Objective To analyze the image and histological results of the combined use of allograft/extracorporeally frozen tumor-bearing bone and vascularized fibular flap for the reconstruction of bony defects following tumor resection,guiding clinical practice.Methods From March 2007 to June 2013,we enrolled 63 patients who had combinative biological reconstruction after bone tumor resection (11 in humerus,22 in femur,21 in tibia,4 in calcaneus).There were 36 male and 27 female in this series.The average age at time of operation was 20 years,ranging from 9 to 48 years.The follow-up ranged from 16 to 102 months with average of 48 months.We investigated the X-ray and CT images for all patients and histological findings of two patients.Patients were assessed functionally with the Musculoskeletal Tumor Society 93 score.Results Three patients with local soft tissue recurrence and one patient with infection underwent amputation.The survival of construct was 93.6％.Bone union achieved in all cases with the average MSTS score of 92.8％.Bone union ranged from 11 to 28 months in allograft group and 9 to 14 months in devitalized tumor bearing bone group.Significant difference of bone union time was found between two groups (Z=-3.638,P=0.000).Viability of the fibular grafts was verified in 58 of 63 patients (92％).Three types of images were observed in complex.Osteopenia and spongy change in fibula were found in 51 patients (81％) with stable fixation of the complex.Five complexes with failed blood supply of fibula and stable fixation revealed no density change of fibula,small amount of callous formation and relative delayed union.In seven complexes (11％) with unstable complex due to patients' incompliance,fibula reacted with dense hypertrophy and microfracture.Fusion of grafts with amount of callus was obviously observed.Union at allograft-host bone junctions occurred by residual host bone-derived external callus and fibular-derived internal callus that bridged the junction and filled the gap between abutting cortices.Callus from fibular graft was mature than that from periosteum of residual host bone.Internal repair was observed at the internal surface of the allografts.Fibula showed significant spongy changes.Conclusion Recycled tumor-bearing bone in combined with fibular flap is a reliable reconstruction as an alternative to traditional Capanna technique.The survival of the fibula is a cornerstone in success of complex reconstruction.Sponginess of fibula and internal repair of allograft compromise the intensity of complex,necessitating the strong instrumentation during reconstruction.

Objective To explore the feasibility and clinical efficacy of long-segmental bone defects after en bloc tumor resection of lower limb segment with composite of titanium alloy 3D printed prosthesis and vascularized fibular autograft and bioceramics.Methods 5 patients with lower extremity tumor (1 high grade chondrosarcoma,1 Ewing sarcoma,1 single metastatic tumor and 2 osteosarcoma) were treated by en bloc resection and precise reconstruction with segmental 3D-printed,custom-made prosthesis from August 2015 to November 2016,which composed of 1 male and 4 females,ranged from 16 to 56 years old,the average was 32± 19.3 years old.Three-dimensional computed tomography reconstructed images of patients' tumors were built before surgery.Custom-made prostheses were manufactured based on the patients' reconstructed images with micro-pores on the surface.After en bloc tumor resection with the help of osteotomy guide plate,the defects were reconstructed with 3D-printed,custom-made prostheses.Vascularized fibular autografts were put inside the prostheses,and the interval space among them was filled with bioceramics.Results All the 5 cases were performed surgical planning before the surgery with prosthesis and guide plate were designed at the same time.After verification of the finite element analysis SLM (2 cases) and the EBM (3 cases) were used to process prosthesis,and were designed into porous sharp with 210.98±66.16 mm in length and 26 901.76±12 903.96 mm3 in volume.Then the prosthesis would be cleaned and sterilized.All 5 operation were proceeded according to the plan of preoperative.The intra-operative guide plate were installed on the bone surface stably.The bone cutting was guided according to the plan of preoperative.By intra-operative frozen pathological examination,there were no malignant tissues in near and far marrow cavity.Unfolded fibular flap with 168.75±49.07 mm in length and porous tricalcium phosphate particle composite implants with 10±4.08 g were used in 4 cases and bone cement was used in 1 cases of metastatic tumor.The average operation time was 261±85 min and average blood loss was 540±182 ml.After a mean follow-up time of 6.4 months (1-15 months),all 5 cases survived with no local recurrence and pulmonary metastasis tumor.2 cases with vascular pedicle fibular transplant confirmed the survival of fibula via bone scan 3 months after operation.All cases were no infection,fractures,prosthesis loosening,except broken screw in 1 case.The Musculoskeletal Tumor Society (MSTS) 93 score was 17-26.Conclusion Long segment tubular titanium alloy 3D printed prosthesis with vascularized fibular autograft and bioceramics could reconstruct the segmental defects caused by tumor resection.

Objective The Network Enhancement Fusion(ne-SNF)method had no denoising strategy for the networks from each omics data type,which would weaken the power of network fusion.To address this problem,we proposed an improved Network Enhancement Fusion(improved ne-SNF)model,and further applied the method to subtype identification of papillary renal cell carcinoma.Methods We conducted simulation studies to compare the performances of the improved ne-SNF method with the ne-SNF and SNF method,and applied improved ne-SNF method to integrate multi-omics data of PRCC.Cox regression model was performed to evaluate the prognostic risk of different subtypes.Differentially expressed mRNAs(DEmRNAs),miRNAs(DEmiRNAs)and differentially methylated genes(DMGs)with different subtypes were screened.KEGG pathway analysis was performed for the overlapping genes of three gene sets.Finally,the immune cell infiltration analysis was performed for patients with different subtypes.Results The improved ne-SNF method outperformed both SNF and ne-SNF approach in various simulation scenarios.In subsequent subtyping application,PRCC patients were divided into high-risk and low-risk groups,and the risk of death was 7.727 times higher in the high-risk group than in the low-risk group.A total of 3511 DEmRNAs,96 DEmiRNAs and 3426 DMGs were identified.Among them,649 overlapping genes yielded 42 KEGG pathways with statistical differences.In addition,3 immune filtrating cells showed statistical significance.Conclusion The improved ne-SNF performed better than SNF and ne-SNF,and the identified subtypes of PRCC may provide important clues and basis for treatment of PRCC patient.

Determining the approach to spread the knowledge and technology for preventing birth defects using the diffusion of innovations theory.Identifying the target group,orientation messages and promotion guidelines based on related literature,laws and clinical epidemiology studies.Pathways integrating both inter-personal communication and IT have pushed the adoption percentage of innovative knowledge for preventing birth defects up from 0％ to 97 ％ in almost no time,helping the region ranking the first in China.The innovation diffusion model has caught attention of both the government and all the community.Prevention measures against birth defects are accepted community wide,while medical workers are regulated by law in their behaviors of mothers and children healthcare services to set a model for prevention of other diseases.

Objective To evaluate effect and safety of first-line chemotherapy regimen combined with rh-endostatin for osteosarcoma of the extremities.Methods Sixty three patients with osteosarcoma were randomly divided into experiment group and control group.There were 32 patients in experiment group,and 31 patients in control group.Nine patients 9 were rejected because they did not meet the standard.Finally,54 patients were enrolled in this study,including 29 patients in experiment group,and 25 patients in control group.In the experiment group,the patients were treated with rh-endostatin combined with MTX,IFO,DDP,and ADM,while patients in control group were treated with MTX,IFO,DDP,and ADM.Several indexes including median progression-free survival time,clinical benefit rate,progression-free survival rate,limb salvage rate,and survival rate were used to assess clinical effect.The safety of rh-endostatin was evaluated by comparing incidence of adverse events in the two groups.Results The median progression-free survival time of experiment group and control group was 18.9 months and 13.1 months,respectively; there was no significant difference.In the experiment group,the clinical benefit rate,progression-free survival rate,survival rate and limb salvage rate were 89.7％,37.9％,65.5％,and 89.7％,respectively; while in the control group,the clinical benefit rate,progression-free survival rate,survival rate,and limb salvage rate were 88.0％,36.0％,68.0％,and 96.0％,respectively.There was no significant difference in 4 indexes mentioned above between two groups.Conclusion After being combined with first-line chemotherapy regimen,rh-endostatin doesn't show significant advantage in controlling tumour progression and improving survival rate.No more toxicity and new side effects are found after using rh-endostatin.

Objective To study the medication law of Professor Zhang Yunling in the treatment of headache based on data mining technology;To provide ideas for the clinical treatment of headache.Methods Professor Zhang Yunling's outpatient TCM prescription data for the treatment of headache from Sep.2017 to Dec.2020 were collected,and the Ancient and Modern Medical Record Cloud Platform 2.3.5 was used to mine the selected TCM prescriptions for herbal medicine frequency statistics,property,taste and meridian tropism statistics,herbal medicine efficacy statistics,correlation analysis,clustering analysis,complex network analysis,etc.Results Through collection and screening,totally 332 prescriptions were included,involving 178 kinds of Chinese materia medica,with a total frequency of 5 380 times.The top 10 kinds of Chinese materia medica were Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Testudinis Carapax et Plastrum,Bambusae Caulis in Taenia,Glycyrrhizae Radix et Rhizoma,Astragali Radix,Amomi Fructus Rotundus,Pinelliae Rhizoma Praeparatum,and Polygalae Radix.They were mainly warm,mild and slightly cold in properties,sweet,pungent and bitter in tastes,and liver,lung,spleen meridian in meridian tropism.In the statistics of herbal medicine efficacy,expelling wind and relieving pain,suppressing liver yang,promoting blood circulation and qi,clearing heart and relieving restlessness,clearing heat and detoxifying,softening liver and relieving pain were used more frequently.The combinations in herbal medicines association included"Atractyodis Macrocephalae Rhizoma-Chuanxiaong Rhizoma","Testudinis Carapax et Plastrum-Paeoniae Radix alba","Glycyrrhizae Radix et Rhizoma-Paeoniae Radix alba","Testudinis Carapax et Plastrum-Chuanxiaong Rhizoma","Bambusae Caulis in Taenia-Chuanxiaong Rhizoma".Herbal medicines clustering clustered 32 kinds of high-frequency herbal medicines used more than 60 times into 6 categories.Complex network analysis screened out the core formula for the treatment of headache:Chuanxiaong Rhizoma,Paeoniae Radix alba,Atractyodis Macrocephalae Rhizoma,Bambusae Caulis in Taenia,Pinelliae Rhizoma Praeparatum,Testudinis Carapax et Plastrum,Astragali Radix,Amomi Fructus Rotundus,and Glycyrrhizae Radix et Rhizoma.Conclusion In the treatment of headache,Professor Zhang Yunling holds that the pathogenesis of headache is deficiency in origin and excess in superficiality,deficiency of qi and blood,loss of nourishment of brain collaterals,stagnation of phlegm and dampness,disturbance of wind pathogen,obstruction of brain collaterals,and the location of the disease is related to the five viscera and involves the stomach.Focuses on tonifying deficiency and reducing excess,treats exterior and interior separately,and gives consideration to both the symptoms and the root causes,which often uses drugs to treat headache,such as dispelling wind and relieving pain,promoting blood circulation and relieving pain,relieving spasm and relieving pains,eliminating phlegm and dampness,invigorating qi and spleen,nourishing blood and yin,eliminating dampness and regulating stomach,relieving depression and restlessness,which can provide some reference for the clinical treatment of headache.

ObjectiveTo explore the medication rules of traditional Chinese medicine compounds for depression in the National Patent Database using data mining， and to provide ideas for the clinical treatment and the development of new drugs for depression. MethodsThe patent data of traditional Chinese medicine compounds for the treatment of depression were searched from inception to July 1st， 2022 on the Patent Publication Announcement website of China National Intellectual Property Administration. The selected traditional Chinese medicine compounds were analyzed by using the data mining section of the ancient and modern medical record cloud platform （V2.3.5） for drug frequency， and based on this， the nature， flavor， channel entry and function of the medicinals were analyzed. Representative high-frequency herbal combinations were obtained through correlation analysis， while the classification of Chinese medicine compounds for depression was analyzed by cluster analysis， and the core combinations of herbs for the treatment of depression were screened out using complex network analysis. ResultsA total of 325 Chinese medicine compounds were included， involving 452 herbs， with a total frequency of 3532 times. The top 10 mostly used herbs were Yujin （Radix Curcumae， 122 times）， Chaihu （Radix Bupleuri， 122 times）， Baishao （Radix Paeoniae Alba， 109 times）， Suanzaoren （Spina Date Seed， 95 times）， Fuling （Poria， 94 times）， Danggui （Radix Angelicae Sinensis， 94 times）， Yuanzhi （Radix Polygalae， 84 times）， Baizhu （Rhizoma Atractylodis Macrocephalae， 72 times）， Shichangpu （Rhizoma Acori Graminei， 71 times）， and Danshen （Salvia Miltiorrhiza， 61 times）. The natures of the herbs were mainly warm （998 times）， neutral （944 times）， slightly cold （596 times） and cold （497 times）； the flavors were mainly sweet （1648 times）， acrid （1392 times）， and bitter （1337 times）； the channels of entry were mainly liver （1695 times）， heart （1521 times）， spleen （1326 times） and lung （1268 times）. The medicinals with the function of soothing liver to relieve constraint， moistening the intestines to promote defecation， calming the heart and the mind， moving qi to relieve constraint were used more frequently. The high frequency herbal combinations by association analysis included “Chaihu （Radix Bupleuri）→ Baishao （Radix Paeoniae Alba）”， “Danggui （Radix Angelicae Sinensis）→Chaihu （Radix Bupleuri）” and “Baishao （Radix Paeoniae Alba）→ Yujin （Radix Curcumae）”. The 22 high frequency medicinals used more than 40 times could be clustered into six categories. Complex network analysis found the core herbal combination for the treatment of depression was the formula of Chaihu （Radix Bupleuri）， Yujin （Radix Curcumae）， Baishao （Radix Paeoniae Alba）， Danggui （Radix Angelicae Sinensis）， Fuling （Poria）， Suanzaoren （Spina Date Seed）， and Xiangfu （Cyperi Rhizoma）. ConclusionTraditional Chinese medicine compounds for the treatment of depression is mainly based on the pathogenesis of constraint， stasis and deficiency， focusing on the liver， heart， spleen and lung， commonly using medicinals with the function of soothing liver to relieve constraint， fortifying spleen and nourishing heart， regulating qi and invigorating blood， and moistening the intestines to promote defecation， which can provide a reference for the clinical treatment and new drug research and development for depression.

