1.Structural insights into the binding modes of lanreotide and pasireotide with somatostatin receptor 1.
Zicheng ZENG ; Qiwen LIAO ; Shiyi GAN ; Xinyu LI ; Tiantian XIONG ; Lezhi XU ; Dan LI ; Yunlu JIANG ; Jing CHEN ; Richard YE ; Yang DU ; Thiansze WONG
Acta Pharmaceutica Sinica B 2025;15(5):2468-2479
Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.
2.Relationship of latent classes of emotional behavior of children with mental disorders with sense of parenting competence and psychological distress of parents
Li SHAN ; Mingyu LI ; Dalei CUI ; Simeng XU ; Lezhi LI
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(6):540-545
Objective:To explore the latent classes of emotional behavior of children with mental disorders, and their relationship with parents' sense of parenting competence and psychological distress.Methods:A survey of 327 parents of children with mental disorders was conducted from September to December 2022 using the general information questionnaire, the sense of parenting competence scale, the Kessler psychological distress scale, and the strengths and difficulties questionnaire (parent version). Mplus 8.0 and SPSS 25.0 softwares were used for statistical analysis.The latent class analysis was used to identify subgroups of children with mental disorders based on their emotional behavior.Multinomial logistic regression was used to analyze the related factors.Results:Latent class analysis showed that the emotional behaviors of children with mental disorders were divided into 3 categories: emotion-conduct problem prominent group (38.53%(126/327)), simple emotional problem group (44.65%(146/327)), and emotion-peer interaction significant group (16.82%(55/327)). The differences among the 3 latent classes were statistically significant (all P<0.05) in terms of parents' parenting competence, satisfaction, and psychological distress scores.Compared with the emotion-conduct problem prominent group, the higher the parental parenting knowledge and parenting competence, the emotional behavior of children with mental disorders tended to be in the simple emotional problem group ( B=0.699, OR=2.011, 95% CI=1.046-3.868; B=0.088, OR=1.092, 95% CI=1.017-1.173). Compared with the " emotion-conduct problem prominent group" , the emotional behavior of children with mental disorders aged 13 to 18 years old tended to be in the " emotion-peer interaction significant group" ( B=1.982, OR=7.255, 95% CI=1.637-32.141). Conclusion:The emotional behavior of children with mental disorders is heterogeneous, and there are differences in sense of parenting competence and psychological distress of parents among different latent classes of children with mental disorders.
3.Status of social avoidance and distress in emerging adults with Type 1 diabetes mellitus and its association with self-management and glycemic control.
Fang LIU ; Lezhi LI ; Rong XU ; Xia LI ; Yuting XIE ; Huilin ZHANG
Journal of Central South University(Medical Sciences) 2020;45(7):834-839
Emerging adult patients with Type 1 diabetes mellitus (T1DM) appear to have a reduced opportunities on learning and exercise, a decreased skill in learning and work, a lower degree of social support due to fear and avoidance of social interaction. This study aimed to assess the level of social avoidance and distress in emerging adults with T1DM, and to explore the correlation between social avoidance and distress and self-management or glycemic control. : A total of 342 T1DM patients aged 18-30 years old were recruited from 8 tertiary hospitals in Hunan Province from September 2014 to February 2019. The questionnaire included general information questionnaire, the Social Avoidance and Distress Scale (SAD), and Self-management Scale of Type 1 Diabetes for Chinese Adults (SMOD-CA). The total scores of SAD in emerging adult patients with T1DM were compared with those of norm. Correlation between glycated hemoglobin (HbA1c) and social avoidance and distress of emerging adult patients with T1DM was analyzed. : The total score of SAD (11.13±6.18) in emerging adults with T1DM was significantly higher than that in healthy adults (=77.06, <0.01). Pearson correlation analysis showed that the scores of SAD, social avoidance subscale, and social distress subscale were negatively correlated with the scores of SMOD-CA (all <0.01), and they were positively correlated with HbA1c (all <0.01). Multivariate linear regression analysis showed that social avoidance and distress, self-management, gender, and educational level were independent influential factors for HbA1c in emerging adults with T1DM. : The degree of social avoidance and distress of emerging adult patients with T1DM is higher than that of healthy people. The higher the degree of social avoidance and distress, the lower the level of self-management and the worse the control of blood sugar. Attention should be paid to social avoidance and distress in emerging adults with T1DM, and targeted interventions should be formulated.
