The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective:To discuss the research status and hotspots of Kaixin Powder.Methods:Literature about Kaixin Powder was retrieved from CNKI, Wanfang Data, VIP, CBM, PubMed and Web of Science databases from the establishment of the databases to January 10, 2023. CiteSpace 6.2.R2 and VOSviewer 1.6.16 software were used to visualize and analyze data on the types of literature included, source journals, publication volume, authors, institutions, keywords, etc.Results:Totally 235 articles were included, mainly Chinese journal article. There were 87 source journals involved, among the Chinese and English journals, China Journal of Chinese Materia Medica and J Ethnopharmacol published the most articles. The overall annual number of articles published in the Kaixin Powder showed an upward trend. It involved 505 authors, forming research teams with Liu Ping, Jiang Yanyan and others as the core; The authors of the included literature came from 99 research institutions, and the cooperation between institutions was mainly based on units with the same or similar geographical area, TCM universities and their affiliated hospitals. The data results of keyword co-occurrence clustering network, keyword co-occurrence time network and keyword emergence analysis showed that the composition of the main active components (ginsenosides, poria acid, fine octyl ethers, ketones and oligosaccharide esters), detection methods (high performance liquid chromatography and liquid chromatography-mass chromatography), pharmacological effects (anti-Alzheimer's disease, antidepressant), mechanism of action and clinical application of the combination were the current research hotspots and trends in development. Conclusion:The research of Kaixin Powder mostly focuses on the mechanism of action and clinical research of Alzheimer's disease, depression and other diseases, among which the research on the main active components in Kaixin Powder is a hot topic in recent years, while the development trend of pharmacological mechanism of action and clinical application is better, and the correlation between active components and efficacy may become a new hot direction in the research of Kaixin Powder.

Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.

Objective:To investigate the current situation of coping styles in Crohn's disease patients and its related influencing factors.Methods:A total of 80 patients with Crohn's disease admitted to our hospital from Apri 2021 to Dec 2022 were selected to evaluate their coping styles with a simple coping style questionnaire,and relevant data were collected.The factors affecting the coping styles of Crohn's disease were analyzed by multivariable logistic regression.Results:Among the 80 patients,29 cases were negative coping,the incidence was 36.25% .There were 51 patients with positive coping(63.75% ).Educational level,simplified Crohn's disease activity index(CDAI)score,adverse psychology,social support and type D personality were associated with negative coping(P＜0.05).Gender,age,family history,working status,monthly family income,place of residence,and marital status were not associated with negative coping in patients with Crohn's disease(P＞0.05).Multivariable logistic regression analysis showed that education level of high school or below(OR=2.945,95% CI:1.139-7.614),higher CDAI score(OR=11.999,95% CI:4.387-32.815),poor psychology(OR=5.950,95% CI:2.180-16.239),low social support(OR=3.598,95% CI:1.370-9.448)and type D personality(OR=3.208,95% CI:1.118-8.904)were risk factors for negative coping in patients with Crohn's disease(P＜0.05).Conclusions:The incidence of negative coping in patients with Crohn's disease is higher,which is related to high school education or below,high CDAI score,poor psychology,low social support,and type D personality.Therefore,clinical measures can be taken to promote patients to actively cope with the disease.

Objective To promote the pharmacist's ability to identify and resolve drug-related problems(DRPs)in Physician-and pharmacist-managed clinic of interstitial lung disease using pharmaceutical care network Europe(PCNE)classification system.Methods Patients of physician-and pharmacist-managed clinic from February 1,2022 to February 1,2023 were included.Problems,causes,intervention types,intervention acceptability,and solution state of DRPs were analyzed using the PCNE classification system.Results A total of 128 patients were included and 178 DRPs were identified,with an average of 1.39 DRPs per patient.The main types of problems were effectiveness(127 cases,71.35%)and safety(39 cases,21.91%);The main causes classification were patient-related(85 cases,47.75%),drug selection(30 cases,16.85%)and dose selection(27 cases,15.17%);The main intervention type was patient-level(176 cases,54.32%).A total of 243 interventions were provided to physicians and patients by pharmacists,in which 231 interventions were accepted with the overall acceptance rate of 95.06%.Ultimately,152(85.39%)DRPs were resolved.Conclusion The PCNE classification system is helpful to improve the efficiency of DRP recognition and resolution in the joint outpatient clinic,promote the standardization,convenience,and precision of the pharmaceutical care model,and improve the rationality,safety,and effectiveness of patients'drug use.

