Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.

Objective:To investigate the current status and longitudinal development trajectory of postoperative cognitive dysfunction (POCD) in elderly patients undergoing hip replacement surgery and analyze the relationship between POCD and postoperative hip joint function recovery.Methods:Using the convenient sampling method, elderly patients who underwent hip replacement surgery in Department of Orthopedics in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2022 were selected as the research objects. The cognitive function at 1 week, 1 month, 2 months and 3 months after surgery was assessed using Mini-Mental State Examination (MMSE), and the longitudinal development trajectory of postoperative POCD was fitted using latent class growth model (LCGM). The differences between cognitive function categories and Oxford Hip Score (OHS) score at 3 months after surgery were compared by ANOVA.Results:A total of 307 elderly patients with hip replacement completed full follow-up and data collection. The incidence of POCD (MMSE<8 points) in patients at four postoperative time points was 30.29% (93/307), 29.97% (92/307), 28.66% (88/307) and 21.17% (65/307), respectively. The MMSE score was lowest at 1 week after surgery. Three potential categories of cognitive function longitudinal development tracks were identified by LCGM, including 208 cases (67.75%) with no cognitive dysfunction, 32 cases (10.42%) with improved cognitive dysfunction, and 67 cases (21.82%) with continuous cognitive dysfunction. Three months after surgery, patients with no cognitive impairment had the lowest OHS score, while patients with persistent cognitive impairment had the highest OHS score. There were statistically significant differences in OHS scores among patients with three longitudinal potential categories of cognitive function ( P<0.05) . Conclusions:The incidence of POCD in elderly patients with hip replacement varies at different postoperative times, with the most significant difference occurring at 1 week after surgery. Medical staff must dynamically evaluate the postoperative cognitive function of elderly patients and adopt targeted nursing strategies for different types of cognitive impairments, to promote the patient's recovery of hip function.

Objective:To assess the effect of mild intraventricular hemorrhage（IVH）on the early motor development of infants at high risk of brain injury,and to guide the intervention according to its characteristics.Methods:A retrospective cohort study was conducted to select neonates discharged from the Neonatal Unit of Xi 'an Children 's Hospital from February 1，2022 to March 31，2023，with one or more high-risk factors of brain injury.The patients were assigned to low-grade IVH group and no IVH group according to ultrasound diagnosis.The research subjects exclucled other brain injury diseases besides mild IVH.Motor development was assessed using test of infant motor performance(TIMP)，reflecting performance in head control，auditory and visual responses，defensive movements，trunk movements，limb movements，and more.Both groups completed TIMP assessment between discharge and 16 weeks of the corrected age(CA).The differences of TIMP scores between two groups were compared . Results:A total of 329 neonates at high risk for brain injury were recruited，including 98 cases with grade Ⅰ-Ⅱ IVH（low-grade IVH group）diagnosed through brain ultrasonography and 231 controls(no IVH group).The Z scores of TIMP in the low-grade IVH group were lower than that in no IVH group（-0.25 ±0.87 vs.0.03 ±0.71， P=0.015）.The risk factors of brain injury were matched for further comparison.At CA2-5 weeks，the scores in low-grade IVH group of TIMP total scores（74.10 ±12.28 vs.84.24 ±7.71），observation items（10.57 ±1.47 vs.11.24 ±1.29），elicitation（63.17 ±12.13 vs.73.00 ±7.36），sitting（9.14 ±2.90 vs.11.65 ±3.26），supine（22.07 ±4.73 vs.24.79 ±3.55），prone position（10.35 ±3.74 vs.12.82 ±3.15）and lateral position（4.00 ±2.85 vs.5.48 ±2.13）were significantly lower than those in no IVH group（ P<0.05）.At CA6-9 weeks，the scores in low-grade IVH group of sitting position（10.44 ±4.01 vs.12.96 ±3.02），supine position（24.04 ±4.60 vs.26.83 ±3.53），lateral position（4.83 ±2.53 vs.6.25 ±2.6）were significantly lower than those in no IVH group（ P<0.05）.At CA12-15 weeks，the low-grade IVH group showed significant differences in TIMP total score（104.00 ±12.98 vs.114.10 ±13.16），elicitation（92.00 ±12.64 vs.102.00 ±13.10），sitting（17.00 ±3.50 vs.19.13 ±3.55）and lateral position（7.35 ±2.14 vs.9.00 ±2.37）compared with those from no IVH group（ P<0.05）. Conclusion:Mild intraventricular hemorrhage affected the early motor development of high-risk infants with brain injury，mainly manifested as a lag in the ability of head control at CA2-5 weeks，and the trend continued until CA12-15 weeks.Early monitoring of motor ability and intervention of head control ability should be carried out in high-risk children with mild intraventricular hemorrhage.

