Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids / 药物分析学报

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and patho-logical conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of＞1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in N-desethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal infor-mation for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.

Research progress of Chiari malformation type I and atlantoaxial instability / 中华骨科杂志

Chiari malformation (CM) is a group of congenital cerebellar tonsillar hernia malformations involving the craniocervical junction. Chiari malformation type I (CMI) is the most common in clinic, however its pathogenesis is still unclear, and there is no consensus on the surgical treatment standard of CMI. At present, the most widely accepted is the theory of posterior fossa incompatibility, so doctors at home and abroad use posterior fossa decompression (PFD) and posterior fossa compression with duraplasty (PFDD) as the gold standard for surgical treatment, and have their own experience and technical improvement. However, the volume of the posterior cranial fossa in some patients is no different from that in healthy people, and about 30% of the patients with CMI have poor results after posterior cranial fossa decompression. As a result, this operation cannot treat all patients with CMI. In recent years, with the development of imaging, the progress of diagnostic technology and the deepening of understanding of CM, some studies have shown that CMI may be related to atlantoaxial instability, and proposed that CMI is the secondary factor of atlantoaxial instability, and atlantoaxial fusion is the standard of surgical treatment, which has caused great controversy in academic circles. Different clinical research results of scholars support or oppose this theory: some studies have shown that the clinical symptom relief rate of patients with CMI treated with atlantoaxial fusion is 96.9%; another study showed that 70% of patients with CMI underwent atlantoaxial fusion had improved neurological function, but the overall postoperative effect was not satisfactory. In short, CMI is related to many diseases and its clinical manifestations are complex. Therefore, individualized management and treatment should be carried out in combination with the clinical manifestations and auxiliary examination results of patients.

Comprehensive chemical profiling and quantitative analysis of ethnicYi medicine Miao-Fu-Zhi-Tong granules using UHPLC-MS/MS / 中国天然药物

Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.

Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets

Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.

Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid / 药物分析学报

Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

Imaging study of simple Chiari malformation type I and atlantoaxial instability / 中华骨科杂志

Objective:To investigate the relationship between simple Chiari malformation type I (CMI) and atlantoaxial instability from the imaging point of view.Methods:A retrospective analysis were performed on 46 patients diagnosed with simple CMI from January 2014 to December 2020. Forty-six normal people matched for age and sex were selected as the normal control group, while 30 patients with atlantoaxial dislocation were selected as the dislocation group. The degree of atlantoaxial joint degeneration in each group was assessed according to Weishaupt degeneration grading; the atlantoaxial joint angulation angle was measured in the control group of patients with simple CMI; and the sagittal imaging parameters of cervical spine X-ray were measured, including C 0-C 1 Cobb angle, C 0-C 2 Cobb angle, C 1-C 2 Cobb angle, C 1-C 7 Cobb angle, C 2-C 7 Cobb angle, C 7 Slope, C 2 Tilt, spino cranial angle (SCA), and C 2-C 7 sagittal vertebral axis (SVA). All radiographic parameters were measured twice independently by two spine surgeons, and intraclass correlation coefficient (ICC) were determined to demonstrate intra- and inter-observer reliability. Results:ICC ranged between 0.842 and 0.974 in the current study, demonstrating "excellent" reliability of radiographic measurements. No significant difference was noted regarding age and the distribution of genders among the three groups. There were significant differences in the distribution of Weishaupt degeneration grading of atlantoaxial joints between simple CMI, normal and dislocation group ( H=53.68, P<0.001 on the left side; H=43.39, P<0.001 on the right side). There were significant differences in the degree of atlantoaxial joint degeneration between the normal group and dislocation group (left, Z=6.60, P<0.001; right, Z=6.29, P<0.001); There were significant differences in the degree of atlantoaxial joint degeneration between the normal group and simple CMI patients (left, Z=5.31, P<0.001; right, Z=4.13, P<0.001); There were significant differences in the degree of atlantoaxial joint degeneration between simple CMI and dislocation group (left, Z=3.20, P=0.001; right, Z=3.15, P=0.002). There were significant difference in the angulation angle of the atlantoaxial articular surface between the normal group and simple CMI patients (left, Z=3.32, P<0.001; right, Z=5.74, P<0.001). There were significant differences in C 0-C 1 Cobb angle ( t=2.41, P=0.018), C 1-C 7 Cobb angle ( t=2.88, P=0.005), C 2-C 7 Cobb angle ( t=3.29, P=0.001), and C 2-C 7 SVA ( t=2.87, P=0.005) between the normal group and simple CMI patients, but there was no significant difference in other parameters. Conclusion:The degree of atlantoaxial joint degeneration in patients with simple CMI is higher than that in normal people, the angulation angle is larger, and the cervical lordosis is larger, suggesting that there may be atlantoaxial joint instability. This study provides further evidence that Chiari malformation type I is associated with atlantoaxial instability.