Photohardening therapy, also known as photodesensitization therapy, refers to the phototherapy and photochemotherapy of idiopathic actinic dermatoses, and its goal is to improve the patients′ tolerance to sunlight and prevent disease flares. Its mechanisms of action involve a variety of cellular and inflammatory factors. This therapy is suitable for all idiopathic actinic dermatoses, with definite efficacy and good safety. However, the treatment specificity usually leads to poor compliance. The development of UVA1 rush hardening and home phototherapy is expected to solve this problem.

Objective:To investigate serum lipidomic profiles in patients with chronic actinic dermatitis (CAD), and to search for biomarkers of CAD.Methods:A retrospective analysis was conducted. Serum samples were collected from 46 patients with CAD and 16 age- and gender-matched healthy controls in the Guangzhou Institute of Dermatology from April 2011 to December 2021. Changes in serum lipid composition and expression were assessed by liquid chromatography-mass spectrometry. Principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis were performed to screen differential biomarkers, and receiver operating characteristic (ROC) curve analysis was conducted to screen diagnostic markers. Comparisons of the age and gender distribution between groups were performed using t test and chi-square test, respectively. Results:The 46 CAD patients were aged from 30 to 84 (60.39 ± 10.52) years, including 41 males and 5 females; the 16 healthy controls were aged from 50 to 89 (59.81 ± 10.72) years, including 14 males and 2 females; there were no significant differences in the age or gender distribution between the two groups (age: t = 0.19, P = 0.853; gender: χ2 = 0.03, P = 0.859). Totally, 4 136 lipid molecules belonging to 40 subclasses were identified in the serum samples from CAD patients as well as healthy controls. Twenty-two differential lipid molecules were identified between the CAD patients and healthy controls, belonging to 9 subclasses (triglycerides, sphingomyelin, phosphatidylserine, phosphatidylethanolamine, monofatty acid glycerides, lysophosphatidylcholine, hexose ceramide, diglycerides, and cardiolipin). When the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, or those of phosphatidylserine (18.0_18.1) and H served as diagnostic markers separately, the areas under the ROC curve (AUCs) were all > 0.8, and the AUCs of 16 differential lipid molecules were all > 0.7. Conclusion:The serum lipid composition differed between healthy controls and CAD patients, and the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, and those of phosphatidylserine (18.0_18.1) and H may be promising biomarkers for the diagnosis of CAD.

Objective:To evaluate the effect of metformin on ultraviolet A (UVA) -induced photoaging of an immortalized human keratinocytes cell line (HaCaT), and to explore its potential mechanisms.Methods:Cell counting kit 8 (CCK8) assay was performed to evaluate the effect of metformin at different concentrations (0 - 100 mmol/L) on the viability of HaCaT cells, and 10 mmol/L metformin was selected for subsequent experiments. Cultured HaCaT cells were divided into a blank control group (conventional culture), a metformin group (treated with culture medium containing 10 mmol/L metformin), a UVA irradiation group (conventional culture for 24 hours followed by 10 J/cm 2 UVA irradiation) and a metformin + UVA group (treated with culture medium containing 10 mmol/L metformin for 24 hours followed by 10 J/cm 2 UVA irradiation) ; UVA irradiation was performed at a dose of 10 J/cm 2 once a day for 3 consecutive days. After 4-day treatment, cells were collected, the β-galactosidase assay was performed to determine the proportion of senescent cells in each group, 2′, 7′-dichlorodihydrofluorescein diacetate assay to detect levels of intracellular reactive oxygen species (ROS), and the comet assay to detect DNA damage levels. Additionally, some HaCaT cells were divided into the blank control group, metformin group, 1.25 μmol/L dorsomorphin (an adenosine monophosphate-activated protein kinase [AMPK] inhibitor) + metformin group, and 2.5 μmol/L dorsomorphin + metformin group, and cells in the latter two groups were treated with 1.25 and 2.5 μmol/L dorsomorphin respectively for 2 hours, followed by the treatment with 10 mmol/L metformin for 24 hours. Western blot analysis was performed to determine the cellular localization and phosphorylation levels of nuclear factor-erythroid 2-related factor 2 (Nrf2). By using the small-interfering RNA (siRNA) -mediated silencing method, siRNA-Nrf2 was transfected into HaCaT cells to knock down Nrf2 expression (siRNA-Nrf2 group) ; 2.5 μmol/L dorsomorphin-treated HaCaT cells or Nrf2-knockdown HaCaT cells were treated with metformin and UVA irradiation (dorsomorphin + metformin + UVA group, siRNA-Nrf2 + metformin + UVA group, respectively), and the proportions of senescent cells were further calculated in each group. Statistical analysis was carried out by using one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Treatment with different concentrations of metformin for 24 hours could affect the viability of HaCaT cells to varying degrees ( F = 5 206.31, P < 0.001) ; there were no significant differences in the relative survival rates of HaCaT cells between the 10 - 20 mmol/L metformin groups and the control group (0 mmol/L metformin group, all P > 0.05), while the relative cell survival rates were significantly lower in the 25 - 100 mmol/L metformin groups than in the control group (all P < 0.05). After UVA irradiation, HaCaT cells shrank significantly and became narrow and elongated, and the intercellular spaces increased; the relative cell survival rate was significantly lower in the UVA irradiation group (76.13% ± 1.03%) than in the blank control group (100.00% ± 1.24%, LSD- t = 14.86, P < 0.001), but significantly higher in the metformin + UVA group (106.69% ± 2.45%) than in the UVA irradiation group (LSD- t = 11.55, P < 0.001). Moreover, the UVA irradiation group showed significantly increased proportions of senescent cells (45.14% ± 4.98%), intracellular ROS levels (144.61% ± 4.91%), and percentages of DNA in the tail (75.33% ± 1.77%) compared with the blank control group (23.84% ± 1.89%, 55.49% ± 1.57%, 1.88% ± 0.29%, respectively, all P < 0.001), while the metformin + UVA group showed significantly decreased proportions of senescent cells (24.26% ± 1.34%), intracellular ROS levels (58.62% ± 2.17%), percentages of DNA in the tail (15.83% ± 1.23%) compared with the UVA irradiation group (all P < 0.001). Western blot analysis showed that the Nrf2 expression in the cytoplasm was lower in the 10 mmol/L metformin group than in the blank control group, while the phosphorylated Nrf2 expression in the nuclei was higher in the 10 mmol/L metformin group than in the blank control group, suggesting that metformin could effectively induce the phosphorylation of Nrf2 and its nuclear translocation; both the pretreatment with 1.25 and 2.5 μmol/L dorsomorphin could significantly reduce the phosphorylation levels of AMPKα and Nrf2 induced by 10 mmol/L metformin. The proportions of senescent cells in the dorsomorphin + metformin + UVA group and the siRNA-Nrf2 + metformin + UVA group were 67.84% ± 2.74% and 65.94% ± 1.33%, respectively, which were significantly higher than those in the metformin + UVA group (37.76% ± 1.64%, t = 14.45, 13.34, respectively, both P < 0.001) . Conclusion:Metformin may inhibit UVA-induced photoaging of HaCaT cells by activating the AMPK/Nrf2 signaling pathway, scavenging ROS and reducing DNA damage.