Objective:To analyze the distribution and genomic characteristics of SARS-CoV-2 variants isolated from imported cases of COVID-19 in Sichuan Province from December 2022 to January 2023.Methods:This study selected 108 nasal and throat swab samples with fluorescence threshold (Ct)≤32 that were collected from imported COVID-19 cases in Sichuan Province from December 2022 to January 2023. Targeted amplification and Illumina NextSeq? 2000 system were used for whole-genome sequencing. Nextclade and Pangolin online platforms were used to determine the virus genotypes and analyze the mutation loci. A phylogenetic tree was constructed using maximum likelihood.Results:A total of 55 SARS-CoV-2 whole genome sequences with coverage of >95% were obtained, and all of the strains were Omicron variants. Compared with the sequence of reference strain Wuhan-Hu-1, the median number of nucleotide mutation sites of 21L, 22B, 22D, 22E, and 22F genotypes were 93, 75, 92, 78, and 92, and the median number of amino acid mutation sites were 68, 53, 68, 69, and 65, respectively. From December 2022 to January 2023, the predominant circulating SARS-CoV-2 variants from imported cases in Sichuan Province were BA.5.2 (10.91%, 6/55), XBB.1.1 (9.10%, 5/55), BF.7.14 (7.23%, 4/55), and BQ.1.1 (7.23%, 4/55).Conclusions:The distribution of SARS-CoV-2 variants can reflect the global epidemic trend to a certain extent. However, it is different from the distribution of local circulating variants in the Chinese mainland. The XXB variants with transmission advantages can be detected in large numbers of inbound travelers before becoming the predominant circulating strains in the Chinese mainland.

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.
Flavonoids/pharmacology* ; Pharmaceutical Preparations/chemistry* ; Biological Availability ; Nanoparticles/chemistry* ; Anti-Inflammatory Agents ; Particle Size

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Aromatic compounds are a class of organic compounds with benzene ring(s). Aromatic compounds are hardly decomposed due to its stable structure and can be accumulated in the food cycle, posing a great threat to the ecological environment and human health. Bacteria have a strong catabolic ability to degrade various refractory organic contaminants (e.g., polycyclic aromatic hydrocarbons, PAHs). The adsorption and transportation are prerequisites for the catabolism of aromatic compounds by bacteria. While remarkable progress has been made in understanding the metabolism of aromatic compounds in bacterial degraders, the systems responsible for the uptake and transport of aromatic compounds are poorly understood. Here we summarize the effect of cell-surface hydrophobicity, biofilm formation, and bacterial chemotaxis on the bacterial adsorption of aromatic compounds. Besides, the effects of outer membrane transport systems (such as FadL family, TonB-dependent receptors, and OmpW family), and inner membrane transport systems (such as major facilitator superfamily (MFS) transporter and ATP-binding cassette (ABC) transporter) involved in the membrane transport of these compounds are summarized. Moreover, the mechanism of transmembrane transport is also discussed. This review may serve as a reference for the prevention and remediation of aromatic pollutants.
Humans ; Adsorption ; Bacteria/metabolism* ; Organic Chemicals ; Biological Transport ; ATP-Binding Cassette Transporters ; Polycyclic Aromatic Hydrocarbons/metabolism*

Objective:To investigate the application effect of preoperative prerehabilitation in elderly patients with knee arthroplasty combined with sarcopenia.Methods:A total of 164 elderly patients who were hospitalized and underwent artificial knee arthroplasty combined with sarcopenia in Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University from July 2020 to December 2021 were included by the convenient sampling method. According to random number table method, they were divided into the control group and the observation group, with 82 cases in each group. The control group received routine preoperative nursing, and the observation group received preoperative pre-rehabilitation intervention on the basis of the control group. Knee range of motion, Hospital for Special Surgery Knee Score (HSS) , skeletal muscle mass index and grip strength were evaluated before intervention and 1 month after operation. Length of stay and postoperative complications were recorded and compared between the two groups.Results:Knee range of motion, HSS of two groups at 1 month after operation were higher than those before intervention, and the differences were statistically significant ( P<0.05) . One month after surgery, the knee range of motion, HSS and grip strength of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . The skeletal muscle mass index of the observation group was higher one month after surgery than before intervention, but the difference was not statistically significant ( P>0.05) . The hospitalization time of observation group was shorter than control group, and the difference was statistically significant ( P<0.05) . The incidence of complications in the observation group and control group was respectively 15.85% (13/82) and 39.02% (32/82) , and the difference was statistically significant ( P<0.05) . Conclusions:Preoperative rehabilitation can effectively improve the knee range of motion and joint function of elderly patients with sarcopenia after knee rarthroplasty, alleviate sarcopenia, shorten the length of hospital stay and reduce postoperative complications.

OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group （group S ），scalding+seawater immersion+delayed fluid replacement group （group SS ）， scalding+seawater immersion+valproic acid+delayed fluid replacement group （group SSV ）according to random number table ，with 60 rats in each group. All groups were subjected to 35％total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ；seawater（30 min）immediately after scalding ，and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail：125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ，and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure （MAP），heart rate （HR），respiration rate （RR），rectal temperature （RT），arterial blood pH ，arterial partial pressure of oxygen （PaO2），arterial blood partial pressure of carbon dioxide （PaCO2），HCO3－，creatine kinase MB isoenzyme （CK-MB）and neuron specific enolase （NSE）were detected before scalding ，at 0，2，5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS （55％）was significantly lower than that of group S （90％）， while that of group SSV （75％）was increased significantly ，compared with group SS （P＜0.05）. Compared with group S ，the levels of MAP ，RT，HR，pH，PaO2 and HCO 3－ in group SS were significantly lowered ，while the levels of CK-MB and NSE were increased significantly at 0，2，5 h after scalding ；the levels of PaCO 2 were increased significantly at 2，5 h after scalding ， while the levels of RR were decreased significantly at 0，2 h after scalding （P＜0.05）. Compared with group SS ，the levels of MAP，RT，HR，pH，PaO2 and HCO 3－ in group SSV were significantly increased ，while the levels of PaCO 2，CK-MB and NSE were decreased significantly at 2，5 h after scalding ；the level of RR was increased significantly at 2 h after scalding （P＜0.05）. At 2，5 h after scalding ，cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ；cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ，hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats ， improve vital signs and blood gas index ，prolong survival time and improve survival rate in rats.

Objective:A clinical prediction model was constructed based on the related factors affecting neonatal early-onset sepsis (EOS).Methods:A retrospective study was conducted. The patients with EOS amditted to the neonatal intensive care unit of Children′s Hospital Affiliated to Xi′an Jiaotong University from April 2015 to April 2020 were enrolled. The demographic data and the clinical indicators within 8 hours after admission were collected. The death 7 days after admission was taken as the end event. The differences of various indexes between the survival group and the death group were compared. After univariate analysis of the indexes that may have an impact on the prognosis, binary logistic regression analysis was performed; The predictive model was established for the factors that may affect the prognosis; the predictive value of the relevant models was analyzed by recevier operating characteristic (ROC) curve, and the model was verified by independent clinical medical records.Results:A total of 139 children were enrolled, and 41 died within 7 days, with a fatality rate of 29.50%. Compared with the survival group, the dead group had higher white blood cells (WBC), serum procalcitonin (PCT), lactic acid (Lac), creatinine (Scr), D-dimer and Paediatric Risk of Mortality (PRISM) score {WBC(×10 9/L): 24.15[4.36, 29.36] vs 21.21[19.14, 28.36], PCT: (67.32±40.36)ng/L vs (37.76±25.11)ng/L, Lac: (8.69±6.17)mmol/L vs (2.34±1.11)mmol/L, Scr: (239.99±68.46)μmol/L vs (65.31±34.34)μmol/L, D-dimer(mg/L): 5.21[2.06, 21.49] vs 0.34[0.26, 0.45], PRISM Ⅲ: (19.52±6.25)s vs (10.63±2.05)s, all P<0.05}, and lower fibrinogen (Fib), platelet count (PLT) and hemoglobin concentration (Hb) [Fib: (1.48±1.19)g/L vs (2.44±0.83)g/L, PLT: (154±58)×10 9/L vs (189±29)×10 9/L, Hb: (169±49)g/L vs (182±52)g/L, all P<0.05]. The incidence of placental/umbilical cord lesions, amniotic fluid pollution, asphyxia, premature delivery, premature rupture of membranes, positive etiology and maternal infection in the death group were higher than those in the survival group, while the gestational age and weight were lower than those in the survival group (all P<0.05); Binary logistic regression analysis showed that Lac, PCT and premature rupture of membranes were independent risk factors for the prognosis of EOS [odds ratio ( OR) and 95% confidence interval (95% CI): Lac was 1.23(1.00-2.05), PCT was 1.05(1.03-1.85), premature rupture of membranes was 2.59(1.89-3.32), all P<0.05]; ROC curve analysis showed that the area under the curve (AUC) of the prediction model was 0.967; the predicted sensitivity was 88.70%; and the specificity was 78.20% respectively. Conclusions:PCT, Lac and premature rupture of membranes are independent risk factors affecting the prognosis of EOS. The clinical prognosis prediction model constructed by combining PLT, gestational age and weight has good prediction efficiency.