Treatment and prognostic risk factors for intracranial infection after craniocerebral surgery.

The objective of this study was to determine risk factors of pejorative evolution course in patients suffering from postoperative cranial infection. The data of patients who developed an intracranial infection after craniocerebral surgery in the neurosurgical intensive care unit of the First Affiliated Hospital of Nanjing Medical University in Nanjing, Jiangsu, China, from February 2018 to August 2019 were retrospectively analyzed. Logistic regression was used to analyze the factors influencing the prognosis of intracranial infection treatment. Sixty-four patients developed an infection after craniocerebral surgery, and 48 of them with negative CSF cultures received experimental anti-infectives. In 16 patients, cerebrospinal fluid culture showed pandrug-resistant pathogens, including 11 Acinetobacter baumannii (11), Klebsiella pneumoniae (3), Escherichia coli (1), and Candida glabrata (1). Nine patients received intraventricular or intrathecal injections of polymyxin B. The mean duration of infection treatment was 22.2 ± 9.9 days, and the clinical cure rate was 85.9% (55/64). Logistic multivariate regression analysis showed that inadequate CSF drainage (OR, 6.839; 95% CI, 1.130-41.383; P = 0.036) and infection with drug-resistant bacteria (OR, 24.241; 95% CI, 2.032-289.150; P = 0.012) were independent risk factors for postoperative intracranial infection. Intracranial infection with positive CSF culture and inadequate CSF drainage are factors contributing to the poor prognosis of intracranial infection. Moreover, early anti-infection treatment and adequate CSF drainage may improve patient outcomes. In particular, intraventricular or intrathecal injection of polymyxin B may be a safe and effective treatment strategy for MDR/XDR gram-negative bacilli infection.

Combined detection of peripheral blood VEGF and inflammation biomarkers to evaluate the clinical response and prognostic prediction of non-operative ESCC.

An association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC). Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA. VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS. The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool.

Peripheral blood cell count ratios are predictive biomarkers of clinical response and prognosis for non-surgical esophageal squamous cell carcinoma patients treated with radiotherapy.

BACKGROUND: Peripheral blood cell count ratios, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been reported to be prognostic factors in many malignancies as markers of inflammation and immune status. The aim of this study was to determine whether NLR, PLR, or LMR can be clinical response and prognostic biomarkers of non-surgical esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy. METHODS: 193 non-surgical ESCC patients who underwent radiotherapy were retrospectively analyzed. The peripheral blood cell count ratios were obtained before, during (weekly) and at the end of the treatment. Then, we compared the subsequent results with the corresponding pretreatment values and computed the rates of change, which were defined as cNLR, cPLR, and cLMR. Univariate and multivariate Cox regression analyses were used for overall survival (OS). Ordinal logistic regression was used to analyze the clinical response. RESULTS: In multivariate analysis, cNLR at week 4(P = .026) and week 5(P = .025) during radiotherapy were significantly associated with OS, along with BMI, tumor stage, tumor length, tumor location, and grade of adverse events. Besides, BMI, tumor stage, tumor length, adverse event grade, cNLR at week 4(P = .044) and week 5(P = .013), and cPLR at week 4(P = .034) and week 5(P = .015) were significantly associated with the clinical response in the multivariate logistic regression analysis. CONCLUSIONS: The cNLR at weeks 4 and 5 was negatively correlated with the OS and clinical response of non-surgical ESCC patients treated with radiotherapy. The elevated cPLR at weeks 4 and 5 was only related to poor clinical response.

Impact of examined lymph node count on long-term survival of T1-2N0M0 double primary NSCLC patients after surgery: a SEER study.

PURPOSE: The relationship between examined lymph nodes (ELN) and survival has been confirmed in several single early-stage malignancies. We studied the association between the ELN count and the long-term survival of T1-2N0M0 double primary non-small cell lung cancer (DP-NSCLC) patients after surgery, based on the Surveillance, Epidemiology and End Results (SEER) database. METHODS: A total of 948 patients were identified and their independent prognostic factors were analyzed. These factors included the ELN count, which related to overall survival (OS) and the cancer-specific survival (CSS) of synchronous (n = 426) and metachronous (n = 522) T1-2N0M0 DP-NSCLC patients after surgery. RESULTS: X-tile analysis indicated that the cutoff value for the sum of ELNs was 22 for both OS and CSS in the synchronous DP-NSCLC group. Patients with a sum of ELNs >22 were statistically more likely to survive than those with ≤22 ELNs. X-tile analysis revealed that the ELN count of the second lesion was related to both OS and CSS in the metachronous DP-NSCLC group. The optimal cutoff value was nine. These results were confirmed using univariate and multivariate Cox regression analyses. CONCLUSION: Our findings indicate that ELN count was highly correlated with the long-term survival of T1-2N0M0 double primary NSCLC patients after surgery.

