ObjectiveBased on ultra performance liquid chromatography-mass spectrometry（UPLC-MS） and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis（CAG） rats with liver-depression and spleen-deficiency， and to look for the correlation between cerebral cortex， hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction， hunger and satiety disorders， chronic restraint and tail clamping stimulation， lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling， 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg^-1 by gavage， and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics， behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex， hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group， the macroscopic characteristics of rats in Chaishao Liujuntang group were improved， such as hair color， mental state and stool properties， and the number of times of crossing and standing in the open field experiment was significantly increased， and the static time of forced swimming was significantly reduced（P<0.01）， and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers， but not enriched in pathways， 26 common potential biomarkers were identified in the hypothalamus， and the key metabolic pathways involved were mainly enriched in purine metabolism， glycerol phospholipid metabolism， D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach， and the key metabolic pathways involved were mainly enriched in thiamine metabolism， valine， leucine and isoleucine biosynthesis， and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex， hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex， hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics， mainly manifested by changes in the content of glycerol phospholipids， fatty acids and bile acid metabolites. Moreover， Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1β, MIP-1α, MCP-1, CCL5, IP-10, and IFN-β, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-β by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.
Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Plant Extracts/metabolism* ; Lipopolysaccharides/pharmacology* ; Macrophages ; Cytokines/metabolism* ; RNA, Messenger/metabolism*

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

Jingjin (muscle region of meridian) is a distal diagnosis and treatment system of the sinew/fascia disorders on the base of the concept of jin in TCM. Jin should be a particular palpable structure rather than a single anatomic structure with a specific distributing course. Yizhi weishu refers to a idea running through the whole process of diagnosis and treatment of sinew/fascia disorders, in which, the results, obtained by the overall observation and palpation of patient's sinew/fascia structure, are taken as the criteria of treatment. Yitong weishu (taking the sites of sensitivity or tenderness as the points) verifies this idea in practice. Under the guidance of yizhi weishu, through identifying the primary from the secondary, and regulating yin and yang, the spasticity and flaccidity of sinews/fascia can be cured and the induced diseases treated. The diagnosis and treatment system of jingjin, based on yizhi weishu, develops the original jingjin theory with vague concept involved, formulates a systematic thinking of treatment for sinew/fascia disorders and provides a new approach to clinical treatment.
Humans ; Meridians ; Acupuncture Therapy ; Muscle Spasticity

OBJECTIVE: To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection. METHODS: Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded. RESULTS: All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients. CONCLUSION Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.
Adult ; Female ; Humans ; Male ; Allografts/pathology* ; Bone Neoplasms/surgery* ; Bone Resorption/pathology* ; Bone Transplantation/methods* ; Femur/surgery* ; Osteosarcoma/pathology* ; Prostheses and Implants ; Retrospective Studies ; Treatment Outcome ; Young Adult ; Middle Aged

Objective:To investigate the efficacy of oblique lumbar interbody fusion (OLIF) combined with percutaneous transforaminal endoscopic decompression (PTED) and posterior pedicle fixation through Wiltse approach in the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis.Methods:From June 2017 to February 2022, 103 patients (50 males and 53 females) of lumbar spondylolisthesis accompanied with lumbar spinal stenosis were performed with OLIF combined with PTED and posterior pedicle fixation. The mean age was 64.1±5.2 years (range, 42-87 years). All involved cases were single-segment and included 83 cases of L 4, 5, 17 cases of L 3, 4, and 3 cases of L 2, 3. Among them, 94 cases were performed for the first time, and other 9 were revision surgery treated by posterior lumbar laminectomy previously. The visual analog scale (VAS) was used to evaluate the low back pain and leg pain, and the Oswestry disability index (ODI) was used to evaluate the lumbar function. The VAS and ODI scores were recorded respectively before the operation, at discharge, 1, 3, 6 months after the operation and at the last follow-up. Macnab criteria was used to evaluate the clinical efficacy at the last follow-up. At the same time, imaging measurements were conducted, including the anterior and posterior disc height, segmental lordotic angle, percentage of slip on lateral X-ray film and the vertebral canal area on axial MRI before and after surgery. Results:All of 103 patients were successfully operated in one stage with an average operation time of 177.7±21.5 min (range, 155-220 min), and an average intraoperative blood loss of 55.9±18.3 ml (range, 30-150 ml). The mean follow-up time were 15.1±2.6 months (range, 6-36 months). There were significant differences in both VAS scores of back and leg and ODI scores at each postoperative time point when compared with preoperative ( F=508.25, F=1524.82, F=1148.68, P<0.001). Macnab criteria of the last follow-up was evaluated as follow: excellent in 85 cases, good in 14, fair in 4, and the excellent and good rate was 96.1%. The radiographic results showed the mean immediate postoperative anterior disc height, posterior disc height, segmental lordotic angle, percentage of slip and axial area of the vertebral canal were 15.23±2.97 mm, 9.32±2.31 mm, 14.36°±4.18°, 3.89%±3.11%, 113.37±47.27 mm 2, and thus all of those increased significantly compared to the mean preoperative 11.93±3.17 mm, 7.21±2.03 mm, 6.15°±3.99°, 23.66%±7.79%, 57.63±28.91 mm 2, respectively ( t=7.84, t=7.07, t=14.91, t=27.62, t=9.68, P<0.001). All cases achieved bony fusion during 6-12 months after operation. The incidence of surgery-related complications was 10.7% (11/103). There were 3 cases of end plate fracture and 2 cases of dural injury, which had no complaint after operation. There was 1 case of pedicle screw entering into the spinal canal by mistake, and the symptoms of nerve damage appeared after operation. After 1 year it basically returned to normal. There were 2 cases of thigh numbness and 1 case of psoas major weakness after operation, all of which relieved after 4 weeks. There was 1 case continuous pain of abdominal incision after surgery. There was 1 case of cage subsidence at the last follow-up. Conclusion:OLIF combined with PTED and posterior pedicle fixation through Wiltse approach is a minimally invasive surgical method for the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis. With the combined minimally invasive techniques, the decompression, fusion and fixation of the lumbar spine can be fulfilled perfectly. It has the advantages of minimally invasive, good clical outcome, few complications and rapid rehabilitation.

Objective:To observe the short-term efficacy of 3D-printed custom-made hemipelvic prosthesis in the treatment of primary malignant bone tumors of the pubis.Methods:From June 2017 to May 2019, a total of 5 patients with pubic primary malignant tumor received type Ⅲ hemipelvectomy and reconstruction with a 3D-printed custom-made hemipelvic prosthesis at Department of Orthopedics, West China Hospital. They were 3 males and 2 females with an average age of 36.3 years (range, from 26 to 46 years). Of them, 3 underwent resection of the upper pubic ramus and 2 resection of both pubic rami. All their tumors were chondrosarcomas, with one case of Enneking stage Ⅱa and 4 cases of Enneking stage Ⅱb. Preoperative CT/MRI image fusion was used to determine the tumor-free resection margin, design guide templates for osteotomy and prosthesis, and simulate surgical procedures. A total of 5 3D-printed custom-made hemipelvic prostheses were designed, including 3 ones with an intramedullary stem to preserve partial pubis and 2 ones with a non-intramedullary stem not to preserve the pubis. The functional recovery was assessed by Musculoskeletal Tumor Society (MSTS) scores. The prosthetic position and osseointegration were evaluated by imaging examination. Oncological outcomes and complications were recorded.Results:R0 resection and precise reconstruction were accomplished in all patients. Their intraoperative blood loss ranged from 300 to 3, 700 mL (mean, 1, 680 mL), operation time from 180 to 430 min (mean, 294 min), and follow-up time from 13 to 29 months (mean, 20.6 months). All the 5 patients were alive with no evidence of disease or tumor recurrence. The functional MSTS scores at the final follow-up ranged from 29 to 31 (mean, 29.8). One male patient complained of erectile dysfunction. Fretting wear around the prosthetic stem was found in 3 patients while bone wear on the normal pubic side in 2. Osseointegration was observed in all patients with no complications like deep infection, prosthesis dislocation, prosthetic or screw breakage.Conclusion:Since 3D-printed custom-made hemipelvic prostheses can result in fine short-term efficacy for pubic primary malignant bone tumors, they may be a reliable method to reconstruct pelvic malignant tumors.

Objective To evaluate the efficacy of the new treatment regimen versus the standardized scheme for the initial treatment of smear-positive tuberculosis in the elderly.Methods A total of 302 elderly patients meeting the inclusion and exclusion criteria were selected from 14 tuberculosis-designated medical institutions in Beijing.The patients received the initial treatment of smear-positive tuberculosis from January 2014 to August 2016 in the combined prospective and retrospective study.All patients were divided into observation group(n=63)receiving treatment with 6L2 HELfx regimen from August 1,2015 to August 31,2016,and control group (n =239) receiving treatment with 6L2HELfx regimen from January 1,2014 to January 31,2015.The nation-unified standard chemotherapy regimen 2RHZE/4RH was used in tuberculosis medical service institutions for all patients.The differences between the two groups were analyzed and compared in the completion of treatment,negative conversion of sputum culture or smear,adverse drug reactions and treatment outcome.Results The completion rate of long-course therapy was significantly higher in the observation group than in control group [90.5％ (57/63) vs.79.5％ (190/239),x2 =4.034,P =0.045].The rate of negative conversion of sputum culture or smear at the end of the 2nd month was higher in the observation group than in control group,but had no significant difference[87.0％ (47/54)vs.81.6％(155/190),x2 =0.879,P=0.349].The incidence of adverse reactions was much lower in observation group than in control group[46.0％ (29/63) vs.65.3％ (156/239),x2 =7.777,P =0.005].The success rate of treatment(cure or completion of long-course therapy)was higher in observation group than in control group [90.5％ (57/63) vs.77.4％ (185/239),x2 =5.350,P =0.021].ConclusioNS As compared with the standard chemotherapy regimen,the L and Lfxcontaining treatment regimen has better effects,higher success rate of treatment and less adverse reactions in elderly patients with the initial treatment of smear-positive tuberculosis.

