Aim To assess the impact of morin and acetyl-resveratrol on the oral bioavailability and pharmacokinetics of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats.Methods Twenty rats were randomized into four groups of equal size, including a control group, two intervention groups and a positive control group, and administered orally 30 mg·kg-1 SQV with or without 40 mg·kg-1 morin or acetyl-resveratrol or verapamil (as positive control).The plasma concentrations of saquinavir were determined using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the PK of SQV was assessed using non-compartmental analysis.Results The PK parameters values of SQV, SQV+morin, SQV+acetyl-resveratrol, SQV+verapamil were as follows: AUC0-t, 381.53 μg·h·L-1,185.53 μg·h·L-1, 360.43 μg·h·L-1, 529.95 μg·h·L-1;AUC0-∞, 409.48 μg·h·L-1, 228.52 μg·h·L-1,446.67 μg·h·L-1, 552.41 μg·h·L-1;Cmax, 110.80 μg·L-1, 86.44 μg·L-1, 139.84 μg·L-1, 423.60 μg·L-1;Tmax, 0.25 h, 0.25 h, 0.25 h, 0.50 h;T1/2, 5.72 h, 5.94 h, 6.78 h, 3.78 h;MRT0-∞, 10.30 h, 9.61 h, 12.30 h, 4.89 h;CL/F, 7.59 mL·kg-1·h-1, 13.88 mL·kg-1·h-1, 7.28 mL·kg-1·h-1, 5.52 mL·kg-1·h-1.Conclusions Multiple peak phenomenon can be observed in the plasma SQV profiles.Morin can significantly reduce the SQV oral bioavailability and affect SQV PK profiles while acetyl-resveratrol cannot significantly affect the SQV oral bioavailability and SQV PK profiles in rats.

OBJECTIVEBy explore the role of serum soluble Fas (sFas) in occurrence and progression of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).

METHODSEnzyme-linked immunosorbent assay (ELISA) was used to detect serum sFas levels in 40 patients with DEACMP in acute stage and convalescent stage, with 36 healthy elderly subjects as the control group.

RESULTSSerum sFas levels of the patients with DEACMP in both the acute and convalescent stages showed no significant difference from those in the control group (P=0.737 and 0.137, respectively), nor was any significant difference found between the patients in acute and exacerbation stages (P=0.059).

CONCLUSIONSerum sFas is not involved in the occurrence and progression of DEACMP.

Adult ; Aged ; Aged, 80 and over ; Brain Diseases ; etiology ; Carbon Monoxide Poisoning ; blood ; complications ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; fas Receptor ; blood

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective To discuss the effectiveness and safety of transarterial chemoembolization(TACE)combined with regorafenib and programmed death receptor-1(PD-1)in the second-line sequential treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 83 patients with advanced HCC,who received TACE combined with regorafenib and PD-1(triple-therapy group)or TACE combined with regorafenib(dual-therapy group)at the Affiliated Hospital of Nantong University and Nantong Municipal Third People's Hospital of China between October 2020 and May 2022,were retrospectively analyzed.The clinical data were collected and evaluated.Modified response evaluation criteria in solid tumors(mRECIST)was used to evaluate the curative effect.The progression-free survival(PFS),overall survival(OS)and treatment-related adverse events(TRAEs)were compared between the two groups.The Kaplan-Meier method was used to draw PFS and OS curves,the Log-rank test was used to compare the relevant data between the two groups,and the COX regression model was drawn to determine the factors influencing PFS and OS.Results There were no statistically significant differences in the baseline data between the two groups(P≥0.05).In the triple-therapy group and the dual-therapy group,the objective response rate(ORR)was 31.1％and 18.4％respectively(P=0.024),and the disease control rate(DCR)was 77.8％and 57.8％respectively(P=0.038).The OS and PFS in the triple-therapy group were higher than those in the dual-therapy group(16.80 months vs 13.20 months,and 9.10 months vs.7.40 months,respectively).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P 0.05).Conclusion In the second-line sequential treatment of advanced HCC,TACE combined with regorafenib and PD-1 is more effective than TACE combined with regorafenib,therefore,it can be used as a preferred second-line treatment for advanced HCC.

Objective:To compare the short-term efficacy of hip arthroscopic surgery assisted by platelet-rich plasma (PRP) and hip arthroscopy alone in the treatment of femoroacetabular impingement (FAI).Methods:A retrospective cohort study was performed on the clinical data of 133 FAI patients admitted to Fourth Medical Center of PLA General Hospital from January 2019 to January 2021. The patients included 86 males and 47 females, aged 19-71 years [(39.1±12.6)years]. A total of 67 patients were treated with hip arthroscopy alone (hip arthroscopy group), and 66 patients were treated with PRP after hip arthroscopy under ultrasound guidance (hip arthroscopy+PRP group). The two groups were compared before, at 12 months after surgery and at the last follow-up regarding the following items: Visual Analogue Scale (VAS), Modified Harris Hip Score, International Hip Outcome Tool-12 (iHOT-12), and Hip Outcome Score Activities of Daily Living Scale (HOS-ADL). The incidence rate of complications after surgery was compared between the two groups.Results:A total of 108 patients were followed up for 24-36 months [(28.5±3.8)months], while 25 patients were lost to follow-up because of withdrawal of consent, wrong telephone number, etc, including 11 patients (16.4%) in the hip arthroscopy group and 14 patients (21.2%) in the hip arthroscopy+PRP group. The values of VAS in the hip arthroscopy group before, at 12 months after surgery and at the last follow-up were 5.00(5.00, 7.00)points, 3.00(2.00, 3.75)points, and 1.00(0.00, 2.00)points, respectively; the values of Modified Harris Hip Score were 49.00(39.00, 57.00)points, 76.00(69.25, 82.00)points, and 86.00(82.00, 88.00)points, respectively; the values of iHOT-12 were 0.45(0.28, 0.58)points, 0.69(0.58, 0.80)points, and 0.81(0.70, 0.92)points, respectively; the values of HOS-ADL were 0.52(0.42, 0.68)points, 0.87(0.75, 0.93)points, and 0.93(0.86, 0.99)points, respectively. The scores of VAS in the hip arthroscopy + PRP group before, at 12 months after surgery and at the last follow-up were 6.00(5.00, 7.00)points, 3.00(2.00, 3.75)points, and 1.00(0.00, 2.00)points, respectively; the values of Modified Harris Hip Score were 46.50(37.00, 56.75)points, 78.00(72.00, 84.00)points, and 84.50(82.00, 88.00)points, respectively; the values of iHOT-12 were 0.42(0.26, 0.51)points, 0.66(0.58, 0.74)points, and 0.81(0.68, 0.88)points, respectively; the values of HOS-ADL were 0.54(0.38, 0.65)points, 0.87(0.72, 0.96)points, and 0.94(0.86, 1.00)points, respectively. In both groups, VAS, Modified Harris Hip Score, iHOT-12, and HOS-ADL were significantly improved at 12 months after surgery and at the last follow-up compared with those before surgery, and were further improved at the last follow-up compared with those at 12 months after surgery (all P<0.01). There were no significant differences in VAS, Modified Harris Hip Score, iHOT-12 and HOS-ADL between the two groups before, at 12 months after surgery and at the last follow-up (all P>0.05). There was no significant difference in the incidence rates of postoperative hip pain and clicking between the two groups (both P>0.05). Conclusion:Hip arthroscopy can considerably improve short-term hip symptoms and function in FAI patients, but the use of PRP treatment after hip arthroscopy cannot further improve its short-term efficacy in FAI patients.

