Objective To study the identification rate of sentinel lymph node (SLN) in patients with breast cancer (BC) and the accuracy in predicting axillary lymph node(ALN) metastasis using methylene blue (MB) and patent blue violet (PBV) injection. Methods From October, 1999 to April, 2001, 94 patients with BC were selected for this study. Of them, 32 patients were injected with 1% MB and 62 patients with 1% PBV to identify SLN. All 94 patients underwent the axillary lymph node dissection. Results In MB group and PBV group , the SLN identification rate were 65.6% (21/32), 88.7% (55/62); the accuracy rate to predict axillary lymph node status were 90.5% (19/21), 98.2% (54/55) respectively. Conclusion Compared with MB ,PVB is the more ideal vital blue dye in identification of SNB.

Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice. The standard chemotherapy of pancreatic cancer has been gemcitabine, but the response rate is low. Therefore, it is in urgent need to explore an effective clinical therapy for this cancer. This paper, a case report, is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer. Methods A 52-year-old female patient was diagnosed with pancreas cancer with liver metastasis at the time of the first visit to our hospital. Systemic chemotherapy with vinorelbine and cisplatin combined with endostatin was conducted. Results Liver metastases almost disappeared after the first cycle of chemotherapy. The primary tumor decreased by one third in size after four cycles and disappeared after the sixth cycle according to the CT scan evaluation. Conclusion Vinorelbine and cisplatin combined with endostatin can be a promising regimen for metastatic pancreatic cancer.

Objective To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9 (MMP-9) gene with phenotype of esophageal cancer. Methods All subjects were unrelated residents in northern regions of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the MMP-9 genotypes. Results The overall distribution of genotypes in the patients was not different from that in the controls (OR=0.77, 95% CI=0.45-1.34; P=0.36). There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age, smoking status, alcohol dependence, pickled diet status, or history of environmental exposure. The patients were further examined with stratifications by age, sex, grade, depth of tumor invasion, lymphatic invasion, venous invasion and TNM staging. The results showed no pronounced association among the stratifications. Conclusion There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.

Objective:To inhibit the Itch gene expression of T-lymphocytes and investigate the immune activity of T lymphocytes using ultrasound-targeted microbubble destruction (UTMD).Methods:T lymphocytes were separated by magnetic bead, and to establish an Itch gene targeted short hairpin RNA (shRNA) plasmid. There were three groups in this study: ①experimental group, Itch-shRNA plasmid-SonoVue microbubbles combined with ultrasound irradiation; ②control group, negative control shRNA plasmid-SonoVue microbubbles combined with ultrasound irradiation; ③blank group, untreated. Forty-eight hours after UTMD transfection, transfection efficiency was detected and analyzed by fluorescence microscopy and flow cytometry, the expression of Itch protein was measured with Western blotting.Seventy-two hours after UTMD transfection, the secretion of interleukin 2 (IL-2) and interferon γ (IFN-γ) in the cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA was used to compare the differences between groups, and LSD- t test was used to compare the differences between groups. Results:The UTMD mediated shRNA transfection rate was 52.3%, and the relative expression levels of Itch protein in the experimental group, control group and blank group were 0.301±0.080, 0.773±0.101 and 0.719±0.090, respectively, and the difference was statistically significant( F=24.441, P<0.01). The Itch gene expression can be effectively suppressed in the experimental group. Seventy-two hours after transfection, the concentrations of IL-2 in the experimental group, control group and blank group were (417.3±37.1)ng/L, (158.7±17.3)ng/L and (147.0±10.2)ng/L, respectively, and the difference was statistically significant( F=118.701, P<0.001) and the concentrations of IFN-γ were (168.3±12.1)ng/L, (74.3±3.7)ng/L and (74.6±7.1)ng/L, respectively, and the difference was statistically significant ( F=126.833, P<0.001). The expression levels of IL-2 and IFN-γ in the experimental group were significantly higher than those in the control group and the blank group. Conclusions:UTMD mediated shRNA transfection can significantly decrease the expression of Itch and promote immune activity of T lymphocyte.

