Objective To evaluate the impact of customized rehabilitation exercise plans based on the results of cardiopulmonary exercise test(CPET)on cardiac function and prognosis in patients with chronic heart failure(CHF).Methods A total of 52 CHF patients admitted to Chengde Central Hospital from February 2020 to September 2021 were selected as the study subjects,and the patients were divided into observation group and control group according to the principle of randomized controlled study,with 26 cases in each group.The control group received rehabilitation treatment excluding exercise.The observation group was given routine rehabilitation treatment and high-intensity rehabilitation exercise plans based on CPET guidance.Above anaerobic threshold Δ50%power was exercise intensity,exercise time was 30 minutes/day,4 days/week,and intervention period was 12 weeks.Before and 12 weeks after intervention,CPET functional indicators,serum brain natriuretic peptide(BNP),left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),and 6-minute walking distance(6MWD)were measured.The Minnesota CHF quality of life questionnaire(LiHFe)was used to evaluate patient's quality of life,readmission rate and cardiogenic mortality within 1 year of follow-up,and univariate and multivariate Logistic regression analysis was used to analyze factors affecting readmission of CHF patients.Results ① Cardiopulmonary function indicators:there was no statistically significant difference in the anaerobic threshold,peak oxygen uptake,and peak oxygen pulse of CPET functional indicators before and after intervention in the control group,after intervention,the CPET functional indicators in the observation group were significantly higher than those before intervention,and the above indexes in the observation group were significantly higher than those of the control group[anaerobic threshold(mL·min-1·kg-1):10.77±1.40 vs.9.59±1.11,anaerobic threshold(%ped):78.95±11.39 vs.70.09±6.48,peak oxygen uptake(mL·min-1·kg-1):15.63±1.36 vs.14.27±1.72,peak oxygen uptake(%ped):72.42±6.91 vs.63.41±7.31,peak oxygen pulse(mL/order):11.38±1.29 vs.9.05±1.64,peak oxygen pulse(%ped):90.23±10.16 vs.80.53±6.73,all P＜0.05].②Serum indicators,cardiac function indicators,exercise ability indicators,and quality of life evaluation:there was no statistically significant difference in serum indicators BNP,cardiac function indicators LVEDD,LVEF,exercise ability indicators 6MWD,and quality of life LiHFe scores between the two groups before intervention.After intervention,BNP and LiHFe scores were significantly reduced compared with before intervention,while LVEF and 6MWD were both increased compared with before intervention,and the changes of the above indexes in the observation group were more significant than those in the control group[BNP(ng/L):313.25±77.91 vs.445.89±110.67,LVEF:0.41±0.08 vs.0.37±0.06,6MWD(m):495.62±91.35 vs.416.04±65.29,LiHFe score:23.27±6.02 vs.29.50±4.61,all P＜0.05].③ Prognostic follow-up:the readmission rate within 1 year in the observation group was significantly lower than that in the control group(23.08%vs.53.85%),and there was no statistically significant difference in the mortality rate of cardiogenic diseases between the two groups.④Logistic univariate analysis showed that hyperlipidemia,New York Heart Association(NYHA)grading,BNP,and rehabilitation exercise were factors that affect the prognosis of CHF patients[odds ratio(OR)and 95%confidence interval(95%CI)were 0.098(0.019-0.494),0.069(0.016-0.294),1.018(1.007-1.029),and 3.889(1.178-12.841),respectively,all P＜0.05].Multivariate analysis showed that after adjusting for other factors,hyperlipidemia,NYHA grading,and BNP were risk factors affecting the prognosis of CHF patients(OR and 95%CI were 0.068(0.007-0.687),0.048(0.005-0.415),1.016(1.002-1.030),respectively,with P＜0.05],the use of rehabilitation exercise therapy was a protective factor affecting the prognosis of CHF patients[OR and 95%CI were 11.179(1.135-10.124),P＜0.05].Receiver operator characteristic curve(ROC curve)analysis showed that hyperlipidemia,NYHA grading,BNP,rehabilitation exercise therapy,and combined testing all had predictive value for the patient's prognosis(all P＜0.05),and the prediction value of joint detection was the highest,with the area under the ROC curve(AUC)=0.984 and P = 0.000.Conclusion Developing a high-intensity individualized cardiac exercise rehabilitation plan under the guidance of CPET can help improve the cardiopulmonary function,cardiac function,and quality of life of CHF patients,which is of great benefit for improving the long-term prognosis of CHF patients and has high safety.

【Objective】 To explore the characteristics of white matter degeneration in amyotrophic lateral sclerosis (ALS) patients with different onset and spreading patterns by using diffusion tensor imaging (DTI). 【Methods】 We enrolled 86 ALS patients and 44 healthy controls. The patients were divided into bulbar- and spinal-onset subgroups according to their onset site, as well as horizon, vertical, interpose/skip, and caudal-rostral subgroups based on the spreading direction of the involved regions. The white matter fiber tracts corresponding to the motor network were set as the region of interest. We used tract-based spatial statistics to evaluate differences between the above groups and the normal controls, with family-wise error (FWE) correction and P<0.05 as statistical significance. 【Results】 The white matter degeneration of ALS patients with bulbar onset was mainly limited to the corona radiation part of the corticospinal tract, while those with spinal onset showed extensive degeneration of corticospinal tract and corpus callosum Ⅲ area (FWE correction, P<0.05). In patients with horizontal and vertical dissemination, decreased integrity of the entire corticospinal tract was found, with patients in the latter group showed extra degeneration in the Ⅲ part of the corpus callosum. Restricted degeneration of the corticospinal tract within bilateral corona radiata was detected in patients with caudal-rostral and interposed/skip spreading pattens (FWE correction, P<0.05). 【Conclusion】 Different onset and disease spread patterns of ALS patients correspond to divergent brain degeneration patterns. The diagnosis, treatment, and management of ALS should fully consider the heterogeneity of the disease.

【Objective】 To investigate changes in thalamus structure and function and their associations with cognitive impairment in patients with amyotrophic lateral sclerosis (ALS). 【Methods】 3D high-resolution structural imaging and resting-state fMRI were applied in 78 ALS patients and 49 healthy volunteers. The shape of the thalamus was assessed using a vortex analysis and functional connectivity between the thalamus subregion and cortex was evaluated by a seed-based correlation analysis. Partial correlation analysis was used to evaluate the correlation between focal thalamus alterations and clinical assessments. 【Results】 Compared with the control group, vertex analysis showed significant atrophy in the prefrontal and temporal subregions of bilateral thalamus in the ALS group. Patients exhibited increased functional connectivity of motor-sensory ROI with the right motor cortex, of temporal ROI with the bilateral lateral occipital cortex, precuneus and right temporal subregion. In contrast, decreased function connectivity was found mainly between temporal ROI and paracingulate gyrus, left dorsomedial prefrontal lobe and left caudate. Partial correlation analysis showed that the functional connectivity of the precuneus, paracingulate cortex, left caudate nucleus and left prefrontal lobe was correlated with multiple cognitive performances. 【Conclusion】 Selective damage of thalamic structure and function in ALS plays an important role in cognitive and behavioral disorders.

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale. Graphical abstract

Background: Colorectal adenoma is the precursor lesion of colorectal cancer, and diabetes mellitus is associated with an increased risk for colorectal cancer. Aims: To investigate the clinicopathological characteristics of colorectal adenoma in patients with type 2 diabetes mellitus (T2DM) and the risk factors for advanced adenoma. Methods: Seven hundred and eighty T2DM patients who underwent initial colonoscopy from January 2018 to December 2020 at the Second Affiliated Hospital of Zhejiang Chinese Medical University were enrolled retrospectively, including 227 patients with colorectal adenoma and 553 patients without colorectal polyps. Furthermore, 227 non-diabetic patients with colorectal adenoma who were 1:1 matched to T2DM-adenoma group for gender, age, body mass index (BMI) and smoking history were collected for a comparison study. The clinical and pathological characteristics of T2DM patients with colorectal adenoma were analyzed, and the risk factors for advanced adenoma were identified by univariate and multivariate analyses. Results: T2DM patients with colorectal adenoma were older than those without colorectal polyps, and male gender, tobacco smoking, and cholelithiasis/cholecystectomy were more frequently seen in T2DM-adenoma group (all P<0.05). The proportions of multiple adenomas and advanced adenoma in T2DM-adenoma group were greater than those in patients without T2DM (16.7% vs. 10.1%, and 21.6% vs. 14.1%, all P<0.05). Multivariate Logistic regression analysis identified that male gender (OR=1.299, 95% CI: 1.041-1.831, P=0.008), age (OR=1.129, 95% CI: 1.001-1.421, P=0.025), BMI (OR=1.118, 95% CI: 1.022-1.715, P=0.038) and T2DM (OR=1.408, 95% CI: 1.141-1.721, P=0.010) were the independent risk factors for advanced adenoma. Conclusions: Multiple colorectal adenomas and advanced adenoma are more likely to be detected in patients with T2DM. Male gender, age, BMI and T2DM are associated with the risk of advanced adenoma.

