[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

[Effect of posterior tibial slope on the short-term outcome in mobile-bearing unicompartmental knee arthroplasty].

OBJECTIVE: To evaluate the relationship between postoperative knee function and the sagittal position of tibial component in unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively enrolled the patients who underwent UKA from January 2016 to May 2020. They were assigned into 2 groups according to postoperative posterior tibial slope (PTS): the normal PTS group (PTS≥3° and PTS < 8°) and the abnormal PTS group (PTS < 3° or ≥8°). The patients were followed up for at least 12 months. The postoperative Knee Society Clinical Score (KSS-C), Knee Society Functional Score (KSS-F) and knee range of motion (ROM) were compared between the two groups. RESULTS: A total of 72 patients (82 knees) were included with 51 patients (58 knees) in PTS normal group and 21 patients (24 knees) in PTS abnormal group. All the patients were followed up with median of 23.6 months. There was no significant difference in the general data [gender, age, body mass index (BMI)], pre-operative knee range of motion, preoperative KSS-C score and KSS-F score (P > 0.01). The KSS-C score, KSS-F score, and knee range of motion significantly improved after surgery (P < 0.01) for all the patients. The postoperative KSS-C score in normal PTS group (88.76±2.79) was significantly higher than the KSS-C score in abnormal PTS group (84.42±3.35, P < 0.01), but no significant difference between the 2 groups was observed in postoperative KSS-F score and knee range of motion (P > 0.01). In addition, there was no correlation between the change of PTS and postoperative KSS-C score (r=-0.034, 95%CI: -0.247 to 0.186, P = 0.759), KSS-F score (r = -0.014, 95%CI: -0.238 to 0.198, P = 0.901) and knee range of motion (r= 0.045, 95%CI: -0.214 to 0.302, P = 0.686). CONCLUSION: The posterior tibial slope between 3° and < 8° can be recommended to improve knee joint function in mobile UKA, and excessive or insufficient PTS should be avoided.

Ageing affects the proliferation and mineralization of rat dental pulp stem cells under inflammatory conditions.

AIM: To comparatively evaluate changes in the proliferation and mineralization abilities of dental pulp stem cells (DPSCs) from juvenile and adult rats in a lipopolysaccharide (LPS)-induced inflammatory microenvironment to provide a theoretical basis for the age-related differences observed in DPSCs during repair of inflammatory injuries. METHODOLOGY: DPSCs were isolated from juvenile (JDPSCs) and adult rats (ADPSCs), and senescence-associated ß-galactosidase staining was used to compare senescence between JDPSCs and ADPSCs. Effects of LPS on JDPSCs and ADPSCs proliferation were investigated by cell counting kit-8 assays and flow cytometry. Alizarin red staining, quantitative reverse transcription polymerase chain reaction and Western blot assay were used to examine the effects of LPS on mineralization-related genes and proteins in JDPSCs and ADPSCs. Immunohistochemistry was used to compare interleukin-1ß (IL-1ß) and osteocalcin (OCN) expression in the pulpitis model. Unpaired Student's t-tests and one-way anova were used for statistical analysis. RESULTS: DPSCs were isolated from juvenile and adult rat dental pulp tissues. At low concentrations (0.1-1 µg mL-1 ), LPS significantly promoted the proliferation of JDPSCs (P < 0.01) and ADPSCs (P < 0.01 or P < 0.05), with the effect being stronger in JDPSCs than in ADPSCs. In addition, mineralized nodules and the expression of mineralization-related genes (OCN, DSPP, ALP, BSP) increased significantly after stimulation with LPS (0.5 µg mL-1 ) in JDPSCs and ADPSCs (P < 0.01 or P < 0.05), and JDPSCs displayed a more obvious increase than ADPSCs. Western blots revealed OCN and ALP expression levels in JDPSCs treated with LPS were significantly upregulated (P < 0.05); meanwhile, ALP expression in ADPSCs increased slightly but significantly (P < 0.05), and OCN expression was not affected. Finally, IL-1ß expression was significantly higher (P < 0.05) and OCN expression was significantly lower (P < 0.05) in the inflamed dental pulp of adult rats than in juvenile rats. CONCLUSIONS: A certain degree of inflammatory stimulation promoted the proliferation and mineralization of DPSCs; however, this effect declined with age. The DPSCs of adult donors in an inflammatory microenvironment have a weaker repair ability than that of juvenile donors, who are better candidates for tissues damage repair.

