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1.
Pain ; 165(9): 1901-1903, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39159470
2.
Surg Endosc ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168861

RESUMO

BACKGROUND: To evaluate the long-term efficacy of single-balloon enteroscopy endoscopic retrograde cholangiography (SBE-ERC) for the treatment of biliary obstruction and to analyze the factors affecting the recurrence of benign bilioenteric anastomotic stricture after SBE-ERC treatment. METHODS: The clinical data of patients with biliary diseases treated with SBE-ERC after choledochojejunostomy in our hospital from January 2015 to December 2021 were analyzed retrospectively for the success rates of diagnosis and treatment and the incidence of complications. Patients who were diagnosed with benign bilioenteric anastomotic stricture were followed up. The independent factors affecting recurrence were obtained by univariate and multivariate analyses using the Kaplan‒Meier method and Cox proportional hazard regression model. RESULTS: A total of 289 SBE-ERCs were performed in 165 patients. The overall success rate was 83.0% (240/289). The incidence of postoperative complications was 5.2% (15/289). The 108 successfully treated patients diagnosed with benign bilioenteric anastomotic stricture were followed up. Twenty-six percent (29/108) of patients had recurrent stricture after SBE-ERC. The biliary patency rates at 1 year, 2 years and 5 years after SBE-ERC were 90.1%, 69.3%, and 53.9%, respectively. Single-factor analysis revealed the absence of intrahepatic biliary gas imaging during endoscopy ( χ 2 =5.366, P = 0.021), a diameter of balloon dilatation during the last endoscopic treatment less than 0.8 cm ( χ 2 =4.552, P = 0.033), and the presence of a thread in the anastomosis ( χ 2 =8.921, P = 0.003) as risk factors for recurrence. A non-indwelling biliary plastic stent ( χ 2 =14.868, P < 0.001) and undergoing only one ERCP treatment ( χ 2 =13.313, P = 0.001) were risk factors for the recurrence of benign stricture after SBE-ERC resection. Multivariate analysis revealed that the absence of a stent (HR = 0.15, 95% CI 0.06-0.40, P = 0.001), absence of intrahepatic biliary gas imaging during endoscopy (HR = 0.39, 95% CI 0.17-0.91, P = 0.03) and the presence of a thread in the anastomosis (HR = 3.69, 95% CI 1.59-8.57, P = 0.002) were independent risk factors for stricture recurrence. CONCLUSIONS: Treating biliary disease after choledochojejunostomy with SBE-ERC is safe and effective, with a good immediate technical success rate and an acceptable incidence of complications. SBE-ERC has long-term efficacy in the treatment of benign bilioenteric anastomotic stricture. The absence of intrahepatic biliary gas imaging during endoscopy, non-indwelling biliary stents and the existence of anastomotic threads are independent risk factors for the recurrence of benign bilioenteric anastomotic stricture.

3.
PLoS One ; 19(7): e0307955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39078854

RESUMO

INTRODUCTION: Individualized treatment of spinal deformity is needed for adolescent idiopathic scoliosis (AIS), and the integration of pelvic rotation correction based on proprioceptive neuromuscular facilitation (PNF) into regular physiotherapy may be a promising approach. However, few high-quality studies have investigated its effects. This study aimed to evaluate the efficacy of pelvic rotation correction combined with Schroth exercises in the treatment of mild AIS. METHODS: This was a randomized controlled trial. Forty-two AIS patients were randomly divided into experimental and control groups. Both groups underwent 20 therapeutic sessions over 24 weeks. All patients (n = 42) performed Schroth exercises at each session. In addition, the experimental group (n = 21) also participated in a pelvic rotation correction program based on PNF at each session. The primary outcome was the concave/convex ratio of hipbone widths, and the secondary outcomes included the Cobb angle, trunk rotation angle, self-perception, apical vertebral translation, and apical vertebral rotation. Patients were evaluated before and after 24 weeks of intervention. RESULTS: There was a significant between-group difference in the change from baseline between the experimental and control groups for the following parameters: concave/convex ratio 2.89% (95% confidence interval [CI], 1.58 to 4.20, P<0.001), trunk rotation angle -1.26° (95% CI, -2.20 to -0.32; P = 0.01), and apical vertebral rotation improved by at least one class from baseline in 3 patients (14.3%) in the control group and 9 patients (42.9%) in the experimental group (P = 0.04). While Cobb angle -1.60° (95% CI, -7.75 to 0.54; P = 0.14), self-image 0.149 (95% CI, 0.001 to 0.297; P = 0.049), apical vertebral translation -0.58 mm (95% CI, -3.83 to 2.67; P = 0.72), and pelvic obliquity 0.10° (95% CI, -0.21 to 0.41; P = 0.52) did not differ significantly. CONCLUSIONS: Pelvic rotation correction combined with Schroth exercises more effectively improved pelvic axial rotation and other spinal deformities, including trunk rotation and apical vertebral rotation, than Schroth exercises alone in the treatment of mild AIS.


