1.501, all P<0.05). In the test of migration ability, the number of cells passed through the Transwell chamber of ASPC1 knockdown group was less than that of ASPC1 blank vector control group (34.08±17.62 vs. 118.76±5.31); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (18.62±9.64 vs. 57.90±12.67); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (134.84±24.65 vs. 37.82±6.73); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (65.79±27.46 vs. 11.68±5.13), and the differences were statistically significant ( t=1.475, 1.322, 1.437 and 1.219, all P<0.05). In the test of invasion ability, the number of cells passed through the Transwell chamber of ASPC1 knockdown group was less than that of ASPC1 blank vector control group (9.79±5.75 vs. 45.76±12.71); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (23.46±11.13 vs. 84.92±17.65); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (156.42±34.50 vs. 42.13±22.17); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (112.64±47.82 vs. 39.09±17.23), and the differences were statistically significant ( t=1.324, 1.635, 1.423 and 1.119, all P<0.05). The number of colony formation of the ASPC1 knockdown group was less than that of ASPC1 blank vector control group (13.15±6.42 vs. 86.79±35.17); that of BXPC3 knockdown group was less than that of BXPC3 blank vector control group (14.93±9.30 vs. 52.93±15.76); that of SW1990 overexpression group was more than that of SW1990 blank vector control group (129.10±57.31 vs. 62.42±37.43); that of CFPAC1 overexpression group was more than that of CFPAC1 blank vector control group (157.98±66.45 vs. 74.35±34.69), and the differences were statistically significant ( t=1.148, 1.290, 1.274 and 1.462, all P<0.05). The MYST2 score of pancreatic cancer tissues was higher than that of adjacent paracancerous pancreatic tissues (3.04±2.23 vs. 1.32 ± 0.70), and the difference was statistically significant ( t=3.479, P<0.05). When the total immunohistochemistry score of MYST2 was 3 point, the area under the curve was the largest (0.888, 95% confidence interval 0.827 to 0.948), and the Youden index was 0.56. Conclusion:MYST2 is associated with the proliferation, invasion and migration of pancreatic cancer cells, and promotes the development of pancreatic cancer.

Objective:To investigate the situation related to HIV infection and influencing factors of traceability efficiency among sex partners of HIV positive men who have sex with men (MSM).Methods:A cross-sectional survey was conducted to investigate the traceability among sex partners of HIV-positive MSM in Ningbo from 2018 to 2020. Limiting-antigen avidity enzyme immunoassay determined recent HIV infection. The classified data was evaluated by chi-square test, and factors of traceability efficiency were analyzed by multivariate logistic regression.Results:A total of 374 newly confirmed HIV-positive MSM were recruited to participate in the HIV test in Ningbo from 2018 to 2020.HIV positive rate of sex partner was 15.7% (75/479,95% CI:12.4%-18.9%). HIV positive rates of sex partner of recent HIV infection MSM was 31.8% (21/66,95% CI:20.3%-43.4%). The proportion of newly confirmed HIV-positive sex partners of recent HIV infection MSM (76.2%) was higher than that of long-term HIV infection MSM (48.1%). The difference was statistically significant ( P=0.028). Results from the multivariate logistic regression analysis showed that HIV traceability efficiency was higher in the following subpopulations as; HIV positive MSM who were 36-45 years old (compared with 18-25 years old, OR=3.973,95% CI:1.364-11.569), HIV active detection (compared with HIV passive detection, OR=1.896, 95% CI:1.083-3.319), recent HIV infection MSM (compared with long-term HIV infection MSM, OR=3.733, 95% CI:1.844-7.556). Conclusions:HIV positive rate among partners of HIV positive MSM was very high. The traceability efficiency, which was recent HIV infection MSM and HIV active detection, was high. It is suggested to strengthen the traceability and focus on the newly confirmed HIV-positive MSM in VCT clinics.

