HMGN1 down-regulation in the diabetic kidney attenuates tubular cells injury and protects against renal inflammation via suppressing MCP-1 and KIM-1 expression through TLR4.

BACKGROUND: Renal tubular injury, accompanied by damaging inflammation, has been identified to drive diabetic kidney disease (DKD) toward end-stage renal disease. However, it is unclear how damage-associated molecular patterns (DAMPs) activate innate immunity to mediate tubular epithelial cell (TEC) injury, which in turn causes with subsequent sterile inflammation in diabetic kidneys. High mobility group nucleosome-binding protein 1 (HMGN1) is a novel DAMP that contributes to generating the innate immune response. In this study, we focused on determining whether HMGN1 is involved in DKD progression. METHODS: Streptozotocin (STZ)-induced diabetic mice model was established. Then we downrergulated HMGN1 expression in kidney with or without HMGN1 administration. The renal dysfunction and morphological lesions in the kidneys were evaluated. The expressions of KIM-1, MCP-1, F4/80, CD68, and HMGN1/TLR4 signaling were examined in the renal tissue. In vitro, HK2 cells were exposed in the high glucose with or without HMGN1, and further pre-incubated with TAK242 was applied to elucidate the underlying mechanism. RESULTS: We demonstrated that HMGN1 was upregulated in the tubular epithelial cells of streptozotocin (STZ)-induced type 1 and type 2 diabetic mouse kidneys compared to controls, while being positively correlated with increased TLR4, KIM-1, and MCP-1. Down-regulation of renal HMGN1 attenuated diabetic kidney injury, decreased the TLR4, KIM-1, and MCP-1 expression levels, and reduced interstitial infiltrating macrophages. However, these phenotypes were reversed after administration of HMGN1. In HK-2 cells, HMGN1 promoted the expression of KIM-1 and MCP-1 via regulating MyD88/NF-κB pathway; inhibition of TLR4 effectively diminished the in vitro response to HMGN1. CONCLUSIONS: Our study provides novel insight into HMGN1 signaling mechanisms that contribute to tubular sterile injury and low-grade inflammation in DKD. The study findings may help to develop new HMGN1-targeted approaches as therapy for immune-mediated kidney damage rather than as an anti-infection treatments.

[Effect of hemoperfusion on protein energy wasting and long-term prognosis in patients on maintenance hemodialysis].

Objective: To explore the effect of hemoperfusion (HP) combined with hemodialysis (HD) (HD+HP) on protein energy wasting (PEW) and long-term prognosis in patients on maintenance HD (MHD). Methods: A prospective multicenter cohort study was conducted. Adult MHD patients who completed PEW assessment and underwent regular dialysis between July 2015 and July 2021 at 23 hemodialysis centers in Guizhou Province were selected. Demographic characteristics, physical indicators, laboratory indicators, 3-day diet diary and HP treatment data of the subjects were collected. The patients were divided into different groups according to the presence or absence of HP, the frequency of HP treatment and the type of cartridge, and then relevant indicators were compared. Multivariate logistic regression model and Cox proportional regression model were used to analyze the influence of HP treatment on PEW risk in MHD patients. Meanwhile, Kaplan-Meier method was used to plot the survival curve. Results: A total of 4 623 MHD patients (2 789 males and 1 834 females) aged (53.7±15.9) years were included in the study, with a median dialysis age of 64.3 (44.3, 92.3) months. There were 3 429 (74.2%) MHD patients treated with HD+HP, and 1 194 patients (25.8%) were not treated with HP. According to the 2008 diagnostic criteria of the International Society for Renal Nutrition and Metabolism (ISRNM), the incidence of PEW was 26.0% (1 204/4 623). Multivariate logistic regression analysis showed that female (OR=2.48, 95%CI: 1.55-3.95, P<0.001), diabetes (OR=1.75, 95%CI: 1.08-2.83, P=0.024) and high-sensitivity C-reactive protein (hs-CRP) (OR=1.02, 95%CI: 1.01-1.03, P=0.003) were risk factors for PEW, while treatment with HD+HP (OR=0.51, 95%CI: 0.31-0.87, P=0.012) and elevated triglyceride levels (OR=0.62, 95%CI: 0.48-0.80, P<0.001) were protective factors. Cox hazard ratio regression showed that among different HP treatment frequencies and cartridge types, 2 times/month (HR=0.40, 95%CI: 0.17-0.95, P=0.037), 3 times/month (HR=0.44, 95%CI: 0.23-0.85, P=0.014), 4 times/month (HR=0.54, 95%CI: 0.34-0.85, P=0.008), HA130 (HR=0.57, 95%CI: 0.36-0.89, P=0.014) and HA230 (HR=0.30, 95%CI: 0.15-0.63, P=0.001) had protective effects on the occurrence of PEW in MHD patients. The all-cause mortality rate was 11.3% (521/4 623) at 33 (24, 48) months of follow-up. Kaplan-Meier analysis showed that patients undergoing 4 times/month HP treatment (χ2=36.78, P<0.001) and using HA230 (χ2=9.46, P=0.002) had the highest survival rate. Conclusion: Treatment with HD+HP is a protective factor for PEW in patients with MHD, and 4 times/month HP treatment or HA230 significantly reduces the risk of PEW and all-cause mortality in patients with MHD.

Detection of SARS-CoV-2 in different human biofluids using the loop-mediated isothermal amplification assay: A prospective diagnostic study in Fortaleza, Brazil.

We adopted the reverse-transcriptase-loop-mediated isothermal amplification (RT-LAMP) to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 salivae, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the gold standard technique reverse-transcription quantitative polymerase chain reaction  (RT-qPCR). The accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis were 96% (95% confidence interval [CI]: 87-99) and 85% (95% CI: 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swabs processed via extraction kit. Accurate and rapid diagnosis could aid coronavirus disease 2019 (COVID-19) pandemic management by identifying, isolating, and treating patients rapidly.

[Relationship between platelet/lymphocyte ratio and cognitive impairment in diabetic patients treated with maintenance hemodialysis].

Objective: To explore the relationship between platelet/lymphocyte ratio (PLR) and cognitive impairment (CI) in diabetic patients treated with maintenance hemodialysis (MHD). Methods: The data of age, gender, underlying diseases, medication history, mini-mental state examination (MMSE) and biochemical indexes of diabetic MHD patients who were treated in 18 hemodialysis center in Guizhou Province between May and August 2019 were collected. According to whether they had CI or not, the patients were divided into CI group and control group, and the clinical characteristics between the two groups were compared. In addition, the patients were divided into four groups according to the quartile of PLR (PLR Q1, Q2, Q3 and Q4 group). Multivariate logistic regression models were used to analyze the relationship between PLR level and CI in diabetic MHD patients. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of PLR in detecting CI in diabetic MHD patients. Results: Totally, 586 diabetic MHD patients (389 males) were included, with a mean age of (63±11) years. Multivariate logistic regression analysis showed that PLR was associated with the risk of CI in diabetic MHD patients, and the risk of CI in PLR Q4 group was 3.022 times of that of PLR Q1 Group (95%CI: 1.866-4.895, P<0.001). After adjusting for gender, age, dialysis age and education level, the risk of CI in PLR Q4 group was 2.529 times of that in PLR Q1 Group (95%CI: 1.536-4.164, P<0.001). After further adjusting for hemoglobin, albumin, creatinine, leukocyte and blood glucose, the risk of CI in PLR Q4 group was 2.281 times of that in PLR Q1 group (95%CI: 1.203-4.326, P=0.012). ROC curve analysis showed that the optimal threshold for PLR to predict CI in diabetic MHD patients was 155.3, with a sensitivity of 57.2% and a specificity of 60.8%, and the area under the curve was 0.608 (95%CI: 0.561-0.644, P<0.001). Conclusion: PLR is associated with CI in diabetic MHD patients.

[Association of systemic immune-inflammation index with protein-energy wasting and prognosis in patients on maintenance hemodialysis].

Objective: To explore the association of systemic immune-inflammation index (SII) with protein-energy wasting (PEW) and prognosis in maintenance hemodialysis (MHD) patients. Methods: A multicenter cohort study was conducted in 11 hemodialysis centers of Guizhou province from July to September 2019. The patients were divided into the PEW group and non-PEW group. After 12 months of follow-up, death was the endpoint event. Multivariate logistic regression analysis was used to assess the independent risk factors of PEW in MHD patients. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of SII for PEW, and the optimal cut-off value of SII was calculated. The Kaplan-Meier method was used to draw the survival curve, and log-rank test was employed to compare the difference of survival rate between the two groups. Results: A total of 859 patients were included [540 males and 319 females, aged (54±15) years], and there were 220 cases (25.6%) and 639 cases (74.4%) in PEW and non-PEW groups, respectively. SII was higher in the PEW group than that of the non-PEW group [600 (440, 915) vs 475 (353, 633), P<0.01]. Multivariate logistic regression analysis showed that SII was an independent predictor for PEW (OR=1.001, 95%CI: 1.000-1.002, P=0.02). ROC curve analysis showed that the area under the curve for SII to predict PEW in MHD patients was 0.725 (95%CI: 0.683-0.766), with the sensitivity and specificity of 69% and 70%, respectively. All patients were followed up for 12 months, and 45 died (with a mortality rate of 5.24%). Patients were divided into SII>520 group and SII≤520 group according to the optimal cut-off value, and subsequent Kaplan-Meier survival analysis showed that the 1-year cumulative survival rate of the SII>520 group (92.3%) was lower than that of SII≤520 group (97.1%) (χ2log-rank=9.707, P=0.002). Further subgroup analysis revealed that, in PEW patients with MHD, the 1-year cumulative survival rate of the SII>520 group (88.5%) was also lower than that of SII≤520 group (92.3%) (χ2log-rank=7.226, P=0.007). Conclusion: SII is an independent risk factor for PEW in MHD patients, and the higher the SII level, the lower the long-term survival rate and the prognosis.

[Association of platelet/lymphocyte ratio and neutrophil/lymphocyte ratio with protein-energy wasting in maintenance hemodialysis patients].

Objective: To explore the association of platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) with protein energy wasting (PEW) in maintenance hemodialysis (MHD) patients. Methods: A multicenter cross-sectional study was conducted in eleven hemodialysis centers of Guizhou province from June to August, 2017. Clinical data, physical parameters, body composition data and laboratory values of MHD patients were collected. PLR and NLR were calculated according to routine blood test. All patients were divided into four groups (Q1-Q4) according to the median and quartile of PLR and NLR. Multivariate logistic regression models were applied to analyze the relationships between PLR, NLR and PEW. The comparison of predictive power of PLR and NLR for PEW was evaluated by receiver operating characteristic curve (ROC). Results: A total of 936 MHD patients were enrolled (519 males, 417 females), with a mean age of (55.6±15.6) years. The prevalence of PEW was 46.2% (432/936). Multivariate logistic regression analysis showed that patients in group PLR Q3 and Q4 were 2.07 (95%CI: 1.03-4.13, P=0.014) and 2.73 (95%CI: 1.58-4.74, P<0.001) times more likely to have PEW, compared with those in group PLR Q1 in unadjusted models. PLR was significantly associated with the development of PEW after adjusting age, sex, history of hypertension, diabetes and hemoglobin. Patients in Group PLR Q3 and Q4 were 2.82 times (95%CI: 1.42-5.60, P=0.003) and 2.93 times (95%CI: 1.50-5.73, P=0.002) times more likely to have PEW than those in Group PLR Q1. The ROC showed that only PLR can predict the development of PEW with a diagnostic threshold of 144.09 [area under curve (AUC)=0.61, 95%CI: 0.56-0.66, P<0.001], with a sensitivity and specificity of 61% and 58%, respectively, while the AUC of NLR is 0.55 (P=0.091). Conclusion: For MHD patients, only PLR could be a relevent factor of PEW and it showed the predictive power of PEW rather than NLR.

[Interpretation of BRAF gene mutation detection by real-time PCR: a study of 8 644 thyroid fine-needle aspiration specimens].