Comparative study of native vertebral osteomyelitis and pyogenic postoperative and analysis of prognostic factors / 中华骨科杂志

Objective:To compare the microbiology, clinical characteristics and therapeutic efficacy of native suppurative spondylitis (NVO) and postoperative suppurative spondylitis (PVO), and analyze the factors affecting the prognosis.Methods:All patients with suppurative spondylitis were retrospectively analyzed from December 2010 to December 2019. A total of 46 patients were enrolled in this study. They were divided into two groups. There were 30 cases in NVO group, 18 males and 12 females; The age was 50.47±20.45 years, aged 15-73 years. There were 16 cases in PVO group, 10 males and 6 females; The age was 52.13±18.80 years, aged 14-73 years. In group NVO, 23 cases (76.7%) were in lumbar vertebrae, 5 cases (16.7%) in thoracic vertebrae and 2 cases (6.7%) in cervical vertebrae; in group PVO, 11 cases (68.8%) in lumbar vertebrae and 5 cases (31.2%) in thoracic vertebrae. Twenty-eight patients had neurological dysfunction before surgery. There were 25 cases of grade D (16 cases in group NVO and 9 cases in group PVO) and 3 cases of grade C (1 case in group NVO and 2 cases in group PVO), following the instructions of American Spinal Injury Association (ASIA) neurological function classification. All patients were given bed rest, nutritional support and antibiotic therapy; surgical treatment for patients with poor outcomes or aggravated symptoms. The patients were followed up after operation, the observation indexes included leukocyte count, erythrocyte sedimentation rate and C -reactive protein to evaluate the postoperative curative effect. The internal fixation device was evaluated for looseness and fracture by imaging examination. At the same time, the changes of visual analogue scale, ASIA neurological function grade were recorded to evaluate the clinical efficacy.Results:Two patients in NVO group were treated with antibiotics, and all the other patients successfully completed the operation. The diseased tissues were sent for pathological examination during the operation. The results showed that they were diagnosed as suppurative spondylitis. All patients were followed up for 12-24 months. Both groups were treated with intravenous and oral antibiotics, and the time of antibiotic treatment in group PVO was longer than that in group NVO without significant difference ( t=1.74, P=0.088). The leukocyte, C-reactive protein, erythrocyte sedimentation rate, visual analogue scale (VAS), were significantly improved in both groups at different time points after operation ( P<0.05) . There was no significant difference in leukocyte, C -reactive protein, erythrocyte sedimentation rate or VAS score between the two groups at the same time point after operation ( P>0.05). The neurological function of patients after operation was significantly improved compared with that before operation. In group NVO, 16 cases recovered from ASIA grade D to grade E, 1 case from grade C to grade D; 9 cases in group PVO recovered from grade D to grade E and 2 cases recovered from grade C to grade D. Till the last follow-up, 3 patients in group NVO recurred, the recurrence rate was 10% (3/30); 7 patients in group PVO recurred, the recurrence rate was 43.8%; the recurrence rate of group PVO was higher than that of group NVO, the difference was statistically significant (χ 2=5.14, P=0.023). Among 39 patients with spinal internal fixation, 12.8% (1 NVO, 4 PVO) had recurrent infection after internal fixation. Therefore, re-operation was performed to remove the internal fixator for infection control, patients recovered after conservative treatment such as immobilization and systemic anti-infection By univariate analysis, multiple vertebral involvement and abscess formation ( OR=11.00, P=0.006; OR=9.00, P=0.047) were significantly associated with pyogenic spondylitis recurrence; there was a tendency for pyogenic spondylitis recurrence among microbial infection ( OR=1.87, P=0.416), spinal prosthesis ( OR=7.20, P=0.074) and allogenic bone ( OR=1.78, P=0.478), yet not obvious. Multivariate analysis indicated that multiple vertebral involvement ( OR=10.49, P=0.038) was a risk factor for pyogenic spondylitis recurrence. Conclusion:The treatment of PVO is more challenging than NVO, especially in the cases of spinal implant infection. Although the antibiotic treatment time of PVO is longer than that of NVO, the recurrence rate of PVO is higher. Longer antibiotic therapy and, if necessary, surgical debridement or removal of implants are important approaches to successful treatment of PVO.