Tunable hybridization of graphene plasmons and dielectric modes for highly confined light transmit at terahertz wavelength.

We theoretically report a novel graphene-based hybrid plasmonic waveguide (GHPW) by integrating a GaAs micro-tube on a silica spacer that is supported by a graphene-coated substrate. In comprehensive numerical simulations on guiding properties of the GHPW, it was found that the size of hybrid plasmonic mode (TM) can be reduced significantly to ~10-4(λ2/4), in conjunction with long propagation distances up to tens of micrometers by tuning the the waveguide's key structure parameters and graphene's chemical potential. Moreover, crosstalk between two adjacent GHPWs that are placed on the same substrate has been analyzed and ultralow crosstalk can be realized. The proposed scheme potentially enables realization of the various high performance nanophotonic components-based subwavelength plasmonic waveguides in terahertz domain.

Diverse effects of pulsed electrical stimulation on cells - with a focus on chondrocytes and cartilage regeneration.

Biological effects of pulsed electrical stimulation (PES) on cells and tissues have been intensively studied with the aim of advancing their biomedical applications. These effects vary significantly depending on PES parameters, cell and tissue types, which can be attributed to the diverse variety of signaling pathways, ion channels, and epigenetic mechanisms involved. The development of new technology platforms, such as nanosecond pulsed electric fields (nsPEFs) with finely tuned parameters, have added further complexity. The present review systematically examines current research progress in various aspects of PES, from physical models to biological effects on cells and tissues, including voltage-sensing domains of voltage-gated channels, pore formation, intracellular components/organelles, and signaling pathways. Emphasis is placed on the complexity of PES parameters and inconsistency of induced biological effects, with the aim of exploring the underlying physical and cellular mechanisms of the physiological effects of electrical stimulation on cells. With chondrogenic differentiation of stem cells and cartilage regeneration as examples, the underlying mechanisms involved were reviewed and analyzed, hoping to move forward towards potential biomedical applications. Hopefully, the present review will inspire more interest in the wider clinical applications of PES and lay the basis for further comprehensive studies in this field.

[The characteristics of recent HIV-1 infection and associated factors in Tianjin].

The newly reported HIV infected cases was collected, and HIV blood samples were detected to identify recent HIV infection in Tianjin during 2008-2015. Factors associated with HIV-1 infection were analyzed by the univariate and multivariate unconditional logistic regression. The recent HIV-1 infection proportion of homosexuals increased from 37.70% in 2008 to 83.68% in 2015. Those cases who aged ≤30 years (OR=1.53, 95%CI: 1.30-1.79), in han ethnic group (OR=1.40, 95%CI: 1.02-1.91), students (OR=1.79, 95%CI: 1.28-2.51) were more likely to be recent infected. The cases who had a high school education (OR=1.28, 95%CI: 1.05-1.56) or collage education (OR=1.23, 95%CI: 1.00-1.50) were more likely to be recent infected than those who had a primary school education. Compared with patients identified by hospitals, the recent HIV infections were more likely to be found through voluntary counseling and testing (VCT), STD outpatients, men who have sex with men (MSM) investigation and unpaid blood donors. Homosexual transmission has become the major route of HIV-1 recent infection in Tianjin.

Expression of APOB, ADFP and FATP1 and their correlation with fat deposition in Yunnan's top six famous chicken breeds.

