In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4％.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P＜0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)％to the latest follow-up(11.30±3.27)％,and there was statistically significant different.The complication rate was 31.3％(45/144),and the reoperation rate was 9.72％(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14％(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.

Objective To explore the effect of gastrodin(GAS)on the polarization of M2 microglia under oxygen and glucose deprivation(OGD)and the effect of p38 MAPK inhibition on the polarization status of microglia.Methods BV2 microglia was divided into the control group(Ctrl),p38 MAPK inhibitor SB203580 group(Ⅰ),OGD group(OGD),OGD+I group,gastrodin treatment group(G+OGD),and G+OGD+Ⅰ group.The expressions of p38 MAPK,phosphorylated p38 MAPK(p-p38 MAPK),M2 microglia marker arginase-1(Arg-1)and chitinase like protein 1/2(YM1/2)were detected by immunofluorescent staining and Western blotting.Results Immunofluorescent staining results showed that the pretreatment with gastrodin reduced the fluorescence expression of p-p38 MAPK in OGD induced BV2 microglia,enhanced the fluorescence expressions of Arg-1 and YM1/2.After pretreatment with SB203580,the fluorescence expressions of p-p38 MAPK further decreased,the fluorescence expressions of Arg-1 and YM1/2 further increased,both were significantly different from the G+OGD group(n=3,P＜0.05).The fluorescence expressions of p38 MAPK in each group was not statistically significant(n=3,P＞0.05).Western blotting results showed that the protein expressions of p-p38 MAPK,Arg-1 and YM1/2 in the OGD group enhanced,compared with that in the control group(n=3,P＜0.05).After the pretreatment with gastrodin,the protein expression of p-p38 MAPK was reduced significantly,the protein expressions of Arg-1 and YM1/2 was enhanced obviously,both were significantly different from the OGD group(n=3,P＜0.05).After pretreatment with SB203580,the protein expressions of p-p38 MAPK was further reduced,the protein expression of Arg-1 and YM1/2 were further enhanced,both were significantly different from the G+OGD group(n=3,P＜0.05).In addition,there was no significant change in p38 MAPK protein expression among groups(n=3,P＞0.05).Conclusion Gastrodin inhibits p38 MAPK signaling activation to promote BV2 microglial polarization towards the M2 phenotype,reducing inflammatory responses and exerting a protective effect.

AIM To prepare artesunate nanomicelles,and to evaluate their in vivo pharmacokinetics and anti-tumor activity.METHODS The nanomicelles were prepared with poly(ethylene glycol)-poly(D,L-lactide)-poly(L-histidine)(mPEG-PLA-PHis)as a carrier,after which the formulation was optimized by single factor test combined with Box-Behnken response surface method,and encapsulation efficiency,drug loading,settling rate,particle size,Zeta potential,in vitro drug release were determined.Twelve H22 tumor-bearing mice were randomly assigned into two groups and given tail vein injection of Artesunate Injection and artesunate nanomicelles(1 mg/kg),respectively,after which blood collection was made at different time points,HPLC was adopted in the plasma concentration determination of artesunate,and main pharmacokinetic parameters were calculated.Thirty-six H22 tumor-bearing mice were randomly assigned into six groups,containing model group(normal saline),positive group(20 mg/kg cyclophosphamide),Artesunate Injection group(30 mg/kg)and artesunate nanomicelles low-dose,medium-dose,high-dose groups(10,20,30 mg/kg),then the body weight,tumor weight were recorded and tumor inhibitory rate was calculated at 3 d after the last administration.RESULTS The optimal formulation was determined to be 10.18∶1 for(mPEG-PLA-PHis)-drug ratio,0.48 mg/mL fo artesunate concentration,and 0.96 h for hydration time,the encapsulation efficiency,drug loading,settling rate,particle size and Zeta potential were(94.27±1.26)%,(8.26±0.18)%,(4.19±0.20)%,(65.14±4.96)nm and-(17.64±1.06)mV,respectively.The accumulative release rate of nanomicelles in mild acidic medium was higher than that in mild alkaline medium,demonstrating pH-sensitivity.Compared with injection,the nanomicelles displayed prolonged t1/2,MRT(P＜0.01),decreased CL(P＜0.01),and increased AUC0-t(P＜0.01).Compared with the model group,the different doses of artesunate nanomicelles groups exhibited no obvious changes in mouse body weight(P＞0.05)and decreased tumor weight(P＜0.05,P＜0.01),especially for the medium-dose group with the tumor inhibitory rate of 55.40%.CONCLUSION High encapsulation efficiency and strong in vivo anti-tumor activity are observable in artesunate nanomicelles.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Humans ; Female ; Carcinoma, Intraductal, Noninfiltrating/surgery* ; Thoracic Wall/pathology* ; Adenocarcinoma, Papillary ; Breast Neoplasms/surgery* ; Carcinoma, Ductal, Breast/pathology*

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.
Humans ; Gastrointestinal Microbiome ; Medicine, Chinese Traditional ; Renal Insufficiency, Chronic/drug therapy*

OBJECTIVE: To explore the feasibility and clinical effect of Stand-alone oblique lateral interbody fusion (OLIF) in the treatment of lumbar intervertebral disc degeneration with Modic changes and endplate sclerosis. METHODS: A retrospective analysis was performed on 16 cases with lumbar intervertebral disc degeneration with Modic changes and endplate sclerosis admitted to three medical centers from January 2015 to December 2018. There were 6 males and 10 females, the age ranged from 45 to 67 years old with an average of (55.48±8.07) years old, the medical history ranged from 36 to 240 months with an average of (82.40±47.68) months. The lesion sites included L_2,3 in 2 cases, L_3,4 in 5 cases, and L_4,5 in 9 cases. All patients presented with chronic low back pain with lower limb neurological symptoms in 3 cases. All patients were treated by Stand-alone oblique lateral lumbar interbody fusion. Clinical and radiological findings and complications were observed. RESULTS: There was no vascular injury, endplate injury and vertebral fracture during the operation. The mean incision length, operation time, and intraoperative blood loss were(4.06±0.42) cm, (45.12±5.43) min, (33.40±7.29) ml, respectively. The mean visual analogue scale (VAS) of the incision pain was (1.14±0.47) at 72 hours after operation. There was no incision skin necrosis, poor incision healing or infection in patients. Sympathetic chain injury occurred in 1 case, anterolateral pain and numbness of the left thigh in 2 cases, and weakness of the left iliopsoas muscle in 1 case, all of which were transient injuries with a complication rate of 25%(4/16). All 16 patients were followed up from 12 to 36 months with an average of (20.80±5.46) months. The intervertebral space height was significantly recovered after operation, with slight lost during the follow-up. Coronal and sagittal balance of the lumbar spine showed good improvement at the final follow-up. There was no obvious subsidence or displacement of the cage, and the interbody fusion was obtained. At the final follow-up, Japanese Orthopaedic Association(JOA) score and Oswestry disability index(ODI) were significantly improved. CONCLUSION As long as the selection of case is strict enough and the preoperative examination is sufficients, the use of Stand-alone OLIF in the treatment of lumbar intervertebral disc degeneration with Modic changes and endplate sclerosis has a good results, with obvious clinical advantages and is a better surgical choice.
Male ; Female ; Humans ; Child, Preschool ; Intervertebral Disc Degeneration/surgery* ; Retrospective Studies ; Sclerosis ; Treatment Outcome ; Lumbar Vertebrae/surgery* ; Spinal Fusion/methods*

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.
Humans ; Chromatography, High Pressure Liquid ; Molecular Docking Simulation ; Network Pharmacology ; Apoptosis ; Hyperplasia ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To analyze the causes of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy, summarize the clinical results, and propose preventive measures. METHODS: Retrospective analysis was made on the data of 8 cases of lumbar spondylopathy and vertebral fracture treated by oblique lateral interbody fusion in three medical centers from October 2014 to December 2018. All were female, aged from 50 to 81 years with an average of 66.4 years. Disease types included 1 case of lumbar degenerative disease, 3 cases of lumbar spinal stenosis, 2 cases of lumbar degenerative spondylolisthesis and 2 cases of lumbar degenerative scoliosis. Preoperative dual energy X-ray bone mineral density test showed that 2 cases had T-value >-1 SD, 2 cases had T-value -1 to -2.5 SD, and 4 cases had T-value <-2.5 SD. Single segment fusion was in 5 cases, two segment fusion in 1 case and three segment fusion in 2 cases. Four cases were treated with OLIF Stand-alone and 4 cases were treated with OLIF combined with posterior pedicle screw fixation. Postoperative imaging examination showed vertebral fracture, and all of them were single vertebral fracture. There were 2 cases of right lower edge fracture of upper vertebral body at fusion segment, 6 cases of lower vertebral body fracture at fusion segment, and 6 cases with endplate injury and fusion cage partially embedded in vertebral body. Three cases of OLIF Stand-alone were treated with pedicle screw fixation via posterior intermuscular approach, while one case of OLIF Stand-alone and four cases of OLIF combined with posterior pedicle screw fixation were not treated specially. RESULTS: The 5 cases of initial operation and 3 cases of reoperation did not show wound skin necrosis or wound infection. The follow-up time was from 12 to 48 months with an average of 22.8 months. Visual analogue scale (VAS) of low back pain was preoperative decreased from 4 to 8 points (averagely 6.3 points) and postoperative 1 to 3 points (averagely 1.7 points) at the final follow-up. Oswestry disability index (ODI) was preoperative 39.7% to 52.4% (averagely 40.2%), and postoperative 7.9% to 11.2% (averagely 9.5%) at the final follow-up. During the follow-up, there was no loosening or fracture of the pedicle screw system, and no lateral displacement of the fusion cage;however, the fusion cage at the vertebral fracture segment had obvious subsidence. The intervertebral space height of vertebral fracture segment was preoperaive 6.7 to 9.2 mm (averagely 8.1 mm), and postoperative 10.5 to 12.8 mm (averagely 11.2 mm). The improvement rate after operation was 37.98% compared to preoperative. The intervertebral space height at final follow-up was 8.4 to 10.9 mm (averagely 9.3 mm), and the loss rate was 16.71% compared with that after operation. At the final follow-up, interbody fusion was achieved in all cases except for one that could not be identified. CONCLUSION The incidence of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy is lower, and there are many reasons for fracture, including preoperative bone loss or osteoporosis, endplate injury, irregular shape of endplate, excessive selection of fusion cage, and osteophyte hyperplasia at the affected segment. As long as vertebral fracture is found in time and handled properly, the prognosis is well. However, it still needs to strengthen prevention.
Humans ; Female ; Male ; Spinal Fractures/surgery* ; Retrospective Studies ; Treatment Outcome ; Lumbar Vertebrae/surgery* ; Spondylolisthesis/surgery* ; Scoliosis ; Spinal Fusion/methods*