BACKGROUND:A new-type nano-bionic anti-adhesion hernia mesh was developed in our previous research.OBJECTIVE:To investigate the mechanical properties and cytocompatibility of the new-type nano-bionic anti-adhesion hernia mesh.METHODS:The tensile strength of the compound hernia mesh was detected using a textile detector.Mouse fibroblasts (L929) were cultured with the compound hernia mesh,and cell structures on the mesh surface were observed under electron microscope at 1,3,5 days after culture.In addition,L929 cells were co-cultured with compound hernia mesh,polypropylene patch,and polyester patch,respectively.Cells cultured alone were used as negative controls.After 1,3,5 days of culture,MTS array was used to detect cell proliferation and evaluate cytotoxicity;after 3 days of culture,western blot was used to detect the content of type Ⅰ and Ⅲ collagens.RESULTS AND CONCLUSION:The average tensile strength of the compound hernia mesh was 31.2 N The number of fibroblasts on the nanofibrous layer of the compound hernia mesh increased as long as cultured.The cells spread along the nanofibers and pseudopodia extended from the cells formed polygon and fusiform structures,with a good cross-linking with the mesh.A complete cell layer covered all pores of the nanofibers at 5 days.The cytotoxicity of the nanofibrous layer of the compound hernia mesh was graded 0,and the cytotoxicity was graded 1 of polypropylene and polyester patches.All the three kinds of patches fulfilled the implantation requirements,and the compound hernia mesh had better biological properties.No significant differences were found among groups in the contents of type Ⅰ and Ⅲ collagens at 3 days of culture.To conclude,the new-type nano-bionic anti-adhesion hernia mesh has good mechanical properties and cytocompatibility.

Objective To explain the concept and surgical technique of 3D printing uncement radius distal prosthesis,evaluate and discuss the medium-term outcome of the prosthesis for giant cell tumor in distal radius.Methods From September 2015 to March 2017,13 patients diagnosed as giant cell tumor in distal radius were performed with en bloc resection combined with 3D print uncement prosthesis.All patients graded Campanacci Ⅲ or occurred local recurrence.Two patients with local recurrence had a local lesion curettage,inactivation and bone cement filling.There were 7 males and 6 females,with an average age of 37.8 years.Through the preoperative three-dimensional CT data,the 3D model of the distal radius was obtained based on the contralateral radius and the 3D printing uncemented distal radius prosthesis was made.Directly reconstrucion was conducted if the wrist joint ligament and joint capsule can be preserved.The surrounding soft tissue,remaining joint ligament and joint capsule were sutured to the prosthesis together combined with a brace if the wrist joint ligament and joint capsule can be only preserved partially.Radiocarpal joint was temporarily fixed by Kuntscher pin if the wrist joint ligament and joint capsule can't be preserved completely.Results In our series,the average resection length of the distal radius measured from the radial styloid process was 65.54±6.70mm.The length of prosthesis was consistent with the resection length and the length ratio of prosthesis to prosthetic stem is 1:1.The follow-up time was 17.77±4.97 months.There were no local recurrence and metastasis.At the end of the followup,except waist flexion,the wrist extension,wrist pronation,wrist supination,hand grip strength and Mayo wrist were significantly improved from 41.69°± 11.35°,41.92°± 11.09°,40.00°±7.64°,16.84±6.28 mmHg,47.69±9.27 points preoperatively to 57.46°±17.18°,55.00°±17.91°,53.46°±19.30°,23.08±6.29 mmHg,70.00±11.55 points,respectively.The DASH score was significantly decreased from 32.07±6.71 points to 19.15±8.41 points postoperatively.During surgery,there was one patient received temporary wrist fixation with kirschner's needle,which got a relatively poor postoperative function.Excluding this patient,comparing the resuits of 8 cases with directly suturing of wrist joint ligament and joint capsule and that of 4 cases with reconstructing by suturing and fixing with a brace,there were no statistical differences.There were no wrist dislocation or subluxation,aseptic prosthesis loosening,wrist joint degenerative changes or other prosthesis related complications.Conclusion 33D printing uncemented distal radius prosthesis is a good choice for the Campanacci grade Ⅲ or recurrent giant cell tumor in distal radius,because of its personalized design and uncemented fixation;in clinical application,we should pay attention to the evaluation of preoperative wrist joint capsule and surrounding ligament and the intraoperative soft tissue repair techniques.