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This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‒1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‒2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‒1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‒1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‒0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‒0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‒8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‒6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Extracellular Matrix Proteins/genetics , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Treatment OutcomeABSTRACT
Objective:To explore the ultrasonographic features of desmoid fibromatosis and provide evidence for clinical management.Methods:The ultrasonic images and clinical data of 22 cases of desmoid fibromatosis confirmed by pathology in the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from 2016 to 2021 were retrospectively analyzed. The location, size, shape, boundary, internal echo, posterior acoustic enhancement, relationship with surrounding tissues and blood flow of the lesion were evaluated.Results:The maximum diameter of lesions in 22 patients ranged from 0.8 cm to 11.3 cm (5.2±2.4)cm. (1) There were 17 cases of extra-abdominal shape: 10 cases of irregular shape, 4 cases of spindle shape, and 3 cases of oval shape. In 10 cases, the lesion boundary was not clear, and the lesion was infiltrated along the muscle, fascia or adipose tissue. Uneven hypoechogenicity was found in 11 cases, and strip or patchy strong echo was found in 4 cases. 5 cases with posterior echogenicity enhancement; color Doppler flow imaging (CDFI) blood flow classification: grade 0 in 2 cases, grade 1 in 7 cases, grade 2 in 7 cases, and grade 3 in 1 case. (2) Abdominal wall type in 5 cases: oval shape in 2 cases, spindle shape in 2 cases, irregular shape in 1 case; In 3 cases, the boundary was not clear and was infiltrative along the muscle. Inhomogeneous hypoecho was found in 4 cases. Posterior echogenicity was enhanced in 1 case. CDFI blood flow classification: grade 1 in 2 cases, grade 2 in 2 cases, grade 3 in 1 case.Conclusions:The sonograms of typical desmoid fibromatosis have certain features. Combined with the patient′s history and clinical manifestations, they can provide an important basis for the clinical management of the disease.
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Since the outbreak of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) discovered in December 2019, the disease has emerged as a global pandemic (Shi et al., 2020; World Health Organization, 2020). Several studies have shown a higher incidence of COVID-19, as well as related poor outcomes in patients with malignancies as compared with those without them (Liang et al., 2020; Tian et al., 2020). The impact of cancer on COVID-19 may be attri‑buted to the use of antitumor treatments that may disturb the host response to SARS-CoV-2 infection (Wang et al., 2020), while the current studies on this topic have drawn controversial conclusions. Some implied that anticancer treatments might elevate the risk of death (García-Suárez et al., 2020; Liu et al., 2020). On the contrary, others pointed out that this association is not significant (Brar et al., 2020; Lee et al., 2020a). Although previous systematic reviews have investigated this important issue (Wang and Huang, 2020), the heterogeneity of findings is obvious and the general conclusion has remained unclear. Considering this ambiguity, it is difficult for clinicians to make therapeutic decisions when facing patients with both cancer and COVID-19; therefore, a high-quality and accurate evaluation of the impact of anticancer treatments on COVID-19 patients is necessary. Accordingly, we conducted a pooled analysis with the original data of each patient for the first time to provide a comprehensive perspective into the association between anticancer regimens and the outcomes of cancer patients with COVID-19.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , COVID-19/complications , Neoplasms/therapy , SARS-CoV-2ABSTRACT
Objective To explore the experience of the family caregivers of the old hip fracture patients with cognition impairment. Methods By using purpose sampling method,11 participants which treating from January to April 2017 were applied semi-structured in-depth interview,and then analysis the material. Results Four themes were analyzed about the caring demands of the family caregivers, including existing heavier caring burden,inadequate knowledge and skills,positive face to the caring task, desire to caregiver support system. Conclusions The family caregivers of the old hip fracture patients with cognition impairment exist heavier caring burden, the medical service institutions should call on national policy support and economic aid for caregivers, care about the mental health of caregivers and improve their coping ability, as well as provide professional knowledge and skills guidance and build a perfect caregiver support system at the same time in order to reduce the burden of caregivers early.
