Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective To study topological structure of a new type of three-dimensional (3D) printed height increasing insoles for leg length discrepancy (LLD) and its effect on biomechanics of lower limbs. Methods Topological structure for middle and rear part of the insole was optimized by solid isotropic microstructures with penalization (SIMP), the force was loaded and the boundary conditions were set according to force area of the insole, and the height increasing insole with thermoplastic polyurethanes (TPU) materials was printed by selected laser sintering (SLS). The insoles were used in 9 patients with LLD, visual analogue scale (VAS) and Maryland foot function scores were used to compare pain and foot function changes of patients before and after using the insole, and the 3D gait analysis system was used to compare spatiotemporal parameters and vertical ground reaction force (vGRF) of both lower limbs. Result sAfter the patient wore 3D printed insole, VAS scores decreased, Maryland foot function scores increased, vGRF of both lower limbs decreased, and the difference of cadence, stance phase and swing phase in both lower limbs decreased. Conclusions The 3D printed height increasing insole after topology optimization can improve coordination of lower limb movement, reduce ground impact, relieve pain and improve foot function, thus providing an effective personalized orthopedic plan for LLD treatment in clinic.

Objective: To compare the differences of water barrier function between keloids and its surrounding normal skin in patients with keloids, and to explore the primary mechanism. Methods: A cross-sectional observational study was conducted. From October 2020 to March 2021, 30 patients with keloids who met the inclusion criteria visited Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 18 females and 12 males, aged 20-48 years. The transepidermal water loss (TEWL) of their keloids and the surrounding normal skin of the 30 patients were measured by multi probe adapter on the reception day. The keloid tissues and normal skin of 5 patients after keloid repair surgery were processed for hematoxylin-eosin staining to measure the thickness of epidermis. Immunohistochemistry was performed on samples from 3 of those 5 patients to detect the expressions of cytokeratin-10, involucrin, and filaggrin in keloids and normal skin. Data were statistically analyzed with paired sample t test and independent sample t test. Results: On the reception day, the TEWL of keloids of 30 patients was 9.0 (6.9, 13.4) g·m^-2·h^-1 and the TEWL of the normal skin was 8.1 (6.4, 18.1) g·m^-2·h^-1, between which the difference was not statistically significant (t=0.44, P>0.05). After keloid repair surgery, the thickness of epidermis in the keloids of 5 patients was (194±44) μm, which was significantly thicker than that of the normal skin (44±11) μm, (t=6.88, P<0.01). Furthermore, increased keratinocytes, lack of normal epidermal ridge structures, and thickened stratum corneum were observed in the keloid area. After keloid repair surgery, the expression level of cytokeratin-10 in keloids was significantly lower than that in normal skin of 3 patients (t=8.50, P<0.01), but there were no statistically significant differences in the expression levels of involucrin or filaggrin between keloids and normal skin (with t values of 0.07 and 0.96, respectively, P>0.05). Conclusions: Keloid tissue from patients with keloids displays increased number of keratinocytes and thickened epidermis. But the water barrier function in keloid area is similar to the surrounding normal skin, suggesting that TEWL may not be the main mechanism lead to the persistent development of keloids.
Adult ; China ; Cross-Sectional Studies ; Female ; Humans ; Keloid/pathology* ; Male ; Middle Aged ; Skin/pathology* ; Water ; Young Adult

Long-term poor dietary habits can cause changes in the intestinal flora, resulting in the production of a large number of lipopolysaccharide, increase intestinal mucosal permeability, and activate the entrance of a large number of inflammatory factors into the portal vein. In addition, a high carbohydrate diet can increase liver metabolic burden, increase mitochondrial oxidative phosphorylation, leading to oxidative stress, generate new fat during adenosine triphosphate synthesis, and thus resulting in ectopic fat accumulation, which further activate nuclear factor-κB signaling pathway and release inflam- matory factors such as tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, and so on. This leads to obesity and insulin resis- tance, ultimately triggering systemic low-grade inflammation. This article reviews the mechanism of poor dietary habits leading to systemic low-grade inflammation, the clinical and experimental research progress of keloids and systemic low-grade inflammation, the association between dietary habits and keloid constitution, and puts forward the hypothesis that poor dietary habits may lead to the occurrence and development of keloids.
Diet/adverse effects* ; Feeding Behavior ; Humans ; Inflammation/metabolism* ; Keloid/physiopathology* ; NF-kappa B/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective To evaluate the efficacy of additive manufacturing scoliosis orthosis, by simulation on interaction of the bone, trunk and orthosis using finite element method. Methods Combined with CT data of the patients, three-dimensional (3D) scanning model of the trunk and full length X-ray of the spine, the bone-trunk-orthosis finite element model was established and proved to be effective. The change and development trend of Cobb angle of the main thoracic scoliosis was calculated under different boundary and load conditions. Results The treatment effect of the additive manufacturing scoliosis orthosis was good. With the increase of orthotic preload, the improvement of Cobb angle and pelvic tilt was more obvious. The Cobb angle was expected to decrease by 6.18° after application of 70 N preload to the orthosis for 6 months. In the case of increasing system stiffness, Cobb angle improvement was not obvious and became even worse. Conclusions Additive manufacturing scoliosis orthosis is effective for treating adolescents with immature bones, while for patients with mature or degenerative bones, its treatment effect is poor.

