Palliative care is recognized as an effective measure to improve the quality of life for patients with end-stage diseases， and the significance and role of such patients participating in clinical trials to conquer major diseases has also become a broad consensus. However， due to the special physical， psychological， and social conditions of terminal trial participants， the ethical problems encountered in the trial process are more serious and complex. Drawing on ethical practice experience， these seemingly common phenomena and issues were deeply analyzed. Combined with the palliative care philosophy for end-stage patients， this paper proposed a series of improvement suggestions throughout the entire life cycle of clinical trials， hoping to promote the quality improvement of clinical research in which end-stage patients participate as subjects， while effectively protecting the safety and rights of the subjects and ensuring they receive appropriate palliative care during their participation in clinical trials or clinical-related scientific research.

ObjectiveTo observe the intervention effect of Huaiqihuang granules （HQH） on immunoglobulin A vasculitis nephritis （IgAVN） mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group， an IgAVN model group， a dexamethasone group （2.5 mg·kg^-1·d^-1）， a low-dose HQH group （4 g·kg^-1·d^-1）， and a high-dose HQH group （8 g·kg^-1·d^-1）. The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling， the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein （24 h UTP）， urine β₂-microglobulin （β₂-MG）， serum total protein， albumin， IgA， etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 （Th17） cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α （AMPKα）， phosphorylated AMPKα （p-AMPKα）， acetyl-CoA carboxylase 1 （ACC1）， and phosphorylated ACC1 （p-ACC1） in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group， the IgAVN model group showed significant increases in 24 h UTP， urine β₂-MG， total cholesterol （P<0.05）， serum interleukin-17 （IL-17）， IgA， Th17 proportion in the spleen cell suspension， and IL-17 expression in the spleen tissue （P<0.01）， and significantly decreased serum total protein， albumin， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.01）. Compared with the IgAVN model group， in the 4th week， the 24 h UTP， urine β₂-MG， serum IL-17， IgA levels， and renal IgA deposition were significantly reduced in each treatment group （P<0.01）， and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased （P<0.05， P<0.01）. Serum albumin levels significantly increased （P<0.05）. Compared with the IgAVN model group， the dexamethasone group and the high-dose HQH group showed increases in serum total protein （P<0.01）， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.05， P<0.01）. The high-dose HQH group showed a significant decrease in total cholesterol level （P<0.05）. Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway， correcting immune inflammatory disorders， and exerting therapeutic effects on IgAVN.

Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P＜0.01),and the E2 level was significantly decreased(P＜0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P＞0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P＜0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P＜0.05),had no difference with the blank group(P＞0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P＜0.01),still being lower than the blank group(P＜0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P＞0.05),while the protein expression level of P450arom was lower than that in the model group(P＜0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P＜0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P＜0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P＜0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P＜0.05 or P＜0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To understand the commercial homosexual behavior characteristics of men who have sex with men (MSM) and the factors associated with unprotected anal intercourse (UAI) in this population, and provide reference for the development of intervention strategy in MSM.Methods:Men who were aged ≥16 years and had anal sex with men in the past 6 months were recruited through internet in Fuzhou from January to December 2023 for a cross-sectional study with a sample size of 283. Multivariate logistic regression model was used to analyze the factors associated with the incidence of UAI in the past 6 months in MSM. The SPSS 25.0 software was used for statistical analysis.Results:In 4 484 MSM, the proportion of those with commercial homosexual behaviors was 9.59% (430/4 484), the average age was (27.00±9.07) years. In the MSM with commercial homosexual behaviors, 70.00% (301/430) had anal sex in the past one week, and 43.02% (185/430) had anal sex with more than 10 partners in the past 6 months. The proportion of MSM with UAI was 75.58% (325/430) in the past 6 months. The results of multivariate analysis showed showed that in MSM with commercial homosexual behaviors in the past 6 months, compared with those who were students, age >18 years at the first sexual intercourse, had not anal sex in the past one week, and anal sex with less than 10 partners in the past 6 months, the risk for UAI was higher in those who were not students (a OR=1.99,95% CI:1.18-3.36), those who were aged ≤18 years at first sexual intercourse sex (a OR=2.04,95% CI:1.26-3.29), those who had anal sex in the past one week (a OR=2.04,95% CI:1.25-3.33), and those who had anal sex with more than 10 partners in the past 6 months (a OR=1.97,95% CI:1.16-3.35). Conclusions:The risk for UAI was high in MSM with commercial homosexual behaviors in Fuzhou, so it is necessary to improve the awareness of safe sex and promote sex with regular partners and condom use, and preventing drug abuse in MSM.

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.

Urine nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving learning and memory ability in APP/PS1 mice of Psoralea corylifolia. All animal experiments were approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (Approval No.: 2020092502). Sixteen APP/PS1 mice were randomly divided into the model group and Psoralea corylifolia group (0.5 g·kg^-1), and eight male C57BL/6J mice of the same background were selected as control group, step-through test and novel object recognition were used as evaluation indexes. Changes in urine endogenous metabolites of mice from eachgroup were determined by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), and differential metabolites were screened, and metabolic pathway enrichment analysis was performed. The results of pharmacodynamic investigation showed that Psoralea corylifolia can reduce the dark incubation period and number of errors in APP/PS1 mice (P < 0.01) and improve the new object recognition index of APP/PS1 mice (P < 0.01). Metabolomics analysis identified 15 differential metabolites, and 9 differential metabolites were significantly call back by Psoralea corylifolia. Metabolic pathway analysis showed that histidine metabolism, citric acid cycle, taurine and hypotaurine metabolism and glucose metabolism were the main metabolic pathways of Psoralea corylifolia in improving learning and memory ability. These studies suggest that Psoralea corylifolia improves the learning and memory ability of APP/PS1 mice, and its mechanism may be related to improving mitochondrial dysfunction, reducing peripheral histamine level, regulating energy metabolism disorders and antioxidant levels.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.