[Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease].

Objective: To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation. Methods: A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University. Results: ① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1ß, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions: Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

Experimental Study on Flame Chemical Composition of Coal and Ammonia Gas-Solid Jet in Flat Flame Burner.

Ammonia as a fuel to partially or completely replace fossil fuels is one of the effective ways to reduce carbon dioxide, and the research on ammonia coal cocombustion is of great significance. The combustion characteristics of ammonia are very different from those of pulverized coal, resulting in the ignition and emission characteristics of ammonia and pulverized coal gas flow that is different from traditional pulverized coal flame. In this paper, the effect of pulverized coal concentration in coal and ammonia mixed combustion jet on the ignition distance and gas-phase components at different positions of the jet flame were studied experimentally on the flat flame burner, and the conditions of ignition and ignition stability of coal and ammonia gas-solid fuel were expounded. It was found that the ammonia mixed with pulverized coal changed the temperature field of the flat flame burner and therefore the ignition characteristics of the jet were changed. The ignition delay time at the same jet speed was positively correlated with the pulverized coal concentration, but when the pulverized coal concentration continued to decrease, the influence on the ignition delay time gradually became smaller. The composition of coal ammonia gas-solid fuel changed the heat transfer path and share during combustion, and finally, the flame temperature was negatively correlated with the concentration of pulverized coal. Therefore, the reduction of the pulverized coal concentration was conducive to the stable combustion of coal ammonia mixed fuel. When HAB = 100 mm, the conversion rate of fuel N to NOx per unit mass of coal ammonia mixture increased with the increase of pulverized coal concentration. The NOx production amount first increased and then decreased with the increase of pulverized coal concentration, and the amount of N2O and NO2 decreased rapidly with the increase of HAB. The proportion of NOx in NO exceeded 94%, which was conducive to achieving low nitrogen combustion of coal and ammonia gas-solid fuel. In general, the O2 concentration in the ammonia coal jet flame decreased, the flue gas temperature, and NOx and CO generation increased after mixing ammonia, and the optimal pulverized coal concentration in this experiment was 0.41 kgc/kga (mass ratio of pulverized coal to the sum of N2 and NH3).

[Progress in research of models for predicting the risk of readmission and mortality among patients with acute heart failure].

Heart failure is a serious and end-stage status of various heart diseases, characterized by comparatively high rate of readmission and mortality, and has become an important public health issue. The risk of readmission and mortality following discharge of an index hospitalization are key indicators to evaluate the quality of medical care among patients with acute heart failure. Therefore, it is important to carry out risk prediction research for patients with acute heart failure, quantify the disease risk, perform risk stratification, optimize clinical decision-making, elevate patients' quality of life and prognosis, and comprehensively improve the medical quality of acute heart failure. During the past 20 years, foreign researchers have developed dozens of models to predict the risk of acute heart failure readmission and mortality, and Chinese researchers have also developed up to 10 models applicable to the Chinese population. However, there is no recommended risk prediction model for acute heart failure in current clinical guidelines across China. In this report, we aim to introduce the major models for predicting the risk of acute heart failure readmission and mortality from home and abroad, focus on putting forward limitations of established models, and initiating potential directions for future studies from the following aspects: integrate multi-source data, mine emerging biomarkers, establish polygenic risk scores, optimize machine learning methods, promote flexible adjustment, and broaden approaches that applicable for various scenarios. Accordingly, this study will help facilitate domestic research in predicting the risk of readmission and mortality among patients hospitalized for acute heart failure.

[Correlation between C-reactive protein to albumin ratio and restenosis after femoral popliteal stenting in patients with lower extremity arteriosclerotic obliterans].

Objective: To investigate the study of the correlation between C-reactive protein to albumin ratio (CAR) and restenosis after stenting in patients with lower extremity atherosclerotic occlusive disease(LEASO). Methods: The clinical data of 95 patients with LEASO admitted to the Department of Vascular Surgery of Nanjing Drum Tower Hospital from June 2020 to December 2022 were retrospectively analyzed. There were 67 males and 28 females,aged (73.1±9.4) years (range:51 to 92 years). The patients were classified into the restenosis group (n=61) and the patency group (n=34) according to the CT angiography results. Independent sample t test,Mann-Whitney U test and χ2 test were used to compare the data between two groups. Risk factors for restenosis after femoropopliteal artery stenting in patients with LEASO were analyzed using multivariate Cox regression. The relationship between preoperative CAR level and restenosis after stent placement was analyzed. Subject operating characteristic(ROC) curves of CAR were plotted to assess the predictive value of CAR for restenosis after stenting,and the results were expressed as area under the curve (AUC). Results: The aortoiliac calcification grade,number of stents,length of stents,C-reactive protein and CAR levels in restenosis group were higher than those in the patency group,and the serum albumin level was lower than that in the patency group(all P<0.05). And the results of multifactorial Cox regression analysis showed that higher pre-procedure CAR level and lower ABI value was an independent risk factor for in-stent restenosis. The AUC of the ROC curve for restenosis was 0.737(95%CI:0.617 to 0.856),the AUC of the ROC curve for 12-month restenosis was 0.709(95%CI:0.602 to 0.815), and the AUC of the ROC curve for 24-month restenosis was 0.702(95%CI:0.594 to 0.811). Conclusion: Higher pre-procedural CAR levels in patients with LEASO is risk factor for in-stent restenosis,and CAR has a predictive value for restenosis after lower extremity arterial stent dilatation and angioplasty.

Natural aging and Alzheimer's disease pathology increase susceptibility to focused ultrasound-induced blood-brain barrier opening.

Focused Ultrasound (FUS) paired with systemically-injected microbubbles (µB) is capable of transiently opening the blood-brain barrier (BBBO) for noninvasive and targeted drug delivery to the brain. FUS-BBBO is also capable of modulating the neuroimmune system, further qualifying its therapeutic potential for neurodegenerative diseases like Alzheimer's disease (AD). Natural aging and AD impose significant strain on the brain and particularly the BBB, modifying its structure and subsequently, its functionality. The emerging focus on treating neurodegenerative diseases with FUS-BBBO necessitates an investigation into the extent that age and AD affect the BBB's response to FUS. FUS-BBBO was performed with a 1.5-MHz, geometrically focused transducer operated at 450 kPa and paired with a bolus microbubble injection of 8 × 108 µB/mL. Here we quantify the BBBO, BBB closing (BBBC) timeline, and BBB permeability (BBBP) following FUS-BBBO in male mice with and without AD pathology, aged 10 weeks, one year, or two years. The data presented herein indicates that natural aging and AD pathology may increase initial BBBO volume by up to 34.4% and 40.7% respectively, extend BBBC timeline by up to 1.3 and 1.5 days respectively, and increase BBBP as measured by average Ktrans values up to 80% and 86.1% respectively in male mice. This characterization of the BBB response to FUS-BBBO with age and AD further clarifies the nature and extent of the functional impact of these factors and may offer new considerations for planning FUS-BBBO interventions in aged and AD populations.

[Regulatory effects of bio-intensity electric field on microtubule acetylation in human epidermal cell line HaCaT].