Objective:To analyze the characteristics and trends of newly reported HIV infection cases in young students in China between 2010 and 2019 and provide evidence for the formulation of AIDS prevention and control measures in young students.Methods:Data were collected from the Basic Web-based HIV/AIDS Case Reporting System. The HIV infection cases in students aged 15-24 years reported between 2010 and 2019 were selected. Their basic characteristics were described, and Joinpoint Regression Model was used to analyze the temporal trends of new diagnosis rates in different age groups.Results:A total of 23 307 HIV/AIDS cases were reported in young students, the male to female ratio was 33.9∶1 (22 640∶667), and the mean age was (19.9±2.05) years. The temporal trends of new diagnosis rates showed two stages, it increased rapidly between 2010 and 2015 (annual percentage changes, APC=32.1), and kept stable between 2015 and 2019 ( APC=0.1, P>0.05). The new diagnosis rates in all age groups showed increasing trends between 2010 and 2015, and the APC of age group 15-17 years was highest (30.2). Between 2015 and 2019, the new diagnosis rates in age group 23-24 years showed decreasing trend ( APC=-17.0). The transmission route was mainly homosexual contact for males, and heterosexual contact for females. For most heterosexual transmission cases, they were infected through non-marital or non-commercial heterosexual contact. The male cases mainly came from HIV voluntary counseling and testing clinics, but the female cases were mainly found in hospitals. The male cases had higher mean first CD 4+T cells counts (CD 4) compared with female cases ( t=3.917, P=0.000). Conclusions:The overall increase trend of newly reported HIV infection in young students slowed slow down trend between 2010 and 2019, but the newly reported HIV infections in age group 15-17 years still showed an increase trend. It is necessary to carry out sex health education effectively in young students to reduce the high-risk sexual behavior and expand HIV test coverage in students.

Objective:To understand the basic characteristics of death cases, analyze the death trends in AIDS patients and the risk factors in China and provide evidence for the development of AIDS prevention and control strategy.Methods:The data were collected from the national basic information system of HIV/AIDS. The information of the cases in AIDS phase were used. The death number and mortality trends in AIDS cases were described, and Cox Proportion Hazards Regression Model was constructed to assess hazard ratios ( HR) for independent variables. Results:By the end of 2019, a total of 582 472 AIDS cases, including 168 391 deaths, had been reported in China. Among the death cases, males accounted for 76.8% (129 343/168 391), heterosexual contact was the main transmission route, accounting for 60.9% (102 516/168 391). The proportion of the death cases who had ever received ART was 54.0% (90 888/168 391). The inter-quartile ( P 25, P 75) of first CD 4＋T cells counts (CD 4) was 34 cells/μl, 240 cells/μl. Up to 43.5% (73 191/168 391) of the deaths occurred within one year after diagnosis. From 2007 to 2019, the annual death number increased from 5 485 to 18 737, the mortality rates decreased form 10.9%% to 4.3%. The average time interval from diagnosis to death ranged from 1.4 year to 4.0 years, showing increase trend by year. The results of Cox regression analysis showed that older age (50- years old: HR=1.50; ≥65 years old: HR=2.00), being male ( HR=1.44)、being in minority ethnic group ( HR=1.10), having lower first CD 4 levels (0- cells/μl, HR=2.73;200- cells/μl, HR=1.33; 350- cells/μl, HR=1.13), heterosexual transmission route ( HR=1.64) and injecting drug use ( HR=1.79) were the risk factors related to deaths in AIDS patients. The higher educational levels (junior middle school: HR=0.86, senior high school and above: HR=0.59) and receiving antiviral treatrment ( HR=0.09) were protective factors. Conclusions:The number of death cases increased, meanwhile the mortality rates decrease year by year in AIDS patients in China during 2007-2019. It is necessary to strengthen the early detection and treatment of AIDS to reduce the mortality.

【Objective】 To select and identify miRNA signatures to predict TMB level in gastric cancer based on The Cancer Genome Atlas (TCGA) database and machine learning methods. 【Methods】 MiRNA expression and somatic mutation profiles of gastric cancer (GC) were downloaded from TCGA database. R "limma" package was performed to select differentially expressed miRNAs between high-TMB and low-TMB groups. Two machine learning algorisms, random forest (RF), and Support Vector Machine-Recursive Feature Elimination were utilized to identify miRNAs with the highest discriminative ability. ROC was used to test the predictive ability of these signatures in multiple datasets. Besides, immune cells of different TMB levels were compared by the CIBERSORT method. 【Results】 A total of 56 differentially expressed miRNAs (DE-miRNAs) were filtered. Functional enrichment analysis showed that these DE miRNAs are mainly enriched in signaling pathways related to tumor occurrence and development as well as immunity-related biological processes. The RF and SVM-RFE algorithms jointly identified 10 diagnostic features of miRNAs, among which only hsa-miR-210-3p is considered the most relevant predictive biomarker for TMB classification. The AUC value of hsa-miR-210-3p in the training, testing, and total sets is 0.822, 0.721, and 0.793, respectively, and has been validated in other cancer types. Besides, CIBERSORT analysis suggests differences in immune cell infiltration between high- and low-TMB groups. Meanwhile, there is a significant positive correlation between the expression of immune checkpoint related genes and mismatch repair related genes and hsa-miR-210-3p. 【Conclusion】 This study successfully identified hsa-miR-210-3p as a predictive biomarker for TMB classification, which can effectively predict TMB values in gastric cancer and other cancer patients and may provide some guidance for immunotherapy.

