1.Research on the application value of peripheral blood parameters in the diagnosis of early-onset colorectal cancer
Wenxuan YAN ; Junhai ZHEN ; Wenhao SU ; Jixiang ZHANG ; Fei LIAO ; Weiguo DONG
Chinese Journal of Digestion 2025;45(4):256-265
Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.
2.Jianpi-Huayu decotion combined with gemcitabine induces ferroptosis and inhibits growth of pancreatic cancer cells through Nrf2/SLC7A11/GPX4 axis
Xinqiu CHEN ; Zhengze ZHANG ; Shuwei LIU ; Xiaoyu ZHU ; Yongheng LAI ; Chongkai FANG ; Junhai HUANG ; Xilin ZHAO ; Chong ZHONG
Chinese Journal of Pathophysiology 2025;41(6):1077-1087
AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.
3.In vivo pharmacological efficacy of intravenously administered cepharanthine hydrochloride in rats based on its exposures
Zengxu YANG ; Bohong ZHENG ; Mengran WANG ; Fengxu CHENG ; Wenpeng ZHANG ; Chunyan LIU ; Junhai XIAO ; Xiaomei ZHUANG
Chinese Journal of Pharmacology and Toxicology 2025;39(1):46-57
OBJECTIVE To establish a liquid chromatography massspectrometry(LC-MS/MS)method for quantitatively determining the concentration of cepharanthine in rat plasma and tissue samples after intravenous injection of cepharanthine hydrochloride.METHODS ①The LC-MS/MS method was adopted.A Phenomenex C18(3.0 mm×50 mm,2.6 μm)column was employed with a mobile phase consisting of 0.05%formic acid-2 mmol·L-1 ammonium acetate-water solution and 0.1%formic acid-acetonitrile solution under gradient elution at a flow rate of 0.6 mL·min-1.The determination was performed using positive ion multiple reaction monitoring mode assays:cepharanthine(m/z:607.3→365.1)and buspirone(IS)(m/z:386.4→122.2).② Blood samples were collected from 6 SD rats at different time points following a single iv administration of cepharanthine to determine the concentration of the drug.The main pharmacokinetic parameters were calculated using a non-compartmental model.③72 SD rats were subjected to tissue distribution experiments after a single and multiple iv administra-tion of cepharanthine,and tissue samples were collected at six different time points(n=6)for the quanti-fication of drug concentrations.④ The whole blood plasma distribution ratio(Rb/p)of cepharanthine hydrochloride(7.5 mg·kg-1)in 3 SD rats was determined 2 h after iv administration.⑤The protein binding of cepharanthine to rat plasma and lung tissue homogenates was determined by equilibrium dialysis before the concentration of the free drug within the lungs was calculated.RESULTS ① An LC-MS/MS method for quantitatively determining cepharanthine in rat plasma and tissue homogenates was devel-oped,which demonstrated an excellent linear relationship(r2>0.999)within the concentration range of 2 to 1000 μg·L-1,with a lower limit of quantification at 2 μg·L-1.The obtained results met all the require-ments for accurate quantitative detection.②The main pharmacokinetic parameters of cepharanthine in rats following a single iv administration were as follows:C0=(686.91±238.43)μg·L-1,t1/2=(29.70±6.29)h,Vz=(62.70±7.93)L·kg-1,Vss=(62.55±11.28)L·kg-1,CL=(1.50±0.23)L·h-1·kg-1 and AUC(0-t)=(4.52±0.61)h·mg·L-1.③ Concentrations in tissues exceeded those in plasma after both a single and multiple iv administration,with the highest levels in the lung.The values of AUC(0-t)in lungs were(2 547.35±156.56)and(4 481.35±479.21)h·mg·L-1 after a single and multiple iv administration,respectively.④ The content of cepharanthine in blood cells was higher than that in plasma,and Rb/p was 3.5±0.8.⑤ After correction by the protein-binding rate,the minimum concentration of free drugs in the lungs(95.04 μg·L-1)exceeded the reported antiviral activity threshold against coronaviruses(EC50=60.67 μg·L-1).CONCLUSION An LC-MS/MS method has been established to rapidly and sensitively determine the concentration of cepharanthine in rat plasma and tissues.Following intravenous administration of ceph-aranthine hydrochloride,the pulmonary exposure level of the drug is significantly higher in plasma and other tissues,providing data for evaluating its in vivo pharmacological activities.
4.Jianpi-Huayu decotion combined with gemcitabine induces ferroptosis and inhibits growth of pancreatic cancer cells through Nrf2/SLC7A11/GPX4 axis
Xinqiu CHEN ; Zhengze ZHANG ; Shuwei LIU ; Xiaoyu ZHU ; Yongheng LAI ; Chongkai FANG ; Junhai HUANG ; Xilin ZHAO ; Chong ZHONG
Chinese Journal of Pathophysiology 2025;41(6):1077-1087
AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.