Assuntos
Terapia por Exercício , Pelve , Escoliose , Humanos , Escoliose/terapia , Escoliose/fisiopatologia , Adolescente , Feminino , Terapia por Exercício/métodos , Masculino , Rotação , Pelve/fisiopatologia , Resultado do Tratamento , Criança , Coluna Vertebral/fisiopatologia
4.
BMC Pediatr ; 24(1): 281, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678261

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. CASE PRESENTATION: This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. CONCLUSIONS: In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Duodenoscópios , Icterícia Obstrutiva , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/terapia , Icterícia Obstrutiva/diagnóstico por imagem , Lactente , Masculino , Colestase/etiologia , Colestase/diagnóstico por imagem , Colestase/terapia
5.
J Back Musculoskelet Rehabil ; 37(2): 337-346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37980642

RESUMO

BACKGROUND: Previous studies have suggested an association between pelvic rotation (PR) and scoliotic deformity in severe adolescent idiopathic scoliosis (AIS), but none have investigated this relationship in mild to moderate AIS. OBJECTIVE: To investigate the relationship between PR and trunk rotation in mild to moderate AIS. METHODS: This was a case-control study. The cases were 32 AIS patients with PR in the opposite direction to the thoracic curve, and the controls were 32 AIS patients with PR in the same direction as the thoracic curve. All patients were assessed with the Adams forwards bend test. Type II trunk rotation was selected as exposure. Logistic regression was used to estimate the association between PR direction and types of trunk rotation while accounting for confounders. Multiple linear regression was used to analyse the relationships between PR magnitude and the angle of trunk rotation (ATR). RESULTS: Logistic regression showed an unadjusted OR of 9.13 (95% CI 2.92-28.50, P< 0.001), and adjustment for sex and Cobb angle only slightly changed the OR (adjusted OR, 8.23; 95% CI, 2.51-27.01; P= 0.001). The concave/convex ratio was associated with ATR measurements in both cases (ß=-0.379; P= 0.030) and controls (ß=-0.468, P= 0.008). CONCLUSION: An association was found between PR and trunk rotation, which may help achieve more effective physiotherapy in mild to moderate AIS.


Assuntos
Cifose , Escoliose , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Vértebras Torácicas , Estudos de Casos e Controles , Modelos Lineares
6.
ACS Photonics ; 10(9): 3302-3309, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37743942

RESUMO

Diamond color centers are promising optically addressable solid-state spins that can be matter-qubits, mediate deterministic interaction between photons, and act as single photon emitters. Useful quantum computers will comprise millions of logical qubits. To become useful in constructing quantum computers, spin-photon interfaces must, therefore, become scalable and be compatible with mass-manufacturable photonics and electronics. Here, we demonstrate the heterogeneous integration of NV centers in nanodiamond with low-fluorescence silicon nitride photonics from a standard 180 nm CMOS foundry process. Nanodiamonds are positioned over predefined sites in a regular array on a waveguide in a single postprocessing step. Using an array of optical fibers, we excite NV centers selectively from an array of six integrated nanodiamond sites and collect the photoluminescence (PL) in each case into waveguide circuitry on-chip. We verify single photon emission by an on-chip Hanbury Brown and Twiss cross-correlation measurement, which is a key characterization experiment otherwise typically performed routinely with discrete optics. Our work opens up a simple and effective route to simultaneously address large arrays of individual optically active spins at scale, without requiring discrete bulk optical setups. This is enabled by the heterogeneous integration of NV center nanodiamonds with CMOS photonics.

7.
Chin Med J (Engl) ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620294

RESUMO

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

8.
Front Immunol ; 14: 1224631, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600788

RESUMO

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (T pre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus T bio), and clinical variables and T pre (base model plus T pre) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre. Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs. 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set. Conclusion: A pathology T-score prediction (T pre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.


Assuntos
Glomerulonefrite por IGA , Falência Renal Crônica , Humanos , Glomerulonefrite por IGA/diagnóstico , Rim , Aprendizado de Máquina , Falência Renal Crônica/etiologia , Algoritmos
9.
J Agric Food Chem ; 71(31): 11860-11874, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37492956

RESUMO

To systematically assess the impact of typical CNMs on the growth effects of cereal crops, we conducted a meta-analysis of 48 independent studies worldwide. The pooled results showed that shoot weight (13.39%) and antioxidant metabolite content (SOD: 106.32%, POD: 32.29%, CAT: 22.63%) of cereal crops exposed to the presence of CNMs were significantly increased, but phytohormones secretion (17.84%) was inhibited. The results of subgroup analysis showed that there were differences in the results of different CNM types with the same exposure concentration on growth effects. Short-term exposure adversely affected the root and photosynthetic capacity of the crop, but prolonged exposure instead showed a promoting effect. Multiple linear regression analysis showed that the concentration of CNMs and cereal variety variables were significantly associated with changes in multiple growth effect values. This work could offer references and fresh perspectives for investigating how nanoparticles and crops interact.


Assuntos
Carbono , Nanoestruturas , Nanoestruturas/análise , Produtos Agrícolas , Antioxidantes
10.
Gland Surg ; 12(2): 243-251, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36915809

RESUMO

Background: Pancreatic fistula (PF) is the main complication in patients undergoing pancreaticoduodenectomy. Computed tomography (CT) value can reflect pancreatic tissue characteristics which is related to PF. This study was designed to study the relationship between the preoperative CT value and pancreatic fistula. Methods: We retrospectively reviewed the clinical and medical data of patients undergoing pancreaticoduodenectomy from 2017 to 2021. The pancreatic CT value and the CT value ratios of the pancreas and abdominal aorta (PCT/ACT) were measured and compared between the PF group and non-PF group. The values in different PF severity groups were compared using variance analysis. A cut-off value was selected by receiver operating characteristic (ROC) curve. Single-factor and multiple-factor analysis were performed to evaluate Correlation between PF and CT. Results: One hundred and twenty-seven cases were included in this study. The PCT/ACT in the PF group was significantly lower than that in the non-PF group (P<0.001), and the PCT/ACT value was correlatively lower in the severe PF group than in the mild PF group (P=0.008). A cutoff value of 0.99 was selected by ROC curves analysis. Further multifactor analysis identified PCT/ACT <0.99 to be an independent preoperative predictor [odds ratio (OR): 11.3, P<0.01]. Conclusions: The preoperative pancreatic CT value can indirectly reflect the histological condition of the pancreas and thus may related to postoperative PF after pancreaticoduodenectomy and provide useful information for surgeons in deciding upon the pancreaticojejunostomy method.

11.
J Invest Dermatol ; 143(8): 1449-1460, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36868499

RESUMO

Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis, and UVB may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is the production of cis-urocanic acid (cis-UCA) by keratinocytes. However, the detailed mechanism is yet to be fully understood. In this study, we found FLG expression and serum cis-UCA levels were significantly lower in patients with psoriasis than in healthy controls. We also noted that cis-UCA application inhibited psoriasiform inflammation through the reduction of Vγ4+ γδT17 cells in murine skin and draining lymph nodes. Meanwhile, CCR6 was downregulated on γδT17 cells, which would suppress the inflammatory reaction at a distal skin site. We revealed that the 5-hydroxytryptamine receptor 2A, the known cis-UCA receptor, was highly expressed on Langerhans cells in the skin. cis-UCA also inhibited IL-23 expression and induced PD-L1 on Langerhans cells, leading to the attenuated proliferation and migration of γδT-cells. Compared to the isotype control, α-PD-L1 treatment in vivo could reverse the antipsoriatic effects of cis-UCA. PD-L1 expression on Langerhans cells was sustained through the cis-UCA-induced mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These findings uncover the cis-UCA-induced PD-L1-mediated immunosuppression on Langerhans cells, which facilitates the resolution of inflammatory dermatoses.


Assuntos
Dermatite , Psoríase , Ácido Urocânico , Humanos , Camundongos , Animais , Células de Langerhans , Imiquimode/farmacologia , Antígeno B7-H1 , Inflamação , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Interleucina-23/farmacologia , Raios Ultravioleta
12.
Gland Surg ; 12(1): 67-80, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36761488

RESUMO

Background: Pancreaticojejunal anastomotic stenosis (PJS) after pancreaticoduodenectomy (PD) is difficult to treat. Single-balloon enteroscope-assisted endoscopic retrograde pancreatography (SBE-assisted ERP) is a safe way to treat PJS with the strength of minimally invasion and repeatability, but since its technical difficulty and few patient number, data on long-term outcomes remain limited. The optimal treatment is still unknown. We aim to study the safety, effectiveness, and long-term outcome of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERP in patients with PJS in this study. Methods: The clinical information of patients undergoing SBE-assisted therapeutic ERP from March 2016 to March 2021 were retrospectively analyzed. All patients were diagnosed as PJS and without any contraindication for therapeutic endoscopy. Treatment details, postoperative complications, factors influencing technical success rate were evaluated. Long-term outcomes results were obtained by clinical or telephone follow-up. Results: Sixteen patients with median age of 51 years were included in this study, surgical reconstruction methods including PD with Whipple reconstruction, PD with Child reconstruction, pylorus-preserving pancreaticoduodenectomy (PpPD) with Whipple reconstruction. Eight patients were successfully treated. No serious complications happened. Risk factors for the failure of pancreaticojejunal anastomotic site identification include the digestive tract reconstruction sequence, pancreaticojejunostomy method, pancreatic duct tube implantation, pancreatic duct width before surgery, and pancreatic fistula during perioperative period. The median follow-up time was 77.2 months, the mean indwelling time of the stent was 62.3 months [interquartile range (IQR), 6.8-153.7 months]. Two of eight patients developed recurrent PJS. The variation in body mass index (BMI) was +2.46 in the non-recurrence group compared to -1.09 in the recurrence group and -2.12 in the endoscopic retrograde cholangiopancreatography (ERCP) treatment failure group. Conclusions: ERP intervention should be carried out early once PJS occurs in order to increase success rate. BMI is a crucial indicator which can reflex PJS rehabilitation degree during follow-up. In order to reduce PJS recurrence rate, a wider pancreatic stent and a longer stent indwelling time are recommended.

13.
Med Oncol ; 40(1): 10, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352295

RESUMO

Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability.


Assuntos
Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Fibrinogênio/metabolismo , Linhagem Celular Tumoral , Metástase Linfática , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica
14.
Microorganisms ; 10(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36144348

RESUMO

Maintaining the homeostasis balance of trace elements is crucial for the health of organisms. Human health is threatened by diseases caused by a lack of trace elements. Saccharomyces cerevisiae has a wide and close relationship with human daily life and industrial applications. It can not only be used as fermentation products and single-cell proteins, but also as a trace elements supplement that is widely used in food, feed, and medicine. Trace-element-enriched yeast, viz., chromium-, iron-, zinc-, and selenium-enriched yeast, as an impactful microelements supplement, is more efficient, more environmentally friendly, and safer than its inorganic and organic counterparts. Over the last few decades, genetic engineering has been developing large-scaled genetic re-design and reconstruction in yeast. It is hoped that engineered yeast will include a higher concentration of trace elements. In this review, we compare the common supplement forms of several key trace elements. The mechanisms of detoxification and transport of trace elements in yeast are also reviewed thoroughly. Moreover, genes involved in the transport and detoxification of trace elements are summarized. A feasible way of metabolic engineering transformation of S. cerevisiae to produce trace-element-enriched yeast is examined. In addition, the economy, safety, and environmental protection of the engineered yeast are explored, and the future research direction of yeast enriched in trace elements is discussed.

16.
Pharmaceuticals (Basel) ; 15(7)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35890193

RESUMO

Pain and itch are both important manifestations of various disorders, such as herpes zoster, atopic dermatitis, and psoriasis. Growing evidence suggests that both sensations have shared mediators, overlapping neural circuitry, and similarities in sensitization processes. In fact, pain and itch coexist in some disorders. Determining pharmaceutical agents and targets for treating pain and itch concurrently is of scientific and clinical relevance. Here we review the neurobiology of pain and itch and discuss the pharmaceutical targets as well as novel compounds effective for the concurrent treatment of these sensations.

