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1.
Front Genet ; 14: 1079795, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36733344

RESUMO

Background: We aimed to construct and validate the esophageal squamous cell carcinoma (ESCC)-related m6A regulators by means of machine leaning. Methods: We used ESCC RNA-seq data of 66 pairs of ESCC from West China Hospital of Sichuan University and the transcriptome data extracted from The Cancer Genome Atlas (TCGA)-ESCA database to find out the ESCC-related m6A regulators, during which, two machine learning approaches: RF (Random Forest) and SVM (Support Vector Machine) were employed to construct the model of ESCC-related m6A regulators. Calibration curves, clinical decision curves, and clinical impact curves (CIC) were used to evaluate the predictive ability and best-effort ability of the model. Finally, western blot and immunohistochemistry staining were used to assess the expression of prognostic ESCC-related m6A regulators. Results: 2 m6A regulators (YTHDF1 and HNRNPC) were found to be significantly increased in ESCC tissues after screening out through RF machine learning methods from our RNA-seq data and TCGA-ESCA database, respectively, and overlapping the results of the two clusters. A prognostic signature, consisting of YTHDF1 and HNRNPC, was constructed based on our RNA-seq data and validated on TCGA-ESCA database, which can serve as an independent prognostic predictor. Experimental validation including the western and immunohistochemistry staining were further successfully confirmed the results of bioinformatics analysis. Conclusion: We constructed prognostic ESCC-related m6A regulators and validated the model in clinical ESCC cohort as well as in ESCC tissues, which provides reasonable evidence and valuable resources for prognostic stratification and the study of potential targets for ESCC.

2.
Am J Hypertens ; 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36738296

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) is widely distributed throughout the nervous system with various antioxidant and anti-inflammatory properties. Hypertension involves an increase in reactive oxygen species (ROS) and inflammation in the hypothalamic paraventricular nucleus (PVN). However, it is unclear how H2S in PVN affects hypertension. METHODS: Our study used spontaneously hypertensive rats (SHR) and control Wistar Kyoto (WKY) rats, microinjected with Adenovirus-Associated Virus (AAV)-CBS (cystathionine beta-synthase overexpression) or AAV-ZsGreeen in bilateral PVN, or simultaneously injected with virus-carrying nuclear factor erythroid 2-related factor 2 (Nrf2)-shRNA for 4w. Blood pressure and plasma noradrenaline level were detected, and the PVN was collected. Finally, levels of CBS, H2S, Nrf2, Fra-LI, ROS, gp91 phox, p47 phox, superoxide dismutase 1, interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-α, tyrosine hydroxylase and glutamate decarboxylase 67 were measured. RESULTS: We found that AAV-CBS increased H2S in the PVN, and blood pressure, neuronal activation, oxidative stress, and inflammation of PVN were substantially reduced. Furthermore, endogenous H2S in the PVN activated Nrf2 and corrected the PVN's imbalance of excitatory and inhibitory neurotransmitters. However, Nrf2 knockdown in the PVN was similarly observed to abolish the beneficial effect of H2S on hypertension. CONCLUSIONS: The findings imply that endogenous H2S in SHR PVN is reduced, and PVN endogenous H2S can alleviate hypertension via Nrf2-mediated antioxidant and anti-inflammatory effects.

3.
Chemistry ; : e202300165, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732878

RESUMO

Invited for the cover of this issue are Lei Jiang and Bo Song at the University of Shanghai for Science and Technology and the Technical Institute of Physics and Chemistry (CAS), and colleagues at Fudan University and South China Normal University. The image depicts how the hydrolysis of cellular energy molecules (i.e., ATP and dNTPs) releases mid-infrared photons to efficiently drive biological processes including DNA replication. Read the full text of the article at 10.1002/chem.202203513.

4.
Clin Cancer Res ; 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36735519

RESUMO

PURPOSE: To investigate the efficacy and safety of the novel orally active phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor in relapsed and/or refractory follicular lymphoma (FL) patients who had received at least two prior systemic treatments. PATIENTS AND METHODS: Histologically confirmed relapsed and/or refractory FL patients with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg qd, po in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression free survival (PFS), overall survival (OS), disease control rate and drug safety profile. Of 114 screened relapsed and/or refractory FL patients, 84 were enrolled in the full analysis set (FAS). RESULTS: The ORR of 84 FAS patients was 79.8% (95%CI: 69.6-87.8, 67 patients), with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (range: 9.3-15.9). The median PFS was 13.4 months (95%CI: 11.1-16.7). The 12-month OS rate was 91.4% (95%CI: 82.7-95.8. and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%) and interstitial lung disease (3.6%). CONCLUSIONS: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory FL patients who had received at least two prior systemic therapies.

5.
J Integr Neurosci ; 22(1): 12, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36722248

RESUMO

BACKGROUND: Second-generation antipsychotics (SGAs) is thought responsible for the metabolic abnormalities of schizophrenic patients, however, some untreated schizophrenic patients had already developed problems with glucose metabolism. The present study examined the hypothesis that schizophrenia itself but not risperidone, an extensively employed SGA, is accountable for metabolic abnormalities. METHODS: A 56-day risperidone regimen (1 mg/kg/day) was employed for rats of social isolation rearing (SIR) beginning at different developmental stage (28 or 56 days after weaning, i.e., adolescent and young adulthood, respectively). Metabolic parameters including body weight, systolic blood pressure (SBP), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and plasma glucose were measured at baseline, 28, and 56 days of the regimen. Oral glucose tolerance test (OGTT) was performed at the end of the regimen. Insulin function was evaluated by area under the curve (AUC) of OGTT, homeostasis model assessment-insulin resistance (HOMA-ir), and Matsuda index. RESULTS: Our results demonstrated that: (i) SIR rats presented higher body weight, plasma triglyceride, and HOMA-ir than social controls. (ii) Higher insulin resistance was specifically presented in young adult rather than adolescent SIR rats. (iii) Adolescent drugged rats showed a lower level of LDL in day 28 of the regimen than young adult. Risperidone led to a lower LDL level in only young adult IR rats in day 56 than undrugged rats. (iv) SIR-induced dysregulation of insulin can be reversed by chronic risperidone treatment beginning at adolescence but not young adulthood. CONCLUSIONS: Our findings support the primary role of schizophrenia in metabolic abnormalities and risperidone appear beneficial when administered earlier.


Assuntos
Antipsicóticos , Resistência à Insulina , Insulinas , Esquizofrenia , Animais , Ratos , Risperidona/farmacologia , Antipsicóticos/farmacologia , Esquizofrenia/tratamento farmacológico , Peso Corporal , Triglicerídeos
6.
Brief Funct Genomics ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36723978

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in December 2019. As of mid-2021, the delta variant was the primary type; however, in January 2022, the omicron (BA.1) variant rapidly spread and became the dominant type in the United States. In June 2022, its subvariants surpassed previous variants in different temporal and spatial situations. To investigate the high transmissibility of omicron variants, we assessed the complex of spike protein 1 receptor-binding domain (S1RBD) and human angiotensin-converting enzyme 2 (hACE2) from the Protein Data Bank (6m0j, 7a91, 7mjn, 7v80, 7v84, 7v8b, 7wbl and 7xo9) and directly mutated specific amino acids to simulate several variants, including variants of concern (alpha, beta, gamma, delta), variants of interest (delta plus, epsilon, lambda, mu, mu without R346K) and omicron variants (BA.1, BA.2, BA.2.12.1, BA.4, BA.5). Molecular dynamics (MD) simulations for 100 ns under physiological conditions were then performed. We found that the omicron S1RBD-hACE2 complexes become more compact with increases in hydrogen-bond interactions at the interface, which is related to the transmissibility of SARS-CoV-2. Moreover, the relaxation time of hydrogen bonds is relatively short among the omicron variants, which implies that the interface conformation alterations are fast. From the molecular perspective, PHE486 and TYR501 in omicron S1RBDs need to involve hydrogen bonds and hydrophobic interactions on the interface. Our study provides structural features of the dominant variants that explain the evolution trend and their increased contagiousness and could thus also shed light on future variant changes.

