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1.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38892321

RESUMEN

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype-phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5' truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3' truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins.


Asunto(s)
Amelogénesis Imperfecta , Amelogenina , Estudios de Asociación Genética , Mutación , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/patología , Humanos , Amelogenina/genética , Masculino , Femenino , Linaje , Fenotipo , Niño , Estrés del Retículo Endoplásmico/genética , Genotipo , Secuenciación del Exoma
2.
J Environ Manage ; 362: 121370, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38838536

RESUMEN

Bamboos are fast-growing, aggressively-spreading, and invasive woody clonal species that often encroach upon adjacent tree plantations, forming bamboo-tree mixed plantations. However, the effects of bamboo invasion on leaf carbon (C) assimilation, and nitrogen (N) and phosphorus (P) utilization characteristics remains unclear. We selected four different stands of Pleioblastus amarus invading Chinese fir (Cunninghamia lanceolata) plantations to investigate the concentrations, stoichiometry, and allometric growth relationships of mature and withered leaves of young and old bamboos, analyzing N and P utilization and resorption patterns. The stand type, bamboo age, and their interaction affected the concentrations, stoichiometry and allometric growth patterns of leaf C, N, and P in both old and young bamboos, as well as the N and P resorption efficiency. Bamboo invasion into Chinese fir plantations decreased leaf C, N, and P concentrations, C:N and C:P ratios, N and P resorption efficiency, and allometric growth exponents among leaf C, N, and P, while it only slightly altered N:P ratios. PLS-PM analysis revealed that bamboo invasion negatively impacted leaf C, N, and P concentrations, as well as N and P utilization and resorption. The results indicate that high N and P utilization and resorption efficiency, along with the mutual sharing of C, N, and P among bamboos in interface zones, promote continuous bamboo expansion and invasion. Collectively, these findings highlight the significance of N and P utilization and resorption in bamboo expansion and invasion and provide valuable guidance for the establishment of mixed stands and the ecological management of bamboo forests.


Asunto(s)
Nitrógeno , Nitrógeno/metabolismo , Especies Introducidas , Fósforo/análisis , Hojas de la Planta/metabolismo , Carbono , Poaceae/crecimiento & desarrollo , Nutrientes/metabolismo , Árboles , Cunninghamia/crecimiento & desarrollo , Cunninghamia/metabolismo , Sasa/metabolismo
3.
Pract Lab Med ; 40: e00408, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38883564

RESUMEN

Background: Iatrogenic blood loss is an important cause of neonatal anemia. In this study, a spreadsheet tool was developed to reduce blood collection, providing a new idea for the prevention of iatrogenic blood loss in newborns. Methods: Based on hematocrit, minimum test volume and dead volume, a new tool was to calculate the minimum blood collection volume and the number of containers required for the test portfolio. We collected data from October 2022 to October 2023 from Xiamen Maternal and Child Health Hospital for analysis and validation. Results: During this year, there were 16,434 patients and 13,696 plasma/serological samples in the neonatology department. Among them, there were 8 test combinations of greater than 1%, and 9490 samples in total. According to the hospital manual, the recommended amount of blood collection is 27,534 ml and 9490 containers. Through the analysis of this tool, total blood collection was 8864.77 ml, marked qnantity of upward containers (closest level to the calculated blood collection volume) was 10301 ml, and the amount of containers was 8835, which decreased by 67.8%, 62.58% and 6.9% respectively. Besides, if the hematocrit information cannot be obtained in advance and the high hematocrit is calculated as 0.8, the recommended amount of blood collection is 14334.3 ml, and the marked amount of the upward container markering is 17340 ml, decreasing by 47.9% and 37.02% respectively. Conclusion: We have developed an auxiliary tool that can manage neonatal blood specimen collection in a fine and personalized way and can be applied among different laboratory instruments by parameters modification.

4.
Sci Bull (Beijing) ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38734586

RESUMEN

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

5.
Pharm Biol ; 62(1): 472-479, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38769628

RESUMEN

CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.


