Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Two sex pheromone receptors for sexual communication in the American cockroach.

Volatile sex pheromones are vital for sexual communication between males and females. Females of the American cockroach, Periplaneta americana, produce and emit two sex pheromone components, periplanone-A (PA) and periplanone-B (PB). Although PB is the major sex attractant and can attract males, how it interacts with PA in regulating sexual behaviors is still unknown. In this study, we found that in male cockroaches, PA counteracted PB attraction. We identified two odorant receptors (ORs), OR53 and OR100, as PB/PA and PA receptors, respectively. OR53 and OR100 were predominantly expressed in the antennae of sexually mature males, and their expression levels were regulated by the sex differentiation pathway and nutrition-responsive signals. Cellular localization of OR53 and OR100 in male antennae further revealed that two types of sensilla coordinate a complex two-pheromone-two-receptor pathway in regulating cockroach sexual behaviors. These findings indicate distinct functions of the two sex pheromone components, identify their receptors and possible regulatory mechanisms underlying the male-specific and age-dependent sexual behaviors, and can guide novel strategies for pest management.

Surgically treating a rare and asymptomatic intraductal papillary neoplasm of the bile duct: A case report.

BACKGROUND: Intraductal papillary neoplasms of the bile duct (IPNBs) are rare and characterized by papillary growth within the bile duct lumen. IPNB is similar to obstructive biliary pathology. In this report, we present an unexpected case of asymptomatic IPNB and consolidate our findings with the relevant literature to augment our understanding of this condition. Integrating relevant literature contributes to a more comprehensive understanding of the disease. CASE SUMMARY: A 66-year-old Chinese male patient was admitted to our hospital for surgical intervention after gallstones were discovered during a routine physical examination. Preoperative imaging revealed a lesion on the left side of the liver, which raised the suspicion of IPNB. A laparoscopic left hemihepatectomy was performed, and subsequent histopathological examination confirmed the diagnosis of IPNB. At the 3-mo postoperative follow-up, the patient reported good recovery and no metastasis. IPNB can manifest both latently and asymptomatically. Radical surgical resection is the most effective treatment for IPNB. CONCLUSION: Hepatic and biliary masses, should be considered to diagnose IPNB. Prompt surgery and vigilant follow-up are crucial in determining prognosis.

Effects of gene polymorphism on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin treatment in stage Ⅲ and Ⅳ colorectal cancer / 中国药房

OBJECTIVE To investigate the effects of GSTP1， XRCC1， ABCB1， MTHFR gene polymorphisms on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin in patients with stage Ⅲ and Ⅳ colorectal cancer patients. METHODS Clinical data of 76 patients with stage Ⅲ and Ⅳ colorectal cancer who received chemotherapy regimen containing oxaliplatin （XELOX，FOLFOX） were collected from the Second Affiliated Hospital of Soochow University from September 2018 to March 2020. The correlation of genotypes with progression-free survival （PFS） and toxic effect was analyzed by using univariate and multivariate COX regression model. RESULTS Carriers of the ABCB1 3435T＞C locus C allele （TC/CC） had a significantly higher risk of progression compared to TT genotype patients [HR＝2.39， 95%CI （1.05，5.50）， P＝0.038]. The risk of progression in patients at stage Ⅳ was significantly higher than those at stage Ⅲ [HR＝8.11， 95%CI（3.39，19.40）， P＜0.001]. Chemotherapy regimen， Karnofsky performance status score and tumor site had no significant effect on disease progression （P＞0.05）. Mutations in gene loci were not correlated with adverse reactions （P＞0.05）. CONCLUSIONS Patients carrying ABCB1 TC/CC and receiving chemotherapy regimen containing oxaliplatin have a higher risk of disease progression， which may be associated with longer PFS in patients （TT genotype） with stage Ⅳ colorectal cancer receiving the chemotherapy， while GSTP1， XRCC1， and MTHFR gene polymorphisms have no significant impact.

Time-of-day discrepancy for the long-term surgical outcome of patients with aortic dissection.