Objective To explore the application of amide proton transfer (APT) imaging in differentiating glioma from treatment effect and to evaluate the diagnostic efficiency of the quantitative APT-related parameters.Methods A total of 23 patients (15 males, 8 females, age: 13-80 years) with 27 lesions who had underwent APT imaging in Tongji Hospital(Wuhan, China) from October 2014 to June 2015 were enrolled in this prospective study.The scan protocols were MRI normal plain scanning, diffusion WI, contrast-enhancement T1WI and APT imaging.Both the magnetization transfer ratio (MTR) and the relative MTR (rMTR) of lesions were manually measured by drawing ROI in the functional post-processing workstation.The results were compared with those of pathologic examinations and radiographic follow-up (≥3 months).Mann-Whitney u test was used to analyze the data.Results Compared with contralateral white matter, the primary gliomas (n=12) and recurrent gliomas (n=8) manifested hyper-intensity, while the treatment induced injuries (n=7) showed iso-or hypo-intensity.The difference of MTR between tumors and treatment effects was significant (102.78(101.93,103.84) vs 100.17(99.94, 100.63);z=-3.76, P<0.01), so was the difference of rMTR between tumors and treatment effects (3.92%(2.69%,4.67%) vs 0.47%(-0.79%,1.11%);z=-3.43, P<0.01).Both those two quantitative parameters exhibited excellent diagnostic performance with the AUC of 0.986 and 0.943.The sensitivity, specificity and accuracy of MTR were 100%(20/20), 6/7 and 96.3%(26/27) in the threshold of 100.68, while those of rMTR were 95.0%(19/20), 6/7 and 92.6%(25/27) in the threshold of 1.66%.Conclusions Combined with the routine MRI images, APT imaging can provide excellent qualitative and quantitative information in differentiating glioma from treatment effect.Both MTR and rMTR are helpful for the differentiation with high sensitivity and specificity and can be used as non-invasive imaging biomarkers in evaluating treatment effect of glioma.

Objective To quantitatively examine the relationship between xeroderma pigmentosum complementation C group (XPC)rs2228000 (C /T)polymorphism and the susceptibility of breast cancer. Methods The relevant case-control studies published up to December 2015 which investigated XPC rs2228000 (C /T)polymorphism and breast cancer risk were identified by searching PubMed,Cochrane Library,Chinese Biomedical Literature Data,Wanfang Database,China National Knowledge Infrastructure and VIP Database. Meta-analysis was conducted using STATA 12.0 software and odds ratio (OR)with its 95%CI were estimated. Results A total of 8 researches involving 9 case-control studies (3 850 breast cancer cases and 5 047 healthy controls) were included.The Meta-analysis showed that there was statistical association between XPC rs2228000(C /T)variance and breast cancer risk in the homozygous model (TT vs.CC:OR =1.28,95%CI:1.08-1.52,Z =2.80,P =0.005)and recessive model (TT vs.TC +CC:OR =1.23,95%CI:1.05-1.43, Z =2.64,P =0.008),but not in the allele model,heterozygote model and dominant model.In the subgroup of ethnicity and genotyping methods,the different significant correlation was existed between them under Asian and PCR-RFLP in genetic models (T vs.C:OR =1.21,95%CI:1.05-1.40,Z =2.63,P =0.009;TT vs. CC:OR =1.55,95%CI:1.13-2.13,Z =2.70,P =0.007;TT +TC vs.CC:OR =1.26,95%CI:1.02-1.55,Z =2.19,P =0.028;TT vs.TC +CC:OR =1.39,95%CI:1.04-1.87,Z =2.23,P =0.026).We also found significant association between them in subgroup of population-based controls in the homozygous model (TT vs.CC:OR =1.27,95%CI:1.02-1.57,Z =2.16,P =0.031).Conclusion XPC rs2228000 (C /T)polymorphism may be associated with the susceptibility of breast cancer,especially in Asian,and gene-type TT may increase the risk of breast cancer.