Objective: To study common problems in BRAF gene mutation detection, and conditions for repetition testing using thyroid fine needle aspiration specimens. Methods: A total of 8 644 cases of thyroid fine-needle aspiration specimens at China-Japan Friendship Hospital were collected between February, 2012 and July, 2018. BRAF gene mutation was detected by real-time PCR. Repeat testing was performed in 237 cases when the results were inconsistent with clinical or cytological diagnosis or when uncertain results were obtained. Results: The final positive rates of BRAF mutation was 22.0% (1 897/8 625). Nineteen cases were excluded due to inadequate DNA samples. The average Ct value of internal quality control was 16.061, and the average Ct value of the positive samples was 19.147. Among 237 repeat tests, 51.4% (19/37) continued to have poor DNA quality and 48.6% (18/37) had adequate DNA resulting in 1 positive case and 17 negative cases. In 40 repetition of initial negative cases, results were unchanged. In initial positive cases, 40.4% (40/99) with a difference of Ct value (between BRAF gene and internal quality control) between 8 to 12 turned negative after repetition, 69.8% (37/53) of these cases with a difference of more than 12 turned negative after repetition. The sensitivity and specificity of BRAF mutation were 83.97% and 96.94%, respectively. Conclusions: Difference between BRAF gene Ct value and internal quality control Ct value is recommended as a reliability index for the test result. Cases with a difference greater than 8 should be subjected to repeat testing.

Impact of intermediate-dose prophylaxis on progression of haemarthropathy in patients with severe haemophilia A: A 10-year, single-centre experience in Korea.

AIM: To determine the impact of 10-year intermediate-dose prophylaxis on haemarthropathy progression in patients with severe haemophilia A (SHA). METHODS: Prophylactic treatment with intermediate dose was given maximally for 10 years to 42 patients with SHA in a haemophilia treatment centre in Korea. Patients were divided into three groups based on prophylactic treatment started age: 1-10 (group A'), 11-20 (group B'), and ≥21 (group C'). Average annual increase of Pettersson score (P-score) was compared between the treatment groups. RESULTS: Average ages and P-scores at initiation of prophylaxis were 4.65±3.43 years and 2.09±3.25, 16.13±1.73 years and 7.37±4.38, and 28.33±7.25 years and 12.33±6.50 for groups A', B', and C'. Average annual increase of P-score in groups A', B', and C' was 0.039±0.11, 0.063±0.123, and 0.078±0.124. Assuming that intermediate-dose prophylaxis started at the average age, P-score and annual increase of P-score would be the average values of each group; it would thus take 210 and 46.5 years to reach -2SD of the average critical level of haemarthropathy (The level of haemarthropathy (P-score 13.0 ± 2.7) above which there is a significant impact on quality of life in Korean) in groups A' and B'. However, it would take 55 and 15.75 years if the annual P-score increase were +2SD of the average value in groups A' and B'. CONCLUSION: Intermediate-dose prophylaxis for patients with SHA in Korea would maintain arthropathy below the critical level for most of the patients' lifetime when started before adolescence. However, this would not be achieved in some adolescent patients with rapid progression of arthropathy and in most adult patients.

[Association of low serum parathyroid hormone with protein-energy wasting in maintenance hemodialysis patients].

Objective: To examine the relationship between low serum parathyroid hormone (PTH) and protein-energy wasting (PEW) in patients who underwent maintenance hemodialysis (MHD) treatment. Methods: A cross-sectional study was conducted in MHD patients between June 2015 and August 2017 in 11 MHD centers from Guizhou province. Body composition and physical parameters were measured, clinical data and other related laboratory values were collected according to the medical record system. Participants were assigned to low serum PTH group (PTH<150 ng/L), target PTH group (150 ng/L≤ PTH ≤300 ng/L) and high serum PTH group (PTH>300 ng/L). Multivariate logistic regression analysis was used to analyze the relationship between low serum PTH and risk of PEW, which was diagnosed according to the diagnostic criteria recommened by the International Society of Renal Nutrition and Metabolism (ISRNM). Results: A total of 873 MHD patients (488 males and 385 females) were included in the final analysis, with a mean age of 55.0 (44.0, 67.0) years and a mean hemodialysis duration of 31.0(17.0, 54.0) months. In unadjusted model, low serum PTH group was associated with PEW (OR=2.12, 95% CI: 1.26-3.54, P=0.004), when compared with high serum PTH group. After adjustment for age and sex, low serum PTH group was still significantly associated with PEW (OR=2.09, 95% CI: 1.23-3.52, P=0.006). Further adjustment for diabetes and hypertension, the correlation between low serum PTH group and PEW was still significant (OR=2.02, 95% CI: 1.04-3.90, P=0.037). However, the correlation was not observed in target PTH group and high serum PTH group. Conclusion: Low serum PTH was associated with risk of PEW, regardless of age, sex, history of diabetes and hypertension, and thus it might be a promising indicator of PEW in MHD patients.