5.In vivo pharmacological efficacy of intravenously administered cepharanthine hydrochloride in rats based on its exposures
Zengxu YANG ; Bohong ZHENG ; Mengran WANG ; Fengxu CHENG ; Wenpeng ZHANG ; Chunyan LIU ; Junhai XIAO ; Xiaomei ZHUANG
Chinese Journal of Pharmacology and Toxicology 2025;39(1):46-57
OBJECTIVE To establish a liquid chromatography massspectrometry(LC-MS/MS)method for quantitatively determining the concentration of cepharanthine in rat plasma and tissue samples after intravenous injection of cepharanthine hydrochloride.METHODS ①The LC-MS/MS method was adopted.A Phenomenex C18(3.0 mm×50 mm,2.6 μm)column was employed with a mobile phase consisting of 0.05%formic acid-2 mmol·L-1 ammonium acetate-water solution and 0.1%formic acid-acetonitrile solution under gradient elution at a flow rate of 0.6 mL·min-1.The determination was performed using positive ion multiple reaction monitoring mode assays:cepharanthine(m/z:607.3→365.1)and buspirone(IS)(m/z:386.4→122.2).② Blood samples were collected from 6 SD rats at different time points following a single iv administration of cepharanthine to determine the concentration of the drug.The main pharmacokinetic parameters were calculated using a non-compartmental model.③72 SD rats were subjected to tissue distribution experiments after a single and multiple iv administra-tion of cepharanthine,and tissue samples were collected at six different time points(n=6)for the quanti-fication of drug concentrations.④ The whole blood plasma distribution ratio(Rb/p)of cepharanthine hydrochloride(7.5 mg·kg-1)in 3 SD rats was determined 2 h after iv administration.⑤The protein binding of cepharanthine to rat plasma and lung tissue homogenates was determined by equilibrium dialysis before the concentration of the free drug within the lungs was calculated.RESULTS ① An LC-MS/MS method for quantitatively determining cepharanthine in rat plasma and tissue homogenates was devel-oped,which demonstrated an excellent linear relationship(r2>0.999)within the concentration range of 2 to 1000 μg·L-1,with a lower limit of quantification at 2 μg·L-1.The obtained results met all the require-ments for accurate quantitative detection.②The main pharmacokinetic parameters of cepharanthine in rats following a single iv administration were as follows:C0=(686.91±238.43)μg·L-1,t1/2=(29.70±6.29)h,Vz=(62.70±7.93)L·kg-1,Vss=(62.55±11.28)L·kg-1,CL=(1.50±0.23)L·h-1·kg-1 and AUC(0-t)=(4.52±0.61)h·mg·L-1.③ Concentrations in tissues exceeded those in plasma after both a single and multiple iv administration,with the highest levels in the lung.The values of AUC(0-t)in lungs were(2 547.35±156.56)and(4 481.35±479.21)h·mg·L-1 after a single and multiple iv administration,respectively.④ The content of cepharanthine in blood cells was higher than that in plasma,and Rb/p was 3.5±0.8.⑤ After correction by the protein-binding rate,the minimum concentration of free drugs in the lungs(95.04 μg·L-1)exceeded the reported antiviral activity threshold against coronaviruses(EC50=60.67 μg·L-1).CONCLUSION An LC-MS/MS method has been established to rapidly and sensitively determine the concentration of cepharanthine in rat plasma and tissues.Following intravenous administration of ceph-aranthine hydrochloride,the pulmonary exposure level of the drug is significantly higher in plasma and other tissues,providing data for evaluating its in vivo pharmacological activities.
6.Research on the application value of peripheral blood parameters in the diagnosis of early-onset colorectal cancer
Wenxuan YAN ; Junhai ZHEN ; Wenhao SU ; Jixiang ZHANG ; Fei LIAO ; Weiguo DONG
Chinese Journal of Digestion 2025;45(4):256-265
Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.
7.Interpretation of the progress in esophageal cancer treatment in the 2024 American Society of Clinical Oncology Gastrointestinal Cancer Symposium
Xuxu ZHANG ; Junhai LI ; Xinyao XU ; Jiahe LI ; Jipeng ZHANG ; Wei LI ; Lei WANG ; Qiang LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):807-813
The 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI) was held in San Francisco, the USA from January 18th to 20th, 2024 (local time). The multiple studies presented in this symposium will have a significant impact on the clinical practice of esophageal cancer. This article will focus on the surgical methods of esophageal cancer, perioperative immunotherapy, drug therapy for advanced esophageal cancer, rescue treatment after immunotherapy resistance, and other relevant aspects. It aims to summarize and interpret the significant advancements in the field of esophageal cancer presented in this symposium.
