Objective:To investigate the potential causal relationships between gut microbiota composition and the risk of developing various subtypes of breast cancer by using bidirectional two-sample Mendelian randomization(MR).Methods:The research utilized genome-wide association studies(GWAS) data on gut microbiota from the MiBioGen database and GWAS data on breast cancer from the Breast Cancer Association Consortium (BCAC). In this MR study, inverse variance weighted (IVW), weighted median, MR Egger, and MR-PRESSO methods were used. Additionally, reverse MR and stratified analyses were conducted to assess reverse causality and the impact on different subtypes of breast cancer.Results:Adlercreutzia (IVW OR=0.92, 95% CI: 0.87-0.98, P=0.01) and Parabacteroides (IVW OR=0.87, 95% CI: 0.79-0.96, P=0.007) exhibited a statistically significant protective effect on breast cancer. Conversely, Sellimonas (IVW OR=1.05, 95% CI: 1.01-1.09, P=0.01) was significantly associated with an increased risk of breast cancer. Desulfovibrio (IVW OR=0.94, 95% CI: 0.88-1.00, P=0.04) and Ruminococcaceae (UCG013) (IVW OR=0.92, 95% CI: 0.86-0.99, P=0.03) presented suggestive protective effects against breast cancer. Furthermore, stratified analysis revealed that the protective effect of Adlercreutzia against breast cancer persisted in the estrogen receptor(ER)-positive subtypes, while Desulfovibrio persisted in the ER-negative subtypes. Sellimonas was causally associated with the risk of ER-positive subtypes. CACNA1S was identified as the functional gene of Adlercreutzia, and associated with favorable prognosis in breast cancer, while ERBB4 was identified as the functional gene of Sellimonas and associated with poor prognosis in breast cancer. Conclusions:This study identifies the causal relationships between gut microbiota and breast cancer, suggesting a novel target for early clinical intervention and treatment, with potential implications for future functional analysis.

The intestine and liver are closely connected both physiologically and pathologically, forming a so-called gut-liver axis, with the gut microbiota serving as a pivotal link in their bidirectional communication. Gut microbiota dysbiosis and gut-liver axis disruption play a key role in the development and progression of colorectal cancer liver metastasis (CRLM), though the underlying mechanisms have not been clearly elucidated. Certain gut microbiota, such as Escherichia coli and Enterococcus spp., can breach the intestinal barrier and translocate to the liver, promoting the formation of pre-metastatic niche. Fusobacterium nucleatum and Enterococcus faecalis enhance tumor cell invasion/migration, while Parabacteroides spp. suppress anti-tumor immunity in the liver TME. Interventions like fecal microbiota transplantation, dietary modifications, and traditional Chinese medicine have shown potential in clinical and preclinical studies to improve patient outcomes by targeting the gut microbiota, but their long-term efficacy and safety require further investigation. Future research should focus on elucidating the effects of specific bacterial species, metabolites, viruses, and fungi on tumorigenesis. Exploring the potential of gut microbiota-based precision medicine and personalized therapies will improve risk stratification and enable more targeted interventions for CRLM patients.

Objective To assess the impact of freeze-drying and dry heat virus inactivation processes on the activity ofα2-macroglobulin(A2M)derived from human plasma Cohn fraction Ⅳ.Methods A2M derived from human plasma Cohn fraction Ⅳ was prepared and subjected to programmed freeze-drying with dry heat virus inactivation.The lyophilized products were evaluated for their appearance,water content,and validation of the viral inactivation process.The bioactivity of the products before and after lyophilization as well as before and after dry heat inactivation was determined via trypsin inhibition,and the comparisons were studied.Results The appearance of the lyophilized product was fluffy,and the water content was(5.83±0.45)％.The specific activities of the samples before and after lyophilization were(10.199±0.137)and(10.033±0.201)μg/mg,respectively,with no statistically significantdifference between the two groups(P＞0.05).The viral inactivation of the samples was carried out by using dry heat inactivation conditions at 100 ℃ for 30 min.After inactivation,the reduction was ≥5.125 LgTCID50/0.1 mL in Pseudorabies virus(PRV)titers,≥4.500 LgTCID50/0.1 mL in Sindbis virus(SinV)titers,≥6.375 LgTCID50/0.1 mL in encephalomyocarditis virus(EMCV)titers,and≥4.500 LgTCID50/0.1 mL in porcine parvovirus(PPV)titers.The specific activities of the samples before and after dry heat were(9.921±0.292)and(10.091±0.278)μ g/mg,respectively,with no statistically significant difference between the two groups.Conclusion A2M derived from human plasma Cohn fraction Ⅳ,when subjected to freeze-drying followed by dry heat inactivation at 100 ℃ for 30 minutes,can effectively inactivate viruses without altering the biological activity of the product.

α2-Macroglobulin(A2M)is a high-abundance plasma protein with a molecular weight of 720×103,containing 1451 residues and 11 domains,and was isolated and identified for the first time in 1946.The capture and inhibitory effect on proteases is the classical biological function of A2M.However,A2M can also interact with membrane receptors,cytokines,and growth factors,and act as a molecular chaperone to affect extracellular protein homeostasis so that it is involved in a wide range of physiological and pathological processes such as immunity,inflammation,and degeneration.This article reviews the structural characteristics of A2M,the reported molecular targets,the mechanism of action,and its biological effects in the hope of providing a new line of thought for the functional exploration and clinical applications of A2M.

Objective To explore the therapeutic effect and prognostic influencing factors of endovascular therapy for periprocedural acute ischemic stroke with large vessel occlusion(AIS-LVO)after cardiac surgery,and to analyze the pathological characteristics of thrombi leading to LVO.Methods This study retrospectively and consecutively enrolled patients who experienced AIS-LVO during the perioperative period of cardiac surgery at the Cardiovascular Surgery Department of Guangdong Provincial People's Hospital from June 1,2017,to March 31,2024.The patients were divided into a surgical group and a non-surgical group based on whether they received endovascular treatment.The clinical and imaging data of the patients were collected,including gender,age,hypertension,diabetes,history of smoking,low-density lipoprotein cholesterol,cardiac surgical methods(coronary artery bypass grafting,total arch replacement[TRA],cardiac valve replacement,other types of surgery[valve repair,atrial septal repair,ventricular septal repair,heart transplantation]),time from cardiac surgery to AIS onset,location of vascular occlusion(vertebral-basilar artery,right internal carotid artery,left internal carotid artery),National Institutes of Health stroke scale(NIHSS)score at the onset of stroke,time from stroke onset to puncture,stroke etiology(embolism,arterial dissection,atherosclerotic stenosis),and imaging data including Alberta stroke program early CT score(ASPECTS)of the anterior circulation,ASPECTS of the posterior circulation(pc-ASPECTS)and CT angiography,CT perfusion,etc.The thrombus samples were stained with hematoxylin-eosin and martius scarlet blue staining.According to the proportion of red blood cells(RBC)in the thrombus,the thrombi were classified as erythrocyte-rich thrombi(RBC proportion≥70%),mixed thrombi(RBC proportion 31%-69%),and fibrin-rich thrombi(RBC proportion≤30%).At 90d after stroke onset,the modified Rankin scale(mRS)was used for both outpatient and telephone follow-up.The mRS score 0-2 indicated a good prognosis,3-6 indicated a poor prognosis,and 6 points indicated death.Factors with P＜0.1 in univariate Logistic regression and those factors may influence the prognosis according to clinical experience were included and further analyzed with multivariate Logistic regression to analyze the 90 d prognostic influencing factors after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.Results A total of 102 patients who experienced AIS-LVO during the perioperative period of cardiac surgery(68 males,34females,with mean age of[58±14]years)were enrolled in this study,50 were in the non-surgery group and 52 in the surgery group.(1)Significant differences were observed between the surgical and non-surgical group in hypertension(32.7%[17/52]vs.54.0%[27/50],P=0.030),NIHSS score at stroke onset(12.3[12.3,21.8]vs.35.0[18.0,35.0],P＜0.01),vascular occlusion site(P=0.048),cardiac surgery type(P＜0.01),ASPECTS/pc-ASPECTS(9[8,9]vs.4[3,6],P＜0.01),favorable90-day prognosis rate(75.0%[39/52]vs.10.0%[5/50],P＜0.01)and 90-day mortality rate(7.7%[4/52]vs.68.0%[34/50],P＜0.01).Other clinical and imaging data showed no significant differences(all P＞0.05).In the surgery group,86.5%(45/52),7.7%(4/52),and 5.8%(3/52)patients were attributed to embolism,arterial dissection,and atherosclerotic stenosis,respectively.(2)Univariate Logistic regression analysis identified NIHSS score at stroke onset,TRA,endovascular therapy,and ASPECTS/pc-ASPECTS score as prognostic factors affecting the 90-day prognosis after stroke.Set the patient's 90-day prognosis(assign favorable prognosis as 1 and poor prognosis as 0)as dependent variable,incorporate factors with P＜0.1 in the univariate Logistic analysis and location of vascular occlusion in a multivariate Logistic regression analysis.The results showed that high NIHSS score on stroke onset(OR,0.86,95%CI 0.78-0.95,P=0.002)and non endovascular therapy(OR,6.93,95%CI 1.05-45.55,P=0.044)were independent risk factors of poor prognosis 90-day after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.(3)Among 45 cardioembolic patients,thrombus samples from 33 patients were analyzed.The analysis revealed no erythrocyte-rich thrombi,3 mixed thrombi,and 30 fibrin-rich thrombi,with 12having a fibrin proportion exceeding 90%.Conclusion Endovascular therapy improved the prognosis and reduces mortality rate in patients with periprocedural AIS-LVO after cardiac surgery,and thrombi in these patients are predominantly fibrin-rich.

