Objective To evaluate the effect of morphine on synaptic long-term potentiation (LTP) in the spinal dorsal horn evoked by electric stimulation of sciatic nerve in rats. Methods Twenty-seven healthy male SD rats aged 60-90 d weighing 180-200 g were randomly divided into 4 groups: group Ⅰ control (group C, n=7), group Ⅱ morphine (group M, n=7), group Ⅲ naloxone (group N, n=6), and group Ⅳ morphine + naloxone (group MN, n=7). The animals were anesthetized with intraperitoneal 10% urethane 1 g/kg, intubated and then mechanically ventilated. The bipolar insulated stainless steel recording electrode (impedance 0.5-1 MΩ, diameter 0.1 mm) was inserted into the left side of the spinal dorsal horn at T13-L1 to stimulate the left side of the sciatic nerve. Single square pulses (15 V, 0.5 ms, 1/60 Hz for 30 min) was applied to evoke spinal field potentials. Normal saline 10 μl, morphine 10 μl (15 μg/μl), naloxone 10 μl (2.5 μg/μl), and the mixture 10 μl of naloxone 5 μl (2.5 μg/μl) and morphine 5 μl (15 μg/μl) was gradually instilled over 2 rain in the 4 groups respectively. Five minutes later, high-frequency and intensity tetanic stimulation (30-40 V, 0.5 ms, 100 Hz, given in 4 trains of 1-s duration at 10-s intervals) was used to induce LTP. Then single square stimuli (15 V, 5 ms, 1/60 Hz) were applied to the sciatic nerve for 210 min. The amplitude and latency period of the field potential were recorded 30 min before tetanic stimulation, and 0-30, 35-60, 65-120 and 125-210 min after titanic stimulation. Results Compared with group C, the amplitude of the field potential was significantly decreased and the latency period prolonged in group M and MN, but there was no significant difference in the above indices between group N and C. Compared with group M, the amplitude of the field potential was significantly increased and the latency period shortened in group MN. Compared with those 30 min before the tetanic stimulation, the amplitude of the field potential was significantly increased and latency period shorted at the time points after the tetanie stimulation in group C and N, the amplitude of the field potential was significantly decreased and latency period prolonged at the time points after the tetanie stimulation in group M, and the amplitude of the field potential was significantly increased 0-30 and 35-60 min after the tetanic stimulation and latency period shortened 0-30 min after the tetanie stimulation, the amplitude of the field potential was significantly decreased and latency period prolonged 65-120 and 125-210 min after the tetanic stimulation in group MN. Conclusion Morphine can inhibit synaptic LTP in the spinal dorsal horn evoked by electric stimulation of sciatic nerve in rats, and it may be one of the mechanisms of the central sensitization inhibition.

[Summary] The effects of lipid components on insulin secretion in patients with type 2 diabetes(T2DM) and control subjects were explored. The results demonstrated that in control group, disposal index( DI)0 was positively correlated with high density cholesterol(HDL-C), while DI30 was negatively correlated with total cholesterol(TC), triglycerides( TG) and low density cholesterol ( LDL-C), and DI120 was also negatively correlated with TC and LDL-C. In T2DM group, DI0 was negatively correlated with TC and LDL-C, DI30 was negatively correlated with TC, TG, LDL-C and TG/ HDL-C, DI120 was negatively correlated with TC, TG, LDL-C and TG/ HDL-C.

Objective The variation of serum thyroid hormones within the euthyroid range may be associated with insulin sensitivity.The study was to investigate whether the variation of thyroid hormones within the euthyroid range could influence insulin sensitivity in elderly patients with type 2 diabetes mellitus (T2DM). Methods 200 elderly inpatients and outpatients with type 2 diabetes were collected from September 2013 to May 2014 in our hospital for T2DM group.150 normal controls with normal glucose metabolism were taken as the control group.Blood samples were collected after 75g oral glucose tolerance test(OGTT) on all the re-search objects.Questionaire survey, physical examination and related metabolic index test were also done on them .Chemilumines-cence method were applied to detect their insulin, thyroid stimulating hormone(TSH), FT3 and FT4. Results FT3 levels were significantly lower in T2DM group than in control group[(4.05 ±0.27 )pmol/L vs (4.61 ±0.5)pmol/L), P<0.05].TSH levels were significantly higher in T2DM group than in control group[(2.75 ±1.07) IU/mL vs (2.28 ±0.89) IU/mL, P<0.05], while there was no significant difference as to FT4 levels between these two groups.All subjects were divided into three groups according to the tertiles of FT3 level, Matsuda index of high FT3 level group were significantly higher in comparison to middle and low FT3 level groups, while there was no significant difference as to HOMA-IR in the three groups.FT3 levels were negatively correlated with HO-MA-IR and positively correlated with Matsuda index .After stepwise regression analysis, there was significant positive association be-tween FT3 and Matsuda index. Conclusion Thyroid hormone especially FT3 is significantly associated with insulin resistance .FT3 may participate in the development of type 2 diabetes, which pro-vides a new treatment for T2DM.

