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2.
J Phys Chem Lett ; 13(16): 3594-3601, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35426677

RESUMO

Designing and tuning the physical properties of two-dimensional (2D) materials at the atomic level are crucial to the development of 2D technologies. Here, we introduce heteroanions into metal-centered octahedral structural units of a 2D crystal breaking the Oh symmetry, together with the synergistic effect of anions' electrons and electronegativity, to realize ternary 2D materials with emerging topological, magnetic, and dielectric properties. Using an intrinsic heteroanionic van der Waals layered material, VOCl, as a prototype, 20 2D monolayers VXY (X = B, C, N, O, or F; Y = F, Cl, Br, or I) are obtained and investigated by means of first-principles calculations. The anion engineering in this family significantly reshapes the electronic properties of VOCl, leading to nonmagnetic topological insulators with nontrivial edge states in VCY, ferromagnetic half-semimetals with a nodal ring around the Fermi energy in VNY, and insulators with dielectric constants in VOY higher than that of h-BN. This work demonstrates the rationality and validity of the design strategy of multiple-anion engineering to achieve superior properties in the 2D monolayers with potential application in electronics and spintronics.

3.
Seizure ; 94: 100-106, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34883461

RESUMO

PURPOSE: Whether patients with epilepsy in long-term remission and interictal epileptiform discharges (IEDs) can stop antiseizure medication (ASM) remains a challenging topic even though multiple studies have investigated ASM withdrawal. This study aimed to estimate seizure relapse and its risk factors in patients with epilepsy in five-year remission and persistent IEDs. METHODS: Patients with epilepsy and persistent IEDs were prospectively recruited from the Affiliated Nanjing Brain Hospital of Nanjing Medical University from Dec.1, 2010 to Dec.30, 2019. All enrolled patients achieved seizure remission for over five years and were divided into the ASM withdrawal and continuous treatment groups according to their personal preference. Seizure outcomes and 24 h video electroencephalogram findings were obtained through clinical visits or telephone interviews every three months until March 31, 2021. The cumulative recurrence rate and its diversity between the ASM withdrawal and continuous treatment groups were tested using Kaplan-Meier analysis. Multivariate Cox regression analysis was performed to explore the independent predictors for seizure recurrence. Relapsed patients were further monitored for their seizure control and prognosis. RESULTS: A total of 83 patients with epilepsy in five-year remission and persistent IEDs were enrolled in this study, including 41 (49.4%) in the ASM withdrawal group and 42 (50.6%) in the continuous ASM treatment group. During the follow-up with a median time of 36.8 months (range from 18.7 to 104.6 months), the seizure relapse in off-medication patients (43.9%, 18/41) was higher than that in on-medication patients (21.4%, 9/42; P = 0.031). In the multivariate analysis model, independent predictors for seizure recurrence were structural-metabolic epilepsy or unknown cause (HR = 6.185, 95% CI 1.166-32.805) and multiple seizure types (HR = 2.807, 95% CI 1.051-7.502). ASM withdrawal was not found to be an independent risk factor for seizure recurrence. Of 27 patients with seizure recurrence, 25 were given reinstitution or continuous ASM therapy, whereas two chose sustained observation without medication. At the end of the follow-up, 70.4% (19/27) of recurrence patients were completely free from seizures for at least one year again, and only one patient developed refractory epilepsy. CONCLUSION: For patients with epilepsy in five-year remission and persistent IEDs, drug withdrawal may be a rational choice after the individualized assessment of benefits and risks. Furthermore, the independent risk factors for the seizure relapse were structural-metabolic epilepsy or an unknown cause, and multiple seizure types. Finally, patients with epilepsy relapsing after ASM withdrawal could achieve seizure remission again after ASM retreatment.


Assuntos
Epilepsia , Síndrome de Abstinência a Substâncias , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Prognóstico , Recidiva , Convulsões/tratamento farmacológico
4.
Blood Cancer Discov ; 2(4): 388-401, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34661159

RESUMO

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia. SIGNIFICANCE: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.See related commentary by Wu et al., p. 300.