Objective:To understand the progression of CD 4+ T cells (CD 4) declining rate in different age groups among MSM and to further explore the pathogenesis of HIV infection. Methods:Data regarding MSM who were diagnosed as HIV positive, aged ≥15 years, with homosexual route of transmission and with more than two records of CD 4 count retained before antiretroviral therapy (ART), were collected from the National AIDS Comprehensive Prevention Information System until May 31, 2019. Linear mixed effect model was used to fit the linear elimination relationship between the square root of CD 4 cell count and infection time before taking up the ART. To get the intercept estimation, we used the results from CD 4 count which containing the dates of last negativity and first positivity on HIV antibody testing. Both t test and Z test were used to test the model parameters. Median intervals from HIV seroconversion to CD 4<500, <350, <200 cells/μl were estimated. Results:A total of 26 754 individuals were included in the study including 146 of them having records on the last date of being test negative. Their median age was 27 years old ( M=27, P25- P75:23-35). The intercept of the liner mixed models among 15-, 25- and ≥35 year olds were 24.84 (95 %CI: 23.76-25.92), 23.94 (95 %CI: 22.86-25.02), 23.44 (95 %CI: 21.91-24.96) and the slope of the liner mixed models among the 15-24, 25-34, 35-44 and ≥45 year olds were -1.31 (95 %CI: -1.33--1.25), -1.37(95 %CI: -1.40--1.33), -1.53 (95 %CI: -1.58--1.47) and -1.59 (95 %CI:-1.68--1.51), respectively. Estimation on the median intervals from HIV seroconversion to CD 4 <500, <350, <200 cells/μl counts were 1.29 (95 %CI: 0.79-1.81), 3.92 (95 %CI: 3.36-4.48) and 7.21 (95 %CI: 6.58-7.81), respectively. The median time of 15-24 age group from HIV seroconversion to reach the three CD 4 thresholds appeared the longest, as 1.89 (95 %CI: 1.05-2.85), 4.68(95 %CI: 3.80-5.77) and 8.17 (95 %CI: 7.23-9.42) years, respectively, the median time of ≥45 age group from HIV seroconversion to reach the three CD 4 thresholds appeared the shortest, as 0.68 (95 %CI: 0.00-1.72)、2.98 (95 %CI: 1.91-4.14)、5.85 (95 %CI: 4.62-7.16) years, respectively. Conclusions:Our findings suggested that the CD 4 declining rate had been accelerated along with ageing. Progression time from HIV seroconversion to different CD 4 thresholds appeared different, which was shorter in the older age group. Again, these findings showed the great impact of HIV infection among older age groups in the MSM population. Early diagnosis and treatment were bound to delay the progression of the disease.

Objective:Using the changing patterns of CD 4+ lymphocytes (CD 4) counts of HIV/AIDS cases, we tried to estimate the number of newly infected HIV in Honghe Hani and Yi autonomous prefecture (Honghe prefecture) Yunnan province, and to provide reference for evaluating the trend of local HIV epidemic. Methods:Among diagnosed HIV infections, those who were at ≥15 years old, having available initial CD 4 records of testing, initiating antiviral therapy before the end of 2018, were selected from the case reporting system of Honghe prefecture, Yunnan province. Both Depletion model of the square root on CD 4 and the time of infection were used to back-calculate the seroconversion time of each individual. Both direct probability distribution method and life table method were used to calculate the distribution rates of diagnosis and the weight of delay. The number of diagnoses over the years was used to reversely estimate the total number of newly HIV infections. Results:At the end of 2018, the total number of HIV infections was estimated 35 977 with the rate of diagnosis as 77.50 % in Honghe prefecture of Yunnan province. The number of new HIV infections appeared as 23 792 in 2008-2018. Cumulatively, the number of new HIV infections was 12 185 up to 2007. The estimated number of new HIV infections decreased from 2 602 in 2008 to 1 480 in 2018. The weight of diagnostic delay decreased from 5.49 in one year to 1.00 in 20 years, and the diagnosis rate increased from 18.2 % to 100.0 % during 20 years. Conclusion:In Honghe prefecture of Yunnan province, the number of newly infection showed a declining trend but the diagnostic rate was still far from reaching the "first 90 % target" . It is expected to expand the timeliness on detection and case-finding so as to reduce the risk of HIV transmission.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic