Objective To establish a submental tumorigenesis model by injecting human hypopharyngeal carcinoma cells to nude mice, and to compare the model with traditional axillary tumorigenesis model. Methods Five-week-old male nude mice were selected and divided into submental tumorigenesis model group (submental group) and axillary tumorigenesis model group (axillary group). Each group was divided into two subgroups by injecting human hypopharyngeal carcinoma cells FADU or HN31, namely sub-FADU, sub-HN31, ax-FADU, and ax-HN31 groups, with 12 nude mice in each group. The nude mice in the submental group were injected with tumor cells in the left side of submental area, and those in the axillary group were injected with tumor cells in the right side of axillary area. The time of tumor formation, tumor volume and body mass of nude mice were measured. The death of nude mice was recorded. After eight weeks, the local tumor growth, infiltration, and organ metastasis such as liver, spleen and kidney of the survival nude mice were examined by ultrasound, and the tumor metastasis was observed by routine H-E staining and immunohistochemical staining. Results On the 7th and 9th days after injection, the tumors were observed in the submental group and the axillary group. On the 33rd day after injection, the tumor volume in the ax-FADU and ax-HN31 groups was significantly bigger than those in the sub-FADU and sub-HN31 groups (P<0.05, P<0.01). The body mass of nude mice in each group reached peak on the 17th to 19th days after injection, and thereafter the body mass in the submental group was gradually decreased and that in the axillary group was still increased. On the 33rd day after injection, the body mass in the ax-FADU and ax-HN31 groups were significantly higher than those in the sub-FADU and sub-HN31 groups, respectively (P<0.01). After eight weeks, there were eight deaths in the sub-FADU group and 10 in the sub-HN31 group, with six mice alive in the submental group; there were six deaths in the ax-FADU group and six in the ax-HN31 group, with 12 alive in the axillary group. There was no significant difference in mortality of nude mice between the four subgroups. Ultrasound and pathological examination showed that four survived nude mice were found with cervical lymph node and liver metastases in the submental group, and only one was found with liver metastases in the axillary group; and the difference between the two groups was statistically significant (P<0.05). There were two pulmonary metastases in the submental group, and one in the axillary group; there was one spleen metastases in the submental group and no spleen metastases in the submental group; and there were no significant differences between the two groups. Conclusion Submental tumorigenesis model and axillary tumorigenesis model have their own characteristics. The submental tumorigenesis model has shorter tumorigenesis time, higher local invasion and higher distant metastasis rate, and is suitable for studying the invasiveness and metastasis of tumor in vivo. The axillary tumorigenesis model has larger volume of tumor, less injury to the adjacent organs and tissues, longer survival time and lower distant metastasis rate, and is suitable for the study of the characteristics of tumor cells.

Objective of this study was to detect the expression of HtrA2 and WT1 mRNA in acute myeloid leukemia (AML) and investigate the relationship of their expression levels with clinical variates and correlation between them. The expression levels of HtrA2 and WT1 were measured by RQ-PCR in bone marrow cells in 104 newly diagnosed AML patients and leukemia cell lines (K562, HL-60, NB4, Kasumi-1, U937), and the relationship between expression level and clinical parameters (age, sex, WBC count, diagnosis and prognosis) was investigated. The results showed that (1) the expression of HtrA2 gene in newly diagnosed AML was lower than that of the normal controls (P < 0.01), while expression of WT1 gene in newly diagnosed AML was higher than that of the normal controls (P < 0.01), the expression levels of HtrA2 and WT1 genes both did not correlate with age, sex and WBC counts of patients. There were no significant difference of HtrA2 gene expression between different NCCN prognosis group, while WT1 gene expression in better-risk group was significantly lower than that in intermediate-risk group (P = 0.003). The HtrA2 expression level rose after treatment in both CR group and non-CR group (P < 0.05), while WT1 expression level significantly decreased after treatment only in CR group (P < 0.01). Negative correlation between HtrA2 and WT1 expression was also observed (r = -0.249, P = 0.011). It is concluded that the low expression of HtrA2 and high expression of WT1 are closely related with occurrence and development of acute leukemia, so up-regulating expression of HtrA2 and interfering expression of WT1 may become the targets for leukemia therapy in the future.
Adolescent ; Adult ; Aged ; Cell Line, Tumor ; Female ; High-Temperature Requirement A Serine Peptidase 2 ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; Middle Aged ; Mitochondrial Proteins ; genetics ; metabolism ; Serine Endopeptidases ; genetics ; metabolism ; WT1 Proteins ; genetics ; metabolism ; Young Adult

This study was purposed to explore the expression of Ang-1, Ang-2, Tie-2, Kindlin-2, Kindlin-3 in different leukemia cell lines and bone marrow of acute myeloid leukemia (AML) patients and its clinical significance. The levels of Ang-1, Ang-2, Tie-2, Kindlin-2, Kindlin-3 in bone marrow of AML patients and nontumorous control group as well as leukemia cell lines (K562, KG-1a, U937, HL-60 and Jurkat) were detected by RQ-PCR. The difference of positive rate and expression level between AML patients and controls was analyzed. The relation between 5 genes and their relationship with typing and prognosis of AML were investigated. The results showed that Ang-1, Ang-2, Kindlin-3 expressed in K562, KG-1a, U937, HL-60 and Jurkat cells. Tie-2 only expressed in KG-1a and HL-60 cells. Kindlin-2 expressed in K562, KG-1a and HL-60 cells. All of these 5 genes expressed in AML patients and nontumorous controls. The expression level of Ang-1 and Ang-2 in patients with higher WBC count (≥ 30 × 10(9)/L) was significantly higher than that in patients with lower WBC (< 30 × 10(9)/L, P < 0.001, P < 0.001). The expression level of Ang-1 and Ang-2 in patients with t(8;21) or t(15;17) was significantly lower (P < 0.001, P = 0.005). In the NCCN better-risk group, Ang-1 expressed lower (P = 0.020). The group with lower expression of Ang-1 showed a higher complete remission (CR) rate (P = 0.027). The expression level of Kindlin-2 was lower in AML patients (P = 0.010), lower in patients with higher WBC (≥ 30 × 10(9)/L, P = 0.020), and higher in patients with t(8;21) or t(15;17). The expression levels of both Kindlin-2 and Kindlin-3 were significantly higher after CR (P < 0.001, P = 0.004). It is concluded that Ang-1 closely correlated with the poor prognosis of AML. Kindlin-2 lowly expresses in AML, which has a close relation with the favorable prognosis of AML. Kindlin-2 can be a marker for favorable prognosis of AML.
Adolescent ; Adult ; Aged ; Angiopoietins ; metabolism ; Case-Control Studies ; Cell Line, Tumor ; Female ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; metabolism ; Male ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Prognosis ; Young Adult

This study was aimed to detect the expression of IKZF1 gene isoforms in bone marrow cells of patients with adult acute lymphoblastic leukemia and to investigate the clinical characteristics and prognosis of patients with IK6 isoform. The expression of IKZF1 gene isoforms were measured by nested RT-PCR in 79 newly diagnosed ALL patients. The clinical characteristics of IK6 positive patients and overall survival, disease-free survival of the IK6 positive group and IK6 negative group were compared. The results showed that IK1 and IK2/3 were the functional isoform while the IK4, IK6, IK8 and IK9 were the dominant negative isoform in adult ALL. The dominant negative isoform IK6 accounted for 34.4% in B-ALL patients and accounted for 22.2% in T-ALL patients. The BCR/ABL1 positive rate and the percentage of high risk patients in IK6 positive group was higher than that of IK6 negtive group in B-ALL patients (P = 0.027, P = 0.048). The expression of IK6 isoform did not correlate with sex, age and WBC count of B-ALL and T-ALL patients. The overall survival and disease-free survival of IK6 positive group were both lower than that of IK6 negtive group in Ph negative B-ALL patients (P = 0.009, P = 0.002). It is concluded that IK6 is a main isoform of the expression of IKZF1 gene in adult ALL patients, and can be used as a prognostic factor for guiding treatment in Ph negative B-ALL patients.
Adolescent ; Adult ; Aged ; Female ; Humans ; Ikaros Transcription Factor ; genetics ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; Prognosis ; Protein Isoforms ; genetics ; Young Adult

