The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

[摘 要] 无义介导的mRNA降解（NMD）作为一种质量控制机制，可降解含有过早终止密码子（PTC）的异常mRNA，参与生长发育、调节免疫功能，且与肿瘤微环境密切相关。NMD对肿瘤有抑制或促进的双重作用：一方面，NMD通过下调促癌蛋白表达、抑制促癌信号通路和应激微环境等途径抑制肿瘤进展；另一方面，NMD通过抑制抑癌基因的表达、癌细胞凋亡和肿瘤新抗原的产生促进肿瘤进展。此外，NMD并非降解所有携带PTC的mRNA，PTC出现的位置可能决定NMD触发或逃逸，由于各基因的高频突变区域各不相同，因此不同基因发生PTC突变后是否触发NMD则具有不同的倾向性。随着二代测序技术的成熟与普及，基因突变筛查已成为临床诊疗常规手段，这使得从多基因层面探究NMD的规律与意义成为可能。因此，在进一步了解NMD的功能及其机制的基础上，通过高通量测序与计算机算法评估NMD水平，有望在临床工作中扬长避短地发挥NMD潜在的临床价值，助力个性化临床诊治与精准医疗的发展。

Objective To evaluate the accuracy of selective laser melting of cobalt-chromium(CoCr)clasps with different build angles and support densities.Methods The 3D software constructed a sample clasp(reference object)with an undercut depth of 0.50 mm,which was then imported to a metal 3D printer to form CoCr clasps at different build angles(0°,45°,and 90°)and support densities(0.50,0.70,0.90,and 1.10 mm).A model scanner was used to obtain scans of all clasps(test objects);the test objects were aligned with the reference object and test subjects were aligned with each other through a best-fit alignment method using Geomagic software to obtain root mean square error(RMSE)values for the accuracy of the clasps.The data were statistically analyzed using one-way analysis of variance or non-parametric rank sum test(α=0.05).Results In terms of trueness,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For the different build angle groups with support densities of 0.70,0.90,and 1.10 mm,the RMSE values ranked as follows:45°group>90°group>0°group.In terms of precision,the different build angle groups with support density of 0.50 mm were ranked by RMSE values as follows:90°group>0°group>45°group.For support density of 0.70 mm,the ranking was 90°group>45°group>0°group,while for support densities of 0.90 and 1.10 mm,the ranking was 45°group>90°group>0°group.Conclusion The accuracy of CoCr clasps varies with the build angle and support density.However,clasps produced at a build angle of 0°and a support density of 0.90 mm exhibit higher accuracy and are recommended for use in clinical and technical laboratories.

Objective:To compare the characteristics of gait disorders between patients with idiopathic normal pressure hydrocephalus(iNPH)and Parkinson's disease(PD)patients.Methods:General clinical data and gait assessment results of 16 iNPH patients, 20 PD patients, and 23 healthy adults seeking treatment at Tianjin Huanhu Hospital between January 2020 and December 2020 were retrospectively analyzed.Gait analysis was conducted using the Mobility Lab? system with APDM Opal sensors from the US.Results:The 16 patients in the iNPH group had a mean age of(68.81±8.73), the 20 patients in the PD group had a mean age of(65.05±10.15), and the 23 adults in the control group had a mean age of(59.96±6.20).There was no significant difference in age between the iNPH group and the PD group( P>0.05).However, the iNPH group was older than the healthy control group( t=3.71, P<0.05).The disease duration of the iNPH group was(22.94±23.19)months, which was shorter than(92.60±53.70)months in the PD group( t=5.23, P<0.05).The mini-mental state examination(MMSE)score(17.13±7.08)and the Montreal Cognitive Assessment(MoCA)score(11.75±5.43)of the iNPH group were significantly lower than those in the PD group[(24.17±4.73), t=3.45, P<0.05、(21.29±5.82), t=4.86, P<0.05]and the control group[(26.70±1.61), t=5.31, P<0.05、(22.78±3.30), t=7.89, P<0.05].Compared with the PD group, the iNPH group had a significantly lower foot clearance[right: (1.65±0.76)cm vs.(2.56±1.30)cm]and smaller bilateral toe-off angles[left: (20.59±6.11)° vs.(28.43±6.36)°; right: (20.78±6.88)° vs.(28.12±7.49)°, t=3.74、3.02, respectively, all P<0.05].There were statistically significant differences in all gait parameters in iNPH patients compared with the control group( P<0.05). Conclusions:iNPH patients exhibit clear gait disturbance, which is more prominent than in PD patients.The wearable gait analysis system can accurately assess gait disorders in iNPH patients, and can be applied to gait assessment and the development of rehabilitation plans.

