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1.
Materials (Basel) ; 16(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38068013

RESUMO

Sodium-potassium (NaK) liquid alloy is a promising candidate for use as an anode material in sodium batteries because of its fluidity, which effectively suppresses the growth of sodium or potassium dendrites. However, the poor wettability of NaK alloy on conventional metal substrates is unfavorable for cell fabrication due to its strong surface tension. In this paper, low-density and low-cost fluorinated aluminum foam is used as a substrate support material for NaK liquid alloy. By combining low-surface-tension NaKC with fluorinated aluminum foam, we obtain a uniformly distributed and structurally stable electrode material. The composite electrode has a cycling stability of more than 3000 h in a symmetrical cell. Furthermore, when coupled with a sulfurized polyacrylonitrile cathode in carbonate electrolyte, it maintains excellent stability even after 800 cycles, with 72% of capacity retention.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(12): 1265-1269, 2023 Dec 15.
Artigo em Chinês | MEDLINE | ID: mdl-38112145

RESUMO

OBJECTIVES: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children. METHODS: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed. RESULTS: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure. CONCLUSIONS: Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.


Assuntos
Cáusticos , Estenose Esofágica , Criança , Humanos , Estenose Esofágica/induzido quimicamente , Estenose Esofágica/terapia , Constrição Patológica/complicações , Dilatação/efeitos adversos , Dilatação/métodos , Estudos Retrospectivos , Resultado do Tratamento
3.
Front Med (Lausanne) ; 10: 1267512, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034530

RESUMO

Introduction: Early stable deep molecular response (DMR) to nilotinib is associated with goal of treatment-free remission (TFR) in patients with chronic-phase chronic myeloid leukemia (CML-CP). It is important to early distinguish between patients who can achieve a DMR and those who are fit for TFR. Methods: We performed a multicenter study to explore the early cumulative MR4.5 rate at 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. Of the 29 institutes, 106 patients with ND-CML-CP received nilotinib (300 mg BID). Results and discussion: The cumulative MR4.5 rate of nilotinib treatment at 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates for nilotinib at 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with an ultra-early molecular response (u-EMR) at 6 weeks were not significantly different in obtaining DMR or MMR by 24 months compared with those without u-EMR (p = 0.7584 and p = 0.9543, respectively). Our study demonstrated that nilotinib treatment in patients with ND-CML-CP contributed to obtain high early MR4.5.

4.
Materials (Basel) ; 16(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687624

RESUMO

To increase the coating thickness and service life of the FeNiCrMo coating, a plasma transferred arc (PTA) double-track alloying technique was employed to enhance the surface triboperformance of the ductile iron. Optical microscopy (OM), X-ray diffraction (XRD), electron probe X-ray microanalyzer (EPMA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Vickers hardness tester, and tribological tester were subsequently used to evaluate the effect of the double alloying treatment tracks on the microstructure and triboperformance of the coating. The results indicate that the content of the cementite in the sample with a double-track treatment increases 3.90 wt.% and the content of the martensite decreases 13.04 wt.% compared with the sample with a single-track treatment, which results in the maximum microhardness of the sample fabricated by double track increasing from 837 ± 10 HV0.2 for the sample fabricated by single track to 871 ± 7 HV0.2. Thus, the wear rate is lower than that of the sample with a single-track treatment. In addition, the distribution of alloying elements is more uniform and coating thickness is higher in the double track than those of the single-track-treated one. Therefore, the double-track PTA alloying treatment is favored for hardfacing ductile iron with a FeNiCrMo alloy coating due to its enhanced triboperformance and longer service life.

5.
Medicine (Baltimore) ; 102(38): e35225, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37746979

RESUMO

RATIONALE: Ghost cell odontogenic carcinoma is a rare malignant odontogenic carcinoma characterized by the presence of ghost cells. It has a nonspecific clinical and radiographic presentation and can be locally destructive and invasive, sometimes with distant metastases. However, no effective systemic therapy is currently recommended for such patients. PATIENT CONCERNS: The patient has been unable to undergo surgery or radiotherapy again. Therefore, he was referred to our department for a more aggressive, multimodal systematic treatment program. DIAGNOSES: The histopathological examination was morphologically suggestive of ghost cell odontogenic carcinomas. INTERVENTIONS: We report a case of locally invasive primary inoperable odontogenic shadow cell carcinoma in a 31-year-old Chinese man who achieved treatment with Toripalimab and chemotherapy, followed by Toripalimab maintenance therapy after 6 cycles. OUTCOMES: He achieved partial remission after treatment. The quality of life significantly improved after treatment. There were no grade 3/4 treatment-related adverse events during treatment. LESSONS: This case presented that Toripalimab and chemotherapy may be a safe and effective systemic therapy for ghost cell odontogenic carcinoma.