Adolescent
;
Adult
;
Blood Glucose
;
Cross-Sectional Studies
;
Diabetes Mellitus, Type 1
;
Glycated Hemoglobin A
;
analysis
;
Humans
;
Self-Management
;
Surveys and Questionnaires
;
Young Adult
4.Effects of aroma therapy and music intervention on pain and anxious for breast cancer patients in the perioperative period.
Yangfan XIAO ; Lezhi LI ; Yijia XIE ; Junmei XU ; Yan LIU
Journal of Central South University(Medical Sciences) 2018;43(6):656-661
To investigate the effect of the aroma therapy and music intervention on anxious and pain for the breast cancer patients in the perioperative period and the potential mechanisms.
Methods: A total of 100 breast cancer patients who received surgical treatment in the comprehensive hospitals of Hunan province were recruited for this study. Patients were assigned randomly into a control group, an aroma therapy group, a music intervention group, and a joint-therapy group (n=25 per group). The patients in the control group received regular post-surgical nursery, while the patients from other groups received aroma therapy, music intervention, or both in addition to the regular nursery. The scale of anxiety and pain were measured. The measurements were carried at three time points, namely 30 min before the surgery (T1), 30 min after the recovery period of anesthesia (T2), and 4 hours after the removal of anesthesia tubing (T3). Repeated ANOVA was used to perform statistic analysis.
Results: The scale of pain was significantly increased at the post-operation (T2, T3) compared to pre-surgery (T1). The therapeutic group showed significant decrease in pain at post-operation (T3) comparing with the control group (P<0.05). The scale of anxiety was the highest at pre-surgery (T1). During anaesthesia recovery, the anxiety of patients at post-operation T2 and T3 in the therapeutic groups significantly decreased compared with the control group (P<0.05).
Conclusion: Both the aroma therapy and the music therapy can decrease the stress-responsive anxiety and pain for the breast cancer patients in the perioperative period.
Analysis of Variance
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Anxiety
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therapy
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Aromatherapy
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Breast Neoplasms
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nursing
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psychology
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surgery
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Female
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Humans
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Music Therapy
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Pain, Postoperative
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therapy
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Perioperative Period
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Preoperative Care
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Time Factors
5.Clinical studies on patient-controlled intravenous analgesia for postoperative pain relief in breast cancer patients with radical mastectomy
Yangfan XIAO ; Mengyue CHEN ; Yan LIU ; Jinmei SHEN ; Jianhua LIU ; Junmei XU ; Lezhi LI
Journal of Chinese Physician 2016;18(4):505-507
Objective To investigate the analgesic effect and adverse reactions of patient-controlled intravenous analgesia (PCIA) in breast cancer patients with radical mastectomy.Methods A total of 210 breast cancer patients who underwent radical mastectomy was randomly divided into two groups,experimental (group A) and control (group B) groups (n =105 cases per group).Patients in group A was used PCIA for 48 hours analgesia,while group B weas applied routine intramuscular injections of pethidine.Visual analogue score (VAS) at 4,8,12,24,and 48 hours after operation were recorded.Pulse,respiration,and blood pressure were monitored and side effects e.g.existed skin itching,nausea,vomiting,and respiratory repression were observed.Results The VAS of group A patients on 4,8,12,24,and 48 hours were2.02 ± 1.47,1.73 ± 1.38,1.68 ± 0.91,1.44 ± 0.65,and 1.21 ± 0.61,respectively;and the VAS of group B patients were 6.95 ± 1.96,6.42 ± 1.57,5.63 ± 1.66,4.99 ± 1.62,and 3.72 ± 1.46,respectively.The VAS was significantly lower in group A patients than in group B (P < 0.05).The incidence of skin itching,nausea,vomiting,and respiratory repression was also distinctly decreased in group A than in group B (P <0.05).The overall satisfaction of patients in group A (96.2%) was remarkably higher than in group B (67.6%) (P <0.01).Conclusions Patient-controlled intravenous analgesia pump can more effectively alleviate the degree of pain,reduce the incidence of skin itching,nausea,vomiting and respiratory repression,improve the satisfactory degree for analgesia in breast cancer patients with radical mastectomy compared to traditional intramuscular way.
6.Impact of sitagliptin on aspirin resistance in patients with Type 2 diabetes mellitus.
Yanhua LI ; Lezhi LI ; Meijun OU ; Xuefeng XU ; Ming LI ; Chenyang CHEN
Journal of Central South University(Medical Sciences) 2015;40(11):1186-1191
OBJECTIVE:
To explore the impact of sitagliptin on aspirin resistance (AR) in patients with Type 2 diabetes mellitus (T2DM).
METHODS:
A total of 68 cases of AR were chosen from 136 cases of T2DM patients. The clinical data, including blood samples, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), and high sensitive C reactive protein (hs-CRP) were collected. Aenosine diphosphate (ADP) and arachidonic acid (AA) -induced platelet aggregation rate (PAG) were detected in 1, 3, 6 and 12 months after the treatment to evaluate the impact of sitagliptin on AR.
RESULTS:
After 6 months of hypoglycemic treatment, FPG and HbAlc in two groups were at the normal level. The hypoglycemic effect was not obviously different (P>0.05), but the hsCRP and ADP or AA-induced PAG were decreased in the sitagliptin group with statistical significance when compared with the metformin group (P<0.05).
CONCLUSION
Sitagliptin can significantly improve the oxidative stress inflammatory state in T2DM patients and AR, which is independent on blood glucose control.
Aspirin
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pharmacology
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Blood Glucose
;
analysis
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C-Reactive Protein
;
analysis
;
Diabetes Mellitus, Type 2
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drug therapy
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Drug Resistance
;
Glycated Hemoglobin A
;
analysis
;
Humans
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Hypoglycemic Agents
;
pharmacology
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Metformin
;
pharmacology
;
Oxidative Stress
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Sitagliptin Phosphate
;
pharmacology
7.Studies on a new experimental system of erythrocyte regulating IL-8 in patients with primary hepatocarcinoma
Lezhi ZHANG ; Feng GUO ; Yu XU
Medical Journal of Chinese People's Liberation Army 1983;0(02):-
Objective To approach the capacity of erythrocyte regulating IL-8 in patients with primary hepatocarcinoma (PHC) by a new experimental system of hemaimmune. Methods 0.2ml suspension of cancer cells (S180: 5?10~6/ml) or NS were added into 0.2ml anticoagulant suspension of whole blood cells or leukocytes and 0.3ml plasma, then incubated for 1 h at 37℃. The content of IL-8 was determined by ELISA. Results In the patients with PHC, the IL-8 levels (pg/ml) in experimental and control groups of whole blood cells, and in experimental and control groups of leukocytes were 376.35?243.96, 353.64?271.92, 461.27?277.11 and 424.97?278.93, respectively; while in the normal human, they were 11.36?6.93, 4.98?4.35, 29.41?30.66 and 20.77?24.20, respectively. In the patients with PHC, the activation rates of cancer cells in the experimental groups of both whole blood cell and leukocyte were 0.22?0.24 and 0.25?0.53, respectively; while in normal human, they were 2.49?2.33 and 0.75?0.21, respectively. In the patients with PHC, the IL-8 adsorption rate of erythrocyte in both experimental and control groups of whole blood cell were 0.22?0.18 and 0.17?0.33, respectively; while in normal human, they were 1.18?2.29 and 0.86?0.49, respectively. The IL-8 activated rates of erythrocyte in the patients with PHC was much lower than in the normal human (P

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