1.Discussion on the Pathogenesis of Osteonecrosis of the Femoral Head Under the System of Non-uniform Settlement During Bone Resorption and Multidimensional Composite Bowstring Working in Coordination with the Theory of Liver-Kidney and Muscle-Bone Based on the Concept of Liver and Kidney Sharing the Common Source
Gui-Xin ZHANG ; Feng YANG ; Le ZHANG ; Jie LIU ; Zhi-Jian CHEN ; Lei PENG ; En-Long FU ; Shu-Hua LIU ; Chang-De WANG ; Chun-Zhu GONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):239-246
From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.
2.Inhibitory effect of miR-133a on liver cancer through tar-geted regulation of G6PD expression
Ya-Dong WANG ; Xue-Jun SUN ; Chun-Yu YANG ; Gui-Ping WANG ; Ming JIN ; He LI ; Jia-Jun YIN
Chinese Journal of Current Advances in General Surgery 2024;27(1):25-29
Objective:To explore if miR-133a is involved in the occurrence and development of hepatocellular carcinoma(HCC)via regulating G6PD.Methods:Bioinformatics analysis predicted the binding sites of miR-133a and G6PD;RT-PCR or western blot was used to assess the expres-sion of miR-133a and G6PD in HCC tissues and the adjacent normal tissues;CCK-8 and flow cy-tometry assays were performed to evaluate the effects of miR-133a/G6PD on cell proliferation,apop-tosis;Fluorescent reporter gene and western blot assays were used to assess the effect of miR-133a on G6PD expression.Results:miR-133a expression was decreased in HCC tissues while G6PD was increased(P0.01);Up-regulation of miR-133a significantly reduced G6PD expression(P<0.01);up-reg-ulation of miR-133a inhibited cell growth and promoted cell apoptosis(P<0.05),whereas these effects induced by miR-133a over-expression were all abolished when G6PD was up-regulated(P<0.01).Conclusion:miR-133a represses the occurrence and development of HCC via targeting G6PD.
3.Multivariate analysis of influencing functional recovery after ankle fracture of type Ⅱ and above supination-external rotation
Chun-Gui HUANG ; Ya-Fei MA ; Jun-Quan WANG
China Journal of Orthopaedics and Traumatology 2024;37(9):910-916
Objective To explore influencing factors of functional recovery after ankle fracture of type Ⅱ degree and above supination-external rotation.Methods Clinical data of 120 patients with ankle fractures of type Ⅱ degree and above supination-external rotation admitted from February 2019 to April 2021 were retrospectively analyzed.According to American Orthopaedic Foot and Ankle Society(AOFAS),patients were divided into excellent group with 73 patients(90 to 100 points),good group with 35 patients(75 to 89 points),and fair group with 12 patients(<50 points).The differences of ankle active range of motion(ROM)and AOFAS score were compared among three groups at the latest follow-up.Multivariate Logistic regression analy-sis was performed to analyze the factors related to functional recovery after ankle fracture of supination-external rotation.Results There were significant differences in postoperative ROM(dorsoextension,plantar flexion,varus and valgus)and com-plications between excellent group and good and acceptable group(P<0.05).Univariate analysis showed there were differences in age above 50 years old,Ⅳ degree of supination-external rotation fracture,lower tibiofibular ligament injury,posterior ankle fracture,no drainage tube placed,infection,antibiotic use time above 7 days(P<0.05).Multivariate Logistic regression analy-sis showed age above 50 years old[OR=2.829,95%CI(1.049,7.628),P=0.040],Ⅳ degree fracture of supination-external ro-tation[OR=6.13,95%CI(1.153,32.593),P=0.033],lower tibiofibular ligament injury[OR=10.785,95%CI(3.338,34.894),P=0.000],and posterior ankle fracture[OR=6.349,95%CI(1.869,21.560),P=0.003]were independent risk factors for func-tional recovery after ankle fracture of supination-external rotation(P<0.05).Conclusion The postoperative excellent outcome of ankle fracture was good,and the recovery of joint motion was better.The older age of patient,Ⅳ degree of supination-exter-nal rotation fracture,the lower tibiofibular ligament injury,and posterior ankle fracture are all adverse factors affecting func-tional recovery after supination-external rotation ankle fracture.In clinical,effective measures should be taken to deal with these influencing factors,and strive to improve the functional recovery after the operation of this type of fracture and reduce the occurrence of related complications.
4.Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study.
Mei ZHANG ; Ke PENG ; Xiao ZHANG ; Yi Shu LIU ; Xiao Ying LIU ; Gui Yuan HAN ; Yu SHI ; Zheng Jing HUANG ; Chun LI ; Zhen Ping ZHAO ; Li Min WANG ; Yi Chong LI
Biomedical and Environmental Sciences 2023;36(4):313-323
OBJECTIVE:
To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.
METHODS:
A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.
RESULTS:
The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).
CONCLUSION
Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.
Humans
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Adult
;
Middle Aged
;
Aged
;
Cross-Sectional Studies
;
Prevalence
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East Asian People
;
Dyslipidemias/prevention & control*
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China/epidemiology*
;
Cholesterol, HDL
;
Risk Factors
;
Triglycerides
5.To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult
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Humans
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Adolescent
;
Imatinib Mesylate/adverse effects*
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Incidence
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Antineoplastic Agents/adverse effects*
;
Retrospective Studies
;
Pyrimidines/adverse effects*
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
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Treatment Outcome
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Benzamides/adverse effects*
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Leukemia, Myeloid, Chronic-Phase/drug therapy*
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Aminopyridines/therapeutic use*
;
Protein Kinase Inhibitors/therapeutic use*
6.Clinical features and prognosis of core binding factor acute myeloid leukemia children in South China: a multicenter study.
Bi Yun GUO ; Yue WANG ; Jian LI ; Chun Fu LI ; Xiao Qin FENG ; Min Cui ZHENG ; Si Xi LIU ; Li Hua YANG ; Hua JIANG ; Hong Gui XU ; Xiang Ling HE ; Hong WEN
Chinese Journal of Pediatrics 2023;61(10):881-888
Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
Male
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Female
;
Humans
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Child
;
Retrospective Studies
;
RUNX1 Translocation Partner 1 Protein/genetics*
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Core Binding Factor Alpha 2 Subunit/therapeutic use*
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Prognosis
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Leukemia, Myeloid, Acute/genetics*
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Cytarabine/therapeutic use*
;
Oncogene Proteins, Fusion/genetics*
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Chromosome Aberrations
7.Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome.
Dan Ying CHENG ; Peng GUO ; Feng Xia SUN ; Xiao Jing WANG ; Wei LI ; Qin CHEN ; Gui Qin ZHOU ; Rong Bing WANG ; Hui Chun XING
Chinese Journal of Hepatology 2023;31(6):608-613
Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.
Humans
;
Antiviral Agents/therapeutic use*
;
Hepatitis B, Chronic/drug therapy*
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Liver Cirrhosis/drug therapy*
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Prospective Studies
;
Treatment Outcome
8.The influence of sacroiliac joint reduction quality on the clinical effect of bionic reduction and internal fixation for pelvic ring injury.
Chun Gui LIU ; Kun ZHANG ; Dong Yang LI ; Da Shuang LI ; Rui LI ; Xing WEI ; Yan ZHUANG ; Hu WANG
Chinese Journal of Surgery 2022;60(9):866-872
Objective: To examine the influence of sacroiliac joint reduction quality on the clinical effect of bionic reduction and internal fixation for pelvic ring injury. Methods: From January 2014 to February 2019,the clinical data of 78 patients diagnosed with pelvic ring injury involving sacroiliac joints and treated with bionic reduction and internal fixation at Honghui Hospital Affiliated to Medical College of Xi'an Jiaotong University were retrospectively analyzed.There were 48 males and 30 females,aged (48.3±8.3)years (range:28 to 68 years).After bionic reduction and internal fixation,the patients were grouped according to the maximum displacement distance (d) of sacroiliac joint residual on the damaged side measured by CT examination. Patients with d≤5 mm were included in anatomical bionic reduction group,and patients with d>5 mm were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,according to the direction of residual displacement,the patients were divided into separation displacement group and anterior-posterior displacement group. The X-ray examination was performed immediately and at the last follow-up after operation.If sacroiliac joint was relocated,or internal plant loosening,displacement,fracture and re-displacement of fracture,it was defined as internal fixation failure.Majeed pelvic fracture scoring system was used to evaluate the postoperative functional status of the two groups,and visual analogue scale (VAS) was used to evaluate the postoperative pain.Comparison between groups was performed by completely random design ANOVA,χ2 test,Fisher's exact test,Mann-Whitney U and Kruskal-Wallis H test. Results: According to the CT examination,28 cases were included in anatomical bionic reduction group,and 50 cases were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,27 cases were divided into separation displacement group and 23 cases were in anterior-posterior displacement group.There was no significant difference in general data among anatomical bionic reduction group,separation displacement group and anterior-posterior displacement group (P>0.05). The follow-up time was (37.8±6.6) months (range:25 to 51 months). At the last follow up,the excellent and good rate of Majeed score in anatomical bionic reduction group was 96.4%(27/28),which was better than that in separation displacement group(74.1%(20/27)) and anterior-posterior displacement group (30.4%(7/23)),the difference was statistically significant (Z=-6.479,P<0.01;Z=-6.256,P<0.01); and the good rate of the separation displacement group was better than that of the anterior-posterior displacement group(Z=-3.607,P<0.01).The VAS of anatomical bionic reduction group (17 cases with 0 point, 11 cases with 1 to 3 points) were lower than that of the displacement group (6 cases with 0 point,16 cases with 1 to 3 points,5 cases with 4 to 6 points) and anterior-posterior displacement group (3 cases with 0 point,7 cases with 1 to 3 points,13 cases with 4 to 6 points),the difference was statistically significant (Z=-3.515,P<0.01;Z=-3.506,P<0.01),and there was no difference between separation displacement group and anterior-posterior displacement group.Total of 8 cases of internal fixation failure occurred,and the failure rate of anatomical bionic reduction group (0,0/28) was lower than that of the separation displacement group (11.1%,3/27) and anterior-posterior displacement group (21.7%,5/23) (P=0.111,P=0.014),and there was no difference between separation displacement group and anterior-posterior displacement group(P=0.444). Conclusions: In the bionic reduction and internal fixation of pelvic fracture involving sacroiliac joint injury,the functional status,pain and internal fixation failure rate of patients with anatomical bionic reduction of sacroiliac joint are significantly better than those in the non-anatomical bionic reduction.The functional recovery of patients with separation displacement is better than that of the patients with anterior and posterior displacement.
Bionics
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Bone Screws
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Female
;
Fracture Fixation, Internal
;
Fractures, Bone/surgery*
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Humans
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Male
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Retrospective Studies
;
Sacroiliac Joint/surgery*
9.Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in children with autism spectrum disorder.
Zheng LI ; Gui-Yuan XIAO ; Chun-Yan HE ; Xia LIU ; Xin FAN ; Yan ZHAO ; Nian-Rong WANG
Chinese Journal of Contemporary Pediatrics 2022;24(2):186-191
OBJECTIVES:
To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD.
METHODS:
A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups.
RESULTS:
The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001).
CONCLUSIONS
The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.
Autism Spectrum Disorder
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Autistic Disorder
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Child
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Child, Preschool
;
Female
;
Humans
;
Insulin-Like Growth Factor Binding Protein 3
;
Insulin-Like Growth Factor I
;
Male
10.Functional characterization of SLC12A1 gene variants in 3 patients with Bartter syndrome type Ⅰ.
Yu Gen SHA ; Chun Li WANG ; Zhi Wei DU ; Bi Xia ZHENG ; Wei ZHOU ; Fei ZHAO ; Gui Xia DING ; Ai Hua ZHANG
Chinese Journal of Pediatrics 2022;60(2):129-133
Objective: To clarify the molecular basis of patients with Bartter syndrome type I and explore the therapeutic effect of trafficking-defective variations by chemical chaperone 4-Phenylbutyric acid(4-PBA). Methods: The clinical characteristics, laboratory findings and genetic data of 3 patients diagnosed with Bartter syndrome type I who were admitted to Department of Nephrology, Children's Hospital of Nanjing Medical University from 2017 to 2018 were retrospectively analyzed. Wild type and variant SLC12A1 gene constructs were transiently overexpressed in HEK293 cells. Western blotting was used to detect the expression levels of Na+-K+-2Cl-cotransporter(NKCC2) protein. Immunofluorescent staining was applied to investigate the subcellular localization of NKCC2 protein. In addition, the effect of the chemical chaperone 4-PBA on the expression and localization of the SLC12A1 gene variants was investigated. Unpaired t test was used for statistical analysis of 4-PBA treatment. Results: All the 3 patients (2 males and 1 female), aged 3.0, 4.0 and 1.2 years, respectively. All patients had antenatal onset with polyhydramnios and were born prematurely. After birth, all patients presented with hypochlorine alkalosis accompanied by hypokalemia and hyponatremia. Sequencing analysis revealed that the 3 patients were homozygotes or compound heterozygotes for variants in the SLC12A1 gene. In HEK293 cells, the surface expression of NKCC2 in 3 variants (p.L463S, p.L479V, p.507-510del) are all lower than in wild type (0.718±0.039, 0.287±0.081, 0.025±0.156 vs. 1.001±0.028, t=5.92, 8.35, 30.49, all P<0.01). Moreover, the total protein expression of p.L479V and p.507-510del group were all lower than that in wild type group (0.630±0.032, 0.043±0.003 vs. 1.000±0.111, t=3.21, 8.65, all P<0.05). 4-PBA treatment increased the mature protein expression level of the p.L463S and p. L479V group in 4-PBA treatment group are all higher than the untreated group (0.459±0.018 vs. 1.123±0.024, 0.053±0.012 vs. 1.256±0.037, t=2.75, 18.35, all P<0.05). Cytoplasmic retention of the L479V and 507-510del variants were observed by immunofluorescent staining. 4-PBA treatment could rescue a number of NKCC2 L479V variants to the membrane. Conclusions: The 3 SLC12A1 variants cause expression or subcellular localization defects of the protein. The findings that plasma membrane expression and activity can be rescued by 4PBA might help to develop novel therapeutic strategy for Bartter syndrome type Ⅰ.
Bartter Syndrome/genetics*
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Child, Preschool
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Female
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HEK293 Cells
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Homozygote
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Humans
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Infant
;
Male
;
Pregnancy
;
Retrospective Studies
;
Solute Carrier Family 12, Member 1/genetics*

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