The association between circulating leukocytes and inflammatory bowel disease: a two-sample Mendelian randomization study.

Background: Inflammatory bowel disease (IBD) is a highly prevalent, recurrent, chronic intestinal inflammatory disease. Several observational studies have shown that circulating leukocytes are strongly associated with IBD. However, whether alterations in leukocytes are causally related to IBD remains uncertain. The present study explores this issue with the Mendelian randomization (MR) analysis method. Methods: The Genome wide association study (GWAS) statistical data related to circulating leukocytes and IBD were obtained from the Blood Cell Consortium and the IEU Qpen GWAS project, respectively. Inverse variance weighting (IVW) was used as the main MR analytical method, coupled with a series of sensitivity analyses to ensure the reliability of the results. Results: The results of IVW showed that increased monocyte count (especially CD14- CD16+ monocyte absolute counts) was negatively correlated with the risk of IBD and its main subtypes. Increased neutrophil count was positively associated with the risk of IBD and ulcerative colitis. Meanwhile, there was no causal relationship between basophil, eosinophil, lymphocyte counts and IBD risk. Conclusion: These results indicate that a causal relationship exists between circulating leukocytes and the risk of IBD and its subtypes, which confirms the important role that the leukocyte immune system plays in IBD. Our findings provide additional research directions for the clinical prevention and treatment of IBD.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

Expression of plasma exosomal circLPAR1 in patients with gastric cancer and its clinical application value.

OBJECTIVE: To determine plasma exosomal circular RNA LPAR1 (circLPAR1) expression in gastric cancer (GC) and analyze its clinical value in GC diagnosis and prognosis evaluation. METHODS: The research subjects were 64 GC patients, 30 chronic gastritis (CG) patients (disease control group) and 30 healthy controls (HCs; healthy control group). RT-PCR quantified circLPAR1 expression in GC tissues and adjacent counterparts of GC patients as well as plasma exosomal circLPAR1 in each group. The correlation of differentially expressed circLPAR1 with clinicopathological indexes was analyzed, and receiver operating characteristics (ROC) and Kaplan-Meier curves were drawn to evaluate the value of plasma exosomal circLPAR1 in GC diagnosis and prognosis assessment. RESULTS: GC patients exhibited lower plasma exosomal circLPAR1 levels than CG patients and HCs (P<0.05). Lower circLPAR1 expression was determined in GC tissues than in adjacent counterparts (P<0.05), and a positive connection between GC tissue circLPAR1 and plasma exosomal circLPAR1 was identified in GC patients (P<0.05). Evidently elevated plasma exosomal circLPAR1 was observed in post-surgical GC patients (P<0.05). ROC curves showed that the areas under the curve (AUCs) of plasma exosomal circLPAR1, serum carcinoembryonic antigen (CEA), and serum carbohydrate antigen 19-9 (CA19-9) for the diagnosis of GC were 0.836, 0.767 and 0.746, respectively, and the AUC of their combined diagnosis was 0.914. Low plasma exosomal circLPAR1 was strongly linked to tumor size, differentiation degree, tumor-node-metastasis (TNM) staging, vascular invasion, lymphatic metastasis, and HER2 expression of GC patients (P<0.05). GC patients with high plasma exosomal circLPAR1 expression had significantly longer prognostic survival time than those with low expression (P<0.05). According to univariate and multivariate Cox regression analyses, tissue differentiation degree (HR=1.415), TNM stage (HR=1.637), HER2 expression (HR=1.831), and low plasma exosomal circLPAR1 expression (HR=2.042) were risk factors for adverse prognosis in GC patients. CONCLUSIONS: circLPAR1 expression is related to GC progression, and the detection of plasma exosomal circLPAR1 has promising clinical application value in assisting the diagnosis and prognosis evaluation of GC.

Expression of Y-Box-binding protein 1 in Chinese patients with breast cancer.

