MicroRNA-384-5p protects against cardiac hypertrophy via the ALPK3 signaling pathway.

Heart failure is a condition caused by a variety of pathophysiological factors. One important pathological change of chronic heart failure is myocardial hypertrophy. In recent years, several studies have found that dysregulated microRNAs are involved in regulating the pathological process of heart failure. In this study, cardiac hypertrophy models were constructed using isoproterenol (ISO)-/angiotensin-II (Ang-II) to explore the role of miR-384-5p in cardiac hypertrophy and its molecular mechanism in vivo and in vitro. Echocardiography, invasive pressure-volume analysis and hematoxylin-eosin staining were used to explore cardiac structure and function. ALPK3 mRNA and protein expression were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis and miR-384-5p expression were assessed via RT-qPCR. Our findings determined that miR-384-5p was notably decreased in cardiac hypertrophic tissues and cells, and overexpression of miR-384-5p could ameliorate pressure overload. Furthermore, ALPK3 was determined to downregulate the ALPK3 expression to aggravate cardiomyocyte hypertrophy. Our findings provided a potential therapeutic target for the treatment of cardiac hypertrophy.

Connexin 37 Regulates the Kv1.3 Pathway and Promotes the Development of Atherosclerosis.

Objective: To investigate the mechanism of Connexin 37 (Cx37) and Kv1.3 pathways in atherosclerosis (AS). Methods: ApoE-/- mice were given a high-fat diet to establish atherosclerosis (AS) model, and macrophages in mice were isolated and extracted to transfect Cx37 vectors with silencing or overexpressing, and Kv1.3 pathway blockers were used to inhibit the pathway activity. The indexes of body weight, blood glucose, and blood lipid of mice were collected. The protein and mRNA expression levels of Cx37 and Kv1.3 were detected by reverse transcription-PCR (RT-PCR), Western blot, and immunofluorescence technique. Oil red O staining was used to observe plaque area. Masson staining was used to detect collagen content. The concentrations of chemokine CCL7 were quantified using the ELISA kits. CCK8 was used to detect cell proliferation. Results: Cx37 and Kv1.3 were highly expressed in macrophages of AS mice, and the expression of Kv1.3 and CCL7 decreased after Cx37 was silenced, and the proliferation of macrophages was also decreased. Wild-type mice and AS model mice were treated with Cx37 overexpression vectors and Kv1.3 pathway blocking, and it was found that Cx37 overexpression could improve the blood lipid and blood glucose levels and increase the area of AS in AS mice. However, blocking the activity of Kv1.3 pathway can reduce the levels of blood lipid and blood glucose, increase the body weight of mice, and reduce the area of AS mice. Blocking the activity of Kv1.3 pathway can slow down the plaque development of AS mice and make its indexes close to wild-type mice. And the use of Kv1.3 pathway blockers on the basis of overexpression of Cx37 indicated that inhibition of Kv1.3 pathway activity did not affect the expression of Cx37, but could inhibit the collagen content in the plaque area of AS mice, inhibit the expression of chemokine CCL7, and reverse the effect of Cx37 overexpression. Conclusion: Cx37 can improve the activity of macrophages by regulating the expression of chemokines and the activity of Kv1.3 pathway in AS mice, and enrich macrophages in inflammatory tissues and expand the area of plaque formation.

Effects of Solution Flow on the Growth of Colloidal Crystals.