The diverse nervous system diseases （NSDs） are common complex refractory systemic diseases in clinical settings， which are manifested as trigeminal neuralgia， facial paralysis， neuromyelitis optica， multiple sclerosis， stroke， vascular dementia， encephalitis B， Parkinson's disease， epilepsy， Alzheimer's disease， amyotrophic lateral sclerosis， and diabetic peripheral neuropathy. Amid the accelerating population aging， the morbidity and prevalence of NSDs have been on the rise， posing a threat to quality of life of patients and bringing a heavy burden to society and individuals. This is also a challenge to the clinical prevention and treatment of the diseases. At the moment， NSDs are mainly treated with western medicine which is effective. However， in the long-term use and progression of the diseases， there are some potential risks such as adverse drug reactions， easy recurrence after withdrawal， drug dependence， and drug resistance. From the holistic view， traditional Chinese medicine （TCM） excels in treating diseases based on syndrome differentiation. According to the etiology， location， and pathogenesis of diseases in TCM， the overall therapy is applied， shows obvious advantages in alleviating disease symptoms， delaying disease progression， and improving the quality of life. TCM has a long history and categorizes NSDs into encephalopathy. According to clinical practice and theories， toxin is an important pathogen of NSDs in TCM. To be specific， the external toxins are insect and beast toxins， food toxin， toxin of six excesses， and epidemic toxin， and the internal toxins are phlegm toxin， dampness toxin， stasis toxin， fire toxin， and turbid toxin. Accumulation of all pathogens will lead to diseases with multiple syndromes. In the case of sudden attack of toxin， the disease is characterized by rapid onset. In the instance of fierce toxin， disease progresses rapidly. If the toxin is dependent， the disease symptoms are diverse. If the toxin is stubborn and frequently occurs， disease recurrence is common. In the case that toxin damages the collaterals， the healthy Qi is impaired. Controlling physiological function of the body， nervous system corresponds to the house of brain in TCM， which is the extraordinary organ， the house of intelligence， and the seat of mental activities that governs the whole body. In the case of toxin damaging the brain collaterals， cerebrospinal injury and orifice obstruction will occur， followed by disharmony of Qi and blood， Yin-yang imbalance， vital activity injury， disorder of primordial spirit， and dysfunction. The treatment principle should be detoxification and eliminating pathogen， and different diseases should be treated with the same method. At the moment， many doctors and scholars have focused on the prevention and treatment of NSDs based on the toxin pathogen. This paper summarizes the research on the clinical application of toxin pathogen causing disease in NSDs， including the peripheral nerve disease， demyelinating disease of the central nervous system， cerebrovascular disease， infectious disease of central nervous system， movement disorders， epilepsy， nervous system degenerative disease and nervous system complications of internal medicine disease， which is expected to provide some ideas and methods for the prevention and treatment of NSDs with TCM.