Objective To investigate the causal association between 91 kinds of circulating inflammatory proteins and different subtypes of breast cancer(estrogen receptor-positive and-negative breast cancer)using a two-sample Mendelian randomization(MR)method.Methods Corresponding exposure and outcome data were extracted from the genome-wide association study database.The data were analyzed by two-sample MR with inverse-variance weighting(IVW)as the primary study method,and MR-Egger,weighted median,simple mode,and weighted mode were used to complement the results.The results were complemented by sensitivity analysis to verify the reliability of the data.Results The IVW results showed that SULT1A1(P=0.0007)was associated with an increased risk of total BC,whereas IL-5(P=0.0011)was associated with a decreased risk of total BC.SULT1A1(P=0.0011)and CX3CL1(P=0.0005)were associated with an increased risk of ER+BC,whereas beta-NGF(P=0.0001)was associated with an increased risk of ER-BC.Supplem-entary analysis methods validated that the findings were consistent in direction and magnitude.The results of the sensitivity analysis showed that the data were reliable and unbiased.Conclusion Using the MR method,this study confirms that SULT1A1 is a risk factor for overall breast cancer,whereas IL-5 is a protective factor for overall breast cancer.SULT1A1 and CX3CL1 are risk factors for estrogen receptor-positive breast cancer,and beta-NGF is a risk factor for estrogen receptor-negative breast cancer.

Objective In this study, a meta-analysis of the expression of G-protein-coupled estrogen receptor (GPER) in breast cancer (BC) and its role in prognosis was conducted to understand the effect of this expression on the survival and clinicopathological characteristics of patients with BC. Methods Identical search strategies were used to search relevant literature in electronic databases updated to November 24, 2022. Individual hazard ratios (HRs) and odds ratios (ORs) with their 95%CI were extracted and pooled to evaluate the strength of the association between positive GPER expression and survival results, the clinicopathological features of patients with BC. Begg's tests, Egger's tests, and funnel plots were used to evaluate publication bias. Heterogeneity and sensitivity were also assessed. All works were completed using Review Manager 5.4.1. Results GPER expression had a favorable effect on OS (HR=0.77; 95%CI: 0.49-1.22; Z=01.10; P=0.27) and an unfavorable effect on DFS/RFS/DDFS (HR=1.03; 95%CI: 0.64-1.65; Z=00.13; P=0.90) in patients with BC. GPER expression was not significantly related to the prognosis of patients with BC, and GPER expression was not an independent prognostic factor. Furthermore, GPER expression was significantly associated with TNM staging (OR=0.31, 95%CI: 0.06-0.55, Z=02.43, P=0.02), distant metastasis (OR=6.82, 95%CI: 1.89-24.55, Z=02.94, P=0.003), histological grade (OR=0.009, 95%CI: −0.16-0.01, Z=02.16, P=0.03), ER expression (OR=1.77, 95%CI: 1.15-2.72, Z=02.59, P=0.009), and PR expression (OR=1.36, 95%CI: 1.00-1.84, Z=01.95, P=0.05). Conclusion GPER may not be an independent prognostic factor for BC. GPER expression was significantly related to some clinicopathological features of patients with BC, including TNM staging, distant metastasis, histological grade, ER expression, and PR expression.

Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.

OBJECTIVETo investigate the effects of different anesthesia depth on stress response in elderly patients undergoing elective laparoscopic surgery for colorectal cancer.

METHODSA total of 105 ASA I-III patients aged 60-91 years undergoing elective laparoscopic surgery for colorectal cancer with general anesthesia were randomized into 3 groups, namely group A with a target Narcotrend index (NI) maintained at D0 level, group B with a NI at D2 level, and group C with a NI at E1 level. The anesthetics (profopol and remifentanil) were adjusted according to Narcotrend monitoring results to maintain the specified anesthesia depth. The patients' heart rate (HR) and mean artery pressure (MAP) were recorded before anesthesia (T0), before intubation (T1), immediately after intubation (T2), at 2 min before pneumoperitoneum (T3), 2 min after pneumoperitoneum (T4), at the end of the surgery (T5) and extubation (T6). Serum levels of cortisol, adrenocorticotropic hormone (ACTH), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by standard ELISA and radioimmunoassay before anesthesia (Ta), at the end of the surgery (Tb) and 1 day after the surgery (Tc).

RESULTSHR and MAP in group A increased significantly at T2, T4, and T6 compared to those at T0 (P<0.05), and were higher than those in group B and group C (P<0.05). The MAP in all the 3 groups all decreased at T1 and T3 (P<0.05 or P<0.01), and was markedly lower in group C than in groups A and B (P<0.05). The incidence of hypertension was significantly higher in group A than in groups B and C (P<0.05), while the incidence of hypotension was much higher in group C (P<0.01). There were no obvious differences in serum levels of cortisol, ACTH, CRP, IL-6, TNF-a, or ET-1 among the groups at Ta (P>0.05). The serum levels of ACTH in the 3 groups all significantly increased at Tb and Tc (P<0.01). CRP, IL-6 and TNF-a levels in group A were increased at Tb and Tc (P<0.05 or P<0.01) and significantly higher than those in groups B and C (P<0.05 or P<0.01). Cortisol in groups A and B increased at Tb and Tc (P<0.05) to a significantly higher level than that in group C (P<0.01). ET-1 level in group C at Tb and Tc was lower than those in groups A and B (P<0.05 or P<0.01).

CONCLUSIONSMaintaining the anesthesia depth for a NI at the D2 and E1 level can both attenuate the stress response in elderly patients undergoing laparoscopic surgery for colorectal cancer, but the hemodynamic stability can be better at a D2 level.

Adrenocorticotropic Hormone ; blood ; Aged ; Aged, 80 and over ; Anesthesia, General ; methods ; Blood Pressure ; C-Reactive Protein ; metabolism ; Colorectal Neoplasms ; surgery ; Elective Surgical Procedures ; Endothelin-1 ; blood ; Heart Rate ; Humans ; Hydrocortisone ; blood ; Interleukin-6 ; blood ; Laparoscopy ; Middle Aged ; Piperidines ; administration & dosage ; Propofol ; administration & dosage ; Tumor Necrosis Factor-alpha ; blood

Objective To investigate the effects of different anesthesia depth on stress response in elderly patients undergoing elective laparoscopic surgery for colorectal cancer. Methods A total of 105 ASA I-III patients aged 60-91 years undergoing elective laparoscopic surgery for colorectal cancer with general anesthesia were randomized into 3 groups, namely group A with a target Narcotrend index (NI) maintained at D0 level, group B with a NI at D2 level, and group C with a NI at E1 level. The anesthetics (profopol and remifentanil) were adjusted according to Narcotrend monitoring results to maintain the specified anesthesia depth. The patients' heart rate (HR) and mean artery pressure (MAP) were recorded before anesthesia (T0), before intubation (T1), immediately after intubation (T2), at 2 min before pneumoperitoneum (T3), 2 min after pneumoperitoneum (T4), at the end of the surgery (T5) and extubation (T6). Serum levels of cortisol, adrenocorticotropic hormone (ACTH), endothelin-1 (ET-1), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by standard ELISA and radioimmunoassay before anesthesia (Ta), at the end of the surgery (Tb) and 1 day after the surgery (Tc). Results HR and MAP in group A increased significantly at T2, T4, and T6 compared to those at T0 (P<0.05), and were higher than those in group B and group C (P<0.05). The MAP in all the 3 groups all decreased at T1 and T3 (P<0.05 or P<0.01), and was markedly lower in group C than in groups A and B (P<0.05). The incidence of hypertension was significantly higher in group A than in groups B and C (P<0.05), while the incidence of hypotension was much higher in group C (P<0.01). There were no obvious differences in serum levels of cortisol, ACTH, CRP, IL-6, TNF-a, or ET-1 among the groups at Ta (P>0.05). The serum levels of ACTH in the 3 groups all significantly increased at Tb and Tc (P<0.01). CRP, IL-6 and TNF-a levels in group A were increased at Tb and Tc (P<0.05 or P<0.01) and significantly higher than those in groups B and C (P<0.05 or P<0.01). Cortisol in groups A and B increased at Tb and Tc (P<0.05) to a significantly higher level than that in group C (P<0.01). ET-1 level in group C at Tb and Tc was lower than those in groups A and B (P<0.05 or P<0.01). Conclusion Maintaining the anesthesia depth for a NI at the D2 and E1 level can both attenuate the stress response in elderly patients undergoing laparoscopic surgery for colorectal cancer, but the hemodynamic stability can be better at a D2 level.

Objective To investigate the effects of different anesthesia depth on stress response in elderly patients undergoing elective laparoscopic surgery for colorectal cancer. Methods A total of 105 ASA I-III patients aged 60-91 years undergoing elective laparoscopic surgery for colorectal cancer with general anesthesia were randomized into 3 groups, namely group A with a target Narcotrend index (NI) maintained at D0 level, group B with a NI at D2 level, and group C with a NI at E1 level. The anesthetics (profopol and remifentanil) were adjusted according to Narcotrend monitoring results to maintain the specified anesthesia depth. The patients' heart rate (HR) and mean artery pressure (MAP) were recorded before anesthesia (T0), before intubation (T1), immediately after intubation (T2), at 2 min before pneumoperitoneum (T3), 2 min after pneumoperitoneum (T4), at the end of the surgery (T5) and extubation (T6). Serum levels of cortisol, adrenocorticotropic hormone (ACTH), endothelin-1 (ET-1), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by standard ELISA and radioimmunoassay before anesthesia (Ta), at the end of the surgery (Tb) and 1 day after the surgery (Tc). Results HR and MAP in group A increased significantly at T2, T4, and T6 compared to those at T0 (P<0.05), and were higher than those in group B and group C (P<0.05). The MAP in all the 3 groups all decreased at T1 and T3 (P<0.05 or P<0.01), and was markedly lower in group C than in groups A and B (P<0.05). The incidence of hypertension was significantly higher in group A than in groups B and C (P<0.05), while the incidence of hypotension was much higher in group C (P<0.01). There were no obvious differences in serum levels of cortisol, ACTH, CRP, IL-6, TNF-a, or ET-1 among the groups at Ta (P>0.05). The serum levels of ACTH in the 3 groups all significantly increased at Tb and Tc (P<0.01). CRP, IL-6 and TNF-a levels in group A were increased at Tb and Tc (P<0.05 or P<0.01) and significantly higher than those in groups B and C (P<0.05 or P<0.01). Cortisol in groups A and B increased at Tb and Tc (P<0.05) to a significantly higher level than that in group C (P<0.01). ET-1 level in group C at Tb and Tc was lower than those in groups A and B (P<0.05 or P<0.01). Conclusion Maintaining the anesthesia depth for a NI at the D2 and E1 level can both attenuate the stress response in elderly patients undergoing laparoscopic surgery for colorectal cancer, but the hemodynamic stability can be better at a D2 level.