Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis， and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine， Chemerin participates in the metabolism of glucose and lipids and inflammation， and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis， suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis， in order to provide new ideas for the diagnosis and treatment of liver fibrosis.

The traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

ObjectiveTo observe the clinical efficacy and safety of Modified Guomin Decoction （加味过敏煎， MGD） in patients with mild to moderate atopic dermatitis （AD） of the traditional Chinese medicine （TCM） pattern of heart fire and spleen deficiency， and to explore its possible mechanisms. MethodsIn this randomized， double-blind， placebo-controlled study， 72 patients with mild to moderate AD and the TCM pattern of heart fire and spleen deficiency were randomly divided into a treatment group and a control group， with 36 cases in each group. The treatment group received oral MGD granules combined with topical vitamin E emulsion， while the control group received oral placebo granules combined with topical vitamin E treatment. Both groups were treated twice daily for 4 weeks. Clinical efficacy， TCM syndrome scores， Visual Analogue Scale （VAS） for pruritus， Dermatology Life Quality Index （DLQI） scores， Scoring Atopic Dermatitis （SCORAD） and serum biomarkers， including interleukin-33 （IL-33）， interleukin-1β （IL-1β）， immunoglobulin E （IgE）， and tumor necrosis factor-α （TNF-α） were compared before and after treatment. Safety indexes was also assessed. ResultsThe total clinical effective rates were 77.78% （28/36） in the treatment group and 38.89% （14/36） in the control group， with cure rates of 19.44% （7/36） and 2.78% （1/36）， respectively. The treatment group showed significantly better clinical outcomes compared to the control group （P＜0.05）. The treatment group exhibited significant reductions in total TCM syndrome scores， including erythema， edema， papules， scaling， lichenification， pruritus， irritability， insomnia， abdominal distension， and fatigue scores， as well as reductions in VAS， DLQI， SCORAD， and serum IgE and IL-33 levels （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had significantly better improvements in all indicators except for insomnia （P＜0.05）. No adverse events occurred in either group. ConclusionMGD is effective and safe in treating mild to moderate AD patients with heart fire and spleen deficiency pattern. It significantly alleviates pruritus， improves TCM syndromes and quality of life， and enhances clinical efficacy， possibly through modulation of immune responses.

AIM:To investigate the role of serum high-sensitivity C-reactive protein(hsCRP)in the pathogenesis and progression of diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM).METHODS:A nested case-control study was conducted involving 187 T2DM patients(187 eyes)who attended at Eye Center, Beijing Tongren Hospital, Capital Medical University from June 2017 to October 2024. Patients were categorized into three groups: the diabetes mellitus(DM)group, non-proliferative DR(NPDR)group, and proliferative DR(PDR)group. Baseline information was collected, including age, sex, duration of DM, and duration of hypertension. All patients underwent fasting biochemical tests and comprehensive ophthalmic examinations.RESULTS: A positive correlation was observed between hsCRP and fasting blood glucose(FBG; P=0.004)and glycated hemoglobin A1c(HbA1c; P=0.048)by Spearman's rank correlation coefficient analysis. After adjusting for confounding factors, multivariable Logistic regression identified hsCRP as a significant risk factor for DR(OR=2.67, 95% CI: 1.19-5.96, P=0.017). CONCLUSION:Serum hsCRP is positively correlated with FBG and HbA1c and can serve as an important predictor of the severity of DR.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

AIM:To investigate the expression of centromere protein-H(CENP-H)in adrenocortical carcino-ma(ACC)and its relationship with disease progression and prognosis,and to explore the impact of CENP-H gene knock-down on the viability and migration of ACC cells.METHODS:The mRNA expression level of CENP-H in 76 ACC pa-tients and 128 healthy controls,and its correlations with tumor stages and prognosis were analyzed by GEPIA2 database.The mRNA expression of CENP-H in different stages of ACC and its correlation with disease prognosis were further ana-lyzed by ULCAN database.The protein expression of CENP-H was examined by immunohistochemical staining of paraffin-embedded ACC and normal adrenal gland specimens.Knockdown of CENP-H by siRNA(siCENP-H)was performed in human ACC cell line H295R.The viabilty of H295R cells transfected with siCENP-H or siNC was measured by CCK-8 as-say,the cell migration was detected by wound-healing assay,and the protein levels of CENP-H,p-ERK1/2,t-ERK1/2,p-P38,t-P38,p-JNK1/2 and t-JNK1/2 were detected by Western blot.RESULTS:The mRNA level of CENP-H was signifi-cantly higher in ACC than that in normal controls,and was correlated with tumor stages and prognosis.The protein level of CENP-H was significantly higher in ACC specimens than that in normal adrenal gland.Knockdown of CENP-H in H295R cells resulted in decreased cell viability and migration.The protein levels of p-P38 and p-JNK1/2 were decreased in si-CENP-H group.CONCLUSION:CENP-H is highly expressed in ACC,and is correlated with tumor stages and poor prognosis.Knockdown of CENP-H can inhibit the viability and migration of ACC cells,and its mechanism may related to inactivation of P38 and JNK signaling pathways.

Objective:To investigate the relationship between the expressions of checkpoint with forkhead-associated and ring finger(CHFR)and metastasis-associated protein 1(MACC1)and the sensitivity of patients with rectal cancer for neoadjuvant concurrent chemoradiotherapy(nCRT).Methods:The medical documents of 166 patients with rectal cancer admitted to First Hospital of Qinhuangdao from March 2017 to February 2022 were collected.All patients only received nCRT before surgery,and the radiotherapy adopted three-dimensional conformal intensity modulated radiotherapy,and chemotherapy adopted Capeox scheme.All patients successfully completed total mesorectal excision after 4-6 weeks of nCRT treatment.Immunohistochemical SP staining method was used to detect the protein expressions of CHFR and MACC1 in rectal cancer and its adjacent tissues.According to the tumor regressive grading(TRG)standard of the Joint Committee on Cancer Staging in the United States,75 patients who were grade 0-2 as TRG after nCRT were included in the nCRT insensitive group,and 91 patients who were grade 3-4 as TRG were included in the nCRT sensitive group.The expression levels of CHFR and MACC1 proteins in cancer tissues before and after treatment between the two groups were compared.And then,the relationship between clinically pathological characteristics of patients and nCRT sensitivity was analyzed,and the influencing factors of nCRT sensitivity were analyzed.The receiver operating characteristic(ROC)curves of them were drawn,and area under curve(AUC)values were calculated,and the predictive values of CHFR and MACC1 for the sensitivity of patients with rectal cancer to nCRT were further analyzed.Results:The CHFR positive expression rate in rectal cancer tissue was significantly lower than that in adjacent tissues of rectal cancer,and the MACC1 positive expression rate in rectal cancer tissue was significantly higher than that in adjacent tissues of rectal cancer(x2=81.373,87.150,P＜0.05),respectively.After 166 patients completed the nCRT treatment,there were 6 cases of TRG grade 0,8 cases of TRG grade 1,61 cases of TRG grade 2,59 cases of TRG grade 3 and 32 cases of TRG grade 4.The sensitivity rate of nCRT was 54.82%(91/166).The CHFR positive expression rate in the nCRT sensitive group was significantly higher than that in the nCRT insensitive group,and the MACC1 positive expression rate in the nCRT sensitive group was significantly lower than that in the nCRT insensitive group(x2=4.613,37.509,P＜0.05).The proportions of T4 stage and N+stage in the nCRT sensitive group were higher than those in the nCRT insensitive group,and the differences were statistically significant(x2=54.432,28.912,P＜0.05),respectively.The expressions of CHFR and MACC1 were respectively independent risk factor affected the sensitivity of patients with rectal cancer to nCRT[OR=2.456(95% CI:1.294-4.563),OR=3.281(95% CI:1.472-6.479),P＜0.05].The sensitivity and specificity of the combined detection of CHFR and MACC1 were respectively 65.89% and 69.46% in predicting the nCRT sensitivity for rectal cancer.The predictive value of the combined detection was higher than that of single CHFR detection and single MACC1 detection(AUC values of them were respectively 0.713,0.564,0.589,P＜0.05),respectively.Conclusion:CHFR and MACC1 are related to the sensitivity of patients with rectal cancer to nCRT,which means patients with high expression of CHFR and low expression of MACC1 are more sensitive to nCRT.Therefore,both of them may be indicators that predict the sensitivity of patients with rectal cancer to nCRT.