Objective To explore the therapeutic effect and prognostic influencing factors of endovascular therapy for periprocedural acute ischemic stroke with large vessel occlusion(AIS-LVO)after cardiac surgery,and to analyze the pathological characteristics of thrombi leading to LVO.Methods This study retrospectively and consecutively enrolled patients who experienced AIS-LVO during the perioperative period of cardiac surgery at the Cardiovascular Surgery Department of Guangdong Provincial People's Hospital from June 1,2017,to March 31,2024.The patients were divided into a surgical group and a non-surgical group based on whether they received endovascular treatment.The clinical and imaging data of the patients were collected,including gender,age,hypertension,diabetes,history of smoking,low-density lipoprotein cholesterol,cardiac surgical methods(coronary artery bypass grafting,total arch replacement[TRA],cardiac valve replacement,other types of surgery[valve repair,atrial septal repair,ventricular septal repair,heart transplantation]),time from cardiac surgery to AIS onset,location of vascular occlusion(vertebral-basilar artery,right internal carotid artery,left internal carotid artery),National Institutes of Health stroke scale(NIHSS)score at the onset of stroke,time from stroke onset to puncture,stroke etiology(embolism,arterial dissection,atherosclerotic stenosis),and imaging data including Alberta stroke program early CT score(ASPECTS)of the anterior circulation,ASPECTS of the posterior circulation(pc-ASPECTS)and CT angiography,CT perfusion,etc.The thrombus samples were stained with hematoxylin-eosin and martius scarlet blue staining.According to the proportion of red blood cells(RBC)in the thrombus,the thrombi were classified as erythrocyte-rich thrombi(RBC proportion≥70%),mixed thrombi(RBC proportion 31%-69%),and fibrin-rich thrombi(RBC proportion≤30%).At 90d after stroke onset,the modified Rankin scale(mRS)was used for both outpatient and telephone follow-up.The mRS score 0-2 indicated a good prognosis,3-6 indicated a poor prognosis,and 6 points indicated death.Factors with P＜0.1 in univariate Logistic regression and those factors may influence the prognosis according to clinical experience were included and further analyzed with multivariate Logistic regression to analyze the 90 d prognostic influencing factors after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.Results A total of 102 patients who experienced AIS-LVO during the perioperative period of cardiac surgery(68 males,34females,with mean age of[58±14]years)were enrolled in this study,50 were in the non-surgery group and 52 in the surgery group.(1)Significant differences were observed between the surgical and non-surgical group in hypertension(32.7%[17/52]vs.54.0%[27/50],P=0.030),NIHSS score at stroke onset(12.3[12.3,21.8]vs.35.0[18.0,35.0],P＜0.01),vascular occlusion site(P=0.048),cardiac surgery type(P＜0.01),ASPECTS/pc-ASPECTS(9[8,9]vs.4[3,6],P＜0.01),favorable90-day prognosis rate(75.0%[39/52]vs.10.0%[5/50],P＜0.01)and 90-day mortality rate(7.7%[4/52]vs.68.0%[34/50],P＜0.01).Other clinical and imaging data showed no significant differences(all P＞0.05).In the surgery group,86.5%(45/52),7.7%(4/52),and 5.8%(3/52)patients were attributed to embolism,arterial dissection,and atherosclerotic stenosis,respectively.(2)Univariate Logistic regression analysis identified NIHSS score at stroke onset,TRA,endovascular therapy,and ASPECTS/pc-ASPECTS score as prognostic factors affecting the 90-day prognosis after stroke.Set the patient's 90-day prognosis(assign favorable prognosis as 1 and poor prognosis as 0)as dependent variable,incorporate factors with P＜0.1 in the univariate Logistic analysis and location of vascular occlusion in a multivariate Logistic regression analysis.The results showed that high NIHSS score on stroke onset(OR,0.86,95%CI 0.78-0.95,P=0.002)and non endovascular therapy(OR,6.93,95%CI 1.05-45.55,P=0.044)were independent risk factors of poor prognosis 90-day after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.(3)Among 45 cardioembolic patients,thrombus samples from 33 patients were analyzed.The analysis revealed no erythrocyte-rich thrombi,3 mixed thrombi,and 30 fibrin-rich thrombi,with 12having a fibrin proportion exceeding 90%.Conclusion Endovascular therapy improved the prognosis and reduces mortality rate in patients with periprocedural AIS-LVO after cardiac surgery,and thrombi in these patients are predominantly fibrin-rich.