As a key regulatory element of gene differential expression, enhancer plays a crucial role in craniomaxillofacial development through regulating the spatiotemporal expression of target genes to promote tissue-specific differentiation. With the development of CRISPR and chromosome conformation capture technique, the function of enhancer and its regulatory mechanism has been explored in depth. This paper gave a systematic review on the mechanism of enhancer regulating target gene expression and the role of enhancer in oral craniofacial development and malformation.
Animals ; Enhancer Elements, Genetic ; Mammals/genetics*

To implement the fundamental task of the Ministry of Education on carrying out curriculum ideological and political education and promoting colleges and universities to implement the morality education, this study tried to carry out ideological and political education for medical students in "medical functional science experimental course", and organically integrated the ideological and political elements of "loving experimental animals and reverencing for life" into the teaching of this course. This paper explored the implementation process and effect evaluation of ideological and political courses from the aspects of teaching objects, design, objectives, in-class and off-class practical activities, and analyzed the current problems and future directions. In order to provide beneficial ideas for the ideological and political construction of college curriculum and help cultivate excellent and innovative medical talents with warmth and feelings.

Malignant tumors in the head and neck seriously threaten the physical and mental health of patients. After treatment, they may cause many complications, such as facial deformity, difficulties with chewing, dysphagia and asaphia. Among them, trismus (restricted mouth opening) is one of the most common complications after treatment of malignant oral-maxillofacial tumors. In severe cases, patients may even suffer from trismus and eating difficulties, finally leading to malnutrition and even cachexia. Therefore, it not only affects the quality of life of patients and even endangers their lives but also brings heavy social and economic burdens. How to effectively prevent and treat posttreatment trismus is a clinical problem that is easily ignored by head and neck surgeons and urgently needs to be solved. The results of a literature review showed that trismus may be related to the tumor clinical stage, tumor site, treatment used, radiotherapy site, radiotherapy dose, radiotherapy type, and other factors. The incidence of trismus tends to be significant 6 months after treatment. Without early intervention, the resulting dysfunction may become more severe. Current studies have shown that the prevention and treatment of restricted mouth opening is based on controlling the progress of restricted mouth opening and restoring function. Exercise intervention for trismus can significantly improve the restricted mouth opening of patients with malignant head and neck tumors after treatment.

OBJECTIVES: This study aimed to explore the effects of silencing isoprenylcysteine carboxyl methyltransfe-rase (Icmt) through small interfering RNA (siRNA) interference on the proliferation and apoptosis of tongue squamous cell carcinoma (TSCC). METHODS: Three siRNA were designed and constructed for the Icmt gene sequence and were then transfected into TSCC cells CAL-27 and SCC-4 to silence Icmt expression. The tested cells were divided as follows: RNA interference groups Icmt-siRNA-1, Icmt-siRNA-2, and Icmt-siRNA-3, negative control group, and blank control group. The transfection efficiency of siRNA was detected by the fluorescent group Cy3-labeled siRNA, and the expression of Icmt mRNA was screened by quantitive real-time polymerase chain reaction (qRT-PCR) selected the experimental group for subsequent experiments. The expression of Icmt, RhoA, Cyclin D1, p21, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) were analyzed by Western blot. The proliferation abilities of TSCC cells were determined by cell counting kit-8 assay. The change in apoptosis was detected by AnnexinV-APC/propidium staining (PI) assay. Cell-cycle analysis was conducted by flow cytometry. RESULTS: The expression of Icmt mRNA and protein in TSCC cells significantly decreased after Icmt-siRNA transfection ( CONCLUSIONS Silencing Icmt can effectively downregulate its expression in TSCC cells, reduce the RhoA membrane targeting localization and cell proliferation, and induce apoptosis. Thus, Icmt may be a potential gene therapy target for TSCC.
Apoptosis ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Protein Methyltransferases ; RNA, Small Interfering ; Tongue ; Tongue Neoplasms

OBJECTIVES: The effect of isoprenylcysteine carboxymethyltransferase (ICMT) silencing on the migration and invasion of tongue squamous cell carcinoma was investigated by constructing the small interfering RNA (siRNA) of ICMT. METHODS: Through liposomal transfection, siRNA was transfected into human tongue squamous cell carcinoma CAL-27 and SCC-4 cells (ICMT-siRNA group) with a negative control group (transfected with NC-siRNA) and a blank control group (transfected with a transfection reagent but not with siRNA). Quantitative real-time polymerase chain reaction was performed to analyze the mRNA expression of ICMT and RhoA in each group of cells after transfection and to measure the silencing efficiency. Western blot was applied to examine the expression levels of ICMT, total RhoA, membrane RhoA, ROCK1, matrix metalloproteinase (MMP)-2, and MMP-9 proteins in each group. The migration and invasion abilities were evaluated via wound healing and Transwell motility assays. RESULTS: After CAL-27 and SCC-4 cells were transfected with ICMT-siRNA, the expression levels of ICMT genes and proteins decreased significantly in the experimental group compared with those in the negative and blank control groups ( CONCLUSIONS The migration and invasion abilities of CAL-27 and SCC-4 cells were reduced significantly after the transfection of ICMT-siRNA, and the involved mechanism might be related to the RhoA-ROCK signaling pathway.
Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Neoplasm Invasiveness ; Protein Methyltransferases ; RNA, Small Interfering ; Tongue ; Tongue Neoplasms ; Transfection ; rho-Associated Kinases