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1.
World J Gastrointest Oncol ; 16(6): 2476-2486, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994164

RESUMO

BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

2.
Cell Stem Cell ; 30(12): 1624-1639.e8, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-37989316

RESUMO

Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating ß-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression. Via a side-by-side comparison with other clinical and preclinical strategies using Cas9 nuclease or conventional BEs (ABE8e and hA3A-BE3), we found that tBE-mediated disruption of the BCL11A-binding motif at the HBG1/2 promoters triggered the highest fetal hemoglobin in healthy and ß-thalassemia patient hematopoietic stem/progenitor cells while exhibiting no detectable DNA or RNA off-target mutations. Durable therapeutic editing by tBE persisted in repopulating hematopoietic stem cells, demonstrating that tBE-mediated editing in HBG1/2 promoters is a safe and effective strategy for treating ß-hemoglobinopathies.


Assuntos
Edição de Genes , Hemoglobinopatias , Humanos , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , gama-Globinas/genética , gama-Globinas/metabolismo , Sistemas CRISPR-Cas , Mutação/genética , Hemoglobinopatias/genética , Hemoglobinopatias/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Fatores de Transcrição/metabolismo
3.
Front Plant Sci ; 14: 1243764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881614

RESUMO

Introduction: Monoecy is usually interpreted as an important evolutionary route of the plant sexual system from hermaphroditism to dioecy. This floral mechanism can effectively reduce self-interference during the reproductive process, and the services provided by pollinators may play an essential role in monoecious species; however, relevant research is still lacking. Thus, we aimed to determine whether monoecious plants could effectively avoid self-interference and promote the evolution of monoecy under the service of pollinators. Methods: Here, we successfully performed manipulation experiments to test self-compatibility, pollinator behavior, and self-interference between male and female functions in Akebia trifoliata, a typical monoecious species. Results: We demonstrated that experimental self-pollination did not yield any fruit, and supplemental pollination significantly increased fruit set and fruit weight compared to natural pollination, suggesting that this species is completely self-incompatible and experiences strong pollen limitation. Simultaneous self- and cross-pollination and self-pollination prior to cross-pollination significantly reduced reproductive fitness, but self-pollination after cross-pollination did not, indicating self-interference in this plant. Moreover, both male flower probing preference and switching modes within inflorescences by pollinators successfully reinforced self-interference and were also responsible for decreasing reproductive fitness in A. trifoliata. Discussion: In summary, pollinator-mediated self-interference significantly reduced selfing, providing potential dynamics for the maintenance and evolution of monoecy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-37797462

RESUMO

A novel sample preparation method based on polarity grouping was developed for the comprehensive determination of 315 undesirable low-weight organic pollutants ranging from polar to weakly polar in wolfberry. The method involves the swelling of the sample in ammonium acetate buffer, two-phase extraction, three-phase extraction, and dispersive solid phase extraction (D-SPE) with the assistance of low-temperature centrifugation and analysis by ultrahigh performance liquid chromatography coupled with electrospray ionization tandem mass (UHPLC-ESI-MS-MS) by using the multiple reaction monitoring mode. The recoveries of the analytes with wide range of polarity were satisfactory. The matrix-fortified standard calibration curves were compared for quantification. The results of linearity were satisfactory with linear regression coefficients (R) ranging from 0.9901 to 1.000. The limits of quantification ranged from 1 µg/kg to 10.0 µg/kg, indicating the compliance of products with legal tolerances. The average recoveries for spiked wolfberry were in the range of 69.3 %-145.2 % with RSD values of 0.2 %-28.6 %. The inter-day precision was in the range of 0.2 %-27.0 %. For over 90 % of the analytes, the recoveries were 70 %-120 % with RSD values below 20 %. The application of this method in routine monitoring programs would imply a drastic reduction of both effort and time.


Assuntos
Lycium , Praguicidas , Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Extração em Fase Sólida , Cromatografia Líquida de Alta Pressão/métodos
5.
World J Gastroenterol ; 29(23): 3715-3732, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37398887

RESUMO

BACKGROUND: Robotic surgery is a cutting-edge minimally invasive technique that overcomes many shortcomings of laparoscopic techniques, yet few studies have evaluated the use of robotic surgery to treat Hirschsprung's disease (HSCR). AIM: To analyze the feasibility and medium-term outcomes of robotic-assisted proctosigmoidectomy (RAPS) with sphincter- and nerve-sparing surgery in HSCR patients. METHODS: From July 2015 to January 2022, 156 rectosigmoid HSCR patients were enrolled in this multicenter prospective study. Their sphincters and nerves were spared by dissecting the rectum completely from the pelvic cavity outside the longitudinal muscle of the rectum and then performing transanal Soave pull-through procedures. Surgical outcomes and continence function were analyzed. RESULTS: No conversions or intraoperative complications occurred. The median age at surgery was 9.50 months, and the length of the removed bowel was 15.50 ± 5.23 cm. The total operation time, console time, and anal traction time were 155.22 ± 16.77, 58.01 ± 7.71, and 45.28 ± 8.15 min. There were 25 complications within 30 d and 48 post-30-d complications. For children aged ≥ 4 years, the bowel function score (BFS) was 17.32 ± 2.63, and 90.91% of patients showed moderate-to-good bowel function. The postoperative fecal continence (POFC) score was 10.95 ± 1.04 at 4 years of age, 11.48 ± 0.72 at 5 years of age, and 11.94 ± 0.81 at 6 years of age, showing a promising annual trend. There were no significant differences in postoperative complications, BFS, and POFC scores related to age at surgery being ≤ 3 mo or > 3 mo. CONCLUSION: RAPS is a safe and effective alternative for treating HSCR in children of all ages; it offers the advantage of further minimizing damage to sphincters and perirectal nerves and thus providing better continence function.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Doença de Hirschsprung , Procedimentos Cirúrgicos Robóticos , Criança , Humanos , Lactente , Pré-Escolar , Doença de Hirschsprung/cirurgia , Doença de Hirschsprung/complicações , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Reto/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos
6.
Diabetes Metab Syndr Obes ; 16: 1931-1939, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37398944

RESUMO

Objective: This study was performed to evaluate the effectiveness of social platform-based continuity of care in improving cognitive and prognostic effects of young age diabetic patients without diabetic retinopathy (DR). Methods: A total of 88 young age diabetic patients admitted to the outpatient clinic of First Affiliated Hospital of Soochow University (Endocrine and Ophthalmology Outpatient) from January 2021 to May 2022 were recruited and assigned via random number table method to receive either routine follow-up care (routine group) or social platform-based continuity of care (WeChat group), with 44 patients in each group. Treatment compliance, cognitive-behavioral ability, self-care ability (self-care responsibility, self-care skills, self-status, knowledge of diabetic retinopathy), quality of life (physical function, psychosocial, symptom and visual function, social activity), and prognosis of the patients were analyzed to investigate the effectiveness of WeChat social platform-based continuity of care. All patients were followed up for one year. Results: Patients receiving WeChat social platform-based continuity of care exhibited obviously higher treatment compliance and better cognitive-behavioral ability, self-care responsibility, self-care skills, self-state, and diabetic retinopathy knowledge follow-up than those with routine care (P<0.05). Patients in the WeChat group had significantly better physical function, mental psychology, symptoms and visual function, and social activity levels than those in the routine group (P<0.05). WeChat-based continuity of care resulted in a significantly lower incidence of visual acuity loss and diabetic retinopathy during follow-up than routine care (P<0.05). Conclusion: WeChat social platform-based continuity of care effectively improves treatment compliance and diabetic retinopathy awareness, and enhances self-care ability of young patients with diabetes mellitus. The life quality of these patients is improved and the risk of poor prognosis has been reduced.