Objective:To investigate the potential causal relationships between gut microbiota composition and the risk of developing various subtypes of breast cancer by using bidirectional two-sample Mendelian randomization(MR).Methods:The research utilized genome-wide association studies(GWAS) data on gut microbiota from the MiBioGen database and GWAS data on breast cancer from the Breast Cancer Association Consortium (BCAC). In this MR study, inverse variance weighted (IVW), weighted median, MR Egger, and MR-PRESSO methods were used. Additionally, reverse MR and stratified analyses were conducted to assess reverse causality and the impact on different subtypes of breast cancer.Results:Adlercreutzia (IVW OR=0.92, 95% CI: 0.87-0.98, P=0.01) and Parabacteroides (IVW OR=0.87, 95% CI: 0.79-0.96, P=0.007) exhibited a statistically significant protective effect on breast cancer. Conversely, Sellimonas (IVW OR=1.05, 95% CI: 1.01-1.09, P=0.01) was significantly associated with an increased risk of breast cancer. Desulfovibrio (IVW OR=0.94, 95% CI: 0.88-1.00, P=0.04) and Ruminococcaceae (UCG013) (IVW OR=0.92, 95% CI: 0.86-0.99, P=0.03) presented suggestive protective effects against breast cancer. Furthermore, stratified analysis revealed that the protective effect of Adlercreutzia against breast cancer persisted in the estrogen receptor(ER)-positive subtypes, while Desulfovibrio persisted in the ER-negative subtypes. Sellimonas was causally associated with the risk of ER-positive subtypes. CACNA1S was identified as the functional gene of Adlercreutzia, and associated with favorable prognosis in breast cancer, while ERBB4 was identified as the functional gene of Sellimonas and associated with poor prognosis in breast cancer. Conclusions:This study identifies the causal relationships between gut microbiota and breast cancer, suggesting a novel target for early clinical intervention and treatment, with potential implications for future functional analysis.

The intestine and liver are closely connected both physiologically and pathologically, forming a so-called gut-liver axis, with the gut microbiota serving as a pivotal link in their bidirectional communication. Gut microbiota dysbiosis and gut-liver axis disruption play a key role in the development and progression of colorectal cancer liver metastasis (CRLM), though the underlying mechanisms have not been clearly elucidated. Certain gut microbiota, such as Escherichia coli and Enterococcus spp., can breach the intestinal barrier and translocate to the liver, promoting the formation of pre-metastatic niche. Fusobacterium nucleatum and Enterococcus faecalis enhance tumor cell invasion/migration, while Parabacteroides spp. suppress anti-tumor immunity in the liver TME. Interventions like fecal microbiota transplantation, dietary modifications, and traditional Chinese medicine have shown potential in clinical and preclinical studies to improve patient outcomes by targeting the gut microbiota, but their long-term efficacy and safety require further investigation. Future research should focus on elucidating the effects of specific bacterial species, metabolites, viruses, and fungi on tumorigenesis. Exploring the potential of gut microbiota-based precision medicine and personalized therapies will improve risk stratification and enable more targeted interventions for CRLM patients.