Study of mass spectrometry imaging metabolomics of paclitaxel based on esophageal cancer multicellular tumor spheroids cultured in vitro / 药学学报

Multicellular tumor spheroids (MCTS) can simulate the structure and metabolic characteristics of tumors in vivo, which is of great significance to study the metabolic phenotype of tumor cells and the mechanism of drug intervention. In this study, esophageal cancer MCTS were constructed, and MCTS frozen sections were prepared after treated with different formulations of paclitaxel (PTX) including common PTX injection, PTX liposome and albumin bound PTX. MCTS mass spectrometry imaging analysis method was established by using air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). The visualization of the permeation and enrichment process of PTX in MCTs after PTX treatment was realized, and the spatially resolved metabolomics of PTX injection group was studied. The results showed that the permeation and enrichment behavior of PTX in MCTs model were related to the formulations. The changes of endogenous metabolites in MCTs of esophageal cancer after treated with PTX injection had temporal and spatial characteristics. The metabolic changes of MCTS during the initial 0-4 hours were dominated by the down-regulation of middle-high polarity metabolites and some lipids in the central region of MCTS, while the metabolic changes of MCTS during 8-72 hours were mainly up-regulated by lipid metabolites in the peripheral region of MCTS. The combination of in vivo tumor-associated MCTs model with label free, highly sensitive and high coverage mass spectrometry imaging technology provided a new method and strategy for the study of pharmacometabolomics.

MR spectroscopy for noninvasive prediction of IDH status in low-grade glioma with 2-hydroxyglutarate integrated with glutamate and glutamine / 中华放射学杂志

Objective:To investigate the functional imaging parameters that effectively distinguish isocitrate dehydrogenase (IDH) gene mutation status in clinical practice with long echo time (TE) point-resolved spectroscopy (PRESS) MRS.Methods:Totally 25 patients with suspected diagnosis of low grade gliomas(LGGs; Grade II) were recruited prospectively and divided into IDH mutation group and IDH wild group according to pathological results in the study. All patients were scanned with long TE PRESS MRS. In addition, IDH mutational status was determined by post-operation Sanger sequencing. The t test or Mann-Whitney U test was used to analyze the differences of 2-hydroxyglutarate (2HG), Glutamate (Glu), Glutamine (Gln) and 2HG/Glu+Gln between the IDH mutation group and the IDH wild group, then ROC curve was plotted with statistically significant indexes to obtain the efficacy of predicting IDH mutation status. Results:Of the 25 patients, 19 had IDH mutant gliomas and 6 had IDH wild-type gliomas. 2HG, Glu, Gln and 2HG/Glu+Gln in IDH mutated group were 1.42 (1.09, 1.93)mmol/L, (1.74±1.31)mmol/L, (1.68±0.66)mmol/L, 0.55 (0.28, 0.77), respectively; while the corresponding values were 0.00 (0.00, 1.30)mmol/L, (3.28±1.02)mmol/L, (2.55±1.47)mmol/L, 0.00 (0.00, 0.26) in IDH gene wild type group, respectively. The differences of 2HG, Glu, and 2HG/Glu+Gln between the two groups were statistically significant ( P values were 0.030, 0.016, 0.004, respectively). The area under the ROC curve of 2HG/Glu+Gln was the largest (0.877), and the sensitivity was the highest (84.2%). Conclusion:The integration of 2HG with Glu and Gln can effectively realize the noninvasive assessment of IDH mutation status.

Effect of proximal thoracic curve and main thoracic curve correction rate on postoperative shoulder balance in Lenke 1 adolescent idiopathic scoliosis / 中华骨科杂志

Objective:To investigate the effects of the correction rate of the proximal thoracic curve and main thoracic curve on postoperative shoulder balance in patients with Lenke1 type idiopathic scoliosis (AIS).Methods:Data of 50 patients with AIS who received posterior spinal deformity correction surgery from January 2013 to January 2020 and were followed up for more than 6 months were retrospectively analyzed, including 12 males and 38 females. The median age was 15 years (14,16) years (range 13 to 18 years). According to the clavicle angle (CA) absolute value >2° and 2.5° and 3° for shoulder imbalances standard, the patients were divided into the postoperative shoulder balance group and shoulder imbalance group. Main thoracic curve Cobb angle, proximal thoracic curve Cobb angle and clavicle angle (CA) were measured preoperative, postoperative and at the last follow-up, and the flexibility of proximal thoracic curve, the flexibility of main thoracic curve, correction rate of proximal thoracic curve, correction rate of the main thoracic curve and other indicators were calculated. Univariate analysis was conducted on the shoulder balance group's related indicators and the shoulder imbalance group, and correlation analysis was conducted with the postoperative shoulder balance and the last follow-up shoulder balance. Multivariate binary logistic regression was performed on statistically significant univariate factors to determine independent risk factors for postoperative shoulder imbalance and the last follow-up shoulder imbalance.Results:The median follow-up time of 50 patients was 18 months (11, 24) months (range 6-36 months). According to the three criteria of shoulder balance, the postoperative correction rate of the proximal thoracic curve in the shoulder imbalance group was significantly lower than that in the shoulder balance group. Under the standard of shoulder imbalance with CA absolute value >2° and 2.5°, there were significant differences in the postoperative correction rate of the main thoracic curve, and the postoperative correction rate of the main thoracic curve in the shoulder balance group was higher than that in the shoulder imbalance group. No matter which shoulder imbalance criteria were used, the postoperative correction rate of the proximal thoracic curve, the correction rate of the main thoracic curve, and the ratio of the correction rate of the main thoracic curve to the proximal thoracic curve was found to be correlated with the postoperative shoulder balance. Only in the group of CA absolute >3°, no correlation was found between the postoperative correction rate of the main thoracic curve and postoperative shoulder balance. The correlation between the correction rate of the proximal thoracic curve and shoulder balance was more significant in the three groups ( P<0.01). Logistic regression analysis showed that the postoperative correction rate of the proximal thoracic curve was an independent protective factor of postoperative shoulder balance ( P<0.05). A better postoperative shoulder balance can be obtained when the main thoracic curve/proximal thoracic curve correction rate was less than 1.5. However, at the last follow-up, no correlation was found between the correction rate and shoulder balance in all three groups. Binary logistic regression analysis showed that preoperative CA was a risk factor for the last follow-up shoulder imbalance. Conclusion:IIn patients with Lenke1 type AIS, the correction rate of the proximal thoracic curve, the correction rate of the main thoracic curve, and their ratio were correlated with postoperative shoulder balance. The matching of the amount of correction of the proximal thoracic curve and main thoracic curve can ensure postoperative shoulder balance, and the amount of correction of the proximal thoracic curve may be a protective factor of postoperative shoulder balance. However, for long-term shoulder balance, the effect of the proximal thoracic curve and main thoracic curve correction rate is not obvious. In contrast, compensatory factors such as proximal thoracic cure aggravation, torso tilt, and lumbar curve aggravation mayaffect.

Unilateral or bilateral posterior fenestration debridement and bone graft fusion for the treatment of lumbosacral brucellosis spondylitis / 中华骨科杂志

Objective:To analyze the application and clinical efficacy of one-stage unilateral or bilateral fenestration, debridement, interbody fusion combined with posterior internal fixation for the treatment of lumbosacral brucellosis spondylitis.Methods:All patients with lumbosacral brucellosis spondylitis were retrospectively analyzed, who underwent fenestration, debridement, interbody fusion combined with posterior internal fixation from June 2013 to June 2019. A total of 48 patients were enrolled in this study. According to the surgical method, they were divided into two groups. Unilateral fenestration group: 27 cases of one-stage posterior unilateral fenestration, debridement, interbody fusion combined with posterior internal fixation were performed, 21 males and 6 females, aged 23-71 years; Bilateral fenestration group: 21 cases of one-stage posterior bilateral fenestration, debridement, interbody fusion combined with posterior internal fixation were performed, aged 26-58 years. There were 16 males and 5 females. The preoperative and postoperative clinical symptoms, neurological function, C-reactive protein, the surgery duration time, the blood loss, and erythrocyte sedimentation rate were observed. The internal fixation device was evaluated for looseness or fracture by imaging examination. The Bridwell classification criteria were used to evaluate the bone graft fusion. Postoperative complications were also assessed.Results:All patients completed the operation successfully, and the diseased tissues were sent for pathological examination during the operation, and all of them were diagnosed as brucellosis. All patients were followed up for 12-48 months (mean 23.7 ±6.3 months). C-reactive protein, erythrocyte sedimentation rate, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association Scores (JOA) were significantly improved in both groups at different time points after operation. There was no significant difference in the general condition before operation between the two groups ( P>0.05). The mean operation time and mean blood loss were 120.5±34.1 min and 214.4±150.2 ml, in the unilateral fenestration group; 187.1±30.3 min and 455.8±250.5 ml in the bilateral fenestration group; and the difference was significant ( t=8.123, t=2.962, P<0.05) . The postoperative lumbar and leg pain were significantly relieved. There was no significant difference in C-reactive protein, erythrocyte sedimentation rate, VAS, ODI and JOA scores between the two groups at the same time point. In the bilateral fenestration group, one patient developed incision infection half a month after the operation, who underwent debridement and drainage, and finally cured. There was no significant difference in the time of bone graft fusion between the two groups ( t=0.542, P>0.05). At the last follow-up, all the patients were completely fused. Conclusion:Unilateral or bilateral fenestration, debridement and bone graft fusion and internal fixation for the treatment of lumbosacral brucellosis spondylitis can achieve good clinical results, and the former has the advantages of short operation time and low cost.

Efficacy of Y type osteotomy in the treatment of severe post-tuberculous thoracolumbar kyphosis / 中华骨科杂志

Objective:To explore the clinical efficacy and surgical indications of Y type osteotomy in the treatment of post-tuberculous thoracolumbar severe angular kyphosis.Methods:From March 2012 to June 2018, 36 patients with post-tuberculous thoracolumbar severe angular kyphosis were treated with Y type osteotomy, including 22 males and 14 females, aged 23.6±5.7 years (range, 7-57 years). The parietal vertebrae of kyphosis were located in the upper thoracic vertebra in 3 cases, the thoracic vertebra in 11 cases, the thoracolumbar segment in 17 cases, and the lumbar vertebra in 5 cases. The Cobb angle of kyphosis before the operation was 92.8°±23.3° (range, 60°-147°). The visual analogue scale (VAS), American Spinal Injury Association (ASIA) neurological function grade, and Kirkaldy-Willis function score were used to evaluate the clinical effect. The imaging evaluation indexes were interbody kyphosis angle and spinal bone fusion.Results:The operation was successful in all the 36 patients. The operation time was 210 ±25.9 min (range, 180-270 min), the intraoperative blood loss was 520 ±110 ml (range, 400-800 ml), and the postoperative follow-up time was 26.38±1.75 months (range, 22-30 months). The postoperative kyphosis Cobb angle was corrected to 16.5°±7.7° (range, 5°-35°), which was significantly improved compared with that before operation( t=25.438, P<0.01), and the correction rate was 82.2%. At the last follow-up, the kyphosis angle was 16.5°±7.1° (range, 6°-32°), which was not significantly different from that after the operation. The preoperative VAS score was 7.3±1.8 (range, 3-9), and the postoperative VAS score was 2.4±0.8 (range, 1-3), while the improvement rate was 67.1%. At the last follow-up, it was 1.1±0.6 (range, 0-2), and the improvement rate was 85.0%. According to the Kirkaldy-Willis functional score, the results were excellent in 25 cases, good in 8 cases, and fair in 3 cases at the last follow-up, with an excellent and good rate of 91.7%. Before the operation, 9 cases were accompanied by neurological dysfunction (ASIA grade: grade C in 2 cases, grade D in 7 cases). At the last follow-up, all the 9 patients recovered to grade E. During the operation, the electrophysiological nerve monitoring was abnormal in 2 patients, and the awakening test was negative in 1 case. In another patient, neuroelectrophysiological monitoring after posterior column osteotomy showed a decrease in bilateral sensory and motor function. There was no compression around the spinal cord in the osteotomy area, so the operating bed was gradually folded and partially restored to kyphosis and temporarily fixed with double rods. Neuroelectrophysiological monitoring suggested the recovery of nerve function. The awakening test showed that the nerve function of both lower limbs recovered close to the preoperative state, and further osteotomy and internal fixation was performed 2 weeks later. The nerve function of both lower limbs returned to normal after 3 months. After the operation, one patient's muscle strength of the lower limbs decreased from grade 5 to grade 3, and the sensory function was normal. After symptomatic support treatment such as neurotrophic drugs, it returned to normal 2 weeks later. 1 case developed delayed neurological dysfunction 1 year after the operation. Neurotrophic drugs and rehabilitation treatment improved it. The sinus of the incision was formed in one case 3 months after the operation and healed after debridement and suture. Conclusion:Y typeosteotomyis a safe and effective method for patients with post-tuberculous thoracolumbar severe angular kyphosis. Compared with traditional osteotomy, anterior support bone grafting can be avoided, and spinal shortening can be reduced.

Effect of laser irradiation on related growth factors in and apoptosis of in vitro cultured infantile hemangioma endothelial cells / 中华皮肤科杂志

Objective:To evaluate the effect of laser irradiation on related growth factors in and apoptosis of in vitro cultured infantile hemangioma endothelial cells. Methods:Cultured infantile hemangioma endothelial cells were divided into 3 groups: intense pulsed light (IPL) group irradiated with IPL at a dose of 23 J/cm 2 for 1 session, laser group irradiated with 1 064-nm Nd:YAG laser at a dose of 90 J/cm 2 for 1 session, control group receiving no irradiation. On days 1, 3 and 7 after irradiation, RT-PCR was performed to measure the mRNA expression of vascular endothelial growth factor (VEGF) , VEGF receptor 2 (VEGFR-2) and basic fibroblast growth factor (bFGF) , and Western blot analysis to determine VEGFR-2 protein expression, enzyme-linked immunosorbent assay to detect the levels of VEGF and bFGF in the culture supernatant, and flow cytometry to detect cell apoptosis. Results:Compared with the control group, the laser group showed significantly decreased mRNA expression of VEGF (0.363±0.021 vs. 1.000±0.023, P< 0.001) , VEGFR-2 (0.483±0.017 vs. 1.001±0.031, P=0.001) and bFGF (0.402±0.040 vs. 1.000±0.004, P< 0.001) , decreased VEGFR-2 protein expression (0.332±0.055 vs. 0.768±0.096, P< 0.05) , decreased levels of VEGF (69.389±24.179 ng/L vs. 334.506±13.084 ng/L, P< 0.001) and bFGF (2.386±0.151 ng/L vs. 9.165±0.232 ng/L, P< 0.001) in the culture supernatant, but significantly increased apoptosis rate (18.413%±2.654% vs. 4.300%±0.036%, P< 0.01) on day 7 after irradiation. Compared with the control group, the IPL group also showed significantly decreased mRNA expression of VEGF (0.436±0.041 vs. 1.000±0.023, P< 0.05) , VEGFR-2 (0.493±0.037 vs. 1.001±0.031, P< 0.05) and bFGF (0.490±0.044 vs. 1.000±0.004, P< 0.05) , decreased VEGFR-2 protein expression (0.406±0.037 vs. 0.768±0.096, P< 0.05) , decreased levels of VEGF (128.858±6.063 ng/L vs. 334.506±13.084 ng/L, P< 0.001) and bFGF (2.723±0.471 ng/L vs. 9.165±0.232 ng/L, P< 0.001) in the culture supernatant, but significantly increased apoptosis rate (16.597%±1.877% vs. 4.300%±0.036%, P< 0.01) on day 7 after irradiation. Conclusion:The 1 064-nm Nd:YAG laser may exert a therapeutic effect on hemangioma by inhibiting hemangioma endothelial cells via regulating key factors on the VEGF/VEGFR-2 signaling pathway and cell apoptosis.

Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

Retrospective analysis of 122 patients with tinea capitis in a third-grade class-A hospital in Xinjiang from 2010 to 2018 / 中华皮肤科杂志

Objective:To analyze characteristics of and distribution of pathogenic fungi in patients with tinea capitis in the First Affiliated Hospital of Xinjiang Medical University from 2010 to 2018.Methods:Clinical data were collected from 122 tinea capitis patients with positive fungal culture results in Department of Dermatology, First Affiliated Hospital of Xinjiang Medical University from 2010 to 2018, and retrospectively analyzed. Fungal culture was carried out, and lactophenol cotton blue staining was performed for morphological identification of the fungal isolates.Results:Of the 122 patients with tinea capitis, 112 (91.8%) were children, including 70 (62.5%) males and 42 (37.5%) females, and there were 58 (51.79%) preschool children and 37 (33.04%) school-age children; 9 (7.38%) were adults, including 7 females and 2 males; 66 (54.1%) were of Uygur nationality, 46 (37.7%) of Han nationality, 5 (4.1%) of Kazakh nationality, 3 (2.46%) of Hui nationality, 1 (0.82%) of Mongolian nationality, and 1 of unknown nationality. The annual number of cases of tinea capitis was more than 20 from 2011 to 2013, and gradually decreased year by year from 2014 (≤ 13 cases/year) . All the patients were infected with a single fungal strain, and a total of 122 strains were identified, including 46 (37.7%) strains of Microsporum ferrugineum, 44 (36.07%) strains of Microsporum canis, 10 (8.2%) strains of Trichophyton violaceum, 9 (7.38%) strains of Trichophyton schoenleini, 6 (4.91%) strains of Trichophyton tonsurans, 4 (3.28%) strains of Trichophyton mentagrophytes, 3 (2.46%) strains of Trichophyton verrucosum. Microsporum ferrugineum (anthropophilic species) mostly affected patients of Uygur nationality (34 cases, 73.91%) , and Microsporum canis (zoophilic species) mostly affected patients of Han nationality (26 cases, 59.09%) . Conclusion:In the Department of Dermatology, First Affiliated Hospital of Xinjiang Medical University from 2010 to 2018, tinea capitis commonly affected male children of Uygur nationality, and Microsporum ferrugineum and Microsporum canis were the dominant pathogenic species.

Multiple Organ Echinococcosis:Report of One Case and Literature Review / 中国医学科学院学报

A patient with multiple-organ echinococcosis suffered from liver echinococcosis,lung echinococcosis,and pelvic echinococcosis successively in the past three decades.From the first operation at 19 years-old,she underwent operations several times due to the recurrence of multiple organ involvement.Echinococcosis is a zoonotic disease.Although the liver usually is the primary site,the disease can also invade many other organs.Diagnosis is typically based on disease history and imaging findings.Thorough removal of the lesions during the first operation is particularly important.Comprehensive evaluations and multi-disciplinary team are helpful in the treatment of patients with multiple organ invasion.

metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. As a result, 38 metabolites related to the arginine-creatinine metabolic pathway, the urea cycle, the serine synthesis pathway, metabolism of lipids, choline, histamine, lysine, and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I. These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions. This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.

