Objective To evaluate the efficacy and toxicity of the docetaxel combined with nedaplatin or cisplatin in the treatment of patients with advanced head and neck carcinoma.Methods 58 patients with advanced head and neck carcinoma were enrolled into the study.These patients were divided into nedaplatin group (27 patients:docetaxel 75mg/m2 on day 1 and nedaplatin 80mg/m2 on day 1 of the 21-day cycle) and cisplantin group( 31 patients:docetaxel 75mg/m2 on day 1 and cisplatin 25mg/m2 on day 1-3 day of 21-day cycle).Each patient should complete two cycle.Results The response rate in nedaplatin group was 59.2％ and in cisplantin group was 54.8％,the difference was statistically significant between the two groups( P ＞ 0.05 ).The rate of white blood cell and plate let reduction in nedaplatin group was 55.5％,40.7％,respectively,and those in cisplantin group was 51.6％,35.4％,respectively,the difference was statistically significant between the two groups ( call P ＜ 0.05 ).The rate of vomit in nedaplatin group was 29.6％,which was lower than that of cisplantin group (64.5％) ( x2 =4.02,P ＜ 0.05 ).Conclusion In the treatment of advanced head and neck carcinoma,the combination of docetaxel and nedaplatin had the same efficacy as the combination of docetaxel and cisplatin,and they appeared to be more-tolerated.

Objective To evaluate the value of D-dimer in assessing severity and predicting longterm prognosis in patients with community acquired pneumonia (CAP).Methods From June 2009 to December 2010,a total of 189 patients with CAP were enrolled.After admission,D-dimer,procalcitonin (PCT) and C-reactive protein (CRP) were measured,and Pneumonia Severity Index (PSI) was calculated.They were assigned into two groups according to their D-dimer levels:high D-dimer levels group (D-dimer levels≥500 μg/L) and normal D-dimer levels group (D-dimer levels ＜ 500 μg/L).The followup time was one year.A Kaplan-Meier survive curve was constructed to assess the 1-year mortality,and multivariate logistic regression analysis were used to assess the value of D-dimer for predicting long-term prognosis.Results D-dimer levels increased with increasing PSI class [class Ⅰ-Ⅲ:378.37 μg/L (216.74,649.50) μg/L; class Ⅳ:673.41 μg/L (544.77,866.85) μg/L; class Ⅴ:831.58 μg/L (591.78,1066.39) μg/L,x2 =56.58,P ＜ 0.01].The Kaplan-Meier survival curve showed that 1-year mortality rate of high D-dimer levels group was higher than normal D-dimer levels group (log-rank test,x2 =52.51,P ＜ 0.01).The multivariate logistic regression analysis showed an independent relationship between higher D-dimer levels and long-term mortality (OR =2.05,95％ CI:1.48-2.61,P ＜ 0.01).Conclusion D-dimer is an independent predictor of severity and long-term prognosis in patients with CAP.

Objective To investigate the application value of ELISA for detecting the serum anti desmoglein (Dsg) 1 and Dsg 3 in the diagnosis and treatment of pemphigus .Methods Forty‐seven patients with pemphigus in our hospital from January to De‐cember 2014 were selected as the observation group and contemporaneous 52 patients with excluding pemphigus were selected as the control group .The Dsg antibodies were detected by using indirect immunofluorescence method and Dsg 1 and Dsg3 were deter‐mined by ELISA ;their correlation with pemphigus characteristics was analyzed .Results The sensitivity and specificity of ELISA for detecting anti‐Dsg antibodies were 95 .74% and 92 .31% respectively ,while which of IIF were 93 .62% and 86 .54% respective‐ly ,showing no statistically significant difference between the two test methods (P>0 .05) .In 30 cases of pemphigus vulgaris ,16 ca‐ses (16/30) were positive Dsg1 and Dsg 3 ,8 cases of pemphigus erythematosus and 5 cases pemphigus foliaceus were positive Dsg1 only ,and 2 cases of pemphigus vegetans were both positive Dsgl and Dsg3 .The Dsgl and Dsg3 titers of pemphigus vulgaris and pemphigus vegetans were 130 .85 ± 86 and 112 .30 ± 85 .05 ,respectively ,and the disease activity score was (5 .10 ± 1 .86) points ,the correlation coefficient(r)=0 .476(P=0 .008) ,r=0 .816(P=0 .001) ,respectively .The Dsgl titer of pemphigus erythematosus and pemphigus foliaceus were 142 .59 ± 78 .52 ,and the disease activity score was (2 .77 ± 0 .92) points(r=0 .800 ,P=0 .001) .Conclu‐sion ELISA for detecting Dsg1 and Dsg3 has high sensitivity and specificity ,and is conducive to the diagnosis of pemphigus and e‐valuation of disease severity .

Objective:The residual cancer burden (RCB) evaluation system was used to analyze the influencing factors of the efficacy of neoadjuvant therapy in breast cancer, and to explore the prognostic value of RCB evaluation in neoadjuvant therapy.Methods:Clinicopathologic data and postoperative RCB grading of 364 breast cancer patients who underwent neoadjuvant therapy in Renmin Hospital of Wuhan University from Nov. 2019 to Nov. 2022 were collected. Chi-square test was used to analyze the relationship between RCB grading and clinicopathological parameters, and Spearman’s rank correlation analysis was performed to evaluate the correlation between RCB grading and clinicopathological characteristics. Factors influencing pathologic complete response (pCR) were analyzed by Logistic regression. Kaplan-Meier survival analysis and log-rank test were used to evaluate cumulative survival.Results:Among the 364 patients who underwent neoadjuvant therapy, 129 cases of RCB grade 0 and 235 cases of RCB gradeⅠ-Ⅲ (including 46 cases of RCB gradeⅠ, 109 cases of RCB grade Ⅱ and 80 cases of RCB grade Ⅲ) were obtained after surgery. Histological classification ( χ 2=21.757, P=0.000), estrogen receptor (ER) ( χ 2=52.837, P=0.000), progesterone receptor (PR) ( χ 2=55.658, P=0.000), human epidermal growth factor receptor-2 (HER2) ( χ2=89.040, P=0.000), Ki67 expression ( χ2=12.927, P=0.005), molecular typing ( χ 2=80.793, P=0.000) and preoperative lymph node status ( χ 2=25.764, P=0.000) were all associated with postoperative RCB grading. Further correlation analysis showed that histological grade ( r=-0.229, P=0.000), HER2 expression ( r=-0.465, P=0.000) and Ki67 expression ( r=-0.179, P=0.000) were negatively correlated with RCB grading, while ER ( r=0.352, P=0.000), PR ( r=0.379, P=0.000) and lymph node metastasis ( r=0.214, P=0.000) were positively correlated with RCB grading. Logistic regression analysis showed that high histological grade, negative expression of ER, PR and AR, positive expression of HER2, high proliferation index of Ki67 and no lymph node metastasis were favorable factors for postoperative pCR, and PR, AR and HER2 were independent predictors of postoperative pCR. Kaplan-Meier survival analysis showed significant differences in postoperative cumulative survival among patients with different RCB grades ( P=0.004) . Conclusions:Postoperative RCB grading of breast cancer is closely related to many clinicopathological features before neoadjuvant therapy and survival prognosis. Clinicopathological factors closely related to RCB grading are also important influencing factors affecting the pCR of patients with neoadjuvant therapy. Therefors, RCB grading has a high prognostic value.

Objective:To investigate the role of Caspase-1/gasdermin D (GSDMD) -mediated cell pyroptosis in anti-tumor effect of cisplatin (DDP) in triple-negative breast cancer (TNBC) .Methods:HE staining and immunohistochemical staining were performed to detect the morphological changes and the expression of pyroptosis/apoptosis pathway related proteins in TNBC tissues before and after DDP-based neoadjuvant chemotherapy (NACT) . The TNBC cell line MDA-MB-231 was treated with DDP and the morphological changes were observed. The type of cell death induced by DDP was analyzed by Annexin V-FITC/PI double staining and flow cytometry. Lactate dehydrogenase (LDH) release assay and ELISA were performed to detect the release of LDH and inflammatory factors (IL-18 and IL-1β) in cell culture supernatant after DDP treatment. Western blot (WB) was performed to detect the expression of pyroptosis/apoptosis pathway related proteins in cells after DDP treatment. MDA-MB-231 cells treated with DDP were co-treated with caspase-1 specific inhibitor to inhibit pyroptois or co-treated with caspase-3 specific inhibitor to inhibit apoptosis. The effect of caspase-1 inhibitor or caspase-3 inhibitor on the anti-tumor effect of DDP was detected by MTT assay, clone formation assay, transwell assay and would healing test.Results:Reactive changes in the breast surgical specimen after DDP-based NACT included cell swelling and inflammatory cell aggregation around the tumor bed, which were more similar to pyroptosis. The up-regulation of key molecules of pyroptosis pathway post-NACT was significantly higher than that of key molecules of apoptosis pathway. Further experiments in vitro showed that DDP could induce MDA-MB-231 cells to show pyroptosis-like changes characterized by large bubbles blowing from the cellular membrane. Flow-cytometry analyses showed that the death type of MDA-MB-231 cells caused by DDP was mainly Annexin V +PI + cells (mainly lytic cells, such as pyroptosis) . Additionally, DDP treatment induced significant activation of caspase-1 and GSDMD, increased the release of LDH, IL-18 and IL-1β, however, the activation level of caspase-3, which dominates the apoptosis pathway, was significantly lower than that of caspase-1/GSDMD. Moreover, caspase-1 inhibitors (blocking the classical pyroptosis pathway) had a significantly greater inhibitory effect on the anti-tumor effect of DDP than caspase-3 inhibitors (blocking the apoptosis pathway) . Conclusion:Caspase-1/GSDMD mediated pyroptosis may play a leading role in the anti-tumor effect of DDP in triple-negative breast cancer.

OBJECTIVETo explore the expression of cancerous inhibitor of phosphatase 2A (CIP2A) protein in small cell lung cancer and their relationship with clinicpathological features and prognosis.

METHODSA total of 112 cases of surgical specimens or bronchoscopic biopsies of small cell lung cancer were collected. There were specimens of 94 cases of SCLC tissues and 40 cases of paracancerous lung tissues. Quantitative RT-PCR and immunohistochemistry analysis were performed to determine the CIP2A expression in SCLC tissues. Kaplan-Meier curves were used to estimate the association between CIP2A expression and clinicopathological characteristics and prognosis of the patients.

RESULTSThe expression of CIP2A in SCLC tissue was 7.605 ± 1.893, significantly higher than that in the paracancerous tissues (1.041 ± 0.786) (P < 0.01). The positive rate of CIP2A expression in cancer tissues was 82.8%, significantly higher than that in the paracancerous tissues (13.3%) (P < 0.01). The median disease-free survival was 9.88 months in the CIP2A-high expressing patients, significantly shorter than the 20.92 months in CIP2A-low expressing patients (P < 0.001). CIP2A expression was significantly correlated with the tumor stage, chemotherapeutic sensitivity, and survival (P < 0.05 for all).

CONCLUSIONSCIP2A expression is associated with the pathogenesis of SCLC, and may become a potential prognostic indicator of SCLC.

Autoantigens ; metabolism ; Biomarkers, Tumor ; metabolism ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; Membrane Proteins ; metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; metabolism ; mortality

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects