1.Innovation and application of traditional Chinese medicine dispensing promoted through integration of whole-process data elements.
Huan-Fei YANG ; Si-Yu LI ; Chen-Qian YU ; Jian-Kun WU ; Fang LIU ; Li-Bin JIANG ; Chun-Jin LI ; Xiang-Fei SU ; Wei-Guo BAI ; Hua-Qiang ZHAI ; Shi-Yuan JIN ; Yong-Yan WANG
China Journal of Chinese Materia Medica 2025;50(11):3189-3196
As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods*
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Drugs, Chinese Herbal
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Humans
2.Clinical observation of proximal femoral nail antirotation internal fixation in the treatment of Basicervical fracture in the elderly.
Xue-Kun HAN ; Ai-Chun WEI ; Jian-Feng JIANG
China Journal of Orthopaedics and Traumatology 2025;38(7):676-679
OBJECTIVE:
To investigate the clinical efficacy and key techniques of proximal femoral nail antirotation (PFNA) in the treatment of Basicervical fracture.
METHODS:
A retrospective analysis was performed on 23 patients with Basicervical fractures who underwent closed reduction and PFNA internal fixation under C-arm X-ray fluoroscopy between March 2019 and March 2023. The cohort included 9 males and 14 females. The age distributions was as follows:7 individuals aged from 60 to 69 years old, 5 individuals aged from 70 to 79 years old, 9 individuals aged from 80 to 89 years old, and 2 individuals aged from 90 to 99 years old. The operative time, intraoperative blood loss and fracture healing time were recorded. Hip function was evaluated according to the Harris score.
RESULTS:
All 23 patients successfully underwent the operation, with the operation time ranging from 30 to 75 minutes and an average of (60.51±9.82) minutes. The intraoperative blood loss varied from 100 to 180 ml, averaging (145.36±25.21) ml, and the hidden blood loss ranged from 150 to 220 ml, with an average of (189.00±30.12) ml. All 23 patients were followed up, and the duration ranged from 6 to 28 months, with an average of (18.56±6.35) months. All incisions healed well, the fracture healing time ranged from 12 to 15 weeks, with an average of (14.30±1.82) weeks. During the follow-up period, one patient experienced a spiral blade cut-out, and no complications such as internal fixation rupture, avascular necrosis of the femoral head, fracture nonunion, hip varus deformity, or refracture occurred. At the latest follow-up, the results were evaluated by Harris hip function score:17 cases were excellent, 4 cases were good, 1 case was fair, and 1 case was poor.
CONCLUSION
PFNA internal fixation in the treatment of Basicervical fracture has the advantages of simple operation, less trauma, short operation time, rigid fixation, postoperative functional recovery and so on, which is an ideal fixation for elderly Basicervical fracture.
Humans
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Female
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Male
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Aged, 80 and over
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Aged
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Retrospective Studies
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Bone Nails
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Middle Aged
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Fracture Fixation, Internal/methods*
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Fracture Healing
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Fracture Fixation, Intramedullary
3.Percutaneous endoscopic discectomy with lateral approach and dual-channel method for the treatment of highly free lumbar disc herniation.
Qi-Ming CHEN ; Chun-Hua YU ; Gang CHEN ; Han-Rong XU ; Yi-Biao JING ; Yin-Jiang LU ; Shan-Chun TAO ; Jian-Bo WU
China Journal of Orthopaedics and Traumatology 2025;38(9):924-929
OBJECTIVE:
To explore clinical efficacy of percutaneous endoscopic discectomy with a lateral approach and dual-channel method in treating highly free lumbar disc herniation(LDH).
METHODS:
A retrospective analysis was conducted on 54 patients with highly free LDH who were treated with spinal endoscopic techniques from January 2021 to December 2022. Twenty-seven patients were treated with lateral approach dual-channel(lateral approach dual-channel group), including 16 males and 11 females, with an average age of (54.6±10.5) years old. Twenty-seven patients were treated with unilateral biportal endoscopic (UBE group), including 17 males and 10 females, with an average age of (52.9±12.3) years old. The number of intraoperative fluoroscopy, operation time and hospital stay, as well as visual analogue scale (VAS) and Oswestry diability index (ODI) of low back and leg pain between two patients before operation, 1 day, 1, 3, and 12 months after operation, and the efficacy was evaluated by the modified MacNab criteria at 12 mohths after operation.
RESULTS:
All patients were successfully completed surgical and were followed up, the time raged from 12 to 22 months with an average of (13.57±4.12) months. There was no statistically significant difference in operation time between two groups (P>0.05). The hospital stay of lateral approach dual-channel group was (3.9±1.1) days, which was shorter than that of UBE group (6.5±1.4) days, the number of intraoperative fluoroscopy in lateral approach dual-channel group was (12.7±2.1) times, which was more than that in UBE group (6.6±1.3) times, the differences were statistically significant (t=5.197, -7.532;P<0.05). VAS and ODI for low back pain at 1 day and 1 month after operation, and VAS for leg pain at 1 day after operation of lateral approach dual-channel group were superior to those of UBE group, and the differences were statistically significant (P<0.05). However, there were no statistically significant differences in VAS and ODI for low back and leg pain between two groups before operation and 3 and 12 months after operation (P>0.05). VAS and ODI of low back and leg pain were significantly improved at each time point before and after operation in both groups, and the difference were statistically significant (P<0.05). At 12 months after operation, according to the modified MacNab criteria, the excellent and good rates of therapeutic effects between lateral approach dual-channel group and UBE group were 92.6% (25/27) and 88.9% (24/27), respectively, and the difference was not statistically significant (χ2=0.22, P>0.05).
