Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective:To compare the efficacy of staged versus elective operation for treating acute closed fracture-dislocation of tarsometatarsal joint complex.Methods:A retrospective cohort study was used to analyze the clinical data of 26 patients with acute closed fracture-dislocation of tarsometatarsal joint complex admitted to Tongji Hospital of Tongji University from January 2017 to January 2021, of whom 18 were males and 8 were females, aged 32-52 years [(44.3±5.2)years]. According to the time from injury to admission, 14 patients admitted within 8 hours after injury underwent staged surgical treatment (staged group), and 12 patients admitted more than 8 hours after injury underwent elective surgery (elective group). In the staged group, emergency reduction and temporary internal fixation with K-wire were done under the supervision of a C-arm X-ray machine in the first stage, while after the swelling subsided, open reduction and internal fixation were done for tarsometatarsal joint fracture-dislocation in the second stage. In the elective group, open reduction and internal fixation were performed for tarsometatarsal joint fracture-dislocation on a scheduled basis after the swelling subsided. The operation time, hospitalization time and fracture healing time were recorded. The visual analogue score (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) midfoot score were evaluated before operation, at 1, 6, 12 months after operation and at the final follow-up. The rate of complications was observed after operation.Results:All patients were followed up for 12-24 months [(18.5±3.8)months]. The operation time, hospitalization time and fracture healing time in the staged group were (77.3±5.6)minutes, (14.3±2.2)days and (12.3±1.2)weeks, respectively, significantly shorter than those in the elective group [(101.5±7.5)minutes, (20.3±5.2)days and (14.3±2.2)weeks] (all P<0.01). VAS significantly decreased and AOFAS midfoot score significantly increased in both groups as postoperative time increased (all P<0.05). There were no significant differences in VAS between the two groups before operation, at 12 months after operation or at the final follow-up (all P>0.05). The VAS at 1, 6 months after operation was (4.4±0.8)points and (2.1±0.4)points in the staged group, significantly lower than those in the elective group [(6.0±1.0)points and (3.5±0.6)points] (all P<0.01). There was no significant difference in preoperative AOFAS midfoot score between the two groups ( P>0.05). The AOFAS midfoot score at 1, 6, 12 months after operation and at the final follow-up was (67.6±4.5)points, (75.7±5.2)points, (83.6±2.2)points and (85.9±4.3)points in the staged group, significantly higher than those in the elective group [(60.2±3.9)points, (70.2±3.4)points, (75.4±3.3)points and (78.7±4.4)points] (all P<0.01). The rate of complications was 14.3% (2/14) in the staged group, significantly lower than that in the elective group [33.3% (4/12)] ( P<0.05). Conclusion:Compared to traditional elective surgery, staged surgery for acute closed fracture-dislocation of tarsometatarsal joint complex has the advantages of shortened operation time, hospitalization time and fracture healing time, eary pain relief, improved functional recovery of the foot and reduced postoperative complications.