Objective: To explore the application of asymmetrical sculpture in the ear reconstruction with autologous cartilage through comparing the difference of the balanced sculpture and asymmetrical sculpture. Methods: We used the method of retrospective survey and classified the patients who had undergone ear reconstruction because of microtia into two groups. Group A included the patients who had undergone operation with the application of balanced sculpture method. Group B included the patients who had undergone operation with the application of unsymmetrical sculpture method. We picked out 35 patients containing 19 patients of group A and 16 patients of group B according to our grouping criteria and exclusion criteria. The number of cases with complications was recorded, such as collapse of framework, exposure of cartilage, necrosis of skin flap and reconstructed ear infection. The clinical outcomes of two methods in refining the delicate structures of the reconstructed ear were evaluated (that is the definition, shape, size, color and projection). The time for sculpture was compared. Then we analysed the results and evaluated the effectiveness, safety and feasibility of asymmetrical sculpture′s application in the ear reconstruction. Results: Group A had 2 cases which suffered skin flap necrosis. One of them had cartilage exposure and then had secondary infection leading to local cartilage necrosis and absorption, but after active treatment and local skin flap transplantation it was cured. Group B had no skin flap necrosis, cartilage extrusion, framework deformation and distortion, framework collapse and necrosis or absorption. Group B had a higher score in definition, shape, size, color and projection, and the difference was significant in definition, shape, color and projection. In our clinical practice, the sculpture time in both group was similarly about 40 minutes after the surgery operator had skillfully mastered both techniques. Conclusions Both methods are safe and feasible. The method of asymmetrical sculpture does not require additional operative time, and the method of asymmetrical sculpture is a better one compared with the method of balanced sculpture in refining the reconstructed ear.

Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their own features and become mesenchymal cells, and more and more studies have shown that EMT plays an important role in the invasion and metastasis of hepatocellular carcinoma (HCC). This article reviews the signaling pathways involved in the progression of HCC and molecules involved in the regulation of EMT, in order to provide a new direction for the treatment of HCC.

Background: Studies showed that aberrant activation of JAK/STAT3 signaling pathway promoted the tumorigenesis and progression of hepatocellular carcinoma (HCC), and transforming growth factor-β1 (TGF-β1) has either tumor-suppressing or tumor-promoting effect in regulation of tumor progression.Aims: To investigate the effect of specific inhibition of JAK/STAT3 signaling pathway on HCC and whether TGF-β1 signaling pathway is involved in this process or not.Methods: Thirty Wistar rats were randomly divided into three groups: control group, HCC group, and HCC+AG490 group.In the latter two groups, diethylnitrosamine was administered in drinking water to induce HCC model, and in HCC+AG490 group, AG490, a specific inhibitor of JAK was injected intraperitoneally in the first week of model establishment.At the end of the 16th week, all rats were sacrificed.The maximum diameter of tumor nodules in the liver was recorded and the number of tumors with maximum diameter greater than 1 cm was counted.Expression and distribution of STAT3 and TGF-β1 in liver tissue were determined by real-time PCR, immunohistochemistry, and immunofluorescence.Results: Compared with the control group, expressions of STAT3 and TGF-β1 mRNA in liver tissue were significantly increased in HCC group (P<0.05).Phosphorylated STAT3 (p-STAT3) and TGF-β1 proteins were absent in liver tissue in control group, and both were up-regulated and co-expressed in HCC group.While in HCC+AG490 group, expressions of STAT3 and TGF-β1 mRNA were significantly lower than those in HCC group (P<0.05);the liver tissue was weakly positive for p-STAT3 and TGF-β1 proteins, and the number of tumor nodules greater than 1 cm and the maximum diameter were markedly reduced when compared with the HCC group [1.20±1.03 and (1.14±0.18) cm vs.4.30±1.06 and (1.78±0.27) cm, P all<0.05].Conclusions: Specific inhibition of JAK/STAT3 signaling pathway may restrain the tumorigenesis and progression of HCC partially by interfering TGF-β1 signaling pathway.

