Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objective:To analyze and compare the short-term efficacy and safety of sintilimab and tislelizumab in neoadjuvant therapy for advanced esophageal squamous cell carcinoma.Methods:The clinical data of 95 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (paclitaxel + nedaplatin) combined with immunotherapy in the Department of Thoracic Surgery of the Affiliated Hospital of North Sichuan Medical College from January 2021 to October 2022 were collected. According to the different use of immune drugs, they were divided into the sintilimab group ( n=58) and the tislelizumab group ( n=37). The objective remission rate (ORR), adverse reactions, R0 resection rate, pathological complete response (pCR) rate, etc. were analyzed and compared between the two groups after neoadjuvant therapy. Results:After 2 cycles of neoadjuvant therapy, the sintilimab group and the tislelizumab group had a similar ORR [72.4% (42/58) vs. 56.8% (21/37), χ2=2.48, P=0.115]. The main adverse reactions of the two groups of patients included gastrointestinal reactions (nausea, vomiting, diarrhea), hematological toxicity, hypothyroidism, alopecia, liver and kidney dysfunction, pneumonia, etc. The incidence of grade 3 adverse reactions was less than 15%, with no grade 4 adverse reactions. The incidence of hypothyroidism in the sintilimab group was significantly higher than that in the tislelizumab group [56.9% (33/58) vs. 16.2% (6/37) ], with a statistically significant difference ( χ2=15.45, P<0.001) ; There was no statistically significant difference in surgical resection ( χ2=1.26, P=0.661) and pCR rate [31.0% (18/58) vs. 32.4% (12/37), χ2=0.02, P=0.886] between the two groups of patients. In terms of postoperative complications, both groups of patients experienced partial pulmonary infections and anastomotic fistulas, but the incidence was relatively low [19.0% (11/58) vs. 24.3% (9/37), 3.4% (2/58) vs. 2.7% (1/37) ], with no statistically significant difference ( χ2=0.39, P=0.532; χ2<0.01, P>0.999) . Conclusion:For preoperative neoadjuvant therapy of advanced esophageal squamous cell carcinoma, the use of either sintilimab or tislelizumab in addition to chemotherapy has good short-term efficacy and safety. Thyroid function should be monitored carefully when using sintilimab.

Minimally invasive esophagectomy is the preferred treatment for esophageal cancer, which has been widely popularized and developed in clinical practice. However, anastomotic complications are still common, such as anastomotic leakage, anastomotic stenosis, and gastroesophageal reflux, which seriously affect the rapid recovery and quality of life of patients after surgery. Esophagogastrostomy is the core and difficulty of the operation. In recent years, different esophagogastric anastomosis methods and techniques have been found to reduce the incidence of anastomotic complications and improve clinical outcomes. This article will summarize the development and progress of esophagogastric anastomosis techniques at home and abroad in recent years in order to provide reference for the majority of thoracic surgeons and to promote the progress of esophagogastric anastomosis techniques.

Esophageal squamous cell carcinoma can easily penetrate into the esophageal wall and invade adjacent organs due to the lack of serosa. Stage cT4b tumors involving organs adjacent to the aorta, vertebral body, trachea, or bronchus were considered unresectable. For unresectable esophageal squamous cell carcinoma, radical chemoradiotherapy or chemotherapy is recommended. However, the therapeutic effect is poor. With the advent of conversion surgery, surgical resection is feasible after induction therapy for patients with esophageal tumors that are initially unresectable due to adjacent organ invasion or distant metastasis. This article reviews the research on conversion surgery for unresectable esophageal squamous cell carcinoma in recent years in order to explore the clinical application prospects of conversion surgery.

Neoadjuvant chemoradiotherapy or chemotherapy combined with surgery for locally advanced esophageal cancer has become the standard treatment, and despite the survival benefit, most patients still experience postoperative recurrence and distant metastasis. Immune checkpoint inhibitors play an anti-tumor role by activating T cells, and immunotherapy has become one of the important strategies for first-line and second-line treatment of advanced esophageal cancer with the continuous evolution of immunotherapy models. Regarding neoadjuvant immunotherapy for esophageal cancer, a large number of studies are being carried out and explored, which are expected to inject new vitality into neoadjuvant therapy for esophageal cancer. This article reviews the current clinical studies on neoadjuvant immunotherapy for esophageal cancer.

OBJECTIVE: To compare the prevalence of chromosomal aneuploidies and pregnancy outcomes of D5 and D6 blastocysts subjected to preimplantation genetic testing for aneuploidy (PGT-A). METHODS: Clinical and laboratory data of 268 couples who underwent PGT-A at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2020 were collected. The prevalence of chromosomal aneuploidies and pregnancy outcomes of D5/D6 biopsied blastocysts were compared. RESULTS: Compared with D6 blastocysts, the euploidy rate of D5 blastocysts was significantly higher (49.1% vs. 41.1%, P = 0.001 1), whilst their aneuploidy rate was significantly lower (50.9% vs. 58.9%, P = 0.001 1). The rate of numerical abnormalities of D6 blastocysts was significantly higher than that of D5 blastocysts (27.9% vs. 20.2%, P = 0.000 5). For patients under 35 years old, the euploidy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (53.8% vs. 44.3%, P = 0.001), whilst the numerical abnormality rate was significantly lower (16.3% vs. 23.9%, P = 0.001). For both D5 and D6 blastocysts, the euploidy rates for patients <= 35 were significantly higher than those for > 35. The elder group had the lowest rates for aneuploidies and live births. Compared with those receiving D6 blastocysts transplantation, the pregnancy rate, implantation rate and live birth rate for those receiving thawed D5 blastocysts transplantation were significantly higher (60.2% vs.37.0%, P = 0.000 3; 59.1% vs.37.0%, P = 0.000 6; 47.7% vs. 28.3%, P = 0.002). CONCLUSION For patients undergoing PGT-A, the chromosomal euploidy rate for D5 blastocysts is higher than that for D6 blastocysts, and the clinical outcome of D5 blastocysts with normal signal is better than that of D6 blastocysts. Elder patients have a higher rate of aneuploidies.
Female ; Pregnancy ; Humans ; Aged ; Adult ; Pregnancy Outcome ; Aneuploidy ; Blastocyst ; Genetic Testing ; Laboratories

Objective:To systematically evaluate the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus surgery versus neoadjuvant chemotherapy (NCT) plus surgery in the treatment of advanced esophageal squamous cell carcinoma.Methods:Clinical controlled trials of comparing the treatment of NCRT plus surgery with NCT plus surgery for esophageal squamous cell carcinoma were electronically searched from the databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, WanFang and VIP from the inception of databases to January, 2019. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of the included studies. And then, a meta-analysis was performed by using RevMan 5.3 software.Results:A total of 8 clinical control studies were included, including 995 patients with esophageal squamous cell carcinoma. Meta-analysis results showed that compared with the NCT group, the R 0 resection rate was significantly higher ( OR=2.14, 95% CI: 1.03-4.45, P=0.040) and the pathological complete response (pCR) rate was significantly higher ( OR=4.19, 95% CI: 1.71-10.28, P=0.002) in the NCRT group. The incidence of postoperative complications ( OR=1.37, 95% CI: 0.76-2.48, P=0.300) and the risk of perioperative death ( OR=1.28, 95% CI: 0.58-2.83, P=0.54) were not significantly different between two groups. The long-term survival of patients with esophageal squamous cell carcinoma in the NCRT group was significantly better compared with that in the NCT group ( HR=0.77, 95% CI: 0.64-0.92, P=0.005). Conclusions:Compared with NCT plus surgery for advanced esophageal squamous cell carcinoma, NCRT plus surgery has higher R 0 resection rate and pCR rate, does not significantly increase the risk of perioperative complications or perioperative death, and significantly improves the long-term survival of esophageal squamous cell carcinoma patients.

Objective:To examine the correlation between neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio (NMR) for postoperative pneumonia or long-term overall survival in patients with esophageal cancer after neoadjuvant therapy.Methods:The clinical data of 137 patients, including 111 males and 26 females, with the age of ( M( Q R))61(10) years (range: 45 to 75 years), undergoing radical resection of esophageal cancer after neoadjuvant therapy admitted at Department of Thoracic Surgery, West China Hospital from January 2016 to May 2019 were analyzed retrospectively. The blood routine one or two days before surgery and the occurrence of pneumonia after surgery were collected via hospital information system. The absolute count of neutrophils, lymphocytes and monocytes was recorded, to calculate NLR, LMR and NMR. The survival of patients was recorded systematically via follow-up. In the first part, the influencing factors of postoperative inflammation were analyzed, to group the patients into two groups according to the occurrence of postoperative pneumonia. χ 2 test, t-test or rank-sum test were conducted for inter-group comparison. In the second part, cut-off values of inflammatory biomarkers were obtained with the receiver operating characteristic (ROC) curve and grouped, with postoperative pneumonia as endpoint criteria. Independent factors correlated with postoperative pneumonia were determined through univariate and multivariate Logistic regression analysis. In the third part, the analysis on prognosis factors was carried on, with the survival as endpoint criteria. Cut-off values of inflammatory biomarkers were obtained with X-Tile software and grouped. The survival analysis was carried on with univariate and multivariate Cox proportional hazards regression model, and the Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results:Median follow-up time was 614 (299) days (range: 382 to 1 612 days). Cut-off values of NLR, LMR, and NMR obtained via the ROC curve were 3.0, 3.9, and 6.2, respectively. According to the multivariate Logistic regression analysis, NLR>3.0 ( OR=2.740, 95% CI: 1.221 to 6.152, P=0.015) and LMR>3.9 ( OR=0.140, 95% CI: 0.022 to 0.890, P=0.037) were independent prognosis factors for postoperative pneumonia in patients with esophageal cancer after neoadjuvant therapy. Cut-off values of NLR, LMR, and NMR obtained with X-Tile software were 3.3, 4.2, and 7.2, respectively. Through multivariate Cox proportional risk regression analysis, late tumor ypTNM staging (8th AJCC) ( HR=2.087, 95% CI:1.079 to 4.038, P=0.029), poor pathologic response ( HR=2.251, 95% CI: 1.117 to 4.538, P=0.023), and LMR>4.2 ( HR=0.347, 95% CI: 0.127 to 0.946, P=0.039) could be independent prognosis factors for overall survival. Kaplan-Meier survival analysis indicated that the overall survival of patients with LMR ≤4.2 was worse ( P=0.002), with the 1-year overall survival rate of 82.9%, and the 1-year overall survival rate of patients with LMR>4.2 was 94.6%. Conclusion:Preoperative LMR ≤3.9 and NLR>3.0 can be considered as independent prognosis factors for postoperative pneumonia, while LMR≤4.2 as one of independent prognosis factors for overall survival.

Objective:To examine the correlation between neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio (NMR) for postoperative pneumonia or long-term overall survival in patients with esophageal cancer after neoadjuvant therapy.Methods:The clinical data of 137 patients, including 111 males and 26 females, with the age of ( M( Q R))61(10) years (range: 45 to 75 years), undergoing radical resection of esophageal cancer after neoadjuvant therapy admitted at Department of Thoracic Surgery, West China Hospital from January 2016 to May 2019 were analyzed retrospectively. The blood routine one or two days before surgery and the occurrence of pneumonia after surgery were collected via hospital information system. The absolute count of neutrophils, lymphocytes and monocytes was recorded, to calculate NLR, LMR and NMR. The survival of patients was recorded systematically via follow-up. In the first part, the influencing factors of postoperative inflammation were analyzed, to group the patients into two groups according to the occurrence of postoperative pneumonia. χ 2 test, t-test or rank-sum test were conducted for inter-group comparison. In the second part, cut-off values of inflammatory biomarkers were obtained with the receiver operating characteristic (ROC) curve and grouped, with postoperative pneumonia as endpoint criteria. Independent factors correlated with postoperative pneumonia were determined through univariate and multivariate Logistic regression analysis. In the third part, the analysis on prognosis factors was carried on, with the survival as endpoint criteria. Cut-off values of inflammatory biomarkers were obtained with X-Tile software and grouped. The survival analysis was carried on with univariate and multivariate Cox proportional hazards regression model, and the Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results:Median follow-up time was 614 (299) days (range: 382 to 1 612 days). Cut-off values of NLR, LMR, and NMR obtained via the ROC curve were 3.0, 3.9, and 6.2, respectively. According to the multivariate Logistic regression analysis, NLR>3.0 ( OR=2.740, 95% CI: 1.221 to 6.152, P=0.015) and LMR>3.9 ( OR=0.140, 95% CI: 0.022 to 0.890, P=0.037) were independent prognosis factors for postoperative pneumonia in patients with esophageal cancer after neoadjuvant therapy. Cut-off values of NLR, LMR, and NMR obtained with X-Tile software were 3.3, 4.2, and 7.2, respectively. Through multivariate Cox proportional risk regression analysis, late tumor ypTNM staging (8th AJCC) ( HR=2.087, 95% CI:1.079 to 4.038, P=0.029), poor pathologic response ( HR=2.251, 95% CI: 1.117 to 4.538, P=0.023), and LMR>4.2 ( HR=0.347, 95% CI: 0.127 to 0.946, P=0.039) could be independent prognosis factors for overall survival. Kaplan-Meier survival analysis indicated that the overall survival of patients with LMR ≤4.2 was worse ( P=0.002), with the 1-year overall survival rate of 82.9%, and the 1-year overall survival rate of patients with LMR>4.2 was 94.6%. Conclusion:Preoperative LMR ≤3.9 and NLR>3.0 can be considered as independent prognosis factors for postoperative pneumonia, while LMR≤4.2 as one of independent prognosis factors for overall survival.