Efficacy of the intralesional treatment with Chenopodium ambrosioides in the murine infection by Leishmania amazonensis

AIM OF THE STUDY: Leishmaniasis, caused by protozoan from Leishmania genus, is an endemic disease in the tropical and subtropical regions of the world. The chemotherapy to this disease is not always effective and can cause several side effects. Chenopodium ambrosioides L. (Chenopodiaceae) is used by the native people in the treatment of cutaneous ulcers caused by different species of Leishmania. The aim of this study was to investigate the effect of the treatment with a hydroalcoholic crude extract (HCE) from the leaves of Chenopodium ambrosioides on the murine infection with Leishmania amazonensis. MATERIAL AND METHODS: The mice were treated for 4-6 weeks post-infection (p.i.) with HCE (5 mg/kg) or meglumine antimoniate (Sb(v)) (28 mg/kg) either by the oral route, once a day, for 15 days or by five intralesional (IL) injections at intervals of 4 days. The thickness of the infected paws was determined weekly and the parasite load evaluated in the draining lymph nodes (LN), the spleen and in the footpad after 7 weeks of infection. The nitric oxide (NO) production was evaluated in cultures with cells from peritoneum or LN. RESULTS: The IL treatment increased the NO production in the LN and peritoneum cultures and reduced the parasite load from the footpad, spleen and LN. On the other hand, the oral treatment decreased did alter neither the NO production nor the parasite load. CONCLUSIONS: IL HCE treatment was more efficient than the oral HCE treatment since the former was able to control the dissemination of infection. This effect can be due to either a direct leishmanicidal effect of HCE or the improvement in the NO production by HCE-stimulated macrophages. The results could justify the topical use of the Chenopodium ambrosioides' leaves in the treatment of the ulcers caused by Leishmania.     

The impact of colorectal surgery on health-related quality of life in older functionally dependent patients with cancer – A longitudinal follow-up study

BackgroundOlder patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery.MethodsIncluded were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index <19. Using mixed-model regression analysis associations between dependency, time and HRQoL outcomes were tested and corrected for confounders.ResultsResponse rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p < .05). In functional independent patients, we observed no clinically relevant change in HRQoL.ConclusionColorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making.     

通腑泄浊汤对肾间质纤维化大鼠α-SMA、LN、ColⅢ表达的影响

目的:研究通腑泄浊汤(黄芪、大黄、石菖蒲、牵牛子、附子、人参、白术、丹参、王不留行、橘皮)对肾间质纤维化大鼠α-SMA、LN、ColⅢ表达的影响,探讨其抗肾间质纤维化的作用机制。方法:采用单侧输尿管梗阻(UUO)诱导大鼠肾间质纤维化的动物模型,以依那普利为阳性对照,将大鼠随机分为假手术组,模型组,依那普利组,通腑泄浊汤高剂量组,中剂量组,低剂量组。术后第12天处死大鼠,收集血清测定肌酐、尿素氮水平、免疫组化半定量检测各组大鼠肾间质α-平滑肌肌动蛋白(α-SMA)、Ⅲ型胶原(ColⅢ)、层连接蛋白(LN)的表达。肾组织用HE、VG染色评定肾小管间质损伤及胶原沉积程度。结果:模型组α-SMA、LN、ColⅢ表达、BUN、Scr及肾小管间质损伤指数、胶原沉积程度高于假手术组(P<0.01),通腑泄浊汤与依那普利组比较α-SMA、LN、ColⅢ、BUN、Scr的表达均明显降低(P<0.05),肾小管间质损伤指数及胶原纤维沉积减轻。结论:通腑泄浊汤可能是通过下调α-SMA、LN、ColⅢ的表达而减轻肾间质纤维化。     

Relationship between chemokine receptor 5 Δ32/W gene polymorphism and lupus nephritis

Results from the published studies on the association between chemokine receptor 5 (CCR5) Δ32/W gene polymorphism and lupus nephritis (LN) are still conflicting. This meta-analysis was performed to evaluate the relationship between CCR5 Δ32/W gene polymorphism and LN and to explore whether CCR5 Δ32 allele, Δ32/Δ32 and W/W genotypes could become a predictive marker for systemic lupus erythematosus (SLE) developing into LN. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of March 1, 2014, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Five investigations were identified for the analysis of association between CCR5 Δ32/W gene polymorphism and LN. In the overall populations, Asians, Caucasian population, the association between CCR5 Δ32/W gene polymorphism and LN susceptibility was not found. Interestingly, a trend toward an association of Δ32 allele and W/W genotype with LN risk was observed in African population. However, this meta-analysis only included one study for the study in Africans. We also found that the gene distribution of CCR5 Δ32/W gene polymorphism between SLE group and LN group were not different. In conclusion, our results indicate that CCR5 Δ32/W gene polymorphism was not associated with LN risk and might be no a significant genetic molecular marker to predict the SLE patients developing into LN. However, more investigations are required to further clarify this association.     

Advantages of preoperative localization and surgical resection of metastatic axillary lymph nodes using magnetic seeds after neoadjuvant chemotherapy in breast cancer

PurposeTo assess the safety and effectiveness of magnetic seeds in preoperative localization and surgical dissection of metastatic axillary lymph nodes (LN+) in breast cancer patients with axillary involvement, after neoadjuvant chemotherapy (NAC). In addition, to assess the impact of targeted axillary dissection (TAD) in reducing the rate of false negatives (FN) in sentinel lymph node biopsy (SLNB).Materials and MethodsA cross-sectional prospective cohort study was conducted from April 2017 to September 2019, including breast cancer patients with axillary lymph node involvement treated with NAC. Prior to NAC, the LN+ were marked by ultrasound-guided clip insertion. After NAC, a magnetic seed (Magseed®) was inserted in the clip-marked lymph node (MLN). During surgery, the MLN was located and removed with the aid of a magnetic detection probe (Sentimag®) and the sentinel lymph node was removed. Axillary lymph node dissection (ALND) was used to determine the rate of FN for SLNB alone and the combination of SLNB and MLN dissection, called TAD.ResultsThe study included 29 patients (mean age, 55; range, 30–78 years). Selective preoperative localization and surgical dissection were successful for all 30 MLNs (100%). The MLN corresponded to the SLN in 50% of cases. After ALND, there were 21.4% (3/14) FN with SLNB alone and 5.9% (1/17) with TAD.ConclusionsFollowing NAC, selective surgical removal of MLN by preoperative localization using magnetic seeds is a safe and effective procedure with a success rate of 100%. Adding TAD reduces the rate of FN associated with SLNB alone.     

慢性乙型肝炎病毒复制与肝纤维化血清学指标相关性分析

目的探讨慢性乙型肝炎患者(chronic hepatitis B,CHB)HBV DNA复制与肝纤维化血清学指标之间的相关性。方法 308例慢性乙型肝炎患者同时接受血清HBV DNA、HBeAg、透明质酸(HA)、Ⅲ型前胶原(PcⅢ)、Ⅳ型胶原(Ⅳ-C)和层粘连蛋白(LN)检测。结果 HBV DNA含量在105~107IU/ml、107IU/ml两组肝纤维化血清学四项指标值均高于103IU/ml组,差异均有统计学意义(P0.05);HBV DNA含量在105~107IU/ml、107IU/ml两组与103~105IU/ml组比较,HA、PcⅢ、Ⅳ-C三项指标值均高于103~105IU/ml组,差异均有统计学意义(P0.05),而LN差异无统计学意义(P0.05);HBV DNA含量103IU/ml与103~105IU/ml组比较、105~107IU/ml与107IU/ml组比较,肝纤维化四项血清学指标之间差异均无统计学意义(P0.05);当HBV DNA含量103IU/ml时,HBeAg阳性组与HBeAg阴性组比较肝纤维化四项指标之间差异无统计学意义(P0.05),当HBV DNA含量高于103IU/ml时,HBeAg阳性组HA、PcⅢ、Ⅳ-C三项指标值均高于HBeAg阴性组,差异有统计学意义(P0.05),而LN差异无统计学意义(P0.05)。结论慢性乙型肝炎患者乙肝病毒的复制与肝纤维化血清学指标之间存在一定的相关性,但不呈线性相关。     

Diagnosis and Management of Benign,Atypical, and Indeterminate Breast Lesions Detected on Core Needle Biopsy

