Objective:To investigate the efficacy and safety of anlotinib combined with gemcitabine + cisplatin (GP) regimen in the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.Methods:A retrospective case controlled study was conducted. The clinical data of 82 patients with nasopharyngeal carcinoma newly diagnosed as distant metastasis or recurrence and metastasis after radical chemoradiotherapy in the Second Affiliated Hospital of Guangxi University of Science and Technology and Laibin People's Hospital from January 2020 to December 2021 were retrospectively analyzed. Among 82 patients, 45 patients receiving anlotinib combined with GP regimen were treated as the treatment group, and 37 patients receiving GP chemotherapy regimen during the same period were treated as the control group. Short-term efficacy and adverse reactions were compared between the 2 groups. Kaplan-Meier method was used to compare the progression-free survival (PFS) and overall survival (OS), and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing the PFS of patients.Results:Among 82 patients, 63 were males and 19 were females, aged (48±10) years. The objective response rate (ORR) and disease control rate (DCR) in the treatment group were higher than those in the control group [ORR: 71.11% (32/45) vs. 62.16% (23/37); DCR: 86.67% (39/45) vs. 81.08% (30/37)], while there were no statistically significant differences (all P > 0.05). The median PFS time was 23.53 months (95% CI: 17.48-29.58 months), 17.40 months (95% CI: 13.33-21.47 months), respectively in the treatment group and the control group, and the difference in PFS was statistically significant ( P < 0.05). The median OS time was 34.03 months (95% CI: 29.42-38.64 months), 30.47 months (95% CI: 28.28-32.66 months), respectively in the treatment group and the control group, and the difference in OS was not statistically significant ( P > 0.05). Oral anlotinib, recurrence or metastasis at initial diagnosis were independent factors influencing the PFS of patients. The main adverse effects of anrotinib were grade 1-2 anorexia, fatigue, granulocytopenia, hypertension, hand-foot syndrome, oral mucositis, and liver function damage. The incidence of grade 3-4 was low, and the adverse reactions in most patients could be controlled after symptomatic treatment and adjustment of drug dosage. Conclusions:For patients with recurrent or metastatic nasopharyngeal carcinoma, oral anlotinib targeted therapy combined with GP chemotherapy regimen can prolong the PFS time of patients. Most anlotinib-related side effects can be tolerated.Objective To investigate the efficacy and safety of anlotinib combined with gemcitabine + cisplatin (GP) regimen in the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma. Methods A retrospective case controlled study was conducted. The clinical data of 82 patients with nasopharyngeal carcinoma newly diagnosed as distant metastasis or recurrence and metastasis after radical chemoradiotherapy in the Second Affiliated Hospital of Guangxi University of Science and Technology and Laibin People's Hospital from January 2020 to December 2021 were retrospectively analyzed. Among 82 patients, 45 patients receiving anlotinib combined with GP regimen were treated as the treatment group, and 37 patients receiving GP chemotherapy regimen during the same period were treated as the control group. Short-term efficacy and adverse reactions were compared between the 2 groups. Kaplan-Meier method was used to compare the progression-free survival (PFS) and overall survival (OS), and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing the PFS of patients. Results Among 82 patients, 63 were males and 19 were females, aged (48±10) years. The objective response rate (ORR) and disease control rate (DCR) in the treatment group were higher than those in the control group [ORR: 71.11% (32/45) vs. 62.16% (23/37); DCR: 86.67% (39/45) vs. 81.08% (30/37)], while there were no statistically significant differences (all P > 0.05). The median PFS time was 23.53 months (95% CI: 17.48-29.58 months), 17.40 months (95% CI: 13.33-21.47 months), respectively in the treatment group and the control group, and the difference in PFS was statistically significant ( P < 0.05). The median OS time was 34.03 months (95% CI: 29.42-38.64 months), 30.47 months (95% CI: 28.28-32.66 months), respectively in the treatment group and the control group, and the difference in OS was not statistically significant ( P > 0.05). Oral anlotinib, recurrence or metastasis at initial diagnosis were independent factors influencing the PFS of patients. The main adverse effects of anrotinib were grade 1-2 anorexia, fatigue, granulocytopenia, hypertension, hand-foot syndrome, oral mucositis, and liver function damage. The incidence of grade 3-4 was low, and the adverse reactions in most patients could be controlled after symptomatic treatment and adjustment of drug dosage. Conclusions For patients with recurrent or metastatic nasopharyngeal carcinoma, oral anlotinib targeted therapy combined with GP chemotherapy regimen can prolong the PFS time of patients. Most anlotinib-related side effects can be tolerated.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

