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PURPOSE: Due to lumbar spinal surgery is frequently accompanied with moderate-to-severe postoperative pain, it is necessary to find an effective postoperative analgesia for patients with this surgery. This study aimed to observe the analgesic effect of dexmedetomidine combined with ropivacaine erector spinae plane block (ESPB) used in posterior lumbar spine surgery. METHODS: In this clinical trial, patients undergoing posterior lumbar spine surgery were recruited and randomly divided into two groups: intervention and control. The intervention group (Group E) received 0.375% ropivacaine with 1 µg/kg dexmedetomidine in a total of 20 ml for ESPB; the control group (Group C) received 20 ml ropivacaine 0.375% for ESPB. US-guided ESPB was performed preoperatively in all patients. Demographics, anesthesia time, surgery time, and ASA grade from the participants were recorded at baseline. The primary clinical outcome measures were 2-, 4-, 8-, 12-, 24-and 48-h visual analog scale (VAS) pain scores after surgery at rest and movement state. Other end points included opioid consumption, number of PCIA presses, flurbiprofen-axetil consumption, quality of recovery and pain management after surgery. RESULTS: One hundred twenty patients were enrolled in the study (mean [SD] ages: Group E, 54.77 [8.61] years old; Group C,56.40 [7.87] years old; P = 0.280). The mean anesthesia time was 152.55 (15.37) min in Group E and 152.60 (16.47) min in Group C (P = 0.986). Additionally, the surgery time was 141.70 (15.71) min in Group E compared to 141.48 (17.13) min in Group C (P = 0.943). In addition, we found that the VAS pain scores in the resting state during the postoperative period at 8-48 h were lower in Group E than in Group C. However, the VAS pain scores in the active state were lower in Group E at 12-48 h (P < 0.05). More importantly, the consumption of opioids and flurbiprofen-axetil after surgery was also lower in Group E (P < 0.05). Subsequently, we administered questionnaires on the quality of recovery and pain management after surgery that were positively correlated with the postoperative analgesic effect. It was worth affirming that the QoR-15 scores and APS-POQ-R questionnaire results were different between the two groups, further confirming that the combination of drugs not only could obtain an ideal analgesic effect but also had no obvious adverse reactions (P < 0.05). CONCLUSIONS: All the findings suggested that dexmedetomidine could significantly relieve postoperative pain and reduce the consumption of opioids in patients undergoing posterior lumbar spine surgery without obvious adverse reactions as a local anesthetic adjuvant. Further studies with larger sample sizes and different drug dosages may be useful in understanding the potential clinical benefits of dexmedetomidine.
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Dexmedetomidina , Bloqueo Nervioso , Niño , Humanos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Músculos Paraespinales , RopivacaínaRESUMEN
PURPOSE: To evaluate the effect of different exposure temperatures during the dilution process on the survival rate of vitrified oocytes and following development. METHODS: Patients were divided at random into two groups for different dilution temperature (20-22 °C, RT group; 37 °C,37 °C group) according to computer-generated random numbers on the day of oocyte warming. The survival and fertilization rates of vitrified oocytes as well as the implantation and clinical pregnancy rates of the resulting embryos were recorded. RESULTS: A total of 662 and 676 oocytes were warmed in the 37 °C group and RT group, respectively, and significant difference was observed in the survival rate between 37 °C group (88.37%) and RT group (79.88%) (P = 0.0000). There was significant difference between the survival rate of 37 °C group (87.27%) and RT group (75.64%) in nondonor patients (P = 0.0001). Multiple linear regression analysis showed that dilution temperature (ß = 0.079, P = 0.017) and clinical outcomes of fresh cycles (ß = 0.063, P = 0.001) were significantly and independently associated with survival rate. No significant difference was found between the 37 °C group and RT group in: fertilization rate (66.67 versus 65.37%), implantation rate (20.0 versus 19.46%), clinical pregnancy rate (37.5 versus 35.0%). CONCLUSIONS: In conclusion, the results of this study give supportive evidence of the application of 37 °C in the dilution process, especially for oocytes of poor quality. Further studies with well-controlled experimental groups are needed to optimize protocols for human oocyte vitrification.
