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BACKGROUND: Cardiovascular disease (CVD) is one among the major causes of mortality all round the globe. Several anti-platelet regimens have been proposed following percutaneous coronary intervention (PCI). In this analysis, we aimed to show the adverse clinical outcomes associated with ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin following PCI in patients with versus without diabetes mellitus (DM). METHODS: Electronic databases were searched by four authors from September to November 2023. Cardiovascular outcomes and bleeding events were the endpoints of this analysis. Revman 5.4 software was used to conduct this meta-analysis. Risk ratio (RR) and 95% confidence intervals (CI) were used to represent the results which were generated. RESULTS: Three studies with a total number of 22,574 participants enrolled from years 2013 to 2019 were included in this analysis. Results of this analysis showed that DM was associated with significantly higher risks of major adverse cardiovascular events (RR: 1.73, 95% CI: 1.49 - 2.00; P = 0.00001), all-cause mortality (RR: 2.15, 95% CI: 1.73 - 2.66; P = 0.00001), cardiac death (RR: 2.82, 95% CI: 1.42 - 5.60; P = 0.003), stroke (RR: 1.78, 95% CI: 1.16 - 2.74; P = 0.009), myocardial infarction (RR: 1.63, 95% CI: 1.17 - 2.26; P = 0.004) and stent thrombosis (RR: 1.74, 95% CI: 1.03 - 2.94; P = 0.04) when compared to patients without DM. However, thrombolysis in myocardial infarction (TIMI) defined minor and major bleedings, bleeding defined according to the academic research consortium (BARC) type 3c (RR: 1.31, 95% CI: 0.14 - 11.90; P = 0.81) and BARC type 2, 3 or 5 (RR: 1.17, 95% CI: 0.85 - 1.62; P = 0.34) were not significantly different. CONCLUSION: In patients who were treated with ticagrelor monotherapy after a short course of DAPT with ticagrelor and aspirin, DM was an independent risk factor for the significantly increased adverse cardiovascular outcomes. However, TIMI and BARC defined bleeding events were not significantly different in patients with versus without DM.
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Diabetes Mellitus , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Ticagrelor , Aspirina/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Mounting evidence supports that matrix metalloproteinase (MMPs) are highly associated with tumor progression and that targeting MMPs may overcome the barrier of immune suppression. Among these, whether MMP2 functions as an immunosuppressive role in melanoma, remains unclear. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to assess the prognosis of MMP2 in melanoma, after which Tumor immune estimation resource (TIMER) was used to explore the relationship between MMP2 expression and cancer associated fibroblasts (CAFs) infiltration. Finally, we evaluated the efficacy of MMP2 inhibitor on CAFs infiltration and immunotherapy using a mouse melanoma model. RESULTS: In general, the expression of MMP2, MMP13, MMP16, MMP17 and MMP25 were significantly associated with skin cutaneous melanoma (SKCM) patients prognosis, among which MMP2 low expression benefited patients the most. Especially, the overall survival (OS) of BRAF mutation patients with high MMP2 expression was significantly lower than the MMP2 low expression group, but there was no significant difference in BRAF wild-type patients. KEGG and GO enrichment analysis indicated that MMP2 related genes were mostly associated with extracellular structure organization, collagen-containing extracellular matrix and extracellular matrix structural constituent. Furthermore, in almost all cancers, MMP2 expression was positively correlated with CAFs infiltration. MMP2 inhibitor works synergistically with PD-1 antibody and induces tumor regression in a mouse melanoma model, which is dependent on decreased CAFs infiltration. CONCLUSIONS: This suggests that MMP2 plays a vital role in the regulation of CAFs infiltration, potentially participating in immunotherapy response, and thus representing a valuable target of immunotherapy in melanoma.
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This study investigated the effects of acute heat stress (HS), sex, and their interaction on growth performance, serum biochemical and redox status in the later stage broilers. Two hundred 38-day-old Ross 308 chicks were allocated in a factorial arrangement of 2 × 2 (temperatures and sexes) with 5 replicates of 10 bird each. Thermoneutral and heat-stressed broilers were raised at 24 ± 1 °C or 32 ± 1 °C from day 38 to 39, respectively. HS decreased the average daily feed intake (ADFI) and average daily gain (ADG) whereas it increased feed conversion ratio (FCR), rectal temperature (RT), and respiratory rate (RR) in broilers exposed to high temperature for 24 h and 48 h. Moreover, RT, RR, serum glucose, and HDL-C levels increased while triglyceride (TG), total superoxide dismutase (T-SOD), and glutathione peroxidase (GPx) decreased in broilers exposed to high temperature for 12 h. Male broilers had higher final body weight (FBW), ADFI, ADG, total protein carbonyl group, and lower FCR and T-SOD than females in HS condition for 24 h and 48 h. Lower RT, serum albumin, HDL-C, activities of T-SOD and GPx were observed when compared with those of males in HS condition for 12 h. There were significant temperature × sex interactive effects on ADFI, ADG, and TG in broilers exposed to high temperature for 24 h and 48 h. The present study suggests that the acute HS negatively affects growth performance which is accompanied by the disorder of serum nutritional metabolism and imbalance of redox status in later stage broilers. Some parameters presented sexual differences that suggested it may be more effective to alleviate the negative effects of HS when broiler producers take into account the gender of broiler.
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Galinhas/fisiologia , Resposta ao Choque Térmico , Oxirredução , Animais , Análise Química do Sangue/veterinária , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Feminino , Masculino , Fatores SexuaisRESUMO
Objective: To determine the prevalence and subtypes of Blastocystis in pet dogs in Anhui and Zhejiang Provinces. Methods: Pet dog fecal samples were collected from veterinary clinics in Baohe District of Hefei City, Xuanzhou District of Xuancheng City, Fengyang County and Mingguang City of Chuzhou City, Longzihu District of Bengbu City, Si County of Suzhou City in Anhui Province, as well as in Yuhang District of Hangzhou City in Zhejiang Province from April to December, 2013. Blastocystis was detected by microscopic examination as well as nested PCR and single-step PCR based on small subunit ribosomal DNA sequences. The PCR products were sequenced, and Blastocystis subtypes were assigned. Results: A total of 315 pet dog fecal samples were collected. The incidence of Blastocystis infection determined by microscopic examination, nested PCR and single-step PCR was 1.3%ï¼4/315ï¼, 1.9%ï¼6/315ï¼ and 1.9%ï¼6/315ï¼, respectively. In addition, the two PCR methods both revealed Blastocystis infection only in Chuzhou Cityï¼3.4%, 1/29ï¼ and Hefei Cityï¼5.6%, 4/72ï¼. The pet dogs in Chuzhou City carried ST1 and ST2 subtypes while those in Hefei carried only ST1. There was no significant difference in infection rate between adult and young dogs and between male and female dogs. Conclusion: Blastocystis infection exists in pet dogs in Chuzhou City and Hefei City.
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Infecções por Blastocystis/veterinária , Blastocystis , Animais , Sequência de Bases , Doenças do Cão , Cães , Fezes , Feminino , Masculino , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
OBJECTIVE: To investigate the prevalence of Neospora caninum infection in the intestine of pet dogs in areas of Anhui and Zhejiang. METHODS: A total of 315 fecal samples from pet dogs were collected in pet clinics from April to December 2013 in Baohe District in Hefei city, Xuanzhou District in Xuancheng city, Fengyang County in Chuzhou city, Longzihu District in Bengbu city, and Si County in Suzhou City in Anhui Province, as well as in Yuhang District in Hangzhou city of Zhejiang province. All samples underwent nested-PCR targeting Neospora-specific gene NCLI-004830. The results were further confirmed by PCR amplification of N. caninum ITS1 followed by sequence analysis. RESULTS: The rate of N. caninum infection in the 315 samples was 1.59% (5/315). The infection rate in Chuzhou and Bengbu was 3.37% and 6.45%, respectively, and no N. caninum infection was found in the remaining areas. There was no association between the infection rate and the sex or age of the dogs. CONCLUSION: N. caninum infection is prevalent in pet dogs in Chuzhou and Bengbu of Anhui.