Assuntos
Carcinoma , Neoplasias Maxilomandibulares , Neoplasias Bucais , Tumores Odontogênicos , Masculino , Humanos , Adulto , Qualidade de Vida , Tumores Odontogênicos/diagnóstico , Tumores Odontogênicos/terapia
6.
Front Immunol ; 14: 1211980, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37646026

RESUMO

Background: Clinically, some patients whose HBsAg becomes negative owing to antiviral therapy or spontaneously still show a low level of HBV DNA persistence in serum. T-lymphocyte subsets, cytokine levels and HBV S gene sequences were analyzed in this study. Methods: A total of 52 HBsAg-negative and HBV DNA-positive patients(HBsAg-/HBV DNA+ patients), 52 persistently HBsAg-positive patients(HBsAg+/HBV DNA+ patients) and 16 healthy people were evaluated. T-lymphocyte subsets of these patients were detected by flow cytometry, serum cytokines and chemokines were detected by the Luminex technique, and the HBV S region was evaluated by Sanger sequencing. T%, T-lymphocyte, CD8+ and CD4+T lymphocyte were lower in the HBsAg-negative group than in the HC group. Compared with the HBsAg-positive group, the HBsAg-negative group had lower levels in T lymphocyte %, CD8+T lymphocyte %, CD8+T lymphocyte and CD4/CD8. These difference were statistically significant (P<0.05). Serum IFN-γ, IFN-α and FLT-3L levels were significantly higher in the HBsAg-negative group than in the HBsAg-positive group (P<0.05). However, levels of many cytokines related to inflammation (i.e., IL-6, IL-8, IL10, IL-12, IL-17A) were lower in the HBsAg-negative group. Fifty-two HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., Y100C, S114T, C124Y, P127L, G130R, T131N, M133T, C137S, G145A) and TMD region substitutions (i.e., E2K/R/D, G7D/R, G10D, A17R, F20L/S, L21V, L22V). Conclusions: According to the results of T-lymphocyte subsets and serum cytokines, it can be deduced that the cellular immune function of HBsAg-negative patients is superior to that of HBsAg-positive patients, with attenuation of liver inflammation. HBsAg-negative patients may show a variety of mutations and amino acid replacement sites at high frequency in the HBV S region, and these mutations may lead to undetectable HBsAg, HBsAg antigenic changes or secretion inhibition.


Assuntos
Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , DNA Viral/genética , Interleucina-12 , Citocinas
7.
Zhen Ci Yan Jiu ; 48(6): 592-9, 2023 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-37385791

RESUMO

OBJECTIVE: To observe the effect of acupuncture at "Houxi"(SI3) and "Huantiao"(GB30) on high mobility group box 1(HMGB1) protein and mRNA in spinal nerve trunk(SNT) of rats with lumbar disc herniation(LDH), so as to explore the mechanisms of acupuncture at this paired points on the treatment for LDH. METHODS: SD rats were randomly divided into sham operation, model, conventional acupuncture(CA) and paired points(PP) groups (with 8 rats in each group). The LDH model was established by injection of autologous suspension made from rats' own nucleus pulsus into the epidural space. Rats in the CA group received acupuncture treatment at bilateral "Weizhong"(BL40), "Dachangshu"(BL25) and "Shenshu"(BL23), while rats in the PP group received acupuncture at bilateral SI3 and GB30, 30 min each time, once daily for 14 consecutive days. The thermal pain threshold of bilateral hind feet of rats was detected by thermal pain stimulator. The contents of serum IL-1ß, IL-6 and IL-8 of rats were detected by ELISA. Western blot and immunofluorescence were used to detect the expression of HMGB1 protein in the lumbar(L)5 SNT of rats. The relative expression of HMGB1 mRNA in L5 SNT was determined by qPCR. HE staining was used to observe the morphological changes of L5 SNT. RESULTS: Compared with the sham operation group, the thermal pain threshold of bilateral hind feet in the model group was decreased (P<0.05); compared with the model group, the thermal pain threshold of bilateral hind feet in the CA group and the PP group were increased (P<0.05). The expressions of HMGB1 protein and mRNA in L5 SNT, and the contents of serum IL-1ß, IL-6 and IL-8 of rats in the model group were significantly increased(P<0.000 1, P<0.001) in contrast to the sham operation group. The expressions of HMGB1 protein and mRNA in L5 SNT, and the levels of serum IL-1ß, IL-6 and IL-8 were significantly decreased (P<0.01, P<0.000 1, P<0.001, P<0.05) in the CA and PP group, in comparison with those of the model group. Compared with the CA group, the above indexes of rats in the PP group recovered more significantly (P<0.05,P<0.001, P<0.01,P<0.000 1). The histomorphological results showed scattered and various-sized nerve fibers, vacuolation, a large number of disintegrating myelin sheath and lysed Schwann cells in the model group. Myelin sheaths regeneration, regularly-arranged nerve fibers were seen in the CA group and the PP group, with more obvious histopathological recovery observed in the PP group than the CA group. CONCLUSION: Acupuncture intervention inhibites the expressions of HMGB1 protein and mRNA in rats with LDH, and further reduces the production of IL-1ß, IL-6 and IL-8, which is beneficial to inflammatory response inhibition and pain alleviation. The therapeutic effect of the PP group is more obvious than that of the CA group.


