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.

Objective To investigate the value of neurite orientation dispersion and density imaging (NODDI) in quantitative evaluation of the microstructural changes in basal ganglia and thalamus in Wilson's disease (WD) patients,and to assess the diagnostic efficacy of NODDI.Methods Totally 27 WD patients (WD group) and 26 age-and sex-matched controls (control group) were enrolled.All subjects underwent MR scanning with NODDI.Parameters of NODDI,including intracellular volume fraction (Vic),orientation dispersion index (ODI) and isotropic volume fraction (Viso) of bilateral caudate nucleus,globus pallidus,putamen and thalamus were compared between the 2 groups.Correlation analysis was performed between each parameter of NODDI and clinical Young scores.Random Forest model was used to assess the relative importance of each parameter and to evaluate the diagnostic efficacy.Results The Vic and ODI of bilateral caudate nucleus,globus pallidus and putamen in WD patients were significantly lower than those in normal controls (all P＜0.05),while Viso was significantly higher than that in normal controls (all P＜0.05).The Vic of bilateral thalamus was lower,while Viso was higher in WD patients than those in normal controls (all P＜0.05),and ODI had no significant difference between the 2 groups (P=0.055).In WD patients,Vic and ODI of bilateral caudate nucleus,globus pallidus and putamen were negatively correlated with clinical Young scores.Viso of globus pallidus and putamen were positively correlated with clinical scores.The prediction accuracy of NODDI was 96.23％,and the area under ROC curve was 0.96.Conclusion NODDI can effectively evaluate changes in microstructures and metabolism during copper deposition in WD patients,and it may be useful in detecting changes of brain deep nuclei and assessing the progression of WD.

Objective To discuss the importance of nutritional intervention through monitoring the growth and the nutritional status of children with food allergy after comprehensive nutritional intervention.Methods A total of 158 children with food allergy who were under 2 years old were divided into an intervention group and an control group according to comprehensive nutritional intervention.The intervention group received diet guidance from a dietitian regu larly and took probiotics.If necessary,nutrients (calcium,iron and zinc) could be provided.The control group was given oral guidance by the pediatrician.After 6 months 1 follow-up,growth situation was assessed in terms of height and weight indexes,and nutritional intake condition was assessed in the light of serum biochemical indexes.Results The prevalence of malnutrition in the intervention group(17.6％) was significantly lower than that in the control group (37.0％),and there was a statistical sigmficance (x2 =22.03,P ＜ 0.05);the level of zinc [(88.5 ± 9.6) μmol/L]and iron [(18.6 ± 3.4) mmol/L] in the serum were significantly higher than those [zinc:(68.2 ± 8.5) μmol/L;iron:(12.8 ±2.7) mmol/L] in the control group,and there were statistical significance (zinc:t =12.264,P ＜ 0.01;iron:t =10.762,P ＜ 0.05);the daily intake of calcium[(596.1 ± 110.3) mg] and zinc [(10.7 ± 3.7) mg] in children (＞ 6-24 months) of the intervention group were significantly higher than those [calcium:(412.8 ± 89.3) mg and zinc:(7.3 ± 2.1) mg] in the control group (calcium:t =4.011,P ＜ 0.05,zinc:t =5.367,P ＜ 0.05),and the daily intake of protein [(42.8 ± 9.4) g] in the children (＞ 12-24 months) of the intervention group was significantly higher than that [(33.2 ± 8.2) g] in the control group,and there was a statistical significance (t =3.245,P ＜0.05).Conclusions Children with food allergy have risks of malnutrition,while comprehensive nutritional intervention can obviously decrease the prevalence of malnutrition and deficiency of iron,zinc and calcium,hence normative guidance of scientific feeding of children with food allergy is needed.

BACKGROUND: At present, bone remodeling biological model study usually applys finite element method combing with computer technique to simulate and predict bone quantity or bone structure. In this study the author integrate inversion method with animal experiment to establish a quantification bone remodeling biological model of in vivo bone tissue in real stress environment.OBJECTIVE: To set up a quantification biological model of bone growth and remodeling adaptation, which integrates animal experiments, parameter inversion identification of mathematical functions, and technique of computer simulation. DESIGN, TIME AND SETTING: The experiment was accomplished in Animal Experiment Center of Dalian Medical University in October 2002.MATERIALS: 60 female Sprague Dawley mice of 6-week old were used in this study. Challenger double-energy X ray bone density device was provided from DMS Company, France. Sensation l6 CT machine was provided from Germany Siemens Company.METHODS: 60 mice were randomly divided into two groups: i 5 animals were in normal control groups. 45 in experiment groups. By designing a new animal experiment, we investigate the effects of stress environments on bone growth and remodeling of rapid growing rats and gather the bone mineral density (BMD) of proximal femur in the same interval for the unknown parameters (B and K) inversion of bone growth and remodeling equation to create the femur three-dimension geometrical model based on CT images. MAIN OUTCOMING MEASURES: Body weight of animal, bone density and CT imagine of proximal femur. RESULTS: Body mass in the experiment group and control group was increased with the rat growing; BMD in the control group and overloading group was also increased with the rat growing; but BMD in the unloading group was decreased in the fifth week. Inversion and experimental data showed that parameter B was rapidly decreased as compared to time, and it was closed to zero in the 10th week. Parameter K was rapidly increased as compared to time. and it was gradually increased from the 5th to the 10th weeks, moreover, it was closed to the horizontal line after 10 weeks. This predicted that rapid growth was over, and bone reconstitution and absorption came into another balance cycle. CONCLUSION: The thought and method used in the model creating in.this paper provide clue and reference to establish human model of bone growth and remodeling.

Presented is a method to set up a quantification model of bone growing and remodeling adaptation, which integrates animal experiments, parameter identification of mathematical functions and technique of computer simulation. By designing a new animal experiment, we investigate the effects of growing and remodeling of the rat femurs in different stress environments, gather the bone mineral density (BMD) of proximal femur in the same interval for the unknown parameter (B and K) inversion of bone growing and remodeling equation and create the femur three-dimensional geometrical model based on CT images. The model in this paper can not only numerically measure the relation between outer stimulus and the femur BMD variation of rapid growing rats, but also predict the growth trend of rat femur under different stress environments in its whole lifecycle. The thought and method of creating the model in this paper can be used for reference to modeling human bone growth and remodeling.
Adaptation, Physiological ; Animals ; Biomechanical Phenomena ; Bone Density ; Female ; Femur ; physiology ; Models, Biological ; Rats ; Rats, Sprague-Dawley ; Stress, Mechanical

By creating two kinds of stress environment in the same animal model, we performed a three-point bending test and a compressing test on the rat femurs growing under different stress conditions to characterize the effect of stress on bone mechanical properties. The right hindlimbs were subjected to sciatic nerve resection to become cripple and were used as unloading group; the left hindlimbs bore excess load and made up the overloading group; the normal rats were used as control group. The animals were encouraged to exercise for half an hour everyday in the morning, noon and evening. The experiment observation finished in four weeks. The biomechanical parameters of femur diaphyses were measured. The experiment results showed that stress environment may change several mechanical parameters of rat femurs. This study indicated that bone tissues can adapt to its stress environment by changing its mechanical properties. The experimental model in this article is practical and reliable.
Animals ; Biomechanical Phenomena ; Diaphyses ; physiology ; Femur ; physiology ; Rats ; Stress, Mechanical

The mechanical model of femur mid-diaphysis with a rectangular open section in the exterior cortex was developed and a finite element method was adopted in calculating and analysing the changes of torsional stiffness and the stress distribution when the dimension of the open section altered. It showed that the open section with a length of 1 OD (femur mid-diaphysis diameter) had little influence on the femur torsional stiffness or stress distribution. The torsional stiffness decreased most dramatically as the length increased from 2 to 4 OD. Shear stress peaked at the center of the open section. This conclusion provides an important theoretical ground for the operative methods and the dimension control of an open section in clinical orthopaedics.
Biomechanical Phenomena ; Femur ; physiopathology ; surgery ; Humans ; Models, Theoretical

6-week old rats were subjected to sciatic nerve resection and the right hindlimbs were then under a low stress environment. Bone mineral density (BMD) of different regions and geome-morphological parameters of femurs were measured. The results showed that the increase in the diameter, subperiosteal area and bone mineral density of femurs were suppressed obviously under low stress environment. But the sensitivity of BMD of different regions of the femur to the low stress environment was different. The suppression of the increase in femoral BMD was composed of an early impairment in the gain of BMD at the femoral metaphysis, which is rich in trabecular bone, and a sustained reduction in the gain of BMD at the femoral diaphysis, which is rich in cortical bone. The results of geome-morphology suggested that the early reduction in the increase of BMD at the metaphysis was due to an enhancement of bone resorption, whereas the suppression of gain in cortical bone mass and size is the result of a sustained reduction of periosteal bone formation.
Animals ; Bone Density ; physiology ; Bone Resorption ; etiology ; Female ; Femur ; pathology ; Immobilization ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; physiology ; surgery ; Stress, Mechanical ; Weight-Bearing ; physiology