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BACKGROUND: An innovative instrument for laparoscopy using indocyanine green (ICG) allows easy detection of sentinel lymph nodes (SLNs) in lateral pelvic lymph nodes (LPLNs). Here, we investigated the safety and efficacy of lateral pelvic SLN biopsy (SLNB) using ICG fluorescence navigation in advanced lower rectal cancer and evaluated the sensitivity and specificity of this technique to predict the status of LPLN. METHODS: From April 1, 2017 to December 1, 2020, we conducted lateral pelvic SLNB using ICG fluorescence navigation during laparoscopic total mesorectal excision and lateral pelvic lymph node dissection (LLND) in 23 patients with advanced low rectal cancer who presented with LPLN but without LPLN enlargement. Data regarding clinical characteristics, surgical and pathological outcomes, lymph node findings, and postoperative complications were collected and analyzed. RESULTS: We successfully performed the surgery using fluorescence navigation. One patient underwent bilateral LLND and 22 patients underwent unilateral LLND. The lateral pelvic SLN were clearly fluorescent before dissection in 21 patients. Lateral pelvic SLN metastasis was diagnosed in 3 patients and negative in 18 patients by frozen pathological examination. Among the 21 patients in whom lateral pelvic SLN was detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLN. CONCLUSION: This study indicated that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure for advanced lower rectal cancer with good accuracy, and no false-negative cases were found. No metastasis in SLNB seemed to reflect all negative LPLN metastases, and this technique can replace preventive LLND for advanced lower rectal cancer.
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Neoplasias del Recto , Ganglio Linfático Centinela , Humanos , Biopsia del Ganglio Linfático Centinela/métodos , Verde de Indocianina , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Colorantes , Escisión del Ganglio Linfático , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Neoplasias del Recto/patologíaRESUMEN
Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Induction of aHSCs senescence by inhibiting SASP may be a potential therapeutic model against hepatic fibrosis. To evaluate the role of atractylenolide III (ATR III) in the development of chemotherapeutic drug-induced SASPs in hepatic stellate cells. Etoposide-induced senescent HSC-LX2 model was established and treated with ATR III at different concentrations (20, 30 and 40 µM). We found that ATR III dose-dependently enhanced senescence in etoposide-induced LX2 cells. ATR III dose-dependently decreased the release and expression of SASP factors (interleukin [IL]-1α, IL-1ß, IL6 and IL-8) in senescent cells. ATR III regulated cyclic GMP-AMP synthase (cGAS)/nuclear factor κ (NF-κB) signalling to affect SASP expression in senescent cells. The addition of 2'3' cGAMP counteracted the effect of ATR III. The release of SASP factors in the conditioned medium from senescent cells could affect cell migration, proliferation and contraction through paracrine manner. Our results indicated ATR III could still enter senescence and prevent the production of SASP and its paracrine effects in senescent cells, an effect that may be related to the possible inhibition of cGAS/NF-κB signalling by ATR III. Our study proves that ATR III may be an effective potential drug against liver fibrosis by promoting aHSC senescence, which can provide a new choice for the future clinical treatment of liver fibrosis.
