Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction(GXB)in improving atherosclerosis(AS)in mice by regulating the gut microbiota(GM)and its metabolites.Methods Thirty-two male ApoE-/-mice were divided randomly into a Blank group,Model group,atorvastatin(Ato)group,and GXB group(n=8 mice per group).AS was established in all mice,except the Blank group,and the respective treatments were administered by gavage.Aortic plaques were detected by Oil red O staining and pathological changes in aortic tissue were detected by hematoxylin and eosin staining.The GM was analyzed using 16S rRNA gene sequencing technology,and mouse GM metabolites,including trimethylamine oxide(TMAO),short-chain fatty acids(SCFA),and serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)were determined.Results Compared with the Blank group,mice in the Model and Ato groups showed an increase in AS plaque area(P＜0.05).Serum levels of TG,TC,and LDL-C were increased(P＜0.001)while levels of HDL-C and NO were decreased(P＜0.01,P＜0.001)in the Model group compared with the Blank group.The plaque area was decreased(P＜0.05),serum levels of TG,TC,and LDL-C were decreased(P＜0.001),and NO levels were increased(P＜0.01)in the Ato and GXB groups,while HDL-C levels were increased in the GXB group(P＜0.05)compared with the Model group.Plaque area was decreased(P＜0.05)and the NO level was increased(P＜0.01)in the GXB group compared with the Ato group.A total of 6345 characteristic sequences were obtained from 16S rRNA analysis.α-Diversity analysis indicated that GXB reduced the richness of the GM in AS mice(P＜0.001)and improved its uniformity(P＜0.05).β-Diversity analysis suggested that the microbial community structure in the GXB group was similar to that in the Blank group.The abundance of microbial communities differed among the groups at the phylum and genus levels.At the phylum level,the abundance of Proteobacteria was increased(P＜0.01)in AS mice,while GXB intervention reduced the abundance of Proteobacteria(P＜0.01)and increased the abundance of Verrucomimicrobiota(P＜0.05).At the genus level,GXB effectively increased the abundance of Akkermansia(P＜0.05).SCFAs were significantly increased(P＜0.01)and TMAO levels were significantly decreased(P＜0.01)in the GXB group compared with the Model group.Conclusions GXB can regulate the intestinal flora and intestinal flora metabolites SCFA and TMAO to improve AS.Akkermansia may be a key bacterial genus of the gut microbiota through which GXB may improve AS.

Objective:This study aimed to assess the infection status of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in healthy populations in China over the past decade and analyze the differences in CMV and EBV infection and related risk factors in healthy populations before and after the lifting of coronavirus disease 2019 (COVID-19) pandemic control measures.Methods:This study retrospectively analyzes the CMV and EBV infection status of 8 827 healthy donors who underwent prehematopoietic stem cell transplantation screening at Peking University People's Hospital from January 2014 to December 2023. Logistic regression analysis was conducted to determine the risk factors for CMV and EBV infection.Results:The CMV and EBV IgG positivity rates were 94.52% and 95.40% among the healthy donors, respectively, with no significant differences before and after the lifting of pandemic control measures (all P value>0.05). However, IgG antibody titers increased [CMV: (100.44±36.50) U/ml vs (109.98±36.31) U/ml, P<0.001; EBV: (281.57±226.79) U/ml vs (361.08±268.58) U/ml, P<0.001] after lifting the COVID-19 restrictions. However, the CMV IgM positivity rate remained unchanged. The EBV IgM positivity rate significantly increased after lifting measures (2.77% vs 6.29%, P<0.001), reaching 8.10% within 3 months. Further analysis of the factors affecting EBV IgM positivity revealed that gender ( OR=1.479, 95% CI 1.169-1.872, P=0.001), age[compared with the group younger than 18 years, the 18-50-year age group ( OR=0.584, 95% CI 0.421-0.820, P=0.002), the >50-year age group ( OR=0.389, 95% CI 0.248-0.610, P<0.001) ], and the lifting of COVID-19 restrictions ( OR=2.360, 95% CI 1.287-3.047, P<0.001) were independent factors influencing EBV IgM positivity in the general population. The EBV IgM positivity rate in individuals under 18 years old was not affected by gender or the lifting of COVID-19 restrictions when stratified by age group. Both genders ( OR=1.499, 95% CI 1.138 - 1.975, P=0.004) and the lifting of COVID-19 restrictions ( OR=2.608, 95% CI 1.940-3.507, P<0.001) were independent factors affecting EBV IgM positivity in the 18-50-year age group. The lifting of COVID-19 restrictions ( OR=2.222, 95% CI 1.101-4.484, P=0.026) was the sole independent factor affecting EBV IgM positivity in individuals over 50 years old. Conclusions:Previous infection rates of CMV and EBV are high in healthy populations in China, which increase with age. COVID-19 infection may increase EBV reactivation rates in healthy individuals, with a more pronounced effect on those aged >18 years.