Assuntos
Hipertermia Induzida , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Tretinoína/uso terapêutico
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(2): 125-134, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34672149

RESUMO

Objective: The new theory of holistic integrative physiology and medicine, which describes the integrative regulation of respiratory, circulatory and metabolic systems in human body, generates the hypothesis of that breath is the origin of variability of circulatory parameters. We investigated the origin of heart rate variability by analyzing relationship between the breath and heart rate variability (HRV) during sleep. Methods: This retrospective study analyzed 8 normal subjects (NS) and 10 patients of chronic diseases without sleep apnea (CDs-no-SA). After signed the informed consent form, they performed cardiopulmonary exercise testing (CPET) in Fuwai Hospital and monitored polysomnography (PSG) and electrocardiogram (ECG) during sleep since 2014. We dominantly analyzed the correlation between the respiratory cycle during sleep and the heart rate variability cycle of the ECG R-R interval. The HRV cycle included the HR increase from the lowest to the highest and decrease from the highest to the lowest point. The number of HRV (HRV-n), average HRV time and other parameters were calculated. The breath cycle included complete inhalation and subsequent exhalation. The number of breath (B-n), average breath time and other breath parameters were analyzed and calculated. We analyzed each person's relationship between breath and HRV; and the similarities and differences between the NS and CDs-no-SA groups. Independent sample t test was used for statistical analysis, with P<0.05. Results: CPET core parameter such as Peak VO2 (83.8±8.9)% in NS were significantly higher than that (70.1±14.9)% in patients of chronic diseases without sleep apnea (P<0.05), but there was no difference between their AHI (1.7±1.3) in NS and AHI (2.9±1.2) in CDs-no-SA (P>0.05). The B-n and the HRV-n (6581.63±1411.90 vs 6638.38±1459.46), the average B time and the average HRV time (4.19±0.57)s vs (4.16±0.62)s in NS were similar without significant difference (P>0.05). The comparison of the numbers in CDs-no-SA were the number (7354.50±1443.50 vs 7291.20±1399.31) and the average times ((4.20±0.69)s vs (4.23±0.68)s) of B and HRV were similar without significant difference (P>0.05). The ratios of B-n/HRV-n in NS and CDs-no-SA were (0.993±0.027 vs 1.008±0.024) and both were close to 1 and similar without significant difference (P>0.05). The average magnitude of HRV in NS ((5.74±3.21) bpm) was significantly higher than that in CDs-no-SA ((2.88±1.44) bpm) (P<0.05). Conclusion: Regardless of the functional status of NS and CDs-no-SA, there is a similar consistency between B and HRV. The origin of initiating factors of HRV is the respiration.


Assuntos
Síndromes da Apneia do Sono , Doença Crônica , Frequência Cardíaca , Humanos , Estudos Retrospectivos , Sono
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(2): 135-141, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34672150

RESUMO

Objective: Based on the hypothesis that respiration causes variability of circulatory indicators proposed by the holistic integrated physiology and medicine theory, the correlation between respiration and heart rate variability during sleep in chronically ill patients with abnormal sleep breathing is analyzed. Methods: Eleven chronically ill patients with abnormal sleep breathing and apnea-hypopnea index (AHI) ≥15 times/hr are recruited. After signing the informed consent, they completed the standardized symptomatic restrictive extreme exercise cardiopulmonary exercise testing (CPET) and sleep breathing monitoring Calculate and analyze the rules of respiratory nasal airflow and ECG RR interval heart rate variability during the oscillatory breathing (OB) phase and the normal steady breathing phase of the patient during sleep, and use the independent sample t test to compare with normal people and no sleep breathing abnormalities in the same period in this laboratory. Of patients with chronic diseases are more similar and different. Results: The peak oxygen uptake and anaerobic threshold (AT) of CPET in chronic patients with abnormal sleep apnea were (70.8±13.6)% Pred and (71.2±6.1)% Pred; 5 cases of CPET had exercise induced oscillatory breathing (EIOB), 6 An example is unstable breathing, which indicates that the overall functional status is lower than normal. In this group of patients with chronic diseases, AHI (28.8±10.0) beats/h, the ratio of the total time of abnormal sleep breathing to the total time of sleep (0.38±0.25); the length of the OB cycle (51.1±14.4)s. The ratio (Bn/HRV-B-n) of the number of breathing cycles in the normal and steady breathing period to the number of heart rate variability cycles in this group of patients with chronic diseases is 1.00±0.04, and the CV (SD of HRV-B-M/x) is (0.33 ±0.11), blood oxygen saturation (SpO2) did not decrease significantly, the average amplitude of heart rate variability (HRV-B-M) of each respiratory cycle rhythm was (2.64±1.59) bpm, although it was lower than normal people (P<0.05) , But it was similar to chronic patients without sleep apnea (P>0.05). In this group of patients with chronic diseases, the ratio of the number of respiratory cycles to the number of heart rate variability cycles (OB-Bn/OB-HRV-B-n) during OB is (1.22±0.18), and the average amplitude of heart rate variability for each respiratory cycle rhythm in OB (OB -HRV-B-M) is (3.56±1.57)bpm and its variability (OB-CV = SD of OB-HRV-B-M/x) is (0.59±0.28), the average amplitude of heart rate variability in each OB cycle rhythm (OB-HRV-OB-M) is (13.75±4.25)bpm, SpO2 decreases significantly during hypoventilation during OB, and the average decrease in SpO2 during OB (OB-SpO2-OB-M) is (4.79±1.39)%. The OB-Bn/OB-HRV-B-n ratio, OB-HRV-OB-M and OB-SpO2-OB-M in the OB period are all significantly higher than the corresponding indicators in the normal stable breathing period Large (P<0.01). Although OB-HRV-B-M has no statistically significant difference compared with HRV-B-M in normal stable breathing period (P>0.05), its variability OB-CV is significantly increased (P<0.01). Conclusion: The heart rate variability of chronic patients with abnormal sleep breathing in the OB phase is greater than that of the normal stable breathing period. When the breathing pattern changes, the heart rate variability also changes significantly. The number of breathing cycles in the stable breathing period is equal to the number of heart rate variability cycles.The ratio is the same as that of normal people and chronically ill patients without sleep apnea, confirming that heart rate variability is respiratory origin; and the reduction of heart rate variability relative to the respiratory cycle during OB is directly caused by hypopnea or apnea at this time, and heart rate variability is also breathing source.


Assuntos
Síndromes da Apneia do Sono , Doença Crônica , Frequência Cardíaca , Humanos , Polissonografia , Respiração
7.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(2): 147-153, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34672152

RESUMO

Objective: To verify that the cardiopulmonary exercise testing (CPET) performed by clinical subjects is the maximum extreme exercise, we designed The Max test(Max)during clinical CPET. We used Max to verify the accuracy of the quantitative CPET evaluation result, and whether it is feasible and safe to use the specific value of a certain index as the standard for stopping CPET. Methods: Two hundred and sixteen cases from Fuwai Hospital were selected during June 2017 to January 2019,including 41 healthy person(control group) and 175with cardiovascular diseases(patient group),The patients had a CPET peak RER ≤ 1.10, or the peak heart rate and peak blood pressure were basically non-responsive.The Max was first attempted in 60 subjects,and this study is further expanded . When the CPET ended, they had a 5-minute break, then the Max, during which, they cycled with a velocity of ≥ 60 r/min, at a constant intensity equivalent to to 130% of peak work,until exhausted.The difference and percentage difference between the peak heart rate and the peak oxygen uptake were calculated. ①If the percentage difference of heart rate and oxygen uptake are all less than -10%,then the Max is defined as failure,otherwise it is succesful. 2 If the percentage difference is between -10%~10%, then the Max is successful, which proved that the CPET is precise.③If the difference is ≥10%, the Max is successful, which proves that the CPET is non-extreme exercise. Results: Patient group's Peak VO2(L/min,ml/(min·kg)),anaerobic threshold (L/min,ml/(min·kg),%pred),Peak VO2/HR(ml/beat, % pred),Peak RER,Peak SBP,Peak WR,peak heart rate,OUEP (ratio,%pred) were lower than those of the control group(P<0.05).The VE/ VCO2 Slope (ratio,%pred)and Lowest VE/ VCO2(ratio,%pred) were higher in the patient group than in the control group (P<0.05).No adverse events occurred during the CPET and Max in all cases. Among the 216 cases,Max was successful in 198 cases(91.7%).CPET was proved to be maximum extreme exercise for 182 cases,non-maximum extreme exercise for 16 cases,and failed in 18 cases(8.3%).Conclusion: For CPET with a low peak RER and a maximum challenge,the Max can confirm the accuracy of the objective quantitative assessment of CPET. Max is safe and feasible,and that deserved further research and clinical application.


