1.Rehmanniae Radix Iridoid Glycosides Protect Kidneys of Diabetic Mice by Regulating TGF-β1/Smads Signaling Pathway
Hongwei ZHANG ; Ming LIU ; Huisen WANG ; Wenjing GE ; Xuexia ZHANG ; Qian ZHOU ; Huani LI ; Suqin TANG ; Gengsheng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):56-66
ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides (RIG) on the kidney tissue of streptozotocin (STZ)-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group, and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model, metformin (250 mg·kg-1), catalpol (100 mg·kg-1), low-dose RIG (RIG-L, 200 mg·kg-1) and high-dose RIG (RIG-H, 400 mg·kg-1) groups (n=11). Mice in each group were administrated with corresponding drugs, while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention, an oral glucose tolerance test (OGTT) was performed, and the area under the curve (AUC) was calculated. After mice were sacrificed, both kidneys were collected. The body weight, kidney weight, and fasting blood glucose (FBG) were measured. Biochemical assays were performed to measure the serum levels of triglycerides (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). Enzyme-linked immunosorbent assay (ELISA) was employed to determine the serum level of fasting insulin (FINS), and the insulin sensitivity index (ISI) and homeostatic model assessment for insulin resistance (HOMA-IR) were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method (IHC) was employed to assess the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), and collagen-3 (ColⅢ) in the kidney tissue. The protein levels of TGF-β1, cell signal transduction molecule 3 (Smad3), matrix metalloproteinase-9 (MMP-9), and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group, the model group showcased decreased body weight and ISI (P<0.01), increased kidney weight, FBG, AUC, FINS, HOMA-IR, TC, TG, SCr, and BUN (P<0.01), glomerular hypertrophy, capsular space narrowing, and collagen deposition in the kidney, up-regulated protein levels of IL-1, IL-6, TNF-α, TGF-β1, ColⅢ, and Smad3 (P<0.01), and down-regulated protein level of MMP-9 (P<0.01) in the kidney tissue. Compared with the model group, the treatment groups had no significant difference in the body weight and decreased kidney weight (P<0.05, P<0.01). The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin, catalpol, and RIG-L groups after treatment for 6-8 weeks (P<0.01). The AUC in the RIG-L, RIG-H, and metformin groups decreased (P<0.05, P<0.01). The levels of TC, SCr, and BUN in the serum of mice in each treatment group became lowered (P<0.05, P<0.01). The level of TG declined in the RIG-L, RIG-H, and metformin groups (P<0.05, P<0.01). The serum level of FINS declined in the catalpol, RIG-L, and metformin groups (P<0.01). Compared with the model group, the treatment groups showed decreased HOMA-IR (P<0.01), increased ISI (P<0.01), alleviated pathological changes in the kidney tissue, and down-regulated expression of IL-1 and TGF-β1. In addition, the protein levels of IL-6, TNF-α, and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated (P<0.05, P<0.01), and the protein levels of IL-6, TNF-α, and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β1, Smad3, and ColⅢ in the RIG-H and metformin groups were down-regulated (P<0.01). Compared with that in the model group, the protein level of MMP-9 was up-regulated in each treatment group (P<0.01). ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β1/Smads signaling pathway.
2.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
3.Comparison of the effects of three time series models in predicting the trend of erythrocyte blood demand
Yajuan QIU ; Jianping ZHANG ; Jia LUO ; Peilin LI ; Mengzhuo LUO ; Qiongying LI ; Ge LIU ; Qing LEI ; Kai LIAO
Chinese Journal of Blood Transfusion 2025;38(2):257-262
[Objective] To analyse and predict the tendencies of using erythrocyte blood in Changsha based on the autoregressive integrated moving average (ARIMA) model, long short-term memory (LSTM) and ARIMA-LSTM combination model, so as to provide reliable basis for designing a feasible and effective blood inventory management strategy. [Methods] The data of erythrocyte usage from hospitals in Changsha between January 2012 and December 2023 were collected, and ARIMA model, LSTM model and ARIMA-LSTM combination model were established. The actual erythrocyte consumption from January to May 2024 were used to assess and verify the prediction effect of the models. The extrapolation prediction accuracy of the models were tested using two evaluation indicators: mean absolute percentage error (MAPE) and root mean square error (RMSE), and then the prediction performance of the model was compared. [Results] The RMSE of LSTM model, optimal model ARIMA(1,1,1)(1,1,1)12 and ARIMA-LSTM combination model were respectively 5 206.66, 3 096.43 and 2 745.75, and the MAPE were 18.78%,11.54% and 9.76% respectively, which indicated that the ARIMA-LSTM combination model was more accurate than the ARIMA model and LSTM model, and the prediction results was basically consistent with the actual situation. [Conclusion] The ARIMA-LSTM model can better predict the clinical erythrocyte consumption in Changsha in the short term.
4.Mechanism of Xinnao shutong capsule alleviating cerebral ischemia-reperfusion injury in rats by regulating ferroptosis
Huani LI ; Changhe LIU ; Xiaoyan GUO ; Xin ZHONG ; Wei ZHANG ; Wenjing GE
China Pharmacy 2025;36(3):306-311
OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury (CIRI) in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group, model group, Xinnao shutong low-dose, high-dose group (220, 440 mg/kg), Ginkgo biloba leaves extract group (positive control, 150 mg/kg). Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days. Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model; the samples were taken 24 h after the operation; the cerebral infarction area of rats was detected, and the cerebral infarction rate was calculated. The pathological changes of brain tissues were observed, and the levels of lipid peroxide (LPO), malondialdehyde (MDA) and glutathione (GSH) in cerebral tissue were detected; mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1) and glutathione peroxidase 4 (GPX4) were all detected in cerebral tissue of rats. RESULTS Compared with model group, the cerebral infarction rate, the content of total iron in cerebral tissue and serum level of LPO (except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group) were all decreased significantly in G. biloba leaves extract group and Xinnao shutong groups (P<0.05 or P<0.01); the serum level of GSH, the protein and mRNA expressions of Nrf2, HO-1 and GPX4 were all increased significantly (P<0.05 or P<0.01). The pathological damage to brain tissue was reduced, the number of nerve cells increased, the edema was alleviated, and the nuclear membrane was flattened. CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI, the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.
5.STAR Guideline Terminology (I): Planning and Launching
Zhewei LI ; Qianling SHI ; Hui LIU ; Xufei LUO ; Zijun WANG ; Jinhui TIAN ; Long GE ; Yaolong CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):216-223
To develop a guideline terminology system and promote its standardization, thereby enhancing medical staff's accurate understanding and correct application of guidelines. A systematic search was conducted for guideline development manuals and method ological literature (as of October 25, 2024). After screening, relevant terms from the guideline planning and launching stages were extracted and standardized. The term list and definitions were finalized through discussion and evaluation at a consensus conference. A total of 36 guideline manuals and 14 method ological articles were included, and 27 core terms were identified. The standardization of guideline terminology is essential for improving guideline quality, facilitating interdisciplinary communication, and enhancing other related aspects. It is recommended that efforts to advance the standardization and continuous updating of the terminology system should be prioritized in the future to support the high-quality development of guidelines.
6.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
7.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
8.Effect and mechanism of Bufei Decoction on improving Klebsiella pneumoniae pneumonia in rats by regulating IL-17 signaling pathway.
Li-Na HUANG ; Zheng-Ying QIU ; Xiang-Yi PAN ; Chen LIU ; Si-Fan LI ; Shao-Guang GE ; Xiong-Wei SHI ; Hao CAO ; Rui-Hua XIN ; Fang-di HU
China Journal of Chinese Materia Medica 2025;50(11):3097-3107
Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals
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Interleukin-17/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
Rats
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Male
;
Klebsiella pneumoniae/physiology*
;
Klebsiella Infections/immunology*
;
Humans
;
Lung/drug effects*
9.Development and Initial Validation of the Multi-Dimensional Attention Rating Scale in Highly Educated Adults.
Xin-Yang ZHANG ; Karen SPRUYT ; Jia-Yue SI ; Lin-Lin ZHANG ; Ting-Ting WU ; Yan-Nan LIU ; Di-Ga GAN ; Yu-Xin HU ; Si-Yu LIU ; Teng GAO ; Yi ZHONG ; Yao GE ; Zhe LI ; Zi-Yan LIN ; Yan-Ping BAO ; Xue-Qin WANG ; Yu-Feng WANG ; Lin LU
Chinese Medical Sciences Journal 2025;40(2):100-110
OBJECTIVES:
To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels.
METHODS:
The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT).
RESULTS:
The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049).
CONCLUSIONS
The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans
;
Adult
;
Male
;
Attention/physiology*
;
Female
;
Middle Aged
;
Reproducibility of Results
;
Young Adult
;
Psychometrics
10.Protocol for development of Guideline for Interventions on Cervical Spine Health.
Jing LI ; Guang-Qi LU ; Ming-Hui ZHUANG ; Xin-Yue SUN ; Ya-Kun LIU ; Ming-Ming MA ; Li-Guo ZHU ; Zhong-Shi LI ; Wei CHEN ; Ji-Ge DONG ; Le-Wei ZHANG ; Jie YU
China Journal of Orthopaedics and Traumatology 2025;38(10):1083-1088
Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans
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Practice Guidelines as Topic/standards*
;
Cervical Vertebrae
;
China

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