1. Adipose differentiation related protein (ADFP), fatty acid transport protein 1 (FATP1) and apolipoprotein B (APOB) are suspected to play an important role in determining intramuscular fat and in overall meat quality. 2. Yunnan's top six famous chicken breeds (the Daweishan Mini, Yanjin Black-bone, Chahua, Wuding, Wuliangshan Black-bone and Piao chicken) are known for the high quality of their meat, but little is known about their expression of these three genes. 3. The present study aimed to examine the ADFP, FATP1 and APOB genes in different tissues of these six breeds at different development stages. The subcutaneous fat from the back midline and front, abdominal fat, liver and muscle tissue was sampled at 28, 49, 70, 91 and 112 days. The expression of ADFP, FATP1 and APOB was measured by real-time PCR. 4. The results showed that the expression of the three genes differed depending on age, tissue types and breeds. However, the expression of the three genes correlated with fat traits. In conclusion, the expression of the ADFP, FATP1 and APOB genes is associated with the fat traits of Yunnan's top six chicken breeds. These results could help with molecular marker screening and marker-assisted breeding to improve the quality of poultry for meat production.

Enhancement of bulk second-harmonic generation from silicon nitride films by material composition.

We present a comprehensive tensorial characterization of second-harmonic generation from silicon nitride films with varying compositions. The samples were fabricated using plasma-enhanced chemical vapor deposition, and the material composition was varied by the reactive gas mixture in the process. We found a six-fold enhancement between the lowest and highest second-order susceptibility, with the highest value of approximately 5 pm/V from the most silicon-rich sample. Moreover, the optical losses were found to be sufficiently small (below 6 dB/cm) for applications. The tensorial results show that all samples retain in-plane isotropy independent of the silicon content, highlighting the controllability of the fabrication process.

Aerobic Stability and Effects of Yeasts during Deterioration of Non-fermented and Fermented Total Mixed Ration with Different Moisture Levels.

The present experiment evaluated the influence of moisture level and anaerobic fermentation on aerobic stability of total mixed ration (TMR). The dynamic changes in chemical composition and microbial population that occur after air exposure were examined, and the species of yeast associated with the deterioration process were also identified in both non-fermented and fermented TMR to deepen the understanding of aerobic deterioration. The moisture levels of TMR in this experiment were adjusted to 400 g/kg (low moisture level, LML), 450 g/kg (medium moisture level, MML), and 500 g/kg (high moisture level, HML), and both non-fermented and 56-d-fermented TMR were subjected to air exposure to determine aerobic stability. Aerobic deterioration resulted in high losses of nutritional components and largely reduced dry matter digestibility. Non-fermented TMR deteriorated during 48 h of air exposure and the HML treatment was more aerobically unstable. On dry matter (DM) basis, yeast populations significantly increased from 10(7) to 10(10) cfu/g during air exposure, and Candida ethanolica was the predominant species during deterioration in non-fermented TMR. Fermented TMR exhibited considerable resistance to aerobic deterioration. Spoilage was only observed in the HML treatment and its yeast population increased dramatically to 10(9) cfu/g DM when air exposure progressed to 30 d. Zygosaccharomyces bailii was the sole yeast species isolated when spoilage occurred. These results confirmed that non-fermented and fermented TMR with a HML are more prone to spoilage, and fermented TMR has considerable resistance to aerobic deterioration. Yeasts can trigger aerobic deterioration in both non-fermented and fermented TMR. C. ethanolica may be involved in the spoilage of non-fermented TMR and the vigorous growth of Z. bailii can initiate aerobic deterioration in fermented TMR.

Genetic dissection of Iddm26 in the spontaneously diabetic BBDP rat.

The 40 Mb T1D susceptibility locus Iddm26 was mapped to chromosome 2 through linkage analysis of a conditioned cross-intercross between the diabetes-prone BBDP and the diabetes-resistant ACI.BBDP-Iddm1,Iddm2 (ACI.1u.Lyp). It is flanked by Iddm32 and Iddm33, which control the kinetics of disease progression. To fine-map Iddm26 and characterize immune phenotypes controlled by this locus, several congenic sublines were generated carrying smaller, overlapping intervals spanning Iddm26 and fragments of Iddm32 and 33. Analysis of disease susceptibility, age of disease onset, and immune phenotypes in these sublines identified subloci regulating these different parameters. Two ACI.1u.Lyp-derived subloci, Iddm26.1 and Iddm26.2, imparted significant protection from diabetes, decreasing the cumulative incidence by as much as 57% and 28%, respectively. Iddm26.2, which overlaps with the human PTPN22 locus, only affected disease susceptibility, whereas Iddm26.1 also significantly affected disease kinetics, delaying T1D onset by more than 10 days compared with the parental BBDP strain. These Iddm26 subloci also regulated various immune phenotypes, including the proportion of splenic macrophages by Iddm26.1, and the proportion of activated T-cells in secondary lymphoid organs by Iddm26.2. The analysis of Iddm26 congenic animals in two different SPF facilities demonstrated that the influence of this locus on T1D is environment-dependent.

[Characteristics of baseline viral load before antiretroviral therapy in newly reported HIV-infected patients in Tianjin, 2019-2022].

Objective: To understand the baseline viral load (VL) of newly reported HIV- infected patients before antiretroviral therapy and related factors in Tianjin. Methods: Data were obtained from the China Disease Control and Prevention Information System, and the study subjects were HIV-infected patients before the first antiretroviral therapy in Tianjin from 2019 to 2022, and the information about their socio-demographic characteristics, baseline CD4+T lymphocyte (CD4) counts before antiretroviral therapy and baseline VL test results were collected, the baseline high VL was defined as ≥100 000 copies/ml. The effect of different factors on viral load were analyzed. Software SPSS 24.0 was used for statistical analysis. Results: A total of 1 296 newly reported HIV-infected patients were included in the study, in whom 15.89% (206/1 296) had high baseline VL, and multifactorial logistic regression analysis showed that those with history of STD (aOR=1.45, 95%CI:1.00-2.08) were more likely to have high baseline VL. Compared with those with baseline CD4 counts <200 cells/µl, those with baseline CD4 counts 200-350 cells/µl (aOR=0.40, 95%CI: 0.27-0.57), 351-500 cells/µl (aOR=0.32, 95%CI: 0.20-0.49), and >500 cells/µl (aOR=0.30, 95%CI: 0.18-0.49) were less likely to have high baseline VL. Conclusions: The proportion of HIV-infected patients with high baseline VL before antiretroviral therapy was low in Tianjin during 2019-2022. History of STD and baseline CD4 counts <200 cells/µl were associated with high baseline VL in HIV-infected patients, to which close attention needs to be paid in AIDS prevention and control.

Prognostic value of the stem cell markers CD133 and ABCG2 expression in esophageal squamous cell carcinoma.

In the light of increasing evidence supporting cancer stem cells (CSCs) theory, the expression of two stem cell markers, CD133 and adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2), in esophageal squamous cell carcinoma (ESCC) was investigated, and their prognostic values were evaluated. Paraffin-embedded tissue sections of 110 ESCC patients were investigated using Immunohistochemistry. The association of CD133 and ABCG2 expression with clinicopathologic characteristics was analyzed by χ(2) test. Survival analysis was carried out using Kaplan-Meier method and Cox proportional hazards model. CD133 and ABCG2 expression were detected in 27.3% and 15.5% of ESCC patients, respectively. The presence of CD133-positive cancer cells was associated with tumor cell differentiation (P= 0.008) but not significantly related to the survival of ESCC patients (P= 0.085). ABCG2 expression was not associated with clinicopathologic characteristics but was a significant prognostic factor for adverse overall survival of ESCC patients (P= 0.005). The median overall survival time for ESCC patients with and without ABCG2 expression were 21.8 and >49.3 months, respectively. A combined analysis of CD133 and ABCG2 expression did not show that ESCC patients with coexpression of these two markers had a worse prognosis than those with only ABCG2 expression (P= 0.934). Moreover, ABCG2 expression was revealed to be an independent prognostic factor along with tumor node metastasis stage in multivariate analysis (hazard ratio of ABCG2, 3.38; 95% confidence interval, 1.61∼7.09; P= 0.001). By survival analysis based on tumor node metastasis stage of ESCC, the association between ABCG2 expression and the patients' prognosis was found significant in the group of relatively early stage (P= 0.005) and marginally significant in the group of relatively late stage (P= 0.058). This is the first time to report the presence of CD133-positive cancer cells in ESCC but not supporting its prognostic value and validity as a CSC marker for ESCC. ABCG2 expression was found to correlate with the survival of ESCC patients, especially those at relatively early stage, suggesting that ABCG2-positive cancer cells may represent a pool of CSCs in ESCC, and relatively early-stage patients with ABCG2 expression may deserve more intensive or targeted therapy.

[HIV infection status in male outpatients in sexually transmitted disease clinics in Tianjin, 2016-2020].

Objective: To understand the HIV infection status in male outpatients in sexually transmitted disease (STD) clinics in Tianjin from 2016 to 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional studies were conducted between April and June during 2016-2020 to collect the information about the awareness of AIDS related knowledge, related sex behaviors, HIV infection, syphilis prevalence and HCV infection of male STD outpatients in Tianjin with a sample seize of 400 in each sentinel clinic. Results: From 2016 to 2020, a total of 4 000 male STD outpatients were surveyed. The HIV positive rate increased from 1.13% (9/800) to 2.25% (18/800) (trend χ2=14.22, P<0.001), the positive rate of syphilis increased from 9.38% (75/800) to 13.00% (104/800) (trend χ2=7.30, P=0.007) in this population during this period. The overall HCV positive rate was 0.45% (18/4 000). Multivariate logistic regression analysis showed that compared with those who were unmarried, had registered residence in Tianjin, had no temporary sexual behavior in the past 3 months, had no anal sex and had negative syphilis test result, the risk factors of HIV infection in the male STD outpatients included cohabitation (aOR=7.53, 95%CI:2.13-26.62), being from other provinces (aOR=3.64,95%CI:1.58-8.38), having temporary sexual behavior in the past 3 months (aOR=2.24,95%CI:1.03-4.89), having homosexual anal sex (aOR=85.99,95%CI:38.76-190.74) and suffering from syphilis (aOR=6.06,95%CI:3.18-11.56). Conclusion: The detection rates of HIV infection and syphilis in male STD outpatients in Tianjin showed upward trends from 2016 to 2020. Having temporary sexual behavior and anal sex, and suffering from syphilis were the main risk factors of HIV infection in male STD outpatients.

Photonic generation of triangular waveform signals by using a dual-parallel Mach-Zehnder modulator.

A photonic approach to generate triangular waveform signals is proposed and analyzed. With active bias control, two sub-MZMs (MZ-a and MZ-b) of a dual-parallel Mach-Zehnder modulator (DP-MZM) operate at minimum transmission point, leaving the main MZM (MZ-c) at quadrature transmission point. Triangular waveform can be observed by a parameter setting of modulation index. The proposal is first analyzed and then validated by simulation. The key significance of the scheme is that it is capable of generating triangular waveform signals via a sinusoid local oscillator.

Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey.

BACKGROUND: The etiology of esophageal squamous cell cancer (ESCC) in high prevalence regions of China remains unclear. METHODS: Endoscopic biopsies were conducted among 7381 inhabitants aged from 25 to 65 of Anyang, China. RESULTS: In this study, 2.57, 0.20 and 0.16% of the participants had mild, moderate and severe squamous dysplasia, respectively; 0.19 and 0.08% showed squamous carcinoma in situ and invasive ESCC. Using deep well (depth >100 meters) as water source (odds ratio=0.72, 95% confidence interval: 0.54-0.96) was negatively associated with ESCC and its precursors, whereas tobacco and alcohol use were not significantly associated with ESCC. CONCLUSIONS: Water source and other factors in this region need further evaluation by longitudinal studies.

