Objective: To observe the clinical efficacy and adverse reactions of pemetrexed in combination with nedaplatin or cisplatin in the treatment of advanced non-small cell lung cancer(NSCLC). Methods: 85 patients with stage Ⅲ B/IV NSCLC diagnosed by pathology or cytology were randomly divided into two groups by random double blind method.The study group(45cases) was treated with pemetrexed combined with nedaplatin, and the control group(40cases) was given pemetrexed combined with cisplatin chemotherapy.The specific method was pemetrexed 500mg/m², the first day of intravenous infusion, cisplatin 75mg/m² or nedaplatin 80mg/m², divided into 3 times, the 2nd, 3rd, 4th day, intravenous infusion, every 21d for a cycle.At the end of the chemotherapy, the efficacy and adverse reaction were analyzed.The patients were followed up to record no progress survival and one-year survival rate. Results: Among 85 patients, there were 35 cases of partial remission(PR), 35 cases of stable(SD) and 15 cases of progression(PD), the total effective rate(ORR) was 42.2%, the disease control rate(DCR) was 82.2%.There were no statistically significant differences in ORR and DCR between the two groups(χ²=0.043, 0.001, all P>0.05). As to the adverse reactions, the incidence rates of the decreased number of white blood cells (42.2% vs.25.0%), the decreased number of neutrophils (35.6% vs.17.5%), the decreased number of platelets (42.2% vs.15.0%), anemia(31.1% vs.12.5%), nausea/vomiting(22.2% vs.70.0%) between the two groups had statistically significant differences (χ²=9.319, 4.664, 7.559, 4.226, 19.556, all P<0.05). There were no significant differences in progression-free survival and one-year survival rate between the two groups (χ²=0.717, 0.226, all P>0.05). Conclusion There was no statistically significant difference in the efficacy between pemetrexed combined with nedaplatin or cisplatin, non-squamous cell carcinoma patients get a better therapeutic effect.Nedaplatin is more likely to cause myelosuppression and intestinal side effects of cisplatin are more common.

OBJECTIVE: To explore the predictive value of serum sodium variability within 72 hours, lactic acid (Lac), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) in predicting the 28-day prognosis of sepsis patients. METHODS: The clinical data of patients with sepsis admitted to the department of intensive care unit (ICU) of the Affiliated Qingdao Municipal Hospital of Qingdao University from December 2020 to December 2021 were retrospectively analyzed, including age, gender, previous medical history, temperature, heart rate, respiratory rate, systolic pressure, diastolic pressure, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), C-reactive protein (CRP), pH value, arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), Lac, prothrombin time (PT), activated partial thromboplastin time (APTT), serum creatinine (SCr), total bilirubin (TBil), albumin (Alb), SOFA, APACHE II score, and 28-day prognosis. Multivariate Logistic regression was used to analyze the risk factors of death in sepsis patients. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of serum sodium variability within 72 hours, Lac, SOFA, APACHE II alone and in combination on the prognosis of patients with sepsis. RESULTS: A total of 135 patients with sepsis were included, 73 survived and 62 died at 28 days, with 28-day mortality of 45.93%. (1) Compared with the survival group, SOFA, APACHE II, Lac and serum sodium variability within 72 hours in the death group were significantly higher [SOFA: 10.00 (8.00, 12.00) vs. 6.00 (5.00, 8.00), APACHE II: 18.00 (16.00, 21.25) vs. 13.00 (11.00, 15.00), Lac (mmol/L): 3.55 (2.90, 4.60) vs. 2.00 (1.30, 2.80), serum sodium variability within 72 hours: 3.4% (2.6%, 4.2%) vs. 1.4% (1.1%, 2.5%)], the differences were statistically significant (all P < 0.01). (2) Multivariate Logistic regression showed that SOFA, APACHE II, Lac, serum sodium variability within 72 hours were independent risk factors of prognosis in patients with sepsis [SOFA: odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.114-1.963, P = 0.007; APACHE II: OR = 1.163, 95%CI was 1.009-1.340, P = 0.037; Lac: OR = 1.387, 95%CI was 1.014-1.896, P = 0.040; serum sodium variability within 72 hours: OR = 1.634, 95%CI was 1.102-2.423, P = 0.015]. (3) ROC curve analysis showed that SOFA, APACHE II, Lac and serum sodium variability within 72 hours had certain predictive value for the prognosis of sepsis patients [SOFA: the area under the ROC curve (AUC) = 0.858, 95%CI was 0.795-0.920, P = 0.000; APACHE II: AUC = 0.845, 95%CI was 0.776-0.913, P = 0.000; Lac: AUC = 0.840, 95%CI was 0.770-0.909, P = 0.000; serum sodium variability within 72 hours: AUC = 0.842, 95%CI was 0.774-0.910, P = 0.000]. The combined predictive value of the four indicators (AUC = 0.917, 95%CI was 0.870-0.965, P = 0.000) was higher than that of any single indicator, and has higher specificity (79.5%) and sensitivity (93.5%), indicating that the combined index has higher predictive value for the prognosis of sepsis patients than any single index. CONCLUSIONS SOFA, APACHE II, Lac, serum sodium variability within 72 hours are independent risk factors for 28-day death in patients with sepsis. The combination of SOFA score, APACHE II score, Lac and serum sodium variability within 72 hours has higher predictive value for prognosis than single index.
Humans ; Lactic Acid ; Prognosis ; Retrospective Studies ; Sepsis ; Sodium

Antiviral Agents ; chemistry ; metabolism ; Crystallography, X-Ray ; Ligands ; Protein Binding ; Protein Structure, Tertiary ; RNA Helicases ; chemistry ; classification ; metabolism ; Static Electricity ; Viral Proteins ; chemistry ; classification ; metabolism ; Zika Virus ; enzymology

The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn(2+) and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn(2+). The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV) apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.
Crystallography, X-Ray ; Protein Domains ; RNA Helicases ; chemistry ; RNA, Viral ; chemistry ; Viral Proteins ; chemistry ; Zika Virus ; enzymology