The purpose of this study was to investigate the expression of Y-Box-binding protein 1 (YB-1) in breast cancer and its correlation with clinicopathological characteristics and prognosis. Paraffin sections were retrospectively collected from 239 cases of stage I-III breast cancer patients and 30 healthy females who received surgery between January 2000 and December 2004 in the Chinese People's Liberation Army General Hospital. The protein expression of YB-1 was detected by immunohistochemistry. The expression difference between the two groups and the correlation between YB-1 expression and clinicopathological characteristics and breast cancer prognosis were analyzed. Within the breast cancer group, YB-1 was expressed in the cytoplasm in 100.0% (239/239) of cases and in the nucleus in 36.8% (88/239) of cases. Within the control group of normal breast tissue, YB-1 was expressed in the cytoplasm in 100.0% (30/30) of cases and in the nucleus in 16.7% (5/30) of cases. The expression of YB-1 in the nucleus of breast cancer cells was significantly higher than that in normal breast tissue (P = 0.029). The expression of YB-1 in the nucleus of breast cancer cells positively correlated with the Scarff-Bloom-Richardson grade (P = 0.007) and HER-2 expression (P = 0.005), negatively correlated with ER expression (P = 0.004), and was independent of the age, menstrual status, pathological type, tumor size, lymph node status, presence of thrombosis, PR expression, and EGFR expression. The 5-year disease-free survival (DFS) and overall survival (OS) of patients with positive YB-1 expression in the nucleus were significantly lower than those of patients who were negative for nuclear YB-1 expression, and the difference was statistically significant (DFS 65.9% vs. 82.1%, P = 0.000; OS 79.5% vs. 92.1%, P = 0.000). Multivariate analysis suggested that the expression of YB-1 in the nucleus is an independent prognostic factor that affects DFS and OS in breast cancer patients (DFS P = 0.015; OS P = 0.035). In conclusion, the expression of YB-1 in the nucleus is related to carcinogenesis and the development of breast cancer. Therefore, YB-1 is an important molecular marker that can be used to predict breast cancer prognosis.

Clinical Value of the Prognostic Nutrition Index in the Assessment of Prognosis in Critically Ill Patients with Stroke: A Retrospective Analysis.

Purpose: The purpose of study was to evaluate the association between prognostic nutritional index (PNI) and all-cause mortality of critically ill patients with stroke. Methods: Clinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day all-cause mortality; secondary endpoints were 90-day mortality and one-year cause mortality. The potential prognostic roles of PNI were analyzed by Cox proportional hazard models. The independent prognostic roles of PNI in the cases were analyzed by smooth curve fitting. Results: Concerning 30-day mortality, the HR (95% CI) for a high PNI (≥39.7) was 0.700 (0.544, 0.900; P = 0.00539), compared to a low PNI (<39.7). After adjusting for multiple confounders, the HR (95% CI) for a high PNI (≥39.7) was 0.732 (0.547, 0.978; P = 0.03514), compared to a low PNI (<39.7). Regarding 90-day and one-year mortality, a similar trend was observed. In addition, a nonlinear association between PNI and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 49.4. On the right side of the IP, there was a positive relationship between PNI and 30-day mortality, and the effect size, 95% CI, and P value were 1.04 (1.01, 1.07), P = 0.0429, respectively. On the left of the IP, the effect size, 95% CI, and P value were 0.97 (0.96, 0.99) and 0.0011, respectively. Conclusions: The PNI was an independent predicting factor of 30-day, 90-day, and 1-year mortality of the critically ill patients with stroke. In addition, there was a U-shaped relationship between PNI and all-cause mortality of stroke patients. PNI was a risk factor for the outcome of stroke when PNI was >49.4, while PNI was a protective factor for outcome of stroke when PNI was <49.4.

Primary site surgery for elderly patients with distant metastatic pancreatic neuroendocrine tumor: to do or not to do?

OBJECTIVE: To investigate the effect of primary site surgery (PSS) on elderly patients (≥65 years) with pancreatic neuroendocrine tumor (pNET) distant metastasis. PATIENTS AND METHODS: We reviewed Surveillance Epidemiology and the End Results database for elderly patients with distant pNET from 1973 to 2015. The variables and survival outcomes of patients with PSS were compared with that of patients with no PSS. After propensity score matching, the survival outcome was compared again between the two groups. Multivariable Cox proportional hazard model was used to identify variables associated with cancer-specific and overall survival. Four sub-groups were divided according to the age and differentiation: 1) age 65-74 years+ well or moderately differentiated; 2) age ≥75 years+ well or moderately differentiated; 3) age 65-74 years+ poorly differentiated or undifferentiated; and 4) age ≥75 years+ poorly differentiated or undifferentiated. Cancer-specific survival was compared between the patients with and without PSS in the above each group. RESULTS: A total of 210 elderly patients with distant pNET were finally confirmed. Of which, 148 patients did not undergo PSS, while 62 patients underwent PSS. Being female (p=0.049), locating on body/tail of pancreas (p=0.006), and well or moderately differentiated (p=0.032) were more likely received PSS. The patients underwent PSS had better survival outcomes both before and after propensity score matching. Multivariable Cox proportional hazard analysis proves PSS and higher histological grade to be protective and risk factors. PSS may improve cancer specific survival in patients of group 1), and no improvement was observed in patients of the other three sub-groups. CONCLUSION: Not all elderly patients with pNET distant metastasis could benefit from PSS. Patients aged 65-74 years with well or moderately differentiated may benefit from primary lesion surgery, but should be evaluated carefully. Prospective randomized controlled trials are worth performing.

Neuroprotective effect of tanshinone IIA weakens spastic cerebral palsy through inflammation, p38MAPK and VEGF in neonatal rats.

As one of main active ingredients of salvia miltiorrhizae, which is a traditional Chinese medicine, tanshinone IIA is the basis of its pharmacological activities. In the present study, the effect of tanshinone IIA on weakening spastic cerebral palsy (SCP) in neonatal rats was investigated. Radial arm water maze and holding tests were used to measure the alterations of spastic cerebral palsy, inflammation was measured using an ELISA kit, and western blot analysis was used to analyze the protein expression of p­p38 mitogen­activated protein kinase (MAPK) and vascular endothelial growth factor (VEGF). The central mechanisms involved in the mediation or modulation of inflammation, p­p38 MAPK and VEGF were also investigated. Treatment with tanshinone IIA effectively inhibited spastic cerebral palsy, and the activities of interleukin (IL)­1ß, IL­6, tumor necrosis factor­α, monocyte chemoattractant protein 1, cyclooxygenase­2 and prostaglandin E2 in a neonatal rat model of SCP. Tanshinone IIA effectively suppressed the protein expression of inducible nitric oxide synthase (NOS), phosphorylated (p­) nuclear factor (NF)­κB, p­p38MAPK and VEGF, and activated the phosphorylation of inhibitor of NF­κB and the protein expression of neuronal NOS in the SCP rat model. These results suggested that the neuroprotective effect of tanshinone IIA weakened SCP through inflammation, p38MAPK and VEGF in the neonatal rats.

Effects of icariside II ameliorates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by activating Akt/NOS/NF-κB signaling.

Icariside II is a flavonoid extracted from Epimedium that has antioxidant, anti­inflammatory and antiapoptotic effects. The aim of the present study was to evaluate the effects icariside II on diabetic cardiomyopathy in streptozotocin-induced diabetic rats. Icariside II treatment improved body weight, heart/body weight ratio and fasting blood glucose in diabetic model rats. Icariside II was demonstrated to reduce the expression levels of creatine kinase and lactate dehydrogenase in serum, and to lower cardiac oxidative stress, inflammation and apoptosis levels in diabetic rats. Icariside II treatment induced phosphoinositide 3­kinase and phosphorylated­Akt expression, and suppressed inducible nitric oxide synthase (iNOS) and nuclear factor (NF)­κB protein expression in diabetic rat. Results from the present study suggested that treatment with icariside II improved diabetic cardiomyopathy in streptozotocin­induced diabetic rats by activating the Akt/NOS/NF­κB pathway.

[Experimental treatment of acute lung injury caused by inundation of thoracic cavity by seawater following open chest wound].

OBJECTIVE: To study the effects of lung protective ventilation and pentoxifylline (PTX) on acute lung injury (ALI) caused by open chest wound with seawater inundation of the thoracic cavity. METHODS: A model of ALI caused by open chest wound and seawater inundation of thoracic cavity was reproduced in dogs. Twenty-four healthy dogs were randomly divided into four groups: no-treatment group (group A), ordinary treatment group (group B), lung protective ventilation treatment group (group C), and lung protective ventilation and PTX treatment group (group D). The parameters of hemodynamics, arterial blood gas analysis, plasma osmotic pressure and serum electrolytes in dogs were determined at 0 and 6 hours after injury and at 2 and 4 hours after treatment. Blood samples and bronchoalveolar lavage fluid (BALF) were collected to assess the changes in cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8. RESULTS: The arterial oxygen partial pressure (PaO(2)) and oxygenation index (PaO(2)/FiO(2)) in group B were still lower than normal values at 2 and 4 hours after treatment, but those parameters in group C and group D distinctly recovered. The parameters of hemodynamics, plasma osmotic pressure and serum electrolytes were all normalized in group B, C and D at 2 and 4 hours after treatment compared with those in group A. The levels of TNF-alpha in peripheral blood in group C and the TNF-alpha and IL-8 levels in peripheral blood and IL-6, IL-8 levels in BALF in group D were significantly lower than those in group A and group B after treatment. The TNF-alpha in peripheral blood and IL-8 levels in BALF in group D were also significantly lower than those in group C after treatment. CONCLUSION: Lung protective ventilation is an effective method in the treatment of ALI caused by open chest wound with inundation of seawater in thoracic cavity. PTX can inhibit inflammatory reaction in the lung and peripheral blood.

Features of continuous glycemic profile and glycemic variability in patients with obstructive sleep apnea syndrome.

AIMS: To investigate glycemic variability (GV) in Obstructive Sleep Apnea Syndrome (OSAS) patients by monitoring continuous blood glucose profile. METHODS: OSAS group (n=86) and normal control group (n=40) were included. Continuous blood glucose was monitored. The relationship of GV, insulin resistance index (IRI) and the respiratory disturbance index (AHI) were analyzed. RESULTS: The daily average blood glucose level was significantly higher in the OSAS patients than in the control group (6.31±0.61vs. 4.94±0.78; P<0.01). The postprandial glycemic peaks in the OSAS patients were significantly higher and prolonged. The indicators of GV were all significantly higher in the OSAS patients, including blood glucose fluctuation coefficient (BGFC, 1.93±0.71vs. 1.21±0.38, P<0.05), mean amplitude of glycemic excursions (MAGE, 4.18±0.65vs. 2.18±0.48; P<0.05) and night mean amplitude of glycemic excursions (NMAGE, 2.00±0.53vs. 1.11±0.43; P<0.05). Pearson correlation analysis showed that among the OSAS patients, the severity of OSAS (AHI) was positively correlated with the IRI (r=0.310); and the GV indicators (MAGE and NMAGE) were positively correlated with IRI and AHI (r=0.318 and 0.349, respectively) (P<0.01 or 0.001). CONCLUSIONS: Continuous glycemic spectrum and GV provide comprehensive glycemic profiles and may reveal important aspects of glucose metabolism abnormality beyond regular examinations, and are therefore of particular significance for glycemic management in OSAS patients.

[The treatment effect of immunoglobulin in AIDS with Guillain-Barre syndrome].

OBJECTIVE: To discuss the treatment effect of immunoglobulin in acquired immune deficiency syndrome (AIDS) with Guillain-Barre syndrome (GBS). METHODS: The clinical data of AIDS with GBS, diagnosed by clinical and laboratory methods, were retrospectively analyzed, and literature retrieval analyzed. RESULTS: After treatment by immunoglobulin and antiviral. The patient's peripheral nerve injury recovered, and the number of HIV decreased. CONCLUSION: Immunoglobulin has a therapeutic effect for HIV infection related GBS, and beneficial to antiviral treatment.

[Clinical analysis in viral encephalitis patients accompanying generalized tonic clonic seizure].

OBJECTIVE: To summarize the value of clinical features, CSF, imaging and EEG in diagnosing viral encephalitis accompanying generalized tonic clonic seizure (GTCS). METHODS: The clinical, imaging and EEG characteristic of 30 patients with viral encephalitis accompanying GTCS were retrospectively analyzed. RESULTS: Of the 30 cases with viral encephalitis, 21 cases GTCS attacked (70%) within 14 days, 9 cases had GTCS (30%) in 15-28 days. 27 cases CSF were abnormal with the pressure, cell number, protein. The incidence of positive pathogenicity was 12/16; 19 cases MRI had abnormal signal. All the patients had abnormal EEG during the disease. CONCLUSION: The clinical features, CSF, imaging and EEG were all important in diagnosing and estimate of viral encephalitis accompanying GTCS.

[Minimal residual disease with wt1 gene expression blocked by wt1 antisense oligonucleotides in vitro].

The aim of this study was to investigate the expression of wt1 gene and the changes of gene expression in minimal residual disease (MRD) models (K562, HL-60 cell lines) and acute leukemia (AL) patients through inhibiting the expression of wt1 gene by antisense oligonucleotides (ASO). The bone marrow (BM) of 56 AL patients with complete remission (CR) was collected, then the BM samples with positive expression of wt1 gene were screened by RT-PCR. The cells of MRD model and screened wt1 gene positive samples were cultured and treated by ASO, then the changes of wt1 gene expression were detected. The results indicated that the sensitivity of wt1 gene was 10(-3)-10(-4), and the positive rate of BM wt1 gene expression in 56 AL patients with CR was 16%. After BM of 9 AL CR patients with MRD and MRD model (K562, HL-60 cells) expressing wt1 gene were treated by ASO, it was found that the wt1 expression in ASO group was blocked, while wt1 gene could be still detected in both sense oligonucleotides (SO) and control groups. It is concluded that ASO can obstruct the expression of wt1 gene on the residual leukemia cells in vitro.