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients' overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion: Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.
Adult ; B-Lymphocytes ; DNA Mutational Analysis ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis

Aim To investigate the potential mechanism of Jiawei Duhuo Jisheng Mixture regulating intestinal flora in the treatment of knee osteoarthritis(KOA)by 16S rRNA sequencing.Methods Eight-week-old male C57 mice were randomly divided into three groups:sham group,DMM group,and model+Jiawei Duhuo Jisheng Mixture group(Mixture group),6 mice per group.KOA model was induced by destabilization of medial meniscus surgery.16.25 mL·kg-1 dose mixture was given daily to the mixture group,and normal saline was given to the sham and DMM group.After eight weeks,the knee joints and colons of mice were collected,and the knee joints were prepared into paraffin sections,and the cartilage changes were observed with Safranin O-Fast Green and immunohistochemistry staining.16S rRNA sequencing of intestinal contents was performed to observe the changes of intestinal flora.Results Compared with model group,Jiawei Duhuo Jisheng Mixture could significantly reduce cartilage wear and OARSI score(P=0.033 5,P=0.029 5).16S rRNA sequencing showed that Jiawei Duhuo Jisheng Mixtrue could change the intestinal flora richness of KOA model mice,and improve the Alpha diversity(Chao1,Simpson)and Beta diversity(PCoA,NMDS).LefSe analysis showed that there were species with significant difference in abundance among the three groups(P=0.001),mainly including Lactobacillus,Firmicutes,Proteobacteria and other species.MetaCyc analysis indicated that Jiawei Duhuo Jisheng Mixture had effects on various metabolic pathways such as fatty acid,sugar and amino acid of intestinal flora(P<0.05).Conclusions Jiawei Duhuo Jisheng Mixtrue can effectively protect the articular cartilage and delay the progression of KOA.The mechanism may be through regulating the intestinal flora structure,protecting the intestinal barrier and reducing the inflammatory response.

BACKGROUND: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. METHODS: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. RESULTS: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01). CONCLUSIONS There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.
Aged ; Aged, 80 and over ; Blood Glucose ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Glucose Intolerance/epidemiology* ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Skin Diseases/epidemiology*

BACKGROUND: With the rapid spread of novel coronavirus pneumonia (NCP) worldwide and the escalation of prevention and control efforts, the routine medical needs of patients have been restricted. The aims were to investigate medical needs of lung cancer patients and their mental health status during the epidemic periods, so as to provide rational recommendations for subsequent diagnosis and treatment. METHODS: The questionnaire was sent in the form of an electronic questionnaire at 7am on 4th, March, 2020, until 7am 6th, March, 2020, 368 questionnaires were recollected from 25 provinces (autonomous regions/municipalities) in 48 h. RESULTS: Of the 368 patients, 18 patients were excluded as they didn't receive anti-tumor treatment, and 350 patients were included in the final analysis. 229 cases were treated with oral targeted drugs, and 121 cases were treated with chemotherapy or immunotherapy. 41.3% of patients treated with intravenous chemotherapy or immunotherapy experienced treatment discontinuation, and the proportion of treatment discontinuation in chemotherapy or immunotherapy was higher than those treated with oral targeted drugs (21.0%). Whether oral targeted drugs or intravenous chemotherapy or immunotherapy, more than 60% of patients experienced delays in imaging examinations. Nearly one third of patients developed new symptoms or exacerbation of existing symptoms. 26.6%-28.9% of patients have changed their treatment plans through online consultation. During novel coronavirus pneumonia, 40%-75% of lung cancer patients have mental health problems, and more than 95% of patients support government's prevention and control measures. CONCLUSIONS During the emergence of NCP, the medical needs of patients with lung cancer have not been enough, especially those who discontinued chemotherapy or immunotherapy. When medical institution resumes work, priority should be given to them. At the same time, mental health problems of patients should be valued and resolved timely.
Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Betacoronavirus ; physiology ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; virology ; Female ; Humans ; Lung Neoplasms ; drug therapy ; psychology ; Male ; Middle Aged ; Pandemics ; Pneumonia ; epidemiology ; virology ; Pneumonia, Viral ; epidemiology ; virology ; Retrospective Studies