Objective To explore the association between Xeroderma pigmentosum complementation C group (XPC) Lys939Gln (A/C) gene polymorphism and the susceptibility of gastric cancer.Methods By searching PubMed,Cochrane Library,Elsevier,Springer-Verlag,China National Knowledge Infrastructure,Chinese Biomedical Literature Data,VIP Database and Wanfang Database,all eligible case-control studies published up to September 2015 were selected and the quality of each article was valuated by two reviewers independently according to the inclusion and exclusion criteria.Meta-analysis was performed by using STATA 12.0 software.Odds ratio (OR) and 95％ confidence interval (CI) were calculated.The text was estimated for the subgroup analysis,sensitivity analysis and publication bias test.Results A total of 7 case-control studies were included,including 2 336 cases with gastric cancer and 3 502 controls.The Meta-analysis showed that compared with the allele A,the allele C increased the risk of gastric cancer (OR =1.09,95％ CI:1.01-1.18,Z =2.12,P =0.034);compared to the genotype AA,the homozygous model (CC) and dominant model (CC + AC) also increased the risk of gastric cancer (CC vs.AA:OR =1.19,95％ CI:1.00-1.42,Z =2.00,P=0.046;CC+ACvs.AA:OR=1.12,95％CI:1.00-1.25,Z=2.03,P=0.042).The Meta-analysis showed the statistical significance between XPC Lys939Gln (A/C) gene polymorphism and the gastric cancer risk in subgroup of Asian people (C vs.A:OR =1.10,95％ CI:1.01-1.20,Z =2.28,P =0.023;CC vs.AA:OR=l.21,95％CI:1.01-1.46,Z=2.02,P=0.043;CC +AC vs.AA:OR =1.13,95％ CI:1.01-1.27,Z =2.11,P =0.035) and the source of community in the control group (C vs.A:OR =1.11,95％ CI:1.01-1.21,Z=2.25,P =0.024;CC vs.AA:OR =1.23,95％ CI:1.02-1.50,Z =2.12,P =0.034).Conclusion XPC Lys939G1n (A/C) gene polymorphism may be associated with the susceptibility of gastric cancer,and genotype CC,CC + AC and allele C can increase the risk of gastric cancer.

Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 (HSP47) is closely related with the development of fibrosis. To explore the potential function of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scleroderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-β. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 may become a pathological marker to assess the progression of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-expression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.
Adolescent ; Adult ; Animals ; Biopsy ; Blotting, Western ; Cells, Cultured ; Collagen ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; Fibrosis ; HSP47 Heat-Shock Proteins ; blood ; genetics ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Mice ; Mice, Inbred C3H ; Middle Aged ; NIH 3T3 Cells ; Protein Binding ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Scleroderma, Systemic ; blood ; genetics ; metabolism ; Skin ; metabolism ; pathology ; Transforming Growth Factor beta ; pharmacology ; Young Adult

The basic mechanical properties of a Radial Shock Wave Therapy Equipment (RSWTE) were experimentally studied in this paper. The output energy of the RSWTE working on the operation frequency of 10 Hz was measured by dynamic pressure transducer under the conditions of different operation pressure. The results showed that both operation pressure and operation frequency have effects on the output energy of the equipment. The output energy increases with the increase of operation pressure, and the magnitude of increased energy decreases with higher operation of frequency. With the increase of operation frequency, the output energy rises up in condition of lower operation pressure and drops off in condition of higher operation pressure. The accurate medical treatment should be selected with the optimized energy and condition according to the treatment requirement to different illness in clinical medical applications.
Equipment Design ; High-Energy Shock Waves ; Physical Therapy Modalities ; instrumentation ; Pressure

The basic mechanical properties of a Radial Shock Wave Therapy Equipment (RSWTE) were experimental y studied in this paper. The output energy of the RSWTE working on the operation frequency of 10 Hz was measured by dynamic pressure transducer under the conditions of different operation pressure. The results showed that both operation pressure and operation frequency have effects on the output energy of the equipment. The output energy increases with the increase of operation pressure, and the magnitude of increased energy decreases with higher operation of frequency. With the increase of operation frequency, the output energy rises up in condition of lower operation pressure and drops off in condition of higher operation pressure. The accurate medical treatment should be selected with the optimized energy and condition according to the treatment requirement to different il ness in clinical medical applications.