Objective:To screen key differentially expressed genes(DEGs)in dead mice with sepsis by spleen high-through-put sequencing combined with bioinformatics.Methods:①A mouse sepsis model was set up by intraperitoneal injection of lipopolysac-charide(LPS),a 7-day survival curve of mice was drawn,and the modeling doses of survival group and death group were screened out.②Expressions of TNF-α,IL-1β,IL-6 and IL-10 in peripheral blood of mice in control group,survival group and death group were verified by ELISA.③High-throughput sequencing was conducted on spleens of survival group and death group,and the key genes were screened by bioinformatics analysis of DEGs.④Expressions of key genes and proteins were detected by RT-PCR and Western blot.Results:①LPS dosage in survival group was 15 mg/kg(with a mortality of 30%),and LPS dosage in death group was 30 mg/kg(with a mortality of 80%).②Expression levels of IL-6,TNF-α and IL-1β in sepsis mice were significantly higher than those of control group,while expression level of IL-10 was decreased(P<0.05).Comparison of sepsis model groups showed that levels of pro-inflammatory factors in death group were higher than those in survival group,while level of IL-10 was lower than that in survival group(P<0.05).③A total of 2999 DEGs in survival group and death group were screened out by bioinformatics,among which 1185 genes were up-regulated and 1814 genes were down-regulated.Top 5 DEGs enrichment pathways were screened out:"hematopoietic cell lineage""primary immunodeficiency""African trypanosomiasis""leishmaniasis"and"B-cell receptor signaling pathway".Ifit1,Ifit3 and Mx1 were three key genes that were screened out.④Compared with survival group,expressions of genes and proteins of Ifit1,Ifit3 and Mx1 were down-regulated in spleen tissues of the death group(P<0.05).Conclusion:By high-throughput sequencing and bioinformatics,Ifit1,Ifit3 and Mx1 are screened out as key genes related to the death outcome of sepsis,which probably influence the outcome of sepsis through the immune mechanism related to virus infection.

Objective To explore the value of multi-parameter spectral CT for differentiating grade G2-3 pancreatic neuroendocrine tumor(pNET)and pancreatic neuroendocrine carcinoma(pNEC).Methods Preoperative double-layer detector spectral CT(DLCT)data of 35 patients with pNET(pNET group,including 25 cases of G2 grade and 10 cases of G3 grade)and 17 patients with pNEC(pNEC group)were retrospectively analyzed.Conventional CT and spectral CT parameters were compared between groups,and those being significant different between groups according to univariate analysis were respectively incorporated into multivariate logistic regression to select the independent predictors for identifying grade G2-3 pNET and pNEC.Conventional CT model and spectral CT model were constructed,and the combined model was constructed based on the two.The efficacy of each model for distinguishing grade G2-3 pNET and pNEC was evaluated.Results CT values of lesions during venous phase(OR=0.939,P=0.025)and vascular invasion(OR=5.049,P=0.027)shown on conventional CT were both independent predictors,and conventional CT model was constructed,its area under the curve(AUC)for distinguishing grade G2-3 pNET and pNEC was 0.808.Normalized iodine concentration during venous phase(OR=0.603)and normalized effective atomic number during venous phase(OR=0.847)on spectral CT were both independent predictors(both P＜0.05),and spectral CT model was constructed.The AUC of spectral CT model was 0.894,higher than that of conventional CT model(Z=2.127,P=0.033).The AUC of combined model was 0.924,higher than that of conventional CT model(Z=2.302,P=0.021)but not significantly different with that of spectral CT model(Z=0.827,P=0.408).Conclusion Multi-parameter spectral CT could effectively differentiate grade G2-G3 grade pNET and pNEC.

Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
Animals ; Rats ; Bacteremia/metabolism* ; Blood-Brain Barrier/microbiology* ; Caveolin 1/metabolism* ; Gingipain Cysteine Endopeptidases/metabolism* ; Permeability ; Porphyromonas gingivalis/pathogenicity* ; Transcytosis ; Virulence Factors/metabolism*