For the versatile potential applications of colloidal crystals, precisely controlling their growth is required to achieve properties such as high crystallinity and large-area crystals. Because colloidal crystallization is a self-assembly process of dispersed particles in a solution, solution flow directly and markedly changes the behavior of particles. Thus, the effects of solution flow on the growth of colloidal crystals were investigated in the present study. We found three different effects of solution flow on the growth of colloidal crystals: enlarging the first layer, facilitating the growth of superlattice structures, and forming a new circular packing structure. Specifically, in the single-component system, because the flow speed is lower closer to the bottom of the cell, the second and further layers dissolve owing to the large flow speed, whereas the first layer remains undissolved at the appropriate flow speed. The dissolved particles (particles that are detached from the crystals and returned back into the aqueous medium) are transported near the first layer, where they facilitate the growth of the first layer. In a binary system, when colloidal crystals with different particles are neighboring each other, the flow dissolves the surface of each crystal, which forms a dense, melt-like phase between crystals, from which a superlattice structure such as AB2 grows. The flow often moves the second layer more than the first layer because the flow speed varies with the distance from the bottom. This causes the second layer to slide above the first layer of the neighboring crystals composed of different particle sizes, which transform from the initial face-centered cubic structure of the first layer into a circular pattern with strain. These findings contribute to establishing a sophisticated control method for growing colloidal crystals.

Complete Genome of Vibrio neocaledonicus CGJ02-2, An active Compounds Producing Bacterium Isolated from South China Sea.

Strain CGJ02-2 was isolated from the coral reefs in South China sea and deposited in South China Sea Institute of Oceanology, Chinese Academy of Sciences. Active compounds including indole, ρ-hydroxybenzaldehyde were isolated from this strain. To explore the biosynthetic way of these compounds and search gene clusters, the complete genome of this strain was sequenced by Single Molecule, Real-Time (SMRT) technology. It was de novo assembled to two circular chromosomes of 3,400,283 bp with GC% 44.77 and 1,845,572 bp with GC% 44.59 respectively and classified as Vibrio alginolyticus. In silico phenotype features of Vibrio alginolyticus CGJ02-2 were also analyzed. The biosynthetic pathway of ρ-hydroxybenzaldehyde and indole in this strain were postulated. Gene clusters of four secondary metabolites including bacteriocin, ectoine, siderophore, arylpolyene were identified. This study provides helpful information for further utilizing Vibrio alginolyticus CGJ02-2 as a source of valuable bioactive compounds.

Small RNA-mediated Cry toxin silencing allows Bacillus thuringiensis to evade Caenorhabditis elegans avoidance behavioral defenses.

Pathogen avoidance behavior protects animal hosts against microbial pathogens. Pathogens have evolved specific strategies during coevolution in response to such host defenses. However, these strategies for combatting host avoidance behavioral defenses remain poorly understood. Here, we used Caenorhabditis elegans and its bacterial pathogen Bacillus thuringiensis as a model and determined that small RNA (sRNA)-mediated Cry toxin silencing allowed pathogens to evade host avoidance behavioral defenses. The B. thuringiensis strain YBT-1518, which encodes three nematicidal cry genes, is highly toxic to C. elegans. However, the expression of the most potent toxin, Cry5Ba, was silenced in this strain when YBT-1518 was outside the host. Cry5Ba silencing was due to the sRNA BtsR1, which bound to the RBS site of the cry5Ba transcript via direct base pairing and inhibited Cry5Ba expression. Upon ingestion by C. elegans, Cry5Ba was expressed in vivo by strain YBT-1518. Cry5Ba silencing may allow B. thuringiensis to avoid nematode behavioral defenses and then express toxins once ingested to kill the host and gain a survival advantage. Our work describes a novel model of sRNA-mediated regulation to aid pathogens in combating host avoidance behavioral defenses.

Heterogeneous Nucleation of Colloidal Crystals on a Glass Substrate with Depletion Attraction.

The heterogeneous nucleation of colloidal crystals with attractive interactions has been investigated via in situ observations. We have found two types of nucleation processes: a cluster that overcomes the critical size for nucleation with a monolayer, and a method that occurs with two layers. The Gibbs free energy changes (ΔG) for these two types of nucleation processes are evaluated by taking into account the effect of various interfacial energies. In contrast to homogeneous nucleation, the change in interfacial free energy, Δσ, is generated for colloidal nucleation on a foreign substrate such as a cover glass in the present study. The Δσ and step free energy of the first layer, γ1, are obtained experimentally based on the equation deduced from classical nucleation theory (CNT). It is concluded that the ΔG of q-2D nuclei is smaller than of monolayer nuclei, provided that the same number of particles are used, which explains the experimental result that the critical size in q-2D nuclei is smaller than that in monolayer nuclei.