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Criopreservación/métodos , Oocitos/fisiología , Resultado del Embarazo , Adulto , Supervivencia Celular , Implantación del Embrión , Transferencia de Embrión , Femenino , Fertilización In Vitro/estadística & datos numéricos , Humanos , Modelos Lineales , Nacimiento Vivo , Oocitos/citología , Embarazo , Índice de Embarazo , Temperatura , Resultado del Tratamiento , VitrificaciónRESUMEN
The penetration rate (PR) of tunnel boring machines (TBMs) is often used to evaluate tunneling performance and predict construction period costs. However, most penetration rate (PR) prediction models are based on a single specific project, which leads to poor universality of the models.Furthermore, the value of the cutter head speed set for the prediction of the construction period in the survey and planning stages depends on manual experience and lacks theoretical guidance. Therefore, based on a set of engineering data from TBM of different surrounding rocks and diameters, this study statistically analyzed the distribution law of the cutter head speed (N) and the relationship between the field penetration index (FPI), geological parameters (uniaxial compressive strength (UCS) and the integrity coefficient of the rock mass (Kv)), and penetration (P). The results show that the FPI is strongly correlated with the geological parameters and the P. The geological and tunnelling parameters are the main factors affecting the penetration rate (PR). On the basis of this, prediction models of the FPI and P and a calculation model of the cutter head speed were developed, and a prediction model of the PR was obtained. The accuracy and reliability of this model were verified and analyzed for the EHe (EH) project. The average prediction error was 15.15 %.
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Immune checkpoint inhibitors (ICIs) block checkpoint receptors that tumours use for immune evasion, allowing immune cells to target and destroy cancer cells. Despite rapid advancements in immunotherapy, durable response rates to ICIs remains low. To address this, combination clinical trials are underway assessing whether adjuvants can enhance responsiveness by increasing tumour immunogenicity. CpG-oligodeoxynucleotides (CpG-ODN) are synthetic DNA fragments containing an unmethylated cysteine-guanosine motif that stimulate the innate and adaptive immune systems by engaging Toll-like receptor 9 (TLR9) present on the plasmacytoid dendritic cells (pDCs) and B cells. Here, we have assessed the ability of AlF-mNOTA-GZP, a peptide tracer targeting granzyme B, to serve as a PET imaging biomarker in response to CpG-ODN 1585 in situ vaccine therapy delivered intratumourally (IT) or intraperitoneally (IP) either as monotherapy or in combination with αPD1. [18F]AlF-mNOTA-GZP was able to differentiate treatment responders from non-responders based on tumour uptake. Furthermore, [18F]AlF-mNOTA-GZP showed positive associations with changes in tumour-associated lymphocytes expressing GZB, namely GZB+ CD8+ T cells, and decreases in suppressive F4/80+ cells. [18F]AlF-mNOTA-GZP tumour uptake was mediated by GZB expressing CD8+ cells and successfully stratifies therapy responders from non-responders, potentially acting as a non-invasive biomarker for ICIs and combination therapy evaluation in a clinical setting.
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Immune checkpoint inhibitors have shown great promise, emerging as a new pillar of treatment for cancer; however, only a relatively small proportion of recipients show a durable response to treatment. Strategies that reliably differentiate durably-responding tumours from non-responsive tumours are a critical unmet need. Persistent and durable immunological responses are associated with the generation of memory T cells. Effector memory T cells associated with tumour response to immune therapies are characterized by substantial upregulation of the potassium channel Kv1.3 after repeated antigen stimulation. We have developed a new Kv1.3 targeting radiopharmaceutical, [18F]AlF-NOTA-KCNA3P, and evaluated whether it can reliably differentiate tumours successfully responding to immune checkpoint inhibitor (ICI) therapy targeting PD-1 alone or combined with CLTA4. In a syngeneic colon cancer model, we compared tumour retention of [18F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [18F]AlF-NOTA-KCNA3P reliably differentiated tumours responding to ICI therapy from non-responding tumours and was associated with substantial tumour infiltration of T cells, especially Kv1.3-expressing CD8+ effector memory T cells.
