Asiaticoside Mitigates Alzheimer's Disease Pathology by Attenuating Inflammation and Enhancing Synaptic Function.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, hallmarked by the accumulation of amyloid-ß (Aß) plaques and neurofibrillary tangles. Due to the uncertainty of the pathogenesis of AD, strategies aimed at suppressing neuroinflammation and fostering synaptic repair are eagerly sought. Asiaticoside (AS), a natural triterpenoid derivative derived from Centella asiatica, is known for its anti-inflammatory, antioxidant, and wound-healing properties; however, its neuroprotective function in AD remains unclear. Our current study reveals that AS, when administered (40 mg/kg) in vivo, can mitigate cognitive dysfunction and attenuate neuroinflammation by inhibiting the activation of microglia and proinflammatory factors in Aß1-42-induced AD mice. Further mechanistic investigation suggests that AS may ameliorate cognitive impairment by inhibiting the activation of the p38 MAPK pathway and promoting synaptic repair. Our findings propose that AS could be a promising candidate for AD treatment, offering neuroinflammation inhibition and enhancement of synaptic function.

The Impact of Food Processing on the Structure and Hypoglycemic Effect of Oat ß-glucan.

The impact of food processing including baking, steaming and bread making, on the structure and hypoglycemic effect of oat ß-glucan was studied. The structural analysis revealed the ß-D-glucopyranosyl units of ß-glucan was unchanged in aforementioned processing. The baking processing endowed ß-glucan with increased molecular weight (Mw) and viscosity, which enhanced the capacity of ß-glucan to delay starch digestion in vitro, such as the rapidly-digestible starch content decreased, the slowly-digestible and resistant starch content increased, and the glycemic index (GI) value decreased. Meanwhile, the inhibitory activity of ß-glucan against α-glucosidase and α-amylase was enhanced by baking processing. By contrast, during steaming and bread making processing, ß-glucan showed decreased Mw and viscosity, which accelerated starch digestion in vitro and reduced the inhibitory activity of ß-glucan against α-glucosidase and α-amylase. Apart from that, baking processing promoted the physiological and antioxidant properties of ß-glucan, but the properties decreased during steaming and bread making processing. The results suggest that oat raw materials can be treated with dry heat and high temperature, avoiding moist heat and fermentation treatments to maximize the hypoglycemic effect of ß-glucan.

Partial hydatidiform mole and coexisting fetus after frozen embryo transplantation: a case report.

Hydatidiform mole and coexisting fetus is a very rare condition of which etiology is still inconclusive. It may occur after assisted reproduction, often leading to the death of normal embryos and other serious complications. We report a case of partial hydatidiform mole and coexisting fetus after frozen embryo transplantation. More than two months after the patient underwent transplantation with two blastocysts (scored 4AB and 4BC), B-ultrasound showed a single live fetus with a large dense dotted strong echo area. The patient was treated with chemotherapy after the termination of pregnancy due to persistently increased human chorionic gonadotropin levels. Many studies have described trophoblast quality as a strong predictor of pregnancy. In the case in question, in addition to partial hydatidiform mole caused by multiple sperm entering the egg, we also speculate that the condition may be related to the poor quality of the trophoblastic ectoderm of the transferred embryo. In the process of assisted reproduction, the transfer of embryos with poor trophoblastic ectoderm in multiple embryo transfers may adversely affect pregnancy outcomes.

Deep Learning-Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.

Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aß, this study uses deep learning and a pharmacological approach to elucidate the potential of pyrroloquinoline quinone (PQQ) as a neuroprotective agent for AD. Using deep learning for a comprehensive molecular dataset, blood-brain barrier (BBB) permeability is predicted and the anti-inflammatory and antioxidative properties of compounds are evaluated. PQQ, identified in the Mediterranean-DASH intervention for a diet that delays neurodegeneration, shows notable BBB permeability and low toxicity. In vivo tests conducted on an Aß1₋42-induced AD mouse model verify the effectiveness of PQQ in reducing cognitive deficits. PQQ modulates genes vital for synapse and anti-neuronal death, reduces reactive oxygen species production, and influences the SIRT1 and CREB pathways, suggesting key molecular mechanisms underlying its neuroprotective effects. This study can serve as a basis for future studies on integrating deep learning with pharmacological research and drug discovery.

YOLOv8-ACU: improved YOLOv8-pose for facial acupoint detection.

Introduction: Acupoint localization is integral to Traditional Chinese Medicine (TCM) acupuncture diagnosis and treatment. Employing intelligent detection models for recognizing facial acupoints can substantially enhance localization accuracy. Methods: This study introduces an advancement in the YOLOv8-pose keypoint detection algorithm, tailored for facial acupoints, and named YOLOv8-ACU. This model enhances acupoint feature extraction by integrating ECA attention, replaces the original neck module with a lighter Slim-neck module, and improves the loss function for GIoU. Results: The YOLOv8-ACU model achieves impressive accuracy, with an mAP@0.5 of 97.5% and an mAP@0.5-0.95 of 76.9% on our self-constructed datasets. It also marks a reduction in model parameters by 0.44M, model size by 0.82 MB, and GFLOPs by 9.3%. Discussion: With its enhanced recognition accuracy and efficiency, along with good generalization ability, YOLOv8-ACU provides significant reference value for facial acupoint localization and detection. This is particularly beneficial for Chinese medicine practitioners engaged in facial acupoint research and intelligent detection.

Calcium signaling in oocyte quality and functionality and its application.

Calcium (Ca2+) is a second messenger for many signal pathways, and changes in intracellular Ca2+ concentration ([Ca2+]i) are an important signaling mechanism in the oocyte maturation, activation, fertilization, function regulation of granulosa and cumulus cells and offspring development. Ca2+ oscillations occur during oocyte maturation and fertilization, which are maintained by Ca2+ stores and extracellular Ca2+ ([Ca2+]e). Abnormalities in Ca2+ signaling can affect the release of the first polar body, the first meiotic division, and chromosome and spindle morphology. Well-studied aspects of Ca2+ signaling in the oocyte are oocyte activation and fertilization. Oocyte activation, driven by sperm-specific phospholipase PLCζ, is initiated by concerted intracellular patterns of Ca2+ release, termed Ca2+ oscillations. Ca2+ oscillations persist for a long time during fertilization and are coordinately engaged by a variety of Ca2+ channels, pumps, regulatory proteins and their partners. Calcium signaling also regulates granulosa and cumulus cells' function, which further affects oocyte maturation and fertilization outcome. Clinically, there are several physical and chemical options for treating fertilization failure through oocyte activation. Additionally, various exogenous compounds or drugs can cause ovarian dysfunction and female infertility by inducing abnormal Ca2+ signaling or Ca2+ dyshomeostasis in oocytes and granulosa cells. Therefore, the reproductive health risks caused by adverse stresses should arouse our attention. This review will systematically summarize the latest research progress on the aforementioned aspects and propose further research directions on calcium signaling in female reproduction.

Reduction-responsive dextran-based Pt(IV) nano-prodrug showed a synergistic effect with doxorubicin for effective melanoma treatment.

Melanoma, the deadliest skin cancer with high metastasis potential, has posed a great threat to human health. Accordingly, early efficient blocking of melanoma progression is vital in antitumor treatment. Herein, a reduction-responsive dextran-based Pt(IV) nano-prodrug (PDPN) was synthesized and used for doxorubicin (DOX) delivery to combat melanoma synergistically. First, PDPN was prepared by one-pot chemical coupling of carboxylated methoxy poly(ethylene glycol) (mPEG), dextran (Dex), and the crosslinking agent cisPt (IV)-COOH. PDPN had a spherical structure (Rh = 34 ± 11.3 nm). Then, DOX was encapsulated into the PDPN core to form DOX-loaded PDPN (PDPN-DOX). The obtained PDPN-DOX displayed reduction-responsive release of DOX and Pt, thus showing a synergistic anticancer effect in B16F10 cells (combination index, 0.46). Furthermore, in vivo experiments demonstrated that PDPN-DOX was effective for the synergistic treatment of subcutaneous melanoma. Collectively, the as-prepared PDPN could serve as a promising and versatile nano-prodrug carrier for the co-delivery of chemotherapeutics in tumor combination therapy.

Hydrocortisone Mitigates Alzheimer's-Related Cognitive Decline through Modulating Oxidative Stress and Neuroinflammation.

Alzheimer's disease (AD), an age-related degenerative disorder, is characterized by ß-amyloid deposition, abnormal phosphorylation of tau proteins, synaptic dysfunction, neuroinflammation, and oxidative stress. Despite extensive research, there are no medications or therapeutic interventions to completely treat and reverse AD. Herein, we explore the potential of hydrocortisone (HC), a natural and endogenous glucocorticoid known to have potent anti-inflammatory properties, in an Aß1-42-induced AD mouse model. Our investigation highlights the beneficial effects of HC administration on cognitive impairment, synaptic function enhancement, and neuronal protection in Aß1-42-induced AD mice. Notably, HC treatment effectively suppresses the hyperactivation of microglia and astrocytes, leading to a reduction in proinflammatory factors and alleviation of neuroinflammation. Furthermore, HC intervention demonstrates the capacity to mitigate the generation of ROS and oxidative stress. These compelling findings underscore the potential therapeutic application of HC in AD and present promising opportunities for its utilization in AD prevention and treatment. The implications drawn from our findings indicate that hydrocortisone holds promise as a viable candidate for adjunctive use with other anti-AD drugs for the clinical management of patients presenting with moderate to severe AD.

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration.

Alzheimer's disease (AD) is a leading neurodegenerative condition causing cognitive and memory decline. With small-molecule drugs targeting Aß proving ineffective, alternative targets are urgently needed. Neuroinflammation, which is central to AD's pathology, results in synaptic and neuronal damage, highlighting the importance of addressing inflammation and conserving neuronal integrity. Cannabidiol (CBD), derived from cannabis, is noted for its neuroprotective and anti-inflammatory properties, having shown efficacy in neuropathic pain management for epilepsy. To investigate the therapeutic efficacy of CBD in AD and to elucidate its underlying mechanisms, we aimed to contribute valuable insights for incorporating AD prevention recommendations into future CBD nutritional guidelines. Aß1-42 was employed for in vivo or in vitro model establishment, CBD treatment was utilized to assess the therapeutic efficacy of CBD, and RNA-seq analysis was conducted to elucidate the underlying therapeutic mechanism. CBD mitigates Aß-induced cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aß toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer's disease prevention.

Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-ß (Aß), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the pathogenesis of AD, currently main therapeutic interventions is limited to symptomatic alleviation. Methylprednisolone (MP), a synthetic glucocorticoid, is recognized for its extensive anti-inflammatory properties. Our study assessed the neuroprotective effect of MP (25 mg/kg) administration to an Aß1-42-induced AD mouse model. Our findings demonstrate that MP treatment can ameliorate cognitive impairment in Aß1-42-induced AD mice and suppress microglial activation in the cortex and hippocampus. RNA-Sequencing analysis reveals that MP ultimately rescues cognitive dysfunction through improving the synapse function and inhibiting the immune and inflammatory processes. Our study suggests that MP could be a promising drug alternative for the treatment of AD, either alone or in combination with other existing drugs.

Dual roles of demethylation in cancer treatment and cardio-function recovery.

There are no effective therapeutic targets or strategies that simultaneously inhibit tumour growth and promote cardiac function recovery. Here, we analyzed targets for cancer treatments and cardiac repair, with demethylation emerging as a common factor in these candidate lists. As DNA methyltransferase 1 (DNMT1) majorly responds to methylation, a natural compound library is screened, identifying dioscin as a novel agent targeted at DNMT1, widely used for heart diseases. Dioscin was found to reduce DNMT activities and inhibits growth in breast cancer cells. Combined with analyses of RNA-seq and MeDIP-seq, the promoters of antioxidant genes were demethylated after dioscin, recruiting NRF2 and elevating their expression. In Nrf2 knockout mice, the cardiac protection role of dioscin was blocked by Nrf2-loss. Furthermore, in tumour-bearing mice with hypertrophy, dioscin was observed to inhibit tumour growth and alleviate cardiac injury simultaneously. This study is the first to identify dioscin as a novel demethylation agent with dual functions of anti-cancer and cardio-protection.

Antifungal Activity of a Neodymium-Doped Yttrium Aluminum Garnet 1,064-Nanometer Laser against Sporothrix globosa by Inducing Apoptosis and Pyroptosis via the NLRP3/Caspase-1 Signaling Pathway: In Vitro and In Vivo Study.

Sporotrichosis is a deep fungal infection caused by Sporothrix species. Currently, itraconazole is the main treatment, but fungal resistance, adverse effects, and drug interactions remain major concerns, especially in patients with immune dysfunction. Therefore, an alternative treatment is greatly in demand. This animal study aimed to investigate the inhibitory effect of neodymium-doped yttrium aluminum garnet (Nd:YAG) 1,064-nm laser treatment on Sporothrix globosa and to explore whether it happens through regulation of the Nod-like receptor thermoprotein domain-related protein 3 (NLRP3)/caspase-1 pyroptosis and apoptosis pathway. After laser irradiation, a series of studies, including assays of viability (using the cell counting kit-8 [CCK-8]), morphological structure changes, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential, oxidative stress, cell cycle progression, and metacaspase activation, were conducted to estimate the effect of Nd:YAG 1,064-nm laser treatment on Sporothrix globosa cell apoptosis in vitro. For in vivo studies, mice were infected with S. globosa and then treated with laser or itraconazole, and their footpad skin lesions and the changes in the histology of tissue samples were compared. In addition, changes in the levels of NLRP3, caspase-1, and caspase-3 were assessed by immunohistochemistry, while the levels of interleukin 17 (IL-17), interferon gamma (IFN-γ), and transforming growth factor ß1 (TGF-ß1) in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). The in vitro growth of S. globosa was inhibited and apoptosis was observed after laser treatment. According to the in vivo studies, the efficacy of the laser treatment was similar to that of itraconazole. Moreover, the NLRP3/caspase-1 pyroptosis pathway was activated, with a Th1/Th17 cell response, and the expression of caspase-3 was also upregulated. Nd:YAG 1,064-nm laser treatment can effectively inhibit the growth of S. globosa by activating fungal apoptosis and pyroptosis through the NLRP3/caspase-1 pathway. Therefore, Nd:YAG 1,064-nm laser irradiation is an alternative for sporotrichosis therapy. IMPORTANCE Nd:YAG 1,064-nm laser irradiation is a useful alternative for the treatment of sporotrichosis, especially in patients with liver dysfunction, pregnant women, and children, for whom the administration of antifungal drugs is not suitable. It may improve the overall treatment effect by shortening the duration of antifungal treatment and reducing tissue inflammation.

Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa.

Improving clinical efficacy and reducing treatment time have been the focus of sporotrichosis therapy. Antimicrobial peptides ToAP2A, ToAP2C, and ToAP2D were synthesized on the basis of ToAP2 (AP02759), a peptide derived from the antimicrobial peptide database by the database filtering technology, and their physicochemical characteristics were analyzed. Compared with template peptide ToAP2, the modified peptides had much shorter length, lower molecular weight but significantly greater stability, which in return resulted in increases in the aliphatic index, hydrophilicity, and protein binding ability. Here, we show that the three derived peptides inhibit the growth of Sporothrix globosa, among which ToAP2D had the strongest anti-fungal activity. ToAP2D showed good serum stability without acute toxicity. The ToAP2D treatment inhibited the growth of S. globosa and enhanced apoptosis, which was evidenced by the upregulation of apoptosis-related protein caspase-3. The scanning electron microscopy analysis revealed deformation and rupture of S. globosa. The levels of mitochondrial membrane potential were decreased and that of the reactive oxygen species (ROS) were increased in S. globosa upon ToAP2D treatment. Moreover, ToAP2D activated metacaspase. In the in vivo study, we further demonstrated that ToAP2D inhibited the S. globosa infection of mice footpads, and its efficiency was nearly comparable to itraconazole. In summary, our results suggest that antimicrobial peptide ToAP2D has the potential for sporotrichosis therapy.

Multiscale Investigation into Chemically Stable NASICON Solid Electrolyte in Acidic Solutions.

Natrium superionic conductor (NASICON) solid electrolyte has been attracting wide attention due to its high ionic conductivity, low cost, and environmental friendliness. In this work, the chemical stability of the NASICON solid electrolyte with the composition of Na3Zr2Si2PO12 was evaluated in acidic solutions with different pH values, and the corrosion mechanism of the NASICON solid electrolyte was revealed at the multiscale level. Variations in bulk impedance, grain boundary impedance, and surface crack impedance with immersion time were determined by an AC impedance method. Comprehensive studies upon scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) etching, X-ray diffraction (XRD), and Raman spectroscopy, the morphological transformation, degradation limit depth, Cl- penetration effect, and proton exchange between H3O+ and Na+ were examined ranging from macro- and meso- to microscales, respectively. With the decrease of the pH of the solution, the exchange rate between H3O+ and Na+ protons increases. The lack of Na+ within the crystallographic lattice leads to the shrinkage of phosphorus-oxygen tetrahedra, which is the main reason for the decrease of unit cell volume, grain refinement, and surface cracks gradually. This work features multiscale characterizations of crystal structure, grain boundaries, surface morphology changes, and Na+ transport, which deepens our physicochemical understanding of solid electrolytes with high chemical stability.

Uncoupling protein 2 is upregulated in melanoma cells and contributes to the activation of Akt/mTOR and ERK signaling.

The aim of the present study was to characterize the expression of uncoupling protein 2 (UCP2) in melanoma and to study the potential mechanisms underlying the involvement of UCP2 in melanomagenesis using human melanoma cell lines. The expression of UCP2 was evaluated in specimens from normal control subjects, patients with compound nevus, and patients with cutaneous and mucosal melanoma. Stable knockdown of UCP2 was achieved in human melanoma cell lines, which were used to examine whether UCP2 knockdown affects the mitochondrial membrane potential and intracellular levels of ATP, reactive oxygen species and lactate. Cell proliferation, invasion, spheroid formation and cisplatin sensitivity were also evaluated in the UCP2 knockdown cells. Finally, the effects of UCP2 knockdown on the Akt/mammalian target of rapamycin (mTOR) and extracellular signal­regulated kinase (ERK) pathways, which are important oncogenic pathways during melanomagenesis, were evaluated. Relatively high expression of UCP2 was detected in human melanoma specimens, which was correlated with Clark level and Breslow thickness. Knockdown of UCP2 suppressed cell proliferation, invasion and spheroid formation, and increased the sensitivity of melanoma cells to cisplatin. Furthermore, the UCP2 knockdown cells exhibited inhibition of Akt/mTOR signaling and ERK activation. Therefore, human melanoma tissues exhibit relatively high UCP2 expression, which may be implicated in the mechanisms underlying tumor progression. The potential role of UCP2 in melanomagenesis may involve enhancing the Akt/mTOR and mitogen­activated protein kinase/ERK pathways.

Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma.

BACKGROUND: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. PURPOSE: We proposed a facile "in situ drug conjugation-induced self-assembly" strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma. METHODS: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)-b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model. RESULTS: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL. CONCLUSION: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.

Fungicidal efficacy of photodynamic therapy using methylene blue against Sporothrix globosa in vitro and in vivo.

Sporothrix schenckii strains are the aetiological agents of sporotrichosis, which is endemic in China. The most common clinical manifestation of sporotrichosis is cutaneous and subcutaneous nodular lesions with lymphangitis involvement. Currently, antifungal therapy is commonly used to treat sporotrichosis, however, drug resistance and complications are the major concerns, especially in patients who have asymptomatic liver injury or existing liver disorders, children, and pregnant women. To assess the in vitro and in vivo antifungal efficacy of photodynamic therapy (PDT) using photosensitizer methylene blue against Sporothrix strains isolated from patients. A light-emitting diode (LED) lamp was used as the light source with a wavelength of 640 ± 10 nm. For the in vitro study, the presence of five Sporothrix strains was assayed following LED irradiation with and without photosensitizer (L + M + , L + M-), with photosensitizer alone (L-M + ), or no exposure to LED light or photosensitizer (L-M-). For the in vivo study, mice were infected with the fungi and then treated with sodium chloride (control group), antifungal itraconazole alone (itraconazole group), and a combination of antifungal itraconazole and PDT (itraconazole +PDT group), or PDT alone (PDT group). The results showed that, in vitro, PDT (L + M + ) effectively inhibited fungal growth at an energy density of 40 J/cm2. In vivo, itraconazole + PDT effectively inhibited growth of the fungus with the highest level of efficacy. PDT with methylene blue is an effective adjuvant therapy for resistant infections of Sporothrix.

UCP2 gene polymorphisms in obesity and diabetes, and the role of UCP2 in cancer.

Mitochondria are the primary sites for ATP synthesis and free radical generation in organisms. Abnormal mitochondrial metabolism contributes to many diseases, including obesity, diabetes and cancer. UCP2 is an ion/anion transporter located in mitochondrial inner membrane, and has a crucial role in regulating oxidative stress, cellular metabolism, cell proliferation and cell death. Polymorphisms of the UCP2 gene have been associated with diabetes and obesity because UCP2 is involved in energy expenditure and insulin secretion. Moreover, UCP2 gene expression is often amplified in cancers, and increased UCP2 expression contributes to cancer growth, cancer metabolism, anti-apoptosis and drug resistance. The present review summarizes the latest findings of UCP2 with respect to obesity, diabetes and cancer.

Vitamin D levels in systemic sclerosis patients: a meta-analysis.

PURPOSE: This study aimed to investigate the association between vitamin D and systemic sclerosis (SSc) by meta-analysis. METHODS: A comprehensive search was performed through June 12, 2017. Pooled standardized mean difference (SMD) was used to estimate the mean vitamin D difference between case and control groups (or between diffused- and limited-type SSc). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used to assess the impact of vitamin D level on clinical characteristics of SSc patients. All statistical analyses were performed using Revman 5.0 software. RESULTS: The search yielded six studies with a total of 554 SSc patients and 321 healthy controls. The meta-analysis showed that SSc patients suffered from decreased vitamin D levels (SMD =-8.72 ng/mL; 95% CI: -10.11 to -7.32) compared with healthy controls. The meta-analysis results of three studies with 240 SSc patients (93 diffused-type and 147 limited-type SSc patients) showed that diffused-type SSc patients exhibited lower vitamin D levels (SMD =-4.71 ng/mL; 95% CI: -8.98 to -0.44) compared with limited-type SSc patients. However, vitamin D level was not found to be associated with Rodnan score (SMD =-2.29 ng/mL, 95% CI: -8.49 to 3.91, P=0.47), systolic pulmonary pressure (SMD =-1.68 ng/mL, 95% CI: -10.79 to 7.43, P=0.72), gastrointestinal ulcer (RR =1.01, 95% CI: 0.53-1.93, P=0.98), or pulmonary involvement (RR =1.01, 95% CI: 0.36-2.86, P=0.99) in SSc patients. CONCLUSION: SSc patients exhibited lower vitamin D levels compared with healthy controls. Vitamin D levels in diffused-type SSc patients were significantly lower than those in limited-type SSc patients. The severity of clinical features was not associated with the extent of vitamin D deficit. Therefore, we hypothesize that SSc patients, especially diffused type, have lower vitamin D levels, and that the decrease of vitamin D levels might not be an accelerating factor of SSc severity.

Mesial temporal lobe epilepsy presenting with rising epigastric sensation as the only clinical symptom: a case report.

Mesial temporal lobe epilepsy is generally manifested as central nervous system disorder, emotional disturbances, and visceral discomfort. We present the case of an elderly male patient with mesial temporal lobe epilepsy presenting with rising epigastric sensation as the only manifestation. A 60-year-old male patient who had been regularly suffering from episodic epigastric sensations three to seven times every day was admitted to our hospital. 'Rising air' initiated from epigastria, ascending to his chest, and terminated in the throat. Brain MRI showed sclerosis of the right hippocampus and enlargement of the right temporal horn. Video electroencephalography showed that the seizure was associated with a high-amplitude spike and slow wave, originating from the right anterior temporal region and extending to the leads in the right hemisphere. Extensive gastrointestinal and cardiothoracic investigations showed no abnormality, and so an underlying seizure disorder was suspected. The patient was prescribed a low dose of carbamazepine of 200 mg daily and was discharged the next day. A repeat video electroencephalography confirmed the satisfactory efficacy of the treatment. During the follow-up period of 22 months, there was no reappearance of epilepsy. Primary physicians, especially gastroenterologists, should be acquainted with the manifestations of simple partial seizures to avoid any dispensable medical examinations, even maltreatments.