7.
Plant J ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602437

RESUMO

The enzyme DWARF27 (D27) catalyzes the reversible isomerization of all-trans- into 9-cis-ß-carotene, initiating strigolactone (SL) biosynthesis. Genomes of higher plants encode two D27-homologs, D27-like1 and -like2, with unknown functions. Here, we investigated the enzymatic activity and biological function of the Arabidopsis D27-like1. In vitro enzymatic assays and expression in Synechocystis sp. PCC6803 revealed an unreported 13-cis/15-cis/9-cis- and a 9-cis/all-trans-ß-carotene isomerization. Although disruption of AtD27-like1 did not cause SL deficiency phenotypes, overexpression of AtD27-like1 in the d27 mutant restored the more-branching phenotype, indicating a contribution of AtD27-like1 to SL biosynthesis. Accordingly, generated d27 d27like1 double mutants showed a more pronounced branching phenotype compared to d27. The contribution of AtD27-like1 to SL biosynthesis is likely a result of its formation of 9-cis-ß-carotene that was present at higher levels in AtD27-like1 overexpressing lines. By contrast, AtD27-like1 expression correlated negatively with the content of 9-cis-violaxanthin, a precursor of ABA, in shoots. Consistently, ABA levels were higher in shoots and also in dry seeds of the d27like1 and d27 d27like1 mutants. Transgenic lines expressing GUS driven by the AtD27LIKE1 promoter and transcript analysis of hormone-treated Arabidopsis seedlings revealed that AtD27LIKE1 is expressed in different tissues and affects ABA and auxin. Taken together, our work reports a cis/cis-ß-carotene isomerase that affects the content of both cis-carotenoid-derived plant hormones, ABA and SLs.

8.
J Enzyme Inhib Med Chem ; 38(1): 2163241, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36629443

RESUMO

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 µM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 µM in the hyperuricemic model mice (723.0 µM), comparable with Allopurinol (325.8 µM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health.


Assuntos
Alopurinol , Hiperuricemia , Humanos , Camundongos , Animais , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Ácido Úrico/uso terapêutico , Ácidos Cumáricos , Hiperuricemia/tratamento farmacológico , Xantina Oxidase/metabolismo
9.
Sci Total Environ ; 866: 161378, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36610624

RESUMO

In order to recycle Uranium (U) for the sustainable development of nuclear energy, diamide bipyridine (DABP) modified hierarchically porous carbon doped boron nitride (BCN-DABP) was synthesized as an adsorbent for the multipurpose removal of U. BCN-DABP displayed good adsorption performance for U in both weakly and highly acidic solutions. The hierarchically porous structure endowed BCN-DABP with ultrafast adsorption kinetics, and adsorption reached equilibrium within 180.0 and 0.5 min under pH = 4.0 and 2.00 mol L-1 HNO3, respectively. Moreover, combination of adsorption isotherm studies and DFT calculations showed that BCN-DABP possessed high adsorption capacities for U and displayed different adsorption performance under different conditions. BCN-DABP adsorbed UO22+ by chelation and electrostatic attraction under pH 4.0 and 2.00 mol L-1 HNO3, the maximum adsorption capacity under two conditions reached 818.7 and 1296.7 mg g-1, respectively. As a result, BCN-DABP is expected to be used for the rapid and efficient removal of U in various kinds of contaminated water. Furthermore, excellent salinity tolerance, good adsorption selectivity, and outstanding radiation resistance also endowed BCN-DABP with great practical potential for removing U in radioactive contaminated water as well as high level liquid waste.

10.
ACS Cent Sci ; 9(1): 72-83, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36712483

RESUMO

Aptamer-based detection and therapy have made substantial progress with cost control and easy modification. However, the conformation lability of an aptamer typically causes the dissociation of aptamer-target complexes during harsh washes and other environmental stresses, resulting in only moderate detection sensitivity and a decreasing therapeutic effect. Herein, we report a robust covalent aptamer strategy to sensitively detect nucleocapsid protein and potently neutralize spike protein receptor binding domain (RBD), two of the most important proteins of SARS-CoV-2, after testing different cross-link electrophilic groups via integrating the specificity and efficiency. Covalent aptamers can specifically convert aptamer-protein complexes from the dynamic equilibrium state to stable and irreversible covalent complexes even in harsh environments. Covalent aptamer-based ELISA detection of nucleocapsid protein can surpass the gold standard, antibody-based sandwich ELISA. Further, covalent aptamer performs enhanced functional inhibition to RBD protein even in a blood vessel-mimicking flowing circulation system. The robust covalent aptamer-based strategy is expected to inspire more applications in accurate molecular modification, disease biomarker discovery, and other theranostic fields.

11.
Endocr Connect ; 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607164

RESUMO

Oxidative stress plays an important role in the pathophysiology of gestational diabetes mellitus (GDM). We investigated the relationship between NADPH oxidase p22phox subunit (CYBA) C242T (rs4673) and myeloperoxidase (MPO) G-463A (rs2333227) genetic variants and GDM in 719 patients with GDM and 1205 control women. Clinical, metabolic, and oxidative stress parameters were analyzed. We found that frequencies of the A allele (15.6% vs. 12.3%) and GA + AA genotype (28.5% vs. 23.2%) of the MPO G-463A variation were significantly higher in patient with GDM than in the control women (OR = 1.318, 95% CI: 1.068-1.625, P = 0.010 for the dominant model; OR = 1.999, 95% CI: 1.040-3.843, P = 0.034 for the recessive model; OR = 1.320, 95% CI: 1.095-1.591, P = 0.004 for the allele model). Genotype GA + AA remained a significant predictor of GDM in a logistic regression model including age and BMI at delivery (OR = 1.282, 95% CI: 1.037 ‒ 1.583, P = 0.021). Furthermore, the -463A allele was associated with higher TG and the 242T allele was related to higher pre-pregnancy BMI and oxidative stress index in all subjects (P <0.05). The 242T allele was also associated with higher HOMA-IR but lower serum total antioxidant capacity in patients with GDM (P <0.05). We conclude that the MPO G-463A, but not the CYBA C242T, genetic variation, is associated with an increased risk of GDM in Chinese women. These two genetic polymorphisms may be linked to obesity, dyslipidemia, insulin resistance, and oxidative stress.

12.
Blood ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626583

RESUMO

In the phase 3 POLARIX study (NCT03274492), polatuzumab vedotin combined with rituximab plus cyclophosphamide, doxorubicin and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with similar safety in previously untreated diffuse large B-cell lymphoma. Patients were randomized 1:1 to 6 cycles of Pola-R-CHP or R-CHOP plus 2 cycles of rituximab alone. For registration of POLARIX in China, consistency of PFS in an Asia subpopulation (defined as ≥50% of the risk reduction in PFS expected in the global population) was evaluated. Overall, 281 patients were analyzed: 160 patients from Asia in the intent-to-treat (ITT) population of the global study and 121 from an ITT China extension cohort. Of these, 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At data cut-off (June 28, 2021; median follow-up 24.2 months), PFS met the consistency definition with the global population and was superior with Pola-R-CHP versus R-CHOP (hazard ratio 0.64; 95% confidence interval [CI], 0.40-1.03). Two-year PFS was 74.2% (95% CI, 65.7-82.7) and 66.5% (95% CI, 57.3-75.6) with Pola-R-CHP and R-CHOP, respectively. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3-4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP versus R­CHOP in the Asian and global populations in POLARIX.

13.
Fertil Steril ; 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36627014

RESUMO

OBJECTIVE: To study the involvement of microRNAs (miRNAs) in the pathogenesis of chronic anovulation and mechanism of metformin treatment in polycystic ovary syndrome (PCOS). DESIGN: Case-control and prospective validation cohort study. SETTING: Tertiary university hospital. SUBJECTS: A total of 146 patients with PCOS and chronic anovulation and 20 non-PCOS controls were enrolled. Patients who resumed ovulation and remained anovulatory after metformin treatment were assigned to the MET-OV and MET-AO groups, respectively. EXPOSURE: All patients with PCOS received metformin treatment for 6 months. MAIN OUTCOME MEASURES: Baseline and chronological changes in the plasma levels of 14 miRNAs (miR-21, 93, 132, 193b, 221, 222, 223, 27a, 125b, 200b, 212, 320a, 429, and 483) selected by literature review, anthropometric data, and hormonal and metabolic profiles were measured. Predictive modeling based on baseline circulatory miRNA levels and clinical parameters was conducted to predict ovulation recovery after metformin treatment. RESULTS: No significant differences were observed in the baseline hormonal and metabolic profiles between the MET-OV and MET-AO groups. However, the expression of miR-27a, miR-93, and miR-222 was significantly higher in the MET-OV group than that for the MET-AO (p=0.038, 0.03, and 0.012, respectively) and control (p<0.0001, 0.0003, and 0.0272, respectively) groups. After six months of metformin treatment, the levels of insulin, luteinizing hormone, and six circulating miRNAs (miR-21, 27a, 93, 221, 222, and 223) and homeostatic model assessment for insulin resistance decreased significantly in the MET-OV group, but remained unchanged in the MET-AO group. The area under curve, sensitivity, and specificity of the adjusted prediction model, based on miRNA levels and clinical parameters using logistic regression analysis for predicting ovulatory response after metformin treatment, were 0.807, 0.892, and 0.632, respectively. CONCLUSION: The present study demonstrated a distinct pattern of baseline expression and chronological changes in the levels of several circulatory miRNAs between the MET-OV and MET-AO groups, suggesting that aberrantly overexpressed diabetogenic miRNAs are involved in the pathophysiology of chronic anovulation in PCOS and their downregulation might contribute toward the therapeutic effects of metformin. This could provide new insights into the mechanism of action and applicability of individualized metformin therapy in women with PCOS.

14.
Physiol Plant ; : e13853, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36628625

RESUMO

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 palys a role in regulating plant growth under abiotic conditions.

15.
J Agric Food Chem ; 71(1): 721-728, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36592095

RESUMO

In order to analyze the molecular rearrangement of terpenes in wine during aging, the changes in linalool, α-terpineol, nerol, and geraniol in model wine were investigated in the dark at low temperature for 90 days. Headspace-gas chromatograph-mass spectrometer/olfactometry was used for qualitative and relative quantitation of terpenes. Quantum mechanical calculation was used to analyze the Gibbs free energy. The results showed that nerol was converted into d-limonene, terpinolene, linalool, and α-terpineol. Geraniol was converted into ß-ocimene, terpinolene, and linalool. Linalool was converted into terpinolene. The conversion rate of nerol to terpinolene was the highest with 5.94%. α-Terpineol was not converted spontaneously into other terpenes due to its lowest Gibbs free energy, indicating that the cyclization and isomerization could occur spontaneously through an exotherm reaction. However, the dehydroxylation of linalool, nerol, and geraniol required an energy source.


Assuntos
Vitis , Vinho , Terpenos , Vinho/análise , Vitis/genética , Monoterpenos
16.
Neoplasma ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36660797

RESUMO

HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the ß-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the ß-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.

17.
Clin Pediatr (Phila) ; : 99228221149551, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36661073

RESUMO

To understand the psychological effects on behavior of girls with idiopathic central precocious puberty (ICPP) and to explore the role of gonadotropin-releasing hormone analog (GnRHa) in the reversal or blocking of the negative psychological effects on behaviors of girls with ICPP. A total of 100 girls with ICPP diagnosed at the Department of Endocrinology of Jiangxi Children's Hospital were divided into the treatment group and observation group with 50 cases in each group. The control group consisted of 50 healthy girls examined at our hospital during the same period. The Achenbach Child Behavior Check List ([CBCL] for parents) was used to evaluate the psychological effects on behavior of the girls diagnosed with ICPP and the girls in the control group, and the scores of related behavioral factors were calculated. At the same time, the psychological effects on behaviors of the girls with ICPP treated with GnRHa were followed up. (1) There were 100 girls with ICPP and 30 with behavioral problems. There were 50 normal healthy girls (control group) with 3 cases of behavior problems. Of the 50 girls with ICPP, after treatment, 8 had behavioral issues. The rate of abnormal psychological effects on behavior in the group of girls with ICPP before treatment was significantly higher than in the control group (P < .01), and after treatment, the rate was lower than before treatment (P < .05). (2) The scores of depression, social withdrawal, poor communication, and school discipline violation in the ICPP group were higher than those in the control group, with a statistical significance (P < .01). (3) After 24 months of GnRHa treatment for girls in the ICPP group, the scores of 4 factors, including depression, social withdrawal, poor communication, and violation of discipline in the Achenbach CBCL, were significantly different before and after treatment (P < .05). (1) Girls with ICPP have low self-esteem, low self-confidence, high incidences of psychological effects on behavior problems, manifested in depression, withdrawal, poor communication, discipline violations, and other aspects; (2) GnRHa treatment can reverse the low self-esteem and low self-confidence of girls with ICPP to varying degrees.

18.
Vaccines (Basel) ; 11(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36679964

RESUMO

BACKGROUND: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. METHODS: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. RESULTS: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. CONCLUSION: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.

19.
World J Clin Cases ; 11(2): 426-433, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36686362

RESUMO

BACKGROUND: Hepatic perivascular epithelioid cell neoplasms (PEComas) are rare. Diagnostic and treatment experience with hepatic PEComa remains insufficient. CASE SUMMARY: Three hepatic PEComa cases are reported in this paper: One case of primary malignant hepatic PEComa, one case of benign hepatic PEComa, and one case of hepatic PEComa with an ovarian mature cystic teratoma. During preoperative imaging and pathological assessment of intraoperative frozen samples, patients were diagnosed with hepatocellular carcinoma (HCC), while postoperative pathology and immunohistochemistry subsequently revealed hepatic PEComa. Patients with hepatic PEComa which is misdiagnosed as HCC often require a wider surgical resection. It is easy to mistake them for distant metastases of hepatic PEComa and misdiagnosed as HCC, especially when it's combined with tumors in other organs. Three patients eventually underwent partial hepatectomy. After 1-4 years of follow-up, none of the patients experienced recurrence or metastases. CONCLUSION: A clear preoperative diagnosis of hepatic PEComa can reduce the scope of resection and prevent unnecessary injuries during surgery.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36669772

RESUMO

CONTEXT: The evidence of long-term polyethylene glycol recombinant human growth hormone (PEG-rhGH) in pediatric growth hormone deficiency (GHD) is limited. OBJECTIVE: This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in real world, as well as to examine the effects of dose on patient outcomes. DESIGN: A prospective, observational, post-trial study (NCT03290235). SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in four individual clinical trials, and received weekly 0.2 mg/kg/week (high-dose) or 0.1-<0.2 mg/kg/week (low-dose) PEG-rhGH for 30 months. MAIN OUTCOMES MEASURES: Height standard deviation score (Ht SDS) at 12, 24, and 36 months. RESULTS: A total of 1170 children were enrolled in this post-trial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup, respectively. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. Besides, the changes in Ht SDS from baseline was significantly improved in the high-dose subgroup than in the low-dose subgroup at 6, 12, 24 and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious AEs. There was no serious AE related to the treatment, and no AEs leading to treatment discontinuation or death occurred. CONCLUSIONS: PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, while PEG-rhGH 0.2 mg/kg/week might show additional benefit.

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