Assuntos
Teste de Esforço , Insuficiência Cardíaca , Limiar Anaeróbio , Exercício Físico , Humanos , Consumo de Oxigênio
8.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(2): 154-161, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34672153

RESUMO

Objective: Cardiopulmonary exercise testing (CPET) was used to investigate the exercise pathophysiology of mitral regurgitation. Methods: 26 patients with moderate and severe mitral regurgitation who completed standardized extreme exercise CPET under strict quality control after signing informed consent since 2016, and 11 normal subjects in the same period as the control group. The core indexes of CPET were analyzed and calculated according to the standard method and compared with normal subjects for intergroup statistical independent sample t-test. At the same time, the patients with heart failure and exercise oscillation breathing (OB) were divided into two subgroups: 11 cases without heart failure, 15 cases with heart failure, 8 cases with non-OB and 18 cases with OB, and their similarities and differences were compared between each subgroup. Results: The core indexes of CPET, such as peak oxygen uptake (85.60 ±9.06)%pred and anaerobic threshold (AT, (87.59 ±15.38)%pred) were normal. The peak oxygen uptake of CPET in patients with mitral regurgitation was (48.15 ±12.11)%pred, peak oxygen pulse was (66.57 ±12.20)%pred, AT was (56.75 ±11.50)%pred, oxygen uptake efficiency plateau was (88.24 ±16.42)%pred , lowest value of carbon dioxide ventilatory efficiency was (125.89 ±27.05)%pred and slope of carbon dioxide ventilatory efficiency was (128.31 ±31.68)%pred. Among them, only oxygen uptake efficiency plateau (OUEP) was normal and low, and the other indexes were significantly abnormal. There were significant differences between the patients and the control group (P<0.01). There was no significant difference between the non-OB group and the OB group, but there was significant difference between the non-OB group and the control group (P<0.05). There was no significant difference between the non-heart failure group and the heart failure group, but there was significant difference between the non-heart failure group and the control group. Conclusion: All the core indexes of cardiopulmonary exercise are significantly abnormal in patients with mitral regurgitation who are significantly lower than those in normal subjects except for the low effectiveness of oxygen ventilation. And with or without heart failure and OB did not affect the cardiopulmonary function.


Assuntos
Insuficiência da Valva Mitral , Exercício Físico , Teste de Esforço , Humanos , Consumo de Oxigênio , Relatório de Pesquisa
9.
Artigo em Chinês | MEDLINE | ID: mdl-34672467

RESUMO

Objective: To study the symptom-restricted extreme cardiopulmonary exercise testing (CPET) to evaluate the improvement of the overall function of patients with long-term chronic diseases after intensive control of personalized precise exercise training for 3 months. Methods: We selected 20 patients with chronic cardiovascular and cerebrovascular metabolic diseases who were intensively controlled by our team from 2014 to 2016. After signing the informed consent form, based on the results of CPET and continuous functional tests, we formulated the overall management plan with individualized moderate exercise intensity as the core. After 3 months, CPET was performed. The changes of CPET indicators before and after intensive control in each patient were analyzed individually. Then the difference value and percentage difference value were calculated. Results: In this study, 20 patients (18 males and 2 females) with chronic cardiovascular and cerebrovascular metabolic diseases, aged (55.75±10.80, 26~73) years, height (172.20±8.63, 153~190) cm, weight (76.35±15.63, 53~105) kg, all patients were not any dangerous events during the period of CPET and intensive control.①After intensive control, the static pulmonary function index, resting systolic blood pressure, rate blood pressure product and fasting blood glucose were significantly improved (P<0.05).②Before intensive control, the peak oxygen uptake is (55.60±15.69, 34.37~77.45) % pred and anaerobic threshold is (60.11±12.26, 43.29~80.63)% pred; after intensive control, the peak oxygen uptake is (71.85±21.04, 42.40~102.00) % pred and anaerobic threshold (74.95±17.03, 51.90~99.47) %pred. Compared with before the intensive control, the peak oxygen uptake and anaerobic threshold of all patients after intensive control were significantly increased by (29.09±7.38,17.78~41.80) % and(25.16±18.38, 1.77~81.86)%(all P<0.01). Other core indexes were also improved significantly, including peak oxygen uptake,peak heart rate, peak work rate, oxygen uptake efficiency plateau, lowest value of carbon dioxide ventilatory efficiency, slope of ventilatory equivalent for carbon dioxide, ramp exercise duration(all P<0.01).③In terms of individualized analysis, after intensive control, the above 8 CPET core indexes were all improved in 15 cases, and 7 indexes in 5 cases were improved; the peak oxygen uptakeof all cases increased by more than 15%, 16 cases > 20%, 13 cases > 25%, 10 cases > 30%. Conclusion: CPET can safely, objectively and quantitatively evaluate the overall functional status and therapeutic effects, and guide the formulation of individualized precise exercise intensity. The overall plan of individualized precision exercise for three months can safely and effectively reverse the overall functional status of patients with long-term cardio-cerebrovascular metabolism diseases.