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It introduced the definition of the caregiver and at home and abroad,and also reviewed influencing factors of family caregiver′s burden of the elderly patients. At last, it put forward the essentiality to perfect the nursing intervention and improve caregivers' coping capacity, as well as the transitional care model and the linkage"hospital-community-family",and improve national legislation and policy support in order to structure the social support system at the same time, so as to provide reference for study of reducing the family caregiver′s burden of the elderly patients.
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Deep vein thrombosis (DVT) has attracted great attention because of its high morbidity in orthopedics department, which could easily cause lethal pulmonary embolism (PE). Based on the domestic and foreign findings from the prophylaxis and nursing of DVT, this thesis summarized the key problems in orthopedic patients. It firstly defined the conception of DVT,and then emphasized the morbidity and severity of DVT in orthopedics department. After that it reviewed the possible risk factors that contributed to DVT. Moreover it also pointed out some matters needing attentions through discussing and analyzing the nursing and prophylactic measures against DVT, and it also gave some recommendations on it. It expounded the nursing progress on prophylaxis of the deep venous thrombosis in department of orthopedics, so as to provide reference for clinical work and study.
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Diabetic rat model was induced by high fat diet combined with streptozotocin (STZ). After the model was established, blood samples were taken from jugular veins to examine plasma adrenocorticotropic hormone (ACTH) and corticosterone, and hypothalamus and pituitary were removed for real-time PCR. There were no significant differences in basal plasma ACTH and corticosterone level among control, obese, and obese diabetic rats (P=0.07). The corticosterone rhythm in obese and obese diabetic rats was impaired. Hypothalamus glucocorticoid receptors (GR) mRNA expressions yielded similar results in the groups, but 11β-HSD1 mRNA expression in obese diabetic rats was up-regulated ( vs control rats, P<0.05 ). The expressions of GR and 11β-HSD1 in pituitary of obese diabetic and obese rats were significantly down-regulated (both P<0.05). In the obese diabetic rats, the impaired glucocorticoid negative feedback was partly due to down-regulation of 11 β-HSD1 and GR expressions in pituitary.
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Objective To evaluate out-patient individual health education prescription by diabetes nurse specialist on related knowledge of type-2 diabetes mellitus and blood glucose.Then combined with patient satisfaction surveys to explore the intervention value of out-patient individual health education prescription.Methods 100 out-patients with type-2 diabetes mellitus were chosen,and gave them individual health education prescription by evaluate individual condition and existing problems with previous treatment protocol unchanged,the prescription content included individual condition,diet,exercise,medication instructions and disease condition monitoring.The grasp of related knowledge of type-2 diabetes mellitus and satisfaction degree with diabetes nurse specialist were investigated by questionnaires.Results 3 months after individual health education,The grasp of related knowledge of type-2 diabetes mellitus,blood glucose and 2 hours' postprandial blood glucose greatly alleviated.Total satisfaction degree of patients reached 94%.Conclusions Paying attention to individualized instruction and out-patient individual health prescription in prevention and treatment of type-2 diabetes mellitus accords with humanization of nursing service,and is a powerful measure to improve health education quality.
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The plasma level and the regulation of cortisol in type 2 diabetic patients were invesligated.Plasma and urinary cortisol levels were measured, and dexamethasonc suppression test and oral cortisone test in vivo were performed. Compared with controls, diabetic patients had higher urinary cortisol level. The activity of hepatic 11 β-hydroxy-steroid dehydrogenase-1 (11β-HSD1) in type 2 diabetic patients was decreased, suggesting that the elevated basal cortisol in type 2 diabetic patiens may due to impaired hepatic degradation of cortisol.
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Objective To investigate the function of the hypothalamic-pituitary-adrenal (HPA) axis in postmenopausal women with type 2 diabetes and visceral obesity. Methods Subjects were divided into three groups:control group(group C),type 2 diabetes mellitus with non-obesity group (group DM) and type 2 diabetes mellitus with visceral obesity group (group DM + OB). General clinical characteristics, morning blood cortisol concentrations and 24 h urine free cortisol of three groups were compared. Serum cortisol levels were also compared after 0.25 mg dexamethasone suppression test and followed by oral intake of 25 mg cortisone acetate. Results (1) There were no significant differences in basal cortisol levels, but after inhibition with dexamethasone the group DM + OB showed significantly higher cortisol level than that in the control group (P < 0.01). (2) Conversion of oral cortisone to plasma cortisol differed significantly between the group C (lower) and group DM + OB (P < 0.05). (3) Plasma LH and FSH concerntrations were significantly lower in group DM + OB compared with group C (P < 0.01). Conclusion In the postmenopausal women with type 2 diabetes mellitus, the negative feedback mechanism and hepatic 11β-HSD-1 activity were impaired, especially in those with visceral obesity.
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OBJECTIVE: To compare safety and efficacy between anterior cervical decompression and fusion procedures as well as compound titanium rete implantation for the treatment of cervical spondylotic myelopathy using Meta analysis. DATA SOURCE: The relative articles were retrieved from Chinese Biomedical Literature Database (CBM) from January 1998 to December 2008, CNKI from January 1994 to December 2008, and VIP from January 1989 to December 2008. DATA SELECTION: A clinically randomized controlled study was used to evaluate safety and efficacy between anterior cervical decompression and fusion procedures as well as compound titanium rete implantation for the treatment of cervical spondylotic myelopathy. Control or vertebroplasty was excluded. MAIN OUTCOME MEASURES: JOA score, complication, and bone fusion rate. RESULTS: Six clinically control studies were included in the final analysis containing 443 patients. Among the patients, 190 cases were treated with anterior cervical decompression and fusion procedures alone, and 253 with anterior cervical decompression and fusion procedures as well as compound titanium rete implantation. All the 6 controls were performed with Meta analysis. ① Efficacy of anterior cervical decompression and fusion procedures as well as compound titanium rete implantation was superior to that of anterior cervical decompression and fusion procedures [OR=2.30, 95%, CI (1.32, 4.01), P
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The effects of estradiol and tamoxifen on the proliferation of estrogen receptor positive cells and the relationship between the tamoxifen tolerance and cell origin were investigated. The tissues of human endometrium and breast cancer were randomly selected following dissection for primary cell culture. After the breast cancer cells and endometrial cells were treated with 1 x 10(-8) mol/L estradiol and/or 1 x 10(-6) tamoxifen, 3H-labelled thymine nucleotide was used to trace the kinetics of cell proliferation. There was no significant difference in the inhibition on the human endometrial cells between tamoxifen-treated group (6.3%) and control group (6.4%), but tamoxifen could significantly inhibit the proliferation of the human breast cancer cells (45.84%) as compared with control group (52.72%). Moreover, tamoxifen could significantly stimulate the proliferation of tamoxifen resistant breast cancer cells (9.64%) as compared with control group (6.32%). Estradiol could significantly stimulate the proliferation of all the three kinds of cells as compare with control group. The combined use of estradiol and tamoxifen could inhibit the proliferation of the endometrial cells and breast cancer cells as compared with estradiol used alone, but on the tamoxifen resistant breast cancer cells, they could more significantly stimulate the proliferation than E2. It was concluded that E2 could stimulate the proliferation of these three kinds of cells. However, the inhibitive effects of tamoxifen on the proliferation of these cells were dependent on the estradiol.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Breast Neoplasms/pathology , Cell Division/drug effects , Cells, Cultured , Drug Interactions , Endometriosis/pathology , Endometrium/pathology , Estradiol/pharmacology , Tamoxifen/pharmacology , Tumor Cells, CulturedABSTRACT
The effects of estradiol and tamoxifen on the proliferation of estrogen receptor positive cells and the relationship between the tamoxifen tolerance and cell origin were investigated. The tissues of human endometrium and breast cancer were randomly selected following dissection for primary cell culture. After the breast cancer cells and endometrial cells were treated with 1 x 10(-8) mol/L estradiol and/or 1 x 10(-6) tamoxifen, 3H-labelled thymine nucleotide was used to trace the kinetics of cell proliferation. There was no significant difference in the inhibition on the human endometrial cells between tamoxifen-treated group (6.3%) and control group (6.4%), but tamoxifen could significantly inhibit the proliferation of the human breast cancer cells (45.84%) as compared with control group (52.72%). Moreover, tamoxifen could significantly stimulate the proliferation of tamoxifen resistant breast cancer cells (9.64%) as compared with control group (6.32%). Estradiol could significantly stimulate the proliferation of all the three kinds of cells as compare with control group. The combined use of estradiol and tamoxifen could inhibit the proliferation of the endometrial cells and breast cancer cells as compared with estradiol used alone, but on the tamoxifen resistant breast cancer cells, they could more significantly stimulate the proliferation than E2. It was concluded that E2 could stimulate the proliferation of these three kinds of cells. However, the inhibitive effects of tamoxifen on the proliferation of these cells were dependent on the estradiol.