8.Clinical characteristics of primary malignant melanoma of esophagus in elderly Chinese patients
Yongkang TAO ; Long FANG ; Geng QIN ; Shuang ZHANG ; Xiangrong ZHANG ; Junhai ZHANG ; Shiyu DU
Chinese Journal of Geriatrics 2024;43(6):716-720
Objective:To analyze and summarize the clinical manifestations, pathological characteristics, treatment, and outcomes of primary malignant melanoma of the esophagus(PMME)in elderly Chinese patients.Methods:A case study of an elderly patient with PMME was conducted at the Department of Gastroenterology in the China-Japan Friendship Hospital.Additionally, literature and case data on elderly PMME cases reported in China up to July 2023 were gathered and analyzed to summarize the epidemiological characteristics, endoscopic manifestations, clinical presentations, diagnosis, treatment, and prognosis of the disease.Results:A comprehensive review of the literature up to July 2023 documented a total of 114 cases of elderly patients with PMME in China, which also included cases from our hospital.Among these cases, there were 68 male patients(59.6%)and 46 female patients(40.4%), ranging in age from 60 to 81 years, with a median age of 65 years.The predominant clinical manifestations observed were dysphagia and choking while eating, followed by chest pain and retrosternal burning sensation.The majority of the lesions were found in the middle and lower segments of the esophagus, predominantly protruding into the lumen, with only 2 cases(1.8%)displaying esophageal mucosal pigmentation.Immunohistochemical analysis revealed that HMB45 was positive in 74 cases(64.9%)and negative in 3 cases(2.6%), while S-100 was positive in 66 cases(57.9%)and negative in 2 cases(1.8%), although data for some patients were not available.Lymph node or distant metastases were present in 45 cases(39.5%), while 38 patients(33.3%)had tumors confined to the esophagus without metastases.Of the 114 patients, 61(53.5%)had a follow-up period ranging from 0.3 to 39 months, with a median follow-up time of 6.75 months.Among the patients who survived during the follow-up period, there were 30 cases(26.3%), with a follow-up time of 1 to 39 months and a median follow-up time of 7.5 months.For the deceased patients, the time from consultation to death ranged from 0.3 to 31 months.Conclusions:Elderly individuals with PMME in China typically present with a gradual onset, nonspecific symptoms, frequent metastasis upon diagnosis, aggressive behavior, and unfavorable outcomes.
9.Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations.
Pengyun LI ; Changkai JIA ; Zhiya FAN ; Xiaotong HU ; Wenjuan ZHANG ; Ke LIU ; Shiyang SUN ; Haoxin GUO ; Ning YANG ; Maoxiang ZHU ; Xiaomei ZHUANG ; Junhai XIAO ; Zhibing ZHENG ; Song LI
Acta Pharmaceutica Sinica B 2023;13(6):2715-2735
Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.
10.Comparison of nutrition and visual health between Tibetan migrant students and local students in Gannan of Lanzhou New District
ZHANG Yonghua,MA Cuiling, ZHANG Xiaoling ,SHI Ying,WANG Chunping,SU Junhai,ZHAO Ai
Chinese Journal of School Health 2021;42(7):1029-1032
Objective:
This paper studies the nutritional and vision health status of Tibetan migrant students and the differences between the local students in Lanzhou and them to provide a theoretical basis for nutrition intervention and vision protection for students.
Methods:
Cluster sampling method was used to select 2 434 students migrating from Gannan Tibetan Autonomous Prefecture to a boarding middle school, and 3 291 students from three middle schools in Qilihe District of Lanzhou from September to December 2020. All the students were administered physical and visual examination. Proportion of nutritional status, poor eyesight and myopia by gender and age groups between Tibetan migrant students and local students were analyzed.
Results:
The detection rate of overweight and obesity in Tibetan migrant boys(2.8%,5.7%) and girls(11.0%,8.3%) was lower than that of local students of the same sex(5.6%,8.3%;24.9%,20.9%) ( χ 2=12.17,7.21, P <0.05; χ 2=81.33,91.34, P <0.05); The detection rate of malnutrition in Tibetan migrant boys(9.9%) was higher than that in local boys(7.2%) ( χ 2=6.65, P <0.05). The detection rate of poor vision in Tibetan migrant boys was lower than that in local boys ( χ 2=3.93, P <0.05). The detection rate of myopia was significantly lower than that of local students ( χ 2=975.82, P <0.01). The detection rate of abnormal color vision in Tibetan migrant boys was higher than that in local boys ( χ 2=8.38, P <0.05). The detection rate of abnormal color vision in Tibetan migrant girls was lower than that in local girls ( χ 2=8.08, P <0.05). The detection rate of mild and moderate visual impairment was lower among Tibetan migrant boys than local boys ( χ 2=3.88, 8.32, P <0.05); the detection rate of mild, moderate and severe myopia was lower than local boys ( χ 2= 13.72 ,55.96, 338.50, P <0.05). The detection rate of mild, moderate and severe myopia was lower among Tibetan migrant girls than local girls ( χ 2=7.62, 37.79,424.00, P <0.05).
Conclusion
Tibetan migrant students was lower than that of local students. More attention should be paid to nutrition intake of Tibetan boys to prevent malnutrition. The detection rate of myopia in Tibetan migrant students is low,but the detection rate of severe poor vision among Tibetan students in the junior high school group is higher than that of local students, and attention should be paid to the visual health of Tibetan students in junior high school.


Result Analysis
Print
Save
E-mail