Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To explore the predictive value of combined detection of serum uric acid and carcinoembryonic antigen (CEA) for lymph node metastasis in gastric cancer.Methods:A retrospective case series study was conducted. A total of 185 patients who underwent radical gastrectomy for gastric cancer at Jincheng People's Hospital from December 2020 to December 2022 were selected. Based on postoperative pathology results, they were divided into lymph node non-metastasis group (group A, 75 cases) and lymph node metastasis group (group B, 110 cases). Logistic regression analysis was performed to identify the risk factors, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of uric acid or CEA detection alone and in combination for predicting lymph node metastasis in gastric cancer.Results:There were 60 males and 15 females in group A, with an age of (62±10) years; there were 91 males and 19 females in group B, with an age of (64±8) years. There was no statistically significant difference in age, gender, tumor differentiation degree, creatinine, urea, urea-to-creatinine ratio, and serum albumin (ALB) between the two groups of patients (all P > 0.05). However, there were statistically significant differences in tumor diameter, uric acid and CEA (all P < 0.05). The tumor diameter [ M ( Q1, Q3)] in group B was longer than that in group A [5.5 (4.0, 7.0) cm vs. 3.5 (2.5, 6.0) cm], and the levels of uric acid [(284±80) μmol/L vs. (245±62) μmol/L] and CEA [2.60 (1.23, 6.49) μg/L vs. 1.69 (1.11, 2.65) μg/L] were higher than those in group A, the differences were statistically significant (all P < 0.05). The results of multivariate analysis showed that tumor diameter ( OR = 1.264, 95% CI: 1.905-1.459, P = 0.001), uric acid ( OR = 1.007, 95% CI: 1.002-1.012, P = 0.008) and CEA ( OR = 1.215, 95% CI: 1.043-1.416, P = 0.013) were independent factors affecting lymph node metastasis in gastric cancer. The area under the ROC curve (AUC) of uric acid detection alone for predicting lymph node metastasis in gastric cancer was 0.644 (the sensitivity was 39.1%, the specificity was 90.7%), CEA detection alone was 0.652 (the sensitivity was 59.1%, the specificity was 70.7%), and the combined detection of the two was 0.722 (the sensitivity was 68.2%, the specificity was 70.7%). Conclusions:Uric acid, CEA and tumor diameter are independent influencing factors for lymph node metastasis in gastric cancer. The combined detection of uric acid and CEA can significantly improve the predictive efficiency of lymph node metastasis in gastric cancer.