CONCLUSION
For patients with highly free lumbar intervertebral disc protrusion, both of lateral approach dual-channel method and UBE endoscopic surgery are safe and effective. Endoscopic surgery with lateral approach and dual-channel method could be performed under local anesthesia, allowing for the removal of the nucleus pulposus under direct vision. It is simpler, more efficient.
Humans
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Male
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Female
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Intervertebral Disc Displacement/surgery*
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Middle Aged
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Diskectomy, Percutaneous/methods*
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Lumbar Vertebrae/surgery*
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Endoscopy/methods*
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Adult
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Retrospective Studies
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Aged
4.Intramedullary administration of tranexamic acid reduces bleeding in proximal femoral nail antirotation surgery for intertrochanteric fractures in elderly individuals: A randomized controlled trial.
Xiang-Ping LUO ; Jian PENG ; Ling ZHOU ; Hao LIAO ; Xiao-Chun JIANG ; Xiong TANG ; Dun TANG ; Chao LIU ; Jian-Hui LIU
Chinese Journal of Traumatology 2025;28(3):201-207
PURPOSE:
Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals.
METHODS:
A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test.
RESULTS:
The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67% in the TXA group and 47.95% in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups.
CONCLUSION
We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.
Humans
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Tranexamic Acid/administration & dosage*
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Hip Fractures/surgery*
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Male
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Aged
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Female
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Fracture Fixation, Intramedullary/adverse effects*
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Blood Loss, Surgical/prevention & control*
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Antifibrinolytic Agents/administration & dosage*
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Aged, 80 and over
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Bone Nails
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Middle Aged
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Blood Transfusion/statistics & numerical data*
5.Type II Leydig cell hypoplasia caused by LHCGR gene mutation: a case report.
Ke-Xin JIN ; Zhe SU ; Yan-Hua JIAO ; Li-Li PAN ; Xian-Ping JIANG ; Jian-Chun YIN ; Jia-Qiang LI
Chinese Journal of Contemporary Pediatrics 2025;27(2):225-228
The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female
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Humans
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Infant
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Disorder of Sex Development, 46,XY/genetics*
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Leydig Cells/pathology*
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Mutation
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Receptors, LH/genetics*
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Testis/abnormalities*
6.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Arthritis, Rheumatoid/drug therapy*
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Glucocorticoids/therapeutic use*
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Medicine, Chinese Traditional
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Retrospective Studies
7.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
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Body Mass Index
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China/epidemiology*
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Male
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Female
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Middle Aged
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Prospective Studies
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Rural Population/statistics & numerical data*
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Aged
;
Follow-Up Studies
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Adult
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Mortality
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Cause of Death
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Obesity/mortality*
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Overweight/mortality*
8.Construction and practice of smart health and elderly care standard system in Shanghai
Jian WANG ; Mianzhi CHENG ; Xiaohua YE ; Weihua GU ; Chun FAN ; Yuyao JIANG ; Min XU ; Yihan XU ; Yang WANG ; Xiaoyan GU ; Yihua JIANG ; Liying YAO ; Shusheng OUYANG ; Xin LIU ; Xijie YUAN ; Jian CHEN ; Ni YANG ; Qi CHEN ; Jingjing FANG
Journal of Navy Medicine 2025;46(1):83-90
With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.