Two-Dimensional Nucleation on the Terrace of Colloidal Crystals with Added Polymers.

Understanding nucleation dynamics is important both fundamentally and technologically in materials science and other scientific fields. Two-dimensional (2D) nucleation is the predominant growth mechanism in colloidal crystallization, in which the particle interaction is attractive, and has recently been regarded as a promising method to fabricate varieties of complex nanostructures possessing innovative functionality. Here, polymers are added to a colloidal suspension to generate a depletion attractive force, and the detailed 2D nucleation process on the terrace of the colloidal crystals is investigated. In the system, we first measured the nucleation rate at various area fractions of particles on the terrace, ϕarea. In situ observations at single-particle resolution revealed that nucleation behavior follows the framework of classical nucleation theory (CNT), such as single-step nucleation pathway and existence of critical size. Characteristic nucleation behavior is observed in that the nucleation and growth stage are clearly differentiated. When many nuclei form in a small area of the terrace, a high density of kink sites of once formed islands makes growth more likely to occur than further nucleation because nucleation has a higher energy barrier than growth. The steady-state homogeneous 2D nucleation rate, J, and the critical size of nuclei, r*, are measured by in situ observations based on the CNT, which enable us to obtain the step free energy, γ, which is an important parameter for characterizing the nucleation process. The γ value is found to change according to the strength of attraction, which is tuned by the concentration of the polymer as a depletant.

Taxol prevents myocardial ischemia-reperfusion injury by inducing JNK-mediated HO-1 expression.

CONTEXT: Ischemia/hypoxia and reperfusion impair mitochondria and produce a large amount of reactive oxygen species (ROS), which lead to mitochondrial and brain damage. Furthermore, heme oxygenase-1 (HO-1) as a cytoprotective gene protects cells against ROS-induced cell death in ischemia-reperfusion injury. Induction of HO-1 is involved in cytoprotective effects of taxol. OBJECTIVE: We hypothesize that taxol protects cardiac myocytes possibly by preserving myocardial mitochondrial function and inducing HO-1 expression through the JNK pathway. MATERIALS AND METHODS: In this project, the perfused Langendorff hearts isolated from rats were randomly divided into five groups: control, ischemic, ischemic + taxol (0.1 µM), ischemic + taxol (0.3 µM), and ischemic + taxol (1 µM). Briefly, following a 15 min equilibration period, the control group was subject to normoxic perfusion for 120 min; the ischemia group, normoxic reperfusion for 120 min after 30 min ischemia; the taxol groups, normoxic reperfusion for 120 min after 30-min ischemia with taxol (0.1, 0.3, or 1 µM). The microtubule disruption score, ROS levels, and the activity of mitochondrial electron transport chain complexes I and III were examined by using immunohistochemical methods and free radical detection kits. Western blot assay was employed to study the underlying mechanisms. RESULTS: After Taxol treatment (0.1 µM), the ischemic microtubule disruption score was reduced to 9.8 ± 1.9%. The study revealed that 0.1, 0.3, and 1 µM taxol reduced the level of ROS by 33, 46 and 51%, respectively (p < 0.05). In additional, 0.3 and 1 µM taxol dramatically increased the activity of mitochondrial electron transport chain complex I (99.11 ± 2.59, 103.49 ± 3.89) and mitochondrial electron transport chain complex III (877.82 ± 12.08; 907.42 ± 16.21; 914.73 ± 19.39, *p < 0.05). Additionally, phosphorylation levels of JNK1 were significantly increased in the taxol group. Furthermore, the expression level of HO-1 increased with taxol treatments, which could be inhibited by the specific inhibitor of JNK, SP600125. DISCUSSION AND CONCLUSION: Taxol stabilized microtubules and effectively reduced ROS levels during ischemia. It also preserved the activity of mitochondrial complexes I and III. Interestingly, taxol induced the expression of HO-1 via the JNK pathway in cardiac myocytes.

