OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

The outbreak of the COVID -19 has had a big impact on the implementation of clinical trials of tumor drugs and the prevention and control measures such as traffic control and home isolation has caused clinical trials couldn’t proceed normally, so the protection of tumor subjects in clinical trials faces many new challenges. Based on Western and Chinese policies and guidelines on the management of clinical trials during the COVID -19, this paper expounded the impacts of the COVID -19 on tumor patients and tumor clinical trials, analyzed the challenges faced by the protection of tumor subjects in the prevention and control of the COVID -19, and then protected tumor subjects from aspects of optimizing the allocation of health resources, improving non-face-to-face informed consent procedures, strengthening subject visit management, and enhancing clinical trial safety evaluation. It is hoped that these optimization measures can face the future and continue to protect subjects after the end of the epidemic or in new public health emergencies.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO₂ nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8⁺ and CD4⁺ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

The outbreak of the COVID -19 has had a big impact on the implementation of clinical trials of tumor drugs and the prevention and control measures such as traffic control and home isolation has caused clinical trials couldn’t proceed normally, so the protection of tumor subjects in clinical trials faces many new challenges. Based on Western and Chinese policies and guidelines on the management of clinical trials during the COVID -19, this paper expounded the impacts of the COVID -19 on tumor patients and tumor clinical trials, analyzed the challenges faced by the protection of tumor subjects in the prevention and control of the COVID -19, and then protected tumor subjects from aspects of optimizing the allocation of health resources, improving non-face-to-face informed consent procedures, strengthening subject visit management, and enhancing clinical trial safety evaluation. It is hoped that these optimization measures can face the future and continue to protect subjects after the end of the epidemic or in new public health emergencies.

The advancement of medicine and biotechnology is based on biomedical research. The rights and safety protection of subjects in biomedical research is one of the core issues of research ethics,and the protection of vulnerable subjects should be the top priority importantly,research ethics should provide special protection for vulnerable subjects. Chinese laws and regulations have not yet given a clear definition of the concept of vulnerability,and the content and regulations related to vulnerability are relatively rough and not perfect. By drawing on the main international and foreign research ethics policies and guidelines,introducing the definition of vulnerability,clarifying the source of vulnerability,and applying vulnerability to the process of biomedical research in China. When applying vulnerabilities,one should avoid using the label approach to include people with common characteristics into vulnerable groups,but mainly analyze the types and sources of vulnerability,and includes as many vulnerable subjects of different types as possible to provide them with more comprehensive and adequate protection in biomedical research.

Objective:To observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD).Methods:A retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 ( IL-8), complement C3 gene ( C3), complement factor H ( CFH), liver lipase ( LIPC), cholesterol ester transfer protein ( CETP), ATP binding cassette subfamily a member 1 ( ABCA1), lipoprotein lipase ( LPL), fatty acid desaturation gene cluster ( FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. Results:There were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio ( OR)=0.310, 95% confidence interval ( CI) 0.106-0.910, P<0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders ( OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) ( OR=3.031, 95% CI 1.036-8.867, P<0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant ( t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment ( IL-8 rs4073: Z=-0.198, -1.651; P=0.843, 0.099; LIPC rs2043085: Z=-0.532, -0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions:Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.

In recent years, the subthreshold micropulse laser is a kind of laser mode which is characterized by long intermittence. It achieves effective therapeutic effect while minimizes the damage to tissues. At present, it has been used to treat diabetic macular edema. Early studies suggested that the laser selectively acts on retinal pigment epithelial cells to reduce macular edema by regulating the expression of inflammatory biomarkers, growth factors, heat shock proteins and other substances. In recent years, with the development of research, more and more emphasis has been placed on the role of retinal glial cells. Müller cells are also considered as one of the target cells affected by micropulse laser, but there is no evidence of direct or indirect effects of micropulse laser on Müller cells. In the near future, it is expected that we will have more clinical evidence to confirm the target cells of the micropulse laser, which may be further confirmed by in vitro experiments through Müller cells or Müller cells co-cultured with retina pigment epithelium cells, so as to make a more detailed statement on the mechanism of it.

Mesenchymal stromal/stem cells (MSCs) are a type of pluripotent stem cells capable of differentiating into osteoblasts, chondrocytes, adipocytes, and cardiomyocytes. MSCs can be obtained from a variety of sources, including bone marrow, adipose tissue, dental pulp, The umbilical cord and the placenta, peripheral blood, skin, and synovial fluid. Studies at home and abroad have shown that MSCs have important research value and great application potential in the treatment of a variety of autoimmune diseases. MSCs have opened a new door for the medical community, and triggered an upsurge of research on MSCs transplantation for autoimmune disease trials. However, in view of the limitations of current MSCs, the safe application of MSCs in the treatment of autoimmune diseases still requires larger and more in-depth trial and clinical data support. In this paper, we will review the therapeutic effect of MSCs in autoimmune diseases and the possible mechanism of its effect.