Chemotherapy is a critical treatment modality for cancer,playing an essential role in oncology.However,chemotherapy-related diarrhea(CRD)remains a troubling adverse effect,often leading to reduced chemotherapy doses,treatment delays or discontinuation,and modifications to therapeutic plans.In severe cases,CRD can be life-threatening.5-fluorouracil and irinotecan are the most common chemotherapy drugs that cause CRD.With the increase in the use of triplet combination chemotherapy regimens,diarrhea-related deaths have increased,which may be related to neutropenic enterocolitis.Loperamide is the main drug for the treatment of CRD.In clinical practice,management of diarrhea that is not responsive to loperamide is of utmost concern.Therefore,based on evidence-based medicine and clinical practice experience,the expert panel carried out a comprehensive assessment and discussion on the definition,pathogenesis,classification,evaluation,diagnosis,intervention,and prevention of CRD.Eventually,the Chinese Expert Consensus on Whole-process Management of Chemotherapy-Related Diarrhea(2025 Edition)was formulated to further standardize the whole-process management of chemotherapy-related diarrhea.The consensus has been registered on Practice guideline REgistration for transPAREncy(PREPARE)with the registration number PREPARE-2024CN1246.

Objective:To compare the clinical outcomes of single oral dydrogesterone with vaginal progesterone gel plus oral dydrogesterone in gonadotropin-releasing hormone (GnRH) antagonist cycles with fresh embryo transfer.Methods:This study retrospectively analyzed 658 treatment cycles of fresh embryo transfer cycle with GnRH antagonist protocol from December 2015 to December 2020 in the Center of Reproductive Medicine of the University of Hong Kong-Shenzhen Hospital. Each cycle was the first fresh stimulation cycle of the patients. The patients were divided into two groups according to different luteal support regimens. Group A included 368 cycles with a regimen of 30 mg dydrogesterone tablets orally daily, while group B included 290 cycles with a regimen of 90 mg vaginal progesterone gel vaginally daily combined with 20 mg dydrogesterone tablets orally daily. A 1∶1 propensity score matching (PSM) was carried out to adjust for numerical differences and to balance between the two groups, and further they were divided into cleavage stage embryo transfer cycles and the blastocyst transfer cycles according to the different type of embryo for layer analysis, and the laboratory results and assisted reproductive outcomes of the two groups were compared.Results:After matching, the baseline characteristics were comparable between the two groups, with 251 cycles remaining in each group for retrospective analysis. After PSM, statistically significant differences were observed between group A and group B in laboratory data including the number of fertilized oocytes [5 (2, 7) vs. 6 (3, 9), P=0.002], cleavage rate [100.0% (86.31%, 100.0%) vs. 87.28% (75.32%, 100.0%), P<0.001], and available embryo rate [80.18% (54.64%, 100.0%) vs. 67.48% (50.62%, 100.0%), P=0.019]. However, there were no significantly statistical differences in other laboratory data and clinical outcomes (all P>0.05). If we divided the data into two comparison according to the different type of embryo, there were no significantly statistical differences in clinical pregnancy rate, embryo implantation rate, live birth rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation syndrome incidence, and ectopic pregnancy rate neither in day 2 cleavage stage embryo transfer cycles nor in the blastocyst transfer cycles. Conclusion:In this study, the clinical outcomes are similar between taking 30 mg of dydrogesterone tablets orally alone and taking 20 mg of dydrogesterone tablets orally combined with vaginal progesterone gel in the fresh embryo transfer cycle of the GnRH antagonist protocol. Moreover, taking dydrogesterone tablets orally alone can be a new option for luteal support in the fresh cycle of the GnRH antagonist protocol.

Objective:To compare the clinical outcomes of single oral dydrogesterone with vaginal progesterone gel plus oral dydrogesterone in gonadotropin-releasing hormone (GnRH) antagonist cycles with fresh embryo transfer.Methods:This study retrospectively analyzed 658 treatment cycles of fresh embryo transfer cycle with GnRH antagonist protocol from December 2015 to December 2020 in the Center of Reproductive Medicine of the University of Hong Kong-Shenzhen Hospital. Each cycle was the first fresh stimulation cycle of the patients. The patients were divided into two groups according to different luteal support regimens. Group A included 368 cycles with a regimen of 30 mg dydrogesterone tablets orally daily, while group B included 290 cycles with a regimen of 90 mg vaginal progesterone gel vaginally daily combined with 20 mg dydrogesterone tablets orally daily. A 1∶1 propensity score matching (PSM) was carried out to adjust for numerical differences and to balance between the two groups, and further they were divided into cleavage stage embryo transfer cycles and the blastocyst transfer cycles according to the different type of embryo for layer analysis, and the laboratory results and assisted reproductive outcomes of the two groups were compared.Results:After matching, the baseline characteristics were comparable between the two groups, with 251 cycles remaining in each group for retrospective analysis. After PSM, statistically significant differences were observed between group A and group B in laboratory data including the number of fertilized oocytes [5 (2, 7) vs. 6 (3, 9), P=0.002], cleavage rate [100.0% (86.31%, 100.0%) vs. 87.28% (75.32%, 100.0%), P<0.001], and available embryo rate [80.18% (54.64%, 100.0%) vs. 67.48% (50.62%, 100.0%), P=0.019]. However, there were no significantly statistical differences in other laboratory data and clinical outcomes (all P>0.05). If we divided the data into two comparison according to the different type of embryo, there were no significantly statistical differences in clinical pregnancy rate, embryo implantation rate, live birth rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation syndrome incidence, and ectopic pregnancy rate neither in day 2 cleavage stage embryo transfer cycles nor in the blastocyst transfer cycles. Conclusion:In this study, the clinical outcomes are similar between taking 30 mg of dydrogesterone tablets orally alone and taking 20 mg of dydrogesterone tablets orally combined with vaginal progesterone gel in the fresh embryo transfer cycle of the GnRH antagonist protocol. Moreover, taking dydrogesterone tablets orally alone can be a new option for luteal support in the fresh cycle of the GnRH antagonist protocol.