Asunto(s)
Enfermedades de la Mama , Medicamentos Herbarios Chinos , Hiperplasia , Medicina Tradicional China , Humanos , Femenino , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Enfermedades de la Mama/tratamiento farmacológico , Medicina Tradicional China/métodos , China
6.
Dalton Trans ; 53(21): 9011-9020, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38726692

RESUMEN

The development of efficient non-noble metal electrocatalysts for the oxygen evolution reaction (OER) under acidic conditions remains a critical challenge. Herein, we report a N-doped carbonaceous component-engineered Co3O4 (NCEC) catalyst synthesized via the sol-gel method. Dopamine hydrochloride (DA)-derived nitrogen-doped carbonaceous components were found to boost the OER performance of Co3O4. The optimized catalyst can reach an overpotential as low as 330 mV in 1 M H2SO4 at a current density of 10 mA cm-2 and maintains a good long-term stability of 60 hours. In particular, we found that the thermodynamic overpotential was inversely proportional to the content of oxidized N and pyridinic N, whereas it was directly proportional to the pyrrolic-N content. Our experiments and density functional theory (DFT) calculations confirm that the optimized catalyst exhibits enhanced charge transfer and the oxidized N species on Co3O4 is responsible for the high catalytic activity. Our study suggests that the performance of NCEC in acidic media can be further optimized by enhancing the content of oxidized N species.

7.
Ann Hematol ; 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38761184

RESUMEN

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

8.
Inorg Chem ; 63(16): 7412-7421, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38600810

RESUMEN

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

9.
Heliyon ; 10(8): e29671, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38660243

RESUMEN

Background: The Proximal Femoral Nail Antirotation (PFNA) device is the most commonly used implant to fix unstable femoral trochanteric fractures (UFTFs), but it has a relatively high incidence of complications. Due to this factor, the modified intramedullary nail (MIN) was created to treat patients with UFTFs. The aim was to exhibit the MIN and make a comparison with PFNA and InterTAN using biomechanical methods. Methods: An adult UFTF model was developed using Mimics software. The PFNA, InterTAN nail, and MIN models were drawn referring to the corresponding parameters and installed in the fracture models. Vertical, anteroposterior (AP) bending, and torsion loads of the femoral head were set in advance and loaded onto the fracture models. The value of maximal displacement and von Mises stress was evaluated via finite element analysis (FEA). Results: The MIN model had smaller values for maximal displacement than that of the PFNA model, and the increase in displacement was less pronounced for the MIN compared to PFNA under increasing vertical loads. For the indicator of von Mises stress, the MIN model showed lower stress compared with the PFNA model in vertical loads ranging from 300 N to 2100 N. Except for the maximal stress at implants under AP bending loads, the MIN demonstrated the most superior biomechanical properties under AP bending and torsional loads. Conclusion: The MIN offered obvious advantages in terms of mechanical stability and stress distribution among the three studied implants, providing a promising implant option for patients with UFTFs.

10.
Chem Sci ; 15(16): 5869-5896, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665521

RESUMEN

With the continuous development of laser technology and the increasing demand for lasers of different frequencies in the infrared (IR) spectrum, research on infrared nonlinear optical (NLO) crystals has garnered growing attention. Currently, the three main commercially available types of borate materials each have their drawbacks, which limit their applications in various areas. Rare-earth (RE)-based chalcogenide compounds, characterized by the unique f-electron configuration, strong positive charges, and high coordination numbers of RE cations, often exhibit distinctive optical responses. In the field of IR-NLO crystals, they have a research history spanning several decades, with increasing interest. However, there is currently no comprehensive review summarizing and analyzing these promising compounds. In this review, we categorize 85 representative examples out of more than 400 non-centrosymmetric (NCS) compounds into four classes based on the connection of different asymmetric building motifs: (1) RE-based chalcogenides containing tetrahedral motifs; (2) RE-based chalcogenides containing lone-pair-electron motifs; (3) RE-based chalcogenides containing [BS3] and [P2Q6] motifs; and (4) RE-based chalcohalides and oxychalcogenides. We provide detailed discussions on their synthesis methods, structures, optical properties, and structure-performance relationships. Finally, we present several favorable suggestions to further explore RE-based chalcogenide compounds. These suggestions aim to approach these compounds from a new perspective in the field of structural chemistry and potentially uncover hidden treasures within the extensive accumulation of previous research.