Objective:To explore the predictive value of combined detection of serum uric acid and carcinoembryonic antigen (CEA) for lymph node metastasis in gastric cancer.Methods:A retrospective case series study was conducted. A total of 185 patients who underwent radical gastrectomy for gastric cancer at Jincheng People's Hospital from December 2020 to December 2022 were selected. Based on postoperative pathology results, they were divided into lymph node non-metastasis group (group A, 75 cases) and lymph node metastasis group (group B, 110 cases). Logistic regression analysis was performed to identify the risk factors, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of uric acid or CEA detection alone and in combination for predicting lymph node metastasis in gastric cancer.Results:There were 60 males and 15 females in group A, with an age of (62±10) years; there were 91 males and 19 females in group B, with an age of (64±8) years. There was no statistically significant difference in age, gender, tumor differentiation degree, creatinine, urea, urea-to-creatinine ratio, and serum albumin (ALB) between the two groups of patients (all P > 0.05). However, there were statistically significant differences in tumor diameter, uric acid and CEA (all P < 0.05). The tumor diameter [ M ( Q1, Q3)] in group B was longer than that in group A [5.5 (4.0, 7.0) cm vs. 3.5 (2.5, 6.0) cm], and the levels of uric acid [(284±80) μmol/L vs. (245±62) μmol/L] and CEA [2.60 (1.23, 6.49) μg/L vs. 1.69 (1.11, 2.65) μg/L] were higher than those in group A, the differences were statistically significant (all P < 0.05). The results of multivariate analysis showed that tumor diameter ( OR = 1.264, 95% CI: 1.905-1.459, P = 0.001), uric acid ( OR = 1.007, 95% CI: 1.002-1.012, P = 0.008) and CEA ( OR = 1.215, 95% CI: 1.043-1.416, P = 0.013) were independent factors affecting lymph node metastasis in gastric cancer. The area under the ROC curve (AUC) of uric acid detection alone for predicting lymph node metastasis in gastric cancer was 0.644 (the sensitivity was 39.1%, the specificity was 90.7%), CEA detection alone was 0.652 (the sensitivity was 59.1%, the specificity was 70.7%), and the combined detection of the two was 0.722 (the sensitivity was 68.2%, the specificity was 70.7%). Conclusions:Uric acid, CEA and tumor diameter are independent influencing factors for lymph node metastasis in gastric cancer. The combined detection of uric acid and CEA can significantly improve the predictive efficiency of lymph node metastasis in gastric cancer.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To analyze the problems and risk factors of the investigator initiated out-of-range trial, propose countermeasures and suggestions, and provide reference for improving project standardization and quality, and preventing research risks.Methods:Through literature analysis and field research, combined with personal work experience, this study sorted and analyzed the problems in the regulation of out-of-range IIT conducted in hospital, and proposed countermeasures.Results:Through analysis, it was found that the current out-of-range IIT trial in China faces 5 problems: imperfect management regulations, incomplete IIT management organizational system in medical institutions, insufficient scientificity of research protocols, insufficient ethical review, and insufficient research funds.Conclusions:Out-of-range IIT is of great significance in promoting pharmaceutical innovation. Standardized management of such projects requires the efforts of regulatory authorities, medical institutions, and ethics committees, as well as the continuous improvement of researchers' awareness and research capabilities to promote the orderly, high-quality, and rapid development of IIT. Based on the above analysis, this article proposed countermeasures and suggestions: at the national level, summarize practical experience from various regions as soon as possible, improve IIT management regulations and technical guidelines; establishing clinical research and design guidance departments in medical institutions and strengthening scientific review; the ethics committee formulates ethical review standards and processes for out-of-range IIT projects to enhance review capabilities; establish a normalized clinical research training mechanism in hospitals; expand and standardize the channels for IIT funding.

【Objective】 To investigate the correlation between D-dimer, serum potassium and thromboelastography parameters and progressive hemorrhagic injury (PHI) after brain injury. 【Methods】 The data of 209 patients with traumatic brain injury (TBI) in our hospital from January 2018 to May 2021 were collected and analyzed. The patients were divided into PHI group (161 cases) and non-PHI group (48 cases) according to CT scan whether the total bleeding lesions had increased by 25%. Univariate analysis and multivariate Logistic regression were used to analyze the risk factors of PHI, and receiver operating curve (ROC) was used to analyze the predictive value of D-dimer, serum potassium and thromboelastography (TEG) parameters used alone and in combination. 【Results】 PHI occurred in 48 (23.0 %) out of 209 TBI patients. In univariate analysis, there were statistically significant differences in GCS score, age, light emission, systolic blood pressure, serum potassium, blood calcium, blood glucose, R value, PT, APTT, INR, D-dimer, arachnoid hemorrhage, subdural hematoma, cerebral contusion and midline location between the two groups (P<0.05). Five independent risk factors were determined by multivariate Logistic analysis (P<0.05): D-dimer ≥3.52 μg/mL, serum potassium <3.70 mmol/L, R value ≥5.65 min, subdural hematoma and cerebral contusion. PHI model was constructed according to independent risk factors, and the maximum area under the curve (AUC) of D-dimer plus serum potassium plus R value plus subdural hematoma plus cerebral contusion was 0.889 9. 【Conclusion】 D-dimer ≥3.52 μg/mL, serum potassium <3.70 mmol/L, R value ≥5.65 min, subdural hematoma and cerebral contusion are significant influences for PHI occurrance in TBI patients.

