Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of Diphylleia sinensi by using various chromatographic methods, including silica gel, MCI gel, Sephadex LH-20, ODS and semi-preparative HPLC. The structures of the isolated compounds were identified as diphyflavonoid A (1), diphyflavonoid B (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside (5) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, and MS). Compounds 1 and 2 were two new flavonoid glycosides, and compounds 3 and 5 were isolated from the genus Diphylleia for the first time.

Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Digital intraoral scanning is a hot topic in the field of oral digital technology.In recent years,digital intra-oral scanning has gradually become the mainstream technology in orthodontics,prosthodontics,and implant dentistry.The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression.However,the operators are less familiar with the intraoral scanning characteristics,imaging process-ing,operator scanning method,oral tissue specificity of the scanned object,and restoration design.Thus far,no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad.To deal with the problems encountered in oral scanning and improve the quality of digital scanning,we collected common expert opin-ions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence.We also describe the scanning strategies under different oral impression requirements.The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images,adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy.The scanning trajec-tories mainly include the E-shaped,segmented,and S-shaped methods.When performing fixed denture restoration,it is recommended to first scan the abutment and adjacent teeth.When performing fixed denture restoration,it is recommend-ed to scan the abutment and adjacent teeth first.Then the cavity in the abutment area is excavated.Lastly,the cavity gap was scanned after completing the abutment preparation.This method not only meets clinical needs but also achieves the most reliable accuracy.When performing full denture restoration in edentulous jaws,setting markers on the mucosal tissue at the bottom of the alveolar ridge,simultaneously capturing images of the vestibular area,using different types of scanning paths such as Z-shaped,S-shaped,buccal-palatal and palatal-buccal pathways,segmented scanning of dental arches,and other strategies can reduce scanning errors and improve image stitching and overlap.For implant restora-tion,when a single crown restoration is supported by implants and a small span upper structure restoration,it is recom-mended to first pre-scan the required dental arch.Then the cavity in the abutment area is excavated.Lastly,scanning the cavity gap after installing the implant scanning rod.When repairing a bone level implant crown,an improved indi-rect scanning method can be used.The scanning process includes three steps:First,the temporary restoration,adjacent teeth,and gingival tissue in the mouth are scanned;second,the entire dental arch is scanned after installing a standard scanning rod on the implant;and third,the temporary restoration outside the mouth is scanned to obtain the three-di-mensional shape of the gingival contour of the implant neck,thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration.For dental implant fixed bridge repair with missing teeth,the mobility of the mucosa increases the difficulty of scanning,making it difficult for scanners to distinguish scanning rods of the same shape and size,which can easily cause image stacking errors.Higher accuracy of digital implant impres-sions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius.The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases,the scanning accuracy decreases accordingly,especially when performing full mouth implant restoration impressions.The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal mor-phology inside the mouth and the lack of relatively obvious and fixed reference objects,which results in insufficient ac-curacy.When designing restorations of this type,it is advisable to carefully choose digital intraoral scanning methods to obtain model data.It is not recommended to use digital impressions when there are more than five missing teeth.

Objective:To investigate the clinical efficacy of reconstruction with the hallux tissue flap for the fingertip defects of thumb and fingers based on the concept and technique of full reconstruction.Methods:From September 2022 to February 2023, the patients with thumb and fingertip defects who were reconstructed using the concept and technology of full reconstruction in Xuzhou Renci Hospital were respective analysised. Based on the degree of defect in the nail bed, bone, and soft tissue of the hand, a hallux osteo-onychocutaneous flap or hallux nail flap was designed and harvested from the same side of the toe, and free transplantation was performed to reconstruct the damaged fingertip. The wounds in the donor site that could not be sutured primarily were treated with dressing change. The surgical complications, the appearance of the reconstructed finger and donor site, Semmes-Weinstein monofilament (SWM) examination, 2-point discrimination (2PD) measurement, and patient satisfaction were regularly recorded. According to the functional evaluation criteria for thumb and finger reconstruction issued by the Hand Surgery of the Chinese Medical Association, the function of the reconstructed fingers was evaluated as excellent (13-15 points), good (9-12 points), fair (5-8 points), and poor (≤4 points). The patients were investigated whether they were satisfied with the outcomes.Results:A total of 8 patients (9 fingers) including 5 males and 3 females were enrolled. The average age was 32.4 years (range, 22-46 years). There were 1 thumb, 2 index fingers, 5 middle fingers, and 1 ring finger. 7 cases (8 fingers) were repaired with the hallux osteo-onychocutaneous flap, and 1 case (1 finger) was repaired with the hallux nail flap. All the reconstructed fingers survived uneventfully, and the recipient site healed primarily, and the donor site healed after dressing change, without infection and other complications. All the 8 patients (9 fingers) were followed up for 3-7 months. The nail plate of the donor site naturally grew and recovered nearly normal. Depression formation was observed at part of the deck junction of the recipient site, and scars were left in the pulp and fibular side of the hallux. At the final follow-up, the reconstructed fingers recovered protective sensation and tactile sense, and the 2PD of the reconstructed fingers was 9 mm and 10 mm in two cases. The SWM score was 3.60-4.31, mean 3.96. The results were the monofilament specifications and indicating the protective sensation was diminished. Functional evaluation of reconstructed fingers: 9 fingers in 8 cases scored 13-14 points, all reaching an excellent level. All patients were satisfied with the surgical results.Conclusion:Based on the concept and technology of full reconstruction, the fingertip defects of the thumb and finger can recover close to normal with the hallux tissue flap in the short-term, while ensuring the overall shape and function of the hallux donor area, achieving a balance between the donor and recipient areas, and achieving satisfactory clinical results.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective To explore the value of droplet digital polymerase chain reaction(ddPCR)in the etiological diagnosis of severe acute pancreatitis(SAP)patients with suspected bloodstream infection(BSI).Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled.When BSI was suspected,venous blood was collected for both ddPCR detection and blood culture(BC)with antimi-crobial susceptibility testing(AST)simultaneously.The time required for two detection methods was recorded,and the detection results of ddPCR and BC were compared.The etiological diagnostic efficacy of ddPCR was calculated,and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored.Results A total of 22 patients were included in the analysis,and 52 venous blood specimens were collec-ted for detection.BC revealed 17 positive specimens(32.7％)and 29 pathogenic strains,while ddPCR showed 41 positive specimens(78.8％)and 73 pathogenic strains.Detection time required for ddPCR was significantly lower than that of BC([0.16±0.03]days vs[5.92±1.20]days,P＜0.001).Within the detection range of ddPCR and taking BC results as the gold standard,the sensitivity and specificity of ddPCR were 80.0％and 28.6％,respective-ly.With the combined assessment of BSI based on non-blood specimen microbial evidence within a week,the sensi-tivity and specificity of ddPCR detection increased to 91.9％and 76.9％,respectively.ddPCR detected resistance genes of blaKPC,blaNDM/IMP,VanA/VanM,and mecA from 19,9,6,and 5 specimens,respectively.Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin(r=0.347,0.414,P＜0.05).Conclusion As a supplementary detection method for BC in BSI diagnosis,ddPCR has the advantages of higher sensitivity and shorter detection time,and is worthy of further exploration in clinical application.