Objective: To investigate the regulatory effects of bio-intensity electric field on directional migration and microtubule acetylation in human epidermal cell line HaCaT, aiming to provide molecular theoretical basis for the clinical treatment of wound repair. Methods: The experimental research methods were used. HaCaT cells were collected and divided into simulated electric field group (n=54) placed in the electric field device without electricity for 3 h and electric field treatment group (n=52) treated with 200 mV/mm electric field for 3 h (the same treatment methods below). The cell movement direction was observed in the living cell workstation and the movement velocity, trajectory velocity, and direction of cosθ of cell movement within 3 h of treatment were calculated. HaCaT cells were divided into simulated electric field group and electric field treatment 1 h group, electric field treatment 2 h group, and electric field treatment 3 h group which were treated with 200 mV/mm electric field for corresponding time. HaCaT cells were divided into simulated electric field group and 100 mV/mm electric field group, 200 mV/mm electric field group, and 300 mV/mm electric field group treated with electric field of corresponding intensities for 3 h. The protein expression of acetylated α-tubulin was detected by Western blotting (n=3). HaCaT cells were divided into simulated electric field group and electric field treatment group, and the protein expression of acetylated α-tubulin was detected and located by immunofluorescence method (n=3). Data were statistically analyzed with Kruskal-Wallis H test,Mann-Whitney U test, Bonferroni correction, one-way analysis of variance, least significant difference test, and independent sample t test. Results: Within 3 h of treatment, compared with that in simulated electric field group, the cells in electric field treatment group had obvious tendency to move directionally, the movement velocity and trajectory velocity were increased significantly (with Z values of -8.53 and -2.05, respectively, P<0.05 or P<0.01), and the directionality was significantly enhanced (Z=-8.65, P<0.01). Compared with (0.80±0.14) in simulated electric field group, the protein expressions of acetylated α-tubulin in electric field treatment 1 h group (1.50±0.08) and electric field treatment 2 h group (1.89±0.06) were not changed obviously (P>0.05), while the protein expression of acetylated α-tubulin of cells in electric field treatment 3 h group (3.37±0.36) was increased significantly (Z=-3.06, P<0.05). After treatment for 3 h, the protein expressions of acetylated α-tubulin of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 300 mV/mm electric field group were 1.63±0.05, 2.24±0.08, and 2.00±0.13, respectively, which were significantly more than 0.95±0.27 in simulated electric field group (P<0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of acetylated α-tubulin in 200 mV/mm electric field group and 300 mV/mm electric field group were increased significantly (P<0.01); the protein expression of acetylated α-tubulin of cells in 300 mV/mm electric field group was significantly lower than that in 200 mV/mm electric field group (P<0.05). After treatment for 3 h, compared with that in simulated electric field group, the acetylated α-tubulin of cells had enhanced directional distribution and higher protein expression (t=5.78, P<0.01). Conclusions: Bio-intensity electric field can induce the directional migration of HaCaT cells and obviously up-regulate the level of α-ubulin acetylation after treatment at 200 mV/mm bio-intensity electric field for 3 h.

[Status of home blood pressure monitoring and influencing factors of regular home blood pressure monitoring among elderly uncontrolled hypertensive patients in Central and Western China].

Objective: To describe the prevalence of home blood pressure monitoring and analyze the factors influencing regular blood pressure monitoring among elderly uncontrolled hypertensive patients in Central and Western China. Methods: It was a cross-sectional study, which enrolled hypertensive patients aged over 60 years with office blood pressure ≥140/90 mmHg (1 mmHg=0.133 kPa) from September 2019 to July 2020 in 72 hospitals in Central and Western China. Patients completed the electronic questionnaires, and were divided into regular and irregular home blood pressure monitoring groups. The proportion of patients using different types of sphygmomanometers and the percentage of patients with regular home blood pressure monitoring (at least weekly) were explored. The generalized linear mixed model was used to define the influencing factors of regular home blood pressure monitoring. Results: A total of 3 857 patients were included in this study. Age was 67(64,71) years old and there were 2 163 males (56.1%). Overall, sphygmomanometer was available at home for 3 044(78.9%) patients, 2 168(56.2%) patients conducted regular home blood pressure monitoring. Among the patients with a sphygmomanometer at home, 2 370(77.9%) of the sphygmomanometers were upper arm electronic device. Older age, higher income, longer history of hypertension, multiple antihypertensive medications and awareness of diagnostic criteria of hypertension and hypertension complications were associated with a higher prevalence of regular home blood pressure monitoring (all P<0.05). Conclusions: Among the elderly hypertensive patients with uncontrolled blood pressure in Central and Western China, there is a relatively high prevalence of home sphygmomanometer ownership and regular monitoring. Age, family income, history of hypertension, number of antihypertensive drugs and knowledge of hypertension are the influencing factors of regular home blood pressure monitoring in this population.

Enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy: A meta-analysis.

INTRODUCTION: We performed a meta-analysis to evaluate the effect of enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy. METHODS: A systematic literature search up to April 2021 was done and 33 studies included 6596 subjects submitted to surgery for radical cystectomy at the start of the study; 3143 of them received enhanced pharmaceutical recovery after surgery and 3453 were controls. The studies reported relationships about the effects of enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effects of enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy using the dichotomous and continuous methods with a random or fixed-effect model. RESULTS: Enhanced pharmaceutical recovery after surgery had significantly lower length of hospital stay (MD, -2.78; 95% CI, -3.59 to -1.97, p < 0.001), complications (OR, 0.75; 95% CI, 0.60-0.94, p = 0.01), readmission within 30 days (OR, 0.80; 95% CI, 0.69-0.94, p = 0.007), and time to defecation (MD, -1.30; 95% CI, -2.22 to -0.37, p = 0.006) compared to control in subjects submitted to radical cystectomy. CONCLUSIONS: Enhanced pharmaceutical recovery after surgery may reduce the length of hospital stay, complications, readmission within 30 days, and time to first bowel movement compared to control in subjects with surgery for radical cystectomy. Furthers studies are required to validate these findings.

[Regulatory effects of bio-intensity electric field on transformation of human skin fibroblasts].

Objective: To investigate the regulatory effects of bio-intensity electric field on the transformation of human skin fibroblasts (HSFs). Methods: The experimental research methods were used. HSFs were collected and divided into 200 mV/mm electric field group treated with 200 mV/mm electric field for 6 h and simulated electric field group placed in the electric field device without electricity for 6 h. Changes in morphology and arrangement of cells were observed in the living cell workstation; the number of cells at 0 and 6 h of treatment was recorded, and the rate of change in cell number was calculated; the direction of cell movement, movement velocity, and trajectory velocity within 3 h were observed and calculated (the number of samples was 34 in the simulated electric field group and 30 in 200 mV/mm electric field group in the aforementioned experiments); the protein expression of α-smooth muscle actin (α-SMA) in cells after 3 h of treatment was detected by immunofluorescence method (the number of sample was 3). HSFs were collected and divided into simulated electric field group placed in the electric field device without electricity for 3 h, and 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group which were treated with electric fields of corresponding intensities for 3 h. Besides, HSFs were divided into simulated electric field group placed in the electric field device without electricity for 6 h, and electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group treated with 200 mV/mm electric field for corresponding time. The protein expressions of α-SMA and proliferating cell nuclear antigen (PCNA) were detected by Western blotting (the number of sample was 3). Data were statistically analyzed with Mann-Whitney U test, one-way analysis of variance, independent sample t test, and least significant difference test. Results: After 6 h of treatment, compared with that in simulated electric field group, the cells in 200 mV/mm electric field group were elongated in shape and locally adhered; the cells in simulated electric field group were randomly arranged, while the cells in 200 mV/mm electric field group were arranged in a regular longitudinal direction; the change rates in the number of cells in the two groups were similar (P>0.05). Within 3 h of treatment, the cells in 200 mV/mm electric field group had an obvious tendency to move toward the positive electrode, and the cells in simulated electric field group moved around the origin; compared with those in simulated electric field group, the movement velocity and trajectory velocity of the cells in 200 mV/mm electric field group were increased significantly (with Z values of -5.33 and -5.41, respectively, P<0.01), and the directionality was significantly enhanced (Z=-4.39, P<0.01). After 3 h of treatment, the protein expression of α-SMA of cells in 200 mV/mm electric field group was significantly higher than that in simulated electric field group (t=-9.81, P<0.01). After 3 h of treatment, the protein expressions of α-SMA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were 1.195±0.057, 1.606±0.041, and 1.616±0.039, respectively, which were significantly more than 0.649±0.028 in simulated electric field group (P<0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of α-SMA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly increased (P<0.01). The protein expressions of α-SMA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were 0.730±0.032, 1.561±0.031, and 1.553±0.045, respectively, significantly more than 0.464±0.020 in simulated electric field group (P<0.01). Compared with that in electric field treatment 1 h group, the protein expressions of α-SMA in electric field treatment 3 h group and electric field treatment 6 h group were significantly increased (P<0.01). After 3 h of treatment, compared with that in simulated electric field group, the protein expressions of PCNA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 100 mV/mm electric field group, the protein expressions of PCNA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 200 mV/mm electric field group, the protein expression of PCNA of cells in 400 mV/mm electric field group was significantly decreased (P<0.01). Compared with that in simulated electric field group, the protein expressions of PCNA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were significantly decreased (P<0.01); compared with that in electric field treatment 1 h group, the protein expressions of PCNA of cells in electric field treatment 3 h group and electric field treatment 6 h group were significantly decreased (P<0.05 or P<0.01); compared with that in electric field treatment 3 h group, the protein expression of PCNA of cells in electric field treatment 6 h group was significantly decreased (P<0.01). Conclusions: The bio-intensity electric field can induce the migration of HSFs and promote the transformation of fibroblasts to myofibroblasts, and the transformation displays certain dependence on the time and intensity of electric field.

[The mid-term effect of corneal collagen cross-linking for progressive keratoconus and the changes in rigid gas permeable contact lens fitting parameters].

Objective: To investigate the effect of corneal collagen cross-linking (CXL) for progressive keratoconus and to evaluate changes in the parameters of rigid gas permeable contact lens (RGPCL) fitting after surgery. Methods: It was a prospective cohort study. Fifty-three eyes of 41 keratoconus patients received accelerated CXL in Qingdao Eye Hospital of Shandong First Medical University from May to December 2018. There were 31 males and 10 females, aged (20.46±4.15) years. According to the corneal thickness, de-epithelial CXL (33 eyes) or trans-epithelial CXL (20 eyes) was performed. The best spectacle-corrected visual acuity, refractive power and the thinnest corneal thickness at baseline and at 6 weeks were compared. Corneal topography was performed at baseline and at 6 weeks, 3, 6 and 12 months postoperatively. Rose K RGPCLs were used before and 6 weeks after surgery, and the fitting status was monitored until 12 months after surgery. The t test was performed to analyze the difference before and after the operation. Results: The best spectacle-corrected visual acuity, refractive power, and the thinnest corneal thickness were not significantly changed over 6 weeks of follow-up, but the Kf, Ks and Kmax values were significantly increased in all patients (all P<0.05). In the de-epithelial group, the Kmax values before the operation, at 3, 6 and 12 months after the operation were (55.00±5.51) diopters (D), (54.73±5.34) D, (54.58±6.15) D and (54.20±5.49) D, respectively, and the decrease at 12 months was significant [(0.80±2.05) D; t=2.25, P=0.001]. In the trans-epithelial group, the Kmax values were (59.43±8.98) D, (57.97±8.79) D, (58.19±8.37) D and (56.94±7.19) D at the four time points, respectively, and the decreases at 3, 6 and 12 months were all significant [(1.46±2.09) D, (1.25±1.82) D, (2.49±3.64) D; t=3.12, 3.06, 3.50; P=0.006, 0.006, 0.007]. The best RGPCL-corrected visual acuity, the diameter and the average diopters of RGPCLs showed no significant change in both groups. The RGPCL base curve decreased by 0.07 mm in the de-epithelial group and by 0.13 mm in the trans-epithelial group (both P<0.05). The design of edge lifting was used in 10 eyes postoperatively in the de-epithelial group compared with 8 eyes preoperatively, and in 4 eyes postopratively in the trans-epithelial group compared with 7 eyes preoperatively. The number of eyes using the toric peripheral design of the lens was increased to 3 compared with 2 preoperatively in the de-epithelial group and from 1 to 4 in the trans-epithelial group. The acceptance rate of RGPCL fitting in both groups increased at 6 and 12 months after surgery compared to 6 weeks after surgery. Conclusions: The corneal curvature became steep slightly at 6 weeks after CXL and gradually recovered and flattened. The Kmax in the trans-epithelial group decreased earlier and more than that in the de-epithelial group. The base curve of the RGPCLs was slightly reduced after 6 weeks, and the toric peripheral design was increasingly needed, but the requirement for the design of the lifted edge was different between the two groups. A good RGPCL fitting can be achieved within 1 year after CXL.