Assuntos
Terapia por Acupuntura , Proteína HMGB1 , Deslocamento do Disco Intervertebral , Animais , Ratos , Ratos Sprague-Dawley , Proteína HMGB1/genética , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/terapia , Interleucina-6/genética , Interleucina-8 , Dor , Nervos Espinhais
8.
J Virol ; 97(5): e0177022, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37129496

RESUMO

Vimentin (VIM), an indispensable protein, is responsible for the formation of intermediate filament structures within cells and plays a crucial role in viral infections. However, the precise role of VIM in classical swine fever virus (CSFV) infection remains unclear. Herein, we systematically investigated the function of VIM in CSFV replication. We demonstrated that both knockdown and overexpression of VIM affected CSFV replication. Furthermore, we observed by confocal microscopy the rearrangement of cellular VIM into a cage-like structure during CSFV infection. Three-dimensional (3D) imaging indicated that the cage-like structures were localized in the endoplasmic reticulum (ER) and ringed around the double-stranded RNA (dsRNA), thereby suggesting that VIM was associated with the formation of the viral replication complex (VRC). Mechanistically, phosphorylation of VIM at serine 72 (Ser72), regulated by the RhoA/ROCK signaling pathway, induced VIM rearrangement upon CSFV infection. Confocal microscopy and coimmunoprecipitation assays revealed that VIM colocalized and interacted with CSFV NS5A. Structurally, it was determined that amino acids 96 to 407 of VIM and amino acids 251 to 416 of NS5A were the respective important domains for this interaction. Importantly, both VIM knockdown and disruption of VIM rearrangement inhibited the localization of NS5A in the ER, implying that VIM rearrangement recruited NS5A to the ER for VRC formation. Collectively, our results suggest that VIM recruits NS5A to form a stable VRC that is protected by the cage-like structure formed by VIM rearrangement, ultimately leading to enhanced virus replication. These findings highlight the critical role of VIM in the formation and stabilization of VRC, which provides alternative strategies for the development of antiviral drugs. IMPORTANCE Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly infectious disease that poses a significant threat to the global pig industry. Therefore, gaining insights into the virus and its interaction with host cells is crucial for developing effective antiviral measures and controlling the spread of CSF. Previous studies have shown that CSFV infection induces rearrangement of the endoplasmic reticulum, leading to the formation of small vesicular organelles containing nonstructural protein and double-stranded RNA of CSFV, as well as some host factors. These organelles then assemble into viral replication complexes (VRCs). In this study, we have discovered that VIM recruited CSFV NS5A to form a stable VRC that was protected by a cage-like structure formed by rearranged VIM. This enhanced viral replication. Our findings not only shed light on the molecular mechanism of CSFV replication but also offer new insights into the development of antiviral strategies for controlling CSFV.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Suínos , Animais , Vírus da Febre Suína Clássica/fisiologia , Vimentina/metabolismo , RNA de Cadeia Dupla , Filamentos Intermediários/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Antivirais , Aminoácidos/genética
9.
J Orthop Surg Res ; 18(1): 282, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37024933