Treatment of non-curable severe tuberculous thoracolumbar kyphosis by posterior deformity correction combined with anterior supporting bone graft / 中华骨科杂志

Objective@#To explore the clinical effect of posterior deformity correction combined with anterior lesion re-moval and bone graft in the treatment of non-curable severe tuberculous thoracolumbar kyphosis.@*Methods@#All of 27 patients with non-curable severe tuberculous thoracolumbar kyphosis treated by posterior deformity correction combined with primary or secondary anterior debridement and bone grafting from January 2013 to July 2017 were retrospective analyzed, including 10 males and 17 females. The age ranged from 2 to 38 years with an average of 17.3±9.9 years. Posterior column osteotomy, spinal cord de-compression, cantilever bar pressing technique and intraoperative longitudinal traction were used to correct kyphosis. According to clinical symptoms, Cobb angle correction rate of kyphosis deformity, sagittal SVA of spine, height difference before and after opera-tion, operation time, intraoperative bleeding volume, complications, and the effect of the operation was evaluated. Symptoms and functional evaluation indicators included visual analogue scale (VAS), American Spinal Injury Association (ASIA) spinal cord inju-ry classification, Oswestry dysfunction index (ODI), and Kirkaldy-Willis functional score. Laboratory tests included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Eck fusion grading standard was used to evaluate the degree of bone graft fusion.@*Results@#All the 27 patients successfully underwent the operation. The operation time was 210-530 minutes, with an aver-age of 343.0±71.5 minutes, while the bleeding volume was 300-2 600 ml, with an average of 1 168.5±606.7 ml. The preoperative Cobb angle ranged from 81 to 144 degrees, with an average of 105.2±17.7 degrees; the postoperative Cobb angle ranged from 5 to 47 degrees, with an average of 28.2±0.3 degrees, and the average correction rate was 72.9%±9.8%; the preoperative sagittal SVA ranged from 96.66 mm to 78.76 mm, with an average of 40.5±20.4 mm; and the postoperative sagittal SVA ranged from 33.61 mm to 44.96 mm, with an average of 26.6±12.6 mm. The height difference before and after operation was 26.8-172.7 mm, with an aver-age of 67.5±37.8 mm. The follow-up period ranged from 12 to 36 months, with an average of 19.3±6.7 months. At the last follow-up, the loss of Cobb angle ranged from 1 degree to 8 degree, with an average of 4.3°±1.8° degree. The postoperative nutritional sta-tus of all patients was significantly improved. At 3 months after operation, the average VAS score was 1.1±0.6 and the improve-ment rate was 47.5%. The difference was statistically significant (t=6.31, P<0.05). At 3 months after operation, the average ODI was 6.5%±4.1%, and the improvement rate was 68.1%. The difference was statistically significant (t=8.41, P<0.05). At the last fol-low-up, all the patients were improved to grade E in ASIA except one patient from grade B to grade D, and one stayed at grade E. Kirkaldy-willis functional score: excellent in 24 cases, good in 2 cases, and good in 1 case, with a total good/good rate of 88.9%. Cerebrospinal fluid leakage occurred in 3 patients after surgery, and pleural effusion occurred in 4 patients after surgery. No recur-rence of tuberculosis, loosening of internal fixation, fracture or loss of obvious correction were found during the follow-up. Accord-ing to the Eck fusion classification standard, at the time of the last follow-up bone graft area of all 27 cases reached I level fusion.@*Conclusion@#For non-curable severe tuberculous thoracolumbar kyphosis with multi-segment vertebral body loss, good deformity correction and proper recovery of vertebral height can be achieved by posterior osteotomy combined with cantilever beam tech-nique and intraoperative longitudinal traction. The combination of anterior debridement and bone graft fusion is a safe and reliable method.

Treatment of non?curable severe tuberculous thoracolumbar kyphosis by posterior deformity correction combined with anterior supporting bone graft / 中华骨科杂志