Objective:This study aimed to assess the infection status of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in healthy populations in China over the past decade and analyze the differences in CMV and EBV infection and related risk factors in healthy populations before and after the lifting of coronavirus disease 2019 (COVID-19) pandemic control measures.Methods:This study retrospectively analyzes the CMV and EBV infection status of 8 827 healthy donors who underwent prehematopoietic stem cell transplantation screening at Peking University People's Hospital from January 2014 to December 2023. Logistic regression analysis was conducted to determine the risk factors for CMV and EBV infection.Results:The CMV and EBV IgG positivity rates were 94.52% and 95.40% among the healthy donors, respectively, with no significant differences before and after the lifting of pandemic control measures (all P value>0.05). However, IgG antibody titers increased [CMV: (100.44±36.50) U/ml vs (109.98±36.31) U/ml, P<0.001; EBV: (281.57±226.79) U/ml vs (361.08±268.58) U/ml, P<0.001] after lifting the COVID-19 restrictions. However, the CMV IgM positivity rate remained unchanged. The EBV IgM positivity rate significantly increased after lifting measures (2.77% vs 6.29%, P<0.001), reaching 8.10% within 3 months. Further analysis of the factors affecting EBV IgM positivity revealed that gender ( OR=1.479, 95% CI 1.169-1.872, P=0.001), age[compared with the group younger than 18 years, the 18-50-year age group ( OR=0.584, 95% CI 0.421-0.820, P=0.002), the >50-year age group ( OR=0.389, 95% CI 0.248-0.610, P<0.001) ], and the lifting of COVID-19 restrictions ( OR=2.360, 95% CI 1.287-3.047, P<0.001) were independent factors influencing EBV IgM positivity in the general population. The EBV IgM positivity rate in individuals under 18 years old was not affected by gender or the lifting of COVID-19 restrictions when stratified by age group. Both genders ( OR=1.499, 95% CI 1.138 - 1.975, P=0.004) and the lifting of COVID-19 restrictions ( OR=2.608, 95% CI 1.940-3.507, P<0.001) were independent factors affecting EBV IgM positivity in the 18-50-year age group. The lifting of COVID-19 restrictions ( OR=2.222, 95% CI 1.101-4.484, P=0.026) was the sole independent factor affecting EBV IgM positivity in individuals over 50 years old. Conclusions:Previous infection rates of CMV and EBV are high in healthy populations in China, which increase with age. COVID-19 infection may increase EBV reactivation rates in healthy individuals, with a more pronounced effect on those aged >18 years.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K⁺ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

OBJECTIVETo compare the short-term efficacy and treatment-related adverse reaction between preoperative three dimensional conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) concurrently combined with chemotherapy in the treatment of locally advanced rectal carcinoma (LARC).

METHODSClinical data of 334 patients with LARC undergoing preoperative 3D-CRT(172 cases) or VMAT(162 cases) with concurrent Xelox chemotherapy (main protocol: capecitabine plus oxaliplatin) and surgery in Sun Yat-sen University Cancer Center from May 2007 to April 2013 were retrospectively analyzed. The total radiation dose of VMAT group was: 50 Gy/2.0 Gy per fraction ×23 fractions for planning target volume 1(PTV1) and 46 Gy/1.84 Gy per fraction ×25 fractions for PTV2; the total radiation dose of 3D-CRT group was: 46 Gy/2.0 Gy per fraction ×23 fractions for PTV. The treatment-related adverse reaction of both groups during chemoradiotherapy was measured according to the criteria of Common Terminology Criteria for Adverse Events v3.0 (CTCAE 3.0). Rate of adverse reaction and short-term efficacy between 3D-CRT and VMAT group were compared, in terms of radiotherapy break, hematological and non-hematological toxicity, average duration of surgery and perioperative hospitalization, intraoperative blood loss, surgical procedures, R0 excision, sphincter preservation, postoperative complications, pathological complete response (pCR), and postoperative pathological staging.

