OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu De-coction,and cell proliferation and migration abilities were assessed.Forty-two BALB/c nude mice were randomly divided into a blank control group,model group,5-fluorouracil(5-FU)group(0.025 g·kg-1),Anzheng Kangliu Decoction low-dose group(7.67 g·kg-1),medium-dose group(15.34 g·kg-1),and high-dose group(30.68 g·kg-1).The inhibitory effect of Anzheng Kan-gliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight,tumor volume,tumor mass,HE staining,im-munohistochemical staining of Ki67 and other indicators.High-throughput transcriptome sequencing was performed to identify differen-tially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group,elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer.Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention.Western blot was employed to detect the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,hexokinase 2(HK2),and lactate dehydrogenase A(LDHA)in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.RE-SULTS In vitro cell experiments demonstrated that,compared with the blank control group,Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells(P<0.01),reduced glucose consumption and lactate production(P<0.05,P<0.01),and downregulated the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).In vivo animal experiments revealed that,compared with the model group,Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice(P<0.01),increased tumor tissue necrosis,decreased glucose consumption and lactate production in tumor tissues(P<0.05,P<0.01),and reduced the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).CONCLUSION Anzheng Kangliu Decoction exerts an in-hibitory effect on colorectal cancer,and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.

Objective:To analyze the safety and short-term efficacy of thoracic radiotherapy combined with anlotinib in the treatment of inoperable non-small cell lung cancer (NSCLC).Methods:A prospective study was conducted on patients with unresectable locally advanced NSCLC who were intolerant to concurrent chemoradiotherapy and treated at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, from October 2020 to September 2023. Anlotinib was administered orally concurrently with radiotherapy (days 1-14, 21 days per cycle, for 3 cycles). Adverse effects and short-term tumor recurrence were observed from the beginning of radiotherapy to the 3-month post-radiotherapy. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) rates from the date of initial treatment (induction therapy), and intergroup comparisons were performed using the log-rank test.Results:The median age was 62 years (range:42-76 years), with a male predominance ( n=36, 88%) of the included 41 patients. The incidence of grade 3-4 acute hematologic adverse events was 20% (8 cases); the incidence of grade 3 hemoptysis was 2% (1 case), with no grade 4 hemoptysis; the incidence of grade 3-4 radiation pneumonitis was 10% (4 cases). No grade 5 adverse events were observed in the entire cohort. With a median follow-up of 19.7 months (range: 7.1-50.1 months), 19 patients (46%) experienced recurrence, including 4 patients (10%) with local recurrence, 6 patients (15%) with regional lymph node recurrence, and 11 patients (27%) with distant metastases. The 1-year PFS rate was 78.3%. 8 patients (20%) died, including 3 patients died from COVID-19 infection during the follow-up period, 1 patient who died from hypostatic pneumonia due to prolonged bed rest after cerebral infarction, and 4 patients died from tumor-related causes. The 1-year OS rate was 78.0%. Conclusions:Thoracic radiotherapy combined with anlotinib demonstrates good safety, manageable adverse events, and favorable short-term efficacy in NSCNC patients intolerant to concurrent chemoradiotherapy.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu De-coction,and cell proliferation and migration abilities were assessed.Forty-two BALB/c nude mice were randomly divided into a blank control group,model group,5-fluorouracil(5-FU)group(0.025 g·kg-1),Anzheng Kangliu Decoction low-dose group(7.67 g·kg-1),medium-dose group(15.34 g·kg-1),and high-dose group(30.68 g·kg-1).The inhibitory effect of Anzheng Kan-gliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight,tumor volume,tumor mass,HE staining,im-munohistochemical staining of Ki67 and other indicators.High-throughput transcriptome sequencing was performed to identify differen-tially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group,elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer.Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention.Western blot was employed to detect the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,hexokinase 2(HK2),and lactate dehydrogenase A(LDHA)in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.RE-SULTS In vitro cell experiments demonstrated that,compared with the blank control group,Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells(P<0.01),reduced glucose consumption and lactate production(P<0.05,P<0.01),and downregulated the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).In vivo animal experiments revealed that,compared with the model group,Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice(P<0.01),increased tumor tissue necrosis,decreased glucose consumption and lactate production in tumor tissues(P<0.05,P<0.01),and reduced the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).CONCLUSION Anzheng Kangliu Decoction exerts an in-hibitory effect on colorectal cancer,and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.

Objective:To analyze the safety and short-term efficacy of thoracic radiotherapy combined with anlotinib in the treatment of inoperable non-small cell lung cancer (NSCLC).Methods:A prospective study was conducted on patients with unresectable locally advanced NSCLC who were intolerant to concurrent chemoradiotherapy and treated at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, from October 2020 to September 2023. Anlotinib was administered orally concurrently with radiotherapy (days 1-14, 21 days per cycle, for 3 cycles). Adverse effects and short-term tumor recurrence were observed from the beginning of radiotherapy to the 3-month post-radiotherapy. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) rates from the date of initial treatment (induction therapy), and intergroup comparisons were performed using the log-rank test.Results:The median age was 62 years (range:42-76 years), with a male predominance ( n=36, 88%) of the included 41 patients. The incidence of grade 3-4 acute hematologic adverse events was 20% (8 cases); the incidence of grade 3 hemoptysis was 2% (1 case), with no grade 4 hemoptysis; the incidence of grade 3-4 radiation pneumonitis was 10% (4 cases). No grade 5 adverse events were observed in the entire cohort. With a median follow-up of 19.7 months (range: 7.1-50.1 months), 19 patients (46%) experienced recurrence, including 4 patients (10%) with local recurrence, 6 patients (15%) with regional lymph node recurrence, and 11 patients (27%) with distant metastases. The 1-year PFS rate was 78.3%. 8 patients (20%) died, including 3 patients died from COVID-19 infection during the follow-up period, 1 patient who died from hypostatic pneumonia due to prolonged bed rest after cerebral infarction, and 4 patients died from tumor-related causes. The 1-year OS rate was 78.0%. Conclusions:Thoracic radiotherapy combined with anlotinib demonstrates good safety, manageable adverse events, and favorable short-term efficacy in NSCNC patients intolerant to concurrent chemoradiotherapy.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

OBJECTIVE To investigate the effect of betulin (BE) on the replication of rotavirus (RV) in vitro.METHODS ①MA104 cells were intervened with BE between 0.03125 and 64μmol·L-1 for 72 h,and MTT assay was used to detect the cell survival.② MA104 cells were infected with RV including Wa strains and SA-11 strains to establish a viral model.MA104 cells were divided into the cell control group,RV group and RV+BE groups.The cytopathic effect (CPE) method combined with MTT assay was used to detect the effect of BE on anti-RV adsorption,anti-RV biosynthesis and direct inhibition of RV.③The grouping was the same as in②,and RT-qPCR,Western blot and IF methods were used to detect the expression of RV structural protein VP6 after 24 h of BE incubation.④The grouping was the same as in②,and the ELISA kit was used to detect the concentrations of pro-inflammatory factors IL-6,IL-1β and TNF-α,anti-inflammatory factor IL-10 and type Ⅱ interferon IFN-γ in the cell supernatant after 24 h of BE incubation.⑤The grouping was the same as in②,and qPCR assay was used to detect the mRNA expression levels of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MYD88) and TNF receptor-associated factor 6 (TRAF6) after 24 h of BE incubation,Western blot assay was used to detect the expression levels of MYD88,IκBα,NF-κB p65,and p-NF-κB p65 after 24 h of BE incubation.RESULTS ① The maximum non-toxic concentration of BE towards MA104 cells was 1 μmol·L-1,and TC50 was 5.795 μmol·L-1.The concentrations of BE in the anti-RV experiments ranged from 0.03125μmol·L-1 to 1μmol·L-1.② In the anti-RV biosynthesis experiment,the inhibition rates of BE for RV-Wa between 0.0625 and 1 μmol·L-1 exceeded 50％,EC50 was 0.0485 μmol·L-1,and the value of TI was 119.48.The inhibition rates of BE for RV-SA-11 between 0.25 and 1 μmol·L-1 were above 50％,EC50 was 0.1226 μmol·L-1,and the value of TI was 47.27.In contrast,the effects of BE on anti-RV adsorption and direct inhibition of RV were not obvious.③ Compared with the RV group,BE inhibited the expression of VP6 (P＜0.01).④ Compared with the RV group,BE reduced the concentrations of IL-6,IL-1β and TNF-α(P＜0.01),but increased the concentrations of IL-10 and IFN-γ(P＜0.01).⑤Compared with the RV group,BE reduced the mRNA levels of TLR4,MYD88 and TRAF6 (P＜0.01),decreased the protein expression levels of MYD88 and p-NF-κB p65,and increased those of IκBα and NF-κB p65 (P＜0.01).CONCLUSION BE has anti-RV biosynthesis effect,and it may reduce inflammatory response caused by RV infection via TLR4/MYD88/NF-κB signaling pathway.

Based on the compound pathogenesis theory of malignant tumor,this article combines the theories of positive-evil,yin-yang,and central qi theories with the theory of cancer toxin,pointing out that the deficiency of positive and excess of evil are the basis for the onset of tumors.The pathogenesis characteristics of tumors are the loss of both yin and yang,stagnation of qi,and cancer toxin deeply lurking.The paper believes that the loss of both yin and yang often originates from the spleen and kidney,stagnation of qi is first blamed on the spleen and stomach,and cancer toxin deeply lurking often accompanies multiple evil qi.Based on this,the detoxi-cation method of warming and nourishing is proposed to treat malignant tumors.It is the combination or sequential application of the three methods of warming,nourishing,and detoxification,which play the role of warming and nourishing together,harmonizing yin and yang;promoting the circulation of qi,relieving depression,and regulating emotions;eliminating cancer and toxin,and breaking the combined evil.

OBJECTIVE To investigate the effect of betulin (BE) on the replication of rotavirus (RV) in vitro.METHODS ①MA104 cells were intervened with BE between 0.03125 and 64μmol·L-1 for 72 h,and MTT assay was used to detect the cell survival.② MA104 cells were infected with RV including Wa strains and SA-11 strains to establish a viral model.MA104 cells were divided into the cell control group,RV group and RV+BE groups.The cytopathic effect (CPE) method combined with MTT assay was used to detect the effect of BE on anti-RV adsorption,anti-RV biosynthesis and direct inhibition of RV.③The grouping was the same as in②,and RT-qPCR,Western blot and IF methods were used to detect the expression of RV structural protein VP6 after 24 h of BE incubation.④The grouping was the same as in②,and the ELISA kit was used to detect the concentrations of pro-inflammatory factors IL-6,IL-1β and TNF-α,anti-inflammatory factor IL-10 and type Ⅱ interferon IFN-γ in the cell supernatant after 24 h of BE incubation.⑤The grouping was the same as in②,and qPCR assay was used to detect the mRNA expression levels of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MYD88) and TNF receptor-associated factor 6 (TRAF6) after 24 h of BE incubation,Western blot assay was used to detect the expression levels of MYD88,IκBα,NF-κB p65,and p-NF-κB p65 after 24 h of BE incubation.RESULTS ① The maximum non-toxic concentration of BE towards MA104 cells was 1 μmol·L-1,and TC50 was 5.795 μmol·L-1.The concentrations of BE in the anti-RV experiments ranged from 0.03125μmol·L-1 to 1μmol·L-1.② In the anti-RV biosynthesis experiment,the inhibition rates of BE for RV-Wa between 0.0625 and 1 μmol·L-1 exceeded 50％,EC50 was 0.0485 μmol·L-1,and the value of TI was 119.48.The inhibition rates of BE for RV-SA-11 between 0.25 and 1 μmol·L-1 were above 50％,EC50 was 0.1226 μmol·L-1,and the value of TI was 47.27.In contrast,the effects of BE on anti-RV adsorption and direct inhibition of RV were not obvious.③ Compared with the RV group,BE inhibited the expression of VP6 (P＜0.01).④ Compared with the RV group,BE reduced the concentrations of IL-6,IL-1β and TNF-α(P＜0.01),but increased the concentrations of IL-10 and IFN-γ(P＜0.01).⑤Compared with the RV group,BE reduced the mRNA levels of TLR4,MYD88 and TRAF6 (P＜0.01),decreased the protein expression levels of MYD88 and p-NF-κB p65,and increased those of IκBα and NF-κB p65 (P＜0.01).CONCLUSION BE has anti-RV biosynthesis effect,and it may reduce inflammatory response caused by RV infection via TLR4/MYD88/NF-κB signaling pathway.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.