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Células Estrelladas Hepáticas , FN-kappa B , Humanos , Senescencia Celular , Etopósido/farmacología , Cirrosis Hepática , FN-kappa B/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/farmacología , SecretomaRESUMEN
BACKGROUND: The diagnostic criteria and effect of persistent descending mesocolon (PDM) on sigmoid and rectal cancers (SRCs) remain controversial. This study aims to clarify PDM patients' radiological features and short-term surgical results. METHOD: From January 2020 to December 2021, radiological imaging data from 845 consecutive patients were retrospectively analyzed using multiplanar reconstruction (MRP) and maximum intensity projection (MIP). PDM is defined as the condition wherein the right margin of the descending colon is located medially to the left renal hilum. Propensity score matching (PSM) was used to minimize database bias. The anatomical features and surgical results of PDM patients were compared with those of non-PDM patients. RESULTS: Thirty-two patients with PDM and 813 patients with non-PDM were enrolled into the study who underwent laparoscopic resection. After 1:4 matching, patients were stratified into PDM (n = 27) and non-PDM (n = 105) groups. The lengths from the inferior mesenteric artery (IMA) to the inferior mesenteric vein (1.6 cm vs. 2.5 cm, p = 0.001), IMA to marginal artery arch (2.7 cm vs. 8.4 cm, p = 0.001), and IMA to the colon (3.3 cm vs. 10.2 cm, p = 0.001) were significantly shorter in the PDM group than those in the non-PDM group. The conversion to open surgery (11.1% vs. 0.9%, p = 0.008), operative time (210 min vs. 163 min, p = 0.001), intraoperative blood loss (50 ml vs. 30 ml, p = 0.002), marginal arch injury (14.8% vs. 0.9%, p = 0.006), splenic flexure free (22.2% vs. 3.8%, p = 0.005), Hartmann procedure (18.5% vs. 0.0%, p < 0.001) and anastomosis failure (18.5% vs. 0.9%, p = 0.001) were significantly higher in the PDM group. Moreover, PDM was an independent risk factor for prolonged operative time (OR = 3.205, p = 0.004) and anastomotic failure (OR = 7.601, p = 0.003). CONCLUSION: PDM was an independent risk factor for prolonged operative time and anastomotic failure in SRCs surgery. Preoperative radiological evaluation using MRP and MIP can help surgeons better handle this rare congenital variant.
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Laparoscopía , Mesocolon , Neoplasias del Recto , Neoplasias del Colon Sigmoide , Humanos , Colon Sigmoide/diagnóstico por imagen , Colon Sigmoide/cirugía , Colon Sigmoide/irrigación sanguínea , Mesocolon/cirugía , Tempo Operativo , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Anastomosis Quirúrgica/efectos adversos , Neoplasias del Colon Sigmoide/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Factores de Riesgo , Arteria Mesentérica Inferior/cirugíaRESUMEN
Epidermal growth factor receptor (EGFR) C797S mutation leads to Osimertinib drug resistance by disturbing the covalent biding of Michael acceptor group to the Cys797 residue in the ATP biding cleft. In this manuscript, a class of 2-amine-4-oxyphosaniline pyrimidine derivatives were designed, synthesized and evaluated as new noncovalent reversible EGFR inhibitors against L858R/T790M/C797S (CTL) triple mutant. The kinases inhibitiory activity evaluation showed that four compounds exhibited significant inhibitory activities against CTL (IC50 < 30 nM). In particularly, the most promising compound 7a showed excellent enzymatic inhibitory activity against CTL with IC50 value of 9.9 nM, which was more potent than control compound Osimertinib. Moreover, cell proliferation assays indicated that 7a effectively inhibited H1975-EGFR L858R/T790M/C797S with IC50 value of 0.33 µM. Furthermore, compound 7a displayed good metabolic stabilities in human, rat and mouse liver microsomes, and the putative biding mode of compound 7a with ATP was revealed by molecular docking study. These findings strongly indicated that compound 7a was a promising L858R/T790M/C797S mutant EGFR inhibitor.
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Receptores ErbB , Neoplasias Pulmonares , Ratones , Ratas , Humanos , Animales , Simulación del Acoplamiento Molecular , Mutación , Aminas/farmacología , Inhibidores de Proteínas Quinasas/química , Pirimidinas/farmacología , Pirimidinas/química , Adenosina Trifosfato/farmacología , Línea Celular Tumoral , Proliferación CelularRESUMEN
BACKGROUND: Laparoscopic surgery has become the standard surgical approach for the treatment of colon cancer. However, the surgical procedure for right colectomy is not standardized. Selection between laparoscopy-assisted right colectomy (LARC) with extracorporeal anastomosis and totally laparoscopic procedures with intracorporeal anastomosis is still a hot topic. The aim of this study was to compare the short-term outcomes of totally laparoscopic right colectomy (TLRC) and LARC in the treatment of right colon cancer. METHODS: This was a retrospective and single-center study conducted between January 2016 and December 2019 featuring 120 TLRC patients and 180 LARC patients following the principles of the CME. We then collated and analyzed the clinicopathological characteristics, operative characteristics, and short-term outcomes. RESULTS: The baseline characteristics were balanced between two groups. TLRC was associated with a significantly lower estimated blood loss (p < 0.01), a shorter incision length (p < 0.01). In terms of postoperative recovery, patients in TLRC group were better, as confirmed by less postoperative pain (p < 0.01), less rescue analgesic usage (p = 0.04), faster to flatus (p < 0.01), defecation (p < 0.01), oral intake (p < 0.01) and discharge (p < 0.01). Incidence of postoperative complications according to Clavien-Dindo classification system was also similar in both groups. CONCLUSIONS: Our data demonstrate that TLRC is technically safe and feasible. This technique could lead to a better cosmetic outcome, a less pain experience and a faster recovery of bowel function.
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Neoplasias del Colon , Laparoscopía , Anastomosis Quirúrgica/métodos , Colectomía/métodos , Neoplasias del Colon/complicaciones , Neoplasias del Colon/cirugía , Humanos , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.
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Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/cirugía , COVID-19/prevención & control , Infección Hospitalaria/prevención & control , Control de Infecciones , Procedimientos Quirúrgicos Vasculares , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico , Rotura de la Aorta/diagnóstico , COVID-19/diagnóstico , COVID-19/transmisión , COVID-19/virología , Prueba de COVID-19 , China , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Flujo de TrabajoRESUMEN
A series of novel pinanyl pyrimidine amine derivatives (1e~1n) and camphoryl pyrimidine amine derivatives (2b~2f) bearing bicyclic monoterpene moieties were designed and synthesized from natural and renewable nopinone and camphor. All chemical structures of target compounds were characterized by 1H NMR, 13C NMR and HRMS spectra analyses, and the antimicrobial activities were evaluated. The results indicated that most compounds showed considerable antibacterial and antifungal activities against Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Methicillin-Resistant Staphylococcus aureus (MRSA), Bacillus cereus and Candida albicans. Among them, 1f showed potent antibacterial activity against all tested bacteria, 1i exhibited excellent inhibition against Streptococcus pneumoniae (1 µg/mL) and Escherichia coli (1 µg/mL), which was better than the control drug amikacin (2 µg/mL). As to antifungal activity against Candida albicans (C. albicans), compound 1l showed comparable activity (16 µg/mL) to the control drug ketoconazole. Furthermore, five active compounds with better antimicrobial activities also showed anti-inflammatory potencies against mouse mononuclear macrophages leukemia cells (RAW). Especially, 1f (IC50 = 1.37 µM) and 2f (IC50 = 1.87µM) are more potent than the control drug aspirin (IC50 = 1.91 µM).
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Antifúngicos , Staphylococcus aureus Resistente a Meticilina , Ratones , Animales , Pruebas de Sensibilidad Microbiana , Antifúngicos/química , Monoterpenos/farmacología , Aminas , Pirimidinas , Antibacterianos/química , Candida albicans , Escherichia coli , Monoterpenos BicíclicosRESUMEN
Sepsis is a systemic inflammatory response syndrome with high mortality. Acute liver injury is an independent predictor for poor prognosis in septic patients. Polygonatum sibiricum polysaccharides (PSP) have been reported to possess anti-inflammatory and hepatoprotective activities. To evaluate the effects of PSP on septic liver injury and demonstrate the potential molecular mechanisms, the septic acute liver injury (SALI) model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS). We found that PSP treatment could remarkably reduce the 48 h mortality rate of septic mice; alleviate liver histopathologic damage; lower the activity of neutrophil infiltration marker MPO in liver tissue; and decrease the levels of liver function indexes AST, ALT, ALP, and TBIL, inflammatory cytokines TNFα and IL-6, and pyroptosis-related inflammatory cytokines IL-18 and IL-1ß in serum. TUNEL staining and detecting GSDMD-NT protein expression level in liver tissue revealed that PSP could restrain excessive pyroptosis. In addition, PSP treatment reversed the upregulations of mRNA expression levels of the NLRP3/GSDMD signals in the liver. Our results indicated the potential protective role of PSP against SALI by inhibiting pyroptosis via NLRP3/GSDMD signals.
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Polygonatum , Animales , Antiinflamatorios/farmacología , Citocinas/farmacología , Interleucina-18 , Interleucina-6/farmacología , Lipopolisacáridos/toxicidad , Hígado , Ratones , Ratones Endogámicos BALB C , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas de Unión a Fosfato/metabolismo , Polisacáridos/farmacología , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Piroptosis , ARN Mensajero , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: Appropriate allocation of nursing staff is key to ensuring efficient nursing in hospitals, and is significantly correlated with patient safety, nursing quality, and nurse job satisfaction. However, there are few studies on nursing workforce allocation in the isolation wards of COVID-19 designated hospitals globally. This study aims to better understand the nursing workforce allocation in the isolation wards of COVID-19 designated hospitals in China, and provide a theoretical basis for efficiently deploying first-line nurses in China and across the world in the future. METHODS: An online survey was conducted among the head nurses (n = 229) and nurses (n = 1378) in the isolation wards of 117 hospitals (selected by stratified sampling), using a self-reported human resource allocation questionnaire. RESULTS: The average bed-to-nurse ratios of different isolation wards were different (Z = 36.742, P = 0.000). The bed-to-nurse ratios of the ICU, suspected COVID-19 cases ward, and confirmed COVID-19 cases ward, were 1:1.88, 1:0.56, and 1:0.45, respectively. The nurse work hours per shift in different isolation wards were also different (Z = 8.468, P = 0.014), with the specific values of the ICU, suspected COVID-19 cases ward, and confirmed COVID-19 cases ward, being 5, 6, and 6 h, respectively. A correlation analysis showed that the average work hours per shift was proportional to the overtime work of nurses (rs = 0.146), the proportion of nurse practitioners was proportional to the overall utilization rate of nursing human resources in the wards (rs = 0.136), and the proportion of nurses with college degrees was proportional to teamwork (rs = 0.142). The proportion of nurses above grade 10 was inversely proportional to teamwork and psychological problems (rs = 0.135, rs = 0.203). The results of multiple stepwise regression analyses showed that the work hours of nurses per shift was the main factor affecting nurse satisfaction and that the proportion of nurses and the work hours of nurses per shift were both independent factors affecting the length of stay (LOS) of patients. CONCLUSION: Hospitals in China have made good nursing workforce allocations during the COVID-19 pandemic, but there are certain shortcomings. Therefore, scientific and efficient nursing workforce allocation practice plans should be established to improve the ability of hospitals to deal with public health emergencies and are urgent problems that need to be addressed soon.
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OBJECTIVES: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome. RESULTS: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment. CONCLUSIONS: ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.
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Oxigenación por Membrana Extracorpórea , Hipertensión Pulmonar , Enfermedades Pulmonares , Síndrome de Circulación Fetal Persistente , Niño , Humanos , Hipertensión Pulmonar/terapia , Recién Nacido , Síndrome de Circulación Fetal Persistente/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Additional surgery is necessary in cases with non-curative endoscopic submucosal dissection. It is still unknown whether preceding endoscopic submucosal dissection (ESD) for T1 colorectal carcinoma affects the short outcomes of patients who underwent additional surgery or not as compared with surgery alone without ESD. METHODS: Patients (101 pairs) with T1 colorectal cancer who underwent additional laparoscopic-assisted surgery after endoscopic submucosal dissection (additional surgery group, n = 101) or laparoscopic-assisted surgery alone (surgery alone group, n = 101) were matched (1:1). Short-term morbidity, operation outcomes, and lymph node metastasis of the resected specimen were compared. RESULTS: There were no significant differences between the additional laparoscopic-assisted surgery and laparoscopic-assisted surgery alone groups in lymph node metastasis (9.9 vs. 5.9%, respectively, p = 0.297), operative time (147.76 ± 52.00 min vs. 156.50 ± 54.28 min, p = 0.205), first flatus time (3.56 ± 1.10 days vs. 3.63 ± 1.05 days, p = 0.282), first stool time (4.30 ± 1.04 days vs. 4.39 ± 1.22 days, p = 0.293), time to intake (5.00 ± 1.18 days vs. 5.25 ± 1.39 days, p = 0.079), blood loss (44.75 ± 45.40 mL vs. 60.40 ± 78.98 mL, p = 0.603), harvest lymph nodes (18.74 ± 7.22 vs. 20.32 ± 9.69, p = 0.438), postoperative surgical complications (p = 0.733), and postoperative length of hospital stay (8.68 ± 4.00 days vs. 8.39 ± 1.94 days, p = 0.401). CONCLUSION: ESD did not increase the difficulty of additional laparoscopic-assisted surgery, hospital stay, or the incidence of postoperative complications. Additional laparoscopic-assisted surgery is safe and recommended for patients with T1 cancer at high risk of lymph node metastasis and residual cancer after non-curative ESD.
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Adenocarcinoma/cirugía , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa , Laparoscopía , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: Severe acute pancreatitis (SAP) is still a big challenge. Accumulated data showed that overexpression of cyclooxygenase-2 (COX-2) in acute pancreatitis and experimental pancreatitis could be attenuated with COX-2 inhibitors. This study was aimed to evaluate whether the occurrence of SAP could be prevented by selective COX-2 inhibitors. METHODS: A total of 190 patients with predicted SAP were randomized into convention group or convention plus COX-2 inhibitors (C+COX-2-Is) group. Besides conventional treatment to all patients in 2 groups, parecoxib (40 mg/d intravenous injection for 3 days) and celecoxib (200 mg oral or tube feeding twice daily for 7 days) were sequentially administrated to the patients in the C+COX-2-Is group. The primary outcome was predefined as the occurrence of SAP. The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) for all of the patients were measured. RESULTS: The occurrence of SAP in the C+COX-2-Is group was decreased 47.08% compared with the convention group, 21.05% (20/95) vs 39.78% (37/93), P = 0.005. A reduction of late local complications was also shown in the C+COX-2-Is group, 18.95% (18/93) vs 34.41% (32/95), P = 0.016. The serum levels of IL-6 and TNF-α were significantly lower in the C+COX-2-Is group than those in the convention group, P < 0.05. Parecoxib relieved abdominal pain more rapidly and decreased the consumption of meperidine. An incremental reduction of cost for 1% decrease of SAP occurrence was RMB475. DISCUSSION: Sequential administration of parecoxib and celecoxib in patients with predicted SAP obtained about half-reduction of SAP occurrence through decreasing serum levels of TNF-α and IL-6. This regimen presented good cost-effectiveness.
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Celecoxib/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Isoxazoles/uso terapéutico , Pancreatitis/prevención & control , Administración Oral , Adolescente , Adulto , Anciano , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.
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Antígenos B7/metabolismo , Neoplasias Colorrectales/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Humanos , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Tasa de Supervivencia , Análisis de Matrices TisularesRESUMEN
Inhibition of the epidermal growth factor receptor (EGFR) has been proved to be one of the most promising strategies for the treatment of non-small cell lung cancers. A series of 2-aryl-4-amino substituted quinazoline derivatives were designed and synthesized with the purpose to overcome L858R/T790M/C797S (CTL) triple mutant drug resistance and the biological activity for inhibition of CTL kinases and EGFR wild type (WT) were evaluated. Three compounds (20, 24 and 27) showed excellent inhibitory activities against EGFR kinases triple mutant CTL (IC50 < 1 µM) and high selectivity (IC50: WT/CTL >10000). Cell line evaluation showed that the most potent compound 27 was significantly potent against H1975-EGFR L858R/T790M (IC50 = 3.3 µM) and H1975-EGFR L858R/T790M/C797S (IC50 = 1.2 µM). Compound 27 also exhibited good microsomes stabilities in human, rat and mouse liver species, but low bioavailability. This work would be very useful for discovering new quinazoline derivatives as tyrosine kinase inhibitors targeting triple mutant L858R/T790M/C797S.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/síntesis química , Quinazolinas/síntesis química , Administración Oral , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Hígado , Masculino , Simulación del Acoplamiento Molecular , Mutación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacocinética , Quinazolinas/administración & dosificación , Quinazolinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
Objective: Meta-analysis to evaluate complications in the use of autogenous bone and bone substitutes and to compare bone substitutes, specifically HA, polyetheretherketone (PEEK) and titanium materials.Methods: Search of PubMed, Cochrane, Embase and Google scholar to identify all citations from 2010 to 2019 reporting complications regarding materials used in cranioplasty.Results: 20 of 2266 articles met the inclusion criteria, including a total of 2913 patients. The odds of overall complication were significantly higher in the autogenous bone group (n = 214/644 procedures, 33.2%) than the bone substitute groups (n = 116/436 procedures, 26.7%, CI 1.29-2.35, p < 0.05). In bone substitutes groups, there was no significant difference in overall complication rate between HA and Ti (OR, 1.2; 95% CI, 0.47-3.14, p = 0.69). PEEK has lower overall complication rates (OR, 0.51; 95% CI, 0.30-0.87, p = 0.01) and lower implant exposure rates (OR, 0.17; 95% CI, 0.06-0.53, p = 0.002) than Ti, but there was no significant difference in infection rates and postoperative hematoma rates.Conclusions: Cranioplasty is associated with high overall complication rates with the use of autologous bone grafts compared with bone substitutes. PEEK has a relatively low overall complication rates in substitutes groups, but still high infection rates and postoperative hematoma rates. Thus, autologous bone grafts should only be used selectively, and prospective long-term studies are needed to further refine a better material in cranioplasty.
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Procedimientos de Cirugía Plástica , Cráneo/cirugía , Trasplante Óseo , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Prótesis e Implantes/efectos adversosRESUMEN
OBJECTIVE: The transanal approach to specimen collection, combined with the prolapsing technique, is a well-established and minimally invasive surgery for treating rectal cancer. However, reports on outcomes for this approach are sparse. We compared short- and long-term outcomes of conventional laparoscopic surgery (CLS) vs. transanal natural orifice specimen extraction (NOSE) using the prolapsing technique for patients with middle- to low-rectal cancer. METHODS: From January 2013 to December 2017, we enrolled consecutive patients with middle- to low-rectal cancer undergoing laparoscopic anterior resection. Totally, 50 patients who underwent transanal NOSE using the prolapsing technique were matched with 50 patients who received CLS. Clinical parameters and survival outcomes between the two groups were compared. RESULTS: Estimated blood loss (29.70±29.28 vs. 52.80±45.09 mL, P=0.003), time to first flatus (2.50±0.79 vs. 2.86±0.76, P=0.022), time to liquid diet (3.62±0.64 vs. 4.20±0.76 d, P<0.001), and the need for analgesics (22%vs. 48%, P=0.006) were significantly lower for the NOSE group compared to the CLS group. The incidences of overall complications and fecal incontinence were comparable in both groups. After a median follow-up of 44.52 months, the overall local recurrence rate (6% vs. 5%, P=0.670), 3-year disease-free survival (86.7% vs. 88.0%, P=0.945) and 3-year overall survival (95.6% vs. 96.0%, P=0.708), were not significantly different. CONCLUSIONS: For total laparoscopic rectal resection, transanal NOSE using the prolapsing technique is effective and safe, and associated with less trauma and pain, a faster recovery, and similar survival outcomes compared to CLS.
RESUMEN
Abatement of mercury emission from coal-fired power plants remains a serious task for public health and environmental societies. Selenium functionalized metal-organic framework MIL-101 (Se/MIL-101) was prepared for mercury removal from power plants. The Se/MIL-101 exhibited a remarkable mercury adsorption capacity of 148.19 mg·g-1, which was about 154 to 705 times larger than that of commercial activated carbons exclusively applied for mercury removal from power plants. The initial mercury adsorption rate for Se/MIL-101 reached up to 44.8 µg·g-1·min-1, which was 89- to 1659-fold higher than those of mercury sorbents reported in the literature. The Se/MIL-101 maintained an excellent mercury adsorption stability under simulated flue gas atmosphere containing SO2, NO, and H2O. Gaseous elemental mercury (Hg0) converted on the Se/MIL-101 to stable and water-insoluble mercury selenide (HgSe), which guaranteed a minimum re-emission even sequestration of mercury. Moreover, the mercury-laden Se/MIL-101 could also immobilize mercury in gypsum and efficiently capture mercury ions from desulfurization effluent to an undetectable level (<0.0035 µg·L-1). With these advantages, Se/MIL-101 appears to be a promising material for efficient and permanent sequestration of mercury from power plants.
Asunto(s)
Mercurio , Estructuras Metalorgánicas , Selenio , Carbón Mineral , Centrales EléctricasRESUMEN
Mineral sulfide based sorbents were superior alternatives to traditional activated carbons for elemental mercury (Hg0) immobilization in industrial flue gas. A systematical study concerning the influence of sulfur trioxide (SO3) on Hg0 adsorption over a nanosized copper sulfide (Nano-CuS) was for the first time conducted. SO3 was found to significantly inhibit the Hg0 removal over Nano-CuS partially because SO3 oxidized the reduced sulfur species (sulfide) with high affinity to mercury to its oxidized sulfur species (sulfate). Moreover, a brand new "oxidation-reduction" mechanism that led to a simultaneous oxidation of sulfide and reduction of mercury on the immobilized mercury sulfide (HgS) was responsible for the inhibitory effect. Even though the released Hg0 from the reduction of mercury in HgS could be oxidized by SO3 into its sulfate form (HgSO4) and recaptured by the sorbent, the "oxidation-reduction" mechanism still compromised the Hg0 capture performance of the Nano-CuS because HgSO4 deposited on the sorbent surface could be easily leached out when environmentally exposed. These new insights into the role of SO3 in Hg0 capture over Nano-CuS can help to determine possible solutions and facilitate the application of mineral sulfide sorbents as outstanding alternatives to activated carbons for Hg0 immobilization in industrial flue gas.
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Mercurio , Carbón Mineral , Minerales , Sulfuros , Óxidos de AzufreRESUMEN
Healthcare professionals responsible for patients with gastrointestinal diseases need a particular level of nursing knowledge and abilities to ensure excellent care. This study aims to propose a set of core competencies for the gastroenterology nursing specialists (GNS) in China. This research integrates quantitative and qualitative research methods. Literature review, semistructured interview, and the Delphi approach were used to develop the core competency items of GNS in China. SPSS 16.0 was used to analyze the data. Finally, 28 of 30 experts participated in the study resulting in a consensual list containing 7 domains (clinical nursing practice, communication and collaboration, education and counseling, critical thinking, leadership, ethical and legal practice, and professional development), 23 aspects, and 66 competencies required for GNS. The authority coefficient (Cr) of the consensus was 0.77, and the Kendall (W) value of each level of competencies all scored above 0.5. Results of the study can serve as a foundation of work performance evaluation for GNS as well as promote nurses' professional development.
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Competencia Clínica , Gastroenterología/educación , Enfermeras Especialistas/educación , Encuestas y Cuestionarios , China , Consenso , Curriculum , Técnica Delphi , Humanos , Investigación CualitativaRESUMEN
Metal-phosphorus-trichalcogenides (MPTs), represented by NiPS3, FePS3, etc, are newly developed 2D wide-bandgap semiconductors and have been proposed as excellent candidates for ultraviolet (UV) optoelectronics. In spite of having superior advantages for solar-blind UV photodetectors, including those free of surface trap states, being highly compatible with versatile integrations as well as having an appropriate band gap, to date relevant study is rare. In this work, the photoresponse characteristic of UV detectors based on few-layer FePS3 has been comprehensively investigated. The responsivity of the photodetector, which is observed to be determined by bias gate voltage, may achieve as high as 171.6 mAW-1 under the illumination of 254 nm weak light, which is comparable to most commercial UV detectors. Notably, both negative and positive photoconductivities exist in the FePS3 photodetectors and can be controllably switched with bias voltage. The eminent and novel photoresponse property paves the way for the further development and practical use of 2D MPTs in high-performance UV photodetections.