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Background:For complete tumor ablation in different tissues, it is necessary to investigate the exact coagulation zone of microwave ablation in different tissues. The aim of this study was to compare the extent of microwave ablation zone in muscle, liver and adipose tissue in ex vivo porcine models and assess the shape of microwave coagulation zone among these tissues. Materials and Methods:Microwave ablations were performed in ex vivo porcine muscle, liver and adipose tissue using 2450-MHz cooled-shaft microwave antenna. The content of water, fat and protein in these three tissues was determined. Two power increments (40 and 80 W) and five time increments (1, 3, 5, 7, and 10 minutes) were used in this study. Diameters and shapes of the ablation zones were assessed on gross specimens. Results:The average percentages of water, fat and protein in these three tissues were significantly different (P < 0.001), respectively. The long-axis and short-axis diameters among these three tissues at each time-power combination were not significantly different (P > 0.05). The coagulation zones were all elliptical in muscle, liver and adipose tissue. When microwave ablation was performed in the tissue containing both muscle and adipose tissue, the coagulation zone was also elliptical. Regardless of the output power, the ellipticity index (EI) value of 1 minute treatment duration was higher than that of 10 minutes treatment duration (P < 0.05). Furthermore, the EI value did not decrease significantly when the treatment duration was more than 5 minutes (P > 0.05). Conclusion:The extent of microwave ablation zones was not significantly different among completely different tissues. Microwave ablations with ≥ 5 minutes time duration can induce coagulation zones with clinical desirable shape. Future clinical studies are still required to determine the role of microwave ablation in different tissues. [ABSTRACT FROM AUTHOR]

The HIV reservoir is more dynamic than previously thought with around 70% of the latent reservoir originating from viruses circulating within 1 year of the initiation of antiretroviral therapy (ART). In an ex vivo model system of HIV latency, it was reported that early exposure to class I histone deacetylase (HDAC) inhibitors might prevent these more recently infected cells from entering a state of stable viral latency. This finding raises the possibility that co-administration of HDAC inhibitors at the time of ART initiation may prevent the establishment of much of the HIV reservoir. Here, we tested the effects of the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and panobinostat co-administered at the time of ART initiation on the formation of the viral reservoir in HIV-infected humanized mice. As previously shown, SAHA and panobinostat were well tolerated in humanized mice. Unexpectedly, co-administration of SAHA resulted in an increase in the frequency of CD4 + cells carrying HIV DNA but did not alter the frequency of cell-associated HIV RNA in HIV-infected, ART-treated humanized mice. Co-administration of panobinostat did not alter levels of cell-associated HIV DNA or RNA. Our in vivo findings indicate that co-administration of HDAC inhibitors initiated at the same time of ART treatment does not prevent recently infected cells from entering latency.IMPORTANCECurrent antiretroviral therapy (ART) does not eradicate cells harboring replication-competent HIV reservoir. Withdrawal of ART inevitably results in a rapid viremia rebound. The HIV reservoir is more dynamic than previously thought. Early exposure to class I histone deacetylase (HDAC) inhibitors inhibit these more recently infected cells from entering a state of stable viral latency in an ex vivo model of latency, raising the possibility that co-administration of HDAC inhibitors at the time of ART initiation may reduce much of the HIV reservoir. Here, we tested the effects of the HDAC inhibitors suberoylanilide hydroxamic acid or panobinostat during ART initiation on the formation of the viral reservoir in HIV-infected humanized mice. Our in vivo study indicates that in contrast to in vitro observations, the co-administration of HDAC inhibitors at the same time of ART initiation does not prevent recently infected cells from entering latency., Competing Interests: The authors declare no conflict of interest.

Introduction: Locoregional recurrent breast cancers have a poor prognosis. Little is known about the prognostic impact of immune microenvironment, and tertiary lymphoid structures (TLSs) in particular have not been reported. Thus, we aimed to characterize the immune microenvironment in locoregional recurrent breast tumors and to investigate its relationship with prognosis., Methods: We retrospectively included 112 patients with locoregional recurrent breast cancer, and hematoxylin-eosin staining and immunohistochemical staining (CD3, CD4, CD8, CD19, CD38, and CD68) were performed on locoregional recurrent tumor samples. The association of immune cells and TLSs with progression-free survival (PFS) were analyzed by survival analysis., Results: We found more immune cells in the peritumor than stroma. After grouping according to estrogen receptor (ER) status, a low level of peritumoral CD3+ cells in ER+ subgroup (p = 0.015) and a low level of stromal CD68+ cells in ER- subgroup (p = 0.047) were both associated with longer PFS. TLSs were present in 68% of recurrent tumors, and CD68+ cells within TLSs were significantly associated with PFS as an independent prognostic factor (p = 0.035). TLSs and immune cells (CD3, CD38, and CD68) within TLSs were associated with longer PFS in ER- recurrent tumors (p = 0.044, p = 0.012, p = 0.050, p < 0.001, respectively), whereas CD38+ cells within TLSs were associated with shorter PFS in ER+ recurrent tumors (p = 0.037)., Conclusion: Our study proposes potential predictors for the clinical prognosis of patients with locoregional recurrent breast cancer, emphasizing the prognostic value of immune cells within TLSs, especially CD68+ cells., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A 2A adenosine receptor (A 2A R), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A 2A R antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of A 2A R antagonists, dual-acting compounds incorporating A 2A R antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of A 2A R. Compound 24e (IHCH-3064) exhibited potent binding to A 2A R ( K i = 2.2 nM) and selective inhibition of HDAC1 (IC 50 = 80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. Intraperitoneal administration of 24e (60 mg/kg, bid) inhibited mouse MC38 tumor growth with a tumor growth inhibition rate of 95.3%. These results showed that dual-acting compounds targeting A 2A R and HDAC are potentially immunotherapeutic agents that are worth further exploring.