Association between 1019C/T polymorphism in the connexin 37 gene and essential hypertension.

OBJECTIVE: To investigate the association between the CX 37 1019C/T polymorphism and the susceptibility to essential hypertension (EH). METHODS: A total of 1126 cases of EH were diagnosed in the People's Hospital of Wuxi City, China. A control group consisted of 874 healthy people, i.e., non-EH patients. All cases were genotyped by DNA sequencing. RESULTS: Polymorphism C1019T on the Connexin37 gene was found in the whole population. The distribution of three genotype frequencies in both groups was in accordance with the Hardy-Weinberg equilibrium. The frequency of the CX37C allele was higher in EH patients (57.4% vs. 42.1%, χ(2)=92.5, P<0.01) compared to the control group. The frequency of C carriers (CC+TC) was 80.5% in EH patients compared to 66.7% in the control (χ(2)=49.0, P<0.01). EH risk was significantly increased in carriers of C the allele (CC+TC) over that in the TT homozygote (OR=2.06, 95% CI: 1.68 ∼ 2.52). Subsequent stratified analyses demonstrate that a significant difference exists in the frequency of C carriers between male EH patients and controls (79.2% vs. 69.1%, χ(2)=13.4, P<0.01) and in female EH patients and the control group (81.8% vs. 64.4%, χ(2)=38.7, P<0.01). The carriers of the C allele had higher EH risk compared with the TT homozygote without sex differences (male: OR=1.71, 95% CI: 1.28 ∼ 2.27; female: OR=2.48, 95%CI: 1.85 ∼ 3.31). CONCLUSION: The C allele in the CX37 gene might be associated with the susceptibility to EH in population of Wuxi, China.

[A multi-center survey on the therapeutic status of patients with acute myocardial infarction in Wuxi city of China].

OBJECTIVE: To explore the characteristics and therapies of patients with acute myocardial infarction (AMI) in Wuxi city, China. METHODS: A network was established to obtain information of patients with AMI who were admitted to 9 designated hospitals between 2011 and 2012. A total of 1 714 patients were enrolled (1 334 males, 754 smokers, 1 076 hypertension, 270 hyperlipidemia and 398 diabetes) including 1 410 patients with acute ST-segment elevation myocardial infarction (STEMI) and 304 patients with acute non ST-segment elevation myocardial infarction (NSTEMI). Patients' characteristics, therapies, the incidence of major adverse cardiovascular events (MACEs) and all-cause mortality were analyzed. RESULTS: (1) Medication therapy was as follows: antiplatelet therapy 98.3% (1 685 cases) , beta-blockers 59.1% (1 013 cases) , ACEI or ARB 67.6% (1 159 cases) , statins 98.1% (1 682 cases) , and nitrates 71.1% (1 218 cases) . Of the patients, 7.1% (132 cases) received temporary pacemakers, 34.0% (480 cases) with acute STEMI underwent reperfusion [direct PCI 18.4% (260 cases) and thrombolysis 15.6% (220 cases)]. (2) According to the hospital admission data, patients were divided into three groups: group A, transported to the hospital by ambulance (n = 361); group B, transported to the hospital by private vehicles (n = 1 318); and group C, AMI occurred in the hospital (n = 35). The median time of AMI onset to physician contact of the 3 groups was 178 min, 368 min, and 9 min, respectively. The median time from AMI onset to the first ECG was 181 min, 379 min, and 10 min, respectively. The median time from AMI onset to cardiology specialist consultation was 187 min, 431 min, and 69 min, respectively. AMI onset-to-physician contact, AMI onset-to-first ECG, and AMI onset-to-specialized treatment time was the shortest in group C, followed by group A and group B. For patients with STEMI underwent reperfusion therapy, the median AMI onset-to-reperfusion therapy time was significantly shorter in group A patients than group B patients [thrombolysis group: 224(171, 514) min vs. 378 (158, 785) min, PCI group: 318 (154, 674) min vs. 489 (143, 816) min, all P < 0.05]. (3) The total incidence of MACEs was 16.3% (279/1 714), the all-cause in-hospital mortality rate was 13.1% (224/1 714). According to the AMI onset-to-physician contact, patients were divided into 4 groups: <3 h, 3-6 h, 6-12 h, and >12 h. The incidence of MACEs [4.4% (23/517), 13.3% (60/451), 19.1% (77/404) and 34.8% (119/342),χ(2) = 114.36, P < 0.01] and all-cause in-hospital mortality rate [4.1% (21/517) , 10.4% (47/451), 18.6% (75/404), 23.7% (81/342), χ(2) = 84.36, P < 0.01] increased in proportion to the time of AMI onset-to-physician contact. Among STEMI patients, the incidence of MACEs [5.8% (15/260) , 12.3% (27/220) , 20.9% (194/930) ,χ(2) = 39.93, P < 0.01] and all-cause in-hospital mortality [1.5% (4/260) , 10.0% (22/220) , 18.2% (170/930) ,χ(2) = 50.90, P < 0.01] was the lowest in the primary PCI group, followed by thrombolysis group and was the highest in the early conservative treatment group. CONCLUSIONS: Guideline is well followed in terms of drug treatments of AMI in this cohort, but only a small proportion of AMI patients in Wuxi received reperfusion therapy. There is a considerable out-of-hospital time delay for AMI patients in this cohort which is shorter in group A than in group B. All-cause in-hospital mortality and MACEs is the lowest in AMI patients underwent primary PCI.

Gavage Strategy for Decoction Formula of Traditional Chinese Medicine in Osteosarcoma Model Mice.

Decoction formula is the most commonly used dosage form in traditional Chinese medicine and applied in clinical practice for thousands of years by trans-oral administration, which is characterized by quick effect, easy absorption, and individualized treatment based on the specific syndromes of patients. The quality of the decoction formula is directly responsible for the clinical efficacy of traditional Chinese medicine; therefore, the standardization process of the decoction formula is important to avoid differences in decoction quality caused by subjective factors. Meanwhile, due to the limitations of performing clinical experiments, small animals bearing human diseases, such as mice, are often used in medical research to explore the therapeutic efficacy and comprehensive mechanisms of different interventions, including the decoction formula for traditional Chinese medicine. Consequently, as an important trans-oral administration method, the skilled gavage technique is particularly important to avoid potential esophagus damage and drug spillage, which will ensure an equal amount of medicine being administered to each model animal, leading to accurate experimental results. Furthermore, the standardized method of decoction formula preparation and skilled gavage strategy are necessary to protect animal welfare and minimize the number of animals used. Here, we reported a detailed standardization process of the decoction formula and gavage technique with Yiqi Jiedu decoction in osteosarcoma mouse model as an example. The efficacy was evaluated by the tumor volume. This protocol will maximize animal protection and improve the reliability of research data, therefore providing effective strategies for future investigating therapeutic efficacy and molecular mechanisms of decoction formula for traditional Chinese medicine in vivo.

Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite the development of new treatment plans in recent years, the prognosis for osteosarcoma patients has not significantly improved. Therefore, it is crucial to establish a robust preclinical model with high fidelity. The patient-derived xenograft (PDX) model faithfully preserves the genetic, epigenetic, and heterogeneous characteristics of human malignancies for each patient. Consequently, PDX models are considered authentic in vivo models for studying various cancers in transformation studies. This article presents a comprehensive protocol for creating and maintaining a PDX mouse model that accurately mirrors the morphological features of human osteosarcoma. This involves the immediate transplantation of freshly resected human osteosarcoma tissue into immunocompromised mice, followed by successive passaging. The described model serves as a platform for studying the growth, drug resistance, relapse, and metastasis of osteosarcoma. Additionally, it aids in screening the target therapeutics and establishing personalized treatment schemes.

