BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective:To compare the effect of in situ and ex situ liver splitting techniques on the short-term outcomes of complete split liver transplantation.Methods:A retrospective analysis was conducted on the perioperative and follow-up data of 81 adult split liver transplant recipients and 42 donors at Ningbo University's Affiliated Lihuili Hospital from Mar 2021 to Dec 2023. Patients were divided into the ex situ and in situ splitting groups, and short-term complications were compared.Results:As of Dec 2023, the follow-up duration ranged from 1 to 30 months, with a median of 19 months. Cold and warm ischemia times were significantly shorter in the in situ splitting group compared to the ex situ group ( P<0.001). Postoperative peak levels of AST and ALT were also lower in the in situ splitting group ( P<0.01). However, the incidence of biliary complications was higher in the in situ splitting group (13 cases vs. 1 case, P=0.028). Conclusions:Compared to ex situ splitting, in situ splitting significantly reduces cold and warm ischemia times and results in less hepatocellular injury. However, it is associated with a higher incidence of biliary complications.

Objective:To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer.Methods:A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ 2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results:After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences ( χ2=14.374, P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ2=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ2=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ2=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ2=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ2=0.130, P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ2=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ2=0.257, P=0.522) between the two groups. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.

Objective:To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R 0 resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit. Results:(1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them ( P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for disease-free survival (DFS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer ( hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5-year DFS rate and 10-year OS rate between patients aged <50 years and ≥50 years ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in TNM stage ⅠA and ⅠB ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the highly, moderately, and poorly differentiated tumors ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with negative and positive vascular invasion ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T2N0M0, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients with positive vascular invasion, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients. Conclusions:Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high-risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.

Objective:To establish the minimum number of negative lymph nodes (nLN) required for patients undergoing gastrectomy.Methods:This was a retrospective cohort study with inclusion criteria as follows: (1) radical gastrectomy; (2) histologically confirmed adenocarcinoma; (3) complete tumor staging information; and (4) known number of lymph nodes harvested. The exclusion criteria were: (1) other concurrent malignant tumors; (2) metastatic or recurrent gastric cancer; (3) initial surgery performed at another hospital; (4) preoperative neoadjuvant therapy; (5) distant metastasis; and (6) incomplete clinical data or follow-up information. Based on the above criteria, a total of 11 167 patients with gastric adenocarcinoma who underwent radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center between January 1, 2000, and December 31, 2022, were included in the study. Among them, there were 7 596 cases in the RSG group and 3 571 cases in the RTG group. Restricted cubic spline (RCS) analysis was used to determine the ideal threshold for nLN for RSG and RTG patients. Survival analysis was conducted using Kaplan-Meier (KM) curves and log-rank tests, and propensity score matching (PSM) was utilized to balance parameters between two groups. Furthermore, subgroup analysis was conducted for RSG patients based on tumor location (upper, middle and lower) to determine the minimum number of nLN in each subgroup.Results:For patients who underwent RSG, the mean number of nLN was 21.9, with a median of 21. RCS analysis showed that more than 21 nLN was associated with better survival. Moreover, both pre- and post-PSM analysis confirmed that patients with nLN ≥21 had better survival benefits compared to those with nLN <21 (overall survival [OS]: P<0.001 before PSM, P=0.013 after PSM; disease-free survival [DFS]: P<0.001 before PSM, P=0.013 after PSM). For patients who underwent RTG, the mean number of nLN was 23.5, with a median of 22. Here RCS analysis indicated that more than 22 nLN was associated with better postoperative survival in RTG patients, and both pre- and post-PSM analysis confirmed that patients with nLN ≥22 had better survival benefits compared to those with nLN<22 (OS: P<0.001 both before and after PSM; DFS: P<0.001 both before and after PSM). Subgroup analysis showed that for RSG patients with tumor located in the upper part, having ≥17 nLN (OS: both P<0.001), and for RSG patients with tumor located in the middle and lower part, having ≥22 nLN (OS: both P<0.001), were associated with better prognoses. Conclusions:For patients who receive RSG, the minimal number of nLN is ideally ≥21 (upper ≥17, middle and lower ≥22). Similarly, for patients who receive RTG, the minimum number of nLN ideally is 22.

Objective:To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R 0 resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit. Results:(1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them ( P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for disease-free survival (DFS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer ( hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5-year DFS rate and 10-year OS rate between patients aged <50 years and ≥50 years ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in TNM stage ⅠA and ⅠB ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the highly, moderately, and poorly differentiated tumors ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with negative and positive vascular invasion ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T2N0M0, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients with positive vascular invasion, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients. Conclusions:Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high-risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.

Objective:To establish the minimum number of negative lymph nodes (nLN) required for patients undergoing gastrectomy.Methods:This was a retrospective cohort study with inclusion criteria as follows: (1) radical gastrectomy; (2) histologically confirmed adenocarcinoma; (3) complete tumor staging information; and (4) known number of lymph nodes harvested. The exclusion criteria were: (1) other concurrent malignant tumors; (2) metastatic or recurrent gastric cancer; (3) initial surgery performed at another hospital; (4) preoperative neoadjuvant therapy; (5) distant metastasis; and (6) incomplete clinical data or follow-up information. Based on the above criteria, a total of 11 167 patients with gastric adenocarcinoma who underwent radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center between January 1, 2000, and December 31, 2022, were included in the study. Among them, there were 7 596 cases in the RSG group and 3 571 cases in the RTG group. Restricted cubic spline (RCS) analysis was used to determine the ideal threshold for nLN for RSG and RTG patients. Survival analysis was conducted using Kaplan-Meier (KM) curves and log-rank tests, and propensity score matching (PSM) was utilized to balance parameters between two groups. Furthermore, subgroup analysis was conducted for RSG patients based on tumor location (upper, middle and lower) to determine the minimum number of nLN in each subgroup.Results:For patients who underwent RSG, the mean number of nLN was 21.9, with a median of 21. RCS analysis showed that more than 21 nLN was associated with better survival. Moreover, both pre- and post-PSM analysis confirmed that patients with nLN ≥21 had better survival benefits compared to those with nLN <21 (overall survival [OS]: P<0.001 before PSM, P=0.013 after PSM; disease-free survival [DFS]: P<0.001 before PSM, P=0.013 after PSM). For patients who underwent RTG, the mean number of nLN was 23.5, with a median of 22. Here RCS analysis indicated that more than 22 nLN was associated with better postoperative survival in RTG patients, and both pre- and post-PSM analysis confirmed that patients with nLN ≥22 had better survival benefits compared to those with nLN<22 (OS: P<0.001 both before and after PSM; DFS: P<0.001 both before and after PSM). Subgroup analysis showed that for RSG patients with tumor located in the upper part, having ≥17 nLN (OS: both P<0.001), and for RSG patients with tumor located in the middle and lower part, having ≥22 nLN (OS: both P<0.001), were associated with better prognoses. Conclusions:For patients who receive RSG, the minimal number of nLN is ideally ≥21 (upper ≥17, middle and lower ≥22). Similarly, for patients who receive RTG, the minimum number of nLN ideally is 22.

Objective:To compare the effect of in situ and ex situ liver splitting techniques on the short-term outcomes of complete split liver transplantation.Methods:A retrospective analysis was conducted on the perioperative and follow-up data of 81 adult split liver transplant recipients and 42 donors at Ningbo University's Affiliated Lihuili Hospital from Mar 2021 to Dec 2023. Patients were divided into the ex situ and in situ splitting groups, and short-term complications were compared.Results:As of Dec 2023, the follow-up duration ranged from 1 to 30 months, with a median of 19 months. Cold and warm ischemia times were significantly shorter in the in situ splitting group compared to the ex situ group ( P<0.001). Postoperative peak levels of AST and ALT were also lower in the in situ splitting group ( P<0.01). However, the incidence of biliary complications was higher in the in situ splitting group (13 cases vs. 1 case, P=0.028). Conclusions:Compared to ex situ splitting, in situ splitting significantly reduces cold and warm ischemia times and results in less hepatocellular injury. However, it is associated with a higher incidence of biliary complications.

Objective:To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer.Methods:A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ 2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results:After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences ( χ2=14.374, P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ2=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ2=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ2=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ2=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ2=0.130, P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ2=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ2=0.257, P=0.522) between the two groups. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.