Objective To explore the clinical characteristics and treatment strategies of patients with Carbapenem-resistant Enterobacteriaceae(CRE)bloodstream infection.Methods A retrospective analysis was conducted on demographic information,microbiological data,and clinical characteristics of patients with CRE bloodstream infections in Sichuan Provincial People's Hospital from September 2018 to December 2021.Results A total of 53 cases of CRE bloodstream infections were identified,with a treatment failure rate of 47.2% .Patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae(CRKP)had a worse prognosis(P<0.05).Patients with treatment failure showed higher levels of procalcitonin,C-reactive protein,lactate dehydrogenase,and prolonged prothrombin time,along with lower levels of globulin(P<0.05).Among the 53 patients included in the outcome analysis following drugs,there was no statistically significant difference between monotherapy(n=15)and combination therapy(n=38)(P>0.05).Treatment regimens containing tigecycline were not superior to other strategies without tigecycline(P>0.05).Univariate analysis results indicated that the prognosis of CRE bloodstream infection was associated with endotracheal intubation,central venous catheterization,bacterial species which lead infection,comorbidities of the hepatobiliary system,and infection occurring after ICU admission(P<0.05).Health issues involving the hepatobiliary system and ICU-onset admission were independent risk factors for the prognosis of CRE bloodstream infection(P<0.05).Conclusion Patients with CRE bloodstream infections have a high mortality rate,and those with elevated procalcitonin and C-reactive protein levels indicate a poor prognosis.The use of tigecycline in combination or alone may not be the optimal treatment choice for CRE-related BSI.

Objective To establish a prognostic model for lung adenocarcinoma (LUAD) based on genes associated with the disulfidptosis (DS) pathway, and to elucidate its potential biological mechanisms. Methods LUAD-related gene sequencing and clinical information were sourced from public databases.The correlation between results of gene set variation analysis (GSVA) and mRNA expression in The Cancer Genome Atlas (TCGA) dataset was used to screen genes that were significantly active in the disulfur death (DS) pathway.The Least Absolute Shrinkage and Selection Operator (LASSO) analysis and Random Forest (RF) algorithm were employed to screen out DS pathway prognosis-related genes (DPRGs) and multivariate Cox regression analysis was used to construct risk score (RS) model, which was validated using external GEO datasets.The samples were divided into high and low-risk groups based on the median score of RS.A protein-protein interaction (PPI) network corresponding to 7 DPRGs was established, with LDHA identified as the protein with the most interactions, thereby further investigating its function and expression patterns. Results In this study, 7 DPRGs were screened, including SLC2A1, LDHA, SNAI2 and ACO2, FGF12, ANP32B and ST13.The prognostic model constructed based on these genes exhibited high validation efficiency.Kaplan-Meier survival analysis revealed significant differences in overall survival of patients between high-risk group and low-risk group in four datasets.Differential expression gene enrichment analysis between the high-risk and low-risk groups showed that these genes were enriched in pathways such as the p53 signaling pathway and cell cycle. Results of real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry indicated that LDHA expression levels were elevated in LUAD tissue compared to normal tissues. Conclusion The LUAD model established based on DPRGs can effectively predict patients'prognosis, potentially offering insights into the treatment and prognosis of LUAD patients.

Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective To evaluate the expression of FUNDC1 and its clinical significance in non-small cell lung cancer. Methods We used TCGA database to analyze the difference of mitochondrial receptors (DRP1, BNIP3, FUNDC1, NIX, RHEB, LC3, OPA1 and MFN1) expression between normal and NSCLC tissues, as well as its effect on the prognosis of NSCLC patients. Immunohistochemistry was used to detect FUNDC1 expression. The correlations between FUNDC1 expression and clinicopathological characteristics, prognosis were evaluated by SPSS 22.0 statistical software. Results FUNDC1 expression was increased in NSCLC tissues, compared with normal tissues. FUNDC1 expression was related to the degree of differentiation and lymph node metastasis, but not to gender, age, pathological type, distant metastasis or TNM classification. The Cox regression analysis showed that FUNDC1 protein expression, lymph node metastasis, differentiation degree were independent prognostic factors of NSCLC. Increased FUNDC1 expression was related to decreased OS and PFS (P < 0.01). Conclusion The up-regulation of FUNDC1 expression can affect the prognosis of patients with NSCLC. It may be a new potential target for treating with NSCLC.

