[摘 要] 目的：探讨卵巢癌组织中PD-L1与唾液酸结合性免疫球蛋白样凝集素15（Siglec-15）的关系及其临床意义以及两者对卵巢癌SKOV3细胞增殖、迁移及侵袭的影响。方法：收集2017年1月至2019年12月福建医科大学附属第二医院妇科50例手术切除的卵巢癌组织和配对输卵管组织的石蜡包埋标本，采用免疫组化染色Envision法检测癌组织和输卵管组织中PD-L1和Siglec-15的表达水平，Kaplan-Meier生存曲线和Logistic回归分析PD-L1和Siglec-15表达与患者预后的关系。利用瞬时转染技术在卵巢癌细胞SKOV3中分别转染si-PD-L1和si-NC，用qPCR和WB法检测SKOV3细胞中PD-L1的表达对Siglec-15的影响，用CCK-8及Transwell法验证PD-L1及Siglec-15表达对SKOV3细胞增殖、迁移及侵袭的影响。结果：50例卵巢癌组织中，PD-L1与Siglec-15均呈高表达（50.00%与42.00%）。PD-L1表达与肿瘤病理类型、有无腹水、淋巴结转移、FIGO分期及卵巢癌复发与否具有关联（均P<0.05）；Siglec-15表达与卵巢癌患者淋巴结转移及FIGO分期具有关联（均P<0.05）。成功构建PD-L1低表达SKOV3细胞株，降低PD-L1表达可使Siglec-15表达升高。结论：PD-L1和Siglec-15在卵巢癌组织中均有较高的阳性表达率，PD-L1是卵巢癌复发的独立风险因素。PD-L1和Siglec-15两者的表达呈负相关，降低PD-L1表达可使Siglec-15表达水平升高而抑制SKOV3细胞增殖、迁移和侵袭的能力。

Objective:To investigate the expression of Mucosal-associated invariant T (MAIT) cells in the peripheral blood of ankylosing spondylitis (AS) patients, and to analyze its clinical significance.Methods:Sixty-four AS patients from September 2020 to September 2022 in Fujian Provincial Hospital and 60 healthy controls were enrolled. The expression of MAIT cells and CD69 +MAIT cells were detected by immunofluorescence. Spondylarthritis research consortium of Canada (SPARCC) scores of sacroiliac joint magnetic resonance imaging (MRI) were calculated and were analyzed based on clinical data. The changes of MAIT cells were observed in 7 patients with AS after treatment. t test, variance analysis and Pearson correlation analysis were used for statistical analysis. Results:The expression of MAIT cells in the peripheral of AS patients was significantly lower than that in the controls [(2.81±0.27)% and (4.46±0.86)% respectively, t=2.33, P=0.022], while CD69 +MAIT cells were significantly higher [(12.0±1.0)% and (7.8±1.2)% respectively, t=2.31, P=0.024]. The level of CD69 +MAIT cells were significantly positively correlated with erythrocyte sedimentation rate (ESR) ( r=0.39, P=0.010), C-reactive protein (CRP) ( r=0.36, P=0.012), ASDAS ( r=0.35, P=0.013) and SPARCC scores ( r=0.38, P=0.006) of AS patients. ASDAS scores and CD69 +MAIT cells obviously decreased in 7 treated AS patients ( F=7.62, P=0.007 and F=4.97, P=0.027 respectively). Conclusion:The expression of peripheral MAIT cells in AS patients is lower than that in healthy controls, but the number of the activated MAIT cells is increased. Levels of activated MAIT cells may in some extent reflect the inflammatory state and disease activity of AS, as well as inflammatory destruction of sacroiliac joint, and therapeutic effect. MAIT cells may partially participate in the inflammatory response and play a role in the pathogenesis of AS.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective:To evaluate the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC) after surgical resection.Methods:A retrospective study was conducted on the clinical data of 156 patients who underwent surgery for ICC in Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University from November 2010 to December 2017, including 94 males and 62 females, aged (60.0±9.5) years. Curative surgery was performed in 114 cases. Of 64 cases were in stage Ⅰ according to American Joint Committee on Cancer (AJCC), including 38 cases of non-lymph node dissection (NLND) and 26 cases of LND; 21 cases were in AJCC stage Ⅱ, including 11 cases of NLND and 10 cases of LND; 22 cases were in AJCC stage Ⅲb, including 14 cases of LND and 8 cases of lymph node resection (LNR); 5 cases were in AJCC stage Ⅲa, 2 cases were in AJCC stage Ⅳ. Univariate and multivariate Cox regression analysis were used for the risk factors of ICC prognosis. The log-rank test compared the survival rates of the two groups.Results:Cox multivariate analysis indicated that lymph node metastasis was independent risk factors for prognosis in patients with ICC ( HR=1.96, 95% CI: 1.09-3.55, P=0.026). A total of 114 patients were included in the curative surgery group. The 1-, 3-, and 5-year overall survival (OS) rates of the negative lymph node group ( n=91) were 65.9%, 47.3% and 35.6%, respectively, which were significantly better than those of the positive lymph node group ( n=23) who had 1-, 3-, 5-year OS rates of 56.5%, 17.7% and 0, respectively (χ 2=8.11, P=0.004 ). In stage Ⅰ and Ⅱ patients, there were no significant differences in 1-, 3-, 5-year OS rates between the NLND group and the LND group (both P>0.05 ). In stage Ⅲb patients, the LND group had 1-, 3-, 5-year OS rates of 71.4%, 29.8% and 0, respectively, significantly better than those of the LNR group who had 1-, 3-, 5-year OS rates of 37.5%, 0 and 0, respectively (χ 2=6.45, P=0.011). Conclusions:Lymph node metastasis is an independent risk factor affecting the prognosis of ICC. Lymph node dissection should be performed cautiously in ICC with AJCC stage Ⅰ and Ⅱ, while routine lymph node dissection is recommended in ICC with AJCC stage Ⅲb.

[摘 要] 目的：探讨甲状腺滤泡癌（FTC）组织中程序性死亡蛋白1（PD-1）和NOD样受体蛋白3（NLRP3）的表达及其与患者临床病理特征和预后的关系。方法：收集2015年1月至2020年6月福建医科大学附属第二医院手术切除的60例FTC患者的癌和配对癌旁组织标本，采用免疫组织化学染色法检测癌及癌旁组织中PD-1和NLRP3的阳性表达率，χ²检验或者Fisher精确检验法分析PD-1和NLRP3表达与FTC患者临床病理特征的关系，Pearson相关性分析PD-1与NLRP3表达的关系，Kaplan-Meier生存和Logistic回归分析PD-1和NLRP3表达与患者预后的关系。结果：在60例FTC组织中，PD-1和NLRP3均有较高的阳性表达率（46.67%与63.33%）。PD-1表达与FTC患者肿瘤分期、肿瘤大小、血管侵犯、复发与否具有显著相关性（均P<0.05），NLRP3表达与患者肿瘤大小、血管侵犯、甲状腺外浸润以及复发具有显著相关性（均P<0.05）。PD-1与NLRP3的表达成负相关，前者与患者更好的预后相关，后者是FTC复发的独立风险因素。结论：PD-1和NLRP3在FTC组织中有较高的阳性表达率，前者与患者更好的预后相关，后者是FTC复发的独立风险因素，且两者的表达呈负相关。

Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

[摘 要] 目的： 探讨程序性死亡蛋白-配体1（programmed death ligand-1，PD-L1）和肿瘤浸润淋巴细胞（tumor-infiltrating lymphocyte, TIL）在三阴性乳腺癌（triple-negative breast cancer，TNBC）组织中的水平及其临床意义。方法：收集2015年1月至2019年1月福建医科大学附属第二医院手术切除的61例TNBC患者的癌及癌旁组织石蜡标本，用免疫组化法检测癌组织中PD-L1表达和CD8+ TIL的水平，用卡方检测方法分析TNBC组织中PD-L1和CD8+ TIL水平与患者临床病理特征及预后的关系。结果： PD-L1和CD8+ TIL在TNBC组织中的阳性率分别为63.9%（39/61）和32.8%（20/61）。PD-L1表达与TNBC患者的肿瘤大小、淋巴结转移、病理分期、复发与否有明显关联（均P<0.05），与患者的年龄、肿瘤分化程度、脉管侵犯以及Ki67表达水平无明显关联（均P>0.05）；CD8+ TIL水平与TNBC患者的肿瘤大小、肿瘤分化程度、淋巴结转移、病理分期、复发与否有明显关联（均P<0.05），与患者的年龄、脉管侵犯以及Ki67表达水平无明显关联（均P>0.05）。PD-L1和CD8+ TIL水平与患者的无进展生存期（PFS）及总生存期（OS）具有显著相关性（均P<0.05），PD-L1+或者缺乏CD8+ TIL与患者更差的PFS及OS相关（均P<0.05）。结论：TNBC组织中存在较高水平的PD-L1和CD8+ TIL，PD-L1阳性表达或缺乏CD8+ TIL与肿瘤侵袭性增加相关，也与患者更差的PFS及OS相关。

Objective:To evaluate the value of improved pulmonary ultrasonography in the follow-up assessment of lung damage in patients who recovered from corona virus disease 2019(COVID-19).Methods:Twenty-two patients who were cured of COVID-19 in Quanzhou First Hospital from January to May 2020 were randomly selected and divided into 7 mild cases, 12 moderate cases and 3 severe cases according to the first high-resolution CT (HRCT) at admission. Six months after recovery, modified lung ultrasonography and HRCT were used prospectively to assess the lung damage and evaluate the correlation and consistency between the two techniques.Results:①There were significant differences in lung damage between the mild group and the moderate group, severe group (all P<0.05), while there was no significant difference between the moderate group and severe group ( P>0.05). ②There was good consistency between the improved lung ultrasound examination and HRCT (Kappa=0.776, P<0.001). ③There was a positive correlation between the score of improved pulmonary ultrasound examination and HRCT Warrick score ( r=0.755, P<0.001). Conclusions:Improved pulmonary ultrasonography can be used as a priority in the evaluation of pulmonary damage follow-up in patients with COVID-19 recovery, reducing the use of CT, and providing favorable evidence for further clinical management.

Objective:To investigate the expression of Mucosal-associated invariant T (MAIT) cells in the salivary gland of primary Sj?gren′s syndrome (pSS) patients, and to analyze its clinical significance.Methods:Thirty-two pSS patients and 27 non-pSS controls who had salivary gland biopsies were enrolled. The expression of MAIT cells was detected by immunofluorescence and then analyzed based on clinical data. T test, variance analysis and Spearman correlation analysis were used for statistical analysis. Results:The expression of MAIT cells in the salivary gland of pSS patients was significantly higher than in controls [(2.40±0.33)/gland and (0.79±0.13)/gland respectively, t=4.24, P<0.01]. In pSS patients with mouth dryness ( n=26), MAIT cells in the sali-vary gland were significantly increased compared with those without [(2.73±0.38)/gland vs (0.95±0.15)/gland, t=2.24, P=0.03]. In patients with dental caries ( n=17), MAIT cells in the salivary gland were also significantly increased [(3.13±0.54)/gland vs (1.57±0.20)/gland, t=2.57, P=0.02]. The expression of MAIT cells in the salivary gland of pSS patients was positively correlated with erythrocyte sedimentation rate (ESR) and European League Against Rheumatism Sj?gren′s Syndrome Disease Activity Index (ESSDAI) scores ( r=0.37, P=0.04 and r=0.65, P<0.01 respectively). In pSS patients with positive SSA antibody ( n=23), the amount of MAIT cells was more than controls [(2.89±0.40)/gland vs (1.13±0.32)/gland, t=2.61, P=0.01]. The level of MAIT cells in the salivary gland was higher in pSS patients with more lymphocytic foci [one foci: (1.50±0.49)/gland, two foci: (2.29±0.52)/gland, three foci(3.66±0.59)/gland; F=4.22, P=0.02]. Conclusion:The expression of MAIT cells in the salivary gland of pSS patients is significantly higher than non-pSS controls, and is correlated with oral symptoms, disease activity and the production of autoantibodies. This may suggest that MAIT cells may participate in the local inflammation response and play a role in the pathogenesis of pSS.

Objective:To evaluate the fitness of bilateral free-end dentition defect removable partial denture framework fabricated by selective laser melting (SLM) technique with different support angles.Methods:After the control group has been set to eliminate the system error, and according to the standard model of bilateral mandibular posterior teeth loss, eighteen titanium alloy removable partial denture frameworks fabricated by SLM technology were divided into 3 groups with support angles of 0° (horizontal group), 45°(45° group) and 90° (vertical group). Plaster cast with duplicated structure of tissue surface of the removable partial denture (RPD) framework was obtained. A three-dimensional scanner was used to scan original and duplicated plaster casts. The gaps between framework and the model in different parts were analyzed using Geomagic Qualify software to evaluate the fitness of the framework with visual method.Results:The framework fits on the plaster model completely, and its tissue surface fitted on the plaster model well. The deviation between frameworks and plaster casts was calculated as follow: the total deviations of the horizontal, 45°, and vertical group were (0.146±0.017), (0.182±0.015) and (0.185±0.022) mm respectively. The mean deviation of the horizontal group was significantly less than those of the 45° group and the vertical group ( P<0.05). Moreover, there was no significant difference in the total deviation between the 45° group and the vertical group. The total deviation of occlusal rest of the horizontal group was significantly less than that of the 45° group ( P<0.05). However, no significant difference was detected in the deviation of occlusal rest among the vertical group, the horizontal group, and the 45° group ( P>0.05). There was no significant difference in the deviation of occlusal rest among the vertical group, the horizontal group, and the 45° group. The deviation of clasp of the horizontal group was significantly smaller than those of the 45° group and the vertical group ( P<0.05). Whereas, there was no significant difference in the deviation of clasp between the 45° group and the 90° group ( P>0.05). No significant difference was found in the deviation of lingual bar among the three groups ( P>0.05). Conclusions:Among the three kinds of bilateral free-end dentition defect RPD framework fabricated by SLM in different support angles, horizontal printing was proved to reach the minimal deviation, even though the fitness of all three kinds of frameworks can fullfil clinical requirements according to previous studies.