Objective:To investigate the professional identity status of nursing students in higher vocational colleges in Shanghai, China, and to analyze the influencing factors.Methods:By cluster sampling, we selected 308 nursing students of grade 2019 from a higher vocational college in Shanghai for a survey with the General Information Questionnaire, Professional Identity Questionnaire for Nurse Students (PIQNS), Stanford Presenteeism Scale-6 (SPS-6), Wong and Law Emotional Intelligence Scale (WLEIS), Workplace Social Capital (WSC), and Nurse Psychological Capital Questionnaire (PCQ). SPSS 22.0 was used for descriptive analysis, the independent samples t-test, one-way analysis of variance, Pearson correlation analysis, and multiple linear regression analysis. Results:The total PIQNS score of the students was (64.93±12.83), the total SPS-6 score was (15.91±4.40), the total WLEIS score was (80.57±15.52), the total WSC score was (32.38±6.33), and the total PCQ score was (95.47±18.63). The PIQNS score was negatively correlated with the SPS-6 score ( r=-0.282, P<0.01), positively correlated with the WLEIS score ( r=0.712, P<0.01), positively correlated with the WSC score ( r=0.659, P<0.01), and positively correlated with the PCQ score ( r=0.681, P<0.01). The multiple linear regression analysis showed that personal interest, emotional intelligence, and psychological capital significantly affected the professional identity of nursing students, entering the regression equation for professional identity. Conclusions:The professional identity of higher vocational nursing students in Shanghai is at a medium level, and personal interest, emotional intelligence, and psychological capital are the main factors influencing professional identity.

Objective:To explore the changes of gait flexibility and stability in patients with Parkinson's disease (PD) 2 years after deep brain stimulation (DBS).Methods:Twenty PD patients accepted DBS in Department of Neurosurgery, Tianjin Huanhu Hospital from October 2019 to November 2021 were enrolled. Motor symptoms were evaluated by Movement Disorder Society-unified Parkinson's disease rating scale III (MDS-UPDRS-III) at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to assess the cognition and 39-item Parkinson's disease questionnaire (PDQ-39) was used to evaluate the quality of life at preoperative medication-on state and postoperative medication-on state. A three-dimensional gait analyzer was used to record the gait parameters during Instrumented Stand and Walk test (ISAW) at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state. Differences in motor symptom scores, cognitive scores, quality of life scores, as well as changes in gait flexibility and stability were compared before and after DBS.Results:(1) The MDS-UPDRS-Ⅲ scores at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state ([45.30±12.57], [24.95±10.74], [15.80±7.19]) were decreased successively, with significant differences ( P<0.05).(2) Compared with those before surgery, PD patients had significantly lower levodopa equivalent daily dose (LEDD), total scores of PDQ-39, and scores of question 9 "degree of concern about falling" in PDQ-39 at 2 years after DBS ([711.84±343.99] mg/d vs. [549.30±301.08] mg/d, 47.00[30.00, 64.00] vs. 13.50[7.75, 27.00], 2.00[0.00, 3.00] vs. 0.00[0.00, 1.75], P<0.05). (3) Compared with that at preoperative medication-off state, the arm swing velocity at postoperative medication-on state statistically increased in PD patients ( P<0.05); compared with those at preoperative medication-off state, the arm swing range and turning speed at postoperative medication-off and medication-on states significantly increased in PD patients ( P<0.05); compared with that at preoperative medication-off state, the turning duration at postoperative medication-off state statistically decreased in PD patients ( P<0.05). Compared with that at preoperative medication-off state, the range of motion of the trunk in the horizontal plane at postoperative medication-off and medication-on states increased significantly in PD patients ( P<0.05); compared with that at preoperative medication-off state, the range of motion in the sagittal plane of the lumbar, coronal plane of the trunk, and sagittal plane of the trunk all increased significantly in PD patients at postoperative medication-on state ( P<0.05); the mean velocity and root mean square acceleration at postoperative medication-on state increased significantly in PD patients compared with that at preoperative medication-off state ( P<0.05); conversely, the swing frequency at postoperative medication-off state decreased significantly in PD patients compared with that at preoperative medication-off state ( P<0.05). Conclusion:Two years after DBS, PD patients exhibit obviously improved gait, with enhanced flexibility, and dynamic and static stability.

Exosomes are double phospholipid membrane vesicles that are synthesized and secreted by a variety of cells, including T cells, B cells, dendritic cells, immune cells, are extracellular vesicles. Recent studies have revealed that exosomes can play a significant role in under both physiological and pathological conditions. They have been implicated in regulation of inflammatory responses, immune response, angiogenesis, tissue repair, and antioxidant activities, particularly in modulating immunity in autoimmune diseases (AIDs). Moreover, variations in the expression of exosome-related substances, such as miRNA and proteins, may not only offer valuable perspectives for the early warning, and prognostic assessment of various AIDs, but may also serve as novel markers for disease diagnosis. This article examines the impact of exosomes on the development of AIDs and explores their potential for therapeutic application.

ObjectiveTo investigate the characteristics of serum perfluoroalkyl substances （PFASs） exposure and potential influencing factors among community residents in Songjiang District， Shanghai. MethodsIn August 2021， residents who underwent routine health checkups in a community in Songjiang District， Shanghai were recruited as study subjects. The inclusion criteria were adult residents who had lived in the area for more than 3 years， had no occupational exposure history， no underlying diseases， were not pregnant， and were able to complete the questionnaire independently and sign the informed consent form. A questionnaire survey was conducted and venous blood samples were collected. The concentrations of 15 PFASs in serum were determined using ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry （UPLC-MS/MS）. Ordered multi-class logistic regression， interquartile range （IQR）， and odds ratio （OR） were used to explore the influencing factors and risk magnitude of serum PFASs concentrations. ResultsOf the 15 PFASs， 14 were detected， and the detection rates of 7 PFASs were higher than 50%. The highest detected concentrations among the PFASs were PFOS （perfluorooctane sulfonate）， PFOA （perfluorooctanoic acid）， and PFHxS （perfluorohexane sulfonate）， with median concentrations of 48.61 μg∙L^-1， 37.29 μg∙L^-1， and 36.51 μg∙L^-1， respectively. The strongest correlation was between PFDA and PFUnDA （r=0.93， P<0.05）， followed by PFOS and PFDA （r=0.86， P<0.05）. Age， frequency of plastic product use， time spent indoors per day， personal annual income， tea consumption， and daily water intake were potential factors for exposure to PFASs. Among them， age was positively correlated with PFASs； tea consumption was positively correlated with PFNA and PFOA； PFHpA was negatively correlated with the frequency of plastic product use and personal annual income； and PFOS was negatively correlated with the time spent indoors per day. ConclusionThe exposure to serum PFASs among community residents in Songjiang District was relatively serious， and the main components were traditional PFOA， PFOS， and PFHx. Different sociodemographic characteristics had varying degrees of influence on the concentrations of PFASs in serum. The impact of PFASs exposure on the health of community residents deserves further investigation.

Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods: and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

Leber’s hereditary optic neuropathy (LHON) is a paradigm maternal hereditary eye disease, mainly involving the retinal and macular fibers of the optic disc in the anterior ethmoid plate of the sclera. LHON has the characteristics of sex bias among males and incomplete penetrance. Primary mitochondrial DNA mutations m.11778G>A, m. 14484T>C, m.3460G>A are the molecular basis of LHON. However, other risk factors, such as secondary mitochondrial DNA mutations, mitochondrial haplotypes, nuclear modification genes, estrogen, vitamin B12 and environmental factors, work together to affect its phenotypic expression. The clinical diagnosis of LHON mainly limited to the detection of the primary mutation site of mitochondrial DNA. Therefore, comprehensive analysis of multiple risk factors of LHON will facilitate to construct multi-dimensional model of prevention, diagnosis and treatment system, which provide accurate and individualized medical services for patients. These may alleviate the incidence in LHON families. It also provides new ideas and different angles for the in-depth study of the pathogenesis of LHON.