Objective To analyze the mortality risk and evaluate the curative effects of surgery and non-surgery on NSCLC with diameter > 7.0 cm. Methods We collected the data of NSCLC patients with diameter > 7.0 cm from 2010 to 2015 from the SEER database. The 1, 2, 3-year survival rates were analyzed by life table method. Overall survival curve was estimated by Kaplan-Meier method. Univariate and multivariate Cox regression models were used to analyze the independent prognostic factors. Results The 1, 2, 3-year survival rates were 51.8%, 33.0% and 25.0%, respectively. In univariate and multivariate analyses, tumor size, N stage and treatment were the independent prognostic factors (P < 0.001). Conclusion Surgery is benefited for the prognosis of stage N0-N1 NSCLC patients with diameter > 7.0 cm. And for stage N2 NSCLC patients with diameter 7.0-9.0 cm, surgical treatment has advantages in improving the prognosis. Surgical and non-surgical patients with tumor diameter ≥9.0 cm or lymph node N3 stage have no statistically significant differences in prognosis. In addition, palliative treatment does not improve the prognosis of patients.

Objective To analyze the factors affecting the prognosis of patients with pulmonary sarcomatoid carcinoma (PSC) and construct a nomogram prediction model for the prognosis of PSC patients. Methods Based on the SEER database, 1671 patients diagnosed as PSC from 1988 to 2015 were collected and divided into modeling group and validation group according to the ratio of 7:3. Univariate and multivariate Cox regression analysis were performed in the modeling group to explore independent risk factors affecting the prognosis and construct a nomogram survival prediction model. The consistency index and calibration curve were used for verification in the modeling group and the test module respectively. Results Age, gender, histological type, TNM stage, tumor diameter > 50mm, surgery, radiotherapy and chemotherapy were independent factors that affected the prognosis of PSC patients. The nomogram prediction model was constructed and verified based on independent factors. The C indexes of the modeling group and the test model were 0.790 (95%CI: 0.776-0.804) and 0.781 (95%CI: 0.759-0.803), respectively. The calibration curves of the modeling group and the test model indicated that the predicted survival rate was basically the same as the actual survival rate. Conclusion The nomogram prediction model constructed based on the results of multivariate analysis can predict the prognosis of PSC patients, and has high accuracy and consistency.

The epidermal growth factor receptor (EGFR) exon 19 deletion (19del) and the L858R point mutation of exon 21 are the most common types of EGFR mutations in non-small cell lung cancer (NSCLC). Treatment with EGFR tyrosine kinase inhibitors (TKI) can provide better survival benefit for some patients with advanced NSCLC. Clinical studies have shown that patients with these two types of mutations have different benefits in EGFR-TKI therapy. However, most patients treated with EGFR-TKI develop resistance after 12 months of treatment, the most common of which is the EGFR gene T790M mutation. In order to study the mechanism of resistance to TKI in NSCLC patients, and to develop new therapeutic methods and rational treatment strategies, further research on tumor characteristics in the whole disease progression and treatment process is indispensable. Exploring and comparing the differences between 19del and L858R and T790M in obtaining resistance to TKI is of great clinical significance.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective To investigate the prognostic value of platelet to lymphocyte ratio (PLR) for early virological response in Entecavir (ETV)-treated chronic hepatitis B (CHB) patients with genotype C infection.Methods Ninety-one genotype C CHB patients with HBV DNA≥1×105 copies/mL were treated with ETV (0.5 mg/d) for 10-13 days.The correlation between PLR and viral load decline was evaluated by Pearson or Spearman's rank correlation coefficient.Stepwise linear regression analysis was used to establish the prediction model of virological response.Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of PLR for early virological response in ETV-treated patients with genotype C hepatitis B virus (HBV) infection.Results After 10-13 days of ETV treatment, HBV DNA decreased ≥1×lg copies/mL from baseline in 89 cases of the 91 patients, while HBV DNA declined ≥2×lg copies/mL in 65 patients and 4 patients achieved HBV DNA<500 copies/mL.HBV DNA decline was positively correlated with baseline PLR levels (r=0.235 09, P<0.05).After adjustment for age, gender, Hepatitis B e Antigen (HBeAg), and treatment days, HBV DNA decline was still positively correlated with baseline PLR levels (r=0.220 26, P<0.05).Area under curve (AUC) of prediction model including age , baseline aspartate transaminase (AST) and HBV DNA was 0.759 (95% CI : 0.660-0.859, P<0.01).After adding PLR to the prediction model, the AUC was 0.780 (95% CI: 0.685-0.875, P<0.01).Conclusions PLR is predictive to early virological response in ETV-treated CHB patients with genotype C infection.Higher baseline PLR level indicates a better virological response.PLR monitoring should be recommended in CHB patients with antiviral treatment in clinical practice.