11.
J Wound Care ; 33(4): 262-270, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38573899

RESUMEN

OBJECTIVE: This study examined changes in wound symptoms and the health-related quality of life (HRQoL) of patients with newly diagnosed malignant fungating wounds, and explored the factors that impacted the changes in HRQoL. METHOD: This prospective longitudinal study included patients from three hospitals in China who had been diagnosed with malignant fungating wounds. Questionnaires were used to assess patients' HRQoL and their wound symptoms at the time of diagnosis (T0), as well as at one, three and six (T1, T2 and T3, respectively) months following the treatment period. Factors related to changes in HRQoL were analysed using generalised estimating equation models. RESULTS: A total of 162 patients were included in the study. The patients reported low overall HRQoL. In three health-related dimensions (functional status, social relations and mental health), patients reported lower functional status at the time of wound diagnosis (T0), which then increased slowly with treatment over time. A lower QoL was associated with odour, exudate, bleeding, pruritus, a low performance status and the need for the dressing of wounds. CONCLUSION: The HRQoL of patients with malignant fungating wounds exhibited significant changes across different periods. It is thus of great importance to formulate pragmatic, patient and family-centred palliative wound care management strategies.


Asunto(s)
Calidad de Vida , Heridas y Lesiones , Humanos , Estudios Prospectivos , Estudios Longitudinales , Vendajes , Hemorragia , Heridas y Lesiones/terapia
12.
J Cancer Res Clin Oncol ; 150(4): 189, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605258

RESUMEN

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).


Asunto(s)
Antineoplásicos , Arsénico , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Antineoplásicos/efectos adversos , Arsénico/uso terapéutico , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pandemias , Resultado del Tratamiento
13.
World J Gastrointest Surg ; 16(2): 601-608, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38463350

RESUMEN

BACKGROUND: Gastric stromal tumors, originating from mesenchymal tissues, are one of the most common tumors of the digestive tract. For stromal tumors originating from the muscularis propria, compared with conventional endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR) can remove deep lesions and digestive tract wall tumors completely. However, this technique has major limitations such as perforation, postoperative bleeding, and post-polypectomy syndrome. Herein, we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR. Feasible treatment options to address this complication are described. CASE SUMMARY: A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography, located at the upper gastric curvature adjacent to the stomach fundus, with a smooth surface mucosa and poor mobility. The lesion was 19.3 mm × 16.1 mm in size and originated from the fourth ultrasound layer. Computed tomography (CT) revealed no significant evidence of lymph node enlargement or distant metastasis. Using conventional ESD technology for mucosal pre-resection, exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis. Based on its morphology and immunohistochemical expression of CD117 and DOG-1, the lesion was proven to be consistent with a gastric stromal tumor. Six days after exposed EFTR, CT showed a large amount of encapsulated fluid and gas accumulation around the stomach. In addition, gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding. Based on these findings, the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor. The patient received combined treatments, such as hemostasis under gastroscopy, gastrointestinal decompression, and abdominal drainage. All examinations were normal within six months of follow-up. CONCLUSION: This patient developed serous surface bleeding in the gastric cavity following exposed EFTR. Serosal bleeding resulting in an encapsulated hemoperitoneum is rare in clinical practice. The combined treatment may replace certain surgical techniques.

14.
Org Lett ; 26(12): 2495-2499, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38506235

RESUMEN

The selective functionalization of remote C-H bonds in free primary amines holds significant promise for the late-stage diversification of pharmaceuticals. However, to date, the direct functionalization of the meta position of amine substrates lacking additional directing groups remains underexplored. In this Letter, we present a successful meta-C-H arylation of free primary amine derivatives using aryl iodides, resulting in synthetically valuable yields. This meta-selective C-H functionalization is achieved through a sequence involving native amino-directed Pd-catalyzed seven-membered cyclometalation, followed by the utilization of a norbornene-type transient mediator.