Artificial selection of the melanocortin receptor 1 gene in Chinese domestic pigs during domestication.

Black coat colour is common in Chinese indigenous domestic pigs, but not among their wild ancestors, and it is thus presumed to be a 'domestication trait.' To determine whether artificial interference contributes to morphological diversification, we examined nucleotide variation from 157 Chinese domestic pigs and 40 wild boars in the melanocortin receptor 1 (MC1R) gene, which has a key role in the coat pigmentation of Sus scrofa. Compared with a pseudogene GPIP, our results showed that the joint effects of demography and selection have resulted in markedly low genetic diversity of MC1R in Chinese domestic pigs. Coalescent simulation and selection tests further suggest that the fixation of two non-synonymous substitutions associated with black colour is the result of artificial selection. In contrast, a much higher genetic diversity and only a single non-synonymous substitution were found among the wild boars, suggesting a strong functional constraint. Moreover, our conclusion is consistent with the preference for black colour in the ancient Chinese sacrificial culture. This case provides an interesting example of a molecular evaluation of artificial livestock selection and its associated cultural impact in ancient China.

Adaptive evolution of the mitochondrial ND6 gene in the domestic horse.

Mitochondria play a crucial role in energy metabolism through oxidative phosphorylation. Organisms living at high altitudes are potentially influenced by oxygen deficits and cold temperatures. The severe environmental conditions can impact on metabolism and direct selection of mitochondrial DNA. As a wide-ranging animal, the domestic horse (Equus caballus) has developed various morphological and physiological characteristics for adapting to different altitudes. Thus, this is a good species for studying adaption to high altitudes at a molecular level. We sequenced the complete NADH dehydrogenase 6 gene (ND6) of 509 horses from 24 sampling locations. By comparative analysis of three horse populations living at different altitudes (>2200 m, 1200-1700 m, and <900 m), we found that the high-altitude population had the lowest genetic diversity and significant negative Tajima's D; both values declined with increasing elevation. Moreover, non-directional selection was identified for the ND6 gene by a tree-based relative ratio test (P = 0.007); the highest proportion of high-altitude horses was found distributed on the selected branches. We conclude that the high-altitude environment has directed adaptive evolution of the mitochondrial ND6 gene in the plateau horse.

Differential bortezomib sensitivity in head and neck cancer lines corresponds to proteasome, nuclear factor-kappaB and activator protein-1 related mechanisms.

Head and neck squamous cell carcinomas (HNSCC) exhibit constitutive activation of transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), which are modulated by the proteasome and promote resistance to cell death. HNSCC show variable sensitivity to the proteasome inhibitor bortezomib in vitro as well as in murine xenografts and patient tumors in vivo, and the mechanisms are not well understood. To address this question, the sensitivities of nine HNSCC cell lines to bortezomib were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and the potential relationship between the sensitivity and bortezomib effects on biological processes was examined in HNSCC lines of differential bortezomib sensitivity. The most sensitive cell line (UM-SCC-11B) underwent cell death at 10(-9) mol/L in vitro and tumor regression at a maximally tolerated dose of bortezomib in a murine xenograft model. The differential sensitivity between UM-SCC-11A and UM-SCC-11B cells corresponded to differences in the extent of suppression of proteasome activity, ubiquitinated protein degradation, and NF-kappaB and AP-1 activation. Lower concentrations of bortezomib transiently increased NF-kappaB and sustained AP-1 activation in UM-SCC-11A cells. AP-1 reporter activity and cell density of UM-SCC-11A were suppressed when bortezomib was combined with c-Jun NH(2)-terminal kinase and p38 kinase pathways inhibitors. Thus, the differential sensitivities to bortezomib corresponded to dissimilar effects on the proteasome, NF-kappaB and AP-1 activities. Inhibition of c-Jun NH(2)-terminal kinase and p38 pathways blocked AP-1 activity and enhanced the antitumor effects. These findings revealed molecular mechanisms of bortezomib sensitivity and resistance, which are under development as biomarkers for clinical trials in patients with HNSCC.