[Resting metabolic rate estimated by bioelectrical impedance analysis and its determinants in maintenance hemodialysis patients].

Objective: To explore the level of resting energy expenditure (REE) estimated by bioelectrical impedance analysis and the association of resting metabolic rate (RMR) with clinical related factors, and provide new ideas for improving protein energy wasting (PEW) in maintenance hemodialysis (MHD) patients. Methods: Seven hundred and sixty-five subjects receiving MHD between July 2015 and September 2016 in 11 hemodialysis centers in Guizhou province were enrolled in this cross-sectional study. Bioelectrical impedance analysis was used to measure RMR and body composition, such as lean body mass, fat mass and body cell mass (BCM). Baseline characteristics, routine blood test indexes and biochemical data of hemodialysis patients were collected. The level of RMR and body composition in hemodialysis patients was compared by gender grouping. Then the patients were divided into four groups according to the cutoff value of RMR quartile. Spearman correlation analysis and multiple linear regression analysis were used to analyze the relationships between RMR and clinical related factors. Results: The average age of MHD patients was (54.96±15.78) years and the duriation of dialysis was (42.3±9.0) months. The level of RMR in male patients (474 cases, 61.96%) was significantly higher than that in female patients [1 591(1 444, 1 764) kcal/d vs 1 226 (1 104, 1 354) kcal/d, P<0.001]. However, this significant difference of RMR between different genders disappeared after adjusting for lean body mass (P=0.193). Multiple linear regression analysis showed that RMR was positively correlated with body surface area (ß=0.817) and lactate dehydrogenase (LDH) (ß=0.198), and negatively correlated with age (ß=-0.141), all P<0.05. Conclusion: RMR levels in patients with maintenance hemodialysis are associated with lactate dehydrogenase level, which may become a new index to evaluate energy consumption.

[Clinicopathologic features of atypical type A thymoma].

Objective: To study the clinicopathologic features, immunophenotype and differential diagnosis of atypical type A thymoma. Methods: Clinicopathologic and follow-up data of three cases of atypical type A thymoma from 2004 to 2016 were reviewed. Immunohistochemical staining was performed. Results: All three patients were male with average age of 59 years. Clinically, the lesions presented as anterior mediastinal masses. Grossly, the tumor ranged in size from 4 to 6 cm in greatest dimension and partially enclosed within fibrous capsule. The cut surface was homogenously fleshy, tan to brown in color, with multinodular and lobulated configurations. Cystic changes and necrosis were seen. Microscopically, the tumor was composed of plump spindle or oval-shaped cells arranged in storiform, microcystic, glandular, rosettes-like and hemangiopericytoma-like histological patterns. The tumor cells showed mild cytological atypia and mitotic activity ranged from 4 to 5/10HPF. Necrosis was present in all tumors. All tumors showed diffuse CK(AE1/AE3), CK19, p63 and vimentin expression. TdT, CK20, CD20, CD5 and CD117 were negative. The proliferative index, as measured with Ki-67, was 15.2% to 26.4%. None of the cases had recurrence or metastases during the follow-up period (9 to 27 months). Conclusions: Atypical type A thymoma presents atypical features including tumor necrosis and increased mitotic activity. However, the implications of such atypical features to the biological behavior of the tumor remain to be determined.

[Expression of PD-1/PD-L1 in lung adenocarcinoma and correlation with epidermal growth factor receptor mutation status].

