Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients， construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7：3. For the modelling group， LASSO regression was applied to screen variables and select predictors， and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve （AUC）， and in addition， calibration analysis and decision curve analysis （DCA） were performed on the model. ResultsLASSO regression identified 14 potential predictive factors， and further logistic regression analysis showed that hepatic injury， surgery， anemia， hypoalbuminemia， illness course， invasive operation， hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables， with an AUC95%CI of 0.980 （0.973， 0.896） for the training set and an AUC95%CI of 0.956 （0.795， 1.000） for internal validation， indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line， and the decision curve analysis （DCA） showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.

Objective:To investigate the clinical effect of Infix combined with hollow screws for the treatment of pelvic injuries with pubic symphysis separation in middle-aged and elderly patients.Methods:Data of 8 middle-aged and elderly patients with pelvic injuries due to pubic symphysis separation undergone treatment from January 2017 to December 2020 were retrospectively analyzed.Results:The average operating time of 8 patients was (46.0±6.2)min(range: 40-62min); the average intraoperative blood loss was (32.0±5.6)ml(range: 25-50 ml); the average length of incisions at the iliac screw was(2.6±0.4)cm(range: 2.0-3.5 cm); the average length of incisions at the hollow screw was (1.1±0.3)cm(range: 0.8-1.5 cm); and the average times of fluoroscopy were (36.0±6.0)times(range: 28-52 times). Postoperative X-ray and CT examinations showed that the reduction of the pubic symphysis was good, the inserted iliac screws and cannulated screws were positioned accurately, and the incision healed well.Based on Matta's criteria, postoperative radiological outcomes were evaluated, with 7 cases rated as excellent and 1 as good, giving an excellent to good rate of 100%(8/8). The average followed up time for all 8 patients was (15.0±4.2)months(range: 6-24 months). Pelvic X-ray and CT examinations at the last follow-up showed that the fractures healed well and the pubic symphysis reduction did not fail.Infix and cannulated screws in the pubic symphysis were removed 10-12 weeks after surgery[average: (10.5±0.5)weeks]. According to the Majeed Pelvic Score, 5 cases were rated as excellent, 2 cases as good and 1 as fair, with an excellent to good rate of 87.5%(7/8). One patient had symptoms related to the lateral femoral cutaneous nerve that disappeared after 3 months.One patient developed deep venous thrombosis after surgery, and the filter was placed and removed 10 weeks later.Conclusions:Using Infix plus cannulated screws for the treatment of pelvic injuries in middle-aged and elderly patients with pubic symphysis separation has the advantages of limited trauma and intraoperative blood loss, good fixation and few complications.

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

Objective: To study the causes and influencing factors of no seeking medical treatment among pneumoconiosis patients. Methods: Using stratified sampling method and typical survey method, we carried out the questionnaire survey in nine provinces in China including the east, the medium and the western region using a questionnaire on the seeking medical behavior pf pneumoconiosis patients and the influencing factors. The subjects include occupational pneumoconiosis cases and clinically diagnosed cases and the response rate is 94.3 percent. The data was entered twice with epidate3.1 and error detection and statistical analysis was completed with SPSS 20.0. Chi-square test was used for univariate analysis, and multivariate logistic regression was used for multivariate analysis. Results: One thousand and thirty-seven subjects were investigated with average age 55.9±11.2 years. Seventy percent of them were silicosis and 21.9 percent were coal worker’s pneumoconiosis with 67.5 percent of them residing permanently in the countryside, and 37.9 percent of their education background were primary school culture and 33.1 percent of them had junior high school culture. Thirty two point six percent of respondents had no personal income with a median monthly income of 1 200 yuan. Four hundred and thirty four of subjects hadn't seek medical treatment since they got the pneumoconiosis accounting for 41.9 percent with three hundred and thirty seven of them hospitalized directly. The reasons of no seeking medical treatment for the respondents mainly include the self-induction symptoms lighter, the high cost of treatment and cannot claiming the payment of the medical expenses, buying drugs in drugstore, thinking that no medicine can cure pneumoconiosis or no effect, complex procedures, too far away from medical institutions, no unaccompanied, needing a long time or no time, communication disorders, etc. accounting for 44.4 percent, 24.6 percent, 10.9 percent, 9.1 percent, 6.9 percent, 4.4percent, 3.2 percent, 2.9 percent, 1.9 percent, 1.5 percent, respectively. The results of multivariate analysis showed the main characteristics of subjects with restrictions to the outpatient health service utilization are as follows: demographic sociological indicators such as registered permanent residence area is western (OR_western=2.18, 95%CI:1.38-3.43) , more than seventy five years old (OR_{over 75}=6.82, 95%CI:2.04-22.9) , unemployment, temporary or permanent employment (OR _unemployment=1.90, 95%CI:1.17-3.08; OR_{temporary employment}=3.11, 95%CI:1.57-6.14; OR_{permanent employment}=2.10, 95%CI:1.18-3.74) , self-rated health score of 50 or above (OR_{self-rated-70}=2.04, 95%CI:1.18-3.51; OR_{self-rated-90}=3.00, 95%CI:1.97-5.37; OR_{self-rated 90}=2.95, 95%CI:1.74-8.07) ; with increase to the outpatient health service utilization are breath with difficulty (OR=0.57, 95%CI:0.41-0.78) , emphysema (OR=0.48, 95%CI:0.26-0.90) , hospitalized with pneumo-coniosis (OR=0.12, 95%CI:0.07-0.20) . Conclusion Pneumoconiosis patients no covered by injury insurance should be orderly included in the basic medical security system, and be given the medical treatment actively; It should be strengthened the health management for the pneumoconiosis patients and correctly guided the utilization of medical services.

Objective The aim is to analyze the spatial-temporal correlation of dysentery incidence in 31 provinces, municipalities and autonomous regions in China from 2004 to 2016, and to predict the short-term incidence of dysentery in China. Methods Data about the incidence of dysentery from 2004 to 2016 was collected. Arcgis and Geoda were used to create visualized grading maps and analyze spatial correlation. The auto-regressive integrated moving average model (ARIMA)was used to predict the incidence of dysentery in 2017 and evaluate the prediction accuracy of the model. Results The incidence of dysentery in China declined with each passing year from 2004 to 2016. The incidence of dysentery in the western region was significantly higher than the eastern region, except high incidence rate in Beijing and Tianjin. There was no significantly global correlation in the incidence rate, but there was local aggregation. Qinghai had turned from high-level aggregation to low-level accumulation. Inner Mongolia and Shanxi had changed from no local aggregation to low-high accumulation. Shaanxi has long been high-high, and the southeast coastal areas had been low-low accumulation for a long time. The optimal model ARIMA (1,0,0) (2,1,1)12 was established to predict the incidence of dysentery, and the prediction results were roughly consistent with the observations. Conclusion The incidence of dysentery from 2004 to 2016 is not spatially mobile but clustered. The incidence of dysentery in Beijing, Tianjin, Shaanxi and most of the western regions is severe. The ARIMA model is suitable for forecasting the incidence of short-term dysentery. And our analysis may help prevent and control the incidence of dysentery in China.

OBJECTIVETo observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS).

METHODSFifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment efficacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flowmetry, and its variations before and after treatment in both groups were compared as well.

RESULTSIn both groups, the VAS scores significantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints significantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05).

CONCLUSIONSWCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

OBJECTIVETo analyze the advantages of spatial measurement of anatomical parameters in a 3D model in surgical planning for laparoscopic partial nephrectomy (LPN).

METHODSFrom February, 2016 to October, 2017, 37 patients diagnosed with T1 renal mass underwent LPN based on 3D reconstruction after enhanced CT scanning using the Uromedix-3D system (group A), and another 38 patients received LPN with conventional CT planning (group B). The anatomical parameters were measured in the reconstructed 3D model and the demographic data, surgical outcome and postoperative data were compared between the two groups.

RESULTSIn group A, the average time for 3D model reconstruction was (29.3∓9.7) min; the length, width and depth of the renal defect in 3D model were 3.2∓1.1 cm, 2.6∓0.9 cm and 1.7∓0.7 cm, respectively; The distance of the tumor from the collecting system was 3.8∓2.2 mm; The mean R.E.N.A.L score of the patients was 7∓1.5, and 3 patients had accessory renal artery and 2 had early branching of the renal artery. LPNs were completed via the retroperitoneal approach in all the 75 patients without conversion to open or total nephrectomy. Group A and group B showed significant differences in warm ischemic time (26.7∓6.4 vs 31.9∓7.0 min), tumor-excision time (8.4∓2.6 vs 10.4∓2.8 min), renal defect suture time (18.3∓3.9 vs 21.5∓3.4 min), 24-h volume of retroperitoneal drainage (88.6∓40.2 vs 134.3∓58.3 mL) and 48-h volume of retroperitoneal drainage (127.9∓54.5 vs 198.1∓86.3 mL), but not in the demographic data, operation time, intraoperative blood loss or postoperative hospital stay.

CONCLUSIONS3D reconstruction of the renal masses can be completed efficiently and accurately using this system. Compared with conventional CT-based measurement, 3D spatial measurement of the anatomical structures helps to increase the precision in the performance of LPN and reduce the warm ischemia time.

Objective: To observe the effect of poloxamer 188 (P188) on megakaryocyte cultivation and induction from cord blood mononuclear cells in order to obtain more megakaryocyte progenitor cells (MPC). Methods: The cord blood mononuclear cells were isolated and inoculated in cell culture bag or cell culture flask respectively. The WIGGENS shaker and cell culture bags were used to mimick WAVE Bioreactor for three-dimensional (3D) cell culture, and the P188 was added to induction medium, The cells were detected for morphology, surface marker, viability, and number on day 14. Results: In the two-dimensional (2D) culture, CD41(+), CD41(+)/CD61(+), CD61(+) megakaryocytic numbers increased significantly after adding P188 (all P<0.01). And in the 3D culture of adding P188, the cell volume became larger and the nuclear shape was irregular, the cytoplasm appeared magenta granules, and the megakaryocyte cells became more mature. By 3D culture, the expression of CD41/CD61 was (36.30±1.27)% vs (23.95±1.34)%, hence the differentiation for MPC was significantly higher than that in the 2D group (P<0.01). Furthermore, adding P188 in 3D culture resulted in highest differentiation efficiency for MPC [(59.45±1.20)%]. There were no significantly differences in terms of cell viability and cell number among 3D culture containing P188, 2D and 3D culture groups (all P>0.05). Conclusion: 3D culture was beneficial for the differentiation of MPC, but the cell viability was lower than 2D group; However, the satisfied cell growth and better induction efficiency were obtained by adding of P188, which might provide a new method of megakaryocytes production for clinical application.
Bioreactors ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; Megakaryocytes ; Poloxamer