The clinical changes of ulcerative colitis （UC） with the main syndrome of large intestine dampness-heat and the alterations of intestinal flora in UC were summarized to reveal the underlying mechanism. After review of the treatment methods for UC with the syndrome of large intestine dampness-heat， we identified the representative traditional Chinese medicines and compound prescriptions and explored the treatment mechanisms. Furthermore， we probed into the associations of UC and the treatment methods with the intestinal flora. The related articles were retrieved from China National Knowledge Infrastructure （CNKI）. The available studies have shown that Akkermansia muciniphila， Escherichia coli， Enterococcus， and probiotics such as Bifidobacterium and Lactobacillus are closely associated with Chinese medicines in UC patients with the syndrome of large intestine dampness-heat. However， due to the shortcomings in clinical research and the susceptibility of intestinal flora to diverse factors， it is still challenging to accurately characterize the intestinal flora changes associated with diseases. Additionally， the research on the mechanisms of Chinese medicines in regulating intestinal flora in UC patients with the syndrome of large intestine dampness-heat remains to be improved. The feasibility of using Chinese medicines and compound prescriptions for precise regulation of intestinal flora in these patients is still debatable. In this regard， scientific issues such as the biological connotation of UC with the syndrome of large intestine dampness-heat and the correlation between syndrome and intestinal flora have become primary research tasks. Additionally， attention should also be paid to the interactions between the intestinal lumen exposure profile of Chinese medicines and intestinal flora. Finally， the thinking of traditional Chinese medicine （TCM） and the concepts of modern medicine should be combined for the research on the formulation of TCM regimens for regulating intestinal flora in treating UC.

Psoraleae Fructus （PF） is a non-toxic Chinese herbal medicine， while the liver injury caused by PF has aroused wide concern in recent years. At present， animal experiments and in vitro studies have been carried out to explore the mechanism， targets， and toxic components of PF in inducing liver injury， which， however， have differences compared with the actual conditions in clinical practice， and there are still some potential hepatotoxic components and targets of PF that have not been discovered. With the continuous progress in systems biology， establishing the drug-induced liver injury model and the liver injury prediction model based on network toxicology can reduce the cost of animal experiments， improve the toxicity prediction efficiency， and provide new tools for predicting toxic components and targets. To systematically explain the characteristics of liver injury in the application of PF and explore the potential hepatotoxic components and targets of PF， we reviewed the related articles published by China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， and PubMed from 1962 to 2021 and analyzed the characteristics and influencing factors of liver injury caused by PF in the patients. Furthermore， we summarized the chemical components of PF and the components entering blood. By reviewing the mechanism， targets， and components of PF in inducing liver injury that were discovered by in vivo and in vitro experiments， we summarized the known compounds in PF that may cause liver injury. Finally， the current methods for building the prediction model of PF-induced liver injury were summarized， and the predicted toxic components and targets were introduced. The possible factors of PF in causing liver injury were explained from three aspects： clinical characteristics， preclinical studies， and computer-assisted network prediction， which provide a reference for predicting the risk of PF-induced liver injury.

Objective:To explore the correlation between subclavian artery stenosis disease (SASD) classification and posterior circulation ischemia.Methods:A retrospective study was performed; the clinical data, and Doppler vascular ultrasound and vascular imaging results of 81 SASD patients, admitted to Cerebrovascular Stenosis Diagnosis and Treatment Center, Second Affiliated Hospital of Qiqihar Medical College and Department of Neurology, Rocket Force Specialty Medical Center from May 2018 to August 2023, were collected. SASD was categorized into 2 types (single type and concurrent type) based on the presence or absence of other posterior circulation artery (basilar artery, vertebral artery, or subclavian artery distal segment) stenosis/occlusion, and into 3 groups (non-posterior circulation ischemia group, posterior circulation transient ischemic attack group and posterior circulation cerebral infarction group) based on the presence or absence of posterior circulation ischemia. Blood stealing pathways in different SASD classifications were analyzed, and correlation of SASD classification with posterior circulation ischemia was discussed.Results:Single-type SASD was noted in 44 patients (54.3%), mainly initiating blood stealing through the vertebral artery to the vertebral artery and then to the subclavian artery ( n=26); concurrent-type SASD was noted in 37 patients (45.7%), mainly initiating blood stealing through the occipital artery to the costocervical trunk and then to the subclavian artery ( n=10). Sixty-five patients (80.2%) were into the non-posterior circulation ischemia group, 4 (4.9%) into the posterior circulation transient ischemic attack group and 12 (14.8%) into the posterior circulation cerebral infarction group. Among the 44 patients with single-type SASD, 39 did not have posterior circulation ischemia, and 3 had posterior circulation cerebral infarction. Among the 37 patients with concurrent-type SASD, 26 did not have posterior circulation ischemia, and 9 had posterior circulation cerebral infarction. Conclusion:Initiation of blood stealing in SASD patients is related to SASD classification, and concurrent-type SASD patients trend to have posterior circulation ischemia.

Objective:To investigate the relationship between white blood cells, neutrophil-lymphocyte ratio(NLR), platelet-lymphocyte ratio(PLR) and monocyte-lymphocyte ratio(MLR) with patients suffering from first episode depression.Methods:This retrospective study was conducted among inpatients of Hebei General Hospital from January 2021 to December 2021.Ultimately, 193 patients with first-episode depression were enrolled.According to the score of Hamilton depression scale-24 (HAMD-24), the patients were divided into mild-moderate depression group(20≤HAMD-24<35 score, n=98) and severe depression group (HAMD-24 score ≥35, n=95). White blood cells and the counts of each cell subtype were detected and the NLR, MLR and PLR were calculated.SPSS 25.0 statistical software was used to analyze the data.Mann-Whitney U test was used to compare differences in the two groups and Binary Logistic regression analyses were performed to recognize the predictive factors of the severity of first episode depression. Results:(1) The white blood cells and NLR in the severe depression group were significantly higher than those in the mild-moderate depression group (white blood cells: 5.77(2.05)×10 9/L vs 5.11(1.31)×10 9/L; NLR: 1.86 (1.04) vs 1.57(0.55), P<0.05). There were no significant differences in PLR and MLR between the two groups ( P>0.05). (2)Multiple regression analysis of NLR, white blood cells and HAMD-24 score showed that there were significant differences in the effect of different white blood cells and NLR levels on HAMD-24 score( B=1.398, P=0.003; B=2.624, P=0.001). (3)Binary Logistic regression revealed that white blood cell count and NLR were risk factors for the severity of depression patients( OR were 1.612 and 2.336, respectively, P<0.05). Conclusion:The results suggest that white blood cells and NLR may be relate with the severity of first episode depression.

Objective:To observe the effect of high expression of polypyrimidine tract-binding protein-associated splicing factor (PSF) on low concentration of 4-hydroxynonenal (4-HNE) induced human retinal microvascular endothelial cells (HRMECs), and explore the possible mechanism.Methods:The HRMECs cultured in vitro were divided into 4-HNE treated group, PSF overexpression group combined with 4-HNE group (PSF+4-HNE group), PSF overexpression+ML385 treatment combined with 4-HNE group (PSF+ML385+4-HNE group), and 4-HNE induced PSF overexpression group with LY294002 pretreatment (LY294002+4-HNE+PSF group). Cell culture medium containing 10 μmmol/L 4-HNE was added into 4-HNE treatment group, PSF+4-HNE group, PSF+ML385+4-HNE group for 12 hours to stimulate oxidative stress. 1.0 μg of pcDNA-PSF eukaryotic expression plasmid were transfected into PSF+4-HNE group and PSF+ML385+4-HNE group to achieve the overexpression of PSF. Also cells were pretreated with ML385 (5 μmol/L) for 48 hours in the PSF+ML385+4-HNE group, meanwhile within the LY294002+4-HNE+PSF group, after pretreatment with LY294002, cells were treated with plasmid transfection and 4-HNE induction. Transwell detects the migration ability of PSF to HRMECs. The effect of PSF on the lumen formation of HRMECs was detected by using Matrigel in vitro three-dimensional molding method. Flow cytometer was used to detect the effect of PSF overexpression on reactive oxygen (ROS) level in HRMECs. Protein immunoblotting was used to detect the relative expression of PSF, nuclear factor E2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1) protein, and phosphoserine threonine protein kinase (pAkt) protein. The comparison between the two groups was performed using a t-test. Results:The number of live cells, migrating cells, and intact lumen formation in the 4-HNE treatment group and the PSF+4-HNE group were 1.70±0.06, 0.80±0.13, 24.00±0.58, 10.00±0.67, and 725.00±5.77, 318.7±12.13, respectively. There were significant differences in the number of live cells, migrating cells, and intact lumen formation between the two groups ( t=12.311, 15.643, 17.346; P<0.001). The results of flow cytometry showed that the ROS levels in the 4-HNE treatment group, PSF+4-HNE group, and PSF+ML385+4-HNE group were 816.70±16.67, 416.70±15.44, and 783.30±17.41, respectively. There were statistically significant differences between the two groups ( t=16.311, 14.833, 18.442; P<0.001). Western blot analysis showed that the relative expression levels of pAkt, Nrf2, and HO-1 proteins in HRMECs in the 4-HNE treatment group, PSF+4-HNE group and LY294002+4-HNE+PSF group were 0.08±0.01, 0.57±0.04, 0.35±0.09, 0.17±0.03, 1.10±0.06, 0.08±0.11 and 0.80±0.14, 2.50±0.07, 0.50±0.05, respectively. Compared with the PSF+4-HNE group, the relative expression of pAkt, Nrf2, and HO-1 proteins in the LY294002+4-HNE+PSF group decreased significantly, with significant differences ( t=17.342, 16.813, 18.794; P<0.001). Conclusion:PSF upregulates the expression of HO-1 by activating the phosphatidylinositol 3 kinase/Akt pathway and inhibits cell proliferation, migration, and lumen formation induced by low concentrations of 4-HNE.

Humans ; Receptors, Chimeric Antigen ; Immune Checkpoint Inhibitors ; Immunotherapy, Adoptive ; Skin Diseases ; Necrosis ; Cell- and Tissue-Based Therapy

Asari Radix et Rhizoma （AR） is a traditional Chinese medicine with a history of more than 2 000 years of medication and has been included in ancient herbal works in the past dynasties. It is effective in releasing the exterior， dispersing cold， dispelling wind， relieving pain， opening orifices， warming the lung， and resolving fluids， and is still widely used in the clinical treatment of influenza， coronavirus disease-2019 （COVID-19） pneumonia， asthma， allergic rhinitis， eye pain， headache， toothache， oral ulcer， eczema， etc. Modern pharmacological studies have shown that AR has antipyretic， anti-inflammatory， analgesic， antibacterial， antiviral， relieving cough and asthma， anti-allergy， and other effects. AR contains a variety of chemical components， in which essential oil is not only associated with functions such as dispelling cold， relieving heat， relieving pain， and resisting inflammation and allergy， but is also toxic. AR also contains lignans， flavonoids， amides， phenanthrenes， alkaloids， and other non-volatile oil components， which play an important role in immunity regulation， anti-inflammation， pain relief， heart strengthening， and blood vessel expansion. The phenanthrene compounds are mainly aristolochic acid analogues， such as aristolochic acid Ⅳ_a and aristolochic lactam Ⅰ. Aristolochic acid Ⅳ_a has been proven to have a significant anti-inflammatory effect. The toxicity of AR is related to safrole， aristolochic acids and their analogues， and is also affected by many factors， such as preparation method， dosage， origin， collection time， medicinal part， and decocting time， which should be comprehensively considered in clinical application. Based on the relevant literature in China and abroad， the present study reviewed the correlation of chemical composition and pharmacological and toxicological effects of AR， and the safety of AR， aristolochic acid， safrole， and other components to provide a new perspective for an objective understanding of AR safety， as well as references for rational clinical application， production risk prevention and control， and drug scientific supervision of AR.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Objective:To analyze the indications for prenatal diagnosis and summarize the pregnancy outcomes and its influencing factors of pregnant women with fetal sex chromosome aneuploidy (SCA).Methods:This study retrospectively enrolled 1 372 fetuses prenatally diagnosed with SCA in Medical Genetics Center of Guangdong Women and Children Hospital from January 2013 to December 2021. The relationship between prenatal diagnosis indications and SCA as well as between ultrasound abnormalities, pregnancy outcomes and SCA types were analyzed by Chi-square test and trend Chi-square test. Results:The most common prenatal diagnosis indication was abnormal non-invasive prenatal testing (NIPT) (61.6%, 845/1 372). The most common SCA type was 47,XXY in cases with indications of abnormal NIPT and advanced maternal age, mosaic in cases with high or borderline risk of Down syndrome, and 45,X in cases with increased nuchal translucency or cystic hygroma. Of 1 372 pregnant women with fetal SCA, 17 were lost to follow-up, seven had intrauterine fetal death, and 1 348 (98.3%) were followed up for pregnancy outcomes including 36.3% (489/1 348) continued pregnancies and 63.7% (859/1 348) terminations. Pregnancy termination rates decreased sequentially in pregnant women carrying fetuses with 45,X, 47,XXY, mosaic, 47,XXX and 47,XYY [99.2% (247/249), 74.5% (307/412), 67.8% (156/230), 36.6% (86/235) and 28.4% (63/222), χ2trend=352.76, P<0.001]. There was no significant difference in pregnancy termination rates among the cases with different mosaic mutations (all P>0.05). The pregnancy termination rate was higher in fetuses with SCA complicated by ultrasound structural abnormalities than in those without ultrasound abnormalities and those with ultrasound soft markers [91.5% (182/199) vs 57.1% (535/937) and 67.0% (142/212), χ2 were 83.68 and 36.85, both P<0.001]. Moreover, the pregnancy termination rate in fetuses with SCA complicated by ultrasound soft markers was higher than those without ultrasound abnormalities ( χ2=7.13, P<0.05). Conclusions:NIPT abnormality is the most common indication for prenatal diagnosis of SCA. The types of SCA and ultrasound findings are important factors determining whether the pregnancy would be continued or not.

Objective:To investigate the relationship of interleukin (IL)-37, osteoprotegerin with coronary artery disease and its stenosisdegree.Methods:The prospective research method was used. From April 2018 to June 2019, two hundred and eleven suspected or diagnosed coronary artery disease patients who had chest pain or discomfort in Dalian Friendship Hospital were selected. The patients underwent selective percutaneous coronary angiography and completed coronary stenosis score (Gensini score). According to the degree of coronary stenosis, 211 patients were divided into the control group(coronary stenosis<50%, 45 cases), single-vessel stenosis group (single-vessel stenosis ≥ 50%, 52 cases), double-vesselstenosis group (double-vesselstenosis ≥ 50%, 58 cases), and triple-vessel stenosis group (triple-vessel stenosis ≥ 50%, 56 cases). The levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a, uric acid, creatinine were measured by the automatic biochemical analyzer. The serum levels of IL-37 and osteoprotegerin were detected by enzyme-linked immunosorbent assay.Results:There were no statistical differences in FBG, uric acid, creatinine, TC, TG, LDL-C, HDL-C, ApoA1 and ApoB among 4 groups ( P>0.05). In the control group, single-vessel stenosis group, double-vessel stenosis group and triple-vessel stenosis group, lipoprotein a was (0.266 ± 0.060), (0.283 ± 0.070), (0.289 ± 0.066) and (0.307 ± 0.084) mg/L respectively; coronary stenosis score was (8.27 ± 7.08), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) scores respectively; IL-37 was (342.27 ± 122.36), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) ng/L respectively; osteoprotegerin was (378.29 ± 111.95), (458.39 ± 115.37), (502.50 ± 116.88) and (533.39 ± 139.83) ng/L respectively; and there were statistical differences among 4 groups ( P<0.05 or <0.01). IL-37, osteoprotegerin and lipoproteina were positively correlated with coronary stenosis score ( r = 0.43, 0.42 and 0.23, P<0.05), the osteoprotegerin was positively correlated with IL-37( r = 0.73, P<0.05). The multivariate linear regression analysis result showed that the IL-37 and osteoprotegerin were independent protective factors of coronary stenosis degree( β = 0.07 and 0.07, t = 2.72 and 2.57, P<0.01 or <0.05),and lipoproteina was independent risk factor of coronary stenosis degree ( β = 0.97, t = 2.89, P<0.01). Conclusions:IL-37 and osteoprotegerin are positively correlated with the degree of coronary stenosis. They are anti-inflammatory and protective factors of coronary heart disease.