Assuntos
Teste de Esforço , Consumo de Oxigênio , Limiar Anaeróbio , Doença Crônica , Exercício Físico , Feminino , Humanos , Masculino
10.
Seizure ; 92: 189-194, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34551365

RESUMO

PURPOSE: This study aimed to investigate the incidence and predictors of epilepsy after anti-neuronal antibody-positive autoimmune encephalitis (AIE). The clinical outcomes of patients with epilepsy after AIE were also explored. METHODS: A total of 111 AIE patients were retrospectively evaluated. Post-AIE epilepsy (PAEE) was defined as at least one unprovoked seizure occurring six or more months after discharge from hospital. RESULTS: The incidence of acute symptomatic seizures was 80.2% (89/111) in our AIE patients. Furthermore, of the 89 AIE patients with seizures, 29 (32.6%) presented with seizures as the initial symptom. Overall, 44 out of 111 AIE patients (39.6%) had unprovoked seizures after six months, meeting our definition of PAEE. The independent risk factors for PAEE incidence included an initial presentation with new-onset refractory status epilepticus (NORSE), delayed immunotherapy treatment, the complication of a lung infection during admission, the requirement for mechanical ventilation during hospitalization, parietal lesions observed in magnetic resonance imaging (MRI), and focal slow waves on electroencephalographic (EEG) monitoring. CONCLUSIONS: Early initiation of immunotherapy and lung infection treatment may reduce the risk of conversion of symptomatic seizures to chronic epilepsy in the acute phase of AIE. In general, PAEE patients could have a good prognosis if treated properly and in a timely fashion.


Assuntos
Epilepsia , Doença de Hashimoto , Eletroencefalografia , Encefalite , Epilepsia/epidemiologia , Epilepsia/etiologia , Epilepsia/terapia , Humanos , Prognóstico , Estudos Retrospectivos
11.
J Phys Chem Lett ; 12(25): 6007-6013, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34165315

RESUMO

The discovery and design of two-dimensional semiconductors with high carrier mobilities is of vital importance for high-speed electronic and optoelectronic devices. Herein, based on high-throughput computations, we identify a group of semiconductors, iridium sulfide halides IrSX' (X' = F, Cl, Br, I), with high carrier mobilities (∼103 cm2 V-1 s-1) and highly efficient light harvesting (∼34%). Moreover, these materials exhibit anisotropic in-plane transport behavior, which is switchable via ferroelastic switching, providing the monolayer (ML) IrSX's great potential for applications in direction-controlled high-speed electronic and optoelectronic devices. The high carrier mobility and anisotropic transport are stemming from the anisotropic distribution of 3d orbitals of Ir atoms at the conduction band minimum (CBM) and valence band maximum (VBM) in the rectangular lattices. The ML IrSX's (X' = F, Cl, Br) show good dynamical and thermal stabilities and are thermodynamically stable based on phase diagram calculations, thus meriting experimental realization in the future.

