The aminophospholipid transporter, ATP8B3, as a potential biomarker and target for enhancing the therapeutic effect of PD-L1 blockade in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is a prevalent malignant tumor globally, contributing significantly to cancer-related mortality. COAD guidelines label MSI (Microsatellite instability) and MSS (Microsatellite stability) subtypes as global classification criteria and treatment strategy selection criteria for COAD. Various combination therapies involving PD-L1 inhibitors and adjuvant therapy to enhance anti-tumor efficacy. METHODS: Datasets from single-cell RNA sequencing and bulk RNA sequencing in the TCGA and GEO databases were utilized to identify differentially expressed genes (DEGs). Furthermore, the correlation between ATP8B3 and PD-L1 was validated using siRNA, shRNA, and western blot analysis. Additionally, the association between ATP8B3 and immune checkpoint blockade (ICB) therapy was investigated through immune infiltration analysis and flow cytometry in both in vivo and in vitro assays. RESULTS: In the COAD patient group, ATP8B3 significantly contributed to the establishment of an immunosuppressive microenvironment. Inhibiting ATP8B3 led to a reduction in PD-L1 expression in colon cancer cell lines. Additionally, ATP8B3 expression levels could serve as a potential guide for PD-L1 treatment in MSI-H COAD patients, with higher ATP8B3 expression associated with increased sensitivity to PD-L1 therapy. However, due to the lack of immuno-killer cells in the microenvironment of MSS subtypes, elevated ATP8B3 expression couldn't increase the sensitivity of MSS COAD patients to PD-L1 inhibitors. CONCLUSION: Our research results support that Inhibiting ATP8B3 could enhance TIL (tumor-infiltrating lymphocyte) infiltration by reducing PD-L1 expression in MSI-H COAD, thereby serving as an effective strategy to improve PD-L1 blocker efficacy. The treatment strategy of combining ATP8B3 inhibitors and immunotherapy for MSI/MSS COAD patients will be the best choice.

The critical role of RAGE in severe influenza infection: A target for control of inflammatory response in the disease.

Controlling the excessive inflammatory response is one of the key ways to reduce the severity and mortality of severe influenza virus infections. RAGE is involved in inflammatory responses and acute lung injuries. Here, we investigated the role of RAGE and its potential application as a target for severe influenza treatment through serological correlation analysis for influenza patients, and treatment with the RAGE inhibitor FPS-ZM1 on A549 cells or mice with influenza A (H1N1) infection. The results showed high levels of RAGE were correlated with immunopathological injury and severity of influenza, and FPS-ZM1 treatment increased the viability of A549 cells with influenza A infection and decreased morbidity and mortality of influenza A virus infection in mice. The RAGE/NF-κb inflammatory signaling pathway is a major targeting pathway for FPS-ZM1 treatment in severe influenza. These findings provide further insights into the immune injury of severe influenza and a potential targeting candidate for the disease treatment.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Development and evaluation of serological screening based on one dried plasma spot for HIV, syphilis, and HCV.

