Immune checkpoint inhibitor for different age patients with NSCLC in efficacy: A systematic review and meta-analysis.

OBJECTIVE: This article is a Meta-analysis aiming to systematically evaluate the difference in efficacy of immune checkpoint inhibitor in patients with non-small cell lung cancer (NSCLC) by age. METHODS: We performed a Meta-analysis of published randomized controlled trials concerning for patients with NSCLC by age. We compared overall survival among three groups (age <65 years, age 65-75 years, age ≥75 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. RESULTS: A total of 10,291 patients from 17 RCTs were included. In the group under age 65 years, immune checkpoint inhibitor can significantly prolong the overall survival of patients with NSCLC (HR = 0.73, 95% CI: 0.66∼0.81, P < 0.00001). In the age 65-75 years group, immune checkpoint inhibitors prolonged overall survival in patients with NSCLC (HR = 0.78, 95% CI:0.71∼0.84, P < 0.00001). However, it has no significant effect on the overall survival of NSCLC patients (HR = 0.88, 95% CI:0.72∼1.08, P > 0.05) in the group older than 75 years. CONCLUSIONS: Immune checkpoint inhibitors prolonged the overall survival of NSCLC patients in the age <65 years group and the age 65-75 years group, but in the age ≥75 years group, there was no significant effect on overall survival. This may be related to innate immune and adaptive immune dysregulation due to "immunosenescence" in older patients.

Investigating the optimal parathyroid autotransplantation strategy in transareolar endoscopic thyroidectomy: A retrospective cohort study.

BACKGROUND: There is ongoing debate about whether intraoperative parathyroid autotransplantation effectively prevents permanent hypoparathyroidism after thyroidectomy. This study aims to examine its impact on postoperative parathyroid function and determine the best autotransplantation strategy. METHODS: A retrospective analysis was conducted on 194 patients who underwent total thyroidectomy with central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC). Patients were divided into four groups based on the number of parathyroid autotransplants during surgery: Group 1 (none, n = 43), Group 2 (1 transplant, n = 60), Group 3 (2 transplants, n = 67), and Group 4 (3 transplants, n = 24). Various clinical parameters were collected and compared among the groups. RESULTS: Parathyroid autotransplantation was identified as a risk factor for temporary hypoparathyroidism (OR: 1.74; 95% CI: 1.27-2.39, P = 0.001) and a protective factor for permanent hypoparathyroidism (OR: 0.27; 95% CI: 0.14-0.55, P < 0.001). At 12 months postoperative, systemic parathyroid hormone (PTH) levels increased progressively from Groups 1 to 4, with significant differences observed only between Group 1 and Group 2 (P < 0.02). Difference values in systemic PTH levels between Month 1 and Day 1 postoperative increased progressively from Groups 1 to 4, with statistically significant differences observed between adjacent groups (P < 0.02). The number of dissected positive lymph nodes increased progressively across the four groups, showing statistical differences (P < 0.02). CONCLUSION: Parathyroid autotransplantation can prevent permanent hypoparathyroidism. Additionally, we recommend preserving parathyroids in situ whenever possible. If autotransplantation is required, it should involve no more than two glands.

[Predictive value of PTH level on day 1 after surgery for papillary thyroid carcinoma in patients with permanent hypoparathyroidism].