Although progress has been made on constructing potent bi-specific broadly neutralizing antibody (bi-bNAb), few bi-bNAbs have been evaluated against HIV-1/AIDS in non-human primates (NHPs). Here, we report the efficacy of a tandem bi-bNAb, namely BiIA-SG, in Chinese-origin rhesus macaques (CRM) against the CRM-adapted R5-tropic pathogenic SHIV SF162P3CN challenge. Pre-exposure BiIA-SG injection prevents productive viral infection in 6 of 6 CRMs with unmeasurable proviral load, T cell responses, and seroconversion. Single BiIA-SG injection, at day 1 or 3 post viral challenge, significantly reduces peak viremia, achieves undetectable setpoint viremia in 8 of 13 CRMs, and delays disease progression for years in treated CRMs. In contrast, 6 of 8 untreated CRMs develop simian AIDS within 2 years. BiIA-SG-induced long-term protection is associated with CD8 + T cells as determined by anti-CD8β antibody depletion experiments. Our findings provide a proof-of-concept that bi-bNAb treatment elicits T cell immunity in NHPs, which warrant the clinical development of BiIA-SG for HIV-1 prevention and immunotherapy., Competing Interests: Declaration of interests Z.C. and H.W. are co-inventors of BiIA-SG., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Radiofrequency ablation (RFA) is a minimally invasive thermal ablation technique. We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of RFA for treating patients with breast cancer., Methods: A literature search was conducted in PubMed, Embase, and Web of Science databases. Eligible studies were clinical trials that assessed RFA in patients with breast cancer. The outcomes included complete ablation rate, recurrence rate, excellent or good cosmetic rates, and complication rate. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies., Results: Fifteen studies, with a total of 404 patients, were included in this meta-analysis. Pooled results showed that 89% (95% confidence interval: 85%-93%) of patients achieved a complete ablation after RFA treatment and 96% of patients reported a good-to-excellent cosmetic result. Although the pooled result for recurrence rate was 0, several cases of relapse were observed at different follow-up times. No RFA-related complications were recorded, except for skin burn with an incidence of 4% (95% confidence interval: 1%-6%)., Conclusion: This meta-analysis showed that RFA can be a promising alternative option for treating breast cancer since it produces a higher complete ablation rate with a low complication rate. Further well-designed randomized controlled trials are needed to confirm the efficacy and safety of RFA for breast cancer.

Objective: To observe the clinical effect of float needle therapy combined with reperfusion activity for pain induced by cyclomastopathy., Methods: Thirty-five female patients with cyclomastopathy were randomly divided into a comprehensive group (18 cases) and a float needle group (17 cases). In the comprehensive group, float needle manipulation was used at the centre of the biceps brachii belly or the ligature between the affected nipple and breast nodule, about 4 cm beside the exterior margin of the breast, and the reperfusion activity of the affected upper limb and breast was combined. In the float needle group, simple float needle therapy was adopted. In the two groups, treatment was started 7 ± 3 days before menstruation, once every other day. After 3-time treatment, the changes of short form McGill Pain Questionnaire (SF-MPQ) scores before and after treatment, the time of pain relieved during the first treatment, recurrence in 3 months after treatment and the adverse reaction were observed. Also, the clinical effects of the two groups were compared., Results: Immediately at the end of the first treatment,after 3-time treatment and while followed up for one month, each item score and the total score of SF-MPQ were decreased apparently than the scores before treatment (all P < 0.05), and all the scores mentioned above of the comprehensive group were declined more obviously than those of the float needle group (all P < 0.05). The time of pain relieved during the first treatment of the comprehensive group was much shorter than that of the float needle group [(94.72 ± 33.67) s vs (162.06 ± 29.16) s, P < 0.01]. The recurrence rate of the comprehensive group in 3 months after treatment was 5.9% (1/17), which was better than 20.0% (3/15) of the float needle group (P < 0.01)., Conclusion: Float needle therapy combined with reperfusion activity and simple float needle therapy can both safely and effectively improve cyclomastopathy, and the combination therapy is better than simple float needle therapy in the aspects of pain relieving effect at once and the long term effect.

Objective: To elucidate the effects of exopolysaccharide from Tolypocladium sinense on murine immunocytes in vitro., Methods: Extracted exopolysccharide (EPS) from cultured Tolypocladium sinense. The effects of EPS on mouse immune parameters were detected in vitro using cell culture techniques., Results: The results indicated that EPS might significantly not only promote mouse macrophage neutral red uptake ability and cytotoxicity (P < 0.05), but also stimulate their thymus lymphocytes proliferation (P < 0.05)., Conclusion: EPS may elevate murine cellular immunity to a certain.