Discussion on Brain Structure and Function in Schizophrenia by Multimodal Magnetic Resonance Imaging.

In order to explore the relationship between hippocampal structure changes and performance symptoms as well as cognitive function in adolescent schizophrenia, taking the brain response signals of psychiatric patients as the research object, the relationship between hippocampal volume drawn by schizophrenia and language memory of negative symptoms is explored based on morphological analysis method. It is found that the left hippocampal volume of schizophrenic patients is abnormal when the whole brain volume is returned, which is significantly lower than that of normal people. It is also found that the left hippocampus volume of schizophrenic patients is a mediator between negative symptoms and speech memory. The results show that the left hippocampus of schizophrenic patients plays an important role in the pathogenesis of schizophrenia.

[Rapid cloning and functional characterization of hypericin synthase gene].

Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, commonly known as St. John's wort. Hypericin has attracted a growing attention of the pharmaceutical industry because of its potential application to various therapies, including the treatment of depression and remarkable antiviral and photodynamic activities, hyp-1 gene encodes for phenolic coupling protein which catalyzes in vitro direct and specific conversion of emodin to hypericin which, however, has not formed common opinion so far. Six pairs of primers specific to hyp-1 gene were synthesized. The rapid cloning of hyp-1 gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pET32ahyp containing hyp-1 gene was constructed and was transformed into E. coli to induce heterologous expression. SDS-PAGE and Western blot results showed the recombinant Hyp-1 protein was expressed successfully in E. coli. The soluble fraction was used to test the function of the recombinant Hyp-1. Hypericin was detected by LC-MS/MS with emodin as a substrate under in vitro conditions. The above results corroborated the Hyp-1 function, a confusing question, which lay a material foundation for the synthesis of hypericin by synthetic biotechnology.

Improvement of amorpha-4,11-diene production by a yeast-conform variant of Vitreoscilla hemoglobin.

Amorpha-4,11-diene is the precursor of the antimalarial compound artemisinin. The effect of Vitreoscilla hemoglobin (VHb) and its yeast-conform variant (VHbm) on amorpha-4,11-diene production in engineered Saccharomyces cerevisiae was investigated. First, the VHb gene was mutated to the yeast-conform variant VHbm based on step-by-step extension of a short region of the gene through a series of polymerase chain reactions (PCR). The artificial VHbm gene contained codons preferred by the yeast translation machinery. Two yeast expression vectors containing VHb or VHbm gene were constructed and introduced into the amorpha-4,11-diene-producing strain S. cerevisiae WK1 to form WK1[VHb] and WK1[VHbm], respectively. Western blot and CO-difference spectrum absorbance assay showed that VHb and VHbm were successfully expressed. In shake flasks, VHbm expression conferred higher cell growth than VHb expression. GC-MS results indicated the amorpha-4,11-diene production in WK1[VHbm] and WK1[VHb] was 3- and 2-fold higher than that in WK1, respectively. This suggests that VHb might improve the amorpha-4,11-diene production in engineered S. cerevisiae.

[Synergistic effect of amorpha-4,11-diene synthase gene in engineered Saccharomyces cerevisiae].

To construct an engineered Saccharomyces cerevisiae producing high titres of amorpha-4,11-diene, we investigated the possible synergistic effect of different vectors containing amorpha-4,11-diene synthase(ADS) gene within one yeast cell. We constructed the ADS recombinant plasmid pGADADS. This plasmid and another ADS recombinant plasmid pYeDP60/G/ADS were alone, or co-transformed into yeast Saccharomyces cerevisiae W303-1B and WK1, respectively, resulting in the following engineered yeasts, W303B[pGADADS], W303B[pYGADS], W303B[pYGADS+pGADADS], WK1[pGADADS], WK1[pYGADS] and WK1[pYGADS+pGADADS]. All of the six strains were cultured for GC-MS analysis of amorpha-4,11-diene. The results showed that all of the engineered yeasts could produce amorpha-4,11-diene. The yield of the product was improved with increasing ADS gene copies while no deleterious effect on the strain growth was found. Moreover, the product yield of the engineered yeast co-transformed with multiple plasmids was much higher than the total yield of the different engineered yeasts with only one plasmid, respectively. In conclusion, there was a distinct synergistic effect between different recombinant ADS plasmids within one cell. Our results facilitate the construction of the engineered yeast with high yield of amorpha-4,11-diene, the precursor of artemisinin.