ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

OBJECTIVES: To investigate the therapeutic effects of cimifugin on Crohn's disease (CD)-like colitis in mice and its possible mechanism. METHODS: Thirty adult male C57BL/6 mice were randomized equally into control group, 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced CD-like colitis model group, and cimifugin treatment (daily gavage at 12.5 mg/kg) group. The therapeutic effect of cimifugin was evaluated by observing changes in body weight, disease activity index (DAI) scores, colon length, histopathological inflammation scores, and inflammatory cytokine levels in the colonic mucosa. Intestinal barrier integrity in the mice was assessed using immunofluorescence assay and Western blotting for claudin-1 and ZO-1; T-helper (Th) cell subset ratios in the mesenteric lymph nodes were analyzed with flow cytometry. Network pharmacology, KEGG enrichment analysis and molecular docking were used to predict the targets of cimifugin and analyze the key pathways and cimifugin-MAPK protein interactions, which were validated by Western blotting in the mouse models. RESULTS: In mice with TNBS-induced colitis, cimifugin treatment significantly attenuated body weight loss and colon shortening, lowered DAI and histopathological scores, decreased IFN-γ and IL-17 levels, and increased IL-4 and IL-10 levels in the colonic mucosa. Cimifugin treatment also significantly improved TNBS-induced claudin-1 dislocation and reduction of goblet cells, upregulated claudin-1 and ZO-1 expressions, reduced Th1 and Th17 cell percentages, and increased Th2 and Treg cell percentages in the colonic mucosa of the mice. KEGG analysis suggested a possible connection between the effect of cimifugin and MAPK signaling, and molecular docking showed strong binding affinity between cimifugin and MAPK core proteins. Western blotting demonstrated significantly decreased phosphorylation levels of JNK, ERK, and p38 in the colonic mucosa of cimifugin-treated mouse models. CONCLUSIONS Cimifugin alleviates TNBS-induced CD-like colitis by repairing intestinal barrier damage and restoring Th1/Th2 and Th17/Treg balance via suppressing MAPK pathway activation.
Animals ; Mice, Inbred C57BL ; Male ; Mice ; Crohn Disease/immunology* ; Colitis/immunology* ; MAP Kinase Signaling System/drug effects* ; Trinitrobenzenesulfonic Acid ; T-Lymphocytes, Helper-Inducer/drug effects* ; Intestinal Mucosa ; Disease Models, Animal

Differentiated thyroid cancer(DTC)accounts for more than 95％of all thyroid cancers.99Tcm-3PRGD2 can specifically bind to integrin αvβ3 receptors highly expressed on the surfaces of neovascular endothelial cells and tumor cells in malignant tumors.With high specificity and safety,99Tcm-3PRGD2 can not only be used for diagnosing DTC and its metastases,but also evaluating the efficacy of anti-angiogenic and anti-αvβ3 therapies.99Tcm-MIBI is a non-specific tumor-avid imaging agent,which may improve diagnostic accuracy combined with 99Tcm-3PRGD2.The research progresses of 99Tcm-3PRGD2 and 99Tcm-MIBI for diagnosis and treatment of DTC were reviewed in this article.

Differentiated thyroid cancer(DTC)accounts for more than 95％of all thyroid cancers.99Tcm-3PRGD2 can specifically bind to integrin αvβ3 receptors highly expressed on the surfaces of neovascular endothelial cells and tumor cells in malignant tumors.With high specificity and safety,99Tcm-3PRGD2 can not only be used for diagnosing DTC and its metastases,but also evaluating the efficacy of anti-angiogenic and anti-αvβ3 therapies.99Tcm-MIBI is a non-specific tumor-avid imaging agent,which may improve diagnostic accuracy combined with 99Tcm-3PRGD2.The research progresses of 99Tcm-3PRGD2 and 99Tcm-MIBI for diagnosis and treatment of DTC were reviewed in this article.

Primary bronchial lung cancer, commonly known as lung cancer, is one of the malignant tumors with high morbidity and mortality in the world. In recent years, the incidence of lung cancer in women has increased, and most of them are lung adenocarcinoma. Because the early symptoms of lung cancer are occult, it is often detected when matastasis has already occurred. Endometrial and cervical metastasis is extremely rare for primary lung cancer. This article retrospectively analyzed the clinicopathological data of a patient with pulmonary microcapillary subtype adenocarcinoma with uterine and adnexal metastasis, and confirmed by morphology, immunohistochemistry and molecular detection, in order to provide references for clinical management of uterine and adnexal metastasis of lung adenocarcinoma.
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Female ; Humans ; Adenocarcinoma of Lung/therapy* ; Lung Neoplasms/therapy* ; Uterine Neoplasms/therapy*

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To observe the expression of interleukin-35(IL-35) in Hashimoto's thyroiditis(HT) patients, and evaluate its regulatory effect on the balance between regulatory T cells(Treg) and T helper 22(Th22) cells.Methods:Forty-two HT patients and eighteen controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMC) were isolated. Treg were purified. Plasma IL-35 and IL-22 were detected with enzyme-linked immunosorbent assay. Treg and Th22 percentages were measured using flow cytometry. Real-time quantitative PCR was used to assess mRNA levels of forhead box protein 3(FoxP3) and aryl hydrocarbon receptor(AhR). Treg were stimulated with exogenous IL-35, and were co-cultured with autologous PBMC to induce Treg-to-Th22 phenotypic differentiation, evaluating the effect of IL-35 on Treg function and differentiation.Results:There was imbalance between Treg and Th22 cells in HT group. HT group had reduced Treg percentage, plasma IL-35 and FoxP3 mRNA( P<0.001), while had elevated Th22 percentage and AhR mRNA( P<0.001). There was no significant difference in plasma IL-22 level between two groups( P=0.775). The suppressive capacity of Tregs in the HT group was diminished( P=0.013), and secretion levels of IL-35 and IL-10 were lower than those in the control group( P<0.001). The ability of Tregs in the HT group to differentiate into Th22 cells was increased, with higher levels of CCR4, CCR6, CCR10, AhR mRNA, and IL-22 secretion compared to the control group( P<0.01). IL-35 stimulation induced elevation of Treg percentage, FoxP3 mRNA, and IL-35/IL-10 secretion( P<0.05), but did not affect Th22 percentage, AhR mRNA, or IL-22 secretion( P>0.05). IL-35 stimulation enhanced Treg function in HT group, increasing proliferation inhibition and secretion of IL-35 and IL-10( P<0.05). IL-35 stimulation reduced the differentiation of Treg to Th22 phenotype in HT group, with decreased levels of CCR4, CCR6 CCR10, AhR mRNA, and IL-22 secretion( P<0.05). Conclusion:IL-35 enhances the immunosuppression of Tregs in HT patients and inhibits its differentiation into Th22 cells, thus regulating the balance between Tregs and Th22 cells.

Objective:We investigated the efficacy of furmonertinib in the treatment of de novo small cell lung cancer (SCLC) carrying epi-dermal growth factor receptor (EGFR) sensitive mutations,and elucidated characteristics of the tumor genome,transcriptome,and immune microenvironment. Methods:We analyzed the case of a female patient initially diagnosed with extensive-stage SCLC who had an exon 19 deletion in her EGFR gene. The patient's disease progressed under first-line standard chemotherapy. She thus received the third-generation EGFR-TKI furmonertinib as her second-line treatment,achieving a partial response (PR) and 5-month progression-free survival. After furmon-ertinib treatment failed,a lung tumor biopsy was performed. Genomic,transcriptomic,and tumor immune microenvironment analyses were performed. Results:The histopathological diagnosis of SCLC was confirmed after progression on furmonertinib. Genetic testing of the treated tumor tissues showed that the patient carried an EGFR exon 19 deletion mutation. Transcriptome analysis revealed that the patient's transcriptional molecular subtype was SCLC-A. The tumor mutational burden,PD-L1 TPS,and density of tumor-infiltrating CD4+and CD8+T cells remained at a low level throughout the course of the disease,suggesting that the immune microenvironment was suppressive. Conclu-sions:Extensive-stage SCLC with EGFR-sensitive mutations exhibits a unique phenotype and tumor immune microenvironment. Furmon-ertinib could be an alternative second-line treatment for this type of tumor entity.

Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.

Objective:To investigate the predictive value of thrombus permeability for poor outcome and symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) in patients with middle cerebral artery occlusion stroke.Methods:Patients with middle cerebral artery occlusion stroke underwent EVT at the Cardiocerebrovascular Disease Hospital, the Affiliated Hospital of Yan'an University from January 2018 to January 2024 were included retrospectively. Thrombus attenuation increase (TAI) was used to evaluate thrombus permeability. The poor outcome was defined as a modified Rankin Scale score >2 at 90 days after procedure. sICH was defined as an increase of ≥4 of the National Institutes of Health Stroke Scale (NIHSS) score relative to baseline or lowest within 7 days after EVT, and CT scan showed cerebral hemorrhage. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor outcome and sICH. Receiver operating characteristic (ROC) curves was used to evaluate the predictive value of TAI for poor outcome and sICH. Results:A total of 77 patients with middle cerebral artery occlusion stroke received EVT treatment were enrolled, including 44 males (57.1%), aged 62.1±12.4 years. Thirty-three patients (48.1%) had poor outcome, 35 (45.5%) experienced hemorrhagic transformation, of which 12 (15.6%) were sICH. Multivariate logistic regression analysis showed that TAI (odds ratio [ OR] 0.930, 95% confidence interval [ CI] 0.883-0.980; P=0.007) and sICH ( OR 0.868, 95% CI 0.784-0.961; P=0.006) were the independent influencing factors of poor outcome. ROC curve analysis showed that the area under the curve of TAI for predicting poor outcome at 90 days was 0.836 (95% CI 0.742-0.930). The cut-off value was 10.135 HU. The sensitivity and specificity were 73.0% and 92.5%, respectively. The area under the curve of TAI for predicting sICH was 0.750 (95% CI 0.637-0.902). The cut-off value was 18.200 HU. The sensitivity and specificity were 94.1% and 64.5%, respectively. Conclusions:TAI has certain predictive value for poor outcome and sICH after EVT in patients with middle cerebral artery occlusion stroke. Patients with higher thrombus permeability are less likely to develop sICH after EVT and have a higher likelihood of good outcome.