Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

Objective:To explore the role of P2Y1Receptor(P2Y1R)-activated astrocytes in delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Methods:SD rats were randomly divided into Control,DEACMP,DEACMP+DMSO,and DEACMP+MRS2179 groups.The latter three groups were exposed to static CO inhalation to establish the DEACMP model,while the Control group inhaled air.The rats in DEACMP+MRS2179 group were injec-ted with 3 μl of P2Y1R antagonist MRS2179 with concentration of 1 mmol/L via lateral ventricle,while the DEACMP+DMSO group an equal volume of DMSO.At 14 and 21 day after DEACMP model establishment,the spatial learning and memory ability of rats were observed by Morris water maze,the injury of pyramidal cells in the CA1 area of the hippo-campus was observed by HE staining.The protein levels of glial fibrillary acidic protein(GFAP)and P2Y1receptor(P2Y1R)in the hippocampal tissues of rats were detected by immunohistochemistry and Western blot.The expressions of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the hippocampal tissues of rats were detected by ELISA.Results:In comparison with the Control group,the escape latency was found to be signifi-cantly prolonged in the DEACMP group and the DEACMP+DMSO group.Furthermore,the expression levels of GFAP,P2Y1R,IL-1β,IL-6,and TNF-α were significantly increased in the pyramidal cells of the CA1 region of the hippocam-pal tissue(P<0.05).In contrast,the escape latency was significantly reduced and the expression levels of GFAP,P2Y1R,IL-1β,IL-6,and TNF-α were significantly decreased in the DEACMP+MRS2179 group when compared with the DEACMP+DMSO group(P<0.05).Conclusion:P2Y1R activates astrocytes to release inflammatory factors lead-ing to the onset of cognitive impairment in DEACMP,and inhibition of P2Y1R reduces the expression of inflammatory factors and thus improves cognitive function in DEACMP.

Objective:To explore the role of P2Y1Receptor(P2Y1R)-activated astrocytes in delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Methods:SD rats were randomly divided into Control,DEACMP,DEACMP+DMSO,and DEACMP+MRS2179 groups.The latter three groups were exposed to static CO inhalation to establish the DEACMP model,while the Control group inhaled air.The rats in DEACMP+MRS2179 group were injec-ted with 3 μl of P2Y1R antagonist MRS2179 with concentration of 1 mmol/L via lateral ventricle,while the DEACMP+DMSO group an equal volume of DMSO.At 14 and 21 day after DEACMP model establishment,the spatial learning and memory ability of rats were observed by Morris water maze,the injury of pyramidal cells in the CA1 area of the hippo-campus was observed by HE staining.The protein levels of glial fibrillary acidic protein(GFAP)and P2Y1receptor(P2Y1R)in the hippocampal tissues of rats were detected by immunohistochemistry and Western blot.The expressions of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the hippocampal tissues of rats were detected by ELISA.Results:In comparison with the Control group,the escape latency was found to be signifi-cantly prolonged in the DEACMP group and the DEACMP+DMSO group.Furthermore,the expression levels of GFAP,P2Y1R,IL-1β,IL-6,and TNF-α were significantly increased in the pyramidal cells of the CA1 region of the hippocam-pal tissue(P<0.05).In contrast,the escape latency was significantly reduced and the expression levels of GFAP,P2Y1R,IL-1β,IL-6,and TNF-α were significantly decreased in the DEACMP+MRS2179 group when compared with the DEACMP+DMSO group(P<0.05).Conclusion:P2Y1R activates astrocytes to release inflammatory factors lead-ing to the onset of cognitive impairment in DEACMP,and inhibition of P2Y1R reduces the expression of inflammatory factors and thus improves cognitive function in DEACMP.

Objective:This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy.Methods:This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression.Results:This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation.Conclusion:Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.

Objective:This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy.Methods:This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression.Results:This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation.Conclusion:Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.

Background::Post-operative acute kidney injury (AKI) is one of the most common and serious complications after major surgery and is significantly associated with increased risks of morbidity and mortality. This meta-analysis was conducted to evaluate the effects of perioperative dexmedetomidine (Dex) administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery.Methods::The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for studies comparing the effects of Dex vs. placebo on kidney function after non-cardiac surgery, and a pooled fixed-effect meta-analysis of the included studies was performed. The primary outcome was the occurence of post-operative AKI. The secondary outcomes included the occurence of intra-operative hypotension and bradycardia, intensive care unit (ICU) admission, duration of ICU stay, and hospital length of stay (LOS). Results::Six studies, including four randomized controlled trials (RCTs) and two observational studies, with a total of 2586 patients were selected. Compared with placebo, Dex administration could not reduce the odds of post-operative AKI (odds ratio [OR], 0.44; 95% confidence interval (CI), 0.18-1.06; P= 0.07; I2= 0.00%, P= 0.72) in RCTs, but it showed a significant renoprotective effect (OR, 0.67; 95% CI, 0.48-0.95; P = 0.02; I2 = 0.00%, P = 0.36) in observational studies. Besides, Dex administration significantly increased the odds of intra-operative bradycardia and shortened the duration of ICU stay. However, there was no significant difference in the odds of intra-operative hypotension, ICU admission, and hospital LOS. Conclusions::This meta-analysis suggests that perioperative Dex administration does not reduce the risk of AKI after non-cardiac surgery. However, the quality of evidence for this result is low due to imprecision and inconsistent types of non-cardiac operations. Thus, large and high-quality RCTs are needed to verify the real effects of perioperative Dex administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery.

Uterus didelphys occurs in ~0.4% of females and is found in ~11%-20% of all uterus defects. It is a risk factor for cervical insufficiency, consequently contributing to late miscarriage or preterm birth. Thus far, only two prior cases of uterus didelphys accompanied by cervical insufficiency treated through laparoscopic cervical cerclage have been reported; however, livebirth only occurred in one hemiuterus. Herein, we report a case of uterus didelphys in a patient diagnosed with cervical insufficiency. Following the placement of a modified laparoscopic cervical cerclage, the patient had two successful livebirths through both hemiuteruses, respectively, with longer gestation age (ie, >36 weeks). The aim of this case report was to provide useful information for clinical practitioners to make better decisions on the management of cervical insufficiency in patients with uterus didelphys, and identify obstetric complications that clinicians should pay attention to during pregnancy.

Uterus didelphys occurs in ~0.4% of females and is found in ~11%-20% of all uterus defects. It is a risk factor for cervical insufficiency, consequently contributing to late miscarriage or preterm birth. Thus far, only two prior cases of uterus didelphys accompanied by cervical insufficiency treated through laparoscopic cervical cerclage have been reported; however, livebirth only occurred in one hemiuterus. Herein, we report a case of uterus didelphys in a patient diagnosed with cervical insufficiency. Following the placement of a modified laparoscopic cervical cerclage, the patient had two successful livebirths through both hemiuteruses, respectively, with longer gestation age (ie, >36 weeks). The aim of this case report was to provide useful information for clinical practitioners to make better decisions on the management of cervical insufficiency in patients with uterus didelphys, and identify obstetric complications that clinicians should pay attention to during pregnancy.

Objective:To investigate the effect of fibrinogenase combined with aspirin on blood viscosity and clinical efficacy in patients with acute cerebral infarction.Methods:Senventy patients with mild to moderate acute cerebral infarction from October 2016 to June 2020 were collected from the Third People′s Hospital of Dalian. Patients were divided into control group and treatment group according to the random number table method, with 35 cases in each group. The control group was given oral aspirin plus an intravenous drip of normal saline equal to the treatment group, while the treatment group was given aspirin plus fibrinogenase by intravenous drip. Both groups were given symptomatic treatment such as management of blood glucose, blood pressure, arteriosclerosis plaque stabilization and improvement of circulation for 10 d. Blood viscosity and neurological deficit score were measured before and after treatment.Results:Compared with baseline values, WBV showed a slight decrease in all shear rates in the control group after treatment compared with that before treatment, but the difference was not statistically significant ( P>0.05). In the treatment group, all shear rates decreased compared with that before treatment ( P<0.05), and the effect of WBV was significant compared with that of the control group ( P<0.05). The improvement of neurological function in the treatment group was better than that in the control group. The significant efficiency and the total effective rate in the treatment group were significantly higher than those in the control group: 34.3% (12/35) vs. 25.7% (9/35), 88.6% (31/35) vs.71.4% (25/35). Conclusions:Fibrinogenase combined with aspirin in the treatment of acute cerebral infarction patients can safely and effectively reduce blood viscosity and improve clinical symptoms.