Objective To explore the therapeutic effect and influencing factors of individualized exercise under continuous glucose profile in patients with typ 2 diabetes mellitus(T2DM).Methods A total of 110 patients with T2DM who were treated in the Department of Endocrinology of our hospital from December 2021 to July 2022 were randomly divided into conventional group and personalized group,with 55 cases in each group.The conventional group was given routine health exercise guidance,the personalized group was given a personalized exercise program.Repeated measurement analysis of variance was used to evaluate the improvement of blood glucose related indicators in the two groups at 3 and 6 months after intervention.Logistic regression was used to analyze the influencing factors of blood glucose(BG)control after 6 months of intervention.Results After 3 and 6 months of intervention,FBG,2 hBG,hemoglobin A1c(HbA1c),mean blood glucose(MBG)and time above target range(TAR)in the personalized group and conventional group were all lower than those before intervention(P<0.05).Time in range(TIR)of glucose within 24 h was higher than that before intervention(P<0.05).After 3 and 6 months of intervention,FBG,2 hBG,HbA1c,MBG and TAR in the personalized group were lower than those in the conventional group at the same time point(P<0.05),and TIR was higher than that in the conventional group at the same time point(P<0.05).After 6 months of intervention,the BG control rate in the personalized group was higher than that in the conventional group(P<0.05).Logistic regression analysis showed that the DM duration,exercise intervention methods and TIR were the influencing factors of BG control.Conclusions Exercise guidance is an effective intervention method to control diabetes.Compared with conventional exercise guidance,personalized exercise program has a better effect on controlling patients'BG level,and has a better effect on patients with short course of disease.

Objective To explore the therapeutic effect and influencing factors of individualized exercise under continuous glucose profile in patients with typ 2 diabetes mellitus(T2DM).Methods A total of 110 patients with T2DM who were treated in the Department of Endocrinology of our hospital from December 2021 to July 2022 were randomly divided into conventional group and personalized group,with 55 cases in each group.The conventional group was given routine health exercise guidance,the personalized group was given a personalized exercise program.Repeated measurement analysis of variance was used to evaluate the improvement of blood glucose related indicators in the two groups at 3 and 6 months after intervention.Logistic regression was used to analyze the influencing factors of blood glucose(BG)control after 6 months of intervention.Results After 3 and 6 months of intervention,FBG,2 hBG,hemoglobin A1c(HbA1c),mean blood glucose(MBG)and time above target range(TAR)in the personalized group and conventional group were all lower than those before intervention(P<0.05).Time in range(TIR)of glucose within 24 h was higher than that before intervention(P<0.05).After 3 and 6 months of intervention,FBG,2 hBG,HbA1c,MBG and TAR in the personalized group were lower than those in the conventional group at the same time point(P<0.05),and TIR was higher than that in the conventional group at the same time point(P<0.05).After 6 months of intervention,the BG control rate in the personalized group was higher than that in the conventional group(P<0.05).Logistic regression analysis showed that the DM duration,exercise intervention methods and TIR were the influencing factors of BG control.Conclusions Exercise guidance is an effective intervention method to control diabetes.Compared with conventional exercise guidance,personalized exercise program has a better effect on controlling patients'BG level,and has a better effect on patients with short course of disease.