12.
Nanotechnology ; 32(35)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34038884

RESUMO

Van der Waals (vdW) heterojunctions constructed by vertical stacking two-dimensional transition metal dichalcogenides hold exciting promise in realizing future atomically thin electronic and optoelectronic devices. Recently, a Janus WSSe structure has been successfully synthesized by using chemical vapor deposition, selective epitaxy atomic replacement, and pulsed laser deposition methods. Herein, based on first-principles calculations, we introduce the structures and performances of MoS2/WSSe vdW heterojunctions with different interfaces and stacking modes. The vdW heterojunctions possess indirect band gaps for S-S interfaces, while direct band gaps for Se-S interfaces. Besides, the potential drop indicates an efficient separation of photogenerated charges. Interestingly, the opposite built-in electric fields formed in the vdW heterojunctions with a S-S interface and a Se-S interface suggest different charge transfer paths, which would motivate further theoretical and experimental investigations on charge transfer dynamics. Moreover, the electronic property is adjustable by applying external in-plane strains, accomplishing with indirect to direct bandgap transition and semiconductor to metal transition. The findings are helpful for the design of multi-functional high-performance electronic and optoelectronic devices based on the MoS2/WSSe vdW heterojunctions.

13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 229-234, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829696

RESUMO

OBJECTIVE: To investigate the effects of morin-regulated NLRP3/Caspase-1 pathway on experimental autoimmune thyroiditis in rats. METHODS: The rats were randomly assigned to 6 groups: control group, experimental autoimmune thyroiditis group (EAT), low-, medium- and high-dose morin groups (post-modeling gavage of 50, 100 and 200 mg/kg morin hydrate per day for 6 weeks) and tripterygium wilfordii polyglycosides group (LGT group, post-modeling gavage of 6.25 mg/kg tripterygium wilfordii polyglycosidesper day for 6 weeks). Except for the control group, the rat model of experimental autoimmune thyroiditis was established by subcutaneous injection of 0.1 mL incomplete Freund's adjuvant containing porcine thyroglobulin. The levels of serum thyroglobulin (TgAb), thyroid peroxidase antibody (TPOAb), triiodothyronine (T3) and tetraiodothyronine (T4) in serum were detected by radioimmunoassay. The mRNA levels of interleukin-17 ( IL-17), interleukin-4 ( IL-4) and interferon γ ( INF- γ) were detected by reverse transcription-polymerase chain reaction. The levels of serum protein carbonyl content, 8-hydroxydeoxyguanosine (8-OHdG), and malondialdehyde (MDA) activity were checked with test kits. Expressions of NLRP3, apoptosis-related speck-like protein (ASC), and Caspase-1 were detected by Western blot. RESULTS: Compared with the EAT group, serum levels of TPOAb, TgAb, T3, and T4 in low-, medium- and high-dose Morin groups and LGT group were reduced ( P<0.01) and the mRNA levels of IL-17, INF-γ and IL-4 were increased ( P<0.01), the protein hydroxyl content, MDA activity, and 8-OHdG levels were reduced ( P<0.01). The levels of NLRP3, ASC and Caspase-1 were reduced ( P<0.01), the levels of 8-OHdG were significantly reduced ( P<0.01), and the levels of NLRP3, ASC and Caspase-1 were significantly reduced ( P<0.01). There were statistically significant differences between the data from the low-dose and the medium-dose Morin groups and the data of the LGT group ( P<0.05), while data from the high-dose Morin group showed no significant difference compared with the data of the LGT group. Data from low-, medium- and high-dose Morin groups showed no statistically significant differences ( P<0.05). CONCLUSION: The findings suggest that Morin improved experimental autoimmune thyroiditis in rats through regulating NLRP3/Caspase-1 pathway.