Objective:To propose a new classification of posterior malleolus fracture to further clarify its pathoanatomy.Methods:Twenty fresh frozen cadaver specimens of normal morphology of lower limbs were selected and dissected and the extent of the tibial insertion of posterior malleolus associated ligaments was measured. At the same time, a retrospective case series analysis was made on the clinical and CT information of 296 patients with posterior malleolus fracture treated at Tongji Hospital of Tongji University from January 2012 to July 2020 or at Karamay Central Hospital from January 2018 to July 2020. The percentage of articular involvement of the fracture, proximal displacement of the posterior malleolus fracture and extent of posterior talar subluxation were measured. A clinically practical new classification system for posterior malleolus fracture was created by correlating posterior malleolus associated ligaments with CT images of posterior malleolus fracture. The new classification included three types: type I was posterior malleolus fracture with only the tibial insertion of inferior transverse tibiofibular ligament involved; type II was posterior malleolus fracture with both the tibial insertions of inferior transverse tibiofibular ligament and posterior inferior tibiofibular ligament involved, which was divided into subtypes IIA and IIB based on the presence of articular cartilage and subchondral bone damage, compression or Die-Punch fragments; type III was posterior malleolus fracture that involved all the tibial insertions of inferior transverse tibiofibular ligament, posterior inferior tibiofibular ligament and posterior tibiotalar ligament, which was sub-classified into subtypes III A and III B according to number of fracture fragments. Anatomic characteristics of the extent of the tibial insertion of posterior malleolus associated ligament, CT imaging parameters for posterior malleolus fracture and corresponding fracture typing were determined. In addition, the new classification system for posterior malleolus fracture was compared with Haraguci classification and Mason classification.Results:Posterior malleolus associated ligaments included the posterior inferior tibiofibular ligament, inferior transverse tibiofibular ligament and posterior tibiotalar ligament from posterolateral to posteromedial tibia. The posterior inferior tibiofibular ligament was attached to the posterolateral tibia and the distance between the highest point of its tibial insertion and the joint line was (45.2±5.6)mm. The inferior transverse tibiofibular ligament was attached to the posterior distal tibia and the distance between the highest point of its tibial insertion and the joint line was (5.5±1.0)mm. The posterior tibiotalar ligament was attached to the posterior colliculus and intercollicular groove of the medial malleolus and the distance between the center of its tibial insertion and the intercollicular groove was (2.5±0.6)mm. Among 296 patients with posterior malleolus fracture, there were 36 patients with type I, 229 with type II (150 type IIA, 79 type IIB) and 31 with type III (11 type IIIA, 20 type IIIB). The percentage of articular involvement of the fracture, proximal displacement of posterior malleolus fracture and extent of posterior talar subluxation in type IIB fracture were significantly greater than those in type II A fracture [23.7(18.6, 28.8)% vs. 18.4(12.7, 21.7)%, 4.1(2.1, 6.0)mm vs. 1.9(0.2, 3.0)mm, 4.7(1.5, 6.2)mm vs. 2.3(1.1, 3.0)mm] (all P<0.01). The proximal displacement of posterior malleolus fracture and extent of posterior talar subluxation in type III fracture were significantly greater than those in type II fracture [7.2(6.0, 8.2)mm vs. 2.7(0.4, 4.0)mm, 10.1(6.0, 15.0)mm vs. 3.1(1.1, 5.0)mm] (all P<0.01). The new classification for posterior malleolus fracture combined the posterior malleolus ligament and injury mechanism of posterior malleolus fracture as compared with Haraguchi classification, which not only further detailed the classification, but also was more practical in clinic for increased the severity of injury was elevated with higher classification level. The new classification was more comprehensive as compared with Mason classification for it mainly added the type of simple-rotation-type posterior malleolus fracture (type IIA of the new classification). Conclusions:In combination with posterior malleolus associated ligaments, injury mechanism and fracture morphology, posterior malleolus fracture is divided into three types. The new classification system more comprehensively describes pathoanatomy of posterior malleolus fracture that contributes to related basic research and clinical diagnosis and treatment.