Objective:To assess the effectiveness of robot-assisted mandibular angle osteotomy using the FACE-Q questionnaire.Methods:A randomized controlled clinical study was conducted in the Second Affiliated Hospital of Zhengzhou University from January 2022 to June 2023. Patients with mandibular angle hypertrophy aged 18 to 40 years old were recruited as research objects, and a randomization and supply management system (Clinflash IRT 2.0) was used to randomly assign the experimental group and control groups in a 1∶1 ratio. Before surgery, Mimics 21.0 software was used to plan the surgical approach and determine the osteotomy plane based on the head CT data of the two groups. The experimental group underwent robot-assisted mandibular angle osteotomy according to the preoperative osteotomy plan, while the control group underwent traditional manual mandibular angle osteotomy according to the preoperative design. Six months after surgery, patients filled in the FACE-Q craniofacial module scale to evaluate the surgical effect, covering 12 indicators in four aspects: appearance satisfaction (including face, jaw and smile), health-related quality of life (including appearance anxiety, psychology, social interaction and speech), postoperative function (including breathing, diet, face and pronunciation), and adverse reactions. Each indicator was scored from 0 to 100 points, with higher scores indicating better evaluation. SPSS 27.0 software was used to process the data, and the measurement data of normal distribution were expressed by Mean±SD, and t-test was used for comparison between groups. The measurement data of non-normal distribution were expressed by M ( Q1, Q3), and Mann-Whitney U test was used for the comparison between groups. P<0.05 was considered statistically significant. Results:The experimental group included 20 patients, 3 males and 17 females, with an age of (27.6±4.4) years (19 to 38 years); the control group included 20 patients, 4 males and 16 females, with an age of (27.4±3.9) years (19 to 35 years). Six months postoperatively, all patients in both groups had good wound healing, and the mandibular hypertrophy was improved to varying degrees. There were no complications such as facial paralysis, facial deviation, or pain. The FACE-Q questionnaire results showed that in terms of appearance satisfaction, the scores for the three indicators of face, mandible, and smile in the experimental group were (72.2±11.7), 86(77, 92), and (63.2±9.5) points, respectively, all higher than those in the control group, which were (49.2±9.9), 43(35.5, 50), and (48.0±7.7) points, respectively, with statistically significant differences ( P<0.01 for all); in terms of health-related quality of life, except for speech, the scores for the three indicators of appearance anxiety, psychology, and social interaction in the experimental group were higher than those in the control group [(71.0±11.5) points vs.(49.1±10.3) points, (66.7±11.7) points vs.(45.4±10.5) points, (75.0±9.7)points vs.(56.4±8.5) points], with statistically significant differences ( P<0.01 for all); in terms of postoperative function, the score for eating in the experimental group was higher than that in the control group [(83.4±10.7) points vs.(71.0±14.9) points] ( P<0.01), but there were no statistically significant differences in the other three indicators ( P>0.05 for all); in terms of adverse reaction, there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The result of the FACE-Q questionnaire assessment confirmed that robot-assisted mandibular angle osteotomy can significantly improve patients’ postoperative appearance satisfaction, psychological state, social adaptability, and eating function without increasing the incidence of complications.

Objective:To assess the effectiveness of robot-assisted mandibular angle osteotomy using the FACE-Q questionnaire.Methods:A randomized controlled clinical study was conducted in the Second Affiliated Hospital of Zhengzhou University from January 2022 to June 2023. Patients with mandibular angle hypertrophy aged 18 to 40 years old were recruited as research objects, and a randomization and supply management system (Clinflash IRT 2.0) was used to randomly assign the experimental group and control groups in a 1∶1 ratio. Before surgery, Mimics 21.0 software was used to plan the surgical approach and determine the osteotomy plane based on the head CT data of the two groups. The experimental group underwent robot-assisted mandibular angle osteotomy according to the preoperative osteotomy plan, while the control group underwent traditional manual mandibular angle osteotomy according to the preoperative design. Six months after surgery, patients filled in the FACE-Q craniofacial module scale to evaluate the surgical effect, covering 12 indicators in four aspects: appearance satisfaction (including face, jaw and smile), health-related quality of life (including appearance anxiety, psychology, social interaction and speech), postoperative function (including breathing, diet, face and pronunciation), and adverse reactions. Each indicator was scored from 0 to 100 points, with higher scores indicating better evaluation. SPSS 27.0 software was used to process the data, and the measurement data of normal distribution were expressed by Mean±SD, and t-test was used for comparison between groups. The measurement data of non-normal distribution were expressed by M ( Q1, Q3), and Mann-Whitney U test was used for the comparison between groups. P<0.05 was considered statistically significant. Results:The experimental group included 20 patients, 3 males and 17 females, with an age of (27.6±4.4) years (19 to 38 years); the control group included 20 patients, 4 males and 16 females, with an age of (27.4±3.9) years (19 to 35 years). Six months postoperatively, all patients in both groups had good wound healing, and the mandibular hypertrophy was improved to varying degrees. There were no complications such as facial paralysis, facial deviation, or pain. The FACE-Q questionnaire results showed that in terms of appearance satisfaction, the scores for the three indicators of face, mandible, and smile in the experimental group were (72.2±11.7), 86(77, 92), and (63.2±9.5) points, respectively, all higher than those in the control group, which were (49.2±9.9), 43(35.5, 50), and (48.0±7.7) points, respectively, with statistically significant differences ( P<0.01 for all); in terms of health-related quality of life, except for speech, the scores for the three indicators of appearance anxiety, psychology, and social interaction in the experimental group were higher than those in the control group [(71.0±11.5) points vs.(49.1±10.3) points, (66.7±11.7) points vs.(45.4±10.5) points, (75.0±9.7)points vs.(56.4±8.5) points], with statistically significant differences ( P<0.01 for all); in terms of postoperative function, the score for eating in the experimental group was higher than that in the control group [(83.4±10.7) points vs.(71.0±14.9) points] ( P<0.01), but there were no statistically significant differences in the other three indicators ( P>0.05 for all); in terms of adverse reaction, there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The result of the FACE-Q questionnaire assessment confirmed that robot-assisted mandibular angle osteotomy can significantly improve patients’ postoperative appearance satisfaction, psychological state, social adaptability, and eating function without increasing the incidence of complications.

Objective To explore the effect and diagnostic value of G protein coupled receptor 4 (LGR4) on the establishment of neovascularization of HPV infected cervical cancer tissue.Methods From March 2016 to December 2017,thirty cases of HPV infected cervical cancer,cervical precancerous lesion and cervical health in Lan County Maternal and Child Health and Family Planning Service Center were selected as subjects.After the consent of the stubjects,specimens were collected.Immunohistochemical method was used to observe the positive rate of LGR4 in three kinds of tissue specimens.The diagnostic value of LGR4 in differentiation,staging and typing of cervical cancer was observed by screening test,and the expression of related pro-angiogenic factors in LGR4-positive tissues was observed.Results The difference in the expression of LGR4 in healthy tissue,precancerous lesions and cervical cancer tissues was statistically significant (x2=24.104,P =0.000).The positive rate of LGR4 expression in cervical cancer tissue was 80％ (24/30),which was significantly higher than that in healthy group 16.7％ (5/30) and precancerous lesion tissue 50％ (15/30),the differences were statistically significant (P ＜ 0.05).The sensitivity of LGR4 was 80.00％,the specificity was 83.33％,the positive predictive value was 82.76％,the negative predictive value was 80.65％,the diagnostic accuracy was 81.67％ and the Kappa value was 0.63,which has good consistency.The differences of LGR4 positive rate in different age,different degree of differentiation and different clinical stages were statistically significant (P＜0.05).Laboratory results showed that CRP,PCT,VEGF and TGF-β3 in LGR4-positive tissues of cervical precancerous lesions and cervical cancer were significantly higher than those in LGR4-negative tissues,the differences were statistically significant (t=9.247,2.925,39.669,15.348,P＜0.05).Conclusion LGR4 can promote the establishment of neovascularization in cervical cancer and has certain diagnostic value for cervical cancer and cervical precancerous lesions.

OBJECTIVE:To observe clinical efficacy of urinary kallidinogenase in the treatment of acute cerebral watershed in-farct (WSI). METHODS:128 patients with WSI were randomly divided into control group and treatment group,each of the 64 cases. Control group was given Shuxuening 15 ml added into 0.9% Sodium chloride 250 ml,ivgtt,qd;treatment group received urinary kallidinogenase 0.15 PNA added into 0.9% Sodium chloride 100 ml,ivgtt,qd. Both groups were treated for consecutive 14 days. Neurologic impairment score(NIHSS)and clinical efficacy were observed in 2 groups before treatment and 3,7 and 14 days after treatment. The blood specimens were collected after 7 and 14 days treatment,to determine serum levels of TCC. RESULTS:After treatment,NIHSS and total effective rate of treatment group were significantly higher than those of control group,with statis-tical significance(P<0.01). There was no statistical significance in TCC between 2 groups before treatment(P>0.05);7 days af-ter treatment,TCC level of 2 groups increased significantly,to 14 days,and a declive;the treatment group was higher than the control group,with statistical significance (P<0.05). CONCLUSIONS:Urinary kallidinogenase can improve clinical efficacy of WSI significantly,and promote neurologic impairment symptom and TCC levels.

Objective:To detect the inhibitory effects of CAL-101, a selective inhibitor of phosphoinostitide-3'-kinase delta (PI3Kδ), on Burkitt's lymphoma cell line Raji and diffused large B-cell lymphoma cell line SUDHL-10 and elucidate its relative mechanism. Methods:Raji and SUDHL-10 cells were treated with various concentrations of CAL-101. Methyl thiazolyl tetrazolium (MTT) assay was performed to determine the inhibitory effect of CAL-101 on lymphoma cells, and cell apoptosis was measured by Annexin V/PI and DAPI staining. Migration assays were performed with transwell to detect the migration of lymphoma cells derived from the stromal cell line HK. Western blot was used to detect the phosphorylation status of the ERK pathway. MTT and CalcuSyn software analyses were preformed to detect whether or not combining CAL-101 with bortezomib induces synergistic cytoxicity. Results:CAL-101 at con-centrations of 5, 10, 15, and 20μmol/L inhibited cell proliferation in a dose-dependent manner. The proliferation rates of the Raji cells treated with 5, 10, 15, and 20μmol/L for 48 h were 29.17%± 1.23%, 38.15%± 1.51%, 46.46%± 1.78%, and 55.8%± 2.01%, respec-tively, which were significantly higher (P<0.05) than that of the control group (1.15% ± 0.02%). Similar results were found in the SUDHL-10 cells after treatment with CAL-101 (P<0.05). CAL-101 also exerted an apoptotic effect on the lymphoma cells. The apop-totic rates of the Raji cells treated with CAL-101 for 21 h were 22.69%± 3.83%and 49.96%± 7.36%, respectively, which were signifi-cantly higher (P<0.05) than that of the control group (5.23%± 2.04%). Similar results were found in the SUDHL-10 cells (P<0.05). Treatment with 5 and 10 μmol/L CAL-101 dose-dependently inhibited the migration activity of lymphoma cells to stromal cells (P<0.05). Western blot analysis showed that the expression level of ERK phosphorylation protein was significantly downregulated in the cells treated with CAL-101. A synergistic effect between CAL-101 and bortezomib was verified. That is, these two drugs can signifi-cantly inhibit the proliferation of lymphoma cells with CI values less than 1. Conclusion:The PI3Kδ-specific inhibitor CAL-101 sup-pressed the proliferation of Raji and SUDHL-10 cells, induced apoptosis, and inhibited stromal cell-derived migration. This inhibitory effect may be induced by blocking the ERK pathway. Overall, our study indicated that CAL-101 is a novel and potential agent in the therapeutic strategy against aggressive B-cell lymphoma.

OBJECTIVETo elucidate the impact of Hes1 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.

METHODSThe expression levels of Hes1 and p21 in AML patient samples and myeloid leukemia cell lines were analyzed by real-time PCR. Hes1 was up-regulated by retrovirus transfection in AML cell lines and the proliferation capacity were assayed by MTT, cell cycle by Hoechst/PY, apoptosis by AnnexinV.

RESULTSThe expression of Hes1 in primary AML cells and HL-60, U937, KG1a cell lines were 0.67 ± 0.24, 0.59 ± 0.43, 0.42 ± 0.03, and 0.32 ± 0.26, respectively, and p21 were 0.54 ± 0.01, 0.44 ± 0.12, 0.36 ± 0.12, and 0.59 ± 0.43, respectively. Hes1 expression levels after transduction in HL-60, U937, KG1a were 4.9 ± 0.2, 5.2 ± 0.4, 5.8 ± 0.5, respectively. Induced activation of Hes1 led to AML cells growth arrest and apoptosis, which was associated with an enhanced p21 expression. Besides, activated Hes1 led to AML cells growth inhibition in vivo.

CONCLUSIONHes1 could mediate growth arrest and apoptosis in AML cells, which may be a novel target for AML.

Apoptosis ; Basic Helix-Loop-Helix Transcription Factors ; Cell Cycle ; Cell Line, Tumor ; Homeodomain Proteins ; Humans ; Leukemia, Myeloid, Acute ; Transcription Factor HES-1 ; Up-Regulation

OBJECTIVETo investigate the effect of CAL-101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL-2 and Jeko-1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma.

METHODSMTT assay was applied to detect the inhibitory effects of CAL-101 and bortezomib either alone or combined on Z138, HBL-2 and Jeko-1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K-p110σ and p-Akt, Akt, p-ERK and ERK proteins after the cells were exposed to different concentrations of CAL-101. Flow cytometry was employed to assess the apoptosis rate. NF-κB kit was used to determine the changes of location of NF-κB P65, and Western blot was applied to detect the level of caswpase-3 and the phosphorylation of Akt in different groups.

RESULTSCAL-101 and BTZ inhibited the proliferation of Z138, HBL-2 and Jeko-1 cells in a dose- and time-dependent manner. CAL-101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL-101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL-101 combined with BTZ induced pronounced apoptosis (P < 0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL-101, BTZ and CAL-101 + BTZ groups were: (2.6 ± 1.8)%, (40.0 ± 3.0)%, (34.0 ± 1.0)%, and (67.4 ± 1.0)%, respectively; and when drug treatment was given to HBL-2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4 ± 0.6)%, (30.7 ± 5.7)%, (12.0 ± 1.0)%, and (85.0 ± 4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor-κB (NF-κB) and Akt inactivation in the MCL cell lines (P < 0.05), however, the casepase-3 activity was up-regulated.

CONCLUSIONSThe combination of CAL-101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines (Z138, HBL-2 and Jeko-1), which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF-κB.

Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Boronic Acids ; Bortezomib ; pharmacology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Class Ia Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Dose-Response Relationship, Drug ; Drug Synergism ; Formazans ; Humans ; Lymphoma, Mantle-Cell ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; NF-kappa B ; metabolism ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Purines ; administration & dosage ; pharmacology ; Pyrazines ; Quinazolinones ; administration & dosage ; pharmacology ; Signal Transduction ; Software ; Tetrazolium Salts

Objective To investigate the effect of CAL?101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL?2 and Jeko?1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma. Methods MTT assay was applied to detect the inhibitory effects of CAL?101 and bortezomib either alone or combined on Z138, HBL?2 and Jeko?1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K?p110σ and p?Akt, Akt, p?ERK and ERK proteins after the cells were exposed to different concentrations of CAL?101. Flow cytometry was employed to assess the apoptosis rate. NF?κB kit was used to determine the changes of location of NF?κB P65, and Western blot was applied to detect the level of caswpase?3 and the phosphorylation of Akt in different groups. Results CAL?101 and BTZ inhibited the proliferation of Z138, HBL?2 and Jeko?1 cells in a dose? and time?dependent manner. CAL?101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL?101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL?101 combined with BTZ induced pronounced apoptosis (P<0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL?101, BTZ and CAL?101+BTZ groups were:(2.6±1.8)%, (40.0±3.0)%, (34.0±1.0)%, and (67.4±1.0)%, respectively; and when drug treatment was given to HBL?2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4±0.6)%,(30.7±5.7)%, (12.0±1.0)%, and (85.0±4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor?κB ( NF?κB) and Akt inactivation in the MCL cell lines (P<0.05), however, the casepase?3 activity was up?regulated. Conclusions The combination of CAL?101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines ( Z138, HBL?2 and Jeko?1) , which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF?κB.