The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules， the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization （WHO） guideline-making norms and the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions （19 items were screened by the nominal group technique）， retrieving evidence （from Chinese and English databases and grey literature）， assessing safety （integrating drug monitoring data and clinical investigations）， and forming recommendations and consensus suggestions （3 recommendations were reached via the GRADE grid method， and 16 consensus suggestions were reached by the majority vote rule）. The results indicate that the consensus clearly states that this medicine （Dieda Huoxue capsules） is applicable to conditions like traumatic injury， blood stasis-induced pain， and sudden lumbar sprains. The recommended dose is 6 capsules each time， twice a day. Combining oral administration with external application can enhance the efficacy， and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis， the Delphi method， and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration， conflict-of-interest statements， and evidence evaluation through 12 appendices， providing methodological support for the clinical translation of the consensus. In the future， it will be continuously improved through a dynamic revision mechanism.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective Zhuanyao decoction is a traditional Chinese herbal compound prescription orignated from Bianzhenglu in Ming Dynasty;Baizhu Zhuanyao decoction(BZZYD),adding spatholobus suberectus,sappanwood,and cyathula root,is intended to enhance the therapeutic effects on the waist and hips.We aimed to investigate the effects of BZZYD on lumbar ligamentum flavum fibrosis and its possible immune regulation mechanism.Methods(i)By using a random number table method,twenty-four male SD rats were divided into the normal,model,chlorophosphate,and BZZYD groups,with six rats per group.The rats in all groups,except for the normal group,were used to establish a rat model of lumbar ligamentum flavum fibrosis using lumbar instability method.The rats in the BZZYD group received Baizhu Zhuanyao decoction through gavage(13.6 g/kg),and the other groups were administered the same amount of saline by gavage once a day for 30 days.The rats in the chlorophosphate group were subcutaneously injected with disodium chlorophosphate liposome(5 g/L,0.5 mL)at the original incision immediately after surgery and at Day 9,18,and 27.After 30 days,the rats were sarcrificed through excessive anesthesia,and the ligamentum flavum was histologically evaluated using HE and Masson staining.The collagen volume fraction(CVF)was calculated.Transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)protein expressions in the ligamentum flavum were detected using immunohistochemical staining.CD163 and TGF-β1 protein expression in M2 macrophages were detected using the immunofluorescence double-labeling method.(ⅱ)M2 macrophage and fibroblast were cultured in the three ways:separately,co-culture,and co-culture of pre-treatment of BZZYD containing serum on M2 macrophage and fibroblast.TGF-β1,TNF-α,and IL-1β mRNA expressions in M2 macrophage and fibroblast were compared using RT-qPCR.Results(ⅰ)Compared with those in the normal group,the ligamentum flavum fibers were dense and twisted,immune cells infiltrated,and the CVF was increased in the model group.TGF-β1,TNF-α,and IL-1β protein expression in the ligamentum flavum tissues of the model group were increased,and TGF-β1 and TNF-α protein expression in the BZZYD group were increased(P<0.05).Compared with that of the model group,extracellular matrix accumulation decreased in the chlorophosphate and BZZYD groups,the CVF was decreased,and TGF-β1,TNF-α,and IL-1β protein expressions in ligamentum flavum tissue were decreased(P<0.05).Compared with that of the chlorophosphate group,extracellular matrix accumulation increased,the CVF was increased,TGF-β1 and IL-1β protein expressions in ligamentum flavum tissue were increased(P<0.05).CD163 and TGF-β1 proteins were not expressed in the normal and chlorophosphate groups.CD163 and TGF-β1 proteins were expressed and co-localized in the model group,and CD163 protein expression was observed in the BZZYD group,however,TGF-β1 expression was low.(ⅱ)The co-culture system increased mRNA expressions of TGF-β1 and IL-1β in M2 macrophages,TNF-α and IL-1β in fibroblasts,compared to the two kinds of cells cultured separately.And after pre-treatment on M2 macrophages,the mRNA expressions all decreased compared co-culture system(P<0.05).Conclusion BZZYD can significantly inhibit lumbar ligamentum flavum fibrosis,reduce TGF-β1 and IL-1β expression in M2 macrophages,affect TNF-α and IL-1β expression in fibroblasts,and inhibit the positive feedback of ligamentum flavum inflammation-fibrosis.

Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.

Objective:To investigate the therapeutic effect of digital technology assisted design of fibula flap for the repair of maxillary tumor defect and implant denture.Methods:A retrospective analysis was performed in patients with benign maxillary tumors who were admitted to Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou Universityfrom March 2018 to October 2020. Before the surgery, the virtual tumor resection, fibula reconstruction and stereomodels were printed for the fabrication of fibular osteotomy guide plates.And titanium plates were prefabricated with the stereomodels. Personalized titanium meshes were prebent manually. During the operation, the tumor was removed according to the osteotomy guide plate.The fibula was reshaped according to the surgical plan and the guide plate.And maxillary defects were reconstructed using the fibular flap combined with a prebent personalized titanium mesh.Straumann implants were implanted 6-9 months after bone grafting.The upper porcelain crown was repaired 3-4 months after implantation to restore the occlusal relationship and masticatory function. The facial appearance, masticatory function and peri-implant inflammation were followed up.Results:A total of 12 cases were included in this study, 7 males and 5 females, aged 20-55 years, with a median age 36 years old. Among them, there were 3 cases of ossifying fibroma, 7 cases of ameloblastoma, and 2 cases of odontogenic myxoma.According to the James Brown classification, there were 4 cases of Type Ⅱb, 3 cases of Type Ⅱc, 3 cases of Type Ⅱd, and 2 cases of Type Ⅲb. Tumor resection and fibula reconstruction went smoothly in 12 patients and all the free fibular flaps survived 14 days after surgery. The patients had maxillofacial symmetry, good occlusal relationship after the implant repair, and normal chewing and masticatory functions, after 12-48 months of follow-up, with an average of 26 months. The mouth opening reached 2.8-3.3 cm, without obvious peri-implantitis.Conclusion:The use of digital technology to design fibula flap to repair the defect after maxillary tumor resection and implant denture can not only restore the patients’ facial contour, but also restore their occlusal relationship and masticatory function.

Platinum-based nanoplatforms can enhance the absorption of X-ray due to the presence of high atomic number element of platinum and are applied to computed tomography imaging.Meanwhile,platinum-based nanomaterials have good near-infrared light absorption properties and photothermal conversion efficiency,which make them capable of photothermal imaging and photoacoustic imaging.In addition,by reducing transverse and longitudinal relaxation time,platinum-based nanoplatforms can mediate MRI imaging.In this paper,we report a multimodal imaging system based on platinum-based nanoplatforms for guiding the development of cancer treatment and diagnosis platform and medical application research,and also summarize the prospects of multimodal imaging technology in cancer diagnosis and treatment,report the research progress of platinum-based nanoplatforms in improving the contrast of medical images and enhancing cancer treatment.

Objective To observe the clinical efficacy of Zhuanyaotang Granules for the treatment of degenerative lumbar spinal stenosis(DLSS).Methods Using a randomized double blind controlled design,104 DLSS patients were divided into an experimental group and a control group using a random number table method,with 52 patients in each group.The treatment group took oral Zhuanyaotang Granules,methylcobalamin tablets and celecoxib capsule simulants.The control group used Zhuanyaotang Granules simulants,methylcobalamin tablets and celecoxib capsules.The course of treatment was 3 weeks for both groups.The follow-ups were conducted at 1 month and 3 months after treatment.The intermittent claudication distance,visual analogue scale(VAS)score and JOA efficacy rating criteria for low back pain score were observed in both groups before treatment,1,2,3 weeks of treatment and 1 month after treatment and 3 months after treatment.Adverse reactions during treatment were recorded.Results There were 5 cases of detachment and 2 cases of exclusion in the experimental group,and 5 cases of detachment and 1 case of exclusion in the control group.Compared with before treatment,there were statistically significant differences in intermittent claudication distance,VAS score,and JOA score between the two groups of patients at various time points during treatment and follow-up(P<0.05);there was no statistically significant difference in intermittent claudication distance,VAS score,and JOA score between the experimental group and the control group before treatment and 1 and 2 weeks of treatment(P>0.05);compared with the two groups at 3 weeks of treatment and 1 and 3 months after treatment,the intermittent claudication distance and JOA score in the experimental group were lower than those in the control group(P<0.05);There was no significant difference in VAS score between the two groups and the control group after 3 weeks of treatment(P>0.05).There were 2 adverse reactions(4.4%)in the experimental group and 5 adverse reactions(10.8%)in the control group,without statistical significance(P>0.05).Conclusion Zhuanyaotang Granules can effectively relieve pain and improve lumbar function in patients with DLSS,which is more effective and safer than oral celecoxib capsules and methylcobalamin tablets.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To investigate the effect of linear echoendoscope guided precise endoscopic sphincterotomy(EST)on positive rates of bile amylase(BA)and bile bacteria as well as occult pancreaticobiliary reflux(OPBR)in patients with calculus of common bile duct after endoscopic retrograde cholangiopancreatography(ERCP).Methods The subjects of this study,146 patients with calculus of common bile duct who underwent EST for ERCP from June 2021 to February 2023,were divided into two groups based on EST type,each with 73 cases.Observation group was administrated with linear echoendoscope guided precise EST,control group was administrated traditional EST.The operation conditions of both groups were observed.Liver function indexes[total bilirubin(TBiL),conjugated bilirubin(CB)and alanine aminotransferase(ALT)],inflammatory and stress indicators[C-reactive protein(CRP),high mobility group box-1 protein(HMGB1),cortisol(Cor),norepinephrine(NE)],and the positive rates of BA and bile bacteria were compared between the two groups before operation and 1,3 days after operation.The postoperative complications and recurrence rate 12 months after operation were recorded.Results There was no significant difference in the success rate of lithotomy and operation time between the two groups(P>0.05).The intraoperative blood loss in the observation group was less than that in the control group,and the hospital stay was shorter than that in the control group,and the differences were statistically significant(P<0.05).1 and 3 days after surgery,TBiL,CB and ALT in two groups were lower than those before surgery,the differences were statistically significant(P<0.05),but there was no statistically significant difference between groups(P>0.05).1 and 3 days after surgery,serum CRP,HMGB1,Cor and NE levels and BA concentration in two groups were higher than those before surgery,and observation group was lower than control group,with statistical significance(P<0.05).The positive rate of biliary bacteria 1 and 3 days after surgery in the control group was higher than that before surgery,the difference was statistically significant(P<0.05);the positive rate of biliary bacteria in the observation group was not significantly different at different time points before and after surgery(P>0.05);the positive rate of biliary bacteria in the observation group was lower than that in the control group 1 and 3 days after surgery(P<0.05).The incidence of OPBR and postoperative recurrence rate at 12 months in the observation group(15.07%and 1.37%)were lower than those in the control group(57.53%and 10.96%),and the differences were statistically significant(P<0.05).Conclusion Linear echoendoscope guided precise EST is more effective in mitigating duodenal papillary sphincter injury,preventing duodenal-biliary reflux,inhibiting BA secretion and bacterial proliferation,and reducing the risk of OPBR than traditional EST.