ObjectiveTo investigate the imaging features of calcium salt deposition and serological markers in patients with alveolar echinococcosis through a retrospective analysis， as well as independent risk factors for the degree of calcium salt deposition in lesions， and to provide a basis for assessing disease process. MethodsA retrospective analysis was performed for the imaging and clinical data of 107 patients with alveolar echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from December 2023 to June 2025， and according to the volume of calcium salt deposition， they were divided into non-deposition group with 16 patients， mild deposition group with 52 patients， moderate deposition group with 16 patients， and severe deposition group with 23 patients. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups， and the χ² test or Fisher’s exact test was used for comparison of categorical data between groups. The four groups were further combined into the low deposition group （no/mild deposition） and the high deposition group （moderate/severe deposition）. A binary logistic regression analysis was used to investigate the independent influencing factors for calcium salt deposition， and a predictive model was established. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model， and the Bootstrap method was used for internal validation. ResultsThere were significant differences between the four groups in sex distribution， involvement of other sites， white blood cell count， lymphocyte percentage， fibrinogen， uric acid， sodium ion， chloride ion， and calcium ion （all P<0.05）. The univariate analysis showed that there were significant differences between the four groups in sex， involvement of other sites， white blood cell count， lymphocyte percentage， fibrinogen， alanine aminotransferase， albumin， creatinine， uric acid， sodium ion， chloride ion， and calcium ion （all P<0.1）. The multi-collinearity diagnosis showed that the VIF values for all continuous variables ranged from 1.104 to 1.760， suggesting that collinearity did not affect modeling. An ordinal logistic regression model was established based on sex， involvement of other sites， calcium ion， lymphocyte percentage， and uric acid. The multivariate analysis showed that lymphocyte percentage （odds ratio ［OR］=1.106， 95% confidence interval ［CI］： 1.041 — 1.174， P=0.001） and blood calcium level （OR=0.005， 95%CI： 0.000 —0.230， P=0.007） were independent influencing factors for the degree of calcium salt deposition. The regression equation was established as Logit（P）=8.231 + 0.100 × lymphocyte percentage -5.344 × calcium ion. The ROC curve analysis showed that the model had an area under the ROC curve of 0.716， with a Youden index of 0.353， a sensitivity of 1.000， and a specificity of 0.353. The Hosmer-Lemeshow test showed that the model had poor calibration （χ²=20.688， P=0.008）. The Bootstrap method with 1000 repeated samples showed that the estimated values of lymphocyte percentage （OR=1.106， 95%CI： 1.049 — 1.186， P=0.002） and calcium ion （OR=0.005， 95%CI： 0.000 — 0.214， P=0.010） were consistent with the original model， and the confidence intervals did not include 1， which further supported the reliability of the model. ConclusionBoth lymphocyte percentage and blood calcium level are independent influencing factors for calcium salt deposition in alveolar echinococcosis， and the degree of calcium salt deposition in alveolar echinococcosis lesions increases with the reduction in blood calcium level and the increase in lymphocyte percentage.

Objective To explore the effect of Huangqi Danzhi Shenmai Decoction in treatment of coronary atherosclerosis patients with qi deficiency and blood stasis syndrome and its influence on the levels of serum malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin-1 β(IL-1β).Methods A total of 120 patients with coronary atheroscle-rosis were selected and randomly divided into control group(conventional treatment+simvastatin)and observation group(conventional treatment+Huangqi Danzhi Shenmai Decoction)by random number table method,with 60 cases in each group.The clinical efficacy of the two groups was evalua-ted.The changes in traditional Chinese medicine(TCM)syndrome scores,blood lipids,inflammatory factors,and oxidative stress indicators before and after treatment were recorded for both groups.Re-sults The total effective rate in the observation group was higher than that in the control group(P＜0.05).After treatment,the TCM syndrome scores in the observation group were lower than those in the control group(P＜0.05).The improvement in blood lipid indicators was more pronounced in the observation group compared to the control group(P＜0.05).The serum levels of TNF-α,IL-1 β,and MDA in the observation group were lower than those in the control group,while the serum levels of SOD and glutathione peroxidase(GSH-PX)were higher than those in the control group,with statis-tically significant differences(P＜0.05).No severe adverse reactions occurred in either group dur-ing the treatment period.Conclusion Huangqi Danzhi Shenmai Decoction has a good clinical effi-cacy in treating coronary atherosclerosis with qi deficiency and blood stasis syndrome,and can im-prove the oxidative stress status,reduce inflammatory responses,and regulate blood lipid levels in patients,so it is worthy of clinical promotion and use.

Prescription sequence symmetry analysis (PSSA) is one of the important methods for post-marketing pharmacovigilance based on the real-world medical prescription databases. It can be used to detect prescription cascades and mine adverse drug reaction (ADR) signals, which has been verified by many studies. PSSA shows high specificity and medium sensitivity in identifying ADR. It can quantify the correlation or risks of ADR. It is easy to use and simple in algorithm, and it has good robustness to some non time-dependent confounding factors. However, the results may be affected by some human confounding factors and data quality. This paper reviews the principle, calculation method, application scope, and precaution of PSSA by reviewing related literature on PSSA domestically and abroad, in order to provide reference for pharmacovigilance in China.

Objective:To understand the application situation and role of prescription sequence symmetry analysis (PSSA) in pharmacovigilance.Methods:The relevant databases at home and abroad were searched (up to April 30, 2024), and the original articles using PSSA as the research method were collected. The basic information of the literature (first author, publication year, country, etc.), the purpose and main content of the study, the index drugs as well as the marker drugs or medical diagnoses involved in the adverse drug reactions (ADRs) were extracted. Descriptive statistical analysis was carried out.Results:A total of 66 articles were included in the analysis. The first article was published in 1996, the number of articles published in recent years has increased significantly, and those published after 2016 accounted for 68.2% (45/66). The top 3 countries in terms of published literature quantity were the United States, Denmark, and Japan. The index drugs most commonly studied were those for the cardiovascular system and the neuropsychiatric system, in 18 and 14 articles respectively. The drugs studied in 3 or more papers were hypolipidemic drugs, antihypertensive drugs, antipsychotics, antiepileptics, proton pump inhibitors, hypoglycemic drugs and anticoagulants. The targeted ADRs/diseases most studied were those about the neuropsychiatric system (in 13 studies), followed by those about the endocrine and metabolic system (in 12 studies). The research objective in 47 articles was to explore the association between index drugs and ADRs/diseases through PSSA. Finally, the associations between 21 ADRs and index drugs were identified in 24 articles, of which 9 were new ADRs not recorded in drug instructions; benefits or potential preventive and therapeutic effects of index drugs on certain diseases were found in 7 studies. Ten studies were conducted to explore ADR information of specific drugs or detect suspicious drugs that cause specific ADRs, and some correlation signals between drugs and ADRs that previously unknown were detected. Nine studies evaluated the prescribing cascades, including the use of antitussive drugs after ACEI, the prescribing cascades related to drug-induced lower urinary tract symptoms and edema, the prescription cascades of statins, and the prescribing cascade relic.Conclusion:PSSA is a useful method for identifying potential prescribing cascades and mining ADR signals using medical prescription databases, especially suitable for the safety monitoring of long-term medication for chronic diseases and the signal detection of ADR that causal relationships are difficult to determine.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Huachansu (Cinobufacini) is active extract isolated from the dry skin of Bufo Bufo gargarizans. It has now been widely used in clinical treatment of cancer, this study is to clarify the material basis of down-regulation of thymidylate synthase (TYMS) induced by Huachansu. METHODS: Our study utilized UPLC-MS/MS to identify major bioactive components from Huachansu. Cell Counting Kit 8 (CCK-8) assay and clone formation assay were used to examine the cell viability of tumor cells. TYMS and γ-H2AX level were detected by using quantitative real-time RT-PCR and/or western blotting. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of TYMS could enhance the suppressive effect of Huachansu on cell growth of HCC cells. RESULTS: In our study, firstly, we identify 21 major bioactive components from Huachansu. CCK-8 assay results showed that Huachansu and its bioactive bufadienolides (Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin) significantly inhibited the proliferation of HepG2 and SK-HEP-1 cells in a dose- and time-dependent manner. Further molecular mechanistic investigation demonstrates that Huachansu significantly suppresses thymidylate synthase (TYMS), the enzyme which provides the sole de novo source of thymidylate for DNA synthesis. The inhibition of TYMS could lead to cell-cycle block and DNA damage of HCC cells. Furthermore, we identified that Huachansu markedly increased γ-H2AX expression, which indicated the presence of DNA damage. Moreover, we confirmed that transfection of cells with small interfering RNA specific to TYMS could increase the suppressive effects of Huachansu on the HCC cells proliferation. Quantitative RT-PCR analysis showed that Huachansu treatment had no effect on the transcription level of TYMS. Furthermore, proteasomal inhibitor MG132 could block TYMS inhibition induced by Huachansu, and concomitant administration of protein synthesis inhibitor cycloheximide (CHX) with Huachansu could further suppress the protein level of TYMS, indicating that Huachansu promotes proteasome-dependent degradation of TYMS in liver cancer cells. More importantly, the bioactive bufadienolides of Huachansu such as Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin could also significantly restrain the protein level of TYMS, revealing the material basis of inhibition of TYMS exposed to Huachansu. 5-Fluorouracil (5-FU) is a TYMS inhibitor, we also evaluate the effects of the combined treatment of Huachansu with 5-FU, the results show that interactions between Huachansu and 5-FU are synergistic or antagonistic. Thus, in clinical, attention should be paid to the dosage of Huachansu in combination with 5-FU. CONCLUSION Huachansu inhibits the growth and induces DNA damage of human HCC cells through proteasome-dependent degradation of TYMS, bioactive bufadienolides are the material basis of down-regulation of TYMS induced by Huachansu.

Luteolin is a natural flavonoid compound exists in various fruits and vegetables. Recent studies have indicated that luteolin has variety pharmacological effects, including a wide range of antidepressant properties. Here, we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power. Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin. Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets. The antidepressant effects of luteolin may involve promoting intracellular noradrenaline (NE) uptake; inhibiting 5-hydroxytryptamine (5-HT) reuptake; upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione S-transferase; and decreasing the expression of malondialdehyde, caspase-3, and amyloid-beta peptides. The antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic-pituitary-adrenal axis regulation, and 5-HT metabolism. Additionally, we identified insulin-like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor alpha (ESR1), and epidermal growth factor receptor (EGFR) as potential targets, luteolin has an ideal affinity for these targets, suggesting that it may play a positive role in depression through multiple targets, mechanisms, and pathways. However, the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.

Objective To investigate the immunomodulatory effect of albumin-bound Paclitaxel combined with Sintilimab on advanced esophageal cancer,and to analyze the survival benefit.Methods A total of 126 patients with advanced esophageal cancer admitted to Rugao People's Hospital from March 2020 to March 2023 were selected,and divided into the observation group(n=63)and the control group(n=63)using a random number table method.The control group was given albumin-bound Paclitaxel,while the observation group was given albumin-bound Paclitaxel combined with Sintilimab.The clinical efficacy,tumor markers[cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCC-Ag),carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA)],immune function indicators(Th1/Th2,Th17/Treg),PD-1/PD-L1 signaling pathway indicators,Karnofsky performance status(KPS)scores,overall survival,and toxic side effects were compared between the two groups.Results The objective remission rate[38.10%(24/63)]and disease control rate[87.30%(55/63)]of the observation group were higher than those of the control group[20.63%(13/63),71.43%(45/63)](P<0.05).After 2 and 4 cycles of treatment,the serum SCC-Ag,CYFRA21-1,CA125 and CEA in the observation group were lower than those in the control group(P<0.05);after 2 and 4 cycles of treatment,compared with the control group,the observation group showed higher Th1/Th2,and lower Th17/Treg,PD-1 and PD-L1(P<0.05).The improvement rate of quality of life,progression free survival and overall survival in the observation group were higher or longer than those in the control group(P<0.05).There was no significant difference in the incidence of abnormal liver dysfunction,nausea and vomiting,decreased hemoglobin and leucopenia between the two groups(P>0.05),but the incidence of rash in the observation group[57.14%(36/63)]was higher than that in the control group[34.92%(22/63)](P<0.05).Conclusion Combination therapy of Sintilimab and albumin-bound Paclitaxel shows significant efficacy in the treatment of advanced esophageal cancer.It can regulate serum tumor marker levels,improve immune function,reduce the activity of the PD-1/PD-L1 signaling pathway to inhibit disease progression,enhance survival benefits,and improve quality of life.However,attention should be paid to the observation of rash reactions during treatment.

Biomimetic wet-adhesive hydrogels mimic the adhesive properties of biological organisms to achieve strong bonding in moist environments.Compared to conventional medical adhesives,these materials are characterized by enhanced biocompatibility,robust ad-hesion,and adjustable physicochemical properties.Although biomimetic wet-adhesive hydrogels have been applied in oral mucosal drug delivery,intraoral wound management,and implant surgery,a systematic review is currently lacking.This article aims to summarize the wet-adhesion mechanisms of bio-inspired materials and their applications in various scenarios and to provide insights and methodolo-gies for the design of novel intraoral dressings.

Objective: To investigate the extraction,purification,and identification methods of Polygonum cuspidatum(P.cuspidatum)-derived exosomes and to obtain high-purity exosomes,and thus providing a reliable material foundation for their functional studies. Methods: Exosomes were isolated from fresh P.cuspidatum using ultracentrifugation combined with sucrose density gradient centrifugation.Morphological characteristics,size distribution,and surface charge properties were analyzed by transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Zeta potential measurements. Results: The purified P.cuspidatum exosomes exhibited characteristic cup-shaped or spherical bilayer morphology with a predominant size distribution of 100-200 nm,consistent with established plant exosome characteristics.The surface of these exosomes exhibits a negative charge,with the Zeta potential absolute value of root-derived exosomes being slightly higher than that of stem/leaf-derived counterparts. Conclusion The study successfully isolates and characterizes P.cuspidatum exosomes,with comprehensive analysis confirming their distinctive structural and biophysical properties.It lays a good material foundation for further exploration of its active ingredients and biological functions.

Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here,we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power.Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin.Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antide-pressant mechanism of luteolin and its antidepressant targets.The antidepressant effects of luteolin may involve promoting intracellular noradrenaline(NE)uptake;inhibiting 5-hydroxytryptamine(5-HT)re-uptake;upregulating the expression of synaptophysin,postsynaptic density protein 95,brain-derived neurotrophic factor,B cell lymphoma protein-2,superoxide dismutase,and glutathione S-transferase;and decreasing the expression of malondialdehyde,caspase-3,and amyloid-beta peptides.The antide-pressant effects of luteolin are mediated by various mechanisms,including anti-oxidative stress,anti-apoptosis,anti-inflammation,anti-endoplasmic reticulum stress,dopamine transport,synaptic protec-tion,hypothalamic-pituitary-adrenal axis regulation,and 5-HT metabolism.Additionally,we identified insulin-like growth factor 1 receptor(IGF1R),AKT serine/threonine kinase 1(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor alpha(ESR1),and epidermal growth factor recep-tor(EGFR)as potential targets,luteolin has an ideal affinity for these targets,suggesting that it may play a positive role in depression through multiple targets,mechanisms,and pathways.However,the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.