OBJECTIVE: To investigate the effects of down-regulating of c-Met expression to the proliferation, invasiveness and apoptosis of human multiple myeloma RPMI 8226 cells. METHODS: According to transfection the RPMI8226 cells were dividide into RPMI 8226 (untreated RPMI 8226), RPMI 8226 /shRNA-Met and RPMI8226/shRNA-control group, respectively. Protein expression level of c-Met was detected by Western blot so as to evaluate transfection condition; the proliferation of the cells was detected by MTT; apoptosis and cycle of the cells were detected by flow cytometry; effect of c-Met/shRNA on RPMI 8226 cell adhesion was detected by RPMI 8226 cell adherence to ECM (Fn and Matrigel) and ECV304 cells. Invasiveness of RPMI 8226 cell was detected by Transwell assay. RESULTS: The c-Met short hairpin RNA (shRNA) was successfully transfected into RPMI 8226 cells, and could inhibit the expression of c-Met significantly. The down-regulation of c-Met could inhibit the proliferation of RPMI 8226 cells significantly. The percentage of cells in the G/G phase and apoptotic rate (sub-G) in the RPMI 8226/shRNA-Met group were higher than those in the control group, the adhesion rate and the number of migrated RPMI 8226/shRNA-Met cells were decreased significantly as compared with control group. There were no significant differences in each indexes between RPMI 8226/shRNA-control and control group. CONCLUSION Knockdown of c-Met can affect the proliferation, adherence, invasiveness and apoptosis of human multiple myeloma RPMI 8226 cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; RNA, Small Interfering

OBJECTIVE: To compare the treatment outcome and prognosis of the newly-treated myc METHODS: 152 double-expression lymphoma patients (myc RESULTS: The median age of 152 DEL patients was 60.5 years old (15-87 years old). 85 patients (55.9%) were Ann Arbor stage III/IV. There was no significant difference in clinical data between the patients in the two groups. Multivariate Cox regression analysis showed that bcl-6 expression, ECOG score, and stage were the independent prognostic factors for the entire group of DEL patients. There was no statistical difference in ORR between the patients in the two groups (χ2=0.749, P=0.387). Kaplan-Meier survival analysis showed that PFS and OS of the bcl-6 CONCLUSION bcl-6
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Prednisolone ; Prognosis ; Vincristine/therapeutic use* ; Young Adult

Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.
Humans ; Gene Editing ; CRISPR-Cas Systems ; Adenine ; HEK293 Cells ; Mutation ; Glucose-6-Phosphatase/metabolism*

Liver cancer is one of the most threatening diseases to the human body， and most patients are already in the advanced stage at the time of diagnosis， resulting in an extremely high mortality rate. The diagnosis and treatment of early-stage liver cancer is the key to improving the prognosis of patients. Medical imaging is an important method that assists in the diagnosis of liver cancer， and currently， intelligent image recognition technology based on medical imaging data has been widely applied in the field of medical diagnosis and has good application prospects. This article reviews the current status of research on artificial intelligence （AI） methods for the diagnosis of focal liver lesions based on liver medical images and proposes the advantages and shortcomings of current AI diagnosis， so as to provide new research ideas for the intelligent diagnosis of liver cancer in the future.

OBJECTIVE: To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis. METHODS: A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome. RESULTS: All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the CONCLUSIONS For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.
Child ; Child, Preschool ; Fever/etiology* ; Humans ; Infant ; Lymphadenitis/diagnosis* ; Pharyngitis/drug therapy* ; Pyrin ; Retrospective Studies ; Stomatitis, Aphthous/genetics*

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation