Romosozumab has a dual effect on bones; it promotes bone formation and inhibits bone resorption and has a strong bone density-increasing effect. There have been various reports on the continuation rates of teriparatide, another drug used for osteoporosis treatment; however, there are few reports on the continuation rate of romosozumab. Therefore, this study aimed to examine the continuation rate of romosozumab and the factors affecting it, and to compare the continuation rates of romosozumab and teriparatide in a rural area. We retrospectively reviewed 199 patients with osteoporosis who were administered romosozumab monthly and teriparatide acetate preparation weekly or twice-weekly in an outpatient clinic. Patient information included age, sex, distance by road to the hospital, reason for the start of treatment, history of osteoporosis treatment and fracture, serum levels of some parameters, bone mineral density, adverse events, and a continuation period within one year. We compared differences in patient backgrounds and continuation rates among the romosozumab (ROM), twice-weekly teriparatide (TW), and weekly teriparatide (W) groups. Furthermore, we examined the factors influencing discontinuation in all patients. The continuation rate of the ROM group (88.9%) was significantly higher than that of the W group (70.2%) (P = 0.0358). In the Kaplan-Meier curves for treatment continuation, the ROM group showed a significantly higher continuation rate than the W group (P = 0.0202). Univariate analyses of all patients showed that romosozumab administration reduced the risk of discontinuation (P = 0.0450). Romosozumab has a considerably higher continuation rate than weekly teriparatide.
Chronic heart failure (CHF) is a prevalent condition with significant morbidity and mortality worldwide. Conventional treatments may not always be effective or may have considerable side effects. Warm yang and promote diuresis blood-activating method (WYLBAM), a traditional intervention, has been proposed as a complementary approach for CHF, but its clinical efficacy and impact on cardiac function have not been systematically evaluated. We performed a comprehensive meta-analysis to assess the clinical efficacy of WYLBAM for CHF. Following PRISMA guidelines, databases were searched for clinical trials comparing WYLBAM with standard care. Data on clinical efficacy rate, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic dimensions (LVEDD and LVESD), 6-minute walk test, and biomarkers BNP and NT-proBNP were extracted. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated with funnel plots and sensitivity analyses. Our search yielded 947 records, with 26 studies included after screening and eligibility assessment. Meta-analysis demonstrated a significant improvement in clinical efficacy rate, LVEF, LV dimensions, and 6-minute walk test distances in patients treated with WYLBAM. Biomarkers BNP and NT-proBNP also improved significantly, indicating a potential reduction in cardiac stress. The I² values suggested substantial heterogeneity, which was addressed through random-effects modeling. Publication bias was not evident in the funnel plot analyses. WYLBAM may be a beneficial adjunctive treatment for improving cardiac function and physical capacity in patients with CHF. However, the presence of heterogeneity suggests that individual patient factors should be considered when applying WYLBAM. Further well-designed large-scale RCTs are warranted to confirm these findings and to explore the underlying mechanisms of action.
Preeclampsia (PE) is a multisystem progressive disease unique to pregnancy, seriously affecting maternal and infant health. Previous studies have shown that PE is associated with changes in vascular endothelial cells, but the specific mechanism is unclear. In this study, we assessed the effects of chemokine C-X-C-motif receptor 4 (CXCR4) on endothelial cells and explored the potential mechanisms. Human placental microvascular endothelial cells (HPVEC) were exposed to protein Z (PZ), qRT-PCR and Western blotting were used to detect the expression of proliferation related genes and proteins, such as PI3K/Akt/ERK. Meanwhile, qRT-PCR and Western blotting were used to detect the expression of anticoagulation markers PGI2 and t-PA. Then, HPVEC were transfected with CXCR4 siRNA or NC siRNA. The expression of proliferation related genes and proteins were also detected. Finally, PZ and CXCR4 were co-cultivated with different fluorescent labels, the binding sites of the two proteins were observed under confocal laser scanning microscopy (CLSM). PZ promoted the proliferation and expression of anticoagulant markers PGI2 and t-PA in HPVEC. CXCR4 silencing could inhibit the proliferation of HPVEC which stimulated by PZ. CLSM showed that the binding site of PZ and CXCR4 was located on the cell membrane. In conclusion, our results suggested that PZ promote the expression of PGI2/t-PA and affect the PI3K/Akt/ERK signaling pathway by binding with CXCR4 which improved our understanding of the molecular mechanisms involved in HPVEC.
The use of dexamethasone in premature infants has adverse effects on neurological function. Vitamin D is considered to be vital nutrient for neurological diseases. Pups were randomly divided into the control, model and treated groups. Treated group received vitamin D on postnatal day1 (60,000 IU/kg). Following, model and treated group received dexamethasone from postnatal day 2 to postnatal day 4 following tapering doses (0.5, 0.3, and 0.1 mg/kg.d, respectively). Pups’ neurological function was assessed by wire-hanging test and Morris water maze task. And apoptotic cells in hippocampus were counted. Vitamin D effectively improved spatial learning and memory impairment induced by dexamethasone. The protective effects of vitamin D may be related to the modulation of apoptosis. Vitamin D may therefore have a role in bronchopulmonary dysplasia treatment process.
Synthetic octacalcium phosphate (OCP) has emerged as a potential precursor for bone apatite crystals, promoting faster bone formation and better biodegradability compared to hydroxyapatite and β-tricalcium phosphate materials. Combining OCP with various polymeric biomaterials enhances its ductility, making it suitable for clinical applications, including dentistry. Preclinical studies on OCP/gelatin (OCP/Gel) composites have shown excellent osteoconductive and osteoinductive properties, indicating potential for bone defect repairs. This study investigates the efficacy of OCP/Gel as a filler for lumbar interbody fusion cages. A miniature swine model underwent surgery using polyetheretherketone (PEEK) cages with different fillers: no filler, autologous rib, and OCP/Gel. Eight weeks post-surgery evaluations using computed tomography, histological assessments, and Fourier transform infrared (FT-IR) spectroscopy revealed that while PEEK cages without fillers showed no bone fusion, those with autologous rib and OCP/Gel demonstrated partial interbody fusion. Histological analysis indicated new bone growth in cages with OCP/Gel, and FT-IR spectroscopy confirmed the degradation of OCP at the vertebral interface and increased bone matrix proteins. The findings suggest that OCP/Gel could be a viable alternative to autologous bone grafts for lumbar interbody fusion surgeries, offering less invasive and more cost-effective solutions. The success of OCP/Gel in clinical applications could pave the way for broader use in orthopedic reconstructive surgeries, potentially eliminating the need for combined use of bone marrow aspirate or expensive growth factors.
Traditional treatments for heart disease, including pharmacotherapy and surgical interventions, are effective in managing symptoms and preventing complications but often fail to fully restore cardiac function or halt the progression of the disease. Additionally, these approaches are frequently associated with significant adverse effects. Inspired by the success of CAR-T cell therapy in oncology, this review examines the potential of CAR-T cell technology for treating heart diseases, detailing how CAR-T cells, engineered by merging antibody-derived targeting domains with T-cell signaling domains. The technology’s core includes an extracellular antigen-binding domain, hinge region, transmembrane domain, and intracellular signaling domain, with the single-chain variable fragment (scFv) playing a crucial role in antigen recognition. The paper delves into the immune mechanisms in cardiovascular diseases like heart failure, hypertension, and myocardial infarction, focusing on the roles of T cells in promoting myocardial fibrosis and the therapeutic potential of regulatory T cells (Tregs) in recovery phases. Additionally, it explores the use of lipid nanoparticles (LNPs) carrying mRNA to produce transient, non-integrative CAR-T cells targeting fibroblast activation protein (FAP) to reduce myocardial fibrosis, a method showing promise in preclinical models by enhancing cardiac function and reducing ventricular fibrosis. Despite its potential, the study acknowledges challenges in clinical translation, such as limited therapeutic effects and severe inflammatory responses, highlighting the need for further optimization and research in CAR-T cell technology for cardiovascular disease treatment.
Histon deacetylase 4 (HDAC4) modulates memory and cognitive impairment, but its association with post-stroke cognitive impairment (PSCI) is unclear. This study aimed to investigate the potential of HDAC4 for predicting PSCI risk. Sixty-nine PSCI patients and 70 control post-stroke (CPS) patients were enrolled in this case-control study. In all stroke patients, HDAC4 in peripheral blood mononuclear cells was detected by quantitative polymerase chain reaction; T-helper 17 (Th17) cells were detected by flow cytometry, and interleukin-17A was detected by enzyme-linked immunosorbent assay. HDAC4 was reduced in PSCI patients compared with CPS patients (P = 0.001). In total stroke patients, HDAC4 showed negative linkages with age (P = 0.003), history of diabetes (P = 0.012), stroke recurrence (P = 0.001), Th17 cells (P = 0.027), and interleukin-17A (P = 0.002). Additionally, multivariate logistic regression analysis revealed that HDAC4 (per unit) [odds ratio (OR) = 0.438, P = 0.024] was independently associated with a lower PSCI risk, but age (per unit) (OR = 1.061, P = 0.016) and multifocal disease (yes vs. no) (OR = 2.490, P = 0.014) were independently associated with a higher PSCI risk. By receiver operator characteristic curves, HDAC4 had an acceptable value for predicting PSCI risk [area under the curve (AUC) = 0.656, 95% confidence interval = 0.566-0.746]. The combination of HDAC4, age, and multifocal disease showed a good value for predicting PSCI risk (AUC = 0.728, 95% confidence interval = 0.644-0.811). HDAC4 may serve as a potential biomarker for predicting PSCI risk, which could facilitate the early screening and prevention of PSCI, thus promoting the management of stroke.