RESUMO

BACKGROUND: To explore the surgical technique and clinical outcomes of cementless total hip arthroplasty (THA) combined with impacted bone grafting for the treatment of moderate and severe acetabular protrusion with rheumatoid arthritis (RA). METHODS: From January 2010 to October 2020, 45 patients (56 hips), including 17 men (22 hips) and 28 women (34 hips) with acetabular impingement secondary to RA, were treated with bioprosthetic THA combined with autologous bone grafting at our hospital. According to the Sotello-Garza and Charnley classification criteria, there were 40 cases (49 hips) of type II (protrusio acetabuli 6-15 mm) and 5 cases (7 hips) of type III (protrusio acetabuli > 15 mm). At the postoperative follow-up, the ROM of the hip joint, the VAS score, and the Harris score were evaluated. The healing of the bone graft, the restoration of the hip rotation center, and the prosthesis loosening were assessed by plain anteroposterior radiographs. RESULTS: The average operation time was 95.53 ± 22.45 min, and the mean blood loss was 156.16 ± 69.25 mL. There were no neurovascular complications during the operation. The mean follow-up duration was 5.20 ± 1.20 years. The horizontal distance of the hip rotation center increased from preoperative 10.40 ± 2.50 mm to postoperative 24.03 ± 1.77 mm, and the vertical distance increased from preoperative 72.36 ± 3.10 mm to postoperative 92.48 ± 5.31 mm. The range of flexion motion of the hip joint increased from 39.48 ± 8.36° preoperatively to 103.07 ± 7.64° postoperatively, and the range of abduction motion increased from 10.86 ± 4.34° preoperatively to 36.75 ± 3.99° postoperatively. At the last follow-up, the Harris score increased from 37.84 ± 4.74 to 89.55 ± 4.05. All patients were able to move independently without assistance. CONCLUSIONS: Cementless THA combined with impacted grafting granule bone of the autogenous femoral head and biological acetabular cup can reconstruct the acetabulum, restore the rotation center of the hip joint, and achieve good medium-term outcomes in the treatment of moderate to severe acetabular herniation secondary to RA.


Assuntos
Artrite Reumatoide , Artroplastia de Quadril , Prótese de Quadril , Masculino , Humanos , Feminino , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/cirurgia , Resultado do Tratamento , Seguimentos , Estudos Retrospectivos
10.
Front Endocrinol (Lausanne) ; 14: 1119201, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025407

RESUMO

Introduction: Type 2 diabetes mellitus (T2DM) has a high incidence rate globally, increasing the burden of death, disability, and the economy worldwide. Previous studies have found that the compositions of oral and intestinal microbiota changed respectively in T2DM; whether the changes were associated or interacted between the two sites and whether there were some associations between T2DM and the ectopic colonization of oral microbiota in the gut still need to be identified. Research design and methods: We performed a cross-sectional observational study; 183 diabetes and 74 controls were enrolled. We used high-throughput sequencing technology to detect the V3-V4 region of 16S rRNA in oral and stool samples. The Source Tracker method was used to identify the proportion of the intestinal microbiota that ectopic colonized from the oral cavity. Results: The oral marker bacteria of T2DM were found, such as Actinobacteria, Streptococcus, Rothia, and the intestinal marker bacteria were Bifidobacterium, Streptococcus, and Blautia at the genus level. Among them, Actinobacteria and Blautia played a vital role in different symbiotic relationships of oral and intestinal microbiota. The commonly distributed bacteria, such as Firmicutes, Bacteroidetes, and Actinobacteria, were found in both oral and intestine. Moreover, the relative abundance and composition of bacteria were different between the two sites. The glycine betaine degradation I pathway was the significantly up-regulated pathway in the oral and intestinal flora of T2DM. The main serum indexes related to oral and intestinal flora were inflammatory. The relative abundance of Proteobacteria in the intestine and the Spirochete in oral was positively correlated, and the correlation coefficient was the highest, was 0.240 (P<0.01). The proportion of ectopic colonization of oral flora in the gut of T2DM was 2.36%. Conclusion: The dysbacteriosis exited in the oral and intestine simultaneously, and there were differences and connections in the flora composition at the two sites in T2DM. Ectopic colonization of oral flora in the intestine might relate to T2DM. Further, clarifying the oral-gut-transmitting bacteria can provide an essential reference for diagnosing and treating T2DM in the future.


Assuntos
Actinobacteria , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Microbiota , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Estudos Transversais , Bactérias/genética , Actinobacteria/genética , Clostridiales/genética
11.
J Virol ; 97(1): e0192922, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36602362

RESUMO

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is an important and highly infectious pig disease worldwide. Kinesin-1, a molecular motor responsible for transporting cargo along the microtubule, has been demonstrated to be involved in the infections of diverse viruses. However, the role of kinesin-1 in the CSFV life cycle remains unknown. Here, we first found that Kif5B played a positive role in CSFV entry by knockdown or overexpression of Kif5B. Subsequently, we showed that Kif5B was associated with the endosomal and lysosomal trafficking of CSFV in the early stage of CSFV infection, which was reflected by the colocalization of Kif5B and Rab7, Rab11, or Lamp1. Interestingly, trichostatin A (TSA) treatment promoted CSFV proliferation, suggesting that microtubule acetylation facilitated CSFV endocytosis. The results of chemical inhibitors and RNA interference showed that Rac1 and Cdc42 induced microtubule acetylation after CSFV infection. Furthermore, confocal microscopy revealed that cooperation between Kif5B and dynein help CSFV particles move in both directions along microtubules. Collectively, our study shed light on the role of kinesin motor Kif5B in CSFV endocytic trafficking, indicating the dynein/kinesin-mediated bidirectional CSFV movement. The elucidation of this study provides the foundation for developing CSFV antiviral drugs. IMPORTANCE The minus end-directed cytoplasmic dynein and the plus end-directed kinesin-1 are the molecular motors that transport cargo on microtubules in intracellular trafficking, which plays a notable role in the life cycles of diverse viruses. Our previous studies have reported that the CSFV entry host cell is dependent on the microtubule-based motor dynein. However, little is known about the involvement of kinesin-1 in CSFV infection. Here, we revealed the critical role of kinesin-1 that regulated the viral endocytosis along acetylated microtubules induced by Cdc42 and Rac1 after CSFV entry. Mechanistically, once CSFV transported by dynein met an obstacle, it recruited kinesin-1 to move in reverse to the anchor position. This study extends the theoretical basis of intracellular transport of CSFV and provides a potential target for the control and treatment of CSFV infection.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Cinesinas , Animais , Vírus da Febre Suína Clássica/fisiologia , Dineínas/metabolismo , Endocitose , Cinesinas/genética , Cinesinas/metabolismo , Microtúbulos/metabolismo , Microtúbulos/virologia , Suínos , Internalização do Vírus , Replicação Viral/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Transporte Proteico
12.
EJHaem ; 3(4): 1220-1230, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36467815

RESUMO

Background: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). Optimizing dose of tyrosine kinase inhibitors (TKIs) in the CML treatment maybe a new challenge to maintain effective and improving patients' quality of life. We hypothesized that administration of low-dose TKIs does not compromise major molecular response (MMR) in patients with CML who have a deep molecular response (DMR). Methods: We did an open-label, randomized trial at eight hospitals in China. Eligible CML-CP patients (aged 18-70 years) had shown continuous response to TKI more than 5 years and maintained MR4.5 (BCR-ABLIS ≤ 0.0032%) in recent 18 months. Patients were randomly assigned (1:1) to the TKI de-escalation group or the discontinuation group. Randomization was done with permuted blocks (block size four) and implemented through an interactive web-based randomization system. Recurrence was defined as the single sample with real time Quantitative PCR (RT-qPCR) measurement greater than 0.1% (MMR). The primary endpoint was 12-month MMR rate in patients who received de-escalation or discontinuation of TKIs. This study was registered at ClinicalTrials.gov (NCT04143087). Results: Around 125 patients were enrolled between October 23, 2019 and October 31, 2020, 62 patients received dose de-escalation of TKIs, while 63 patients in the discontinuation group. In the de-escalation group, molecular recurrence-free survival at 12 months was 88.32% (95% CI 79%-98%), whereas molecular recurrence-free survival in the discontinuation group at 12 months was 59.98% (95% CI 47-73). No progressions occurred at the data cut-off date. All 29 recurrence cases restart TKI treatment returned to MMR. Cytolytic NK cells as a proportion of lymphocyte cells were significantly increased from baseline after 6 months whether in the de-escalation or TKIs cessation group (P = 0.048, 0.001, respectively); compared with the relapsing patients, Tregs proportion was decreased (P = 0.003), and higher proportion of NK cells were found in non-relapsing patients whether in TKI de-escalation or discontinuation group (P = 0.011, 0.007, respectively). We also found that the de-escalation group showed better disease-specific HRQOL in regards to its impact on emotional functioning, fatigue, pain, and financial difficulties. Conclusion: With 88.32% MMR in 12-months follow-up after de-escalation TKIs' treatment, dose-halving could become a new treatment paradigm for CML patients who with DMR under continuing maintenance therapy with TKIs.

13.
Front Immunol ; 13: 984697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203614

RESUMO

Background: The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown. Methods: A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing. Results: Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni's correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients' gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P<0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients (P<0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative. Conclusion: The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis.


Assuntos
Microbioma Gastrointestinal , Cirrose Hepática Biliar , Feminino , Microbioma Gastrointestinal/genética , Genes MHC da Classe II , Antígenos HLA/genética , Cadeias HLA-DRB1/genética , Humanos , Cirrose Hepática Biliar/genética , Masculino , RNA
14.
Gynecol Endocrinol ; 38(11): 928-934, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36050880

RESUMO

Introduction: The efficacy of selenium supplementation was elusive for polycystic ovary syndrome. This meta-analysis aimed to explore the efficacy of selenium supplementation for polycystic ovary syndrome. Methods: PubMed, EMbase, Web of science, EBSCO, Cochrane library database, CNKI, Chongqing VIP database and Wanfang databases have been searched through July 2022 and we included randomized controlled trials (RCTs) reporting the effect of selenium supplementation versus placebo in patients with polycystic ovary syndrome. Results: Five RCTs were included in the meta-analysis. Compared with placebo group for polycystic ovary syndrome, selenium supplementation was associated with significantly reduced total testosterone (SMD=-0.42; 95% CI=-0.78 to -0.06; p = 0.02) and cholesterol (SMD=-0.71; 95% CI=-1.41 to -0.02; p = 0.04), but revealed no remarkable influence on SHBG (SMD=-0.52; 95% CI=-1.29 to 0.25; p = 0.19), triglyceride (SMD=-1.45; 95% CI=-3.62 to 0.73; p = 0.19), LDL (SMD=-0.17; 95% CI=-0.72 to 0.37; p = 0.53), FPG (SMD=-0.95; 95% CI=-3.72 to 1.82; p = 0.50) or HOMA-IR (SMD=-0.51; 95% CI=-3.79 to 2.77; p = 0.76). Conclusions: Selenium supplementation may be able to improve the metabolic response for polycystic ovary syndrome, and this finding should be interpreted with caution.


Assuntos
Síndrome do Ovário Policístico , Selênio , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Selênio/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Testosterona/uso terapêutico , Suplementos Nutricionais
15.
ACS Appl Mater Interfaces ; 14(40): 45382-45391, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36170595

RESUMO

Sodium is one of the most promising anode candidates for the beyond-lithium-ion batteries. The development of Na metal batteries with a high energy density, high safety, and low cost is desirable to meet the requirements of both portable and stationary electrical energy storage. However, several problems caused by the unstable Na metal anode and the unsafe liquid electrolyte severely hinder their practical applications. Herein, we report a facile but effective methodology to construct an in situ polymer electrolyte and Na-rich artificial solid-electrolyte interface (SEI) layer concurrently. The obtained integrated Na metal batteries display long cycling life and admirable dynamic performance with total inhibition of dendrites, excellent contact of the cathode/polymer electrolyte, and reduction of side reactions during cycling. The modified Na metal electrode with the in situ polymer electrolyte is stable and dendrite-free in repeated plating/stripping processes with a life span of above 1000 h. Moreover, this method is compatible with different cathodes that demonstrate outstanding electrochemical performance in full cells. We believe that this approach provides a practical solution to solid-state Na metal batteries.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(8): 917-922, 2022 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36036131

RESUMO

A girl aged 12 years and 2 months presented with recurrent abdominal pain and vomiting for more than 2 years and arthrodynia for 3 months. She was diagnosed with recurrent acute pancreatitis with unknown causes and had been admitted multiple times. Laboratory tests showed recurrent significant increases in fasting serum triglyceride, with elevated immunoglobulin and positive antinuclear antibody. The girl was improved after symptomatic supportive treatment. The girl developed arthrodynia with movement disorders 3 months before, and proteinuria, hematuria, and positive anti-double-stranded DNA antibody were observed. The renal biopsy was performed, and the pathological examination and immunofluorescence assay suggested diffuse lupus nephritis (type Ⅳ). She was finally diagnosed with systemic lupus erythematosus (SLE), lupus nephritis (type Ⅳ), and recurrent acute pancreatitis. Pancreatitis was suspected to be highly associated with SLE. She was treated with oral hydroxychloroquine sulfate and intravenous methylprednisolone sodium succinate and cyclophosphamide. Arthrodynia was partially relieved. She was then switched to oral prednisone acetate tablets. Intravenous cyclophosphamide and pump infusion of belimumab were regularly administered. Now she had improvement in arthrodynia and still presented with proteinuria and hematuria. It is concluded that recurrent acute pancreatitis may be the first clinical presentation of SLE. For pancreatitis with unknown causes, related immunological parameters should be tested, and symptoms of the other systems should be closely monitored to avoid delaying the diagnosis.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Pancreatite , Dor Abdominal , Doença Aguda , Anticorpos Antinucleares , Ciclofosfamida , Feminino , Hematúria , Humanos , Proteinúria , Triglicerídeos , Vômito
17.
Clin Lymphoma Myeloma Leuk ; 22(9): e867-e873, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35842355

RESUMO

BACKGROUND: Brand-name dasatinib was approved for newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP) patients due to its deeper and faster molecular response than imatinib. Generics, as the alternative, low-cost forms, are much in demand. This study aimed to evaluate the efficacy and safety of generic dasatinib (Yinishu) as a first-line treatment in CML-CP. MATERIALS AND METHODS: This was a prospective, multicenter, single-arm study from May 2016 to October 2018 with a 2-year follow-up analysis. All patients were given 100 mg/d (initial dose) of the generic dasatinib once a day. The primary endpoint was the major molecular response (MMR) calculated based on the BCR-ABL1 gene mutation rate of ≤ .1% at 12 months. RESULTS: Among 55 patients in CP observed for at least 3 months, 80.4% achieved MMR at 12 months. The cumulative MR4.5 was 58.2% by 24 months. Responses occurred rapidly, with 69.1% of patients achieving complete cytogenetic response (CCyR) by 3 months and 70.9% achieving CCyR by 6 months. The estimated 2-year PFS and OS were both 96%, with a median follow-up time of 24 months. Grade 3 neutropenia occurred in 8.5% of patients, and thrombocytopenia occurred in 11.9% of patients. Nonhematologic toxicity was usually mild and manageable. Pleural effusion occurred in 20.3% of patients, and only 1 patient (1.7%) had a grade 3 pleural effusion. No grade 4 adverse events were observed. CONCLUSION: Generic dasatinib is an effective option for newly diagnosed CML-CP patients, producing an MMR early in a greater number of patients during their therapy.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Derrame Pleural , Antineoplásicos/efeitos adversos , Dasatinibe/efeitos adversos , Medicamentos Genéricos/efeitos adversos , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento
18.
Stem Cell Res Ther ; 13(1): 340, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35883157

RESUMO

BACKGROUND: Nucleus pulposus mesenchymal stem cells (NPMSCs) transplantation is a promising treatment for intervertebral disc degeneration (IVDD). However, the transplanted NPMSCs exhibited weak cell proliferation, high cell apoptosis, and a low ability to resist the harsh microenvironment of the degenerated intervertebral disc. There is an urgent need to explore feasible methods to enhance the therapeutic efficacy of NPMSCs transplantation. OBJECTIVE: To identify the optimal concentration for NPMSCs pretreatment with hydrogen peroxide (H2O2) and explore the therapeutic efficacy of NPMSCs transplantation using H2O2 pretreatment in IVDD. METHODS: Rat NPMSCs were pretreated with different concentrations (range from 25 to 300 µM) of H2O2. The proliferation, reactive oxygen species (ROS) level, and apoptosis of NPMSCs were detected by cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry in vitro. The underlying signalling pathways were explored utilizing Western blotting. A rat needle puncture-stimulated IVDD model was established. X-ray, histological staining, and a multimode small animal live imaging system were used to evaluate the therapeutic effect of H2O2-pretreated NPMSCs in vivo. RESULTS: NPMSCs pretreated with 75 µM H2O2 demonstrated the strongest elevated cell proliferation by inhibiting the Hippo pathway (P < 0.01). Meanwhile, 75 µM H2O2-pretreated NPMSCs exhibited significantly enhanced antioxidative stress ability (P < 0.01), which is related to downregulated Brd4 and Keap1 and upregulated Nrf2. NPMSCs pretreated with 75 µM H2O2 also exhibited distinctly decreased apoptosis (P < 0.01). In vivo experiments verified that 75 µM H2O2-pretreated NPMSCs-transplanted rats exhibited an enhanced disc height index (DHI% = 90.00 ± 4.55, P < 0.01) and better histological morphology (histological score = 13.5 ± 0.5, P < 0.01), which means 75 µM H2O2-pretreated NPMSCs can better adapt to the environment of degenerative intervertebral discs and promote the repair of IVDD. CONCLUSIONS: Pretreatment with 75 µM H2O2 was the optimal concentration to improve the proliferation, antioxidative stress, and antiapoptotic ability of transplanted NPMSCs, which is expected to provide a new feasible method to improve the stem cell therapy efficacy of IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Animais , Apoptose , Peróxido de Hidrogênio/farmacologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Proteína 1 Associada a ECH Semelhante a Kelch , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Núcleo Pulposo/metabolismo , Ratos
19.
World J Clin Cases ; 10(10): 3251-3260, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35647125

RESUMO

BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a clinically rare and aggressive fungus mainly found in contaminated water, wetlands, decaying plants, stagnant water, and potted plants in hospitals. The lung, bone, joint, eye, brain, skin, and other sites are easily infected, and there is a marked risk of misdiagnosis. There have been few case reports of infection by S. apiospermum of the lumbar vertebrae; most reports have focused on infection of the lung. CASE SUMMARY: An otherwise healthy 60-year-old man presented with a 4-mo history of lumbosacral pain, stooping, and limited walking. The symptoms were significantly aggravated 10 d prior to hospitalization, and radiating pain in the back of his left lower leg developed, which was so severe that he could not walk. Movement of the lumbar spine was significantly limited, anterior flexion was about 30°; backward extension, right and left lateral curvature, and rotational mobility were about 10°; tenderness of the spinous processes of the lumbar 3-5 vertebrae was evident, and the muscle strength of both lower limbs was grade IV. Imaging suggested bony destruction of the lumbar 3, 4, and 5 vertebrae and sacral 1 vertebra; in addition, the corresponding intervertebral spaces were narrowed and the lumbar 5 vertebra was posteriorly displaced and unstable. Lumbar vertebral infection was also noted, and the possibility of lumbar tuberculosis was considered. We first performed surgical intervention on the lesioned lumbar vertebrae, cleared the infected lesion, and performed stable fixation of the lesioned vertebral body using a lumbar internal fixation device, which restored the stability of the lumbar vertebrae. Cytological and pathological examination of the lesioned tissue removed during surgery confirmed S. apiospermum infection of the lumbar vertebrae; on this basis, the patient was administered voriconazole. At the 6-mo follow-up, efficacy was significant, no drug-related side effects were observed, and imaging examination showed no evidence of recurrence. CONCLUSION: S. apiospermum infection can occur in immunocompetent individuals with no history of near drowning. Voriconazole is effective for the treatment of S. apiospermum infection of the lumbar vertebrae for which it is suitable as the first-line therapy.

20.
World J Pediatr ; 18(8): 538-544, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35771382

RESUMO

BACKGROUND: Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated occurrence. This review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital's previous experiences with the diagnosis and treatment of severe acute hepatitis for reference. DATA SOURCES: Websites including the UK Health Security Agency, European Centre for Disease Prevention and Control, CDC, WHO, and databases including PubMed/Medline, Cochrane Library, Embase and Web of Science were searched for articles on severe acute hepatitis in children. RESULTS: As of May 26, 2022, a total of 650 cases have been reported in 33 countries; at least 38 (6%) children required liver transplantation, and nine (1%) died. Cases are predominantly aged between 3 and 5 years old, and there are no epidemiological links among them. The common manifestations are jaundice, vomiting and pale stools. Adenovirus tested positive in most cases, and SARS-CoV-2 and other viruses were detected in a few cases, but virus particles were not found in liver tissue. Adenovirus immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver samples. The hierarchical treatment includes symptomatic and supportive therapy, management of coagulation disorders and hepatic encephalopathy, artificial liver support, and liver transplantation (approximately 6%-10% of cases require liver transplant). CONCLUSIONS: The etiology of this severe acute hepatitis in children is not clear. The clinical features are severe acute hepatitis with significantly elevated liver enzymes. Clinicians need to be alert to children with hepatitis.


Assuntos
Hepatite , Doença Aguda , Criança , Pré-Escolar , Hepatite/diagnóstico , Hepatite/prevenção & controle , Hepatite/terapia , Humanos
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