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Objective @#To investigate the effects of DNA demethylation drugs combined with histone deacetylase inhibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression .@*Methods@#Human oral cancer cell lines C al27 and SCC⁃9 were treated with decitabine (DAC) , an inhibitor of DNA methyltransferase , combined with trichostatin A ( TSA) and valproic acid ( VPA) , inhibitors of histone deacetylase . Then reverse transcription⁃polymerase chain reaction ( RT⁃PCR) , quantitative real ⁃time PCR ( qRT⁃PCR) and Western blot were used to detect the expression of FMR1NB and pyrosequencing was used to detect the methylation of FMR1NB promoter. @*Results @#Compared with the blank control group , DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in C al27 and SCC⁃9 cells . Compared with DAC alone group , FMR1NB mRNA expression of each DAC⁃combined drug groups significantly increased , but FMR1NB protein did not significantly change in C al27 cells; for SCC⁃9 cells , except for DAC + TSA group , the mRNA and protein levels of FMR1NB significantly increased in all other groups . In addition , there was no significant difference in the expression of FMR1NB mRNA and protein between the three⁃combined drugs group and two-combined drugs groups . Further methylation assay showed that the methylation level of the overall FMR1NB promoter and its each CpG site measured were reduced to varying degrees in all treatment groups except for three⁃combination drug group of SCC⁃9 .@*Conclusion @#DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter , wherein the enhanced expression effect of the combination of the two drugs is stronger , suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.
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Objective:To compare the clinical efficacy between a single palmar lateral transverse approach and the modified Henry approach in the locking plate fixation for distal radius fractures.Methods:A retrospective study was conducted to analyze the data of 82 patients with distal radius fracture who had undergone locking plate fixation through either a single palmar lateral approach or the modified Henry approach between January 2016 and December 2022 at Department of Traumatic Orthopaedics, Taihe Hospital, Affiliated to Hubei University of Medicine. There were 25 males and 57 females, with an age of (53.8±12.7) years. Based on the difference in surgical approach, the patients were divided into a single transverse approach group ( n=42) and a modified Henry approach group ( n=40). The 2 groups were compared in terms of injury cause, injury location, time from injury to surgery, AO fracture classification, tourniquet time during surgery, incision length, fracture reduction, Patient and Observer Scar Assessment Scale (PSAS & OSAS) and Disability of the Arm, Shoulder, and Hand (DASH) score at the last follow-up, and complications after surgery. Results:There were no statistically significant differences in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (8.2±3.5) months. Follow-ups revealed one case of injury to the palmar cutaneous branch of the median nerve but no other complications like infection, non-union, internal fixation failure, or tendon injury in the single transverse approach group. The single transverse approach group was significantly superior over the modified Henry approach group in incision length [(2.4±0.9) cm versus (5.3±1.6) cm], OSAS (8.1±4.2 versus 10.3±5.7), and PSAS (10.1±5.8 versus 14.7±6.4) ( P<0.05). There were no significant differences between the 2 groups in tourniquet time, fracture reduction quality, and DASH score at the last follow-up ( P>0.05). Conclusion:In locking plate fixation for distal radius fractures, in comparison with the modified Henry approach, a single palmar lateral approach is more minimally invasive so that more aesthetically pleasing outcomes can be achieved to facilitate patients' rapid return to work and society.
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OBJECTIVE To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism. METHODS The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group （0.5% sodium carboxymethyl cellulose solution）， dioscin low-dose， medium-dose and high-dose groups （30， 60， 120 mg/kg） and dexamethasone group （positive control， 10 mg/kg）， with 12 rats per group； another 12 rats were selected as the sham operation group （0.5% sodium carboxymethyl cellulose solution）. After 15 minutes of modeling， rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration， the levels of creatinine （Cr）， blood urea nitrogen （BUN）， neutrophil gelatinase associated lipocalin （NGAL）， kidney injury molecule-1 （KIM- 1）， interleukin 6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） in serum and malondialdehyde （MDA） in renal tissue， superoxide dismutase （SOD） activity and the protein expressions of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NOD-like receptor protein 3 （NLRP3） were detected； renal histomorphology was observed. RESULTS Compared with model group， pathological injury of renal tissue was improved significantly in dioscin low-dose， medium-dose and high-dose groups； the levels of Cr， BUN， NGAL， KIM-1， IL-6， IL-1β and TNF-α in serum， MDA level and protein expression of NLRP3 in renal tissue were decreased significantly （P＜0.05）； SOD activity in renal tissue， protein expressions of Nrf2 and HO-1 were increased significantly （P＜0.05）， in a dose-dependent manner （P＜0.05）. The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group， and there was no statistically significant difference in the levels of the above indicators （P＞0.05）. CONCLUSIONS Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome， and realize the inhibition of inflammatory factors and oxidative stress， so as to protect the kidney injury in sepsis.
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OBJECTIVE To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism. METHODS The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group （0.5% sodium carboxymethyl cellulose solution）， dioscin low-dose， medium-dose and high-dose groups （30， 60， 120 mg/kg） and dexamethasone group （positive control， 10 mg/kg）， with 12 rats per group； another 12 rats were selected as the sham operation group （0.5% sodium carboxymethyl cellulose solution）. After 15 minutes of modeling， rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration， the levels of creatinine （Cr）， blood urea nitrogen （BUN）， neutrophil gelatinase associated lipocalin （NGAL）， kidney injury molecule-1 （KIM- 1）， interleukin 6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） in serum and malondialdehyde （MDA） in renal tissue， superoxide dismutase （SOD） activity and the protein expressions of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NOD-like receptor protein 3 （NLRP3） were detected； renal histomorphology was observed. RESULTS Compared with model group， pathological injury of renal tissue was improved significantly in dioscin low-dose， medium-dose and high-dose groups； the levels of Cr， BUN， NGAL， KIM-1， IL-6， IL-1β and TNF-α in serum， MDA level and protein expression of NLRP3 in renal tissue were decreased significantly （P＜0.05）； SOD activity in renal tissue， protein expressions of Nrf2 and HO-1 were increased significantly （P＜0.05）， in a dose-dependent manner （P＜0.05）. The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group， and there was no statistically significant difference in the levels of the above indicators （P＞0.05）. CONCLUSIONS Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome， and realize the inhibition of inflammatory factors and oxidative stress， so as to protect the kidney injury in sepsis.
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ObjectiveTo observe and compare the intervention effect of modified Cangfu Daotantang on glucose and lipid metabolism in simple obese children with phlegm dampness and stagnation. MethodA total of 60 children with simple obesity were randomly divided into two groups according to the simple randomization method of the random number table. The odd number was included in the test group， and the even number was included in the basic treatment group， with 30 cases in each group. On the basis of signing the informed consent notice， the treatment group was given modified Cangfu Daotantang combined with basic treatment， while the control group was only given basic treatment. After three months of treatment， the body mass index （BMI）， glucose and lipid metabolism level ［total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， fasting plasma glucose （FPG）， fasting insulin （FINS）， and homeostasis model assessment-insulin resistance （HOMA-IR）］， the change in the total score of traditional Chinese medicine （TCM） syndromes， and the effective rate of treatment were observed and compared. ResultAfter treatment， the BMI of the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the BMI level in the observation group decreased significantly （P<0.05）. After treatment， the levels of TC， TG， and LDL-C in the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the levels of TC， TG， and LDL-C in the observation group decreased significantly （P<0.05）. In addition， the level of TC in the observation group improved significantly compared with that in the control group （P<0.01）. The levels of FPG， FINS， and HOMA-IR in the observation group and the control group were significantly lower than those before treatment （P<0.05）. After treatment， compared with the control group， the levels of FPG， FINS， and HOMA-IR in the observation group were significantly reduced （P<0.05）. The level of FPG in the observation group was significantly improved compared with that in the control group （P<0.01）. After treatment， the total score of TCM syndromes in the two groups decreased significantly （P<0.01）. Compared with the control group， the total score of TCM syndromes in the observation group was lower （P<0.01）. After treatment， the total effective rate of treatment was 86.67% （26/30） in the observation group and 73.33% （22/30） in the control group. By rank sum test， the total effective rate of the observation group was better than that of the control group （Z=-2.100， P<0.05）. ConclusionModified Cangfu Daotantang combined with basic treatment can effectively reduce the BMI of obese children and improve their glucose and lipid metabolism. It has good clinical effects and high clinical application value， which is worth further in-depth research and promotion.
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Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.
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It is a challenge to determine the cause of death in cases caused by both injury and disease in forensic pathology examinations.Here,we retrospectively analyzed 140 such cases enrolled in the Sun Yat-sen University Forensic Identification Center from 2013 to 2021.It was found that the cases caused by both injury and disease accounted for 2.89%of the total number of cases during the same period.The male-to-female ratio was 5.09.Cardiovascular disease accounted for 71.43%of the death-leading diseases,and coronary heart disease accounted for 49.29%.Among the three types of injury and disease relationship,the proportion of disease-based and injury-assisted cases accounted for more than half(65.86%),and the proportion of injury and disease with the same effect cases was the least(12.14%).Medical treatment was involved in as more as 82.86%of the cases.Re-identification were carried out in 10.71%of the cases,53.33%of which were with a≤24-hour-survival time,higher than the proportion(20.80%)of this survival time in initial identification cases(x2 = 13.84,P = 0.000 2).This study revealed the epidemiological characteristics of cases caused by both injury and disease,and supplied useful data for improving the level of forensic identification in such cases.
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Objective To analyse the effects of the lung recruitment manoeuvre(RM)mode implemented by ICU specialist nurses on remission of the patients with acute respiratory distress syndrome(ARDS),with the aim to explore the safety,feasibility and effectiveness of clinical implementation,and to further provide a new mode for patient management in nursing practice.Methods A total of 40 ARDS patients admitted into the ICU from January 2018 to August 2021 were randomly selected and divided into control group and trial group in equal number with a random number table.Patients in the control group was treated with a conventional RM mode implemented by doctors,and the RM mode implemented by the ICU specialist nurses was applied to the patients in trial group.The indexes of arterial blood gas analysis,mechanical ventilation time,length of ICU stay,number of RM,number of adjustments to a RM plan,and complication rate were compared between the two groups after the second RM implementation.Results There was no statistically significant difference in arterial partial pressure of oxygen,arterial partial pressure of carbon dioxide and oxygenation index between the groups at 1h and 24h after the second RM implementation(P>0.05).There was no statistically significant difference in the number of RM,mechanical ventilation and length of ICU stay between the groups(P>0.05).The number of modifications of the RM plan in the trial group was significantly more than that in the control group(P<0.05).There was no complication of RM in both groups.Conclusions The RM mode implemented by ICU specialist nurses could achieve good clinical effects in the treatment of patients with ARDS. The approach is safe and practicable.
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Objective:To analyze the influence of serological indexes on the liver cirrhosis (LC) in patients with chronic hepatitis B, and to construct a nomogram model.Methods:The clinical data of 220 patients with chronic hepatitis B in Xianning Central Hospital from January 2019 to December 2021 were retrospectively analyzed. Among them, 42 patients developed LC (LC group), and 178 cases did not develop LC (non-LC group). The patient′s fasting peripheral venous blood was taken in the morning. The platelet, red blood cell, white blood cell, fasting blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triacylglycerol (TG), total cholesterol (TC), total bilirubin (TBiL), albumin, globulin, alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), prothrombin time (PT), thrombin time (TT), D-dimer (D-D), alpha-fetoprotein (AFP) and C-reactive protein (CRP) were detected. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of each index in predicting LC in patients with chronic hepatitis B. Multivariate Logistic regression was used to analyze the independent risk factors for LC in patients with chronic hepatitis B. The R software "rms" package was used to construct a nomogram model to predict the LC in patients with chronic hepatitis B, the correction curve was used to internally verify the prediction model, and the decision curve evaluated the efficacy of the prediction model.Results:The TBiL, ALP, GGT, PT, TT, D-D, AFP and CRP in LC group were significantly higher than those in non-LC group: (50.57 ± 5.61) μmol/L vs. (46.69 ± 3.92) μmol/L, (105.23 ± 30.60) U/L vs. (75.14 ± 26.45) U/L, (68.73 ± 19.47) U/L vs. (50.39 ± 14.21) U/L, (13.88 ± 1.98) s vs. (13.01 ± 2.10) s, (18.88 ± 2.56) s vs. (15.98 ± 2.43) s, (2.62 ± 1.04) mg/L vs. (1.34 ± 0.63) mg/L, (4.19 ± 1.95) μg/L vs. (2.66 ± 1.21) μg/L and (8.54 ± 1.22) mg/L vs. (7.47 ± 0.79) mg/L, the platelet, ALT, AST and albumin were significantly lower than those in the non-LC group: (129.63 ± 32.66) × 10 9/L vs. (183.53 ± 56.31) ×10 9/L, (131.27 ± 22.19) U/L vs. (157.57 ± 38.67) U/L, (112.76 ± 19.57) U/L vs. (125.16 ± 21.84) U/L and (29.79 ± 6.17) g/L vs. (33.52 ± 5.89) g/L, and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in red blood cell, white blood cell, fasting blood glucose, TG, TC and globulin between the two groups ( P>0.05). ROC curve analysis result showed that the area under the curve (AUC) of AFP, platelet, ALT, AST, ALP, GGT, TBiL, albumin, D-D, CRP, PT and TT for predicting LC in patients with chronic hepatitis B were 0.731, 0.798, 0.723, 0.676, 0.766, 0.762, 0.710, 0.673, 0.856, 0.759, 0.603 and 0.786, and the optimal cut-off values were 4.64 μg/L, 162.56 × 10 9/L, 155.67 U/L, 122.37 U/L, 95.17 U/L, 68.96 U/L, 49.95 μmol/L, 28.8 g/L, 1.64 mg/L, 8.55 mg/L, 12 s and 18 s. Multivariate Logistic regression analysis result showed that AFP (>4.64 μg/L), platelet (≤162.56 × 10 9/L), ALP (>95.17 U/L), GGT (>68.96 U/L), D-D (>1.64 mg/L) and TT (>18 s) were independent risk factors for LC in patients with chronic hepatitis B ( OR = 1.278, 1.428, 1.488, 1.356, 1.513 and 1.369; 95% CI 1.109 to 1.369, 1.269 to 1.623, 1.217 to 1.894, 1.127 to 1.669, 1.342 to 1.878 and 1.169 to 1.583; P<0.05 or <0.01). The AFP, platelet, ALP, GGT, D-D and TT were used as predictors to construct a nomogram model for predicting the LC in patients with chronic hepatitis B. The correction curve of the nomogram model to predict the LC in patients with chronic hepatitis B was close to the ideal curve (C-index was 0.739, 95% CI 0.615 to 0.876); the decision curve analysis result showed that the prediction model had higher clinical net benefit when the risk threshold > 0.26 than a single index, and that it had significantly additional clinical net benefit. Conclusions:The AFP, platelets, ALP, GGT, D-D and TT are independent risk factors for LC in patients with chronic hepatitis B, and the nomogram model constructed based on these factors could provide important guidance for the prevention and treatment of LC in patients with chronic hepatitis B.
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Objective:To explore the probability, influencing factors, and management strategies of the re-increase of parathyroid hormone (PTH) in patients with primary hyperparathyroidism (pHPT) after successful surgery.Methods:A retrospective analysis of the clinical data of 40 pHPT patients treated at Beijing Tsinghua Chang Gung Hospital from Jan 2016 to Mar 2021 was conducted.Results:Of the 40 pHPT patients, 21 (53%) experienced a re-increase of PTH after surgery, but their serum calcium levels were normal and no new parathyroid lesions were found on neck ultrasonography. Univariate analysis showed that there were significant differences in tumor diameter, preoperative PTH level, preoperative serum calcium level, and preoperative alkaline phosphatase level between the postoperative PTH re-increase group and the normal group ( t=-2.042, P=0.045; t=-2.600, P=0.013; t=-2.223, P=0.043; t=-2.162, P=0.037). Regression analysis showed that preoperative PTH level >236 ng/L was an independent risk factor for postoperative PTH re-increase ( OR=5.180, 95% CI: 1.032-25.995). Vitamin D deficiency was common among pHPT patients (88%), and there was a negative correlation between preoperative PTH and 25-hydroxy vitamin D levels. After vitamin D supplementation, the PTH levels of four patients with postoperative PTH re-increase returned to normal. Conclusions:The probability of PTH re-increase in pHPT patients after successful parathyroidectomy was 53%, and most cases occurred in the short term after surgery (within 8 weeks), but it did not indicate disease recurrence. A higher preoperative PTH level was an independent risk factor for postoperative PTH re-increase. Vitamin D deficiency was more common among pHPT patients, and correction of vitamin D deficiency can help restore normal PTH levels after surgery.
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Complete mesocolic excision (CME) and D3 resection of right colon cancer have been widely implemented, but the definition and identification of the completeness of the mesentery have not been fully agreed, especially the dorsal and medial borders. In this paper, we proposed the dorsal fascia of the colonic mesentery as the dorsal border of the mesocolon and the line connecting the roots of the ileocolic artery and the middle colic artery (ICA-MCA line) as the medial border of the CME by systematically studying the relationship between the mesentery and the mesenteric bed from the theory of membrane anatomy, combined with surgical experience and in-depth review of ontogenetic anatomy. We also proposed the visible "superior mesenteric vein notch" and "middle colic artery triangle" on surgical specimens as identifiers of mesocolic completeness.
الموضوعات
Humans , Mesocolon/surgery , Lymph Node Excision , Colectomy , Laparoscopy , Colonic Neoplasms/surgeryالملخص
Objective@#To study the expression of long non-coding RNA LINC01152 in glioma and its influence on the malignant biological behavior of glioma cells．@*Methods@#LINC01152 expression in glioma was analyzed by LncSpA V2．0 and GEPIA database．qRT-PCR was applied to detect the expression of LINC01152 mRNA in 10 samples of human normal brain tissues，40 samples of glioma tissues and 5 glioma cell lines．GO and KEGG enrichment analysis of LINC01152 co-expressed genes were performed using the DAVID database to predict the related functions． The AnoLnc2，TargetScan，LinkedOmics and miRDB databases were used to predict the LINC01152 related miRNAs and target genes to construct a ceRNA regulatory network．LINC01152 expression was knocked down in glioma cell lines by small interfering RNA (siRNA) transfection．The CCK-8 test，scratch healing experiments，Transwell，flow cytometry and Western blot experiments were used to measure the influence of LINC01152 on the proliferation，migra- tion，invasion and apoptosis of glioma cells. @*Results @#Database analysis showed that compared with other tumor types，LINC01152 was highly expressed in glioblastoma (GBM) and low grade glioma (LGG) ，and was higher than normal brain tissue．qRT-PCR showed that the expression of LINC01152 mRNA in glioma tissues was significantly higher than that in normal brain tissues (P＜0. 01)．The expression of LINC01152 was correlated with Ki-67 (P < 0. 05) ，but not with clinical parameters such as gender，age，tumor size，P53 protein，glial fibrillary acidic protein (GFAP) ，O-6-methylguanine-DNAmethyltransferase ( MGMT) and WHO grade of glioma patients． Functional enrichment analysis of co-expressed genes indicated that the LINC01152 was mainly involved in biological processes such as cell adhesion and synaptic signaling．LINC01152-miRNA-mRNA regulatory network was constructed according to predicted target genes．After down-regulation of LINC01152 expression，the proliferation，migration and invasion abilities of A172 and U87 cells decreased(P＜0. 01) ，while the apoptosis of glioma cells significantly increased (P＜0. 001) ．@*Conclusion@#LINC01152 is highly expressed in glioma，which can promote the malignant biological behavior of glioma cells by enhancing proliferation，migration as well as invasion and inhibition of apoptosis.
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IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition of autoimmune etiology in recent twenty years, mainly manifesting as mass-forming lesions in single or multiple organs. In the past, it was often missed or misdiagnosed as inflammation or tumor. Patients may die from multiple organ failure due to end-stage fibrosis if they are not treated promptly. However, the number of clinically confirmed cases has gradually increased with the improvement of diagnostic level in recent years, and these patients have benefited greatly after receiving early treatment. Although patients generally respond well to traditional immunosuppressors including glucocorticoids and disease-modifying anti-rheumatic drugs, refractory and recurrent cases, even patients with glucocorticoid contraindication are common. Important mechanistic insights have been derived from studies of B-cell depletion therapy, but greater awareness of the pathophysiology of IgG4-RD is still badly needed to identify novel therapeutic targets. In this article, we reviewed the pathogenesis progress and promising therapy of IgG4-RD to seek better clinical management of IgG4-RD.
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Background Indoor air pollution is an important risk factor affecting health of the respiratory system. Studies on indoor air pollution in China are mostly limited to the central and eastern regions, and there are few studies in the rural areas of northwest China. Objective To explore the influencing factors of lung ventilation function and its relationship with indoor air pollution in rural areas of Gansu Province based on a cross-sectional investigation. Methods A total of 399 subjects were selected from four villages in Baiyin and Yuzhong of Gansu Province. Questionnaires were used to collect demographic information, lifestyle, disease history, fuel use, and other information, and physical and functional tests were ordered such as height, weight, and lung function. The Indoor Air Pollution (IAP) exposure index was calculated based on smoking, fuel type, and weekly ventilation. IAP > 5 was defined as a high level of indoor air pollution. Lung function indexes included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, forced vital capacity as a percentage of predicted value (FVC%), and forced expiratory volume in the first second as a percentage of predicted value (FEV1%), which were used to determine pulmonary ventilation dysfunction. Logistic regression model was used to evaluate the relationship between indoor air pollution and pulmonary ventilation function, and subgroup analysis was further conducted according to home address and BMI , in order to identify the high-risk population of pulmonary ventilation dysfunction. Results The mean age of the subjects was (56.75±7.31) years old; 155 subjects (38.85%) had normal pulmonary ventilation function, and the other 244 subjects (61.14%) had impaired pulmonary ventilation function; about 89.97% of the subjects were exposed to high level of indoor air pollution (IAP > 5). We found that IAP > 5 (OR=2.327, 95%CI: 1.089-4.974) and use of bituminous coal as the main heating fuel in winter (OR=3.467, 95%CI: 1.197-10.037) increased the risk of pulmonary ventilation dysfunction after adjusting for age, BMI, residence, gender, smoking, drinking, and cardiovascular disease. The subgroup analysis results showed that no ventilation in the living room/bedroom (OR=3.460, 95%CI: 1.116-10.268) increased the risk of pulmonary ventilation dysfunction in Baiyin. Heating with coal stoves and Chinese Kang in the bedroom (OR=2.092, 95%CI: 1.030-4.247) and cooking in the bedroom in winter ( OR =2.954, 95% CI : 1.046-8.344) also increased the risk of pulmonary ventilation dysfunction in the residents with BMI≤24 kg·m−2. IAP > 5 (OR=3.739, 95%CI: 1.147-12.182) was associated with a significantly increased risk of pulmonary ventilation dysfunction in the BMI > 24 kg·m−2 subgroup. Conclusion The pulmonary ventilation function of rural residents in Gansu is poor, which is negatively correlated with indoor air pollution. Coal use, overweight, cooking in bedroom, and use of coal stoves and Chinese Kang for heating may increase the risk of pulmonary ventilation dysfunction, while room ventilation is a beneficial factor.
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Background With the change of the national energy development layout, Qingyang has seen a situation where oil exploitation and agriculture go hand in hand, which may lead to local soil pollution if not taken seriously. Objective To evaluate the distribution characteristics, possible sources, and ecological risks of heavy metals in farmland soils around the main production areas of Changqing Oilfield. Methods A total of 60 farmland soil samples were collected from Zhengning County, Zhenyuan County, and Qingcheng County of Qingyang City, and the contents of heavy metals such lead (Pb), mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As) in farmland soil were detected according to GB 15618-2018 Soil environmental quality—Risk control standard for soil contamination of agricultural land (on trial). The soil background value of Gansu Province was used as the denominator in the calculation of pollution index, and the pollution characteristics and ecological characteristics of selected five heavy metals in farmland soil were evaluated by single-factor pollution index (Pi), Nemerow comprehensive pollution index (PN), and potential ecological risk index. Results The levels of Pb, As, and Hg in farmland soils around Changqing Oilfield, the levels of Cr and Cd in Qingcheng County, and the level of Cd in Zhengning County were higher than the corresponding soil background values of Gansu Province, but lower than the national soil environmental quality standard. The single-factor pollution indexes (Pi) were: Hg, 2.14; Pb, 1.24; As, 1.13; Cr, 0.78; Cd, 0.67, which indicated that Hg were graded as moderate pollution, Pb and As were slight pollution, and Cd and Cr were not polluted. The Nemerow comprehensive pollution indexes (PN) were: Cr, 0.92; Cd, 1.08; As, 1.20; Pb, 1.68; Hg, 3.85, which indicated that Cr was graded as no pollution, Cd, Pb and As were mild pollution, and Hg was severe pollution. The variation coefficients of Hg and Cd in Zhenyuan County and that of Hg in Qingcheng County were 60.00%, 50.00%, and 50.00%, respectively, which were all greater than 50%, indicating that the pollution of above heavy metals in the location was subject to human activities. The potential ecological risk indexes (Er) of Pb, Cr, Cd, As, and Hg were 6.20, 1.55, 20.05, 11.28, and 81.64, respectively, indicating that Hg was graded as strong ecological risk, and the other four heavy metals were mild ecological risk. The comprehensive potential ecological risk index (RRI) was 124.48. Combined with the potential ecological risk index of Hg, the comprehensive potential ecological risk of the five heavy metals in local farmland soils was considered to be at a strong ecological risk level. Conclusion Although the average values of selected five heavy metals in farmland soils surrounding the main production areas of Changqing Oilfield are qualified with the national soil environmental quality standards, they exceed corresponding soil background values of Gansu Province, and there are signs of human influence and potential ecological risks of different degrees.
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bjective To observe the changes of upper extremity sensory function in patients with radicular cervical spondylosis and evaluate the treatment effect, by using the method of suspension exercise therapy (SET) and soft tissue manipulation. Methods A total of 72 patients with cervical spondylosis were divided into observation group (treated by SET combined with manipulation)and control group (treated by purely cervical traction) by simple random method. Both groups received 4-week continuous treatment for 6 times per week. The somatosensory evoked potential(SEP), current perception threshold (CPT) before and after the treatment in two groups were separatedly tested, and changes in visual analogue scale (VAS) pain scores of the affected limbs were examined, so as to determine the effective rate of treatment. Results After treatment, the latency of SEP was shortened mainly in brachial plexus potential N9 and cervical spinal potential N13 in two groups (P<0.05). The CPT levels and the VAS pain scores of the affected limbs were reduced in two groups (P<0.01), and the treatment effect in observation group was better that in control group (P<0.01)．Conclusion SET combined with soft tissue manipulation can effectively promote the repair of nerve sense function of cervical spondylotic radiculopathy.
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@# Objective: To evaluate the effect of erianin on the viability, migration, and invasion of KB cells and elucidate its underlying mechanisms. Methods: Cell Counting Kit-8, colony formation, wound healing, and Transwell assays were used to determine the proliferation, migration, and invasion of oral cancer KB cells. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels were determined. Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions. Additionally, the expressions of ferroptosis-related proteins, NF-E2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting assays. Results: Erianin induced ferroptosis and inhibited the proliferation, migration, and invasion of KB cells. Moreover, erianin decreased GSH level, increased MDA level, elevated intracellular ROS and Fe
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Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.
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N 6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m6A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m6A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.
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Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations | Δ G FEP - Δ G EXP | < 2 kcal/mol) than those ΔG MM-PBSA or ΔG MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.