In order to improve the poor photostability of nifedipine, this study designed a cocrystal based on the principles of crystal engineering and prepared nifedipine-imidazole cocrystal by suspension method. The new cocrystal was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and infrared spectroscopy (IR) to confirm the formation of the cocrystal. The photostability of nifedipine and its cocrystal was measured by powder X-ray diffraction and high-performance liquid chromatography (HPLC). The results showed that the nifedipine-imidazole cocrystal improved the photostability of nifedipine to a certain extent. This study provides guidance for the development of nifedipine cocrystals and the improvement of its druggability.

Objective To investigate the effects and mechanism of circTRIM33-12 on proliferation,apoptosis and epithelial-mesenchymal transition(EMT)of brain glioma cells by miR-191/DAB2 axis.Methods The expressions of circTRIM33-12,miR-191 and DAB2 in brain glioma cell CHG-5 and human normal brain glial epithelial cells HEB were detected by RT-PCR.The cultured CHG-5 cells were divided into the siRNA NC group,the circTRIM33-12 siRNA group,the DAB2 siRNA group;the mimics NC group,the miR-191 mimics group;the circTRIM33-12 WT+mimics NC group,the circTRIM33-12 WT+miR-191 mimics group,the circTRIM33-12 MUT+ mimics NC group,the circTRIM33-12 MUT+miR-191 mimics group;the inhibitor NC group,the miR-191 inhibitor group;the pcDNA+ mimics NC group,the pcDNA-TRIM33-12+mimics NC group,the pcDNA+miR-191 mimics group,the pcDNA-TRIM33-12+miR-191 mimics group;the DAB2 WT+mimics NC group,the DAB2 WT+miR-191mimis group,the DAB2 MUT+mimics NC group,the DAB2 MUT+ miR-191 mimis group.CCK-8 assay was used to detect the effects of the expressions of circTRIM33-12,miR-191 and DAB2 on the prolifera-tion ability of CHG-5 cells;flow cytometry was used to detect the effects of the expressions of circTRIM33-12,miR-191 and DAB2 on the apoptosis of CHG-5 cells;Western blot was used to detect the effects of the expressions of circTRIM33-12,miR-191 and DAB2 on EMT of CHG-5 cells.TargetScan database was used to analyze the correlations among miR-191,circTRIM33-12 and DAB2,and dual luciferase reporter gene assay was used to verify their relationships;RT-qPCR was used to detect the effect of circTRIM33-12 on DAB2 expression through miR-191.Results Compared with HEB cells,the expression of circTRIM33-12 in CHG-5 cells was down-regulated(P<0.01),the expression of miR-191 was up-regulated(P<0.01),and the expression of DAB2 was down-regulated(P<0.01).Compared with the siRNA NC group,the proliferation activity and N-cadherin expression of CHG-5 cells in the circTRIM33-12 siRNA group and the DAB2 siRNA group were significantly increased(P<0.01),while the apoptosis rate and E-cadherin expression were decreased(P<0.01).circTRIM33-12 targeted miR-191,and miR-191 targeted DAB2.Compared with the inhibitor NC group,the proliferation activity and N-cadherin expression of CHG-5 cells in the miR-191 inhibitor group were significantly decreased(P<0.01),while the apoptosis rate and E-cadherin expression were increased(P<0.01).circTRIM33-12 overexpression inhibited CHG-5 cell proliferation and EMT through miR-191.Conclusion circTRIM33-12 may regulate the proliferation,apoptosis and EMT of brain glioma cells through the miR-191/DAB2 axis.

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

This study analyzed the clinical features of 5 children with hereditary spherocytosis (HS) and the characteristics of ANK1 and SPTB gene mutations. All 5 children were confirmed with HS by peripheral blood genetic detection. Anemia, jaundice and splenomegaly were observed in all 5 children. Three children had an increase in erythrocyte osmotic fragility. All 5 children had negative results of the Coombs test, glucose 6 phosphate dehydrogenase test, sucrose hemolysis test, acidified-serum hemolysis test and thalassemia gene test. Peripheral blood smear showed an increase in spherocyte count in one child. High-throughput sequencing revealed ANK1 gene mutations in patients 1 to 3, namely c.3398(exon29)delA, c.4306C>T and c.957(exon9)_c.961(exon9)delAATCT, among which c.3398(exon29)delA had not been reported before. Patient 4 had c.318delGExon3 mutation in the SPTB gene. Patient 5 had mutations in the SPTB and SLC4A1 genes, among which c.3484delC in the SPTB gene was a spontaneous mutation; the mutation site of the SLCA4A1 gene was inherited from the father and was a non-pathogenic gene. This study suggests that anemia, jaundice and splenomegaly are major clinical manifestations of HS children. Most children with HS do not have the typical spherocytic changes. Genetic detection may help with the accurate diagnosis of HS.
Ankyrins ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Spectrin ; genetics ; Spherocytosis, Hereditary ; genetics

OBJECTIVE: To discuss the clinical effects of clomiphene citrate combined with low molecular weight heparin calcium in the treatment of patients with polycystic ovarian syndrome(PCOS)infertility. METHODS: A total of 105 patients with PCOS infertility who were admitted to the Outpatient Department of Women and Children's Hospital of Qingdao University from September 2016 to April 2018 were taken as research subjects.They were randomly divided into observation group(57 cases)and control group(48 cases).The control group received clomiphene citrate for ovulation treatment,the observation group was given clomiphene citrate combined with low molecular weight heparin calcium for ovulation treatment,and the endometrial receptivity changes,pregnancy rate and the incidence of adverse reactions of patients were compared between the two groups.RESULTS: In the observation group,the endometrial thickness,blood flow index(FI),endometrial spiral arterial blood flow resistance index(RI)and pulsatility index(PI)decreased,and the pregnancy rate was better than that in the control group;the difference was statistically significan(t P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).CONCLUSION: Clomiphene citrate combined with low molecular weight heparin calcium in the treatment of polycystic ovary syndrome infertility can improve the treatment efficiency,and is safe and reliable.It is worthy of clinical promotion.

Objective:To explore the relationship between unexplained palpitation in children and head-up tilt test (HUTT).Methods:A total of 142 children with the main symptom of unexplained palpitation were admitted to the Specialist Out-Patient Clinic of Children's Cardiovascular Disease from Sept.2008 to Feb.2017 in the Second Xiangya Hospital,Central South University.Among them,63 cases were male,79 cases were female,with the mean age of (10.12±2.88) years old.The detailed history,physical examinations,conventional 12 electrocardiogram,chest X-ray,echocardiography,myocardial enzymes and thyroid function were all examined.The disorders of heart disease,systemic disease and drug effect were ruled out.The HUTT inspection was then given to them.Results:Among the 142 palpitation cases,79 cases were HUTT positive (55.6％) and 63 cases were HUTT negative (44.4％).The age in HUTT positive patients was older than that in HUTT negative patients (P＜0.05),with no significant difference in gender (P＞0.05).There were three types of hemodynamic changes in HUTT positive patients.Among them,38 cases were postural orthostatic tachycardia syndrome (48.1％),36 cases were the vasovagal syncope vasodepressive type (45.6％) and 5 cases were the vasovagal syncope mixed type (6.3％).There were no hemodynamic types for vasovagal syncope cardioinhibitory type,orthostatic hypotension and orthostatic hypertension.Conclusion:Among the clinically unexplained palpitations children,more than half are caused by unbalanced autonomic nervous function.HUTT can help clear the cause of unexplained palpitations.