Background Light-induced retinal damage results in the damage of retinl pigment epithelial (RPE) cells and therefore affects the pathogenesis and development of age-related macular degeneration (AMD).Studies showed that tissue factor (TF) is overexpressed in oxidative damaged RPE cells and the choroidal neovascularization (CNV) of AMD,speculating that the suppression of TF can prevent the damage of RPE cells and inhibit CNV.Objective This study was conducted to observe the protective effects of TF targeting peptide (TFTP),a new drug of autologous synthesis,on human RPE-cells induced by blue light.Methods Human RPE cells were isolated from donor eye and cultured.Cultured cells were divided into blank control group,model group and TFTP treated group.Light-induced RPE cell damage model was established by exposuring the cells in the blue light of (4.0±-0.5) mW/cm2 for 12 hours in the model group,and different concentrations (10,100,150,200,300 μmol/L) of TF-TP were added into the medium to pretreat the cells for 24 hours and then exposed the cells to the blue light for 12 hours in the TF-TP groups.The cell viability was determined by CCK-8 assay.The morphology and ultrastructure in the cells were observed under the inverted microscope and transmission electron microscope.The apoptosis of the cells was assayed by Hoechst staining.The expressions of TF and apoptosis-related protein bax,bcl-2 in the cells were determined by Western blot.Results CCK-8 assay showed that there was no significant difference in the cell viability among blank control group and different concentrations TF-TP groups (F=2.15,P =0.11).The cell survival rate of blank control group,model group and 150 μmol/L TF-TP group was (100.0±0.00) ％,(43.79±6.55) ％ and (63.45±3.57) ％,and the survial rate was increased in the 150 μmol/L TF-TP group compared with the model group (P =0.00),and 150 μmol/L was detemined as a optimal concentration of TF-TP.A lot of shrinkage,deformation,suspension cells were exhibited under the optical microscope,and decrease of microvilli structure,rupture of mitochondrial cristae and vacuolar degeneration of the cells were found in the model group,and the damage of the cells were evidently lightened in the 150 μ mol/L TF-TP group.The apoptosis rate of the cells were (0.98 ±0.19)％,(9.98 ±0.82) ％ and (5.73 ±0.88) ％ in the blank group,model group and 150 μmol/L TF-TP group,respectively,with a significant difference among the groups (F =206.18,P =0.00),and the apoptosis rate of the cells in the 150 μmol/L TF-TP group was significantly lower than that in the model group (P＜0.05).Compared with the blank control group,the relative expression of bax and TF was obviously increased and that of bcl-2 was decreased in the model group;while the expression of bax and TF was lower,and that of bcl-2 was higher in the 150 μmol/L TF-TP group compared with the model group (all at P ＜ 0.05).Conclusions Pretreation of TF-TP can lessen cell apoptosis and increase cell survival rate and therefore plays a protective role to blue light-induced human RPE cells possibly by inhibiting bax/bcl-2 apoptotic pathways mediated by TF.

Objective To evaluate the clinical application of TCM nursing therapies and identify the problems during the therapy implementation, in order to explore the countermeasures to promote its clinical improvement. Methods A descriptive cross-sectional study was conducted,and a self-designed questionnaire was employed to investigate 218 nurses from 148 grade A class three TCM hospitals in China. Results 25 TCM nursing therapies were implemented in these hospitals. Ear acupressure therapy was the most frequently implemented,accounting for 83.5%(182/218);while wax therapy was the least implemented, accounting for 7.8%(17/218). The implementation frequency of these technologies varied significantly, 0~860 times a week. The top three of them were acupoint application therapy, hot compression of Chinese medicine and ear acupoints therapy.TCM nursing therapies were considered to be the most frequently used in insomnia, headache, edema, arthralgia, cold, epigastric pain, hypochondriac pain and fever.Storage of TCM nurses,lacking of TCM knowledge and inapposite therapy implementation were the main problems in the application. Conclusions Scientific and rational allocation of human resources, cultivation of the TCM-specific nursing professional, enhancement of nurses'awareness of Chinese medicine, establishment of a reasonable charging standard, and strengthening the risk management in implementation will promote its clinical development.