This study was aimed to optimize the hydrolysis conditions of Coix prolamin, which occupied the highest content in total protein of it, and then evaluate the angiotensin-converting enzyme (ACE) inhibitory activity of the corresponding hydrolysates. Pepsin was used to hydrolyze prolamin and OPA method was applied to determine the degree of hydrolysis. The optimum conditions of hydrolyzing prolamin were obtained by orthogonal design subse-quently. The ACE inhibitory activity of small molecular weight (less than 3 kD) peptides gained by ultrafiltration of the hydrolysates was assayed by RP-HPLC method. The result showed that the optimized hydrolysis conditions were substrate concentration of 1%, enzyme-to-substrate ratio of 1:5 and hydrolysis duration for 48 h. The hydrolysates exhibited an ACE inhibitory ratio of (83.40 ± 0.93)% at the concentration of 0.1 mg·mL-1. It was concluded that prolamin hydrolysates displayed a high ACE inhibitory activity in vitro, which provided guidance for further research of antihypertensive component and development of functional food from Coix.

Objective To compare drug therapy in patients suffering from chronic heart failure between Tianjin and Kashi region of Xinjiang autonomous region and to analyse their disparities in drug uses by guideline between the two regions.Methods All data were retrospectively taken from the hospitalized chronic heart failure cases from June 2005 to June 2006 in the 2nd Hospital of Tianjin Medical University and the 2nd People's Hospital of Kashi in Xinjiang respectively.The heart functions level NYHA Ⅱ-Ⅳ were recorded for analysis of drug use in the two regions.Results 749 cases were enrolled,491 from Tinajin and 258 from Kashi of Xinjiang.The average age of group Tianjin[(70.39±10.84)yrs]was older than that[(62.91±12.54)yrs]of group Kashi(t=8.488,P＜0.01).The distribution of≥165 cases in the group Tianjin(75.6%)was higher than that of group Kashi(51.2%)(X2=45.642,P＜0.01).The male cases in group Tianjinwere 264(53.8%)andthatwere 134(51.9%)in group Kashi with no significant differences in sex distribution between the two groups(P＞0.05).The first three etiological diseases were coronary heart disease(84.9%),rheumatic heart disease(5.9%)and dilated cardiomyopathy (3.3%)in group Tianjin,and that were coronary heart disease(63.2%),pulmonary heart disease(19.8%)and dilated eardiomyopathy(6.6%)in group Kashi respectively.The proportions of level NYHA Ⅱ,Ⅲ,Ⅳ on admission were 29.7%,39.1%and 31.2%in group Tianjin respectively,and that were 15.5%,39.5%and 45.0%in group Kashi respectively,with significant difference in heart function levels between the two groups(X2=22.770,P＜0.01).Theusages of nitrides and β-blockers in group Tianjin were more than that in group Kashi(both P＜0.01).The usages of diuretics,digitalis was more in group Kashi(all P＜0.01).There was no difference in ACEI usages between the two groups.The dosages of drugs in group Tianjin achieved the target dosages by the guideline and the dosages in group Kashi did not achieve the targets.The use frequency of β-blockers was more in male cases and＜65yrs respectively of group Tianjin.The usage frequency of uretics and aldosterone antagonist were more in＜65yrs cases of group Kashi and the usages of nitrides,ACEI,B-blockers,calcium antagonists,aldosterone antagonist of male cases were more than that of female cases(all P＜0.05)in this group.The usages of uretics,digitalis,aldostemne antagonist increased following the grading of heart function of the two groups(P＜0.05).Moreover the usage of ACEI decreased following the worsen heart function in group Tainjin and this was not the same in group Kashi.Conclusion There are differences in drug medications for chronic heart failure between Tianjin and Kashi.The majority of treatment drugs in Tianjin is approaching the guideline and there is a gap from guideline in Kashi of Xinjiang,especially on the dosage.