1.Multi-evidence Integration Methodology for Traditional Chinese Medicine: the MERGE Framework
Honghao LAI ; Zhe WANG ; Ying LI ; Wenjing TANG ; Beibei WANG ; Peidong SUN ; Mingyao SUN ; Jiajie HUANG ; Zhipan XIAO ; Ying LI ; Chen ZHAO ; Hongcai SHANG ; Kehu YANG ; Jie LIU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(1):172-182
In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.
2.Risk factors for proximal junctional kyphosis in adult spinal deformity patients with concurrent osteoporosis undergoing long-segment spinal fusion surgery
Honghao YANG ; Zhangfu LI ; Hanwen ZHANG ; Xinuo ZHANG ; Yong HAI
Chinese Journal of Orthopaedics 2024;44(11):740-747
Objective:To investigate the risk factors for proximal junctional kyphosis (PJK) in adult spinal deformity patients with concomitant osteoporosis undergoing long-segment spinal fusion surgery.Methods:A retrospective analysis was conducted on 76 adults spinal deformity patients with osteoporosis who underwent long-segment spinal fusion surgery at the Department of Orthopaedics, Beijing Chaoyang Hospital, between June 2013 and December 2019. The cohort included 19 males and 57 females, with a mean age of 66.26±6.10 years (range, 54-78 years). Patients were categorized into two groups based on the occurrence of PJK within a 2-year postoperative follow-up: the PJK group (21 cases) and the non-PJK group (55 cases). Comparative analyses were performed on baseline characteristics, surgical details, preoperative and postoperative spinal-pelvic parameters, Hounsfield Units (HU) of the vertebral bodies, and paraspinal muscle morphology between the groups. Spinal-pelvic parameters included the main Cobb angle, lumbar lordosis (LL), lumbosacral lordosis (LSL), sagittal vertical axis (SVA), T 1 pelvic angle (TPA), pelvic tilt (PT), sacral slope (SS), and pelvic incidence (PI). Preoperative CT was used to measure HU values at the upper instrumented vertebra (UIV), UIV+1, and UIV+2. Paraspinal muscle morphology, including the relative functional cross-sectional area (rFCSA) and functional muscle-fat index (FMFI) at the L 4 lower endplate level, was assessed using preoperative MRI. Optimal cutoff values for HU and paraspinal muscle parameters were determined using receiver operating characteristic curve analysis. Multivariable logistic regression was employed to identify independent risk factors for PJK. Results:Significant differences were observed between the PJK and non-PJK groups in preoperative PT (17.60°±8.39° vs. 24.12°±9.37°), postoperative LL (35.61°±10.62° vs. 42.22°±13.11°), LSL (30.24°±10.10° vs. 35.87°±11.12°), and SVA (37.82°±20.46° vs. 21.37°±17.35°). The differences were statistically significant ( P<0.05). The HU values of UIV (113.62±17.25 vs. 133.94±16.61), UIV+1 (123.14±16.03 vs. 138.27±13.69), and UIV+2 (121.00±15.91 vs. 134.47±15.53) were significantly lower in the PJK group ( P<0.05). Optimal cutoff values for HU at UIV, UIV+1, and UIV+2 were identified as 120.72, 127.51, and 121.50, respectively. Significant differences were also found in rFCSA (156.87±48.06 vs. 204.87±50.16) and FMFI (0.31±0.10 vs. 0.23±0.09). The differences were statistically significant( P<0.05), with optimal cutoff values of 175.43 for rFCSA and 0.24 for FMFI. Multivariable logistic regression analysis indicated that postoperative SVA [ OR=1.049, 95% CI (1.003, 1.097), P=0.037], HU of UIV [ OR=0.938, 95% CI (0.887, 0.991), P=0.024], and rFCSA of paraspinal muscles [ OR=0.883, 95% CI (0.792, 0.983), P=0.023] were independent risk factors for PJK. Conclusion:Reduced HU values of the UIV, decreased rFCSA of lumbar paraspinal muscles, and inadequate sagittal alignment correction are independent risk factors for PJK in adult spinal deformity patients with osteoporosis undergoing long-segment spinal fusion surgery.
3.Expert consensus on the clinical application of cortical bone trajectory for lumbar pedicle screws: results from a modified Delphi study
Yiqi ZHANG ; Jingwei LIU ; Honghao YANG ; Qiang WANG ; Yong HAI ; Yuzeng LIU
Asian Spine Journal 2024;18(5):690-698
Methods:
From May 2021 to August 2021, panelists were chosen to collect expert feedback using the modified Delphi method, and 74 spine surgeons from across China agreed to participate. Four rounds were conducted: one in-person meeting and three subsequent survey rounds. Each question received at least 70.0% agreement, indicating a consensus. The grade A, B, and C recommendation were defined as having ≥90.0%, 80.0%–89.9%, and 70.0%–79.9% agreement on each question, respectively.