Objective:To investigate the relationship between parathyroid hormone（PTH） level and permanent hypoparathyroidism（PHPP） on the first day after radical papillary thyroidectomy, and its predictive value. Methods:A total of 80 patients with papillary thyroid cancer who underwent total thyroid resection and central lymph node dissection were collected and analyzed from January 2021 to January 2022. According to whether PHPP occurred after surgery, the patients were divided into hypoparathyroidism group and normal parathyroid function group, and univariate and binary logistics regression were used to analyze the correlation between PTH and serum calcium levels and PHPP on the first day after surgery in two groups. The dynamic changes of PTH at different time points after operation were analyzed. The area under the receiver operating characteristic was used to evaluate the predictive power of PTH on the development of PHPP after surgery. Results:Among the 80 patients with papillary thyroid cancer, 10 cases developed PHPP, with an incidence rate of 12.5%. Binary logistics regression analysis showed that PTH on the first postoperative day（OR=14.534, 95%CI: 2.377-88.858, P=0.004） was an independent predictive risk factor for postoperative PHPP. Taking PTH=8.75 ng/L on the first postoperative day as the cut-off value, the AUC of the area under the curve was 0.874（95%CI: 0.790-0.958, P<0.001）, the sensitivity was 71.4%, the specificity was 100%, and the Yoden index was 0.714. Conclusion:PTH level on the first day after total thyroid papillary carcinoma surgery is closely related to PHPP, and is an independent predictor of PHPP.

Clinical application of parathyroid autotransplantation in endoscopic radical resection of thyroid carcinoma.

Purpose: This study aimed to examine the effect of selective inferior parathyroid gland autotransplantation on central lymph node dissection(CLND) and incidence of postoperative hypoparathyroidism in patients undergoing endoscopic radical resection of thyroid carcinoma. Methods: The data of 310 patients undergoing endoscopic radical resection of thyroid carcinoma will be retrospectively analyzed. The patients will be divided into the experimental group and the control group according to whether they combined with parathyroid autotransplantation. Statistics of the incidence rate of postoperative hypoparathyroidism, the concentration of PTH and Calcium in the systemic circulation at different time points in the two groups, the concentration of PTH in the cubital fossa vein in the transplantation region in the experimental group, and the number of central lymph nodes and positive lymph nodes dissection will be carried out. Results: The incidence rate of temporary and permanent hypoparathyroidism in the experimental group was 33.75% and 0.625%, respectively, and in the control group was 22% and 5%, respectively; its difference was statistically significant (X2 = 10.255, P=0.006). Parathyroid autotransplantation increased incidence of transient hypoparathyroidism (OR, 1.806; Cl, 1.088-2.998; P=0.022), and lower incidence of permanent hypoparathyroidism (OR, 0.112; Cl, 0.014-0.904; P=0.040). The diameters of thyroid cancer nodules was not associated with the occurrence of transient hypoparathyroidism (OR, 0.769; Cl, 0.467-1.265; P=0.301) or permanent hypoparathyroidism (OR, 1.434; Cl, 0.316-6.515; P=0.641). Comparison of systemic circulation PTH, between the two groups showed that the PTH of patients in the experimental group was higher than that in the control group from 1 week to 12 months after the operation, and the difference was statistically significant (P<0.05). In the experimental group, from 1 week to 12 months after surgery, PTH concentrations was significantly higher in the cubital fossa of the transplantation side than in the contralateral side, and the differences were statistically significant (P<0.05). The mean number of central lymph node dissected per patient was significantly higher in the experimental group (7.94 ± 3.03 vs. 6.99 ± 2.86; P <0.05); The mean number of positive nodes per patient was significantly higher in the experimental group (3.16 ± 1.86 vs. 2.53 ± 1.59; P <0.05). Conclusions: In endoscopic radical resection of thyroid carcinoma, parathyroid autotransplantation is more beneficial to postoperative parathyroid glands function recovery, effectively preventing postoperative permanent hypoparathyroidism and realizing more thorough CLND.

Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells.