7.
Altern Ther Health Med ; 29(6): 242-247, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37295012

RESUMO

Context: Gynecological malignancies can pose a serious threat to women's physical and mental health, and lymphedema is one of the common complications after surgery for malignant tumors. Comprehensive nursing might be able to reduce the lymphedema that occurs after surgery and help accelerate patients' postoperative rehabilitation process. Objective: The study intended to explore the effects of a comprehensive nursing intervention for patients with lower-limb lymphedema after surgery for malignant gynecological tumors. Design: The research team performed a retrospective controlled study. Setting: The study took place at Sichuan Cancer Hospital in Chengdu, China. Participants: Participants were 90 patients who received surgical treatment at the hospital for malignant gynecological tumors between April 2020 and July 2021. Intervention: The research team divided participants into two groups: (1) 45 in the intervention group who received a comprehensive nursing intervention based on a meta-heuristic learning model, and (2) 45 in the control group, who received routine nursing. The nursing intervention occurred for both groups for one year, from admission for surgery, baseline, to the end of treatment, postintervention. Outcome Measures: The research team: (1) assessed the efficacy postintervention of the nursing intervention for the two groups, (2) measured the circumference of participants' lower-limb edema at baseline and postintervention, (3) determined the incidence of lymphedema between baseline and postintervention in the two groups, (4) measured the nursing satisfaction scores of the two groups postintervention, and (5) evaluated participants' quality of life using the Abbreviated World Health Organization Quality-of-Life (WHOQOL-BREF) scale at baseline and postintervention. Results: Postintervention: (1) the efficacy of the nursing intervention for the intervention group was 95.56%, which was a significantly higher rate than that of the control group, at 82.22% (P = .044); (2) the intervention group's decrease in the mean circumference at 10 cm below the knee was significantly greater, from 40.43 ± 1.75 cm to 34.93 ± 1.94 cm, than that of the control group, from 39.93 ± 2.01 cm to 35.89 ± 2.27 cm (P = .034), and that group's decrease in the mean circumference at 10 cm above the knee was also significantly greater, from 49.50 ± 3.06 cm to 44.12 ± 2.14 cm, than that of the control group, from 49.13 ± 3.11 cm to 46.10 ± 1.94 cm (P < .001); (3) of the 45 participants in the intervention group, only one had lymphedema (2.22%), which was a significantly lower rate than that of the control group, at six participants out of 45 (13.33%), with P = .049; (4) the intervention group's mean score for nursing satisfaction was 86.59 ± 3.96, which was significantly higher than that of the control group, at 82.22 ± 5.61 (t = 4.269, P < .001); and (5) the intervention group's mean score on the WHOQOL-BREF scale was 25.52 ± 2.94, which was significantly higher than that of the control group, at 22.28 ± 3.00 (t = 5.174, P < .001). Conclusions: A comprehensive nursing intervention after surgery for patients with gynecological malignancies can reduce the incidence of lymphedema, be more effective, and enhance patients' satisfaction with nursing care and their quality of life.


Assuntos
Neoplasias dos Genitais Femininos , Linfedema , Humanos , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Projetos de Pesquisa , Linfedema/cirurgia
8.
Exp Anim ; 72(3): 413-424, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37019682

RESUMO

The imbalance of bone resorption and bone formation causes osteoporosis (OP), a common skeletal disorder. Decreased osteogenic activity was found in the bone marrow cultures from N-acetylglucosaminyl transferase V (MGAT5)-deficient mice. We hypothesized that MGAT5 was associated with osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and involved in the pathological mechanisms of osteoporosis. To test this hypothesis, the mRNA and protein expression levels of MGAT5 were determined in bone tissues of ovariectomized (OVX) mice, a well-established OP model, and the role of MGAT5 in osteogenic activity was investigated in murine BMSCs. As expected, being accompanied by the loss of bone mass density and osteogenic markers (runt-related transcription factor 2, osteocalcin and osterix), a reduced expression of MGAT5 in vertebrae and femur tissues were found in OP mice. In vitro, knockdown of Mgat5 inhibited the osteogenic differentiation potential of BMSCs, as evidenced by the decreased expressions of osteogenic markers and less alkaline phosphatase and alizarin red S staining. Mechanically, knockdown of Mgat5 suppressed the nuclear translocation of ß-catenin, thereby downregulating the expressions of downstream genes c-myc and axis inhibition protein 2, which were also associated with osteogenic differentiation. In addition, Mgat5 knockdown inhibited bone morphogenetic protein (BMP)/transforming growth factor (TGF)-ß signaling pathway. In conclusion, MGAT5 may modulate the osteogenic differentiation of BMSCs via the ß-catenin, BMP type 2 (BMP2) and TGF-ß signals and involved in the process of OP.


Assuntos
Células-Tronco Mesenquimais , Osteoporose , Animais , Camundongos , beta Catenina/metabolismo , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Osteogênese/genética
9.
Zhongguo Gu Shang ; 36(2): 110-5, 2023 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-36825408

RESUMO

OBJECTIVE: To evaluate the clinical outcomes of reverse total shoulder arthroplasty as a revision procedure for the failed fixation of proximal humeral fractures in the elderly patients. METHODS: A retrospective analysis was performed on 8 patients with failed internal fixation of proximal humeral fractures from May 2014 to March 2020, including 3 males and 5 females, aged from 65 to 75 years old. All 8 patients underwent reverse total shoulder arthroplasty, and the mean time between initial fixation and reverse total shoulder arthroplasty ranged from 8 to 16 months. Range of motion(ROM), University of California at Los Angeles(UCLA) shoulder score, visual analogue scale (VAS), self-rating anxiety scale(SAS), and Constant-Murley score of shoulder function were assessed pre-operatively and at the last follow-up. Complications relating to the surgery were recorded. RESULTS: All 8 patients successfully followed up. The mean follow-up after reverse total shoulder arhroplasty ranged from 16 to 28 months. The range of motion (forward flexion, external rotation, abduction and internal rotation) of the affected shoulder was significantly improved after surgery, and the post-operative VAS, SAS and UCLA scores were also significantly improved. For the Constant-Murley score of shoulder joint function, the total scores and the subscores of pain, daily activities, range of motion and strength test at the last follow-up were all significantly improved. Scapular glenoid notch was observed in patient, which was evaluated as grade 1 on imaging. All the other patients did not develop specific or non-specific complications. CONCLUSION: Reverse total shoulder arhroplasty is an appropriate treatment as a revision surgery for failed fixation of proximal humeral fractures. It has shown satisfactory clinical outcomes, accelerating the rehabilitation of shoulder function and improving the quality of life.


Assuntos
Artroplastia do Ombro , Fraturas do Ombro , Articulação do Ombro , Masculino , Feminino , Humanos , Idoso , Ombro/cirurgia , Artroplastia do Ombro/efeitos adversos , Artroplastia do Ombro/métodos , Estudos Retrospectivos , Resultado do Tratamento , Qualidade de Vida , Articulação do Ombro/cirurgia , Fraturas do Ombro/cirurgia , Úmero/cirurgia , Amplitude de Movimento Articular
10.
Cell Rep ; 42(2): 112075, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36774551

RESUMO

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.


Assuntos
Infecções Irruptivas , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais
11.
Acta Pharmacol Sin ; 44(4): 841-852, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36253561

RESUMO

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.


Assuntos
Arsenicais , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Neoplasias Pulmonares/patologia , Linhagem Celular Tumoral , Ftalazinas/farmacologia
12.
Surg Endosc ; 37(1): 31-47, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913517

RESUMO

BACKGROUND: Most commonly, cyst excision and Roux-en-Y hepaticojejunostomy reconstruction are the optimal treatment for choledochal cysts (CC). Robotic surgery (RS) is being conducted with increasing frequency to treat CC. It is unclear whether RS can overcome the limitations of laparoscopic surgery (LS) and improve the prognosis of patients. In terms of efficacy, evidence concerning which minimally invasive surgery is preferred is, however, sparse. Our objective is to further compare the efficacy of RS and LS in children with CC and draw a useful clinical conclusion. METHODS: Studies meeting inclusion criteria were identified from a series of databases, consisting of PubMed, Embase, Scopus, Web of Science, the Cochrane Library and their reference list of articles up to May 2022. Eligible articles comprised at least five objects that were younger than 18 years of age and the language was limited to English. Two authors independently evaluated selected studies and extracted data for analysis. RESULTS: Forty studies were selected for analysis, with thirty-six reporting data on LS and eight containing data on RS. The pooled conversion rate and pooled postoperative complication rate of RS were lower than those of LS, but none of them was statistically significant. Moreover, comparisons of the following detailed postoperative complication rates were not statistically significant, such as intestinal obstruction or ileus, anastomotic bleeding, anastomotic or bile leakage, and anastomotic stenosis. However, the intraoperative blood loss and the postoperative hospital stay in RS group were significantly lower than those in LS group. CONCLUSIONS: RS is a safe and feasible option for children with CC. Further studies with more cases, long-term efficacy and health economics analysis are needed to confirm whether RS is more advantageous.


