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 ascertain the endemic status of paragonimiasis in Zhejiang Province.Methods:From 2005 to 2020, 2-3 villages in 1-2 counties (cities, districts, hereinafter refferred to as counties) in historical endemic areas of paragonimiasis in Zhejiang Province were selected for monitoring each year. In each village, 50 to 150 local residents were selected as monitoring subjects, venous blood samples were collected, and serum Paragonimus antibody was detected by enzyme-linked immunosorbent assay (ELISA). Fifty to 100 intermediate hosts crabs or crayfish were collected in each village, and the infection of Paragonimus metacercaria was detected by crushing precipitation. Results:The positive rate of Paragonimus antibody was 2.9% (94/3 297); 3 929 crabs or crayfish were divided into 2 749 groups, 790 of which were found to have Paragonimus metacercaria infection, with a Paragonimus metacercaria infection rate of 28.7%. Conclusions:Paragonimus transmission chain exists in some counties of Zhejiang Province, which still has the potential risk of Paragonimus epidemic. Therefore, it is necessary to strengthen monitoring and carry out extensive health education to improve residents' self-protection awareness.

Objective:To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19).Methods:Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV.Results:Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs.Conclusions:The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

Objective To discuss the surgical strategy and clinical effects of robotic assisted laparoscopic antegrade inguinal lymphadenectomy for penile cancer.Methods We retrospectively analyzed the clinical data and surgical strategy on the 7 cases,who undergoing robotic assisted laparoscopic antegrade inguinal lymphadenectomy,from August of 2016 to August of 2017.The mean age of 7 patients was (49.7 ± 7.5) years old,ranged from 40 to 62 years old,the mean BMI was (27.97 ± 3.86) kg/m2,ranged from 21.76 to 33.21 kg/m2 . There were 4 cases of T1,2 cases of T2,1 case of T3,1 case of N1,3 cases of N2,3 cases of N3 according to TNM stages.Preoperative preparation was as follows,preoperative cardiopulmonary assessment,inguinal and pelvic CT or MRI,ultrasound of lower extremity venous,bowel preparation.The patients were placed in a supine position,with an indwelling catheter,with the head positioned lower than the hip at an angle of about 15 degrees,legs were spread apart around 45 degrees,and both knees were slightly bent and externally rotated.The da Vinci robotic patient cart was pushed forward between legs of the patient.A blunt separation was carried out between Scarpa's fascia and the surface of the aponeurosis of the obliquus externus abdominis prior,then subcutaneous space was established by a self-made balloon dilatation.Results 7 cases were completed successfully without robot reposition without any conversion.Operative time of each side ranged from 50 to 90 min (70.0 ± 12.5)min.The blood loss of each side was less than 10 ml.In the 7 cases,the number of nodes removed from left inguinal region ranged from 7 to 18 (14.0 ±3.3).The number of nodes removed from right ranged from 5 to 21 (11.0 ± 3.3).Pelvic lymphadenectomy was completed in the meantime by original trocar site on 4 cases.Till now,no perioperative complications,such as flap necrosis,delayed healing of incision,cellulitis,occurred in inguinal region,except lymphorrhagia in 3 cases.During a follow-up within 3-14 months,there was no recurrence or metastasis in 6 cases except one died from tumor progression with systemic metastasis.Conclusions Antegrade inguinal lymphadenectomy for penile cancer by using Da Vinci robotic surgical system is safe and effective.This technique also appears to diminish the wound related complications associate with the standard open approach.Compared with the similar surgery,we conducted bilateral inguinal lymphadenectomy without patient cart reposition,which simplify the procedure and reduce the using of trocar.According to individual clinical conditions,pelvic lymphadenectomy also can be completed in the meantime by original trocar.

Objective To explore the effects of low tube voltage and contrast dose on the prospective ECG gating coronary artery imaging in overweight patients.Methods A total of 80 overweight patients were randomly divided into control group (traditional tube voltage and contrast medium dose) and observation group (low tube voltage and contrast medium dose),and effect of prospective ECG gating coronary artery imaging was compared.Results In the observation group,the excellent rate of imaging quality was 90％,and which in the control group was 92.5％ (P ＞ 0.05).There were significant differences in values of CT coronary artery imaging,image noise,image signal-tonoise ratio and radiation dose between two groups (P ＜ 0.05).Conclusion Low tube voltage and contrast dose can significantly reduce the patient's radiation dose.

Objective To explore the effects of low tube voltage and contrast dose on the prospective ECG gating coronary artery imaging in overweight patients.Methods A total of 80 overweight patients were randomly divided into control group (traditional tube voltage and contrast medium dose) and observation group (low tube voltage and contrast medium dose),and effect of prospective ECG gating coronary artery imaging was compared.Results In the observation group,the excellent rate of imaging quality was 90％,and which in the control group was 92.5％ (P ＞ 0.05).There were significant differences in values of CT coronary artery imaging,image noise,image signal-tonoise ratio and radiation dose between two groups (P ＜ 0.05).Conclusion Low tube voltage and contrast dose can significantly reduce the patient's radiation dose.

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

OBJECTIVETo investigate the correlation of neurochemical metabolism in hippocampus with memory function in young adult patients with first-episode depression.

METHODSTwenty patients with first-episode depression (patient group) and fifteen health subjects (control group) were enrolled in the study. The neurochemical metabolism, including the levels of N-acetylaspartate (NAA), Choline (Cho), Creatine (Cr), Myoinositol (mI) were measured by proton magnetic resonance spectroscope (1H-MRS) in bilateral hippocampus. Wechsler Memory Scale (WMS) were used to examine the memory function in both groups.

RESULTSThe memory quotient (89.15 ±6.62) of patient group was significantly lower than that of controls (P <0.01),the scores of long-term memory,short-term memory and immediate memory in patients were also lower than those of controls (P<0.05 or 0.01). In patient group, the ratio of NAA/Cr (1.34 ±0.08) in the left hippocampus was significantly lower than that of control group (P<0.01); and the ratio of mI/Cr in the bilateral hippocampus [(0.63 ±0.13) in left and (0.6 ±0.1) in right] was significantly higher than those in control group (P<0.05). In patient group,the ratio of NAA/Cr in the left hippocampus was positively correlated with WMS scores (P<0.01), and the ratio of mI/Cr in the left hippocampus was negatively correlated with WMS scores (P<0.05).

CONCLUSIONThe memory deficit and abnormal metabolism function of neuron cell in hippocampus coexist in young adult patients with first-episode depression, and the lower NAA/Cr and higher mI/Cr ratio in the left hippocampus may result in the memory deficit.

Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Creatine ; metabolism ; Depressive Disorder ; metabolism ; physiopathology ; Female ; Hippocampus ; metabolism ; Humans ; Inositol ; metabolism ; Magnetic Resonance Spectroscopy ; Male ; Memory ; Neuropsychological Tests ; Young Adult

Background and purpose: Extraskeletal myxoid chondrosarcoma (EMC) is a malignancy of uncertain differentiation tumor characterized by a multinodular structure and abundant myxoid matrix. Its preferred sites were the deep soft tissues of the extremities. The aim of this study was to investigate the clinicopathologic characteristics, diagnosis and differential diagnosis of EMC. Methods: Seven cases of EMC were analyzed for clinicopathological and immunohistochemical features with review of the related literature. Results: It occurred predominantly in females (male/female=2︰5). Five cases were located in low extremities and two in upper limb girdles, more commonly near the joint. Grossly, the masses showed as grey, lobular and somewhat transparent with a relatively well-deifned margin. Microscopically, the small ovary or plump spindle-shaped cells arranged in strand and cord patterns and lobular architecture which separated by delicate fibrous networks with an abundant myxoid but hypovascular background. And the tumors were immunoreactive for vimentin, and partly for S-100 and EMA, meanwhile, negative for CK. Conclusion:EMC is a rare soft tissue sarcoma with distinctive histopathological features. It should be distinguished from some mimics especially those tumors with a myxoid stroma or chondroid differentiation, such as chordoma and chondrosarcoma.

ObjectiveTo explore the relationship between sleep quality and glucose level,diabetic complications in elderly type 2 diabetes mellitus.Methods A total of 130 hospitalized elderly type 2 diabetes in our hospital were included in the study. Questionnaires and other related clinical data were collected within one week after admission.Patients were divided into two groups:poor-sleeper group and good-sleeper group according to Pittsburgh Sleep Quality Index(PSQI).ResultsSixty percent (78/130) of these patients were poor sleepers. The following parameters differed in the two groups:the duration of diabetes [ (7.9 ± 1.8 ) years vs ( 7.2 ± 1.5 ) years,t =2.318 ],systolic blood pressure [ ( 148 ± 30 ) mm Hg ( 1 mm Hg =0.133 kPa) vs ( 138 ± 23 ) mm Hg,t =2.037 ],fasting plasma glucose (FPG) [ ( 10.7 ± 2.2) mmol/Lvs ( 9.8±1.9)mmol/L,t =2.410],hemoglobin A1c (HbA1c) [(8.6 ±2.2)％ vs (7.8±2.1 ) ％,t =2.068],high-sensitive C-reactive protein (hs-CRP) [ (5.27 ± 2.34) mg/L vs (4.44 ± 1.76)mg/L,t =2.179 ],ratio of diabetic complications ( 61％ vs 32％,x2 ＝ 4.257 ),percentage of depression ( 20％ vs 8％,x2 =3.722 ),score of life quality [ ( 98 ± 19 ) scores vs ( 89 ± 13 ) scores,t ＝ 2.980 ],and proportion of patients treated with insulin (32％ vs 12％,x2 =4.489). All the above parameters were significantly higher in poor-sleeper group than the good-sleeper group (all P value＜ 0.05 ). Multiple correlation analysis showed that the factors affecting sleep quality were FPG,HbA1c,duration of diabetes,diabetic complications,depression,life quality and insulin application (r =0.213,0.257,0.223,0.335,0.422,0.3451,0.231,respectively ; all P value ＜ 0.05 ).By multivariate logistic regression analysis,the followings were found:FPG (β =1.29,P ＜ 0.05 ) and PSQI (β =1.07,P ＜ 0.05 ) were found to be correlated with HbA1c.With increasing of PSQI,FPG,HbA1c,diabetic complications and life quality were changed significantly( all P value ＜ 0.05 ).The indcpcndcnt risk factors of diabetic complications were duration of diabetes ( OR ＝ 1.32,95％ CI 1.01-2.01 ),HbA1c ( OR =2.01,95％ CI 1.63-2.67 ),hs-CRP( OR =1.12,95％ CI 1.08-1.21 ) and PSQI ( OR =1.71,95％ CI 1.58-2.02).ConclusionsElderly type 2 diabetes mellitus are usually poor sleepers. Sleep quality probably affects blood glucoseregulation, and is closely correlated with the occurrence of complications.In addition,poor sleep quality results in poor life quality.