Objective To explore the clinical effect of posterior deformity correction combined with anterior lesion re?moval and bone graft in the treatment of non?curable severe tuberculous thoracolumbar kyphosis. Methods All of 27 patients with non?curable severe tuberculous thoracolumbar kyphosis treated by posterior deformity correction combined with primary or secondary anterior debridement and bone grafting from January 2013 to July 2017 were retrospective analyzed, including 10 males and 17 females. The age ranged from 2 to 38 years with an average of 17.3±9.9 years. Posterior column osteotomy, spinal cord de?compression, cantilever bar pressing technique and intraoperative longitudinal traction were used to correct kyphosis. According to clinical symptoms, Cobb angle correction rate of kyphosis deformity, sagittal SVA of spine, height difference before and after opera?tion, operation time, intraoperative bleeding volume, complications, and the effect of the operation was evaluated. Symptoms and functional evaluation indicators included visual analogue scale (VAS), American Spinal Injury Association (ASIA) spinal cord inju?ry classification, Oswestry dysfunction index (ODI), and Kirkaldy?Willis functional score. Laboratory tests included erythrocyte sedimentation rate (ESR) and C?reactive protein (CRP). Eck fusion grading standard was used to evaluate the degree of bone graft fusion. Results All the 27 patients successfully underwent the operation. The operation time was 210-530 minutes, with an aver?age of 343.0±71.5 minutes, while the bleeding volume was 300-2 600 ml, with an average of 1 168.5±606.7 ml. The preoperative Cobb angle ranged from 81 to 144 degrees, with an average of 105.2±17.7 degrees; the postoperative Cobb angle ranged from 5 to 47 degrees, with an average of 28.2±0.3 degrees, and the average correction rate was 72.9%±9.8%; the preoperative sagittal SVA ranged from 96.66 mm to 78.76 mm, with an average of 40.5±20.4 mm; and the postoperative sagittal SVA ranged from 33.61 mm to 44.96 mm, with an average of 26.6±12.6 mm. The height difference before and after operation was 26.8-172.7 mm, with an aver?age of 67.5±37.8 mm. The follow?up period ranged from 12 to 36 months, with an average of 19.3±6.7 months. At the last follow?up, the loss of Cobb angle ranged from 1 degree to 8 degree, with an average of 4.3°±1.8°degree. The postoperative nutritional sta?tus of all patients was significantly improved. At 3 months after operation, the average VAS score was 1.1±0.6 and the improve?ment rate was 47.5%. The difference was statistically significant (t=6.31, P<0.05). At 3 months after operation, the average ODI was 6.5%±4.1%, and the improvement rate was 68.1%. The difference was statistically significant (t=8.41, P<0.05). At the last fol?low?up, all the patients were improved to grade E in ASIA except one patient from grade B to grade D, and one stayed at grade E. Kirkaldy?willis functional score: excellent in 24 cases, good in 2 cases, and good in 1 case, with a total good/good rate of 88.9%. Cerebrospinal fluid leakage occurred in 3 patients after surgery, and pleural effusion occurred in 4 patients after surgery. No recur?rence of tuberculosis, loosening of internal fixation, fracture or loss of obvious correction were found during the follow?up. Accord?ing to the Eck fusion classification standard, at the time of the last follow?up bone graft area of all 27 cases reached I level fusion. Conclusion For non?curable severe tuberculous thoracolumbar kyphosis with multi?segment vertebral body loss, good deformity correction and proper recovery of vertebral height can be achieved by posterior osteotomy combined with cantilever beam tech?nique and intraoperative longitudinal traction. The combination of anterior debridement and bone graft fusion is a safe and reliable method.

Clinical efficacy of one-stage posterior debridement,Smith-Petersen osteotomy,compressive fusion and instrumentation for treatment of thoracolumbar tuberculosis / 中华骨科杂志

Objective To discuss the clinical efficacy and surgical indications of one-stage posterior debridement,Smith-Petersen osteotomy(SPO), compressive fusion and instrumentation for treatment of thoracolumbar tuberculosis. Methods All of 32 patients with thoracolumbar spinal tuberculosis were retrospectively analyzed,treated by one-stage posterior debridement,SPO, compressive fusion and instrumentation from March 2010 to October 2016,including 23 males and 9 females,aged 2 to 77 years old,average(39.2±17.8)years.All patients were treated by preoperative quadruple anti-tuberculosis drugs therapy for 2-4 weeks, postoperative regular chemotherapy for 12-18 months.Preoperative and postoperative changes in clinical symptoms,nervous func-tion,the situation of the erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)with strict follow-up,as well as other re-lated complications were observed.The spinal fusion rate and fusion situation,changing of the physiological curvature,as well as loosening or breaking of the internal fixation device were detected through regular imaging examination.Results The surgery du-ration time was 90-150 min,average(120±19.6)min,and the blood loss was 150-600 ml,average(320±88.9)ml.Postoperative follow-up time was 1 to 3 years,average 2.3 years.The symptoms of tuberculosis poisoning in all patients were obviously relieved and the nutritional status was improved gradually. The visual analogue scale(VAS) improvement rate was about 92%. The VAS score in the preoperative and the last follow-up was statistically significant.All patients'ESR and CRP returned to normal levels at the last follow-up.The Kirkaldy-Willis function score showed that the total fine rate was 93.75%.9 patients with spinal neurologi-cal impairment were postoperative improved significantly.Except 1 patient's Asia grade improved from the B to C,others returned to normal condition.30 cases recovered.Pleural effusion was observed in 3 cases treated with closed thoracic drainage and antibi-otics.The drainage tube was removed after 5-7 d.Incision fistula were observed in 1 patient at 1 month after discharge and recov-ered after debridement and drugs adjustment.Internal fixation loosening was found in 1 elderly patient after 6 months after surgery which was treated with hyperextended brace and anti-osteoporosis drugs.No tuberculosis recurrence was found.Conclusion One-stage posterior debridement, SPO, compressive fusion and instrumentation is a simple, effective and safety surgical approach, which has great application value for surgical treatment of patients with thoracolumbar spinal tuberculosis.