18.
Front Pharmacol ; 13: 879748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662690

RESUMO

Breast cancer is the most prevalent cancer and the second leading cause of cancer death in women. Cisplatin is a commonly used chemotherapeutic drug for breast cancer treatment. Owing to serious side effects, the combination of cisplatin with other drugs is an effective strategy to simultaneously reduce side effects and increase the anticancer efficacy. GLUT1 is an emerging target for cancer treatment since cancer cells usually consume more glucose, a phenomenon called the Warburg effect. In this study, we found that the combination of cisplatin and a novel GLUT1 inhibitor #43 identified from our previous high-throughput screening exerted a synergistic anticancer effect in MCF-7 and MDA-MB-231 breast cancer cells. Mechanism studies in MCF-7 cells revealed that combination of cisplatin and #43 significantly induced apoptosis, intracellular reactive oxygen species, and loss of mitochondrial membrane potential. Furthermore, #43 enhanced the DNA damaging effect of cisplatin. Akt/mTOR downstream signaling and the ERK signaling pathway usually involved in cell growth and survival were inhibited by the combination treatment. On the other hand, phosphorylation of p38 and JNK, which may be associated with apoptosis, was induced by the combination treatment. Altogether, our data indicate that oxidative stress, DNA damage, the Akt/mTOR and MAPK signaling pathways, and apoptosis may be involved in the synergism of cisplatin and #43 in breast cancer cells.

19.
Chemosphere ; 301: 134689, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35469898

RESUMO

Monohaloacetic acids (mono-HAAs), a class of disinfection by-products widely occurred in drinking water, receives significant attention due to their extremely high toxicity. Many studies on the biological toxicity of mono-HAAs have been reported, yet the toxic effects of mono-HAAs on human renal cells (kidney is one of the target organs for disinfection by-products) has not been involved. Studies on organic precursors for mono-HAAs formation were also very limited due to their lower levels as compared to di-HAAs and tri-HAAs. Based on this, the formation of mono-HAAs after chlorination of some typical source water samples and their relationship with water quality parameters were investigated. Meanwhile, the cytotoxicity of monochloroacetic acid (MCAA), monobromoacetic acid (MBAA), and monoiodoacetic acid (MIAA) were tested using human embryonic kidney cells (HEK-293 T cells). The results showed that the levels of mono-HAAs formed during chlorination of source water samples were between 0.44 and 0.87 µg/L. Formation of MBAA positively (p < 0.05) correlated with bromide ion and dissolved organic carbon, but negatively (p < 0.01) correlated with SUVA254 (specific UV absorbance at 254 nm), while formation of MCAA was only positively (p < 0.05) related with SUVA254. These results suggested that although MCAA and MBAA both belong to the mono-HAAs, the characteristics of their organic precursors differ significantly. MCAA precursors have high aromaticity and are more hydrophobic, yet MBAA precursors have low aromaticity and are more hydrophilic. The half-lethal concentrations (LC50) of MCAA, MBAA, and MIAA on HEK293T cells were 1196-1211 µM, 16.07-18.96 µM, and 6.08-6.17 µM, respectively. An in-depth analysis showed that the cytotoxicity of mono-HAAs on HEK 293 T cells could not be explained by the parameters concerning cellular uptake (e.g., logP and pKa), but the SN2 reaction of C-X bond with cellular molecules (e.g., glyceraldehyde-3-phosphate dehydrogenase, etc) may be the relevant cause for the cytotoxicity of mono-HAAs on HEK 293 T cells.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Ácidos , Desinfetantes/química , Desinfecção , Células HEK293 , Halogenação , Humanos , Trialometanos/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos
20.
Transl Pediatr ; 10(10): 2506-2513, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765474

RESUMO

BACKGROUND: The indications for endoscopic retrograde cholangiopancreatography (ERCP) in infant patients (age <1 year) differ from those in adults. A paucity of data and concerns about the potential lower effectiveness and more adverse effects limit its utility, even in tertiary care centres. In this study, we retrospectively analysed the indications, success rates, and adverse effects of ERCP in these groups. METHODS: From June 2014 to March 2018, 17 ERCPs were performed in 15 children [median age: 10.4 months (6-12 months); median weight: 6.6 kg (3.3-10.7 kg)]. A conventional duodenoscope was utilized in all procedures. All patients were followed up as inpatients. RESULTS: Fifteen therapeutic and two diagnostic procedures were managed by licensed paediatric endoscopist. Successful cannulation was obtained in all patients (100%). A high proportion (47.1%) of pancreaticobiliary maljunction (PBM) and therapeutic procedures (88.2%) were identified. Two cases of mild pancreatitis were recorded, accounting for 12.5% of the post-ERCP pancreatitis (PEP) rate. By multivariable analysis, recurrent acute pancreatitis and pancreatic duct (PD) cannulation/injection were identified as PEP-related risk factors. All complications were managed conservatively. CONCLUSIONS: ERCP in infant patients (0.5< age <1 year) could be safely completed by conservational endoscopy. A high proportion of PBM and therapeutic procedures were identified in our study cohort. The overall adverse-event rate was acceptable, and no serious complication occurred. The PEP-related independent risk factors included recurrent acute pancreatitis and PD cannulation/injection.

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