Results:
The panelist group consisted of 74 experts, and 72, 70, and 69 questionnaires were collected in three rounds, respectively. In total, 24 questions with 59 options reached consensus after the Delphi rounds, including indications (adjacent vertebral diseases after lumbar internal fixation) and contraindications (previous surgery or bone destructive diseases lead to the destruction or absence of bone in the lamina or isthmus); advantages (intraoperative traction of paravertebral soft tissue is small) and disadvantages (not three-column fixation.); preoperative evaluation; complications; and postoperative follow-up evaluation, of CBT.
Conclusions
The modified Delphi method achieved expert consensus on the clinical use of CBT for lumbar pedicle screws. This consensus document establishes clear guidelines for indications, contraindications, surgical techniques, and postoperative management, thereby enhancing clinical decision-making and promoting the safe and effective use of CBT. While the initial study focused on Chinese surgeons, future research will seek to validate and expand these findings from a broader international perspective.
4.Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia
Kexin AI ; Mu CHEN ; Zhao LIANG ; Xiangyang DING ; Yang GAO ; Honghao ZHANG ; Suwan WU ; Yanjie HE ; Yuhua LI
Biomolecules & Therapeutics 2024;32(5):582-600
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.
5.Expression and molecular mechanism of DKK1 in tongue squamous cell carcinoma
Yue Sun ; Honghao Wang ; Tingyu Li ; Mingen Yang ; Hanxiao Huang ; Jun Hou
Acta Universitatis Medicinalis Anhui 2023;58(6):948-953
Objective:
To investigate the expression and molecular mechanism of dickkopf 1 ( DKK1 ) in tongue squamous cell carcinoma (TSCC) by bioinformatics method and molecular biology experiments.
Methods:
The patients information wasdownload from TCGA-TSCC database,the differentially expressed genes between the cancer and normal tissues were screened by NetworkAnalysed site,the key genes and clinical prognosis were identified through Kaplan-Meier analysis and Lasson regression,the functions and pathways of differentially expressed genes were gained by GO and KEGG database,the expression of DKK1 mRNA and protein in TSCC as well as its relationship with clinicopathological features were analyzed by UALCAN database and immunohistochemistry.Western blot assay was conducted to detect the protein expression of DKK1 in TSCC cells,and siRNA was used to konck down the expression of DKK1 protein in Cal27 cells.
Results :
The three key genes DKK1,CYP19A1 and IRX4, which were highly expressed in tongue squamous cell carcinoma and the survival rate of TSCC patients with high expression group was poor,were screened through NetworkAnalysed ,Kaplan-Meier analysis and Lasson regression method.UALCAN database showed that the mRNA level of DKK1 in TSCC tissues was higher than that in normal tissues,and its high expression was significantly correlated with clinical stage,histological grade and lymph node metastasis of TSCC patients.The immunohistochemistry assay suggested that the positive rate of DKK1 protein in clinical stage Ⅲ + Ⅳ TSCC tissues was significantly higher than that in stage Ⅰ + Ⅱ TSCC tissues.In addition, the expression level of DKK1 protein in TSCC tissues was significantly higher than that in adjacent tissues.Western blot assay also showed that the protein expression of DKK1 in TSCC cell Cal27 was much higher than normal oral epithelial cell HOEC.When knock down the protein expression of DKK1 in Cal27,the expression of β-catenin、p- p65 和 p65 werealso reduced.
Conclusion
DKK1 is highly expressed in tongue squamous cell carcinoma tissues and cells and plays an important role.It may be a new target for early diagnosis and drug treatment of TSCC.
6.A Patient with Sequential Diseases of Langerhans Cell Sarcoma, Langerhans Cell Histiocytosis, and Acute Lymphoblastic Leukemia
Yu TIAN ; Dong WANG ; Ang WEI ; Ying YANG ; Liping ZHANG ; Honghao MA ; Chanjuan WANG ; Lei CUI ; Zhigang LI ; Rui ZHANG ; Tianyou WANG
JOURNAL OF RARE DISEASES 2022;1(3):311-317
Langerhans cell histiocytosis(LCH)and Langerhans cell sarcoma(LCS)are characterized by clone proliferation of Langerhans-type cells, which may occur concurrently or sequentially with T-cell acute lymphoblastic leukemia (T-ALL) and other Lymphoid neoplasms. A 15-year old female patient diagnosed with T-ALL developed LCH involving multiple systems during maintenance chemotherapy of T-AL. After treated with chemotherapy with improved result, the patient showed progression of the illness and refractory to the second-line treatment. We found c.G35A (p.G12D)mutation in the KRAS gene and used the targeted drug Trametinib for treatment. The treatment proved effective, leading to partial remission within a week. Three months after Trametinib treatment, the patient developed new lymphadenopathy. Biopsy revealed the existence of LCS. The disease progressed quickly, and the patient died 7 days after diagnosis of LCS. The case of patients with T-ALL then developing LCH and LCS sequentially is extraordinarily rare. The causes of the case is unclear and may be related to cell transdifferentiation, clonal evolution, and chemotherapy. Targeted drugs can contain this disease for a short time.
