Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

Objective To compare the macular retinal thickness characteristics of diabetic kidney disease(DKD)patients with different blood pressure levels and explore the relationship between blood pressure and macular retinal damage in DKD patients.Methods A total of 435 DKD patients were selected and divided into four groups based on medical history and blood pressure:the non-hypertensive group(NH group,n=100),the well-controlled blood pressure group(G0 group,n=176),the grade 1 hypertension group(G1 group,n=118)and the grade 2 hypertension group(G2 group,n=41).General information,routine laboratory test results as well as the average thickness of the macular retinal nerve fiber layer(RNFL),ganglion cell layer(GCL),ganglion cell complex(GCC),choroidal layer(CL)and central macular retinal thickness(CMT)were compared between the four groups.The correlation between macular retinal thickness in both eyes and clinical data was analyzed.Results Compared with the G1 group and the G2 group,the G0 group had a longer duration of hypertension.Compared to the NH group,the G2 group had higher fasting plasma glucose(FPG).Compared to the G0 group,the G1 group and the G2 group had higher FPG,and the G2 group had higher glycated hemoglobin(HbA1c)and lower estimated glomerular filtration rate(eGFR).Compared to the NH group,the G0 group had decreased thickness in the GCL and GCC(P<0.05).The macular retinal thickness of the GCL and GCC in both eyes was negatively correlated with diastolic blood pressure(r=-0.158 and-0.195,respectively,P<0.05).Conclusion Macular retinal thickness is helpful in assessing the long-term effects of hypertension on optic nerve and microvascular damage in DKD patients.

OBJCTIVE To evaluate the therapeutic efficacy of intranasal administration of pirfeni-done in treating paraquat-induced pulmonary fibrosis in mice across treatment durations.METHODS Eight-week-old male C57BL/6 mice were randomly divided into six groups(n=8 per group):the normal control group(saline),pirfenidone control group,paraquat group,and three treatment groups receiving a combination of paraquat and pirfenidone for 15,10 and 5 d,respectively.Except the normal and pirfeni-done control groups,all the mice received intraperitoneal injection of paraquat(35 mg·kg-1)to induce pulmonary fibrosis.In the treatment groups,pirfenidone(20 mg·kg-1)was delivered intranasally once daily,beginning on days 1,6,and 11 post-paraquat exposure,until day 15.Fifteen days after paraquat exposure,pulmonary function tests,micro-CT imaging,and arterial blood gas analysis were performed.Histopathological changes and collagen fiber deposition in lung tissues were examined using HE and Masson staining respectively.The protein expression levels of fibrosis markers,including fibronectin(FN),collagen typeⅠ(CollⅠ),E-cadherin(E-cad),vimentin(Vim),and α-smooth muscle actin(α-SMA),were detected by Western blotting.Additionally,inflammatory and pro-fibrotic cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-8,IL-1β,and connective tissue growth factor(CTGF),were quantified using ELISA.RESULTS Compared with the normal control group,mice treated with paraquat exhibited significant respiratory alterations,including prolonged expiratory time(TE),increased enhanced pause(PENH),and reduced tidal volume(TV).CT imaging revealed reticular high-density shadows and ground-glass opacities in paraquat-treated mice.Blood gas analysis showed reduced partial pressure of oxygen(PaO2),oxygen saturation of blood(SaO2),fractional oxygen saturation of hemoglobin(FO2 Hb),and central venous oxygen saturation(ScvO2),along with increased partial pressure of carbon dioxide(PaCO2)and fractional deoxyhemoglobin saturation(FHHb),indicating that mice exposed to para-quat exhibited severe hypoxemia and hypercapnia.Histological evaluation highlighted pronounced lung interstitial thickening,alveolar collapse,inflammatory infiltration,and extensive fibrotic changes marked by collagen accumulation.Furthermore,exposure to paraquat significantly increased the protein levels of FN,CollⅠ,vimentin,and α-SMA,markedly reduced E-cadherin levels and elevated the levels of inflam-matory cytokines(TNF-α,IL-6,IL-8 and IL-1β)as well as the pro-fibrotic cytokine CTGF.Pirfenidone treat-ment demonstrated time-dependent efficacy,with the 15 d group showing the most significant improvements in pulmonary function as evidenced by reduced PENH levels and increased TV,EV and MV.CT imaging revealed a decrease in high-density opacities and improved lung transparency after pirfenidone treatment.In addition,arterial blood gas measurements indicated markedly elevated levels of PaO2,SaO2 and FO2 Hb.Histological analysis showed that pirfenidone alleviated lung interstitial thick-ening,reduced inflammatory cell infiltration,and decreased collagen deposition.At the molecular level,pirfenidone significantly reduced the protein expressions of FN,CollⅠ,Vim and α-SMA,while increasing E-cad levels.Furthermore,inflammatory cytokines,particularly IL-6 and IL-1β,were notably suppressed following pirfenidone intervention.CONCLUSION Intranasal administration of pirfenidone can exhibit potent time-dependent anti-fibrotic efficacy in paraquat-induced pulmonary fibrosis,with early interven-tions delivering the most substantial therapeutic benefits.

Objective To compare the macular retinal thickness characteristics of diabetic kidney disease(DKD)patients with different blood pressure levels and explore the relationship between blood pressure and macular retinal damage in DKD patients.Methods A total of 435 DKD patients were selected and divided into four groups based on medical history and blood pressure:the non-hypertensive group(NH group,n=100),the well-controlled blood pressure group(G0 group,n=176),the grade 1 hypertension group(G1 group,n=118)and the grade 2 hypertension group(G2 group,n=41).General information,routine laboratory test results as well as the average thickness of the macular retinal nerve fiber layer(RNFL),ganglion cell layer(GCL),ganglion cell complex(GCC),choroidal layer(CL)and central macular retinal thickness(CMT)were compared between the four groups.The correlation between macular retinal thickness in both eyes and clinical data was analyzed.Results Compared with the G1 group and the G2 group,the G0 group had a longer duration of hypertension.Compared to the NH group,the G2 group had higher fasting plasma glucose(FPG).Compared to the G0 group,the G1 group and the G2 group had higher FPG,and the G2 group had higher glycated hemoglobin(HbA1c)and lower estimated glomerular filtration rate(eGFR).Compared to the NH group,the G0 group had decreased thickness in the GCL and GCC(P<0.05).The macular retinal thickness of the GCL and GCC in both eyes was negatively correlated with diastolic blood pressure(r=-0.158 and-0.195,respectively,P<0.05).Conclusion Macular retinal thickness is helpful in assessing the long-term effects of hypertension on optic nerve and microvascular damage in DKD patients.

OBJCTIVE To evaluate the therapeutic efficacy of intranasal administration of pirfeni-done in treating paraquat-induced pulmonary fibrosis in mice across treatment durations.METHODS Eight-week-old male C57BL/6 mice were randomly divided into six groups(n=8 per group):the normal control group(saline),pirfenidone control group,paraquat group,and three treatment groups receiving a combination of paraquat and pirfenidone for 15,10 and 5 d,respectively.Except the normal and pirfeni-done control groups,all the mice received intraperitoneal injection of paraquat(35 mg·kg-1)to induce pulmonary fibrosis.In the treatment groups,pirfenidone(20 mg·kg-1)was delivered intranasally once daily,beginning on days 1,6,and 11 post-paraquat exposure,until day 15.Fifteen days after paraquat exposure,pulmonary function tests,micro-CT imaging,and arterial blood gas analysis were performed.Histopathological changes and collagen fiber deposition in lung tissues were examined using HE and Masson staining respectively.The protein expression levels of fibrosis markers,including fibronectin(FN),collagen typeⅠ(CollⅠ),E-cadherin(E-cad),vimentin(Vim),and α-smooth muscle actin(α-SMA),were detected by Western blotting.Additionally,inflammatory and pro-fibrotic cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-8,IL-1β,and connective tissue growth factor(CTGF),were quantified using ELISA.RESULTS Compared with the normal control group,mice treated with paraquat exhibited significant respiratory alterations,including prolonged expiratory time(TE),increased enhanced pause(PENH),and reduced tidal volume(TV).CT imaging revealed reticular high-density shadows and ground-glass opacities in paraquat-treated mice.Blood gas analysis showed reduced partial pressure of oxygen(PaO2),oxygen saturation of blood(SaO2),fractional oxygen saturation of hemoglobin(FO2 Hb),and central venous oxygen saturation(ScvO2),along with increased partial pressure of carbon dioxide(PaCO2)and fractional deoxyhemoglobin saturation(FHHb),indicating that mice exposed to para-quat exhibited severe hypoxemia and hypercapnia.Histological evaluation highlighted pronounced lung interstitial thickening,alveolar collapse,inflammatory infiltration,and extensive fibrotic changes marked by collagen accumulation.Furthermore,exposure to paraquat significantly increased the protein levels of FN,CollⅠ,vimentin,and α-SMA,markedly reduced E-cadherin levels and elevated the levels of inflam-matory cytokines(TNF-α,IL-6,IL-8 and IL-1β)as well as the pro-fibrotic cytokine CTGF.Pirfenidone treat-ment demonstrated time-dependent efficacy,with the 15 d group showing the most significant improvements in pulmonary function as evidenced by reduced PENH levels and increased TV,EV and MV.CT imaging revealed a decrease in high-density opacities and improved lung transparency after pirfenidone treatment.In addition,arterial blood gas measurements indicated markedly elevated levels of PaO2,SaO2 and FO2 Hb.Histological analysis showed that pirfenidone alleviated lung interstitial thick-ening,reduced inflammatory cell infiltration,and decreased collagen deposition.At the molecular level,pirfenidone significantly reduced the protein expressions of FN,CollⅠ,Vim and α-SMA,while increasing E-cad levels.Furthermore,inflammatory cytokines,particularly IL-6 and IL-1β,were notably suppressed following pirfenidone intervention.CONCLUSION Intranasal administration of pirfenidone can exhibit potent time-dependent anti-fibrotic efficacy in paraquat-induced pulmonary fibrosis,with early interven-tions delivering the most substantial therapeutic benefits.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

In 2022, the European Association for the Study of the Liver issued Clinical practice guidelines on sclerosing cholangitis. With reference to the 2017 edition of Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline (2017) and in comparison to the corresponding contents in Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021) issued by Chinese Society of Hepatology, Chinese Medical Association, in 2021, this article summarizes the updates in diagnosis, treatment, monitoring, and management of special populations and analyzes the basis for updated recommendations and their guiding significance in optimizing the clinical management of primary sclerosing cholangitis (PSC). The comparative analysis shows that the new version of the guidelines is similar to the Chinese guidelines in terms of diagnosis, treatment, and follow-up, and it is worth learning from the technical details such as the recommended dose of ursodeoxycholic acid and long-term follow-up plan. Since PSC is a chronic refractory disease, the drugs recommended by current guidelines cannot delay or reverse disease progression, and there is still a lack of consensus statements on immunotherapy and screening protocols for end-stage complications, which might be the directions for further research.