Subject(s)
Adult , Female , Humans , Middle Aged , Antineoplastic Agents, Hormonal , Pharmacology , Breast Neoplasms , Pathology , Cell Division , Cells, Cultured , Drug Interactions , Endometriosis , Pathology , Endometrium , Pathology , Estradiol , Pharmacology , Tamoxifen , Pharmacology , Tumor Cells, CulturedABSTRACT
The relationship between the hepatic ischemia/reperfusion (I/R) injury and the balance of nitric oxide/endothelins (NO/ET) was studied. The changes of the ratio of NO/ET and the hepatic injury were observed in a rat hepatic I/R model pretreated with several tool drugs. In the acute phase of hepatic I/R injury, the ratio of plasma NO/ET was reduced from 1.58 +/- 0.20 to 0.29 +/- 0.05 (P < 0.01) and the hepatic damage deteriorated. NO donor L-Arg and ET receptor antagonist TAK-044 could alleviate the hepatic I/R injury to some degree, whereas NO synthase inhibitor L-NAME aggravated the damage. It was concluded that the hepatic I/R injury might be related with the disturbance of the NO/ET balance. Regulation of this balance might have an effect on the I/R injury.
Subject(s)
Arginine , Endothelins/blood , Liver/blood supply , NG-Nitroarginine Methyl Ester , Nitric Oxide/blood , Receptors, Endothelin/antagonists & inhibitors , Reperfusion Injury/bloodABSTRACT
The relationship between the hepatic ischemia/reperfusion (I/R) injury and the balance of nitric oxide/endothelins (NO/ET) was studied. The changes of the ratio of NO/ET and the hepatic injury were observed in a rat hepatic I/R model pretreated with several tool drugs. In the acute phase of hepatic I/R injury, the ratio of plasma NO/ET was reduced from 1.58 +/- 0.20 to 0.29 +/- 0.05 (P < 0.01) and the hepatic damage deteriorated. NO donor L-Arg and ET receptor antagonist TAK-044 could alleviate the hepatic I/R injury to some degree, whereas NO synthase inhibitor L-NAME aggravated the damage. It was concluded that the hepatic I/R injury might be related with the disturbance of the NO/ET balance. Regulation of this balance might have an effect on the I/R injury.
Subject(s)
Animals , Female , Male , Rats , Arginine , Endothelin Receptor Antagonists , Endothelins , Blood , Liver , NG-Nitroarginine Methyl Ester , Nitric Oxide , Blood , Reperfusion Injury , BloodABSTRACT
The endogenous free radical clearing agent SOD andblood CAT in the blood and urine of 2 groups of pro-lapse of intervertebral disc and cervical spondylopathywere all lower than that of the healthy control group,while the—SH reflecting the metabolic disturbance offree radical was higher,After massotherapy,bloodSOD,CAT were increased,while LPO,—SH in urinewere all decreased,demonstrating that there is a dis-tinct parallel relationship existing in the changes ofthese enzyme in blood and urine.