BACKGROUND: In the effort to prevent and control HIV/AIDS, China has established a national sentinel surveillance system. However, some sentinel sites face limitations in environmental resources and accessibility, prompting the exploration of alternative sample strategies. Dried plasma spots (DPS) samples are viewed as promising alternatives to traditional plasma samples due to their advantages, including sample stability, easy storage, and convenient transport. This study aims to develop a method for screening HIV, Treponema pallidum (TP), and Hepatitis C Virus (HCV) using DPS samples and assess their performance. METHODS: Based on existing commercial assay kits, a detection method was established through the optimization of experimental parameters, including the amount of plasma on filter paper, the volume of elution solution applied to dried plasma spots, the size of dried plasma spots, elution solution volume, elution solution components, elution temperature, and elution time. A series of laboratory evaluation panels were constructed for laboratory assessments, including the laboratory basic panel, laboratory interference panel, and laboratory precision panel. Additionally, clinical samples were used for evaluation. RESULTS: Optimal conditions for DPS sample extraction were: plasma volume, 100 µL; DPS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1‰ Tween20; elution time, 2 h; elution temperature, room temperature. A total of 619 paired plasma/DPS samples were tested by both methods. The DPS-based ELISA method exhibited 100% sensitivity/specificity for HIV, 98.6%/100% for TP, and 99.6%/100% for HCV. Kappa values between the plasma samples and DPS samples were 100% for HIV, 99% for TP, and 100% for HCV. The DPS-based ELISA method failed to detect 1 HCV mono-infected sample and TP in 1 HIV/HCV/TP co-infected sample. For the HIV/HCV/TP co-infected sample, the S/CO in the plasma sample was 2.143 and in the DPS sample was 0.5. For HCV, the S/CO (sample OD/cut-off) was 3.049 in the plasma sample and 0.878 in the DPS sample. CONCLUSIONS: A single DPS, following one-time standardized processing, can be used to detect HIV, HCV, and TP. Researching and establishing laboratory testing methods better suited for China's sentinel surveillance have significant practical applications in improving HIV testing in resource-constrained environments.

Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial.

We assessed the efficacy and safety of sintilimab [an anti-programmed death (PD-1)] plus bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC). The patients received sintilimab (200 mg) plus IBI305 (7.5 mg/kg) and HAIC (FOLFOX for 23 h) and were treated every 3 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC) per mRECIST v1.1. Twenty-nine patients were enrolled in our clinical trial (1 patient voluntarily withdrew due to adverse events after the initial treatment). Objective response was reached in 17/29 (58.6%) patients per mRECIST. A total of 19/29 (65.5%) patients became eligible for further treatment; 14 of them completed surgical resection; 1 (5.3%) achieved pathological complete response (pCR); and 5 (26.3%) reached major partial response (mPR). The 1-year OS rate was better in the PR or pCR+mPR+PR group than in the PD+SD group by either mRECIST or pathological assessment (p=0.039 and 0.006). The 1-year EFS rate was better in the PR group than in the PD+SD group by pathological assessment (p=0.007). The most common treatment-related adverse events (TEAEs) in 30 HCC patients included thrombocytopenia (40.0%), hypertension (23.3%), and leukopenia (23.3%). The grade 3-5 TEAEs that were observed were hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients.

Tumor-associated macrophage-derived transforming growth factor-ß promotes colorectal cancer progression through HIF1-TRIB3 signaling.

Tumor-associated macrophages (TAMs), one of the most common cell components in the tumor microenvironment, have been reported as key contributors to cancer-related inflammation and enhanced metastatic progression of tumors. To explore the underlying mechanism of TAM-induced tumor progression, TAMs were isolated from colorectal cancer patients, and the functional interaction with colorectal cancer cells was analyzed. Our study found that coculture of TAMs contributed to a glycolytic state in colorectal cancer, which promoted the stem-like phenotypes and invasion of tumor cells. TAMs produced the cytokine transforming growth factor-ß to support hypoxia-inducible factor 1α (HIF1α) expression, thereby upregulating Tribbles pseudokinase 3 (TRIB3) in tumor cells. Elevated expression of TRIB3 resulted in activation of the ß-catenin/Wnt signaling pathway, which eventually enhanced the stem-like phenotypes and cell invasion in colorectal cancer. Our findings provided evidence that TAMs promoted colorectal cancer progression in a HIF1α/TRIB3-dependent manner, and blockade of HIF1α signals efficiently improved the outcome of chemotherapy, describing an innovative approach for colorectal cancer treatment.

Diverse and conserved roles of the protein Ssu72 in eukaryotes: from yeast to higher organisms.

Gene transcription is a complex biological process that involves a set of factors, enzymes and nucleotides. Ssu72 plays a crucial role in every step of gene transcription. RNA polymerase II (RNAPII) occupies an important position in the synthesis of mRNAs. The largest subunit of RNAPII, Rpb1, harbors its C-terminal domain (CTD), which participates in the initiation, elongation and termination of transcription. The CTD consists of heptad repeats of the consensus motif Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 and is highly conserved among different species. The CTD is flexible in structure and undergoes conformational changes in response to serine phosphorylation and proline isomerization, which are regulated by specific kinases/phosphatases and isomerases, respectively. Ssu72 is a CTD phosphatase with catalytic activity against phosphorylated Ser5 and Ser7. The isomerization of Pro6 affects the binding of Ssu72 to its substrate. Ssu72 can also indirectly change the phosphorylation status of Ser2. In addition, Ssu72 is a member of the 3'-end cleavage and polyadenylation factor (CPF) complex. Together with other CPF components, Ssu72 regulates the 3'-end processing of premature mRNA. Recent studies have revealed other roles of Ssu72, including its roles in balancing phosphate homeostasis and controlling chromosome behaviors, which should be further explored. In conclusion, the protein Ssu72 is an enzyme worthy of attention, not confined to its role in gene transcription.

Evaluation of seven rapid diagnostic tests for detection of hepatitis C virus antibodies in China.

Rapid diagnostic tests as an attractive alternative to enzyme immunoassay could identify hepatitis C virus (HCV) infected persons more expeditiously. The availability of high performing and quality-assured rapid diagnostic tests are essential to scale-up HCV screening. The study was undertaken to evaluate the performance of seven domestic HCV rapid diagnostic tests kits. The kits were evaluated by using HCV serum panels, including HCV basic panel, analytical specificity panel, mixed titre performance panel, characteristic panel, seroconversion panel, and genotype qualification panel. The results showed that clinical sensitivity, clinical specificity and analytical specificity of seven rapid diagnostic tests kits ranged from 94% (95% CI: 83.2-98.6) to 100% (95% CI: 91.5-100). Furthermore, specimens with HCV genotypes 1b, 2a, 3a, 4a, 5a, 6 could be detected by HCV rapid diagnostic tests kits, whereas specimens with genotypes 1a and 2b could not be detected. Additionally, most HCV rapid diagnostic tests kits had great performance in diagnosing different titres and/or different bands samples, but some low S/CO value specimens may not be fully detected by few rapid diagnostic test kits. In conclusion, seven HCV rapid diagnostic tests reagents presented high sensitivity, specificity, good anti-interference and detection ability of early infection, which could meet the requirements of clinical HCV antibody screening.

ABCB1 and ABCG2 restricts the efficacy of gedatolisib (PF-05212384), a PI3K inhibitor in colorectal cancer cells.

BACKGROUND: Overexpression of ABC transporters is a big challenge on cancer therapy which will lead cancer cells resistance to a series of anticancer drugs. Gedatolisib is a dual PI3K and mTOR inhibitor which is under clinical evaluation for multiple types of malignancies, including colorectal cancer. The growth inhibitory effects of gedatolisib on colorectal cancer cells have been specifically studied. However, the role of ABC transporters on gedatolisib resistance remained unclear. In present study, we illustrated the role of ABC transporters on gedatolisib resistance in colorectal cancer cells. METHODS: Cell viability investigations of gedatolisib on colorectal cancer cells were determined by MTT assays. The verapamil and Ko143 reversal studies were determined by MTT assays as well. ABCB1 and/or ABCG2 siRNA interference assays were conducted to verify the role of ABCB1- and ABCG2-overexpression on gedatolisib resistance. The accumulation assays of gedatolisib were conducted using tritium-labeled paclitaxel and mitoxantrone. The effects of gedatolisib on ATPase activity of ABCB1 or ABCG2 were conducted using PREDEASY ATPase Kits. The expression level of ABCB1 and ABCG2 after gedatolisib treatment were conducted by Western blotting and immunofluorescence assays. The well-docked position of gedatolisib with crystal structure of ABCB1 and ABCG2 were simulated by Autodock vina software. One-way ANOVA was used for the statistics analysis. RESULTS: Gedatolisib competitively increased the accumulation of tritium-labeled substrate-drugs in both ABCB1- and ABCG2-overexpression colorectal cancer cells. Moreover, gedatolisib significantly increased the protein expression level of ABCB1 and ABCG2 in colorectal cancer cells. In addition, gedatolisib remarkably simulated the ATPase activity of both ABCB1 and ABCG2, suggesting that gedatolisib is a substrate drug of both ABCB1 and ABCG2 transporters. Furthermore, a gedatolisib-resistance colorectal cancer cell line, SW620/GEDA, was selected by increasingly treatment with gedatolisib to SW620 cells. The SW620/GEDA cell line was proved to resistant to gedatolisib and a series of chemotherapeutic drugs, except cisplatin. The ABCB1 and ABCG2 were observed overexpression in SW620/GEDA cell line. CONCLUSIONS: These findings suggest that overexpression of ABCB1 and ABCG2 may restrict the efficacy of gedatolisib in colorectal cancer cells, while co-administration with ABC transporter inhibitors may improve the potency of gedatolisib.

Efficacy of cryoablation combined with sorafenib for the treatment of advanced renal cell carcinoma.

OBJECTIVE: To determine the safety and efficacy of cryoablation combined with sorafenib for the treatment of advanced renal cell carcinoma. MATERIAL AND METHODS: We conducted an observational study in 156 patients with advanced renal cell carcinoma unsuitable for surgical treatment. Participants received cryoablation + sorafenib (n = 67) or sorafenib only (n = 89). Objective response rate (ORR), disease control rate (DCR), progression-free survival time (PFS), overall survival (OS), change in immune function after treatment, rate of adverse events, and quality of life were compared between the two groups. RESULTS: In the cryoablation + sorafenib group, ORR and DCR were significantly higher and PFS and OS were significantly longer than in the sorafenib only group (both p < .05). Immune function-related indicators were significantly improved after treatment in the cryoablation + sorafenib group (p < .05), but no significant difference was found between before and after treatment in the sorafenib only group (p > .05). The incidence of targeted drug-related side effects was not significantly different between the groups (p > .05), and cryoablation did not increase the risk of side effects of targeted drugs. CONCLUSION: Cryoablation combined with sorafenib had superior clinical efficacy compared with sorafenib-only for the treatment of advanced renal cell carcinoma unsuitable for surgical treatment. Moreover, this combined therapy may enhance the body's anti-tumor immunity and effectively prolong PFS and OS without compromising patient quality of life, thus representing a new treatment strategy for advanced renal cell carcinoma.

CT-guided percutaneous cryoablation combined with systemic chemotherapy for liver metastases from esophageal carcinoma: Initial experience.

OBJECTIVE: To explore the feasibility, safety and effectiveness of percutaneous cryoablation combined with systemic chemotherapy in the treatment of liver metastases from esophageal carcinoma (ECLM). MATERIALS AND METHODS: We retrospectively collected data of 16 patients who received CT-guided percutaneous cryoablation concurrent systemic chemotherapy for liver metastases after primary esophageal carcinoma resection. Functional Assessment of Cancer Therapy-General (FACT-G) was used for the assessment of quality of life (QOL), and overall survival (OS), progression-free survival (PFS) and complications were also evaluated. RESULTS: The technical success rate was 96%, and no major complications related to cryoablation procedure were detected. Median OS and PFS after cryoablation were 14.5 months (range, 4-51 months) and 7.5 months (range, 1-31 months), respectively. The 1-year, 2-year, and 3-year survival rates were 56.3%, 31.3%, and 18.8%, respectively. The PFS rate at 6-month, 1-year, and 2-year after procedure were 68.8%, 31.3% and 18.8%, respectively. Furthermore, the QOL of patients was improved after cryoablation therapy compared with preoperative scores (P < 0.05). CONCLUSIONS: Percutaneous cryoablation combined with systemic chemotherapy is a safe, feasible and effective method to treat liver metastases from esophageal carcinoma. And to a certain extent, this approach is very efficacious in improving the QOL of patients with ECLM.

Receiver performance characteristics of single-photon lidar in a strong background environment.

The detection performance of the single-photon lidar (SPL) receiver is investigated as a function of optical attenuation and superconducting nanowire single-photon detector (SNSPD) parameters (detection efficiency and dead time) in a strong background environment. With detection theory, it is found that there is optimal attenuation to make detection probability the highest at a given false alarm probability, namely, optimal working conditions. Optical attenuation is proved to be required only when the background photon number is higher than a certain value; otherwise, it is not necessary. Furthermore, the performance of a Geiger-mode avalanche photodiode (GMAPD) is compared. Under optimized working conditions, the SNSPD-based receiver exhibits higher detection performance in a strong background environment than that of the GMAPD-based receiver due to shorter dead time, while in a low-noise environment, attenuation is not essential, and detection efficiency becomes the dominant factor. The theoretical result gives a reference for the SPL receiver system design to achieve optimal detection performance.

The oncologic results of cryoablation in prostate cancer patients with bone metastases.

OBJECTIVE: To explore the role of whole gland cryoablation plus ADT in prostate cancer (PCa) with bone metastases compared with ADT treatment alone in metastatic PCa. METHODS: A total of 30 patients with biopsy-proven PCa with bone metastases underwent cryoablation and ADT treatment. The control group consisted of 30 men who were initially treated with ADT only and who were followed until progression, development of castration resistant PCa or death. Patients were pair matched for age, PSA level, clinical stage, preoperative biopsy Gleason score and bone metastases. Time to clinical progression, time to CRPC, cancer-specific survival and overall survival were analysed using descriptive statistical analysis. RESULTS: Age at diagnosis, baseline PSA, biopsy Gleason score and ECOG status were comparable between the two groups. Prostate cryoablation was well tolerated and no serious complications occurred. At the last follow-up, patients in the cryoablation and ADT treatment group had a lower median PSA nadir (0.4 ng/ml vs. 0.8 ng/ml, p < 0.01) and longer time to CRPC (33 ± 0.9 mo vs. 22 ± 0.8 mo, p < 0.01). Further analyses detected the statistically significant benefits of cryoablation treatment not only in PFS (41 ± 1.4 mo vs. 22 ± 0.8 mo, p < 0.01), but also in CSS (52 ± 1.9 mo vs. 32 ± 2.4 mo, p ± 0.01) and OS (41 ± 1.5 mo vs. 28 ± 1.7 mo, p < 0.01). Moreover, there were fewer palliative procedures for local progression in the cryoablation group than the controls. CONCLUSIONS: Cryoablation plus ADT might be a treatment option in the multimodality management of metastatic prostate cancer. Further investigations are warranted.

Immunological response induced by cryoablation against murine H22 hepatoma cell line in vivo.

OBJECTIVES: To describe immunological consequences induced by cryoablation against H22 cells in vivo. METHODS: Adult BALB/c mice underwent subcutaneous implantation of H22 cells. All of them were assigned into three groups randomly: group A (false surgery), group B (cryoablation) and group C (cryoablation plus Freund's adjuvant). Animals were sacrificed 1, 2 and 3 weeks after treatment. Serum IFN-γ and IL-4, Th1/Th2 in spleens and cytotoxicity were detected. RESULTS: Compared with that of group A, (1) INF-γ of group B was higher, but IL-4 was lower; cryoablation plus Freund's adjuvant enhanced these effects. (2) Th1/Th2 rose significantly in both group B and group C. (3) Strong cytolytic activity against H22 cells of group B and group C was found on day 7, 14 and 21. CONCLUSIONS: Our study showed a marked shift toward Th1 and IFN-γ expression after cryoablation, with an immuno-stimulatory effect against murine H22 hepatoma Cell.

Transmission network characteristics based on env and gag sequences from MSM during acute HIV-1 infection in Beijing, China.

Molecular epidemiology can be used to identify human immunodeficiency virus (HIV) transmission clusters, usually using pol sequence for analysis. In the present study, we explored appropriate parameters to construct a simple network using HIV env and gag sequences instead of pol sequences for constructing a phylogenetic tree and a genetic transmission subnetwork, which were used to identify individuals with many potential transmission links and to explore the evolutionary dynamics of the virus among men who have sex with men (MSM) in Beijing. We investigated 70 acute HIV-1 infections, which consisted of HIV-1 subtype B (15.71%), the circulating recombinant forms CRF01_AE (47.14%), CRF07_BC (21.43%), CRF55_01B (1.43%), and CRF65_cpx (4.29%), and an unknown subtype (10.00%). By exploring the similarities and differences among HIV env, gag and pol sequences in describing the dynamics of the HIV-1 CRF01_AE transmission subnetwork among Beijing MSM, we found that four key points of the env sequences (strains E-2011_BJ.CY_16014, E-2011_BJ.FT_16017, E-2011_BJ.TZ_16064, and E-2011_BJ.XW_16035) contained more transmission information than gag sequences (three key points: strains G-2011_BJ.CY_16014, G-2011_BJ.FT_16017, and G-2011_BJ.XW_16035) and pol sequences (two key points: strains P-2011_BJ.CY_16014 and P-2011_BJ.XW_16035). Although the env and gag sequence results were similar to pol sequences in describing the dynamics of the HIV-1 CRF01_AE transmission subnetwork, we were able to obtain more precise information, allowing identification of key points of subnetwork expansion, based on HIV env and gag sequences instead of pol sequences. Taken together, the key points we found will improve our current understanding of how HIV spreads between MSM populations in Beijing and help to better target preventative interventions for promoting public health.

Efficacy and Safety of CT-guided Percutaneous Cryoablation for Hepatocellular Carcinoma at High-risk Sites.

OBJECTIVE: This study aims to assess the efficacy and safety of CT-guided percutaneous cryoablation in treating hepatocellular carcinoma (HCC) located explicitly in high-risk sites. MATERIALS AND METHODS: Data were collected retrospectively from 685 HCC patients undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. Of these, 106 patients had lesions in high-risk sites, defined as a minimum distance of less than 10 mm from the heart/great vessels, diaphragm, gastrointestinal tract, and gallbladder, as determined by preoperative CT or MRI imaging. Technical success rate, complete ablation rate, and complications at 1, 12, and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted, utilizing propensity score matching (PSM) to mitigate patient selection bias. Univariate and multivariate logistic regression analyzes were performed to identify risk factors for the incidence of coronary heart disease. RESULTS: The study comprised 106 cases in the high-risk group and 218 cases in the non-high-risk group. After PSM analysis until December 2021, 95 matched pairs were included. Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. Follow-up ranged from 24 to 38 months. The complete ablation rate was 82.1% and 71.7% in the high-risk group and 83.9% and 73.9% in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups before and after PSM (P > 0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤ 5 mm and preoperative transarterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. CONCLUSION: CT-guided percutaneous cryoablation proves to be a safe and effective approach for HCC patients with high-risk sites, serving as an alternative to surgical treatment.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

Objectives: This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Methods: This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. Results: The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. Conclusions: BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

HIV and syphilis prevalence among men who have sex with men: a cross-sectional survey of 61 cities in China.

BACKGROUND: Human immunodeficiency virus (HIV) has rapidly spread among men who have sex with men (MSM) in China in recent years; the magnitude of the epidemic is unclear. We sought to test 3 hypotheses: (1) The prevalence of both HIV and syphilis among MSM in China is high, (2) the 2 epidemics each have unique geographical distributions, and (3) demographic and sexual behavior characteristics are different among segments of the MSM population in China. METHODS: A total of 47 231 MSM from 61 cities in China participated in a cross-sectional survey conducted from February 2008 to September 2009. Demographic and behavioral data were collected and analyzed and blood samples tested for HIV and syphilis. Three subgroups among the broader MSM sample were described. Main outcome measures were HIV and syphilis prevalence. RESULTS: An overall prevalence of 4.9% (2314/47 231; 95% confidence interval [CI], 4.7%-5.1%) for HIV and 11.8% (5552/47 231; 95% CI, 11.5%-12.0%) for syphilis was found. Syphilis-positive MSM had the highest HIV prevalence, 12.5% (693/5552; 95% CI, 11.6%-13.4%). However, correlations between HIV and syphilis prevalence were found in only 3 of 6 geographical regions (Northwest: r = 0.82, P = .0253; East: r = 0.78, P = .0004; and South-central: r = 0.63, P = .0276). Three subgroups-nonlocal MSM, Internet-using MSM, and female-partnering MSM-were found to have different profiles of characteristics and behaviors. CONCLUSIONS: HIV and syphilis prevalences among MSM in China are high and the 2 epidemics are largely separate geographically. Three segments of the Chinese MSM population each have different demographic and sexual risk "profiles" that suggest high potential for bridging infection across geographies, generations, and sexes.

Prevalence and risk factors of hepatitis C and B virus infections in hemodialysis patients and their spouses: a multicenter study in Beijing, China.

Hemodialysis patients are at risk for hepatitis C and B virus infections. This study investigated the prevalences and risk factors of HCV and HBV infection and the distribution of HCV genotypes among hemodialysis patients and their spouses. From August to November 2011, a cross-sectional study was conducted on 20 hemodialysis units in Beijing to investigate prevalences and risk factors for markers of HCV and HBV among 2,120 patients and 409 spouses. In hemodialysis patients, prevalences of anti-HCV, HCV RNA, and hepatitis B surface antigen (HBsAg) were 6.1%, 4.6%, and 7.0%, respectively. The prevalence of HCV antibodies among spouses was 0.5%, of HCV RNA was 0.2%, and of HBsAg was 4.2%. Risk factors for HCV infection were dialysis duration, blood transfusion, and attending more than one dialysis unit. HBV infection was independently associated with age, family member with hepatitis infection, gender, and surgery. The predominant HCV genotypes were 1b (89.0%) and 2a (7.7%), and genotypes 3a, 3b, and 6a were each 1.1%. A significant decrease in HCV and HBV prevalences in Chinese dialysis units showed that infection control measures were effective. However, because nosocomial transmissions persist, strict adherence to infection control measures should be emphasized to reduce the risk of transmission.

[Epidemiological survey on the hepatitis C virus and its genotyping analysis in Henan province in 2012].

OBJECTIVE: To investigate the prevalence and distribution of hepatitis C virus (HCV) genotypes in Henan province in 2012. METHODS: A total of 32 203 permanent residents (1 to 74 years old) in Henan were recruited using multi-stage random samping method from March to June 2012. All participants were asked to complete a questionnaire to collect demographic information, past medical history and the exposure history of risk factors. A blood sample of 5 ml was collected at the same time. The condition of anti-HCV and HCV RNA was determined through the ELISA test and nested RT-PCR. HCV RNA positive samples were further subject to the nonstructural protein 5 region (NS5B) gene amplification and sequencing. The sequence was amplified for the phylogenetic tree and genetic analysis. The differences of the positive rate of anti-HCV and HCV RNA and the HCV genetic subtype distribution in different respondents'characteristics were analyzed. RESULTS: Among 32 203 subjects, the overall positive rate of anti-HCV and HCV RNA were 0.48% (153/32 203) and 0.24% (78/32 203), in which men were 0.42% (65/15 634), and 0.23% (36/15 634), and women were 0.53% (88/16 569) and 0.25% (42/16 596). The differences between men and women were not statistically significant (χ(2) values were 2.26, 0.18, respectively, both P values > 0.05). The results of NS5B genotyping and molecular evolution analysis showed that there were six subtypes in the 71 HCV RNA positive samples.In those six subtypes, the proportion of genotypes 1b, 6a, 3a, 2a, 3b and 1a were 56.3% (40/71), 19.7% (14/71), 11.3% (8/71), 8.5% (6/71), 2.8% (2/71) and 1.4% (1/71), respectively. The HCV genetic subtypes of infestor were mainly present with two branches of 1b and 6a, and the two subtypes Bootstrap values were 0.95. CONCLUSION: The prevalence of HCV infection was high in Henan. The major HCV genotypes in patients with HCV infection were 1b and 6a.