Assuntos
Cisto do Colédoco , Obstrução Intestinal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Criança , Humanos , Anastomose em-Y de Roux , Cisto do Colédoco/cirurgia , Obstrução Intestinal/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(5): 798-804, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36224681

RESUMO

Objective: To investigate the effect of hydrogen sulfide (H 2S) on reactive oxygen species (ROS)-mediated endoplasmic reticulum stress in myocardial injury caused by sepsis. Methods: A sepsis model was induced in Sprague-Dawley (SD) rats by cecal ligation and puncture (CLP). The rats were randomly divided into sham operation (sham) group, sepsis (CLP) group, and sepsis+sodium hydrosulfide (NaHS) (CLP+NaHS) group. The left ventricular function of the rats was observed with echocardiography and their plasma H 2S levels were measured. Lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH) levels were measured and HE staining was done to evaluate the level of myocardial oxidative stress in rats. HE staining was done to observe the morphological changes of rat myocardium, and transmission electron microscope was used to observe the ultrastructure of myocardial mitochondria. Western blot was done to examine changes in the expression of two endogenous hydrogen sulfide synthases, cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3-MST), and changes in the expression of endoplasmic reticulum stress (ERS) marker proteins, including phosphorylated (p) protein kinase R-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic translation initiation factor 2α (p-eIF2α), p-inositol requires enzyme 1α (IRE1α), recombinant activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). TUNEL staining was performed to observe the changes of cardiomyocyte apoptosis in rats. Results: Left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS) and plasma H 2S decreased in septic rats ( P<0.05). Plasma H 2S exhibited linear correlation with LVEF and LVFS ( r 2=0.62 and r 2=0.64, all P<0.05). The ROS levels were significantly elevated in rats of the CLP group. In addition, these rats showed increased level of LDH ( P<0.05), increased expression of MDA ( P<0.05), and decreased expression of GSH ( P<0.05). Inflammatory cell infiltration and cardiomyocyte edema were observed in HE staining. Transmission electron microscopic observation revealed significant mitochondrial damage, observable mitochondrial edema, and cristae structure dissolution. The Western blot results showed that the expression levels of CSE and 3-MST decreased ( P<0.05), while the ERS marker proteins, including p-PERK, p-eIF2, IRE1α, ATF4, and CHOP, were expressed at increased levels ( P<0.05). TUNEL staining showed significant increase of apoptosis in cardiomyocytes ( P<0.05). After NaHS treatment, LVEF and LVFS increased ( P<0.05) and plasma H 2S increased in septic rats ( P<0.05). Myocardial oxidative stress levels decreased. HE staining and transmission electron microscopy showed improved myocardial morphology. Mitochondrial damage was reduced and CSE and 3-MST levels were significantly increased ( P<0.05). The expression of p-PERK, p-eIF2α, p-IRE1α, and CHOP proteins decreased ( P<0.05). A decrease in cardiomyocyte apoptosis levels was observed by TUNEL staining ( P<0.05). Conclusion: H 2S reduces septic cardiomyocyte apoptosis by inhibiting ROS-mediated ERS, thereby improving myocardial dysfunction in sepsis.


Assuntos
Sulfeto de Hidrogênio , Sepse , Animais , Ratos , Fator 4 Ativador da Transcrição/farmacologia , Apoptose , Cistationina gama-Liase/farmacologia , Estresse do Retículo Endoplasmático , Endorribonucleases/farmacologia , Fator de Iniciação 2 em Eucariotos/farmacologia , Glutationa , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Inositol/farmacologia , Lactato Desidrogenases , Malondialdeído , Proteínas Serina-Treonina Quinases , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Volume Sistólico , Sulfetos , Enxofre/farmacologia , Função Ventricular Esquerda
15.
Zhongguo Gu Shang ; 35(9): 853-8, 2022 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-36124456