Japan has the largest aged population globally, and the number of older people requiring medical and long-term care is increasing yearly. Therefore, providing older people with appropriate medical and long-term care in their living setting is essential. This study will clarify the characteristics of older patients who started medical and long-term care in their place of living following acute inpatient treatment, focusing on the differences between their homes and nursing homes. The analysis was conducted using Japan’s nationwide administrative database. We collected discharge records of patients aged 65 and older who received acute inpatient treatment. Those who started medical and long-term care at home or admission a nursing home at the time of discharge were selected and categorized into the home group and the nursing home group. Patient characteristics were shown by group, and factors determining group differences were estimated using univariate and multivariate logistic regression analysis. We selected 89,705 people in the home group and 92,969 in the nursing home group. The home group had a significantly higher rate of cancer, while the nursing home group had a significantly higher age, long-term care need level, and dementia. It became clear that the home group was highly dependent on medical care, and the nursing home group was highly reliant on long-term care. Furthermore, the age group of those admissions to nursing homes varied by sex. These results are expected to provide basic information useful in practice for medical professionals, care workers, and policymakers.
Gastric cancer (GC) is one deadly malignancy globally. The potential clinical values of circular RNAs (circRNAs) in cancer diagnosis, prognosis, and treatment have been demonstrated in increasing studies. This research aimed at delving into the specific role of circRNA hsa_circ_0007376 (circMAP2K2) in GC development. CircMAP2K2, miR-556-5p, and CREB5 levels in GC cells and tissues were tested by RT-qPCR. Subcellular fractionation assay was employed for determining the distribution of circMAP2K2 in GC cell cytoplasm and nucleus. The binding potentials between circMAP2K2 (or CREB5) and miR-556-5p were confirmed through luciferase reporter assay. GC cell viability, growth, and metastasis were examined via CCK-8, colony formation, and Transwell assays. CREB5 protein level was assessed via western blot analysis. CircMAP2K2 was upregulated in GC cells and tissues vs. normal controls. CircMAP2K2 depletion hindered GC cell growth, migration, and invasion. Mechanically, circMAP2K2 elevated CREB5 level by completely binding with miR-556-5p. Overexpressing CREB5 abrogated the suppression of circMAP2K2 silencing on GC cell malignant behaviors. CircMAP2K2/miR-556-5p/CREB5 axis plays an oncogenic role in GC tumorigenesis.
Analyzing the pathogenic mechanism of dry eye disease provides a new research point for the treatment of patients. A total of 86 patients with dry eye disease and the same number of healthy individuals were recruited as the patient group and normal group. The levels of small nucleolar RNA host gene 7 (SNHG7) in tear samples and human conjunctival epithelial cells (HCECs) were determined by a quantitative real-time PCR (RT-qPCR). Meanwhile, TNF-α and IL-6 mRNA levels in HCECs were also detected by RT-qPCR. The molecular mechanism of SNHG7 was analyzed by biological prediction and luciferase activity assay. The correlation between the expression of SNHG7 and microRNA-146a-5p (miR-146a-5p) with clinical indicators in dry eye disease patients using Pearson analysis. SNHG7 expression in tears samples and HCECs from dry eye disease patients was significantly increased (P < 0.001). The levels of TNF-α mRNA and IL-6 mRNA were upregulated in the HCECs model group while silencing SNHG7 suppressed their expression (P < 0.05). SNHG7 level was negatively correlated with miR-146a-5p, break-up time (BUT) and Schirmer’s test (SIT) value, while positively correlated with corneal fluorescein staining (CFS) score (P < 0.001). miR-146a-5p was positively proportional to BUT and SIT, and inversely proportional to CFS score (P < 0.001). SNHG7 expression was enhanced, while miR-146a-5p expression was decreased in dry eye disease. Down-regulation of SNHG7 reduced the level of inflammation in HCECs. SNHG7 and miR-146a-5p were closely related to the development of disease, probably as biological targets for treatment in dry eye disease.
The infection of Vibrio vulnificus (V. vulnificus) can cause numerous clinical manifestations with high mortality. Aquatic products and sea water are typically the primary routes of infection. This article narrates a case of V. vulnificus infection in a farmer from an inland mountain area, who, unusually, contracted the infection through insect-borne transmission. The patient had a medical history of fatty liver disease and chronic alcohol consumption, which significantly increased the risk of V. vulnificus infection. He presented with swelling and pain in the lower left leg, along with scattered areas of skin necrosis and localized hemorrhagic bullae. His condition rapidly progressed to septic shock. Regrettably, the patient suffered a cardiac arrest during an emergency fasciotomy and passed away within 12 hours of admission. The retrospective analysis of this case aims to re-examine the way of infection of the disease, improve the understanding of clinicians in non-coastal areas of V. vulnificus infection, and achieve early diagnosis and treatment.