[Papillary renal neoplasm with reverse polarity: a clinicopathological analysis].

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.

[A prospective cohort study on BMI levels and risk of acute pancreatitis].

Objective: To investigate the effects of body mass index (BMI) levels at different baseline on the risk of new-onset acute pancreatitis (AP). Methods: The subjects were from the Kailuan Study Cohort and divided into 3 groups according to baseline BMI levels: BMI<24 kg/m2, normal weight; BMI 24-28 kg/m2, overweight; BMI≥28 kg/m2, obesity. The incidence of new-onset AP in these three groups was analyzed. The survival curve was plotted by Kaplan-Meier method, the cumulative incidence was calculated and tested by log-rank method. Multivariate Cox proportional hazards regression model was used to calculate HR of baseline BMI levels for AP. Results: A total of 123 841 subjects were included and followed up for (11.94±2.13) years, during which, 395 cases were found with AP. The incidence of AP was 2.67 per 10 000 person years in total population, and the incidences of AP were 2.20, 2.72 and 3.58 per 10 000 person-years in the normal, overweight and obesity groups, respectively. The cumulative incidences of AP was 0.32%, 0.40% and 0.49% in normal, overweight and obesity groups, respectively, which showed a significant inter-group difference by log-rank test (χ 2=13.17,P<0.01). The results of multivariable adjusted Cox proportional hazards regression model analysis indicated that obesity group (HR=1.45, 95%CI: 1.10-1.92) had a higher risk for AP compared with the normal BMI group. The subgroup analyses by age and sex showed that compared with the normal weight group,the HRs for AP in the obesity group was 1.58(95%CI:1.14-2.19) and 1.40(95%CI:1.03-1.90) among subjects younger than 60 years old and male subjects, respectively. After excluded onset AP within two years from baseline,with a control group from normal weight,the results of multivariate Cox proportional hazards regression model analysis indicated that the AP in the obesity group was 1.60 (95%CI: 1.18-2.15). Conclusion: Obesity may increase the risk of developing AP, particularly among young and middle-aged men.

Effects of PIM3 in prognosis of colon cancer

Purpose PIM kinase is called proto-oncogene, but there are less research on PIM family in colon cancer. This study was designed to explore the prognosis of PIM3 in colon cancer. Methods In this study, we downloaded RNA-seq and clinical information of colon cancer from the Gene Expression Omnibus (GEO) database. Kaplan–Meier method was used for analyzing the impact of PIM3 on the survival of patients with colon cancer. Single-factor and multi-factor cox regression analysis were used for verifying the prognostic value of PIM3. Spearman correlation analysis was used for screening PIM3 related genes. Functional enrichment analysis was used for analyzing the biological functions and pathways in which PIM3 related genes may be involved. STRING online tools were used for building a co-expression network. Cytoscape was used for co-expression network visualization. Results Compared with the low expression group, the patients in the PIM3 high expression group lived longer time. Single-factor and multi-factor cox regression analysis indicated that PIM3 was an independent prognostic factor for colon cancer. Sixty-two PIM3 related genes were screened, and GO and KEGG enrichment analyses suggested that PIM3 related genes might be involved in the MAPK and WNT pathways. The co-expression network showed a strong correlation between PIM3 and MLKL, MYL5, PPP3R1 and other genes. Conclusions PIM3 is an independent prognostic factor of colon cancer and may be a target for the diagnosis and treatment of colon cancer (AU)

Effects of PIM3 in prognosis of colon cancer.

PURPOSE: PIM kinase is called proto-oncogene, but there are less research on PIM family in colon cancer. This study was designed to explore the prognosis of PIM3 in colon cancer. METHODS: In this study, we downloaded RNA-seq and clinical information of colon cancer from the Gene Expression Omnibus (GEO) database. Kaplan-Meier method was used for analyzing the impact of PIM3 on the survival of patients with colon cancer. Single-factor and multi-factor cox regression analysis were used for verifying the prognostic value of PIM3. Spearman correlation analysis was used for screening PIM3 related genes. Functional enrichment analysis was used for analyzing the biological functions and pathways in which PIM3 related genes may be involved. STRING online tools were used for building a co-expression network. Cytoscape was used for co-expression network visualization. RESULTS: Compared with the low expression group, the patients in the PIM3 high expression group lived longer time. Single-factor and multi-factor cox regression analysis indicated that PIM3 was an independent prognostic factor for colon cancer. Sixty-two PIM3 related genes were screened, and GO and KEGG enrichment analyses suggested that PIM3 related genes might be involved in the MAPK and WNT pathways. The co-expression network showed a strong correlation between PIM3 and MLKL, MYL5, PPP3R1 and other genes. CONCLUSIONS: PIM3 is an independent prognostic factor of colon cancer and may be a target for the diagnosis and treatment of colon cancer.

Research on the relationship between RAGE and its ligand HMGB1, and prognosis and pathogenesis of gastric cancer with diabetes mellitus.

OBJECTIVE: To investigate the relationship between the expression of receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB1) and the clinical and pathological parameters and prognosis of the patients with gastric cancer (GC) with diabetes mellitus (DM). PATIENTS AND METHODS: 30 normal gastric mucosa, 30 tissues with GC, 90 tissues with GC and DM and their clinical data were collected. The expression levels of RAGE and HMGB1 were detected by immunohistochemistry. Kaplan-Meier survival curve was used to analyze the relationship between the expression levels of RAGE and HMGB1 and the 5-year survival rate. MTT and cell scratch assays were used to detect the effects of knockdown RAGE and HMGB1 on the proliferation and migration of BGC-823 cells. Real-Time PCR was used to detect the regulation of RAGE and HMGB1 on PTBP-1, and Spearman correlation analysis was performed to analyze the correlation between RAGE and HMGB1 and Polyprimidine tract protein (PTBP-1). RESULTS: Compared with the normal gastric mucosa group, the expression levels of RAGE and HMGB1 were significantly higher in the GC group, GC with DM group. The expression of RAGE and HMGB1 was related with lymph node metastasis, TNM staging, and tumor invasion (p<0.05). Age, TNM stage, tumor infiltration depth, the expression of RAGE and HMGB1 were related with prognosis of patients with GC and DM (p<0.05). Tumor infiltration depth, the expression of RAGE and HMGB1 could affect the 5-year survival rate of patients with GC and DM (p<0.05). CONCLUSIONS: Knockdown RAGE and HMGB1 increased the expression of PTBP-1, and RAGE and HMGB1 were negatively regulated with PTBP-1. RAGE and HMGB1 are independent risk factors for the prognosis of patients with GC with DM. RAGE and HMGB1 may regulate the expression of PTBP-1 and inhibit the glycolysis of cells, which may affect the cell proliferation and migration of GC.

[Effects of bio-strength electric field on the motility and CD9 expression of human epidermal cell line HaCaT and mouse epidermal cells].

Objective: To investigate the regulatory effect of bio-strength electric field (EF) on the motility and CD9 expression of human epidermal cell line HaCaT and mouse epidermal cells. Methods: The experimental research method was used. Human immortal epidermal cell line HaCaT cells in logarithmic growth phase and primary epidermal cells isolated from 16 BALB/c mice (no matter male or female) aged 1-3 days were used for experiments. HaCaT cells were divided into EF group treated for 3 h at the EF intensity of 200 mV/mm and sham EF group with simulated treatment. The cell migration (direction, displacement velocity, and trajectory velocity, with 46 samples in EF group and 34 samples in sham EF group) and arrangement were observed in the living cell workstation, and the distribution and expression of CD9 protein were detected by immunofluorescence method. Both HaCaT cells and mouse epidermal cells were divided into sham EF group (simulated treatment) and EF groups treated respectively for 3 h at the corresponding EF intensity of 50, 100, 200, and 400 mV/mm. Both HaCaT cells and mouse epidermal cells were divided into blank control group without any treatment, and 1 h group, 3 h group, and 6 h group treated with EF at the intensity of 200 mV/mm for corresponding time respectively. The expression of CD9 protein was detected by Western blotting (n=3). Data were statistically analyzed with Mann-Whitney U test, one-way analysis of variance, independent sample t test and least significant difference test. Results: Within 3 hours of treatment, HaCaT cells in EF group tended to move towards the negative electrode obviously, while HaCaT cells in sham EF group moved randomly around the origin; compared with those of sham EF group, the directivity of HaCaT cells in EF group was significantly enhanced, and the displacement velocity and trajectory velocity were significantly increased (Z=-3.975, -6.052, -6.299, P<0.01). After 3 hours of treatment, the long axis of HaCaT cells in EF group was perpendicular to the direction of EF, while HaCaT cells in sham EF group arranged randomly. After 3 hours of treatment, the expression of CD9 protein in HaCaT cells in EF group was significantly down-regulated compared with that of sham EF group (t=4.527, P<0.01), although both expressed on cytomembrane. After 3 hours of treatment, the expression of CD9 protein in HaCaT cells and mouse epidermal cells in sham EF group, 50 mV/mm group, 100 mV/mm group, 200 mV/mm group, and 400 mV/mm group were 0.332±0.021, 0.283±0.032, 0.254±0.020, 0.231±0.041, 0.212±0.031 and 0.565±0.021, 0.453±0.022, 0.389±0.020, 0.338±0.021, 0.233±0.011, respectively. For both types of cells, compared with that of sham EF group, the expression of CD9 protein in cells was significantly decreased in the four groups of EF treatment (P<0.01); compared with that of 50 mV/mm group, the expression of CD9 protein in cells was significantly decreased in the other three groups of EF treatment (P<0.01); compared with that of 100 mV/mm group, the expression of CD9 protein in cells was significantly decreased in 200 mV/mm group and 400 mV/mm group (P<0.01); compared with that of 200 mV/mm group, the expression of CD9 protein in cells was significantly decreased in 400 mV/mm group (P<0.01). The expression levels of CD9 protein in HaCaT cells and mouse epidermal cells in blank control group, 1 h group, 3 h group, and 6 h group were 0.962±0.031, 0.784±0.020, 0.531±0.021, 0.409±0.011 and 0.963±0.031, 0.872±0.031, 0.778±0.040, 0.591±0.041, respectively. For both types of cells, compared with that of blank control group, the expression of CD9 protein in cells was significantly decreased in 1 h group, 3 h group, and 6 h group (P<0.01); compared with that of 1 h group, the expression of CD9 protein in cells was significantly decreased in 3 h group and 6 h group (P<0.05 or P<0.01); compared with that of 3 h group, the expression of CD9 protein in cells was significantly decreased in 6 h group (P<0.01). Conclusions: The bio-strength intensity EF can induce the directional migration and arrangement of HaCaT cells and down-regulate the expression of CD9 in HaCaT cells and mouse epidermal cells in a time-dependent and intensity-dependent manner.

High expression of WISP1 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to explore the expression level of Wnt1-inducible signaling pathway protein 1 (WISP1) and its clinical significance in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression level of WISP1 in HCC tissues and cells. Kaplan-Meier curves and Cox proportional hazard regression model were chosen for single and multiple factor analysis of survival analysis, respectively. Furthermore, wound healing assay and transwell assay were used to verify the effect of WISP1 on HCC cell metastasis in vitro. RESULTS: The expression level of WISP1 in HCC tissues was significantly higher than that in para-cancer tissues (p<0.05). WISP1 expression was positively correlated with lymph node metastasis and clinical stage of HCC. Kaplan-Meier curve showed that HCC patients with higher WISP1 expression exhibited significantly worse progression free survival (PFS) time and overall survival (OS) time. Both univariate and multivariate analysis indicated that high expression of WISP1 was an independent predictor of poor prognosis in HCC. In addition, WISP1 significantly promoted the invasion and migration of HCC cells in vitro. CONCLUSIONS: WISP1 might contribute to the development of HCC, serving as a clinical biomarker and therapeutic target for HCC patients.