RESUMO

OBJECTIVE: To analyze clinical effect of intervention strategies based on Caprini thrombosis risk assessment model for preventing deep vein thrombosis (DVT) after total hip replacement (THR). METHODS: From January 2018 to December 2021, 197 patients with THR were selected as retrospective cohort study subjects, including 114 males and 83 females, aged from 45 to 80 years with an average of (66.81±10.34) years old. Caprini thrombosis risk assessment model introduced in May 2019 was used as boundary and divided into two groups, 94 patients were performed routine intervention strategies(control group) and 103 patients were received intervention strategies based on Caprini thrombosis risk assessment model (observation group). Incidence of DVT, visual analogue scale (VAS), circumference difference of affected limb, serum D-dimer (D-D) level and Harris score of hip function between two groups were analyzed. RESULTS: One-hundred and ninty-seven patients were followed up from 1 to 3 months with an average of (2.57±0.31) months. Incidence of DVT was 1.94% in observation group and 11.70% in control group, and there was statistical difference between two groups (χ2=6.642, P=0.010). VAS scores between two groups decreased gradually (P<0.001). There was significant difference between two groups in VAS score on the 1st, 2nd, 3rd and 7th day after operation (P<0.05), but no difference between two groups on the 10th day after operation (P>0.05). Difference in circumference of the affected limb between two groups after operation was gradually reduced (P<0.001), and the difference in circumference of the affected limb between two groups was statistically significant on the 1st, 2nd, 3rd, 7th, and 10th day after operation(P<0.05). Levels of serum D-D between two groups were gradually decreased after operation(P<0.05), and differences in serum D-D levels between two groups on the 8th, 24th, 48th, and 72th hour after operation were statistically significant (P<0.05). Pain score and Harris total scores between two groups were significantly increased as tomes goes on(P<0.001), no difference in VAS at 3 months after discharge, and there were statistically significant differences in Harris scores between two groups immediately after discharge, 1 month and 3 months after discharge (P<0.001). CONCLUSION: Intervention strategy based on Caprini thrombosis risk assessment model could reduce incidence of DVT in patients with THR, improve postoperative pain and swelling of the affected limb, and promote recovery of hip joint function.


Assuntos
Artroplastia de Quadril , Trombose Venosa , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
16.
Int J Clin Pharmacol Ther ; 60(10): 448-458, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35979900

RESUMO

OBJECTIVE: To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects. MATERIALS AND METHODS: An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed. RESULTS: Cmax were 3.58 ± 2.74 ng/mL and 6.01 ± 3.93 ng/mL, and AUC0-∞ were 35.71 ± 18.68 h×ng/mL and 52.15 ± 31.31 h×ng/mL for the T and R formulations, respectively. The tmax of both formulations was 5.00 hours. The cumulative fecal excretion rate (Fe0-96h/F) of fidaxomicin and its main active metabolite OP-1118 were similar for both formulations. The geometric mean ratios and 90% confidence intervals (CI) of AUC0-t, AUC0-∞, and Cmax were not completely within the range of 80.00 - 125.00%. Significant within-subject and inter-subject coefficients of variation (> 30%) were found. CONCLUSION: Despite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.


Assuntos
Medicamentos Genéricos , Espectrometria de Massas em Tandem , Área Sob a Curva , Disponibilidade Biológica , China , Cromatografia Líquida , Estudos Cross-Over , Medicamentos Genéricos/farmacocinética , Fidaxomicina , Humanos , Projetos Piloto , Comprimidos , Espectrometria de Massas em Tandem/métodos , Equivalência Terapêutica
17.
Comput Intell Neurosci ; 2022: 6925670, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35607474

RESUMO

As an extension of intuitionistic fuzzy sets (IFSs), picture fuzzy sets (PFSs) can better model and represent the hesitancy and uncertainty of decision makers' preference information. In this study, we propose a multicriteria group decision making (MCGMD) method based on picture fuzzy sets. We first define some basic picture Einstein operations with closed properties among PFSs on the basis of the Einstein t-norms and t-conorms. Then, utilizing the hybrid-weighted operator and the developed picture Einstein operations laws, we put forward a picture fuzzy Einstein hybrid-weighted aggregation operator for aggregating PFSs and discuss its several important properties. Furthermore, we present a new MCGMD method based on the proposed picture fuzzy Einstein hybrid-weighted aggregation operator. Finally, an example is conducted to validate the effectiveness of the proposed MCGMD method.


Assuntos
Tomada de Decisões , Lógica Fuzzy , Incerteza
18.
Huan Jing Ke Xue ; 43(4): 1829-1843, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393807

RESUMO

In order to obtain the ammonia emission level and space-time distribution characteristics of the poultry production industry in the Yangtze River Delta, an online high-resolution monitoring system was used to continuously monitor the atmospheric ammonia concentration in the breeding house and compost shed in a typical large-scale layer farm. By obtaining the ammonia emission level and emission factor during each growth stage, we established the localized ammonia emission inventory for the poultry production industry in the Yangtze River Delta. The results showed that the average daily ρ(NH3) in the breeding house and compost shed for spring, summer, autumn, and winter were (1.85±0.38), (4.58±0.33), (3.87±0.12), and (2.83±0.47) mg·m-3 and (2.04±0.50), (4.04±1.04), (2.51±0.67), and (1.55±0.16) mg·m-3 respectively. Ammonia emissions showed a significant daily hourly change trend. The highest hourly ammonia concentration in the layer house appeared from 13:00-14:00 in the afternoon, and the minimum appeared from 01:00-03:00 in the morning. The highest hourly ammonia concentration in the compost shed occurred between 16:00-19:00 in summer and autumn, whereas the diurnal changes in spring and winter were not significant. Hourly changes in ammonia emissions during the day were mainly affected by daily temperature, poultry activities, and manure management. Ammonia concentrations at different growth stages of laying hens showed significant differences. ρ (NH3) from young chickens, laying hens, and pre-eliminated chickens were (1.85±0.38), (2.83±0.47), and (1.61±0.32) mg·m-3, respectively. The ammonia emission rate from laying hens reached 1.53 times and 1.65 times that of young chickens and pre-eliminated chickens, respectively. Metabolism levels and feed intake at different growth stages were the main reasons for the differences in ammonia emissions. Ammonia emission factors for the layer house and compost shed in spring, summer, autumn, and winter were (0.13±0.02), (0.54±0.01), (0.39±0.01), and (0.17±0.01) g·(bird·d)-1 and (0.07±0.01), (0.17±0.02), (0.08±0.01), and (0.04±0.01) g·(bird·d)-1, respectively. Annual ammonia emission factors reached (0.11±0.06) kg·(bird·a)-1 and (0.03±0.02) kg·(bird·a)-1, respectively. Our results suggest that ambient temperature, ventilation mode, chicken house type, and manure removal frequency were the main influencing factors of ammonia emissions from poultry production. The uncertainty ranges of the ammonia emission coefficients reached±122%,±79%, and±74%, and±56%, respectively. Great uncertainties were generated when empirical emission factors were used for emission inventory establishment. Based on the results of online monitoring, model simulation, and literature analysis, we established an ammonia emission inventory for the poultry production industry within the Yangtze River Delta region by adopting the emission factors of (0.16±0.08) kg·(bird·a)-1. In 2019, the total ammonia emission from poultry production was (108.81±54.41) kt. In terms of spatial distribution, ammonia emission intensities in the northern regions were significantly higher than those in the southern parts. The ammonia emission intensities during summer were 3.38-3.56 times higher than those in spring and winter.


Assuntos
Amônia , Esterco , Agricultura , Amônia/análise , Animais , Galinhas , Fazendas , Feminino , Aves Domésticas
20.
Anim Biosci ; 35(7): 975-988, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35240026

RESUMO

OBJECTIVE: In this study, we aimed to identify long non-coding RNAs (lncRNAs) that play important roles in starvation stress, analyze their functions, and discover potential molecular targets to alleviate starvation stress to provide a theoretical reference for subsequent in-depth research. METHODS: We generated a piglet starvation stress animal model. Nine Yorkshire weaned piglets were randomly divided into a long-term starvation stress group (starved for 72 h), short-term starvation stress group (starved for 48 h), and the control group. LncRNA libraries were constructed using high-throughput sequencing of piglet ileums. RESULTS: We obtained 11,792 lncRNAs, among which, 2,500 lncRNAs were novel. In total, 509 differentially expressed (DE)lncRNAs were identified in this study. Target genes of DElncRNAs were predicted via cis and trans interactions, and functional and pathway analyses were performed. Gene ontology functions and Kyoto encyclopedia of genes and genomes analysis revealed that lncRNA-targeted genes mainly participated in metabolic pathways, cellular processes, immune system processes, digestive systems, and transport activities. To reveal the mechanism underlying starvation stress, the interaction network between lncRNAs and their targets was constructed based on 26 DElncRNAs and 72 DEmRNAs. We performed an interaction network analysis of 121 DElncRNA-DEmRNA pairs with a Pearson correlation coefficient greater than 0.99. CONCLUSION: We found that MSTRG.19894.13, MSTRG.16726.3, and MSTRG.12176.1 might play important roles in starvation stress. This study not only generated a library of enriched lncRNAs in piglets, but its outcomes also provide a strong foundation to screen key lncRNAs involved in starvation stress and a reference for subsequent in-depth research.

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