[HIV infection status and related factors in men who have sex with men in sentinel surveillance in Tianjin, 2016-2018].

Objective: To understand the HIV infection status and related factors in men who have sex with men (MSM) in Tianjin during 2016-2018. Methods: According to the sentinel surveillance protocol, continuous cross-sectional studies were conducted to collect the information about the awareness of AIDS, related behaviors, HIV infection, syphilis prevalence and HCV infection in the MSM in Tianjin with the annual sample seize of 400 between April and June during 2016-2018. Results: From 2016 to 2018, a total of 1 200 MSM were surveyed. The condom use rate in anal sex was 45.4% (544/1 198) in the past 6 months. The HIV test rate in MSM recruited through network declined with year (trend χ(2)=42.742, P<0.001). The overall HIV infection rate was 3.3% (40/1 200). The HIV-1 infection rate was 2.6% (95%CI: 1.7%-3.5%). The overall prevalence rate of syphilis was 6.7% (80/1 200). The overall HCV infection rate was 0.8% (9/1 200). Results from multivariate logistic regression analysis showed that the risk factors associated with HIV infection in the MSM included divorced or widowed (compared with unmarried, aOR=7.137, 95%CI: 1.621-31.419) and syphilis positive group (compared with syphilis negative group, aOR=3.684, 95%CI: 1.520-8.932). The protective factors for HIV infection in the MSM included consistent use of condom in the past 6 months (compared with occasional use of condom, aOR=0.343, 95%CI: 0.126-0.932) and HIV test (compared with receiving no HIV test, aOR=0.314, 95%CI: 0.123-0.801). Conclusions: The HIV infection rate in the MSM in Tianjin was high from 2016 to 2018. Syphilis prevalence status in MSM should not be neglected. The rate of consistent condom use in anal sex was low in the MSM. It is necessary to take effective measures to promote condom use and strengthen HIV test in MSM.

A signal network involving coactivated NF-kappaB and STAT3 and altered p53 modulates BAX/BCL-XL expression and promotes cell survival of head and neck squamous cell carcinomas.

Abrogation of apoptosis to sustain cell survival is an essential step in development of cancer. Aberrant activation of signal transcription factors NF-kappaB or STAT3, alterations in p53 status, or BCL/BAX family expression have each been reported to affect cell survival in cancer, including head and neck squamous cell carcinomas (HNSCC). However, molecular targeting of these alterations individually has yielded disappointing results. In our study, we examined the hypothesis that alterations in a signal network involving NF-kappaB, STAT3 and p53 modulates expression of proapoptotic BAX and antiapoptotic BCL-XL proteins, and promotes cell survival of HNSCC. We found that NF-kappaB and STAT3 are coactivated together, and with cytokine stimulation or siRNA knock-down, both modulate BAX/BCL-XL. Greater modulation among HNSCC lines expressing low wt p53 than those over-expressing mt p53 protein suggested that decreased p53 expression might enhance activation of NF-kappaB, STAT3 and BCL-XL. Reexpression of wt p53 suppressed NF-kappaB and STAT3 nuclear binding activity, and BCL-XL expression, while inducing p21 and BAX. Over-expression of p53 together with inhibition of NF-kappaB or STAT3 induced greater increase in the BAX/BCL-XL ratio and apoptosis than modulation of these transcription factors individually. Conversely, NF-kappaB or STAT3 inducing cytokines decreased the BAX/BCL-XL ratio. Thus, a network involving signal coactivation of NF-kappaB and STAT3, differentially modified by p53 inactivation or mutation, promotes altered BAX/BCL-XL expression and cell survival in HNSCC. Inhibition of signal activation of both NF-kappaB and STAT3 together with reexpression of p53 could be the most effective strategy to restore BAX/BCL-XL regulation and for cytotoxic therapy of HNSCC.