Endu combined with concurrent chemotherapy and radiotherapy for stage IIB-IVA cervical squamous cell carcinoma patients.

BACKGROUND: In recent years, the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles, posing a serious threat to women's physical and mental health. AIM: To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma. METHODS: A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects. They were equally divided into the test group and the control group (60 patients each) with a random number table. The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy, and the control group was treated with concurrent radiotherapy and chemotherapy. We compared the serum thymidine kinase 1 (TK1), human epididymis protein 4 (HE4), vascular endothelial growth factor (VEGF), and squamous cell carcinoma-associated antigen (SCC-Ag) levels, the clinical effects and survival before and after radiotherapy and chemotherapy, the quality score, and the 3-year follow-up outcomes between the two groups. RESULTS: After chemotherapy, the complete remission + partial remission rate was 85.00% in the test group and 68.33% in the control group; the difference was not statistically significant (P > 0.05). Before chemotherapy, the serum TK1, HE4, VEGF, and SCC-Ag levels of the two groups were not significantly different (P > 0.05). After chemotherapy, the levels of serum TK1 (1.27 ± 0.40 pmol/L), HE4 (81.4 ± 24.0 pmol/L), VEGF (235.1 ± 38.0 pg/mL), and SCC-Ag (1.76 ± 0.55 ng/mL) were lower than those in the control group [TK1 (1.58 ± 0.51 pmol/L), HE4 (98.0 ± 28.6) pmol/L, VEGF (284.2 ± 54.1 pg/mL), and SCC-Ag (2.34 ± 0.78 ng/mL)]. The difference was statistically significant (P < 0.05). Before chemotherapy, there were no significant differences in the physical, role, mood, cognition, social and symptom scale scores of the two groups (P > 0.05). After chemotherapy, the physical, role, mood, cognitive and social scores were higher in the test group than in the control group, and the difference was statistically significant (P < 0.05). The symptom scale scores of the test group were all lower than those of the control group, and the difference was statistically significant (P < 0.05). The 3-year progression-free survival (PFS) rate was 43.33% in the test group and 26.67% in the control group; the overall survival (OS) rate was 48.33% in the test group and 33.33% in the control group; the differences were not statistically significant (P > 0.05). The 3-year PFS time of the test group was 20.0 mo, which was longer than that of the control group (15.0 mo), and the difference was significant (P < 0.05). The OS time of the test group was 30.0 mo, which was longer than that of the control group (18.0 mo), and the difference was significant (P < 0.05). CONCLUSION: Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients, prolonging the PFS and OS times of patients, and improving the quality of life.

Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV.

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS: The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.

Targeting YTHDF1 effectively re-sensitizes cisplatin-resistant colon cancer cells by modulating GLS-mediated glutamine metabolism.

Colorectal cancer (CRC) has a high mortality rate and poor prognosis. Despite chemotherapeutic agents such as cisplatin, which has achieved a better prognosis and survival rate against cancer, drug resistance leads to significant challenges. Accumulating evidence suggests that YTHDF1, the N 6-methyladenosine (m6A) "reader," is an important regulator in tumor progresses. Herein, we report that YTHDF1 was significantly upregulated in human colon tumors and cell lines. Overexpression of YTHDF1 decreased the cisplatin sensitivity of colon cancer cells. From the established cisplatin-resistant CRC cell line (LoVo CDDP R), we detected that YTHDF1 was significantly upregulated in cisplatin-resistant CRC cells. Intriguingly, RNA sequencing (RNA-seq) results revealed that glutamine metabolism enzymes were clearly upregulated in LoVo CDDP R cells. Glutamine uptake, that is, glutaminase (GLS) activity, was upregulated in LoVo CDDP R cells. Furthermore, bioinformatics analysis indicated that the 3' UTR of GLS1 contained a putative binding motif of YTHDF1, and an interaction was further validated by a protein-RNA interaction assay (RNA immunoprecipitation [RIP]). Furthermore, we demonstrated that YTHDF1 promoted protein synthesis of GLS1. Inhibiting GLS1 effectively synergizes with cisplatin to induce colon cancer cell death. Finally, that YTHDF1 mediated cisplatin through the GLS1-glutamine metabolism axis was validated by an in vivo xenograft mouse model. In summary, our study reveals a new mechanism for YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report.

BACKGROUND: Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART). METHODS: From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group. RESULTS: From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/µL) in the NK + ART group and (144 to 176 cells/µL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (ß = 54.59, P = 0.006) and CD8 level (ß = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course. CONCLUSIONS: This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).

Underwater vs conventional endoscopic mucosal resection in treatment of colorectal polyps: A meta-analysis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) of colorectal lesions is emerging as an alternative method to conventional endoscopic mucosal resection (EMR); however, it is still controversial whether there is a difference in the effectiveness between UEMR and EMR. AIM: To evaluate the effectiveness and safety of UEMR in the treatment of colorectal polyps. METHODS: Clinical studies comparing the effectiveness or safety of UEMR in the treatment of colorectal polyps were searched in medical databases, including PubMed, Embase, Cochrane Library, CNKI, and Wanfang Data, monographs, theses, and papers presented at conferences. Statistical analyses were performed using Revman 5.3 software. RESULTS: Seven non-randomized controlled trials and one randomized controlled trial met the inclusion criteria. In total, 1382 patients (1511 polyps) were included in the study, including 722 who received UEMR and 789 who received EMR. In the UEMR and EMR groups, the en bloc resection rates were 85.87% and 73.89%, respectively, with a relative risk (RR) value of 1.14 (95% confidence interval [CI]: 1.01-1.30; P < 0.05). In the sub-group analysis, the en bloc resection rate showed no statistically significant difference between the EMR and UEMR groups for polyps less than 20 mm in diameter. However, a statistically significant difference was found between the EMR and UEMR groups for polyps equal to or greater than 20 mm in diameter. The post-endoscopic resection recurrence rates at 3-6 mo of the UEMR and EMR groups were 3.26% and 15.17%, respectively, with an RR value of 0.27 (95%CI: 0.09-0.83; P < 0.05). The post-endoscopic resection recurrence rates of UEMR and EMR at 12 mo were 6.25% and 14.40%, respectively, with an RR value of 0.43 (95%CI: 0.20-0.92; P < 0.05). Additionally, the incidence of adverse events was 8.17% and 6.21%, respectively, with an RR value of 1.07 (95%CI: 0.50-2.30; P > 0.05). CONCLUSION: UEMR is an effective technique for colorectal polyps and appears to have some advantages over EMR, particularly with regard to some treatment outcomes.

Presence of pink-color sign within 1 min after iodine staining has high diagnostic accordance rate for esophageal high-grade intraepithelial neoplasia/invasive cancer.

BACKGROUND/AIM: The dramatic color change after iodine staining (from white-yellow to pink after 2-3 min), designated as the "pink-color sign" (PCS), is indicative of esophageal high-grade intraepithelial neoplasia (HGIN) or an invasive lesion. However, no study has yet examined the association between the time of PCS appearance and histopathology. We investigated the association between the time of PCS appearance and esophageal histopathology in 456 lesions of 438 patients who were examined for suspected esophageal cancer. MATERIALS AND METHODS:: The records of 495 consecutive patients who had suspected esophageal cancer based on gastroscopy and who underwent Lugol's chromoendoscopy from January 2015 to March 2018 were retrospectively reviewed. The time of PCS appearance was recorded in all patients, and tissue specimens were examined. RESULTS: We examined 456 lesions in 438 patients. Use of PCS positivity at 2 min for the diagnosis of HGIN/invasive cancer had a sensitivity of 84.1%, a specificity of 72.7%, and an accuracy of 80.4%. We classified the PCS-positive patients in whom the time of PCS appearance was recorded (168 lesions) into 4 groups: 0-30, 31-60, 61-90, and 91-120 s. Based on a 60-s time for appearance of the PCS, the area under the receiver operating characteristic curve was 0.897, indicating good validity. At the optimal cutoff value of 60 s, the sensitivity was 90.2% and the specificity was 82.3%. The appearance of the PCS within 60 s had a diagnostic accordance rate of 88.6%, significantly higher than appearance of the PCS within 2 min (79.7%, P < 0.05). CONCLUSION: Appearance of the PCS within 1 min after iodine staining has a higher diagnostic accordance rate for esophageal HGIN/invasive cancer than appearance of the PCS at 2 min.

Assessment of dietary phytoestrogen intake via plant-derived foods in China.

The potential influence of dietary phytoestrogen exposure on human health during different life phases including early childhood is a matter of scientific debate. In order to improve the risk-benefit assessment of exposure to dietary phytoestrogen, reliable and age-stratified exposure data are desirable. For contributing to the database on phytoestrogen exposure, in the present study plant-derived foods from the Chinese market were analysed by LC-MS/MS for their contents of phytoestrogens, including daidzein, genistein, secoisolariciresinol, glycitein and coumestrol. The analytical data showed the presence of phytoestrogens in a concentration range of less than 0.1 to about 50 µg g(-1). Dietary intake was assessed on the basis of average food intake data obtained from interviewing 1000 randomly selected people with the help of food frequency questionnaires. Based on the overall population sampled, the average total phytoestrogen intake was estimated at 232 µg kg(-1) day(-1). Genistein contributed to about 66%, secoisolariciresinol and glycitein to about 10% each, and daidzein to about 7% of the overall intake. Coumestrol was present only in trace amounts. Age-related exposure assessment indicated that pre-pubertal children (aged 0-14 years) were exposed at the highest level with an average total phytoestrogen intake of 621 µg kg(-1) day(-1). The substantially higher average exposure of children as compared with adults should trigger further research into the potential health effects of early life exposure to phytoestrogen.

[Synergistic effects of nano-sized magnetic particles and uncoupler to the characteristics of activated sludge].

For improving the performance and sludge settling property of an activated sludge reduction process with uncoupler, in this investigation, uncoupler and nano-sized magnetic particles were added simultaneously to a sequencing batch reactor for exploring their synergistic effects to the characteristics of activated sludge. The results showed that the volume reduction of sludge reached 41% with single 2,4,5-Trichlorophenol (TCP) Comparing with the control experiment, the biodegradability and settling properties of the activated sludge decreased. Under the actions of TCP combined with nano-sized magnetic particles, the volume reduction of sludge reached 34%, the removal efficiencies of COD, nitrogen, and phosphorus as well as the sludge settling property were not significantly influenced. After 31 d's operation, the dehydrogenase activity was improved by 10%-18% and exhibited an accumulative effect over time. It was observed with an optical microscope that the species and amounts of protozoon and metazoan increased and a compact structure of sludge floc was formed. The results also indicated that using nano-sized magnetic particles and uncoupler could restrict the yield of excess sludge and improve the performance of an activated sludge system.

Pharmacokinetic study of lappaconitine hydrobromide in mice by LC-MS.

A high sensitive and rapid method was developed for the analysis of lappaconitine in mouse plasma using liquid chromatography coupled to mass spectrometry (LC-MS). Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 585 --> m/z 535 and m/z 356 --> m/z 192, for the quantification of lappaconitine and tetrahydropalmatine (internal standard, IS), respectively. The method was linear over the concentration range of 3.0-2000.0 ng x mL(-1). The lower limit of quantification was 3.0 ng x mL(-1). Intra- and inter-run precisions (RSD) were both less than 9.9% and accuracy (RE) within +/- 4.8%. After single intravenous injections of lappaconitine hydrobromide at 1.0, 2.0 and 4.0 mg x kg(-1), the elimination half-lives (t(1/2)) were 0.47, 0.48 and 0.49 h, and the areas under the curve (AUC(0-t)) were 55.5, 110.5 and 402.9 ng x h x mL(-1), separately. The pharmacokinetic profile of lappaconitine was linear at relatively lower dose levels (1.0-2.0 mg x kg(-1)). When the dose increased farther to 4.0 mg x kg(-1), the Vz and CL decreased, and the increase fold of the AUC was much larger than that of the dose.

Changes of serum p53 antibodies and clinical significance of radiotherapy for esophageal squamous cell carcinoma.

AIM: To explore the relationship between serum p53 antibodies (p53-Abs) and clinicopathological characteristics and therapeutic effect in patients with esophageal carcinoma (EC), and to investigate sequential changing regularity of serum p53-Abs after radiotherapy. METHODS: The serum p53-Ab levels were detected in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay (ELISA). The blood samples were collected on the day before radiotherapy and on the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and 60 Gy/30 f/36 d after radiotherapy. RESULTS: The level and positive rate of serum p53-Abs in EC patients were significantly higher than those in normal individuals (P<0.05). Serum anti-p53 antibodies were positive in 18 of 46 EC patients (39.1%). The positive rate of p53-Abs in EC was related to histological grade, disease stage and lymph node metastasis (P<0.05), but it was not significantly related to sex, age and to the size and site of tumor. The level and positive rate of p53-Abs had significant differences between before radiotherapy and after administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d (P<0.05 or P<0.01). The positive rate of p53-Abs in EC patients with effect was significantly lower than that in those without effect after radiotherapy (P<0.0001). CONCLUSION: Detection of serum p53-Abs is helpful to the diagnosis of esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before and after radiotherapy in patients with esophageal carcinoma is also useful to evaluate the response to the treatment and prognosis of the patients.

[Construction of the recombinant adenovirus vector of interleukin-1 receptor II and its expression in eutopic stromal cells of endometriosis].

AIM: To develop a gene therapy vector of interleukin-1 receptor II(IL-1RII) with recombinant adenovirus and express IL-1RII in the eutopic stromal cells of endometriosis(EM). METHODS: Get full length of cDNA with IL-1RII gene was obtained by PCR. The gene was then subcloned into the pShuttle-CMV shuttle vector. The resultant plasmid (pShuttle-CMV-RII) was cotransduced into E.coli BJ5183 cells with pAdEasy-1 plasmid to undergo homologous recombination by electroporation. The linearized recombinant plasmid (pAd-RII) was transfected into 293 cells. The recombinant adenovirus was detected by examining the expression of IL-1RII while the recombinant adenovirus of LacZ gene was constructed as control. The stromal cells of EM were infected by the recombinant adenovirus and the expression of IL-1RII was detected by immunohistochemistry(IHC). RESULTS: It was confirmed by sequencing that the two ligand products had no mutation of IL-1RII. Restriction endonuclease analysis confirmed the successful cloning of the gene into the pShuttle-CMV and the recombinants(pAd-RII) were selected for kanamycin resistance. Presence of the recombinant adenovirus was confirmed by the X-gal stain of LacZ and the expression of soluble IL-1RII was detected by ELISA. IL-1RII was expressed in the stromal cells of EM by IHC. CONCLUSION: The recombinant adenovirus of IL-1RII has been successfully constructed and expressed in the stromal cells of EM, which provides a basis for the research into the role of IL-1RII and the effect of biological treatment in EM.