ObjectiveTo study the changes and clinical significance of DNA ploidy,S-phase fraction(SPF),proliferating index(PI) in colorectal carcinoma.MethodsIn 40 cases of colorectal carcinoma (colorectal carcinoma group ),40 cases corresponding cancer-adjacent tissue (cancer-adjacent tissue group ),12 cases of precancerous lesions (precancerous lesions group) and 10 cases of normal colorectal mucosa coli (normal colorectal mucosa coli group),DNA ploidy,SPF and PI were detected with flow cytometry and compared.ResultsDNA diploid was 7 cases,DNA heteroploid was 33 cases in colorectal carcinoma group,35,5 cases in cancer-adjacent tissue group,10,2 cases in precancerous lesions group,10,0 case innormal colorectal mucosa coli group,there were significant differences among them(P＜ 0.01 ).SPF and PI in colorectal carcinoma group (35.36 ± 7.45,42.92 ± 6.81 ) were significantly higher than those in cancer-adjacent tissue group (20.82 ±5.51,31.34 ±4.88),precancerous lesions group (21.13 ± 5.07,31.70 ±5.59) and normal colorectal mucosa coli group ( 19.93 ± 3.73,32.01 ± 4.99),there were significant differences among them(P＜ 0.01 ).DNA ploidy was significantly correlated with Dukes staging (P=0.027) and the differentiation of colorectal carcinoma (P =0.030).ConclusionsDNA ploidy,SPF,PI may get some molecular biologycharacteristic and proliferation activity of colorectal carcinoma at molecule level,which may be helpful for treatment and evaluation of prognosis of colorectal carcinoma.

ObjectiveTo summarize the experience of gastric D2 operation and evaluate the feasibility and safety of peripheral vascular choroid of lymph node dissection.Methods A retrospective study was adopted to analyze the redical D2 operation procedure and operation results 24 advanced gastric cancer cases,summarizing the experience of D2 radical gastrectomy operation for gastric cancer.The number of resected lymph nodes,operation bleeding volume,postoperative complications were analyzed to evaluate the feasibility and safety of operation.Results All 24 cases undergoing D2 radical gastrectomy operation of advanced gastric cancer were successful,and got the R0 resection.A total of 634 lymph nodes were excised in all the cases,averaged 26.42.A totle of 206 metastatic lymph nodes were found,metastasis rate being 32.49％.Operation bleeding volume was averaged 264.58 mL.The postoperative complication rate was 25％,anastomotic bleeding in 1 case,input loop jejunum fistula of esophageal jejunum anastomosis in 1 case,hyperamylasemia and 2 cases reflux esophagitis in 2 cases respectively.Conclusions D2 radical gastrectomy operation of gastric cancer is safe and feasible on the basis of mastering perigastric anatomy and master of lymph node excision technology and anatomical hierarchy separation.

Objective To study the effect of histone deacetylase inhibitors on cell cycle of breast cancer cell line MCF-7.Methods The breast cancer cell line MCF-7 was treated by histone deacetylase inhibitors (TSA、SAHA、CS055、MS-275)respectively and observed by MTT assay after 24 hours,48 hours,72 hours,96 hours.The chosen inhibitor was used to treat MCF-7 cell in different concentration.The flow cytometry was used to detect the Sphase cell and Cyclin A2,Cyclin D1.SPSS 10.0 was used to analyze the data.Results Within the four inhibitors,SAHA showed the most powerful effect of depression of cell growth and time-effect relation.The percentage of Sphase cells and level of Cyclin A2 decreased,the level of Cyclin D1 increased.Conclusions SAHA is the most powerful histone deacetylase inhibitors for breast cancer cell MCF-7,the effect of depression of cell growth shows time-effect relation.Cyclin A2 and Cyclin D1 were involed in this regulation of cell cycle.