9.The role of SIRT7 in regulating epithelial-mesenchymal transition(EMT)to promote glioma cell proliferation and migration
Jiang-Ting WANG ; Kai SUN ; Mou GAO ; Gang CHENG ; Wen-Ying LYU ; Chun-Hui ZHOU ; Lei LIANG ; Jian-Ning ZHANG
Medical Journal of Chinese People's Liberation Army 2025;50(1):57-68
Objective To investigate the expression of the histone deacetylase SIRT7 in glioma cells and its impact on epithelial-mesenchymal transformation(EMT),as well as its effects on proliferative,migratory and invasive capabilities of glioma cells.Methods Bioinformatics analysis was conducted on data from glioma patients in the Cancer Genome Atlas(TCGA)and the Chinese glioma Genome Atlas(CGGA)databases to explore the expression of SIRT7 gene in gliomas and its correlation with tumor grading,molecular characteristics and patient clinical prognosis.Glioma cells were randomly divided into control,SIRT7 knockdown,SIRT7 overexpression,drug treatment(10 μmol/L hydrochlorothiazide)and drug(10 μmol/L hydrochlorothiazide)+SIRT7 overexpression groups.The CCK-8 assay,cell scratch assay and Transwell assay were used to observe the effects of upregulating and downregulating SIRT7 expression on glioma cell proliferation,migration and invasion.RT-qPCR and Western blotting were employed to detect the effects of SIRT7 on the expression of neural cadherin(N-cadherin),Vimentin,E-cadherin,transforming growth factor-β(TGF-β),Ki-67,and Smad3 protein in glioma cells.Nude mouse tumor-bearing experiments were conducted to observe the effect of SIRT7 knockdown on glioma growth.Results Higher expression levels of SIRT7 gene were associated with poorer clinical prognosis(P<0.0001).SIRT7 expression levels were significantly correlated with tumor grading and 1p19q coding status(P<0.01).Compared with normal HA cells,glioma cells showed significantly increased SIRT7 expression levels(P<0.01).CCK-8 assay results indicated that,compared with control group,the proliferation activity of glioma cells in SIRT7 knockout group was significantly decreased(P<0.01),while SIRT7 overexpression group showed significantly increased proliferation activity(P<0.01).EdU assay results showed that,compared with control group,the proportion of glioma cells in the proliferative stage was significantly decreased in SIRT7 knockdown group(P<0.01),and significantly increased in SIRT7 overexpression group(P<0.01).Western blotting results revealed that,compared with control group,the protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin were significantly decreased in SIRT7 knockdown group(P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05).SIRT7 overexpression group showed significantly increased protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin(P<0.05),and a significantly decrease in E-cadherin protein expression level(P<0.05).Scratch assay results indicated that,compared with control group,the migration ability of cells in SIRT7 knockdown group and drug group was significantly decreased(P<0.01),and SIRT7 overexpression group showed significantly increased cell migration ability(P<0.05).Compared with drug group,drug+SIRT7 overexpression group exhibited significantly increased cell migration ability(P<0.01).Transwell assay results showed that,compared with control group,the migration and invasion abilities of cells in SIRT7 knockdown group and drug group were significantly decreased(P<0.01),and SIRT7 overexpression group exhibited significantly increased migration and invasion abilities(P<0.01).Compared with drug group,drug+SIRT7 overexpression group showed significantly increased migration and invasion abilities(P<0.01).Nude mouse tumor-bearing assay results indicated that the volume and weight of glioma in SIRT7 knockdown group were significantly reduced compared with control group(P<0.01).Conclusions Glioma patients with high SIRT7 expression have poorer clinical prognosis.SIRT7 can regulate the TGF-β/Smad3 pathway to mediate EMT,promoting the proliferation and migration of glioma cells.SIRT7 knockdown can inhibit the growth of transplanted gliomas in nude mice.
10.DNA Polymerase θ: a Multifunctional and Error-prone DNA End Repair Enzyme
Yao WANG ; Guo-Jiang CHEN ; Jian-Nan FENG ; Yan-Chun SHI ; Jing WANG ; Yuan-Qiang ZHENG
Progress in Biochemistry and Biophysics 2024;51(3):493-503
DNA polymerase theta (Polθ), also known as DNA polymerase θ, is the member of the DNA polymerase A family and plays a crucial role in the repair of DNA double-strand breaks (DSB). Polθ has 3 distinct structural domains: the N-terminal helicase-like domain with a conserved sequence, the C-terminal polymerase domain, and the central domain, which is a disordered sequence connecting these two regions. Notably, Polθ is the only known polymerase in eukaryotes that possesses helicase activity. However, it is also an error-prone polymerase. When DNA DSBs occur, a specialized network consisting of at least 4 pathways, including classical-non homologous end joining (C-NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative-end joining (Alt-EJ), is responsible for repairing DNA damage caused by DSBs. In the absence of major DNA repair pathways like HR, cells rely on Alt-EJ pathway mediated by Polθ to repair damaged DNA and maintain genomic stability. Nevertheless, due to the low fidelity of Polθ, Alt-EJ repair often leads to errors. Depletion of Polθ has shown to increases DSB formation and compromise genomic stability. Conversely, overexpression of Polθ has been associated with increases DNA damage markers and impairs cell cycle progression. As a result, the impact of Polθ on genome stability remains controversial. Furthermore, overexpression of Polθ is frequently observed in cancer and is associated with a characteristic mutational signature and poor prognosis. Depleting Polθ in an HR-deficient background has been shown to impair cell viability, suggesting a synthetic lethal (SL) relationship between Polθ and HR factors. In recent years, targeted chemotherapy drugs that inhibit tumor growth have gained significant attention. However, off-target effects and drug resistance pose challenges for clinical application, particularly with poly-ADP-ribose polymerase inhibitor (PARPi). Blocking Polθ activity in HR-deficient tumor cells has been found to reverse PARPi resistance, making Polθ a very promising therapeutic target in cancer treatment. The availability of crystal structures for both helicase and polymerase domain has facilitated the design of potent inhibitors of Polθ. Currently, several highly specific and effective small molecule inhibitors targeting Polθ, such as Novobiocin, RP-6685, and ART558, have been reported to effectively block various cancers with HR deficiency. The initial success of these inhibitors points to new directions for treating BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.

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