Chemotherapy is one of the few effective choices for patients with advanced or recurrent gastric cancer (GC). However, the development of mutidrug resistance (MDR) to cancer chemotherapy is a major obstacle to the effective treatment of advanced GC. Additionally, the mechanism of MDR remains to be determined. In the present study, we tested IC50 of cisplatin (DDP), vincristine (VCR) and 5-fluorouracil (5-FU) in SGC7901, SGC7901/DDP and SGC7901/VCR gastric cancer cells using an MTT assay. The expression of let-7b and c-Myc in these cells was detected by qPCR and western blot analysis. The relationship between let-7b and c-Myc was explored using a luciferase reporter assay. Transfection of let-7b mimic or inhibitor was used to confirm the effect of let-7b on drug sensitivity in chemotherapy via the regulation of c-Myc expression. We found that the expression of let-7b was lower in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells than that in chemotherapy-sensitive SGC7901 cells. By contrast, the expression of c-Myc was higher in SGC7901/DDP and SGC7901/VCR cells than that in SGC7901 cells. Furthermore, we confirmed that let-7b suppresses c-Myc gene expression at the mRNA and protein levels in a sequence-specific manner, while transfection of let-7b mimic increases drug sensitivity in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR cells by targeting downregulation of c-Myc. In SGC7901 drug-sensitive cells, however, the sensitivity of chemotherapy was significantly decreased following let-7b inhibitor transfection. The present study results demonstrated that let-7b increases drug sensitivity in chemotherapy­resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells by targeting the downregulation of c-Myc and that, let-7b mimic reverses MDR by promoting cancer stem cell differentiation controlled by double-negative autoregulatory loops (Lin28/let-7 and Myc/let-7) and a double-positive autoregulatory loop (Lin28/Lin28B/Myc) existing in GC cells, which remains to be confirmed.

Egg consumption and breast cancer risk: a meta-analysis.

The relationship between egg consumption and breast cancer risk has been inconsistent, so it is necessary to conduct a meta-analysis to evaluate the relationship. PubMed, EMBASE and ISI Web of Knowledge were searched to find cohort studies or case control studies that evaluated the relationship between egg consumption and breast cancer risk. A comprehensive meta-analysis software was used to conduct the meta-analysis. 13 studies were included. The meta-analysis results showed that egg consumption was associated with increased breast cancer risk (RR 1.04, 95 % CI 1.01-1.08). Subgroup analyses showed egg consumption was also associated with increased breast cancer risk based on cohort studies (RR 1.04, 95 % CI 1.00-1.08), among European population (RR 1.05, 95 % CI 1.01-1.09), Asian population (RR 1.09, 95 % CI 1.00-1.18), postmenopausal population (RR 1.06, 95 % CI 1.02-1.10), and those who consumed ≥2, ≤5/week (RR 1.10, 95 % CI 1.02-1.17), but not in case-control studies (RR 1.06, 95 % CI 0.97-1.15), among American population (RR 1.04, 95 % CI 0.94-1.16), premenopausal population (RR 1.04, 95 % CI 0.98-1.11) and those who consumed ≥1, <2/week (RR 1.04, 95 % CI 0.97-1.11) or >5 eggs/week (RR 0.97, 95 % CI 0.88-1.06). Egg consumption was associated with increased breast cancer risk among the European, Asian and postmenopausal population and those who consumed ≥2, ≤5/week.

Piperine exerts anti-seizure effects via the TRPV1 receptor in mice.

The mechanisms involved in the anti-seizure property of piperine (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]-(E,E)-piperidine, C17H19NO3) are still unclear. Piperine could activate transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, and the rapid activation of whole-cell currents is antagonized by the competitive TRPV1 antagonist capsazepine. Interestingly, recent studies have reported that TRPV1 may be a novel anti-epileptogenic target which led us to hypothesize that the anti-seizure property of piperine involves the TRPV1 receptor. To test this hypothesis, we examined the effect of piperine on seizures induced in mice and identified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) models. Piperine, administered at doses of 40 and 80 mg/kg, significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with the vehicle-treated animals. Piperine also significantly reduced the incidence of MES-induced tonic hindlimb extension (THE) and PTZ-induced Fos immunoreactivity in the dentate gyrus. The anti-seizure effects of piperine were blocked by a TRPV1-selective antagonist capsazepine. Taken together, these data support the further investigation of piperine as a TRPV1 agonist for anti-seizure therapy.