Assuntos
Tireoidite Autoimune , Animais , Caspase 1/genética , Caspase 1/metabolismo , Flavonoides , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Carbonilação Proteica , Ratos , Suínos
14.
Oxid Med Cell Longev ; 2021: 9034376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927798

RESUMO

Various pharmacological agents and protective methods have been shown to reverse pneumoperitoneum-related lung injury, but identifying the best strategy is challenging. Herein, we employed lung tissues and blood samples from C57BL/6 mice with pneumoperitoneum-induced lung injury and blood samples from patients who received laparoscopic gynecological surgery to investigate the therapeutic role of hydromorphone in pneumoperitoneum-induced lung injury along with the underlying mechanism. We found that pretreatment with hydromorphone alleviated lung injury in mice that underwent CO2 insufflation, decreased the levels of myeloperoxidase (MPO), total oxidant status (TOS), and oxidative stress index (OSI), and increased total antioxidant status (TAS). In addition, after pretreatment with hydromorphone, upregulated HO-1 protein expression, reduced mitochondrial DNA content, and improved mitochondrial morphology and dynamics were observed in mice subjected to pneumoperitoneum. Immunohistochemical staining also verified that hydromorphone could increase the expression of HO-1 in lung tissues in mice subjected to CO2 pneumoperitoneum. Notably, in mice treated with HO-1-siRNA, the protective effects of hydromorphone against pneumoperitoneum-induced lung injury were abolished, and hydromorphone did not have additional protective effects on mitochondria. Additionally, in clinical patients who received laparoscopic gynecological surgery, pretreatment with hydromorphone resulted in lower serum levels of club cell secretory protein-16 (CC-16) and intercellular adhesion molecule-1 (ICAM-1), a lower prooxidant-antioxidant balance (PAB), and higher heme oxygenase-1 (HO-1) activity than morphine pretreatment. Collectively, our results suggest that hydromorphone protects against CO2 pneumoperitoneum-induced lung injury via HO-1-regulated mitochondrial dynamics and may be a promising strategy to treat CO2 pneumoperitoneum-induced lung injury.


Assuntos
Lesão Pulmonar Aguda/etiologia , Dióxido de Carbono/efeitos adversos , Heme Oxigenase-1/metabolismo , Hidromorfona/uso terapêutico , Dinâmica Mitocondrial/genética , Pneumoperitônio/complicações , Lesão Pulmonar Aguda/fisiopatologia , Animais , Hidromorfona/farmacologia , Masculino , Camundongos
15.
Eur J Drug Metab Pharmacokinet ; 46(3): 353-371, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677821

RESUMO

BACKGROUND AND OBJECTIVE: Prior olanzapine population pharmacokinetic (PPK) models have focused on the effects of sex and smoking on olanzapine clearance. This PPK model in Chinese adult psychiatric patients also investigated the influence of comedications and co-occurrence of infections on olanzapine clearance, and explored how to personalize oral olanzapine dosage in the clinical setting. METHODS: A total of 1546 serum concentrations from 354 patients were collected in this study. A one-compartment model with first-order absorption was employed to develop the PPK model using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, co-occurrence of infection and concomitant medications (including dangguilonghui tablets, a Chinese herbal medicine for constipation). Bootstrap validation (1000 runs) and external validation of 50 patients were employed to evaluate the final model. Simulations were performed to explore the personalization of olanzapine dosing after stratification by sex, smoking, and comedication with valproate. RESULTS: Typical estimates for the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) were 0.30 h-1, 12.88 L/h, and 754.41 L, respectively. Olanzapine clearance was increased by the following variables: 1.23-fold by male sex, 1.23-fold by smoking, 1.23-fold by comedication with valproate, 1.16-fold by sertraline, and 2.01-fold by dangguilonghui tablets. Olanzapine clearance was decreased by the following variables: 0.75-fold by co-occurrence of infection, 0.70-fold by fluvoxamine, and 0.78-fold by perphenazine. The model evaluation indicated that the final model's performance was good, stable, and precise. CONCLUSION: This study contributes to the personalization of oral olanzapine dosing, but further studies should be performed to verify the effects of infection and comedications, including valproate and dangguilonghui.


This study included a total of 1546 serum olanzapine concentrations from 354 Chinese adult psychiatric patients that were analyzed by a complex mathematical model. The goal was to explore how oral olanzapine is eliminated from the body in Chinese psychiatric patients and how to personalize its dosing. Prior studies using similar complex mathematical models only studied the effects of sex and smoking on olanzapine elimination. This study also investigated the influence of co-occurrence of infection and comedications, including dangguilonghui tablets. This is a Chinese herbal medicine used to treat constipation, including constipation secondary to olanzapine treatment. Olanzapine elimination was increased by the following variables: 1.23-fold by male sex, 1.23-fold by smoking, 1.23-fold by comedication with valproate, 1.16-fold by sertraline, and 2.01-fold by dangguilonghui tablets. Olanzapine elimination was decreased by the following variables: 0.75-fold by co-occurrence of infection, 0.70-fold by fluvoxamine, and 0.78-fold by perphenazine. This study contributes to the improvement of oral olanzapine dosing personalization, but further studies are needed to verify the effects of infection and comedications, including valproate and dangguilonghui.


Assuntos
Antipsicóticos/farmacocinética , Transtornos Mentais/tratamento farmacológico , Modelos Biológicos , Olanzapina/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/administração & dosagem , Simulação por Computador , Interações Medicamentosas , Feminino , Humanos , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Olanzapina/administração & dosagem , Estudos Prospectivos , Fatores Sexuais , Fumar/epidemiologia , Distribuição Tecidual , Adulto Jovem
17.
J Phys Condens Matter ; 33(14)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33461183

RESUMO

Two-dimensional (2D) materials with both auxetic effect and ferroelasticity are rare, however, have great application potential in next generation microelectromechanical and nanoelectronic devices. Here, we report the findings of an extraordinary combination half-auxetic effect and ferroelasticity in a single p2mm-type TiSe monolayer by performing first-principles calculations. The unique half-auxetic effect, namely the material expand laterally under both uniaxial tensile strain, and compressive strain, is reported and explained by considering both the nearest and the next-nearest interactions. The ferroelasticity is stemming from the degeneracy breaking of the3d-orbitals of Ti atoms in a distorted tetrahedron crystal field, or the so-called Jahn-Teller effect. The results provide a guideline for the future design of novel 2D multiple functional materials at the nanoscale.

18.
Chin J Integr Med ; 27(12): 933-939, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33140205

RESUMO

OBJECTIVE: To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA). METHOD: A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund's adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11-7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted. RESULT: (1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1ß (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P<0.05 or P<0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P<0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P<0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P<0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11-7082+MA group decreased significantly and continued until day 5 and 7 (P<0.05 and P<0.01, respectively), and the NFκB p65 expression of CFA+BAY 11-7082+MA was significantly reduced compared with CFA+DMSO+MA (P<0.01). CONCLUSION: Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.


Assuntos
Analgesia por Acupuntura , Eletroacupuntura , Pontos de Acupuntura , Animais , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de Sinais
19.
Curr Med Sci ; 40(4): 618-624, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32767259

RESUMO

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Centro Germinativo/imunologia , Pneumonia Viral/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Imunidade Adaptativa , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Estudos de Casos e Controles , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Evolução Fatal , Feminino , Centro Germinativo/patologia , Humanos , Linfopenia/imunologia , Linfopenia/mortalidade , Linfopenia/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , SARS-CoV-2 , Linfócitos T Auxiliares-Indutores/patologia
20.
Clin Neurol Neurosurg ; 196: 106082, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682224

RESUMO

OBJECTIVE: This study was to investigate the clinical characteristics and prognosis of autoimmune encephalitis (AE) associated with anti-Glutamic Acid Decarboxylase 65 (GAD65). PATIENTS AND METHODS: From Jan 2016 to Aug 2018, three patients diagnosed as anti-GAD65 AE in our hospital were retrospectively analyzed for their general demographic characteristics, clinical presentation, cerebrospinal fluid (CSF) cytology, brain imaging, EEG, treatment and prognosis. RESULTS: We found that Anti-GAD65 AE may be more common in young and middle-aged women, with initial presentations of refractory status epilepticus or cognitive decline following the disease progresses, but with less psychiatric symptoms than other types of AEs. The abnormal signals of MRI may be obvious in bilateral frontal, temporal lobe and hippocampus. CONCLUSION: The production of anti-GAD65 may have a certain latency period, and it is usually negative at the onset stage. More studies need to be performed on larger populations and further understand the potential mechanisms underlying the above clinical features of anti-GAD65 AE.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Encefalite/imunologia , Glutamato Descarboxilase/imunologia , Adulto , Autoantígenos/imunologia , Encéfalo/patologia , Encefalite/patologia , Feminino , Humanos
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