OBJECTIVE To prepare berberine/piperine co-loaded self-microemulsion drug delivery system （BBR/PIP- SMEDDS）， evaluate its physicochemical properties， in vitro release and pharmacokinetic characteristics. METHODS The drug loading mass ratio of berberine （BBR） and piperine （PIP） in the preparation was determined by the everted intestinal sac method. The oil-phase， emulsifier and co-emulsifier were determined by solubility detection， compatibility evaluation and pseudo-ternary phase diagram， respectively. The formulation of blank self-microemulsion drug delivery system （SMEDDS） was optimized and verified by central composite design-response surface methodology with the amount of oil-phase and the mass ratio of emulsifier to co-emulsifier as factors， and the comprehensive score of particle size and Zeta potential as response value. According to the optimal prescription， BBR/PIP-SMEDDS was prepared by adding excessive BBR and PIP raw materials under magnetic stirring， and its physicochemical properties， in vitro release behavior and pharmacokinetic characteristics in rats were investigated. RESULTS The drug loading mass ratio of BBR and PIP was 1∶1. The optimal prescription included oil-phase （ethyl oleate） accounted for 18.54%， emulsifier （Tween-80） accounted for 52.16%， and co-emulsifier （polyethylene glycol 400） accounted for 29.30%. Three verification experiments showed that the average particle size of blank SMEDDS was （16.49±0.49） nm； the Zeta potential was （－16.22±0.77） mV； the comprehensive score was 0.97， the relative deviation of which from the predicted value （0.95） was 2.11%. The prepared BBR/PIP-SMEDDS was an oil-in-water microemulsion， which was a golden yellow oily liquid with a spherical shape. The average particle size was （32.90±0.38） nm， and the Zeta potential was （－19.17±0.70） mV. The encapsulation efficiency of BBR was （90.44±0.88）% ， and the drug loading was （10.18±0.17） mg/g. The encapsulation efficiency of PIP was （87.48±1.13）%， and the drug loading was （9.41±0.17） mg/g. BBR/PIP-SMEDDS had good stability at low temperature （4 ℃ ） in the dark， centri-fugation and dilution. The results of in vitro release showed that the cumulative release percentage of BBR in simulated intestinal fluid for 24 h was significantly higher than that of the raw drug after the preparation of SMEDDS. The pharmacokinetic results in rats showed that the peak concentration and area under the drug- concentration time curve （AUC0－）t of BBR/PIP-SMEDDS were 4.61 and 7.07 times higher than those of the raw drug respectively， and the relative bioavailability was 707.484%. CONCLUSIONS BBR/PIP-SMEDDS is successfully prepared， and the in vitro release and bioavailability of the preparation are greatly improved compared with the raw material.

Metal pollutants in the natural environment and industrial environment can enter organisms through the respiratory tract and digestive tract causing adverse health effects. Many kinds of literatures confirm that metal pollutants have neurotoxicity. Recent studies have showed that astrocytes play an important role in neurotoxicity induced by metal pollutants. In this review, the latest progress of neurotoxicity induced by lead, mercury, cadmium, antimony and copper through astrocytes in recent years is summarized, which provides a new clue for the neurotoxicity research of metal pollutants.

Objective To explore the correlation between serum fibroblast growth factor-23 (FGF23) concentration and heart failure and all-cause death in patients with end-stage renal disease (ESRD).Methods The prospective cohort study design was used in the present study.The ESRD patients who were admitted to the department of ne-phropathy in the Hospital and without heart failure symptoms were recruited in this study.The data of patients was collected through baseline questionnaires, physical examinations, echocardiography, and laboratory examinations.The serum FGF23 levels were measured by enzyme-linked immunosorbent assay (ELISA) .The follow-up time was 2 years.The onset of heart failure (ACC/AHA stage C-D) and all-cause death were composite endpoint events.The Cox proportional risk model was used to explore the risk factors of outcome events.Through subgroup analyses and interaction analyses, further exploration was conducted to determine whether there was heterogeneity in the as-sociation between FGF23 and outcome events in different subgroups.Results Ultimately,107 ESRD patients were included in this study, with an average age of (52.00 ± 12.51) years.There were 39 males (36.45％), and the median follow-up time was 23 months (21, 25 months).There were 32 (29.9％) outcome events, of which 22 (20.6％) onset of heart failure and 10 (9.3％) all-cause of deaths.The results of this study showed that the con-centration of FGF23 in the outcome event group was significantly higher than that in the non-event group [ (4.40 ± 1.16) pmol/ml vs (3.85 ± 0.82) pmol/ml,P<0.05].The Cox proportional risk model showed that the elevated FGF23 was associated with increased risk of the composite endpoint events in ESRD patients (HR=1.730 , 95％CI:1.164-2.570 , P=0.007) .Subgroup analyses showed that there was an interactive effect between FGF23 levels and gender on the risk of cardiovascular outcome events.Especially in male ESRD patients, the increased FGF23 level was correlated with a higher risk of cardiovascular events (P-interaction <0.05).Conclusion Elevated serum FGF23 is an independent risk factor for the onset of heart failure and all-cause of mortality in ESRD patients, especially in male patients.