OBJECTIVES: It has been suggested that the time of day when cardiovascular surgery is performed may affect the surgery outcomes. This study investigated whether there was a difference in risk-adjusted mortality and morbidity outcomes between patients undergoing acute aortic dissection (AAD) during the day or the night. METHODS: Consecutive patients who had undergone Stanford A AAD surgery were enrolled between 2016 and 2020. In the daytime group, surgery was performed between 08:00 and 20:00, and in the nighttime group between 20:00 and 8:00. The primary outcome was in-hospital overall mortality, and the secondary outcomes were overall mortality within a median follow-up time of 35.2 (17.0, 53.5) months and the occurrence of re-entry tears and major bleeding. RESULTS: A total of 925 patients were enrolled. The primary outcome of in-hospital overall mortality did not differ significantly between patients who received daytime or nighttime surgery. Similarly, the secondary outcomes of overall mortality during the follow-up and incidence of re-entry tears and major bleeding did not differ significantly between the groups. Subgroup analysis was also performed according to the surgery type (modified triple-branched stent graft implantation or frozen elephant trunk implantation) and surgical approach (partial upper sternotomy or full median sternotomy) confirming that the time of surgery did not significantly influence the outcomes. Cox regression analysis showed that time from onset to admission (P = 0.036) and time from the onset to surgery (P = 0.045) were significant risk factors for increased mortality during follow-up. CONCLUSIONS: The time of day when thoracotomy was performed did not significantly affect the clinical outcome and is therefore not a consideration for the improvement of outcome in Stanford A AAD patients.

TAK-242 protects against oxygen-glucose deprivation and reoxygenation-induced injury in brain microvascular endothelial cells and alters the expression pattern of lncRNAs.

Background: Deep hypothermic circulatory arrest (DHCA) is a technique used during the surgical treatment of aneurysms of the thoracic aorta in adult patients, and complex congenital heart disease in neonates. And brain microvascular endothelial cells (BMECs) are essential components of the cerebrovascular network and participate in maintaining the blood-brain barrier (BBB) and brain function. In our previous study, we found that oxygen-glucose deprivation and reoxygenation (OGD/R) activated Toll-like receptor 4 (TLR4) signaling in BMECs, and induced pyroptosis and inflammation. In this study, we further investigated the potential mechanism of ethyl(6R)-6-[N-(2-Chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate (TAK-242) on BMECs under OGD/R, as in patients with sepsis, the TAK-242 was tested in clinical trials. Methods: To confirm the function of TAK-242 on BMECs under OGD/R, cell viability, inflammatory factors, inflammation-associated pyroptosis, and nuclear factor-κB (NF-κB) signaling were determined using Cell Counting Kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay (ELISA), and western blotting, respectively. To investigate the lncRNAs associated with TLR4 during OGD/R, long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression patterns were profiled with RNA deep sequencing. Moreover, to confirm whether lncRNA-encoded short peptides, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. Results: Relative control group, OGD/R inhibited the cell viability, increased the section of inflammatory factors secretion, including IL-1ß, IL-6, and TNF-α, and promoted the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB. However, TAK-242 + OGD/R group promoted OGD/R cell viability, decreased OGD/R-induced inflammatory factors secretion, and inhibited the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB. In addition, AABR07000411.1, AABR070006957.1, and AABR070008256.1 were decreased in OGD/R cells compared with controls, but TAK-242 restored their expression under OGD/R condition. AABR07000473.1, AC130862.4, and LOC10254972.6 were induced by OGD/R, but were suppressed in TAK-242 + OGD/R cells compared with OGD/R. Moreover, AABR07049961.1, AC127076.2, AABR07066020.1, and AABR07025303.1-encoded short peptides were dysregulated in OGD/R cells, and TAK-242 attenuated the dysregulation of AABR07049961.1, AC127076.2, and AABR07066020.1-encoded short peptides. Conclusions: TAK-242 alters the expression pattern of lncRNAs in OGD/R cells, and differently expressed lncRNAs may exert a protective effect against OGD/R injury through a mechanism of competing endogenous RNA (ceRNA) and encoding short peptides. These findings maybe provide a new theory basis for the treatment of DHCA.

Optimization of glutathione production in Saccharomyces cerevisiae HBSD-W08 using Plackett-Burman and central composite rotatable designs.

BACKGROUND: Glutathione is an important bioactive tripeptide and is widely used in the food, medicine, and cosmetics industries. The aim of this study was to provide an efficient method for producing GSH and to explore its synthesis mechanism. Saccharomyces cerevisiae strain HBSD-W08 was screened for GSH production, and its fermentation medium was optimized using single-factor experiments of the Plackett-Burman and central composite rotatable designs. This method was used to analyze the effects of the presence and concentration of various carbon sources, organic and inorganic nitrogen sources, metal ions, and precursor amino acids on GSH production and catalase, superoxide dismutase, and γ-glutamylcysteine synthetase activity. RESULTS: The three most significant factors affecting GSH production were peptone (optimal concentration [OC]: 2.50 g L- 1), KH2PO4 (OC: 0.13 g L- 1), and glutamic acid (OC: 0.10 g L- 1). GSH productivity of HBSD-W08 was obtained at 3.70 g L- 1 in the optimized medium. The activity of γ-GCS, which is a marker for oxidative stress, was found to be highly positively correlated with GSH production. CONCLUSIONS: This finding revealed an underlying relationship between GSH synthesis and oxidative stress, providing useful information for developing effective GSH fermentation control strategies.

Immune-Related Pancreatitis Caused by Immune Checkpoint Inhibitor Nivolumab:Report of One Case / 中国医学科学院学报

In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.

Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation / 中国药房

OBJECTIVE To analyze influential factors for dabigatran exposure in elderly patients with non-valvular atrial fibrillation. METHODS The clinical information of 75 elderly patients diagnosed with non-valvular atrial fibrillation was collected from our hospital in Jan. 2019-Jun. 2020. One or two steady-state blood drug concentration samples were collected from each patient. NONMEM 7.2.0 software was used to establish a population pharmacokinetics model of dabigatran； the effects of different covariates on the apparent clearance of dabigatran were investigated， and the final model was verified by goodness of fit and Bootstrap method； NONMEM 7.2.0 software was used to analyze the drug exposure of ordinary elderly patients and elderly patients after taking dabigatran ester in different disease states. RESULTS Totally 122 blood concentration samples of dabigatran were collected. Advanced age， creatinine clearance and history of chronic heart failure were screened out as three significant covariates that influenced the clearance of dabigatran in elderly patients. The exposure of population with advanced age increased by about 50% compared with the general elderly， the exposure of population with history of chronic heart failure increased by nearly 30% compared with population without， and the exposure of population with moderate and severe renal injury increased by about 30% and 80% compared with mild. CONCLUSIONS Advanced age， renal injury and history of chronic heart failure are influential factors for elevated systemic exposure of dabigatran.

CircFBXW7 Inhibits Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer Cells by Regulating miR-492.

Background: CircFBXW7 has been determined to be involved in various cancers; however, its role in nonsmall cell lung cancer (NSCLC) remains unclear. This study examined the function and potential mechanism of circFBXW7 in NSCLC. Methods: The structure of circFBXW7 was verified via RT-PCR and Sanger sequencing. The expression of circFBXW7 in NSCLC was determined by qRT-PCR. The effect of circFBXW7 overexpression on the proliferation, migration, and invasion of NSCLC cells was examined by CCK-8 and Transwell assays. Furthermore, a circFBXW7-miRNA network was established to explore their interaction. Predicted miRNA was determined by qRT-PCR. Moreover, the miRNA mimics were synthesized, wherein its effect on proliferation, migration, and invasion of NSCLC cells overexpressed circFBXW7 was assessed. Results: The circularity of circFBXW7 was verified. The expression of circFBXW7 was found to be downregulated in NSCLC cells compared with that in normal human lung epithelial BEAS-2B cells. Overexpression of circFBXW7 reduced cell proliferation, migration, and invasion. Furthermore, according to the circFBXW7-miRNA network prediction and qRT-PCR validation, miR-492 was identified to be the target of circFBXW7. The inhibitory effect of circFBXW7 overexpression on cell proliferation, migration, and invasion was reversed by miR-492 mimics. Conclusion: CircFBXW7 is downregulated in NSCLC. CircFBXW7 inhibits NSCLC cells proliferation, migration, and invasion by regulating miR-492.

The mitochondrial genome and phylogenetic position of a conehead katydid Euconocephalus pallidus (Insecta: Orthoptera).

The complete mitochondrial genome of a conehead katydid Euconocephalus pallidus was determined. The mitochondrial genome is 15,888 bp in size with an A + T content of 71.67%. It contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. The order and orientation of these genes conform to the ancestral form of insects. Phylogenetic analysis supports a close relationship between E. pallidus and E. nasutus.

Observation of the spin-Hall effect in Pt/GaAs by circular polarized photoconductivity.

Electrically generated spin accumulation due to the spin Hall effect of Pt/GaAs is detected by circular polarized photoconductivity (CPPC), which shows electron spins with different polarizations accumulated around opposite sample boundaries. An optical absorption model incorporating spin is used to explain these features. The detailed analysis of the observed degree of circular polarization of the photocurrent strongly suggests that Pt and GaAs have the same spin accumulation length in the Pt/GaAs heterostructure.

Evaluation of Reference Genes for Transcriptional Profiling in Two Cockroach Models.

The German cockroach, Blattella germanica, and the American cockroach, Periplaneta americana are the most common and synanthropic household pests of interest to public health. While they have increasingly served as model systems in hemimetabolous insects for studying many biological issues, there is still a lack of stable reference gene evaluation for reliable quantitative real-time PCR (qPCR) outputs and functional genomics. Here, we evaluated the expression variation of common insect reference genes, including the historically used actin, across various tissues and developmental stages, and also under experimental treatment conditions in these two species by using three individual algorithms (geNorm, BestKeeper, and NormFinder) and a comprehensive program (RefFinder). RPL32 in B. germanica and EF1α in P. americana showed the overall lowest variation among all examined samples. Based on the stability rankings by RefFinder, the optimal but varied reference genes under specific conditions were selected for qPCR normalization. In addition, the combination of RPL32 and EF1α was recommended for all the tested tissues and stages in B. germanica, whereas the combination of multiple reference genes was unfavorable in P. americana. This study provides a condition-specific resource of reference gene selection for accurate gene expression profiling and facilitating functional genomics in these two important cockroaches.

Anomalous circular photogalvanic effect in p-GaAs.

The anomalous circular photogalvanic effect (ACPGE) is observed in p-GaAs with a thickness of 2 µm at room temperature, in which circularly polarized light is used to inject spin-polarized carriers and the spin diffusion can generate a macroscopic detectable charge current due to the inverse spin Hall effect. The normalized ACPGE signals show first increasing and then decreasing with increasing the doping concentration. The role of the doping impurities is discussed by both extrinsic and intrinsic models, and both can well explain the variation of ACPGE with the doping concentration.

Peripheral blood inflammation indices are effective predictors of anastomotic leakage in elective esophageal surgery.

BACKGROUND: This study investigated the predictive value of peripheral inflammatory indices, including neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in anastomotic leakage during elective esophageal surgery. METHODS: This retrospective study included all patients who underwent esophagectomy for esophageal squamous cell carcinoma from 2016 to 2020 in our institution. The peripheral blood inflammatory indices were obtained on preoperative days 1-7 (PRD 1-7), and postoperative days 1-3 (POD 1-3) and 4-7 (POD 4-7). Univariate, multivariate logistic, and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic value of these peripheral blood inflammatory indices. RESULTS: A total of 198 patients were included in the study, and 25 (13%) patients experienced anastomotic leakage. Multivariate analyses identified diet, neutrophil count, and PLR on POD 1-3, and NLR on POD 4-7 as independent factors associated with anastomotic leakage. Using the receiver operating characteristic curve, the variable with the best area under curve was a neutrophil cutoff count of 4.1 [0.737; 95% CI: 0.639-0.835], with a sensitivity and specificity of 60.0% and 66.5%, respectively. This was followed by an NLR cutoff value of 9.5 on POD 4-7 (0.628; 95% CI: 0.505-0.752) and a cutoff PLR value of 220.1 on POD 1-3 (0.643; 95% CI: 0.536-0.750). Diet showed a poor result on the receiver operating characteristic curve analysis. CONCLUSIONS: Neutrophil count and PLR on POD 1-3 and NLR on POD 4-7 were shown to have predictive value for anastomotic leakage in elective esophageal surgery.

Increased risk of cardiovascular disease in elderly population with carotid plaque and low ankle brachial index / 中华心血管病杂志

Objective: To investigate whether the co-presence of carotid plaques and low ankle-brachial index (ABI) might increase the risks of ischemic cardiovascular and cerebrovascular event in elderly population. Methods: It was a prospective study. Participants from the elderly cohort of the Kailuan Study, who completed a carotid sonography and ABI examination, were included in this study. Participants underwent physical examinations between 2010 and 2011 and were divided into 3 groups: no carotid plaque and ABI>0.9 group (n=526), carotid plaque and ABI>0.9 group (n=1 067), and carotid plaques and ABI≤0.9 group (n=49). Follow up ended on the 31 December 2016. The incidence of ischemic cardiovascular and cerebrovascular event was compared between the 3 groups, the relationship between carotid plaque and low ABI with ischemic cardiovascular and cerebrovascular event was analyzed. Results: A total of 1 642 participants were included (age, (67.1±6.4) years). There were 1 028 males (62.6%) and 1 028 females(37.4%). The average follow-up time was 5.41 years, the incidence of ischemic cardiovascular and cerebrovascular event in the 3 group was 2.1%(11/526), 5.5%(59/1 067), and 12.2%(6/49),respectively; the incidence of myocardial infarction in the 3 group was 0.2%(1/526), 1.6%(17/1 067), 10.2%(5/49), respectively; the incidence of cerebral infarction in the 3 group was 1.9%(10/526), 3.9%(42/1 067) and 2.0%(1/49), respectively. Multivariate Cox risk proportional regression analysis showed that compared with the group without carotid plaque and ABI>0.9, the HR values (95%CI) of ischemic cardiovascular and cerebrovascular event in the group with carotid plaque and ABI>0.9, carotid plaques and ABI≤0.9 group were 3.52 (1.49-8.35), 7.16(2.11-24.26) respectively, after adjusting for sex,age,systolic blood pressure,fast blood glucose,body mass index,total cholesterol,smoke,alcohol consumption and lipid-lowering medication and antihypertensive medication. Conclusions: Co-presence of carotid plaques and low ankle-brachial index may further increase the risk of ischemic cardiovascular and cerebrovascular event among elderly population in this cohort.

The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality from COVID-19

Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and preclinical data suggest alpha-1 adrenergic receptor antagonists (1-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of 1-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any 1-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63 to 0.85; p [≤] 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65 to 0.84; p [≤] 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03 to 0.94; p = 0.028) compared to matched controls not on any 1-AR antagonist at the time of admission. These findings suggest that use of 1-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.

Outcomes associated with SARS-CoV-2 viral clades in COVID-19

BackgroundThe COVID-19 epidemic of 2019-20 is due to the novel coronavirus SARS-CoV-2. Following first case description in December, 2019 this virus has infected over 10 million individuals and resulted in at least 500,000 deaths world-wide. The virus is undergoing rapid mutation, with two major clades of sequence variants emerging. This study sought to determine whether SARS-CoV-2 sequence variants are associated with differing outcomes among COVID-19 patients in a single medical system. MethodsWhole genome SARS-CoV-2 RNA sequence was obtained from isolates collected from patients registered in the University of Washington Medicine health system between March 1 and April 15, 2020. Demographic and baseline medical data along with outcomes of hospitalization and death were collected. Statistical and machine learning models were applied to determine if viral genetic variants were associated with specific outcomes of hospitalization or death. FindingsFull length SARS-CoV-2 sequence was obtained 190 subjects with clinical outcome data. 35 (18.4%) were hospitalized and 14 (7.4%) died from complications of infection. A total of 289 single nucleotide variants were identified. Clustering methods demonstrated two major viral clades, which could be readily distinguished by 12 polymorphisms in 5 genes. A trend toward higher rates of hospitalization of patients with Clade 2 was observed (p=0.06). Machine learning models utilizing patient demographics and co-morbidities achieved area-under-the-curve (AUC) values of 0.93 for predicting hospitalization. Addition of viral clade or sequence information did not significantly improve models for outcome prediction. ConclusionSARS-CoV-2 shows substantial sequence diversity in a community-based sample. Two dominant clades of virus are in circulation. Among patients sufficiently ill to warrant testing for virus, no significant difference in outcomes of hospitalization or death could be discerned between clades in this sample. Major risk factors for hospitalization and death for either major clade of virus include patient age and comorbid conditions. FundingSupported by NIH P30EY001730, the Mark J. Daily, MD Research Fund (RVG), the Alida and Christopher Latham Research Fund (RVG, AYL, CSL), NIH K23EY029246 (AYL), US Food and Drug Administration (QYL)