Objective:To analyze the correlation between the posterior malleolus fracture and fixation and the rotational stability of the ankle and to explore the surgical indications for posterior malleolus fracture aiming to provide the theories for the diagnosis and treatment of disorder.Methods:Twenty fresh frozen cadaver specimens were selected. Further, the extent of the tibial insertion of the posterior inferior tibiofibular ligament (PITFL) and inferior transverse tibiofibular ligament (ITTFL) complex was dissected and measured. Based on the tibial insertion of the ligament complex, the model for the supination-external rotation degree 3 ankle fracture with a posterior malleolar fragment and syndesmosis diastasis was created. Moreover, the area threshold of the posterior tibial insertion of posterior malleolus fracture was biomechanically assessed. The difference of the antirotating ability of the ankle-stiffness between simple posterior malleolus fixation and simple syndesmotic fixation was analyzed statistically.Results:The PITFL and ITTFL were presented in all specimens with relatively broad in PITFL tibial insertion. The PITFL was attached to the posterolateral tibia. The distance between the highest point of the tibial insertion and the articular line was 45.2±5.6 mm, while the ITTFL was attached to the posterior distal tibia. The distance between the highest point of the tibial insertion and the articular line was 5.5±1.0 mm. The width of the tibial insertion of the PITFL and ITTFL complex decreased as the distance from the joint line increased. Biomechanical analysis showed that the threshold of posterior area of posterior malleolus fracture was 1/4S. The stiffnesses of posterior malleolus fixation and syndesmosis stabilization were 0.264±0.080 N·m/° and 0.164 ± 0.061 N·m/°, respectively. The percentage of stiffness restored by posterior ankle fixation was 60.9%±10.2%, which was greater than that by syndesmosis stabilization 37.5%±7.9% ( t=17.09, P<0.001) . Conclusion:The surgical technique for posterior malleolus fracture should consider restoration of the axial and rotational stability of the ankle simultaneously. Posterior malleolus fracture fixation is recommended when the syndesmosis is unstable with the area ratio of posterior tibial insertion of posterior malleolus fracture greater than or equal to 1/4. Syndesmotic fixation is proposed to restore and maintain the rotational stability of the ankle when the syndesmosis is unstable with the area ratio less than 1/4. Regardless of the area ratio, the surgical indications for stable syndesmosis depend on the impact of the posterior malleolus fracture on the axial stability of tibiotalar joint, on the involved articular surface area and on the displacement degree of posterior malleolus fragment.

Objective To investigate the relationship between forkhead/winged helix transcription factor (Foxp) 3 gene polymorphisms and susceptibility and phenotype of Crohn's disease (CD) in Han nationality in Zhejiang province.Methods From January 2007 to December 2015,268 diagnosed CD patients and 490 healthy controls were enrolled.The four single nucleotide polymorphism (SNP) of Foxp3 rs3761547,rs2232365,rs2294021 and rs3761548 were examined by a SNaPshot technique,and their relation with the efficacy of infliximab was evaluated.The linkage disequilibrium (LD) and haplotype were also analyzed.Unconditional Logistic regression analysis was performed for statistical analysis.Results There was no significant difference in the four mutant alleles and genotype frequencies between 31 patients with effective infliximab treatment and 19 patients with ineffective treatment (all P＞0.05).The results of LD analysis indicated that the above four SNP were in a tight linkage.The frequency of haplotype GCGC of male CD group was 29.20％ (40/137),which was higher than that of male healthy control group (19.37％,43/222),and the difference was statistically significant (odd ratio (OR)=1.717,95％ confidence interval (CI) 1.045 to 2.820,P=0.032).The frequency of haplotype ACGA of female CD group was 13.36％ (35/262),which was lower than that of female healthy control group (19.03％,102/536),and the difference was statistically significant (OR=0.656,95％CI 0.433 to 0.995,P=0.046).The frequency of haplotype ATAC of male colon (L2) type was 25.93％ (7/27),which was lower than that of ileocecal colon (L3) type (75.38％,49/65),and the difference was statistically significant (OR=0.114,95％CI 0.041 to 0.320,P＜0.01).The frequency of haplotype GCGC of male L2 type was 51.85％ (14/27),which was higher than that of L3 type (9.23％,6/65),and the difference was statistically significant (OR=10.590,95％CI 3.423 to 32.758,P＜0.01).The frequency of haplotype ATAC of male stenotic (B2) type was 73.21％ (41/56),which was higher than that of nonstenotic and nonpenetrated (B1) type (47.30％,35/74),and the difference was statistically significant (OR=0.328,95％CI 0.156 to 0.693,P=0.003).The frequency of haplotype GCGC of male B2 type was 17.86％ (10/56) which was lower than that of nonstenotic and nonpenetrated (B1) type (39.19％,29/74),and the difference was statistically significant (OR=2.946,95％CI 1.295 to 6.784,P=0.009).The frequency of haplotype ACGA of male penetrated (B3) type was 71.43％ (5/7),which was higher than that of nonstenotic and nonpenetrated (B1) type (12.16％,9/74),and the difference was statistically significant (OR =0.055,95％ CI 0.009 to 0.329,P ＜ 0.01).Conclusion Foxp3 (rs3761547,rs2232365,rs2294021,rs3761548) gene polymorphisms are associated with the susceptibility and phenotype of CD in Chinese Han patients,but not related with the efficacy of infliximab.

Objective To explore the relation between genetic polymorphisms and the expression in colonic tissues of solute-linked carrier family 26 member A3 (SLC26A3) and susceptibility of Crohn's disease (CD) in Han population of Zhejiang Province.Methods A total of 265 CD patients and 566 gender-and age-matched healthy individuals were enrolled.Alleles and genotypes of SLC26A3 (rs17154444,rs7810937,rs7785539,rs2108225,rs6951457) were examined by SNaPshot.The linkage disequilibrium (LD) and haplotype were also analyzed.Eight patients with colonic CD and eight genderand age-matched patients with benign colonic polyps (control group) were selected.The expression level of SLC26A3 protein in the colonic tissue was detected by immunohistochemistry.T test and rank-sum test were performed for statistical analysis.Unconditional Logistic regression analysis was used to analyze the distributions of SLC26A3 polymorphisms and their effects on the clinicopathological features of CD patients.Results The frequencies of mutant allele of rs2108225,rs7785539 and rs6951457 of the CD group were 53.77％ (285/530),4.72％ (25/530) and 2.83％ (15/530),and the frequencies of mutant genotype were 76.23 ％ (202/265),9.43 ％ (25/265) and 5.66 ％ (15/265),which were lower than those of the control group (60.95％,690/1 132;8.13％,92/1 132;6.10％,69/1 132;83.92％,475/566;15.37％,87/566 and 11.84％,67/566),and the differences were statistically significant (all P＜0.05).The frequencies of mutant allele of rs17154444 and rs7810937 of the CD group were 10.19％ (54/530) and 34.91 ％ (185/530),and the frequencies of mutant genotype were 18.49 ％ (49/265) and 56.23 ％ (149/ 265),compared with those of the control group (8.30％,94/1 132;30.92％,350/1 132;15.55％,88/566 and 51.77％,293/566),the differences were not statistically significant (all P＞0.05).The frequency of mutant allele G of rs2108225 in patients with ileal CD was 47.89 ％ (91/190),and the frequency of mutant genotypeAG+GG was 65.26％(62/95),which were both lower than those of colonic CD (61.62％,122/198 and 85.86％,85/99),and the differences were statistically significant (both P＜0.012 5).rs7810937,rs7785539 and rs2108225 were in a strong linkage disequilibrium.The frequencies of haplotypes AGG and ACA of the CD group were 53.96％ (286/530) and 4.34％ (23/530),which were lower than those of the control group (60.07％,680/1 132 and 7.51％,85/1 132),and the differences were statistically significant (52 =5.534,P=0.019;x2 =5.967,P=0.015).And the frequency of haplotype AGA of the CD group was 8.30％ (44/530),which was higher than that of the control group (1.15％,13/1 132),and the difference was statistically significant (x2 =7.793,P＜0.01).Furthermore,the expression level of SLC26A3 protein in colonic tissues of eight colonic CD patients was 0.19±0.07,which was lower than that of patients with benign colonic polyps (0.26 ±-0.03),and the difference was statistically significant (t=2.55,P=0.023).In addition,the expression levels of SLC26A3 protein in patients carrying genotype GG or AG of rs2108225 were 0.19±0.03 and 0.10±0.01,respectively,which were lower than that of patients carrying genotype AA (0.26± 0.02),and the differences were statistically significant (t=3.19,P=0.033;t=9.06,P=0.003).Conclusions The genetic polymorphismns and their haplotypes of SLC26A3 (rs7785539,rs2108225 and rs6951457) are associated with the susceptibility of CD,and SLC26A3 (rs2108225) polymorphism may affect the expression level of SLC26A3 protein in the colonic tissues.

Objective To investigate the relationship between gene polymorphisms of T cell immunoglobulin domain and mucin domain protein-3 (Tim-3) and ulcerative colitis (UC) in Han nationality of Zhejiang.Methods A total of 391 UC patients and 573 healthy controls were recruited.Two single nucleotide polymorphisms (SPNs) of Tim-3 (rs1036199 and rs10515746) were examined by the improved multiple ligase detection reaction technique.Chi-square test or Fisher's exact test was performed to analyze the differences in the distribution of Tim-3 gene polymorphisms and its influence on the location and severity.Haploview 4.2 software was used to analyze linkage disequilibrium (LD) and haplotype.Results The frequencies of genotype CA+AA and mutant allele A of rs10515746 in UC were lower than those in healthy controls (1.79％,7/391 vs 4.19％,24/573;0.90％,7/782 vs 2.18％,25/1 146;x2=4.295 and 4.712,P=0.038 and 0.030).However,there was no significant differences in frequencies of genotype CA+ CC and mutant allele C of gene rs1036199 between UC patients and the healthy controls (1.79％,7/891 vs 8.49％,20/578;0.90％,7/782 vs 1.74％,20/1 146;both P＞0.05).The frequencies of genotype CA+AA and mutant allele A of rs10515746 in mild and moderate UC patients were both higher than those in severe UC patients (2.87 ％,7/244 vs 0;1.43 ％,7/488 vs 0),and the differences were statistically significant (Fisher's exact test,P=0.049 and 0.048).The analysis for LD indicated that rs1036199andrs10515746 were closeLD (D'=0.92,r2=0.72).Furthermore,the frequency of haplotype CA formed by the mutant alleles C and A of these two SNPs was lower in UC patients than that in healthy controls (0.64％,5/782 vs 1.74％,20/1 146),and the difference was statistically significant (x2 =4.441,P=0.035).Conclusions Tim-3 (rs10515746) gene mutation may not only decrease the incidence,but also reduce the severity of UC.Moreover,the haplotype CA formed by the mutant alleles of rs1036199 and rs10515746 may also reduce the incidence of UC.

Objective To investigate the application value of Photoshop in grading invasive risk of gastric stromal tumors (GSTs). Methods EUS image of 97 cases of GSTs confirmed by pathological and immunohistochemical examination were collected. GSTs were divided into four groups (very low risk, low risk, intermediate risk, high risk) by tumor size, mitotic count and rupture of tumor. Mean gray value (intensity of echo) and gray value standard deviation (uniformity of echo) of EUS images of the lesions were determined by Photoshop and then the differences of each group were found by statistical analysis. Results It is difficult to differentiate EUS images of GSTs from each group by visual observation. The mean gray value of EUS image of very low risk group,low risk group, intermediate risk group and high risk group of GSTs respectively were (56.54 ± 6.10), (59.20 ± 7.51), (77.77 ± 10.90) and (83.43 ± 12.47). There was no significant difference between very low risk group and low risk group (P > 0.05). There was no significant difference between intermediate risk group and high risk group (P > 0.05). In addition, the others all had significantly different from that of each group (P < 0.05). The mean gray value standard deviation of EUS image of very low risk group, low risk group, intermediate risk group and high risk group of GSTs respectively were (8.46 ± 2.59), (12.57 ± 5.89), (12.84 ± 4.15) and (16.69 ± 4.69). There was no significant difference between low risk group and intermediate risk group (P > 0.05). In addition, the others all had significantly different from that of each group (P < 0.05). Conclusions The higher risk of GSTs, the higher of echo intensity and the worse of echo uniformity under EUS. Photoshop combined with EUS is helpful for differentiating different risk of GSTs by analyzing mean gray value and gray value standard deviation of the lesions.

Background and objective hTere is no high-level evidence for the time of whole brain radiotherapy (WBRT) for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) and brain metastases. hTe aim of this study is to assess the appropriate timing of WBRT for patients withEGFR-mutated NSCLC and brain metastases (BM).Methods hTere were 78 patients diagnosed withEGFR-mutated NSCLC and BM in Beijing Chest Hospital between August 2009 and May 2015. 48 untreated patients who received both WBRT and EGFR-tyrosine kinase inhibitors (TKIs) therapy. Prognostic factors of intracranial progression-free survival (PFS) and overall survival (OS) were identiifed byCox proportional hazards modeling.Results Intracranial objective response rate was 81.3% and disease control rate was 93.8%. Median intracranial PFS was 10 months. Median OS was 18 months. Multivariate analysis of intracranial PFS revealed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (HR=30.436, 95%CI: 4.721-196.211, P<0.001) and early WBRT (HR=3.663, 95%CI: 1.657-8.098,P=0.001) had a better intracranial PFS. Multivariate analysis of OS revealed that PS 0-1 (HR=57.607, 95%CI: 6.135-540.953,P<0.001), early WBRT (HR=2.757, 95%CI: 1.140-6.669,P=0.024), and stereotactic radiosurgery (HR=5.964, 95%CI: 1.895-18.767,P=0.002) were independent prognostic factors of OS.Conclusion Early WBRT combined with EGFR-TKIs can improve outcomes of patients withEGFR-mutated NSCLC and BM, but it needs to be conifrmed by large-sample-size and multicenter prospective clinical trials.

Objective To investigate the value of CT perfusion imaging in evaluation of therapeutic effect and prognosis in radiotherapy for lung cancer.Methods Fifty-one cases of lung cancer who were unable or refused to be operated on,36 males and 15 females,aged 37 - 80,underwent CT perfusion imaging,29 of which only before radiotherapy and 22 before and after radiotherapy twice.The images were collected by cine dynamic scanning (5 mm/4 slices ) and input into the GE AW4.0workstation for data processing.The slice positions of CT imaging were determined according to the largest tumor size in CT scan.Regions of interest of tumor were drawn at the region corresponding to the original images of CT perfusion.Radiotherapy was performed after CT perfusion imaging.Relevant parameters,including blood flow ( BF),blood volume ( BV),mean transit time ( MTT),and permeability surface (PS) were calculated.The treatment response after radiotherapy was evaluated by RECIST.At 2 -4 weeks after the treatment,CT examination was conducted once more.Results The tests of the 51 patients showed that the BV was 13.6 ml·100 g-1,the BF was 129.5 ml·min-1 ·100 g-1,the MTT was 9.1 s,and the PS was 10.0 ml· min- 1· 100 g-1 before radiotherapy.The tests of the 22 of the 51 patients showed that the values of BV and BF after radiotherapy were 7.6 ml· 100 g-1 and 97.8 ml·min-1· 100 g-1,respectively,both lower than those before radiotherapy (11.2 and 108.7 ml·min-1·100g-1,respectively),however,both not significantly ( t =1.28,0.40,P ＞ 0.05 ) ; and the values of MTT and PS after radiotherapy were 8.9 s and 7.8 ml·min-1· 100 g-1,respectively,both not significantly higher than those before radiotherapy ( 7.2 s and 6.8 ml· min -1· 100 g-1,respectively,t =- 1.15,- 0.57,P ＞0.05 ).The mean area of tumor after radiotherapy was 1189.6 mm2,significantly less than that before radiotherapy ( 1920.3 mm2,t =3.98,P ＜0.05).The MTT of the SCLC patients was 12.9 s,significantly longer than that of the NSCLC patients (6.5 s,t =2.54,P ＜0.05).The MTT of the tumor with the area ≤ 10 cm2 was 11.2 s,significantly longer than that of the tumors with an area ＞ 10 cm2(5.8 s,t =2.59,P ＜ 0.05 ).The BV of the responder group was 19.2 ml· 100 g- 1,significantly higher than that of the nonresponder group (4.6 ml· 100 g - 1,t =3.62,P ＜ 0.05 ).There were not significant differences in all the perfusion characteristics between the cases with the disease-free advanced survival time ≤ 10 months and those with disease-free advanced survival time ＞ 10 months.Conclusions CT perfusion imaging helps in diagnosis and radiotherapy of lung cancer to a certain degree.