Imaging abnormalities detected by mammographic screening often lead to diagnostic evaluations, with suspicious abnormalities subjected to image-guided core needle biopsy (CNB) to exclude malignancy. Most CNBs reveal benign pathological alterations, termed benign breast disease (BBD). Adoption of CNB presents challenges with pathologic classification of breast abnormalities and management of patients with benign or atypical histological findings. Patient management and counseling after CNB diagnosis of BBD depends on postbiopsy determination of radiologic-pathologic concordancy. Communication between radiologists and pathologists is crucial in patient management. Management is dependent on the histological type of BBD. Patients with concordant pathologic imaging results can be reassured of benign biopsy findings and advised about the future risk of developing breast cancer. Surgical consultation is advised for patients with discordant findings, symptomatic patients, and high-risk lesions. This review highlights benign breast lesions that are encountered on CNB and summarizes management strategies. For this review, we conducted a search of PubMed, with no date limitations, and used the following search terms (or a combination of terms): atypical ductal hyperplasia, atypical hyperplasia, atypical lobular hyperplasia, benign breast disease, cellular fibroepithelial lesions, columnar cell lesions, complex sclerosing lesion, core needle biopsy, fibroadenomas, flat epithelial atypia, lobular carcinoma in situ, lobular neoplasia, mucocele-like lesions, phyllodes tumor, pseudoangiomatous stromal hyperplasia, radial scar, and vascular lesions. The selection of references included in this review was based on study relevance and quality. We used additional articles culled from the bibliographies of retrieved articles to examine the published evidence for risk factors of BBD.     

血清肝纤四项检测在诊断原发性肝癌的应用

目的探讨血清肝纤四项检测在诊断肝癌中的应用。方法采用化学发光法检测46例原发性肝癌、51例转移性肝癌、46例肝外恶性肿瘤患者血清PCⅢ、Ⅳ-C、LN和HA的含量。结果原发性肝癌组PCⅢ、Ⅳ-C、LN和HA水平明显高于转移性肝癌组和肝外恶性肿瘤组（P〈0.05）。结论肝纤四项指标与原发性肝癌关系密切,血清肝纤四项检测对原发性肝癌肝纤维化程度的判断、鉴别转移性肝癌有一定的价值。     

Analysis of biological and technical variability in gene expression assays from formalin-fixed paraffin-embedded classical Hodgkin lymphomas

Formalin-fixed paraffin-embedded (FFPE) tissues are invaluable sources of biological material for research and diagnostic purposes. In this study, we aimed to identify biological and technical variability in RT-qPCR TaqMan® assays performed with FFPE-RNA from lymph nodes of classical Hodgkin lymphoma samples. An ANOVA-nested 6-level design was employed to evaluate BCL2, CASP3, IRF4, LYZ and STAT1 gene expression. The most variable genes were CASP3 (low expression) and LYZ (high expression). Total variability decreased after normalization for all genes, except by LYZ. Genes with moderate and low expression were identified and suffered more the effects of the technical manipulation than high-expression genes. Pre-amplification was shown to introduce significant technical variability, which was partially alleviated by lowering to a half the amount of input RNA. Ct and Cy₀ quantification methods, based on cycle-threshold and the kinetic of amplification curves, respectively, were compared. Cy₀ method resulted in higher quantification values, leading to the decrease of total variability in CASP3 and LYZ genes. The mean individual noise was 0.45 (0.31 to 0.61 SD), indicating a variation of gene expression over ~ 1.5 folds from one case to another. We showed that total variability in RT-qPCR from FFPE-RNA is not higher than that reported for fresh complex tissues, and identified gene-, and expression level-sources of biological and technical variability, which can allow better strategies for designing RT-qPCR assays from highly degraded and inhibited samples.     

Comparison between Nu/Nu and normal BALB/c T-helper activity in anti-hapten and anti-carrier responses

Nu/nu BALB/c mount a primary in vivo anti-TNP response to T-dependent TNP-antigens in the range of normal BALB/c mice. However, the response against the carrier (horse red blood cells, HRBC) was in the magnitude of about 5% as compared to normal BALB/c mice. Neither against the hapten, nor against the carrier a secondary response was observed. It could be shown by in vitro experiments that nu/nu contain a small population of TNP specific as well as HRBC specific T-helper (THTNP, THHRBC) cells. But even within the small nu/nu T-cell population, TH cells are less frequent than in T-cell populations of normal mice. Furthermore, the difference in help between nu/nu and normal BALB/c was more pronounced with respect to the anti-HRBC than the anti-TNP response. These observations could explain the lack of a secondary in vivo response being due to the low number of TH cells and the apparent in vivo unresponsiveness against HRBC as a consequence of the low frequency of THHRBC.