1.Association of mixed exposure to lithium, vanadium, uranium, and bismuth in early pregnancy with gestational weight gain
Jiao LI ; Qi LI ; Shuang CHENG ; Jiayi SONG ; Xiaohui GUO ; Xiang WANG ; Di CHENG ; Kefeng FAN ; Ju WANG
Journal of Environmental and Occupational Medicine 2026;43(4):475-484
Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11+0 to 13+6 weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35+0 to 37+6 weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L−1, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g−1 (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.
2.Expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of mice with aortic dissection
Hong MA ; Xueling DING ; Qi WANG ; Hui LYU ; Albusm ASYA ; Xinyi CHENG ; Xiang MA
Chinese Journal of Tissue Engineering Research 2026;30(4):858-863
BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P<0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P<0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.
3.Expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of mice with aortic dissection
Hong MA ; Xueling DING ; Qi WANG ; Hui LYU ; Albusm ASYA ; Xinyi CHENG ; Xiang MA
Chinese Journal of Tissue Engineering Research 2026;30(4):858-863
BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P<0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P<0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.
4.Clinical Application and Pharmacological Effects of Guizhi Fulingwan in Treatment of Uterine Fibroids: A Review
Xiang ZHANG ; Xiaoli WEN ; Biting CHENG ; Hongning LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):299-307
Uterine fibroids are a common benign tumor of the female reproductive system, characterized by increased menstrual flow, lower abdominal pain, and prolonged menstrual periods. Modern medicine believes that the onset of this disease is related to genetic factors, environmental factors, hormone levels, et al, while the specific mechanism remains unclear, and the prevention and treatment of uterine fibroids has become a hot topic of concern for many experts and scholars in the medical field. At present, the treatment of uterine fibroids in clinical practice is mainly based on hormone drugs and uterine artery embolization, and severe cases require hysterectomy. However, the use of hormone drugs for treatment has serious side effects and is prone to recurrence after surgery. Since hysterectomy can cause severe harm to women, it is necessary to explore safer and more effective treatment methods. Traditional Chinese medicine (TCM) has rich clinical experience in the treatment of uterine fibroids, advocating for syndrome differentiation and treatment. The TCM methods that regulate Qi and blood and balance Yin and Yang have been commonly adopted, with significant efficacy and minimal side effects, being more conducive to the recovery. Guizhi Fulingwan are first recorded in the Synopsis of the Golden Chamber written by the famous medical expert ZHANG Zhongjing during the Eastern Han dynasty. This prescription has the effects of activating blood, resolving stasis, and eliminating mass, and it is thus mainly used for treating abdominal mass in women. In recent years, Guizhi Fulingwan has also been applied in the clinical treatment of tumors and has demonstrated definite efficacy in the treatment of uterine fibroids. Studies have shown that the therapeutic mechanisms of Guizhi Fulingwan for uterine fibroids involve regulating cell proliferation and apoptosis, improving immune function, reducing inflammation, improving hemorheological indicators, inhibiting tumor angiogenesis, and regulating sex hormone levels. This article mainly reviews the treatment of uterine fibroids with Guizhi Fulingwan from three aspects: theoretical basis, clinical application, and pharmacological mechanism. It is expected to provide scientific research ideas and guidance for exploring the clinical treatment of uterine fibroids.
5.Application of"integration of four dimensions"teaching mode in the un-dergraduate compulsory education on"Healthcare-associated Infection Control"based on KANO model
Ling ZENG ; Xiuhua KANG ; Minyu LIU ; Yun ZHOU ; Tianxin XIANG ; Na CHENG
Chinese Journal of Infection Control 2025;24(6):800-807
Objective To investigate the application of the"integration of four dimensions(mainline teaching-on-line course-medical case-mind map)"teaching mode in the undergraduate compulsory teaching course"Health-care-associated Infection Control",and provide reference for further improving the design of undergraduate compul-sory course on infection control.Methods A questionnaire survey on undergraduate students' satisfaction for com-pulsory course"Healthcare-associated Infection Control"was conducted using KANO model.A total of 4 dimen-sions and 21 quality indicators were set up.KANO attribute classification,satisfaction degree,and importance coef-ficients etc.were analyzed,and curriculum design was optimized.Results The overall questionnaire reliability Cronbach's a coefficient was 0.915,and the validity analysis Kaiser-Meyer-Olkin(KMO)measure of sampling adequacy value was 0.867.Among the 21 quality indicators,12 were charismatic attributes,which accounted for the largest proportion(57.14%)of the total indicators.Most quality indicators received high student satisfaction ratings.The indicators with the highest satisfaction coefficients were"playing teaching videos in class"(4.73),along with"in-tegrating typical healthcare-associated infection cases into the curriculum for relevant teaching""maintaining a relax-ed and pleasant teaching atmosphere",and"humorous and witty teaching style of the teacher"(all scoring 4.71).Four important but currently with low satisfaction indicators were"combining course content with utilitarian exam preparation""adopting a completely offline teaching format""adopting relatively strict assessment methods",and"reflecting differentiation based on difficulty coefficient in final assessment".Conclusion This course has achieved certain efficacy in undergraduate compulsory education,but there is still room for improvement in the setting of cur-riculum assessment methods.In the future,the course system should be integrated,the assessment mode of combi-ning theory and practice should be optimized,and course improvement and innovation should be promoted.
6.Impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer: a national multicenter real-world study
Zhipeng LIU ; Cheng CHEN ; Jie BAI ; Yan JIANG ; Dong ZHANG ; Wei GUO ; Zhixin WANG ; Xiang LAN ; Yufu YE ; Zhaoping WU ; Jinxue ZHOU ; Shuo JIN ; Yi ZHU ; Wei CHEN ; Dalong YIN ; Yao CHENG ; Haisu DAI ; Lei ZHANG ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2025;24(7):874-881
Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.
7.Effect of autologous bone and allogeneic bone in repair of bone defect after microwave in situ inactivation for bone giant cell tumor around the knee
Ping-guang XIA ; Xiang JIANG ; Bao-cheng ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(9):795-799
Objective To investigate the clinical effect of autologous bone combined with allogeneic bone in repairing bone defect after microwave in situ inactivation for bone giant cell tumor around the knee.Methods A retrospective analysis was conducted on the clinical data of 39 patients with bone giant cell tumor around the knee treated in our hospital from January 2015 to December 2022.The tumor tissues of all patients were performed microwave in situ inactivation first,then followed by curettage;the subchondral bone defect adjacent to the articular surface was reconstructed with autologous bone graft,and the remaining tumor cavity was filled with a composite of autologous and allogeneic bone;then a locking plate was applied for protective fixation.The early outcomes including operative time,intraoperative blood loss,hospital stay,wound healing,and surgery-related complications were recorded.The regular follow-up was conducted after surgery,then the tumor recurrence or metastasis was observed and the status of internal fixation and bone graft fusion along with its fusion time were recorded.The knee functions before operation and at the end of follow-up were evaluated with the Musculoskeletal Tumor Society(MSTS)scoring system.The radiographic joint degeneration was evaluated by the Aboulafia classification system at the end of follow-up.Results The patients showed a mean operative time of(134.7±14.2)minutes,an averaged intraoperative blood loss of(153.9±23.0)mL,and a mean hospital stay of(17.4±3.2)days.The patients obtained Ⅰ phase wound healing without any surgery-related complications such as neurovascular injury.All patients underwent the postoperative follow-up,without local recurrence or metastasis cases during the follow-up.At the end of follow-up,the MSTS score of patients was higher than that before operation(P<0.05),with an excellent and good rate of knee function recovery of 89.7%.At the end of follow-up,X-ray films showed good filling of the lesion and bone graft fusion,with a mean fusion time of(9.4±2.1)months.No collapse or fracture of the articular surface occurred.According to the Aboulafia classification,there were 20 cases of grade 0,11 cases of grade 1,and 8 cases of grade 2.Conclusion The autologous bone and allogeneic bone in repair of bone defect after microwave in situ inactivation for bone giant cell tumor around the knee has perfect knee function recovery,and can effectively prevent the collapse and degeneration of articular surfaces,which helps in the reconstruction of tumor cavity.
8.Senecio scandens Buch.-Ham alleviates inflammatory pain through inhibiting mast cell P2X7 receptors
Fan YE ; Li-hui LIAO ; Jing-yue TANG ; Jia-hui CHEN ; Jiang CHENG ; Gong-xi CHEN ; Zong-xiang TANG
Chinese Pharmacological Bulletin 2025;41(1):131-137
Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P<0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P<0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P<0.05;1 g·L-1:P<0.01;3 g·L-1:P<0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P<0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.
9.Bibliometric analysis of hot topics and trends in thyroid cancer nursing research at home and abroad from 2004 to 2023
Yu JIANG ; Shiyu YIN ; Chunyuan QIN ; Junping ZHONG ; Miao XIANG ; Zhaoting CHENG
Chinese Journal of Practical Nursing 2025;41(25):1970-1977
Objective:To analyze the hotspots and trends in thyroid cancer nursing research from 2004 to 2023 at home and abroad through bibliometric methods, so as to provide references and ideas for future research in this field.Methods:A systematic search was conducted for core journal documents on thyroid cancer nursing research included in China National Knowledge Infrastructure, Wanfang Database, VIP Chinese Journal Network and Web of Science Core Collection from January 1, 2004 to December 31, 2023, using CiteSpace6. 3.R1 software performs visual analysis.Results:A total of 119 domestic documents and 417 international documents were included for analysis. From 2004 to 2023, the number of publications in the field of thyroid cancer nursing research at home and abroad showed an upward trend. Domestic research hotspots mainly include four directions: perioperative nursing, symptom nursing, care for radioactive iodine-131 treatment, and physical and mental health promotion. Foreign research hotspots mainly include three directions: nursing practice exploration and guideline formulation, care for radioactive iodine-131 treatment, and quality of life.Conclusions:The field of thyroid cancer nursing has received continuous attention from scholars at home and abroad. In future research, it is recommended that domestic scholars actively carry out cross-institutional and multi-center team cooperation in accordance with local needs, focus on the research of physical and mental care and health promotion of thyroid cancer patients at different survival stages, and the construction of clinical nursing guidelines. With the help of core research institutions and expert teams, actively promote the development of high-quality nursing research in this field.
10.Clinical Questions Construction in Clinical Practice Guidelines:Based on Case-guided Approach
Yicheng GAO ; Zijin YU ; Yaqi WANG ; Rui FANG ; Cheng WANG ; Yuanyuan LI ; Yingjie DENG ; Xue BAI ; Wenyuan XIANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2025;16(1):198-203
Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

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