7.Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.
Chenxue MAO ; Juan CHEN ; Ting ZOU ; Yuankang ZHOU ; Junyan LIU ; Xi LI ; Xiangping LI ; Min LI ; Pinhua PAN ; Wei ZHUO ; Yang GAO ; Shuo HU ; Desheng XIAO ; Lin WU ; Zhan WANG ; Heng XU ; Wen YANG ; Yingjie XU ; Haihua XIAO ; Kazuhiko HANADA ; Wei ZHANG ; Honghao ZHOU ; Jiye YIN ; Zhaoqian LIU
Acta Pharmaceutica Sinica B 2022;12(3):1514-1522
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
8.QUADAS-C—A tool for assessing risk of bias regarding Quality Assessment of Diagnostic Accuracy Studies-Comparative
Qiuyu YANG ; Yao LU ; Xinling XIE ; Honghao LAI ; Chen TIAN ; Meng NIU ; Jinhui TIAN ; Ni LI ; Jiang LI ; Long GE
Chinese Journal of Epidemiology 2022;43(6):938-944
This paper introduced the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), illustrated the comparison with the QUADAS-2, and using QUADAS-C together with QUADAS-2 to present QUADAS-C results through systematic reviews. Like the domain for QUADAS-2, QUADAS-C retained four domains, including patient selection, index test, reference standard, flow, and timing, and comprised additional questions for each QUADAS-2 part. Unlike the QUADAS-2 tool, the starting question of each domain for QUADAS-C was designed to summarize the risk of biased information captured by QUADAS-2. QUADAS-C only dealt with the risk of bias but did not include the part of concerns regarding applicability. The answers to signaling questions for each domain of QUADAS-C would lead to a 'low''high' or 'unclear' risk of biased judgment for the original study.
9.Portable Pulse Detection System Based on IoT.
Qijun DAI ; Yuping ZHAO ; Qianqian WANG ; Tao LYU ; Yulin SUN ; Hufei DUAN ; Meili LIU ; Jinna YANG ; Honghao WANG
Chinese Journal of Medical Instrumentation 2021;45(2):125-130
Aiming at the current situation of high cost, huge volume, complex operation and difficulty in real application of pulse analyzer, this study designs and implements a portable pulse detection system based on IoT. The design utilizes Raspberry Pi 3B+, STM32 series MCU and cloud server to collect, store, display and recognize pulse signals at CUN, GUAN and CHI. The system is small in size and low in cost, which can be connected with cloud server through network to make full use of resources. The experimental results show that the recognition accuracy of the main feature points of the pulse signal by the portable pulse analyzer is higher than 97%, which has a broad prospect of development and application.
Computers
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Heart Rate
10.Resuscitation aortic balloon occlusion and resuscitation thoracotomy in the treatment of non- compressible torso hemorrhage: a Meta-analysis
Honghao HUANG ; Ke YANG ; Xiqiang WU ; Song WU ; Jian LIU ; Jinbao ZHANG
Chinese Journal of Trauma 2021;37(12):1112-1118
Objective:To systematically compare the prognosis in non-compressible torso hemorrhage(NCTH)treated by resuscitative endovascular balloon occlusion of the aorta(REBOA)and resuscitation thoracotomy(RT).Methods:Data were searched form MEDLINE, EMBASE, PubMed, WanFang, CNKI and VIP databases to collect studies on the prognosis of patients with NCTH undergone REBOA and RT from inception to December 2020. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the quality of the included studies. The Meta-analysis was performed using Revman 5.3. The patients were divided into REBOA group and RT group according to the different surgical treatment methods on admission, and the prognosis of each group was evaluated. The difference of mortality rate, reoperation rate of laparotomy after operation, reoperation rate of embolization after operation and mortality rate in different operating room area were compared between the two groups. Publication bias was assessed using the Egger test.Results:A total of 2 prospective studies and 4 retrospective studies involving 2, 588 subjects were included. There were 1, 591 patients in REBOA group and 997 patients in RT group. Significant differences were observed in the mortality rate( I2=68%, OR=0.33, 95% CI 0.26-0.42, P<0.01), reoperation rate of laparotomy after operation( I2=76%, OR=1.41, 95% CI 1.11-1.77, P<0.01)and reoperation rate of embolization after operation( I2=84%, OR=0.76, 95% CI 0.59-0.99, P<0.05)between REBOA group and RT group. Subgroup analysis showed that the mortality rate in the ICU were not statistically different between the two groups( I2=83%, OR=0.69, 95% CI 0.45-1.05, P>0.05), but the mortality rate in the emergency room was lower in REBOA group than that in RT group( I2=94%, OR=0.52, 95% CI 0.38-0.70, P<0.01). Egger test showed that publication bias had little effect on the results. Conclusions:For patients with NCTH, REBOA can reduce the mortality rate and reoperation rate of embolization after operation, but increase the reoperation rate of laparotomy after operation when compared with RT. In addition, the emergency room may be a more suitable operationg room area for REBOA.


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