OBJECTIVE To study the effects and mechanisms of serum containing Wenjing Tongluo Decoction on interleukin-1β(IL-1β)-induced mouse primary chondrocyte injury.METHODS The IL-1β-induced primary chondrocyte injury model was estab-lished,and the mRNA expression of inflammatory factors IL-1β,IL-6,TNF-α,cartilage degradation-related proteases matrix metal-loproteinase 3(MMP3),MMP9,MMP13,ADAM metallopeptidase containing thrombospondin 1 motif 4(ADAMTS4),and glycoly-sis-related enzymes lactate dehydrogenase A(LDHA),M2 pyruvate kinase(PKM2),reduced coenzyme Ⅱ oxidase 2(NOX2)and re-duced coenzyme Ⅱ oxidase 4(NOX4)in the cells was detected;the intracellular MMP3,MMP13,P65,IκB-ζ,hypoxia-inducible factor 1α(HIF-1α)and LDHA protein expression levels were determined;the concentrations of nitric oxide(NO),malondialdehyde(MDA)and lactic acid in the cell supernatant were further detected,and the ratio of the reduced state(NADH)and oxidized state(NAD+)of intracellular coenzyme Ⅰ(NAD),as well as intracellular reactive oxygen species(ROS)levels were assayed.RESULTS Serum containing Wenjing Tongluo Decoction significantly inhibited the mRNA expression of IL-1β,IL-6,and TNF-α in IL-1β chondrocytes(P＜0.01),reduced the NO concentration in the cell supernatant(P＜0.05,P＜0.01),and downregulated the protein ex-pression of IκB-ζ(P＜0.05)and P65(P＜0.05,P＜0.01).Serum containing Wenjing Tongluo Decoction significantly downregulated the mRNA expression of MMP3,MMP9,MMP13 and ADAMTS4(P＜0.01),and inhibited the protein expression of MMP13(P＜0.05,P＜0.01)and MMP3(P＜0.05).In terms of oxidative stress,it significantly suppressed the production of ROS in chondrocytes,increased the NADH/NAD+ratio,reduced the MDA concentration in the supernatant,and downregulated the expression of HIF-1α protein(P＜0.01).The serum containing Wenjing Tongluo Decoction significantly reduced the lactic acid concentration,downregulated the expression of LDHA,PKM2,NOX2 and NOX4,and reduced the level of intracellular glycolysis(P＜0.05,P＜0.01).CONCLU-SION The serum containing Wenjing Tongluo Decoction can alleviate IL-1β-induced mouse primary chondrocyte injury by inhibiting inflammation,cartilage degradation,oxidative stress and glycolysis,which may be related to the regulation of IκB-ζ/HIF-1α/LDHA axis.

【Objective】 To assess the prevalence and treatment of high cardiovascular disease （CVD） risk， and identify individual characteristics related to high CVD risk. 【Methods】 Based on the data of the China Patient-Centered Evaluative Assessment of Cardiac Events （PEACE） Million Persons Project （MPP） from 2016 to 2019， this study enrolled local residents aged 35 to 75 years from 39 counties or districts in Northwest China. Rates of high CVD risk and individual characteristics were assessed in the overall study population. Statin and aspirin use was also evaluated among those at high risk for CVD. Multivariable mixed models were fitted to evaluate the relationship between individual characteristics and high CVD risk. 【Results】 Among 364 537 participants， the average age was （54.6±9.7）years， and 5.8% was at a high risk for CVD. Multivariate mixed models showed that individuals who were currently using alcohol， overweight or obese tended to have a high risk for CVD， while married persons， those with a higher education level or a higher household income were correlated with a lower risk for CVD （all P<0.05）. Among high-risk persons， hypertension was the most prevalent risk factor （98.1%）， and only 1.3% and 3.5% reported their use of statins and aspirin， respectively. 【Conclusion】 Of the 364 537 participants， about 1 in 17 had a high risk for CVD. Among those at a high CVD risk， only less than 4% reported taking statins or aspirin. These findings indicate that there is still much room for risk mitigation in this population in China.