Radiomics analysis using magnetic resonance imaging of bone marrow edema for diagnosing knee osteoarthritis.

This study aimed to develop and validate a bone marrow edema model using a magnetic resonance imaging-based radiomics nomogram for the diagnosis of osteoarthritis. Clinical and magnetic resonance imaging (MRI) data of 302 patients with and without osteoarthritis were retrospectively collected from April 2022 to October 2023 at Longhua Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. The participants were randomly divided into two groups (a training group, n = 211 and a testing group, n = 91). We used logistic regression to analyze clinical characteristics and established a clinical model. Radiomics signatures were developed by extracting radiomic features from the bone marrow edema area using MRI. A nomogram was developed based on the rad-score and clinical characteristics. The diagnostic performance of the three models was compared using the receiver operating characteristic curve and Delong's test. The accuracy and clinical application value of the nomogram were evaluated using calibration curve and decision curve analysis. Clinical characteristics such as age, radiographic grading, Western Ontario and McMaster Universities Arthritis Index score, and radiological features were significantly correlated with the diagnosis of osteoarthritis. The Rad score was constructed from 11 radiological features. A clinical model was developed to diagnose osteoarthritis (training group: area under the curve [AUC], 0.819; testing group: AUC, 0.815). Radiomics models were used to effectively diagnose osteoarthritis (training group,: AUC, 0.901; testing group: AUC, 0.841). The nomogram model composed of Rad score and clinical characteristics had better diagnostic performance than a simple clinical model (training group: AUC, 0.906; testing group: AUC, 0.845; p < 0.01). Based on DCA, the nomogram model can provide better diagnostic performance in most cases. In conclusion, the MRI-bone marrow edema-based radiomics-clinical nomogram model showed good performance in diagnosing early osteoarthritis.

Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

The resolution and regeneration of a cointegrate plasmid reveals a model for plasmid evolution mediated by conjugation and oriT site-specific recombination.

Cointegrate plasmids are useful models for the study of plasmid evolution if their evolutionary processes can be replicated under laboratory conditions. pBMB0228, a 17 706 bp native plasmid originally isolated from Bacillus thuringiensis strain YBT-1518, carries two nematicidal crystal protein genes, cry6Aa and cry55Aa. In this study, we show that pBMB0228 is in fact a cointegrate of two plasmids and contains two functional replication regions and two functional mobilization regions. Upon introduction into B. thuringiensis strain BMB171, pBMB0228 spontaneously resolves into two constituent plasmids via recombination at its oriT1 and oriT2 sites. The resolution does not require conjugation but can be promoted by conjugation. We further confirm that the resolution is mediated by oriT site-specific recombination requiring Mob02281 or Mob02282. Additionally, the two constituent plasmids of pBMB0228 are mobilizable, and can fuse back via oriT site-specific integration after entering into the same cell by conjugation. Our study confirms that native plasmid can reversibly interconvert between a cointegrate structure and its constituent plasmids. This study provides insight into the evolution of cointegrate plasmids, linking plasmid evolution with conjugation and the oriT site-specific recombination function of relaxase.

[Association between 1019C/T polymorphism of Connexin 37 gene and restenosis after coronary stenting].