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Coccidiose , Neospora , Animais , China , Doenças do Cão , Cães , Fezes , Intestinos , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
OBJECTIVE: To determine the prevalence of Giardia lamblia and Cryptosporidium species infection in pet dogs, and identify the G. lamblia assemblages and Cryptosporidium species. METHODS: A total of 315 fresh fecal samples were collected from pet clinics in five counties of Anhui Province and in Hangzhou of Zhejiang Province. Hemi-nested-PCR targeting the GDH gene of G. lamblia and nested-PCR targeting the SSU rRNA gene of Cryptosporidium were performed in all the fecal samples. The PCR products were sequenced and analyzed using bioinformatics methods to identify the G. lamblia assemblages and Cryptosporidium species. RESULTS: The positive rates of G. lamblia and Cryptosporidium spp. infections in the 315 fecal samples were 3.2% (10/315) and 1.6% (5/315), respectively. Specifically, the two indicators were both significantly higher in dogs ≤12 months (17.8% and 11.1%, respectively) than in adult dogs (0.7% and 0.0%)(P<0.05). However, there was no significant difference in the two indicators between male and female dogs. In addition, two G. lamblia assemblages were identified, assemblages B (n=6) and D (n=4). Sequence analysis of PCR products of the SSU rRNA gene showed that the five Cryptosporidium isolates were C. canis (n =5). CONCLUSION: The prevalences of G. lamblia and Cryptosporidium infection in pet dogs in Anhui and Zhejiang Provinces were 3.2 % and 1.6 %, respectively. The assemblages of G. lamblia in this study are of types B and D.
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Cryptosporidium/isolamento & purificação , Cães/parasitologia , Giardia lamblia/isolamento & purificação , Animais , China , Criptosporidiose/diagnóstico , Doenças do Cão/diagnóstico , Doenças do Cão/parasitologia , Fezes/parasitologia , Feminino , Giardíase/diagnóstico , Giardíase/veterinária , MasculinoRESUMO
Background: The GIMAP family genes play a key role in immune function. Increasing evidence suggests that GIMAP genes were implicated in the tumorigenesis of lung adenocarcinoma (LUAD). This study aimed to investigate the clinical significance of GIMAP family genes in LUAD. Methods: In this study, we explored the expression, mutation, prognostic value of GIMAP family genes and the correlation with immune microenvironment in LUAD. We further investigated the relationship between GIMAP family genes expression and immunotherapy response in GEO LUAD and melanoma cohorts. Results: Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP2, GIMAP4, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly lower in LUAD tumor tissues than normal tissues. Most GIMAP genes were closely related to age, tumor grade and T stage, but not significantly related to sex, N stage and M stage. In the overall population, patients with high expression of GIMAP family genes had a significant longer overall survival (OS). GO and KEGG enrichment analysis showed that GIMAP family genes were highly enriched in immune-related biological process. The expression of GIMAP family genes was positively correlated with immune cell infiltration and immune checkpoint molecules. Furthermore, high expression of GIMAP family genes were correlated with therapeutic response to immunotherapy in LUAD and melanoma patients. Conclusion: In this study, we identified that GIMAP family genes were significantly associated with immune cell infiltration and immune checkpoint molecules. They potentially play a critical role in anti-tumor immunity and serve as immunotherapy biomarkers.
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Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-ß, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) in vitro primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α in vitro PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) in vitro PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-ß1 by PRRSV and considerably enhanced PRRSV replication in vitro PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/ß/γ/λ1 and TNF-α) during PRRSV infection in vitro and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.
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BACKGROUND: Pneumoconiosis is an important occupational disease; the association between pneumoconiosis and depression was largely unknown. This study aimed to investigate the relationship between pneumoconiosis and the risk of subsequent depression. METHODS: A retrospective cohort study was conducted using Taiwan's National Health Insurance database. The study included 16,795 patients diagnosed with pneumoconiosis between 2008 and 2018 and a comparison cohort of 67,180 individuals without pneumoconiosis, propensity score matched in a 1:4 ratio based on age, sex, monthly income, residential urbanization level, and date of pneumoconiosis diagnosis. The development of depression was monitored until the end of 2019. RESULTS: The incidence of depression was 1.68 times higher in the pneumoconiosis cohort than that in the comparison cohort, with an incidence rate of 10.07 versus 5.99 per 1000 person-years (adjusted hazard ratio [aHR] = 1.84, 95 % confidence interval [CI] = 1.70-1.99). The risk of depression increased with an increased mean annual number of emergency department visits for pneumoconiosis, with aHRs of 1.34 (95 % CI = 1.13-1.59) and 2.31 (95 % CI = 1.94-2.76) for 1 ≤ n < 2, and n ≥ 2 compared to n < 1, respectively. LIMITATION: The database lacked detailed socioeconomic history, family history, and clinical variables. CONCLUSION: This study found that patients with pneumoconiosis have a significantly higher risk of depression than those without pneumoconiosis. Furthermore, the risk of depression increases with the frequency of emergency department visits for pneumoconiosis. Healthcare professionals should pay close attention to the mental health of patients with pneumoconiosis.
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Depressão , Pneumoconiose , Humanos , Estudos Retrospectivos , Depressão/psicologia , Pneumoconiose/epidemiologia , Renda , Fatores de Risco , Taiwan/epidemiologia , IncidênciaRESUMO
BACKGROUND AND AIMS: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy. METHODS: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model. RESULTS: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 µmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort. CONCLUSIONS: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/terapia , PrognósticoRESUMO
INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava carcinoma tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors (TKIs) is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and one patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in one and three patients, respectively. Treatment-related adverse events of any grade occurred in of 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in one patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.
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Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti-PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , ChinaRESUMO
Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.
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The coronavirus disease (COVID-19) pandemic has resulted in an increasing population that is experiencing a wide range of long-lasting symptoms after recovery from the acute infection. Long COVID refers to this specific condition and is associated with diverse symptoms, such as fatigue, myalgias, dyspnea, headache, cognitive impairment, neurodegenerative symptoms, anxiety, depression, and a sense of despair. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. We conducted a literature search between 1 January 2019 and 30 October 2023, focusing on the clinical efficacy and utility of HBOT for treating long COVID and found ten clinical studies that fit the review topic, including one case report, five one-group pretest-posttest design studies, one safety report from a randomized controlled trial (RCT), and three complete reports of RCTs. Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations.
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A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion (p = 0.033) and abduction (p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) (p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 (p = 0.042) and S100A9 (p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.
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Fc gamma receptor-mediated antibody-dependent enhancement (ADE) can promote virus invasion of target cells, sometimes exacerbating the severity of the disease. ADE may be an enormous hurdle to developing efficacious vaccines for certain human and animal viruses. ADE of porcine reproductive and respiratory syndrome virus (PRRSV) infection has been demonstrated in vivo and in vitro. However, the effect of PRRSV-ADE infection on the natural antiviral immunity of the host cells is yet to be well investigated. Specifically, whether the ADE of PRRSV infection affects the levels of type II (interferon-gamma, IFN-γ) and III (interferon-lambdas, IFN-λs) interferons (IFNs) remains unclear. In this study, our results showed that PRRSV significantly induced the secretion of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in porcine alveolar macrophages (PAMs) in early infection, and weakly inhibited the production of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in PAMs in late infection. Simultaneously, PRRSV infection significantly increased the transcription of interferon-stimulated gene 15 (ISG15), ISG56, and 2', 5'-oligoadenylate synthetase 2 (OAS2) in PAMs. In addition, our results showed that PRRSV infection in PAMs via the ADE pathway not only significantly decreased the synthesis of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 but also significantly enhanced the generation of transforming growth factor-beta1 (TGF-ß1). Our results also showed that the ADE of PRRSV infection significantly reduced the mRNAs of ISG15, ISG56, and OAS2 in PAMs. In conclusion, our studies indicated that PRRSV-ADE infection suppressed innate antiviral response by downregulating the levels of type II and III IFNs, hence facilitating viral replication in PAMs in vitro. The ADE mechanism demonstrated in the present study furthered our understanding of persistent pathogenesis following PRRSV infection mediated by antibodies.
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Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.
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Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.
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OBJECTIVE: To investigate the effect of the liquid resuscitation therapy strategy using intra-abdominal pressure (IAP) and oxygenation index (PaO2/FiO2) as the end point in patients with severe acute pancreatitis (SAP). METHODS: A retrospective study was performed, including 84 patients with SAP in emergency intensive care unit of Qingzhou Hospital Affiliated to Shandong First Medical University from January 2018 to August 2021. According to the status of fluid balance at admission, all patients were divided into the positive fluid balance group (43 cases) and the negative fluid balance group (41 cases). The clinical data including gender, age, etiology, underlying disease, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) of all patients were collected. Fluid balance, PaO2/FiO2, IAP, compliance rate, new mechanical ventilation rate and overall hospital stay of 1 week after admission were recorded and compared between the two groups. RESULTS: After 72 hours of treatment, the cumulative fluid balance was (5 219.5±1 038.4) mL in the positive fluid balance group; IAP was higher than that before treatment [mmHg (1 mmHg ≈ 0.133 kPa): 11.9±2.0 vs. 11.7±2.1], but no significant difference was found (P > 0.05); PaO2/FiO2 was significantly higher than that before treatment (mmHg: 299.8±51.4 vs. 220.5±50.4, P < 0.05). After 72 hours of treatment, the cumulative fluid balance in negative fluid balance group was (-3 542.4±1 310.6) mL; IAP was significantly lower than before treatment (mmHg: 11.4±1.8 vs. 15.2±1.9, P < 0.05); PaO2/FiO2 was significantly higher than that before treatment (mmHg: 309.9±50.9 vs. 215.4±49.7, P < 0.05). In the fluid resuscitation goals, after 72 hours of treatment, the compliance rate in the negative fluid balance group was significantly higher than that in the positive fluid balance group [82.93% (34/41) vs. 62.79% (27/43), P < 0.05]; 1 week after admission, the new mechanical ventilation rate in the negative fluid balance group was significantly lower than that in the positive fluid balance group [21.95% (9/41) vs. 41.86% (18/43), P < 0.05]; however, there was no significant difference in overall hospital stay between the two groups (days: 41.2±10.9 vs. 39.1±11.5, P > 0.05). After treatment, 70 patients survived and 14 patients died (including 9 cases in the positive fluid balance group and 5 cases in the negative fluid balance group). CONCLUSIONS: Using IAP and PaO2/FiO2 to guide liquid therapy could result in effective fluid resuscitation in SAP. The treatment strategy effectively improved prognosis of patients with SAP.
Assuntos
Pancreatite , Doença Aguda , Hidratação , Humanos , Pancreatite/terapia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Antibody-dependent enhancement (ADE) is an event in preexisting sub-, or non-neutralizing antibodies increasing the viral replication in its target cells. ADE is one crucial factor that intensifies porcine reproductive and respiratory syndrome virus (PRRSV) infection and results in PRRSV-persistent infection. Nevertheless, the exact mechanisms of PRRSV-ADE infection are poorly understood. In the current research, the results of the ADE assay showed that porcine immunoglobulin G (IgG) specific for the PRRSV significantly enhanced PRRSV proliferation in porcine alveolar macrophages (PAMs), suggesting that the ADE activity of PRRSV infection existed in pig anti-PRRSV IgG. The results of the RNA interference assay showed that knockdown of the Fc gamma receptor I (FcγRI) or FcγRIII gene significantly suppressed the ADE activity of PRRSV infection in PAMs, suggesting that FcγRI and FcγRIII were responsible for mediating PRRSV-ADE infection. In addition, the results of the antibody blocking assay showed that specific blocking of the Sn1, 2, 3, 4, 5, or 6 extracellular domain of the sialoadhesin (Sn) protein or selective blockade of the scavenger receptor cysteine-rich (SRCR) 5 domain of the CD163 molecule significantly repressed the ADE activity of PRRSV infection in PAMs, suggesting that Sn and CD163 were involved in FcγR-mediated PRRSV-ADE infection. The Sn1-6 domains of porcine Sn protein and the SRCR 5 domain of porcine CD163 molecule might play central roles in the ADE of PRRSV infection. In summary, our studies indicated that activating FcγRs (FcγRI and FcγRIII) and viral receptors (Sn and CD163) were required for ADE of PRRSV infection. Our findings provided a new insight into PRRSV infection that could be enhanced by FcγRs and PRRSV receptors-mediated PRRSV-antibody immune complexes (ICs), which would deepen our understanding of the mechanisms of PRRSV-persistent infection via the ADE pathway.