RESULTSThere were no significant differences in baseline clinical parameters between 3D-CRT and VMAT group (all P>0.05), except for the distance from lower tumor margin to anal verge (P=0.009). The median radiation dose for all the patients was 46 (45 to 70) Gy. There was no significant difference in the rate of radiotherapy cessation between 3D-CRT and VMAT group [1.7%(3/172) vs. 1.2%(2/162), P=1.000]. During concurrent chemotherapy, incidences of grade 2 to 3 hematological toxicities, grade 2 diarrhea, and grade 3 non-hematological toxicities were not significantly different(all P>0.05), while in grade 2 non-hematological toxicities, ratio of radiodermatitis and hand-foot syndrome was higher in VMAT group as compared to 3D-CRT group [25.9%(42/162) vs. 10.5%(18/172), P=0.000; 3.7%(6/162) vs. 0, P=0.012]. There was no grade 4 adverse event in both groups. Surgical procedure, average duration of surgery, R0 excision, anus preservation, postoperative complications, pCR, and postoperative pathological staging were not significantly different(all P>0.05). As compared to 3D-CRT group, VMAT group had less intraoperative blood loss [(114.6±100) ml vs. (169±143.9) ml, P<0.001] and shorter perioperative hospitalization [16(8 to 84) d vs. 20(10 to 47) d, P<0.001]. There was no death case in two groups within 30 days after operation.

CONCLUSIONSCompared with 3D-CRT technique, preoperative VMAT technique can not significantly reduce the incidence of treatment-related adverse reaction and improve the short-term efficacy in the treatment of LARC.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Middle Aged ; Organoplatinum Compounds ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Rectal Neoplasms ; radiotherapy ; Retrospective Studies

Objective To study the inhibitory effect of knocking down miR-30a-5p on the U87 human glioma xenograft growth and its possible mechanism.Methods Nude mice bearing subcutaneous U87 human glioblastoma were established and separated into three groups (eight for each group) by randomized digital table method,including control group,scr-ODN treated group and AS-miR-30a-5p treated group.After relevant subcutaneous injection treatment,tumor size was measured every other day until the observation period ended.Researchers executed the animals after the treatment,stripped tumor tissues and extracted RNA and protein.Real-time PCR was conducted to detect the expression of miR-30a-5p.The histopathological characteristics and proliferation and apoptosis biological characters (including SEPT7,PCNA,cyclin D1,MMP-2,apoptosis related factor P53,bcl-2 and caspase3) were evaluated by HE and immunohistochemical staining,Westem blot analysis respectively,and the cell apoptosis was detected by TUNEL method.Results In AS-miR-30a-5p treated group,the tumor growth was delayed and the final tumor volume was smaller than that in the control and scr-ODN treated group (F =7.167,P ＜0.05),and the expression of miR-30a-5p was knocked down.The expression of PCNA,cyclin D1 were significantly downregulated while P53,SEPT7 and caspase3 up-regulated.Apoptotic index was increased significantly.Conclusion As-miR-30a-5p suppresses the growth of U87 human gliomas xenografts significantly.Malignant phenotype of tumors are reversed to a considerable degree.Therefore,miR-30a-5p can be a candidate for targeted therapy of human glioma.

The miR-17-92 cluster,consisting of six individual microRNAs,including miR-17,miR-20a,miR-18a,miR-19a,miR-19b and miR-92a-1,is a kind of typical oncogenic polycistron microRNA.MiR-19 (containing miR-19a and miR-19b),as the key oncogenic component in miR-17-92 cluster,is overexpressed in human cancers including lymphomas,leukaemia,lung cancer,breast cancer and multiple myeloma,and has been one of research focus in recent years.It is found that miR-19 promotes tumor growth,invasion and metastasis through negative regulation of target genes such as PTEN,PP2A,Bim,SOCS1,and is correlated strongly with PI3K-AKT-mTOR pathway.MiR-19 plays an important role in tumor genesis and development.