OBJECTIVE: To assess the association between 1019C/T polymorphism of Connexin 37 (CX37) gene and susceptibility to restenosis after percutaneous coronary intervention (PCI) in ethnic Han Chinese patients from Wuxi. METHODS: Five hundred and thirty-two patients with coronary artery disease (CAD) who had undergone PCI underwent coronary angiography (CAG) in 3 months, and were divided into in stent restenosis (ISR) group (n=67) and no instent restenosis (NISR) group (n=465). Five hundred and one healthy individuals have served as the control group. All cases were genotyped with DNA sequencing. RESULTS: Compared with healthy controls, the frequency of CX37 C allele was higher in CAD patients (57.05% vs. 41.32%, P< 0.01). The frequency of C carries (CC+TC) was 79.32% in CAD patients, against 65.47% in healthy controls (P<0.01). The risk for CAD was significantly increased in carriers of C allele (CC+TC) compared with TT homozygotes (OR=2.03, 95% CI: 1.53-2.80). Stratified analysis has indicated a significant difference in the frequency of C allele carriers between both male and female CAD patients and healthy controls (79.63% vs. 72.45%, P=0.02; 78.00% vs. 51.50%, P< 0.01). For both genders, carriers of C allele had a higher risk for CAD compared with TT homozygotes (males: OR=1.48, 95% CI: 1.06-2.09; females: OR=3.34, 95% CI: 1.90-5.86). Compared with NISR group, the frequency of CX37 C allele and C carries (CC+TC) were significantly higher in ISR group (72.39% vs. 54.84%, P< 0.01; 89.55% vs. 77.85%, P=0.027). Compared with TT homozygotes, the risk for restenosis has significantly increased in carriers of C allele (CC+TC) (OR=2.44, 95% CI: 1.08-5.50). Stratified analysis also suggested that the frequency of C carriers was significantly higher in male ISR group compared with male NISR group (92. 86% vs. 77.66%, P=0.008). The risk for restenosis has increased by nearly four fold in carriers of C allele (CC+TC) compared with TT homozygotes (95% CI: 1.32-10.64). However, for female patients, no significant difference was detected in the ISR risk between carriers of CC+TC type and TT homozygotes (P=0.655). CONCLUSION: The C allele of 1019C/T polymorphism in the CX37 gene is associated with susceptibility to CAD as well as restenosis after coronary stenting in male patients from Wuxi.

Clinical Efficacy of Small Needle Knife Therapy on Stage I-II Frozen Shoulder.

Frozen shoulder is a kind of aseptic inflammatory disease of the shoulder caused by strain, trauma, and other reasons, resulting in shoulder joint pain and limited function. The protocol presented here demonstrates the operation of a small needle knife in treating frozen shoulders, including patient management, material preparation, positioning, operation, and postoperative care. The purpose of this protocol is to relieve the pain and functional limitations and improve the living ability of patients with frozen shoulders. In our study, 76 stage I-II frozen shoulder patients who met the inclusion criteria were randomly divided into a control group and a treatment group (n=38). Patients in the control group received functional exercise, while the treatment group received small needle knife therapy with functional exercise. The visual analogue scores (VAS), the Constant and Murley scores (CMS), and the thickness of the coracohumeral ligament (CHL) under ultrasound were evaluated. After small needle knife therapy, the VAS score was significantly lower in the treatment group (5.11 ± 0.89) than in the control group (5.49 ± 0.65; t=-2.065, p<0.05); the CMS score was significantly higher in the treatment group (64.72 ± 4.78) than in the control group (60.97 ± 6.00; t=2.947, p<0.05); the CHL thickness was significantly decreased in the treatment group (2.38 ± 0.36) than in the control group (2.57 ± 0.42; t=-2.117, p<0.05). These results indicate that the small needle knife significantly relieved the pain symptoms, improved the shoulder function, reduced the CHL thickness, and improved the quality of life and, therefore, had significant therapeutic efficacy in stage I-II frozen shoulder patients.

Left Ventricle Segmentation in Echocardiography with Transformer.