Chemotherapy is a critical treatment modality for cancer,playing an essential role in oncology.However,chemotherapy-related diarrhea(CRD)remains a troubling adverse effect,often leading to reduced chemotherapy doses,treatment delays or discontinuation,and modifications to therapeutic plans.In severe cases,CRD can be life-threatening.5-fluorouracil and irinotecan are the most common chemotherapy drugs that cause CRD.With the increase in the use of triplet combination chemotherapy regimens,diarrhea-related deaths have increased,which may be related to neutropenic enterocolitis.Loperamide is the main drug for the treatment of CRD.In clinical practice,management of diarrhea that is not responsive to loperamide is of utmost concern.Therefore,based on evidence-based medicine and clinical practice experience,the expert panel carried out a comprehensive assessment and discussion on the definition,pathogenesis,classification,evaluation,diagnosis,intervention,and prevention of CRD.Eventually,the Chinese Expert Consensus on Whole-process Management of Chemotherapy-Related Diarrhea(2025 Edition)was formulated to further standardize the whole-process management of chemotherapy-related diarrhea.The consensus has been registered on Practice guideline REgistration for transPAREncy(PREPARE)with the registration number PREPARE-2024CN1246.

Sodium butyrate is a sodium salt of four-carbon short chain fatty acids produced by dietary fiber under the action of intestinal microorganisms,it can provide energy for intestinal epithelial cells,and plays an important role in maintaining the integrity of intestinal epithelial cells,inhibiting intestinal inflamma-tion and tumor.In recent years,many studies have indicated that sodium butyrate can mediate apoptosis of colorectal cancer cells by inhibiting histone deacetylase activity,cysteine protease mediation and endoplastic re-ticulum (ER) stress,suggesting that sodium butyrate may be a potential anti-colorectal cancer drug.This arti-cle aims to review the advance progress in the role and mechanism of sodium butyrate in colorectal cancer cell apoptosis,and briefly describe the relationship between sodium butyrate in maintaining intestinal microenvi-ronment and enhancing the immune barrier function of intestinal mucosa with inhibiting intestinal inflamma-tion in order to provide reference for the development of sodium butyrate as first-line anti-colorectal cancer drugs.

Objective:To understand the status quo of emotional intelligence, emotional labor, and humanistic caring ability of medical staff, and to clarify their internal relationship.Methods:Convenience sampling was used to select 713 medical staff from a grade A tertiary hospital in Chengdu, Sichuan Province, China. Emotional Intelligence Scale, Humanistic Caring Scale, and Emotional Labor Scale were used to measure the emotional intelligence, humanistic caring ability, and emotional labor of medical staff. SPSS 22.0 software was used to establish a database for statistical description and analysis. Process 3.2 software was used to analyze the mediating effect.Results:In humanistic caring ability, the average score of comprehension dimension was the highest (75.62±8.20) and the average score of patience dimension was the lowest (58.53±5.01). In emotional labor, the average score of the deep action dimension was the highest (23.39±3.85) and the average score of the surface action dimension was the lowest (17.73±3.18). In emotional intelligence, the average score of self-emotion evaluation dimension was the highest (21.76±3.30) and the average score of other-emotion evaluation dimension was the lowest (20.07±3.71). Positive correlations were found between humanistic caring ability and emotional intelligence, between humanistic caring ability and emotional labor, and between emotional intelligence and emotional labor ( P<0.01). Humanistic caring ability had a partial mediating effect between emotional intelligence and emotional labor. Humanistic caring ability had direct and indirect effects on emotional labor, and the effect sizes were 0.279 and 0.029, respectively. Conclusion:Emotional intelligence has a direct positive predictive effect on emotional labor, humanistic caring ability as an intermediary variable indirectly and positively predicts emotional labor. Humanistic caring ability plays a partial mediating role between emotional intelligence and emotional labor. Attention should be paid to the emotional labor of medical staff, and the emotional labor of medical staff should be improved through targeted training on emotional intelligence and humanistic caring ability. These efforts will improve the current situation and establish a harmonious doctor-patient relationship.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody

Objective:To investigate the effects and the mechanism of FoxO6 on the proliferation and invasion of colorectal cancer cells.Methods:FoxO6 siRNA was transfected into colorectal cancer cell HCT116 and SW480. The overexpression vector pcDNA.3.1-c-Myc was constructed and co-transfected into HCT116 and SW480 cells with FoxO6 siRNA. Real-time fluorescent quantitative PCR (RT-qPCR) and western blot were used to detect the mRNA and protein expressions of FoxO6, c-Myc, and p21 in HCT116 and SW480 cells. Bromodeoxyuridine (BrdU) was used to detect cell proliferation and Transwell assay was performed to detect the invasion ability of these cells. SW480 cells transfected with FoxO6 shRNA lentivirus (LV-FoxO6) and were injected into the right armpit of BAL b/c nude mice to construct a tumor-bearing mode and the tumor volumes were measured on the days of 10, 13, 16, 19, 22, and 25 after injection.Results:The FoxO6 mRNA were 0.91±0.04, 1.72±0.07, and 2.03±0.06, and protein expression were 0.70±0.04, 1.35±0.08, and 1.56±0.07 in normal colon cell FHC, colorectal cancer cells HT116 and SW480, respectively. The protein and mRNA levels of FoxO6 in HCT116 and SW480 were significantly higher than those in FHC (both P<0.05). Knockdown of FoxO6 in HCT116 and SW480 cells decreased the mRNA and protein expressions of FoxO6 (both P<0.05), the cell proliferation ability (absorbances were 0.26±0.07 and 0.27±0.06, both P<0.05), cell invasion ability (the invaded cell numbers were 42.3±3.3 and 45.7±4.1, both P<0.05), and the mRNA and protein expressions of c-Myc, while increased the mRNA and protein expressions of p21 (both P<0.01). Overexpression of Myc in FoxO6 silenced HCT116 and SW480 cells decreased the expression of p21, while increased the cell proliferation ability (absorbances were 0.54±0.09 and 0.58±0.07, both P<0.01) and invasion ability (the invaded cell numbers were 79.2±5.9 and 80.5±6.4, both P<0.01). On the 25th day after cell inoculation in nude mice, the tumor volume of LV-FoxO6 group was (190.6±36.2) mm 3, significantly lower than (437.8.6±69.2) mm 3 of LV-NC group ( P<0.05). Conclusion:FoxO6 promotes the proliferation and invasion of colorectal cancer cells through facilitating c-Myc mediated p21 expression inhibition.

Objective:To investigate the effects and the mechanism of FoxO6 on the proliferation and invasion of colorectal cancer cells.Methods:FoxO6 siRNA was transfected into colorectal cancer cell HCT116 and SW480. The overexpression vector pcDNA.3.1-c-Myc was constructed and co-transfected into HCT116 and SW480 cells with FoxO6 siRNA. Real-time fluorescent quantitative PCR (RT-qPCR) and western blot were used to detect the mRNA and protein expressions of FoxO6, c-Myc, and p21 in HCT116 and SW480 cells. Bromodeoxyuridine (BrdU) was used to detect cell proliferation and Transwell assay was performed to detect the invasion ability of these cells. SW480 cells transfected with FoxO6 shRNA lentivirus (LV-FoxO6) and were injected into the right armpit of BAL b/c nude mice to construct a tumor-bearing mode and the tumor volumes were measured on the days of 10, 13, 16, 19, 22, and 25 after injection.Results:The FoxO6 mRNA were 0.91±0.04, 1.72±0.07, and 2.03±0.06, and protein expression were 0.70±0.04, 1.35±0.08, and 1.56±0.07 in normal colon cell FHC, colorectal cancer cells HT116 and SW480, respectively. The protein and mRNA levels of FoxO6 in HCT116 and SW480 were significantly higher than those in FHC (both P<0.05). Knockdown of FoxO6 in HCT116 and SW480 cells decreased the mRNA and protein expressions of FoxO6 (both P<0.05), the cell proliferation ability (absorbances were 0.26±0.07 and 0.27±0.06, both P<0.05), cell invasion ability (the invaded cell numbers were 42.3±3.3 and 45.7±4.1, both P<0.05), and the mRNA and protein expressions of c-Myc, while increased the mRNA and protein expressions of p21 (both P<0.01). Overexpression of Myc in FoxO6 silenced HCT116 and SW480 cells decreased the expression of p21, while increased the cell proliferation ability (absorbances were 0.54±0.09 and 0.58±0.07, both P<0.01) and invasion ability (the invaded cell numbers were 79.2±5.9 and 80.5±6.4, both P<0.01). On the 25th day after cell inoculation in nude mice, the tumor volume of LV-FoxO6 group was (190.6±36.2) mm 3, significantly lower than (437.8.6±69.2) mm 3 of LV-NC group ( P<0.05). Conclusion:FoxO6 promotes the proliferation and invasion of colorectal cancer cells through facilitating c-Myc mediated p21 expression inhibition.