Objective To compare the biomechanical characteristics of lengthened sacroiliac screw and long sacroiliac screw fixated in different ways for the treatment of central vertical sacral fractures to provide reference for clinical practice.Methods A finite element model with three dimensions of Tile type C pelvic ring injury (central type Denis Ⅲ fracture of sacrum) was produced.The central sacral fractures were fixated with lengthened sacroiliac screw or long sacroiliac screw in 7 types of models respectively as follows.(1) One long sacroiliac screw was fixated in S1 segment from the right (C1);(2) One long sacroiliac screw was fixated in S2 segment from the right (C2);(3)Two long sacroiliac screws were fixated in S1 and S2 segments respectively from the right (C12);(4) One long sacroiliac screw was fixated in S1 segment from the right and one long sacroiliac screw was fixated in S2 segment from the left (C12hybrid);(5) One lengthened sacroiliac screw was fixated in S1 segment from the right (J1);(6) One lengthened sacroiliac screw was fixated in S2 segment from the right (J2);(7)Two lengthened sacroiliac screws were fixated in S1 and S2 segments respectively from the right (J12).The shift and angle displacement of the central superior surface of sacrum in the case of standing on both feet were measured and compared.The maximum Von Mises stresses in different positions were measured.And various mechanical indices (including stresses of various parts and stress distribution of screws and pelvis,etc) were also quantified and compared.Results The stability of the posterior ring-screw complex was optimal when the sacrum was fixated with S1 & S2 lengthened sacroiliac screws.The maximum Von Mises stresses of screw were affected by sacral segments,namely,S1 ＞ S2 ＞ S1& S2.The maximum Von Mises stress of screws in S1 and S2 segments were similar.The maximum stress of the lengthened sacroiliac screw was lower than that of the long sacroiliac screw.The maximum Von Mises stress of bilateral sacroiliac joints in the lengthened sacroiliac screw fixation model was similar to that of normal pelvis.The maximum stress in the left sacroiliac joint of the long sacroiliac screw fixation model was larger than that of the normal pelvis.The maximum Von Mises stress of screw-bone interface of the long sacroiliac screw fixation model was larger than that of the lengthened sacroiliac screw fixation model.The screw stress distribution of the lengthened sacroiliac screw was superior to that of the long sacroiliac screw,and the screw stress distribution of the double segment fixation was superior to that of the single segment fixation.There was relatively less difference between the pelvic stress distribution of double segment fixation model and that of the normal pelvic model.Conclusion The fixation of S1 & S2 lengthened sacroiliac screws utilized in central sacral fractures of Tile C pelvic ring injury results in a more stable posterior pelvic ringscrew complex,more dispersed screw stress and better pelvic stress distribution which is closed to normal,and can also reduce the risk of internal fixation failure as well as lower back pain.

OBJECTIVETo observe metabolomic changes in urine of chronic superficial gastritis (CSG) patients with Pi-qi deficiency syndrome (PQDS) or Pi-Wei dampness-heat syndrome (PWDHS), thereby providing scientific evidence for syndrome typing of them.

METHODSUrine samples were collected from CSG patients with PQDS/PWDHS and healthy volunteers, 10 in each group. Proton nuclear magnetic resonance spectroscopy (1H-NMR) based metabonomic analysis was performed on urine samples. Contents of related biomarkers were analyzed by principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and urivariate statistical analysis.

RESULTSPLS-DA analysis showed that metabolites among CSG patients with PQDS/PWDHS and healthy volunteers could be mutually distinguished. Seven differentially identified metabolites were screened from urines of CSG patients with PQDS and healthy volunteers included glutamate, methionine, α-oxoglutarate, dimethylglycine, creatinine, taurine, and glucose. Four differentially identified metabolites were screened from urines of CSG patients with PWDHS and healthy volunteers included 2-hydroxybutyric acid, trimethylamine oxide, taurine, and hippuric acid. Eleven differentially identified metabolites were screened from urines of CSG patients with PQDS and PWDHS included fucose, β-hydroxybutyric acid, alanine, glutamate, methionine, succinic acid, citric acid, creatinine, glucose, hippuric acid, and lactic acid.

CONCLUSIONThe metabolic differences of CSG patients PQDS and PWDHS mainly manifested in glycometabolism, lipid metabolism, and amino acids catabolism, and 1H-NMR based metabonomics may be used in classified study of Chinese medical syndrome typing.

Biomarkers ; urine ; Discriminant Analysis ; Gastritis ; urine ; Hot Temperature ; Humans ; Hydroxybutyrates ; Ketoglutaric Acids ; Least-Squares Analysis ; Medicine, Chinese Traditional ; Metabolome ; physiology ; Metabolomics ; Principal Component Analysis ; Proton Magnetic Resonance Spectroscopy ; Qi ; Syndrome