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In this study, we identified eight survival-related metabolic genes in differentially expressed metabolic genes by univariate Cox regression analysis based on the therapeutically applicable research to generate effective treatments (n = 84) data set and genotype tissue expression data set (n = 396). We also constructed a six metabolic gene signature to predict the overall survival of osteosarcoma (OS) patients using least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Our results show that the six metabolic gene signature showed good performance in predicting survival of OS patients and was also an independent prognostic factor. Stratified correlation analysis showed that the metabolic gene signature accurately predicted survival outcomes in high-risk and low-risk OS patients. The six metabolic gene signature was also verified to perform well in predicting survival of OS patients in an independent cohort (GSE21257). Then, using univariate Cox regression and Lasso Cox regression analyses, we identified an eight metabolism-related long noncoding RNA (lncRNA) signature that accurately predicts overall survival of OS patients. Gene set variation analysis showed that the apical surface and bile acid metabolism, epithelial mesenchymal transition, and P53 pathway were activated in the high-risk group based on the eight metabolism-related lncRNA signature. Furthermore, we constructed a competing endogenous RNA (ceRNA) network and conducted immunization score analysis based on the eight metabolism-related lncRNA signature. These results showed that the six metabolic gene signature and eight metabolism-related lncRNA signature have good performance in predicting the survival outcomes of OS patients.
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PURPOSE: Chemotherapeutic adjuvants, such as oxaliplatin (OXA) and 5-fluorouracil (5-FU), that enhance the immune system, are being assessed as strategies to improve durable response rates when used in combination with immune checkpoint inhibitor (ICI) monotherapy in cancer patients. In this study, we explored granzyme B (GZB), released by tumor-associated immune cells, as a PET imaging-based stratification marker for successful combination therapy using a fluorine-18 (18F)-labelled GZB peptide ([18F]AlF-mNOTA-GZP). METHODS: Using the immunocompetent CT26 syngeneic mouse model of colon cancer, we assessed the potential for [18F]AlF-mNOTA-GZP to stratify OXA/5-FU and ICI combination therapy response via GZB PET. In vivo tumor uptake of [18F]AlF-mNOTA-GZP in different treatment arms was quantified by PET, and linked to differences in tumor-associated immune cell populations defined by using multicolour flow cytometry. RESULTS: [18F]AlF-mNOTA-GZP tumor uptake was able to clearly differentiate treatment responders from non-responders when stratified based on changes in tumor volume. Furthermore, [18F]AlF-mNOTA-GZP showed positive associations with changes in tumor-associated lymphocytes expressing GZB, namely GZB+ CD8+ T cells and GZB+ NK+ cells. CONCLUSIONS: [18F]AlF-mNOTA-GZP tumor uptake, driven by changes in immune cell populations expressing GZB, is able to stratify tumor response to chemotherapeutics combined with ICIs. Our results show that, while the immunomodulatory mode of action of the chemotherapies may be different, the ultimate mechanism of tumor lysis through release of Granzyme B is an accurate biomarker for treatment response.
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Neoplasias del Colon , Granzimas/metabolismo , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Tomografía de Emisión de Positrones , Animales , Línea Celular Tumoral , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Modelos Animales de Enfermedad , Linfocitos Infiltrantes de Tumor/metabolismo , RatonesRESUMEN
Depression is a chronic and progressive syndrome and commonly associated with several neuropsychiatric comorbidities, of which depression is the most studied. It has been demonstrated that statins also have anti-inflammatory and immunomodulatory properties, which being explored for potential benefits in depression. However, the role of statins in the treatment of diabetes-related depression has not been well examined. Herein, we investigated the effects of atorvastatin on depressive behaviors and neuroinflammation in streptozotocin-induced diabetic mice. Our data indicated that oral administration of atorvastatin at 10 or 20 mg/kg for 3 weeks markedly ameliorated diabetes-associated depressive behaviors reflected by better performance in sucrose preference test (SPT), tail suspension test (TST), and novelty-suppressed feeding test (NSFT). The study further showed that atrovastatin decreased the expression of nucleus NF-κB p65 expression and ameliorated neuroinflammatory responses in prefrontal cortex as evidenced by less Iba-1-positive cells and lower inflammatory mediators including IL-1ß and TNF-α. As expected, atorvastatin-treated diabetic mice exhibited significant improvement of hyperlipidemia rather than hyperglycemia. These results suggest that atorvastatin has the potential to be employed as a therapy for diabetes-related depression.
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Atorvastatina/uso terapéutico , Depresión/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Mediadores de Inflamación/antagonistas & inhibidores , Estreptozocina/toxicidad , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Atorvastatina/farmacología , Depresión/metabolismo , Depresión/psicología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/psicología , Relación Dosis-Respuesta a Droga , Suspensión Trasera/efectos adversos , Suspensión Trasera/psicología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The self-assembly of rhenium-based rectangular boxes with a large inner cavity can be achieved via a simple one-step synthetic route; these molecules selectively recognize planar aromatic molecules, benzene in particular.
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Benceno/química , Renio/química , Cristalografía por Rayos X , Modelos Moleculares , Conformación Molecular , Especificidad por SustratoRESUMEN
Objective:To improve the understanding of hemodialysis complicated with mesenteric artery calcified stenosis and mesenteric ischemia through the analysis of the case and review of related literature.Methods:A case of hemodialysis with intractable abdominal pain as the main manifestation was reported, and its clinical features, diagnosis and treatment were summarized.Results:The case was a maintenance hemodialysis patient with persistent dull pain around the umbilicus, which worsens after meal and hemodialysis. The results showed multiple vascular calcification, superior mesenteric artery stenosis so the patient was diagnosed with chronic mesenteric ischemia. Mesenteric revascularization under intervention was planned but the guide wire failed to enter the superior mesenteric artery after repeated attempts during the operation. Surgical treatment was recommended, but the patient and family refused surgery and were discharged.Conclusions:Dialysis patients with intractable abdominal pain should be carefully identified and alert for mesenteric artery disease and mesenteric ischemia.
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OBJECTIVES@#Long-term elevated blood pressure may lead to kidney damage, yet the pathogenesis of hypertensive kidney damage is still unclear. This study aims to explore the role and significance of leucine-rich alpha-2-glycoprotein-1 (LRG-1) in hypertensive renal damage through detecting the levels of LRG-1 in the serum and kidney of mice with hypertensive renal damage and its relationship with related indexes.@*METHODS@#C57BL/6 mice were used in this study and randomly divided into a control group, an angiotensin II (Ang II) group, and an Ang II+irbesartan group. The control group was gavaged with physiological saline. The Ang II group was pumped subcutaneously at a rate of 1.5 mg/(kg·d) for 28 days to establish the hypertensive renal damage model in mice, and then gavaged with equivalent physiological saline. The Ang II+irbesartan group used the same method to establish the hypertensive renal damage model, and then was gavaged with irbesartan. Immunohistochemistry and Western blotting were used to detect the expression of LRG-1 and fibrosis-related indicators (collagen I and fibronectin) in renal tissues. ELISA was used to evaluate the level of serum LRG-1 and inflammatory cytokines in mice. The urinary protein-creatinine ratio and renal function were determined, and correlation analysis was conducted.@*RESULTS@#Compared with the control group, the levels of serum LRG-1, the expression of LRG-1 protein, collagen I, and fibronectin in kidney in the Ang II group were increased (all P<0.01). After treating with irbesartan, renal damage of hypertensive mice was alleviated, while the levels of LRG-1 in serum and kidney were decreased, and the expression of collagen I and fibronectin was down-regulated (all P<0.01). Correlation analysis showed that the level of serum LRG-1 was positively correlated with urinary protein-creatinine ratio, blood urea nitrogen, and blood creatinine level in hypertensive kidney damage mice. Serum level of LRG-1 was also positively correlated with serum inflammatory factors including TNF-α, IL-1β, and IL-6.@*CONCLUSIONS@#Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage.
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Animales , Ratones , Ratones Endogámicos C57BL , Fibronectinas , Irbesartán , Creatinina , Riñón/fisiología , Hipertensión/complicaciones , Angiotensina II , Colágeno Tipo IRESUMEN
OBJECTIVE To analyze the effects of the national centralized drug procurement (NCDP) policy on drug availability and the structure of drug use in public hospitals. METHODS Using hypoglycemic, lipid-lowering, antiviral drugs, and psychiatric drugs for the treatment of mental illness and depression as objects, the interrupted time series model was used to quantitatively evaluate the changes in consumption sum of drugs, consumption amount and daily cost of the target drugs in national sample hospitals as well as the changes in per capita medication frequency, outpatient prescription amount, and medical insurance surplus of target drugs in a third grade class A hospital before and after the implementation of NCDP policy. RESULTS After the implementation of the NCDP policy, the volume for the four bid-winning drugs increased significantly (P<0.01 for the remaining three categories except for hypoglycemic drugs), but DDDc (P<0.01) and the amount of related drugs (P<0.001) decreased significantly. The volume for the non-winning drugs (except for lipid-lowering drugs) decreased significantly (P<0.05), and DDDc also decreased significantly (P<0.05 for other 3 categories except for psychiatric drugs); the volume (P<0.01) and DDDc (P<0.01 only for psychiatric drugs) for alternative drugs all increased except for antiviral drugs. The structure of drug use for different drugs was affected differently by the NCDP policy,and that of hypoglycemic drugs was affected obviously; the proportion of alternative drugs increased after centralized procurement. The outpatient prescription amount of each hospital significantly decreased after centralized procurement,and the decrease in the cost paid by the patients using lipid-lowering and antiviral drugs related to centralized procurement was greater than 0.60; the remaining medical insurance amount for bid-winning drugs was approximately 1.252 5 million yuan. CONCLUSIONS NCDP policy effectively alleviates the burden of medical expenditure and also drives the structure changes of drug use such as the substitution of generic drugs for original drugs, the growth of the volume of alternative drugs.
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Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.
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Femenino , Humanos , Recién Nacido , Embarazo , Peso al Nacer , Cesárea , Edad Gestacional , Recién Nacido Pequeño para la Edad Gestacional , Preeclampsia/epidemiología , Estudios ProspectivosRESUMEN
Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.
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Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Estadificación de Neoplasias , Metástasis Linfática , Escisión del Ganglio Linfático , Estudios Retrospectivos , Pronóstico , Quimioradioterapia/métodos , Carcinoma de Células Escamosas/patologíaRESUMEN
BACKGROUND@#Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys.@*METHODS@#In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining.@*RESULTS@#15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI.@*CONCLUSION@#Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
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Humanos , Ratones , Animales , Transcriptoma/genética , Ligandos , Riñón/metabolismo , Lesión Renal Aguda/metabolismo , Isquemia/metabolismo , Daño por Reperfusión/metabolismo , Análisis de Secuencia de ARN , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The impact of parental obesity on offspring health attracts increasing attention with the rising obese population worldwide. Much more studies have concentrated on the influences of maternal obesity, while studies regarding paternal obesity were relatively few and mainly focused on glucose and insulin regulation, adiposity, etc. Several large cohort studies and animal experiments have shown that paternal obesity can damage the neuropsychological development in offspring, which has become a risk factor for autistic spectrum disorders, cognitive disorders, and lower intelligence quotient, and epigenetic studies have explored the related mechanisms. This review summarizes the progress in this field, aiming to provide a reference for basic and clinical research in the future.
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Objective: To explore the predictive values of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score on the death risk of severe burn patients. Methods: A retrospective case series study was conducted. From February 2018 to November 2019, 260 severe burn patients who met the inclusion criteria were admitted to the Department of Burns of the First Affiliated Hospital of Nanchang University, including 158 males and 102 females, aged 36 (3, 53) years. According to the final outcome, the patients were divided into survival group (n=229) and death group (n=31). Data of patients were compared and statistically analyzed with chi-square test or Mann-Whitney U test between the two groups, including the gender, age, cause of burn, site of burn, total burn area, depth of burn, combined inhalation injury, and combined underlying diseases on admission, and the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score calculated based on part of the aforementioned data. The Kendall tau-b coefficient method was used to analyze the consistency of the above-mentioned three scores in 260 severe burn patients. The receiver operating characteristic (ROC) curves of the above-mentioned three scores predicting the death risk of 260 severe burn patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of AUC of the above-mentioned three scores was compared by Delong test. Results: The gender, site of burn, and depth of burn of patients between the two groups were all similar (P>0.05). The age, total burn area, proportion of flame burn, proportion of combined inhalation injury, and proportion of combined underlying diseases of patients in death group were significantly higher than those in survival group (with Z values of 5.53 and 17.78, respectively, χ2 values of 16.23, 15.89, and 17.78, respectively, P<0.01); the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score of patients in death group were 142 (115, 155), 7 (5, 7), 2 (2, 3), all significantly higher than 64 (27, 87), 1 (0, 3), 0 (0, 1) in survival group (with Z values of 7.91, 7.64, and 7.61, respectively, P<0.01). In 260 severe burn patients, the results between the modified Baux score and Ryan score, modified Baux score and Belgian Outcome in Burn Injury score, Ryan score and Belgian Outcome in Burn Injury score were significantly consistent (with Kendall tau-b coefficients of 0.75, 0.71, and 0.86, respectively, P<0.01). The AUCs of ROC curves of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score for predicting the death risk of 260 severe burn patients were 0.92, 0.89, and 0.85, respectively (with 95% confidence intervals of 0.86-0.98, 0.83-0.95, and 0.78-0.93, respectively, P<0.01); the optimal thresholds were 106.5, 4.5, and 1.5 points, respectively; the sensitivity under the optimal threshold were 88.5%, 76.9%, and 73.1%, respectively, and the specificity under the optimal threshold were 88.5%, 87.2%, and 86.3%, respectively. The modified Baux score was similar to Belgian Outcome in Burn Injury score in the AUC quality (z=1.25, P>0.05), which were both significantly better than the AUC quality of Ryan score (with z values of 2.35 and 2.11, respectively, P<0.05). Conclusions: The modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score have good ability in predicting the death risk of severe burn patients. From the perspective of clinical practice, the modified Baux score is more suitable as a predictive tool for the prognosis of severe burn patients.
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Adulto , Femenino , Humanos , Masculino , Quemaduras , Hospitalización , Pronóstico , Curva ROC , Estudios RetrospectivosRESUMEN
INTRODUCTION@#Adults aged ≥60 years contribute to disproportionately higher visits to the emergency departments (ED). We performed a systematic review to examine the reasons why older persons visit the ED in Singapore.@*METHODS@#We searched Medline, Embase and Scopus from January 2000 to December 2021 for studies reporting on ED utilisation by older adults in Singapore, and included studies that investigated determinants of ED utilisation. Statistically significant determinants and their effect sizes were extracted. Determinants of ED utilisation were organised using Andersen and Newman's model. Quality of studies was evaluated using Newcastle Ottawa Scale and Critical Appraisal Skills Programme.@*RESULTS@#The search yielded 138 articles, of which 7 were used for analysis. Among the significant individual determinants were predisposing (staying in public rental housing, religiosity, loneliness, poorer coping), enabling (caregiver distress from behavioural and psychological symptoms of dementia) and health factors (multimorbidity in patients with dementia, frailty, primary care visit in last 6 months, better treatment adherence). The 7 included studies are of moderate quality and none of them employed conceptual frameworks to organise determinants of ED utilisation.@*CONCLUSION@#The major determinants of ED utilisation by older adults in Singapore were largely individual factors. Evaluation of societal determinants of ED utilisation was lacking in the included studies. There is a need for a more holistic examination of determinants of ED utilisation locally based on conceptual models of health seeking behaviours.
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Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Servicio de Urgencia en Hospital , Fragilidad , Conductas Relacionadas con la Salud , SingapurRESUMEN
BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
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Animales , Humanos , Ratones , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales , Hemaglutininas , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Subtipo H7N9 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Gripe Humana/prevención & controlRESUMEN
OBJECTIVES@#Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.@*METHODS@#The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.@*RESULTS@#A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).@*CONCLUSIONS@#PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.