Asunto(s)
Aminas , Paladio , Aminas/química , Paladio/química , Estructura Molecular , Catálisis , Norbornanos/química
15.
Photodermatol Photoimmunol Photomed ; 40(2): e12957, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38470033

RESUMEN

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.


Asunto(s)
Trastorno Depresivo Mayor , Terapia por Luz de Baja Intensidad , Humanos , Trastorno Depresivo Mayor/terapia , Proyectos Piloto , Electroencefalografía , Estimulación Magnética Transcraneal
16.
Cereb Cortex ; 34(3)2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38517175

RESUMEN

Intermittent theta-burst stimulation (iTBS) is emerging as a noninvasive therapeutic strategy for Alzheimer's disease (AD). Recent advances highlighted a new accelerated iTBS (aiTBS) protocol, consisting of multiple sessions per day and higher overall pulse doses, in brain modulation. To examine the possibility of applying the aiTBS in treating AD patients, we enrolled 45 patients in AD at early clinical stages, and they were randomly assigned to either receive real or sham aiTBS. Neuropsychological scores were evaluated before and after treatment. Moreover, we detected cortical excitability and oscillatory activity changes in AD, by the single-pulse TMS in combination with EEG (TMS-EEG). Real stimulation showed markedly better performances in the group average of Auditory Verbal Learning Test scores compared to baseline. TMS-EEG revealed that aiTBS has reinforced this memory-related cortical mechanism by increasing cortical excitability and beta oscillatory activity underlying TMS target. We also found an enhancement of local natural frequency after aiTBS treatment. The novel findings implicated that high-dose aiTBS targeting left DLPFC is rapid-acting, safe, and tolerable in AD patients. Furthermore, TMS-related increase of specific neural oscillation elucidates the mechanisms of the AD cognitive impairment ameliorated by aiTBS.


Asunto(s)
Enfermedad de Alzheimer , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Enfermedad de Alzheimer/terapia , Corteza Prefrontal/fisiología , Encéfalo , Corteza Prefontal Dorsolateral
17.
J Diabetes Investig ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426644

RESUMEN

Insulin-deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi-closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high-risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin-producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin-deficient diabetes, these inhibitors have resulted in robust glucose-lowering responses and generation of insulin-producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 19-24, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38433626

RESUMEN

Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy. Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for complementary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diversity and caregiver self-efficacy for complementary feeding of infants and young children. Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56%(474/770) for all the infants and young children and 45.00%(108/240),69.16%(287/415),and 68.70%(79/115) for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respectively.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing factor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR=1.42,95%CI=1.17-1.73,P<0.001). Conclusion The dietary diversity for infants and young children in rural Nanchong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.


Asunto(s)
Cuidadores , Autoeficacia , Niño , Lactante , Humanos , Preescolar , Dieta , China
19.
J Obstet Gynaecol ; 44(1): 2321321, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38425012

RESUMEN

BACKGROUND: The aim was to assess the causal relationship between depression and anxiety disorders and endometrial cancer. METHOD: We performed two-sample Mendelian randomisation analysis using summary statistics from genome-wide association studies to assess associations of major depressive disorder, anxiety and stress-related disorders with endometrial cancer. The genome-wide association studies(GWASs) data were derived from participants of predominantly European ancestry included in the Genome-wide Association Research Collaboration. Inverse variance-weighted, MR-Egger and weighted median MR analyses were performed, together with a range of sensitivity analyses. RESULTS: Mendelian randomisation analysis showed no statistically significant genetic responsibility effect of anxiety and stress-related disorders on any pathological type of endometrial cancer. Only the effect of major depressive disorder under the inverse variance weighting method increasing the risk of endometrial endometrial cancer (effect 0.004 p = 0.047) and the effect of major depressive disorder under the MR-Egger method decreasing endometrial cancer of all pathology types (effect -0.691 p = 0.015) were statistically significant. Other Mendelian randomisation analyses did not show a statistically significant effect. CONCLUSION: Major depressive disorder(MDD), anxiety and stress-related disorders(ASRD) are not genetically responsible for endometrial cancer. We consider that emotional disorders may affect endometrial cancer indirectly by affecting body mass index. This study provides us with new insights to better understand the aetiology of endometrial cancer and inform prevention strategies.


This study used public genomic data to analyse association between affective disorders, including depression and anxiety, and endometrial cancer. Genes treated as instrumental variables help us understand the causal link between affective disorders and endometrial cancer through bioinformatics. In addition to this, we added type 2 diabetes, body mass index, polycystic ovary syndrome, and age at menopause for multivariate Mendelian randomisation analyses with the aim of reducing confounding bias. Because we consider these factors may potentially influence the relationship between affective disorders and endometrial cancer. Ultimately we believe that the association between depression and endometrial cancer is not as strong as that of obesity, due to the genetic correlation between depression and obesity.


Asunto(s)
Carcinoma Endometrioide , Trastorno Depresivo Mayor , Neoplasias Endometriales , Humanos , Femenino , Trastorno Depresivo Mayor/genética , Estudio de Asociación del Genoma Completo , Neoplasias Endometriales/genética , Ansiedad , Polimorfismo de Nucleótido Simple , Análisis de la Aleatorización Mendeliana
20.
BMC Infect Dis ; 24(1): 315, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486167

RESUMEN

BACKGROUND: This study aims to explore the infection and age distribution of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Herpes simplex virus type II (HSV II) among the outpatients of Reproductive Medicine Center in Putian, Fujian Province to provide a clinical basis for the early diagnosis and treatment of various reproductive tract diseases and infertility in this region. METHODS: A total of 1736 samples of secretions and exfoliated cervical cells were collected from the outpatients of the Reproductive Medicine Center of the Affiliated Hospital of Putian University from December 2021 to April 2023. The infections of UU, CT, NG and HSVII were detected by real-time fluorescence polymerase chain reaction (PCR), and the infection statuses of the patients with different genders, ages and diagnoses were analysed. RESULTS: Among the 1736 patients, 611 were male and 1125 were female. The male patients had higher UU infection rate but lower HSV II infection rate than the female patients. No significant difference in CT and NG infection rates was observed between the genders. The CT infection rate gradually decreased with the increase in the age. The difference in UU, NG and HSV II infection rates among the different age groups was not statistically significant. For UU infection, the male infertile patients had the highest rate of 37.72% (172/456). Meanwhile, the differences in CT, NG and HSV II infection rates among the different diagnosis groups were not statistically significant. Among the male and female infertile patients, the CT infection rate was the highest in the 21-25 years of age group at 11.11% (2/18) and 9.47% (9/95), respectively. No statistically significant difference in UU, CT, NG and HSV II infection rates was observed among the different age groups of patients diagnosed in relation to the family planning guidance and between the male and female patients with other diagnoses results. CONCLUSIONS: This study showed that UU was the most frequently identified pathogen in infertile men in Putian, Fujian Province. The CT infection rate was the highest in people under 20 years old, and the infection showed a tendency toward young individuals. Therefore, the publicity of sexual health knowledge must be strengthened, and the prevention and treatment of venereal diseases among young and middle-aged people must be improved. Moreover, the pathogen infection is related to infertility to a certain extent, which is conducive to clinical diagnosis and treatment.


Asunto(s)
Infecciones por Chlamydia , Herpes Simple , Infertilidad , Infecciones del Sistema Genital , Persona de Mediana Edad , Femenino , Humanos , Masculino , Adulto Joven , Adulto , Pacientes Ambulatorios , Estudios Retrospectivos , Distribución por Edad , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis , Herpesvirus Humano 2 , Neisseria gonorrhoeae
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