Objective To investigate the experience of intrauterine device(IUD)removal in patients with cervical cancer after radiotherapy.Methods A total of 23 patients with cervical cancer after radiotherapy underwent abdominal ultrasound guided hysteroscopic removal of IUD in our department from January 2020 to December 2022.For vaginal and/or cervical adhesions,blunt separation of adhesions was performed by using hysteroscope head or curved forceps under abdominal ultrasound guidance.If it was difficult to separate the adhesions for hysteroscope head entering the uterine cavity,a probe was inserted into the uterine cavity under ultrasound guidance,and the cervical canal was gradually expanded to 6-caliber dilation rod.Then the hysteroscope was inserted again into the uterine cavity.For obvious cervical atrophy that was tough in which cervical forceps could not be used to clamp the cervix,a 1-0 absorbable suture line was used to suture the anterior and/or posterior lips of the atrophied cervix at the top of the vagina,with an assistant firmly pulling and fixing the cervix.Results There were 4 cases of vaginal partial adhesions and cervical contracture,10 cases of cervical contracture,and remaining 9 cases having no vaginal adhesions and cervical contracture.Under hysteroscopy,there were 3 cases of cervical adhesions,2 cases of endometrial polyps,1 case of submucosal uterine fibroids,2 cases of uterine abscess,2 cases of incarcerated IUD,and remaining 13 cases having normal uterine cavity morphology.All the 23 cases of IUD were successfully removed by using abdominal ultrasound guided hysteroscopy(circular shaped in 12 cases,uterine shaped in 6 cases,V-shaped in 2 cases,Y-shaped in 1 case,T-shaped in 1 case,and umbrella shaped in 1 case).The surgical time was(19.2±10.9)min,and there were no complications such as false passage formation,uterine perforation,organ damage,massive vaginal bleeding,transurethral resection of the prostate syndrome,infection,embolism,or shock.The 23 cases were followed up for 2-24 months postoperatively,with a median of 12 months.One case continued concurrent radiotherapy and chemotherapy,3 cases continued post-loading radiotherapy,1 case continued chemotherapy,and 2 cases received targeted treatment(distant metastasis).The remaining 16 cases recovered well in regular reviews without complications such as abdominal pain,fever,or vaginal bleeding.Conclusions If the size and location of the cancer lesion do not affect the removal of IUD after radiotherapy for cervical cancer,it should be removed as soon as possible.The application of abdominal ultrasound guided hysteroscopy in IUD removal in patients with cervical cancer after radiotherapy is safe and feasible to a certain extent.

Objective     To analyze the clinical efficacy and survival outcome of totally thoracoscopic redo mitral valve replacement and evaluate its efficiency and safety. Methods     The clinical data of patients with totally thoracoscopic redo mitral valve replacement in Guangdong Provincial People’s Hospital between 2013 and 2019 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to determine the risk factors for postoperative death. Results     There were 48 patients including 29 females and 19 males with a median age of 53 (44, 66) years. All the procedures were performed successfully with no conversion to median sternotomy. A total of 15, 10 and 23 patients received surgeries under non-beating heart, beating heart and ventricular fibrillation, respectively. The in-hospital mortality rate was 6.25% (3/48), and the incidence of early postoperative complications was 18.75% (9/48). Thirty-five (72.92%) patients had their tracheal intubation removed within 24 hours after the operation. The 1- and 6-year survival rates were 89.50% (95%CI 81.30%-98.70%) and 82.90%(95%CI 71.50%-96.20%), respectively. Age>65 years was an independent risk factor for postoperative death (P=0.04). Conclusion     Totally thoracoscopic redo mitral valve replacement is safe and reliable, with advantages of rapid recovery, reducing blood transfusion rate, reducing postoperative complications and acceptable long-term survival rate. It is worthy of being widely popularized in the clinic.