Objective:To investigate the drug-resistant mutations of human immunodeficiency virus-1 (HIV-1) in patients who received highly active antiretroviral therapy (HAART) from 2014 to 2018.Methods:A total of 880 patients with HIV-1 infection who had been treated with HAART for more than six months in Chongqing Infectious Disease Medical Center from May 2014 to December 2018 were enrolled. Plasma samples were collected, and one-step reverse transcription-polymerase chain reaction (PCR) and nested PCR were taken to amplify protease and reverse transcriptase regions of HIV-1 pol gene region. The obtained amplified nucleotide sequences were compared with the drug resistance database for antiviral drug resistance analysis. Viral genotyping tool software was used to analyze HIV-1 subtype distribution. The categorical variables were compared using chi-square test. Results:Among 880 patients, the plasma HIV-1 viral load was (4.12±0.63) lg copies/mL, the CD4 + T lymphocyte count was (251±124)/μL, and the median duration of antiviral therapy was 26 months. In the subtypes analysis, the circulating recombinant form (CRF) 01-AE subtype was the largest proportion of HIV-1 subtypes, accounting for 38.9%(342/880), and the CRF07-BC subtype accounted for 28.5%(251/880), B+ C subtypes accounted for 16.2%(143/880). Drug-resistant mutations were detected in 534 patients, with a total drug resistance rate of 60.7%. The drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) were 51.0%(449/880), 58.6%(516/880) and 1.7%(15/880), respectively. The drug resistances to lamivudine, emtricitabine, efavirenz, and nevirapine were serious, and the medium/high resistance rates were 46.8%(412/880), 46.8%(412/880), 51.3%(451/880), and 53.6%(472/880), respectively, while those to zidomidudine (6.0%, 53/880), etravirin (9.0%, 451/880) and PI were not serious. M184IV (47.3%), K65R (22.2%) and K70RE (12.6%) were the most frequent mutations for NRTI. K103NS (25.1%), V106A (19.7%) and V179DE (14.4%) were the most frequent mutations for NNRTI. The most common drug-resistant mutations for PI were L10FIV (7.4%) and A71IVT (6.5%). The drug resistance rate of CRF01-AE subtype (69.3%, 237/342) was higher than those of CRF07-BC subtype (49.8%, 125/251) and B+ C subtype (51.0%, 73/143), the differences were statistically significant ( χ2=22.6 and 14.6, respectively, both P<0.05). Conclusions:The incidence of drug resistance is high among HIV-1 infected patients after six-month HAART treatment in Chongqing City. The drug resistance to NNRTI is the most common, followed by NRTI, while PI is less resistant. Drug resistance is the main reason for the virological breakthrough in HIV-1 infected patients.

Surgical resection is the best method for patients with colorectal cancer liver metastases. However, tumor recurrence rate is still high after surgery. Preoperative chemotherapy can help shrink the tumor, test biological behavior, and reduce recurrence rate; but it may also cause liver injury and delay surgery. There is still controversy whether neoadjuvant chemotherapy should be performed and how to select patients from chemotherapy before surgery. Thus, in this article, combined the research progress and the clinical experience of author's center, we discuss this issue in 4 aspects: the development of neoadjuvant chemotherapy; the indications and guideline recommendation for neoadjuvant chemotherapy; the selection of neoadjuvant chemotherapy regimens; common problems in neoadjuvant chemotherapy.

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult

When faced with a case of bilateral breast cancer (BBC), understanding how to differentiate bilateral primary breast cancer from contralateral metastatic breast cancer is essential for treatment, but clear identification criteria have not been established to date. Diverse events play different roles in the therapy and prognosis of BBC; hence, it is of great significance to detect a more comprehensive and convincing technique to make an accurate differential diagnosis. We report a rare case of synchronous BBC in a 61-year-old Chinese woman. Based on her clinical and pathological features and the use of whole exome sequencing and cancer genome analysis, we concluded that the patient developed contralateral metastatic breast cancer which metastasized from left to right. Therefore, together with clinical, pathological and cancer genomics information, we could precisely define the origin and evolution of BBC.
Asian Continental Ancestry Group ; Breast Neoplasms ; Breast ; Diagnosis ; Diagnosis, Differential ; Exome ; Female ; Genome ; Genomics ; Humans ; Middle Aged ; Neoplasm Metastasis ; Prognosis

Objective To evaluate the clinical efficacy of different combinations with "Shugan Jianpi" acupuncture and Yintang acupoint magnetic stimulation in the treatment of depression with liver depression and spleen deficiency type.Methods 160 patients with depression treated in hospital from December 2013 to June 2017 were divided into 4 groups according to the random number table,with 40 cases in each group.Group A received basic drug therapy," Shugan Jianpi" acupuncture combined with Yintang acupoint magnetic stimulation,group B received basic drug therapy combined with Yintang acupoint magnetic stimulation,group C received basic drug therapy combined with " Shugan Jianpi" acupuncture treatment,group D was treated with basic medicine only for 4 weeks.Hamilton Depression Scale (HAMD) was used to assess the short-term and long-term efficacy for 4 groups before treatment,after 2 weeks of treatment,after 4 weeks and 2 months after treatment and the safety of these 4 types of therapy was evaluated with the side effects scale (TESS).2 months after the treatment,the quality of life universal scale (SF-36) was evaluated for patients in 4 groups.Results After 2 weeks,4 weeks and 2 months of treatment,HAMD scores in the 4 groups were significantly lower than those before treatment (P＜0.05).After 2 weeks of treatment,HAMD score of A group was (15.28±3.45),and HAMD score of B,C,D group were ((18.30±3.57),(22.50±3.71),(27.30±4.82)) respectively.HAMD score of A group was significantly lower than those of B,C,D group (P＜0.05).After 4 weeks of treatment,HAMD scores in A,B group were significantly lower than those in C,D group (P ＜0.05).After 2 months of treatment,HAMD scores in all the 4 groups were further declined compared with those after 4 weeks of treatment (P＜ 0.05),however,there was no significant difference between the four groups (P＞0.05).The scores of each dimension of SF-36 in group A were significantly higher than those of group B,C and D (P＜0.05),and which in group B and C were significantly higher than those in D group after 2 months of treatment.(P＜0.05).There was no statistical difference among the 4 groups in TESS scores (P ＞0.05).Conclusion The results suggest that there is a synergistic effect in combination of the " ShuganJianpi" acupuncture combined with Yintang acupoint magnetic stimulation in the treatment of depression of liver qi stagnation and spleen deficiency type,and it can effectively reduce the degree and improve their quality of life in patients with depression.

OBJECTIVE:To observe clinical efficacy and safety of salvianolate in the treatment of acute exacerbation of chron-ic obstructive pulmonary disease(AECOPD). METHODS:80 AECOPD patients were selected and randomly divided into observa-tion group and control group,with 40 cases in each group. Both groups received mechanical ventilation. Control group was given routine treatment of theophyllinum,bronchodilators and glucocorticoid;treatment group was additionally given Salvianolate injec-tion 200 mg,qd,ivgtt,on the basis of control group. Clinical efficacy was observed in 2 groups,blood hemorheology indexes were also observed before and after treatment. The mechanical ventilation time,ICU residence time and ADR were recorded in 2 groups. RESULTS:Clinical total effective rate of observation group was 95.00%,which was significantly higher than 70.00% of control group,with statistical significance(P<0.05). Before treatment and 2 d after treatment,blood rheology indexes of treatment group were improved significantly(all P>0.05),and whole blood reduction viscosity of control group was improved significantly(P<0.05). Mechanical ventilation time and ICU residence time of treatment group was significantly shorter than that of control group (P<0.05). No ADR was found in 2 groups. CONCLUSIONS:Salvianolate can significantly improve the blood coagulation status of AECOPD patients receiving invasive mechanical ventilation,and has the advantages of good clinical efficacy and low cost of medical treatment.

ObjectiveTo explore the efficacy and safety of bevacizumab combined with preoperative chemotherapy for colorectal cancer patients with liver metastases.MethodsClinical data of 89 colorectal cancer patients with liver metastases admitted and treated in Sun Yat-sen University Cancer Center between May 2009 and August 2013 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. According to the first-line chemotherapy regimens, the patients were divided into the bevacizumab combined with preoperative chemotherapy group (bevacizumab group,n=32) and the simple preoperative chemotherapy group (the chemotherapy group,n=57). Among the patients in the bevacizumab group, 24 were males and 8 were females with the age ranging from 29 to 74 years old and the median of 59 years old, 22 were with colon cancer and 10 were with rectal cancer. Among the patients in the chemotherapy group, 42 were males and 15 were females with the age ranging from 28 to 74 years old and the median of 57 years old, 42 were with colon cancer and 15 were with rectal cancer. The progression-free survival, response rate, resection rate and conversion rate of liver metastases and adverse effect incidence of preoperative therapy in two groups were observed and compared. The rates were compared using Chi-square test, and the survival analysis was conducted using Kaplan-Meier method and Log-rank test.ResultsThe median progression-free survival was 16 months in the bevacizumab group and 13 months in the chemotherapy group, and no significant difference was observed in the progression-free survival rate between two groups (χ2=0.030,P>0.05). The response rate, resection rate and conversion rate of liver metastases were respectively 59%(19/32), 69%(22/32) and 53%(17/32) in the bevacizumab group and 39%(22/57), 54%(31/57) and 40%(23/57) in the chemotherapy group, and no signiifcant differences were observed (χ2=3.561, 1.755, 0.983;P>0.05). The overall incidence of adverse events was 12%(4/32) in the bevacizumab group with 2 cases of neutropenia, 1 case of hand-foot syndrome and 1 case of gradeⅢ gums bleeding, while the overall incidence of adverse events was 9%(5/57) in the chemotherapy group with 3 cases of thrombocytopenia, 1 case of neutropenia and 1 case of liver function impairment. And no signiifcant difference was observed between two groups (χ2=0.313, P>0.05).ConclusionsBevacizumab combined with preoperative chemotherapy is safe and has potential curative effect to prolong the disease-free survival for colorectal cancer patients with liver metastases.