Objective To investigate the irfluence of PET/CT positioning on the effect of late-course accelerated hyperfractionated and three-dimensional conformal radiotherapy for stage Ⅲ lung squamous cell carcinoma.Methods 79 stage Ⅲ lung squarnous cell carcinoma patients were enrolled and divided into PET/CT group(n =37 cases,PET/CT positioning) and general CT group (n =42 cases,general CT positioning) according to the way of positioning.The conventional fractionated 3 DCRT( about 40 Gy) was used in previous 2/3 time and hyperfractionated( about 1.5 Gy) was used in later 1/3 time.Both groups used chemotherapy as adjuvant therapy.Full course of the treatment was a month or so.And the clinical efficacy and a variety of adverse reactions of the two groups was observed.Results The total rate of remission in PET/CT group were 73.0％,and 71.4％ in general CT group,and there was no significant difference in the two groups (x2 =1.347,P ＞ 0.05 ).The major radiation injury were radioactive pulmonary injury and tracheal damage,incidence rates were 56.8％and 57.1％ in acute stage,and there was no significant difference in the two groups( x2 =2.178,P ＞ 0.05 ) ; but in late stage 69.0％ in general CT group was significantly higher than 62.2％ in PET/CT group(x2 =4.142,P ＜0.05).Ater followed-up 1 year,the recurrence rate of hillar and mediastinal lymph node in PET/CT group was 43.7％,lower than that of the general CT group( 59.4％ ) ( x2 =4.732,P ＜ 0.05 ).Conclusion PET/CT positioning in late-course accelerated hyperfractionated and three-dimensional conformal radiotherapy for stage Ⅲ lung squamous cell carcinoma could reduce late stage radioactive pulmonary injury and tracheal damage,lower the recurrence rate of hillar and mediastinal lymph node.

BACKGROUNDBrain metastasis has become one of the most important factors of the failure of treatment of locally advanced non-small cell lung cancer (LANSCLC). There is no conclusion whether NSCLC patients should receive prophylactic cranial irradiation (PCI) or not. The aim of this study is to analyze the risk factors of brain metastasis of LANSCLC after surgery to find out the sign of PCI for LANSCLC.

METHODSA total of 223 patients with stage III NSCLC who received surgical resection were retrospectively analyzed. The risk factors of brain metastasis were determined to set up a mathematic model for brain metastasis.

RESULTSThe median survival time after surgery was 28.0 months. The 1-, 2- and 3-year survival rate was 84.3%, 56.9% and 44.8% respectively. The incidence of brain metastasis was 38.1% (85/223). Patients with extensive mediastinal lymph node metastasis, more node metastasis and non-squamous carcinoma showed significantly higher incidence of brain metastasis than those with limited mediastinal lymph node metastasis, fewer positive mediastinal lymph nodes and squamous carcinoma (P=0.000, P=0.000, P=0.013). The mathematic model of brain metastasis was: logit(P)=8.215-0.903×NPN-0.872×RT-0.714×HG-1.893×LE-0.948×HS-1.034×PC (NPN=No. of positive nodes, RT=resection type, HG=histology, LE=location and extent of mediastinal lymph node metastasis, HS=histologic stage, PC=postoperative chemotherapy). P≥0.44 meant high risk for brain metastasis.

CONCLUSIONSHigh risk factors of brain metastasis in LANSCLC patients after complete resection of the cancer include non-squamous carcinoma, extensive and more mediastinal lymph node metastasis. P≥0.44 may be considered a sign of PCI in clinical trial.

OBJECTIVESTo identify predictors of survival following pneumonectomy for non-small cell lung cancer (NSCLC) and provide evidence for the revision of patient selection criteria.

METHODS81 cases of pneumonectomy for NSCLC from January 1990 to May 1996 at our hospital were reviewed retrospectively. There were 65 men (80.2%) and 16 women (19.8%), with a mean age 53.4 +/- 9.4 years (range 20 - 68 years). Predominant histological types included squamous cell carcinoma (54.3%), adenocarcinoma (24.7%), and squamoadenocarcinoma (17.3%). After follow-up for more than 5 years, data were examined using the chi-square test, Kaplan-Meier method, and Cox-mantel test. The possible factors affecting survival were tested with univariate and multivariate analysis.

RESULTSThe 5-year survival of N(0), N(1) and N(2) disease of NSCLC following pneumonectomy was (20.8 +/- 9.9)%, (15.4 +/- 10.0)% and (4.0 +/- 2.8)%, respectively. There was no perioperative death. The operative complications morbidity was 22.2%. Factors adversely affecting survival with univariate analysis included age over 60 years for right pneumonectomy, cardiopulmonary complications, adenocarcinoma, peripheral location, tumor greatest dimension more than 10 cm, chest wall involvement and N(2) disease. Factors adversely affecting survival with multivariate analysis included cardiopulmonary complications, greatest tumor dimension more than 10 cm, chest wall involvement and N(2) disease.

CONCLUSIONSPneumonectomy provides survival benefit with a high operative complications morbidity. Old age (>/= 60 years) for right pneumonectomy, cardiopulmonary complications, adenocarcinoma, and N(2) disease may be negative prognostic factors of long-term survival. Patient selection should be based on cardiopulmonary evaluation and the stage of disease.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; Prognosis ; Retrospective Studies ; Survival Rate