Left ventricular ejection fraction (LVEF) plays as an essential role in the assessment of cardiac function, providing quantitative data support for the medical diagnosis of heart disease. Robust evaluation of the ejection fraction relies on accurate left ventricular (LV) segmentation of echocardiograms. Because human bias and expensive labor cost exist in manual echocardiographic analysis, computer algorithms of deep-learning have been developed to help human experts in segmentation tasks. Most of the previous work is based on the convolutional neural networks (CNN) structure and has achieved good results. However, the region occupied by the left ventricle is large for echocardiography. Therefore, the limited receptive field of CNN leaves much room for improvement in the effectiveness of LV segmentation. In recent years, Vision Transformer models have demonstrated their effectiveness and universality in traditional semantic segmentation tasks. Inspired by this, we propose two models that use two different pure Transformers as the basic framework for LV segmentation in echocardiography: one combines Swin Transformer and K-Net, and the other uses Segformer. We evaluate these two models on the EchoNet-Dynamic dataset of LV segmentation and compare the quantitative metrics with other models for LV segmentation. The experimental results show that the mean Dice similarity of the two models scores are 92.92% and 92.79%, respectively, which outperform most of the previous mainstream CNN models. In addition, we found that for some samples that were not easily segmented, whereas both our models successfully recognized the valve region and separated left ventricle and left atrium, the CNN model segmented them together as a single part. Therefore, it becomes possible for us to obtain accurate segmentation results through simple post-processing, by filtering out the parts with the largest circumference or pixel square. These promising results prove the effectiveness of the two models and reveal the potential of Transformer structure in echocardiographic segmentation.

Effects of resistance and balance exercises for athletic ability and quality of life in people with osteoporotic vertebral fracture: Systematic review and meta-analysis of randomized control trials.

Purpose: This study aimed to use meta-analysis to determine the impact of resistance and balance training on athletic ability and quality of life for patients with osteoporotic vertebral fracture (OVF). Methods: This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria for systematic reviews and meta-analyzes. The PubMed, Web of science, Cochrane, Embase, and CNKI databases were searched for randomized controlled trials (RCTs) up to September 2022. The search strategy was related to the intervention measures, population, and results, and was structured around the search terms: "Exercise," "Osteoporotic vertebral fracture," and "activities of function." Two reviewers strictly implemented the inclusion and exclusion criteria. Subgroup analyzes of age and training duration were performed for the main outcomes. Results: We included 12 RCTs (n = 1,289) of resistance and balance training in patients with OVF. Compared with controls, the intervention group showed improvements on the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis, visual analog pain scale, Timed Up and Go, falls efficacy scale international (FES-I), kyphosis, and functional reach. On subgroup analysis, the effect was more significant when training continued >10 weeks. Conclusion: Resistance and balance exercise training improved function and balance, and reduced fall risk in patients with OVF. We recommend resistance and balance training for at least 10 weeks. Future multicenter, large sample trials are needed for more reliable conclusions.

[Cathepsin B promoted the apoptosis of vascular smooth muscle cells as induced by tumor necrosis factor-α].

OBJECTIVE: To establish the cathepsin B over-expression group and cathepsin B gene-silencing group so as to investigate whether cathepsin B was capable of promoting the apoptosis of VSMC (vascular smooth muscle cell) induced by TNF-α/act D. METHODS: Human aortic smooth muscle cell (HA-VSMC) was transfected with pcDNA3.1-cathepsin B and pSilencer2.1-cathepsin B plasmids by lipofection to establish the over-expression and gene-silencing groups. Through TNF-α induced apoptosis, the cell viability was observed by MTT assay, morphological observation and assays of apoptotic proteins as indicators of apoptosis. RESULTS: The cathepsin B over-expression and gene-silencing group were successfully established. MTT assay showed no significant difference between the transfected cell and blank control. After the intervention of TNF-α, the HA-VSMC viability decreased significantly. As compared with control group, the over-expression group significantly decreased (9.98% ± 1.04% vs 14.60% ± 1.34%). As compared with the over-expression group, the E64d and CA-074ME groups (18.23% ± 1.05%, 17.40% ± 1.03%) increased significantly while the silent group (21.30% ± 2.37%) significantly increased. The analysis of acridine orange/ethidium bromide staining showed similar results. Western blot showed the Bcl-2 protein were significantly higher in the silent group than that in the control group. And the over-expression group was significantly lower than the control group. The E64d and CA-074ME groups were significantly higher than that in the over-expression group. But the Bax protein level had no significant difference among all groups. CONCLUSION: The over-expression of cathepsin B promotes TNF-α-induced VSMC apoptosis while Cathepsin B gene silencing and the addition of cathepsin inhibitor in over-expression group inhibit the TNF-α induced VSMC apoptosis.