Objective: To investigate the expression of programmed cell death-1(PD-1) and programmed cell death-ligand 1(PD-L1) in lung adenocarcinoma in correlation with clinical pathological parameters, especially with regard to different epidermal growth factor receptor (EGFR) mutation status. Methods: One hundred and nine cases of lung adenocarcinoma were collected during the period from Aug. 2010 to Jan. 2016, including 51 cases of EGFR wild type and 58 cases of EGFR mutations. Immunohistochemistry was used to detect PD-1/PD-L1 protein expression. Chi-square test was used to analyze the correlation between PD-1 and PD-L1 expression, and in correlation with clinicopathological parameters. All statistical analyses run by SAS 9.1 software. Results: The positive rates of PD-1 and PD-L1 expression were 68.8% (75/109) and 27.5% (30/109), respectively, with significant correlation between the two (P<0.05). PD-1 and PD-L1 expression rates were higher in 51 cases with EGFR wild type status (74.5% and 39.2%) than those in 58 EGFR mutation cases (63.8% and 17.2%); PD-1 expression was significantly associated with age (P<0.05); that of PD-L1 was closely correlated with histological type, tumor size, lymph node metastasis and EGFR status (P<0.05). Conclusions: PD-1 and PD-L1 expression profiles and their correlation with EGFR mutations are different from those with native EGFR. PD-L1 overexpression is closely correlated with larger tumor size and lymph node metastasis, suggesting it is a high-grade marker for lung adenocarcinoma.

Positioning of double-lumen tubes based on the minimum peak inspiratory pressure difference between the right and left lungs in short patients: a prospective observational study.

BACKGROUND: Peak inspiratory pressures (PIPs) during one-lung ventilation (OLV) have served as a clinical marker that could indirectly verify the proper positioning of double-lumen tubes (DLTs). Patients of short stature are highly susceptible to initial DLT malpositioning. OBJECTIVES: We investigated the usefulness of positioning left-sided DLTs using minimum PIP differences between the right and left lungs by comparing with the previously used method of auscultation without fibreoptic bronchoscopy (FOB). We also evaluated the difference in PIPs between the two lungs during OLV after the DLT was ideally positioned with FOB examination. DESIGN: Prospective, observational study. SETTING: A university hospital. PATIENTS: One hundred and two female patients of short stature (≤160  cm). INTERVENTIONS: Verification of DLT position was conducted by three sequential steps: auscultation; minimising the difference in PIP during each OLV; and verifying the resulting position by FOB. MAIN OUTCOME MEASUREMENTS: Fibreoptic bronchoscopic view results of DLT position followed by the position adjustment using the minimum PIP difference method. RESULTS: Repositioning the DLT using the minimum PIP difference led to clinically successful positioning of the DLT in 88% of patients and a more ideal placement of the tube than auscultation alone (69.6 vs. 11.8%, P <0.001). Additionally, the ideal position of DLTs verified by FOB showed that PIP differences were zero or ±1  mmHg in 93% of patients. CONCLUSION: Positioning the DLT based on the minimum PIP difference between the right and left lungs as a supplementation to routine auscultation serves as an easy and reliable method for DLT positioning and may improve the accuracy of DLT positioning as an adjuvant to FOB in short patients. TRIAL REGISTRATION: Clinicaltrial.gov identifier: NCT01533012.

Primary clear cell adenocarcinoma of the peritoneum presents as Sister Mary Joseph's nodule: a case report and literature review.

BACKGROUND: Sister Mary Joseph's nodule (SMJN) is a raised nodule around the umbilicus and is often a clinical sign of metastatic malignancy with poor prognosis. Primary clear cell adenocarcinoma of the peritoneum is rare. Herein the authors describe a case of primary peritoneal clear cell adenocarcinoma presenting with SMJN as an initial sign. CASE: A 59-year-old woman was admitted into the present hospital complaining of an enlarged, painful umbilical nodule, and increasing abdominal distention. After the biopsy of the peritoneal nodule, primary clear cell adenocarcinoma of the peritoneum was diagnosed. The patient underwent multiple courses of aggressive chemotherapy combined with radiotherapy and surgery and has survived for more than four years. CONCLUSION: Considering that SMJN is a rare sign of visceral malignancies, clinicians should be aware of this rare clinical sign when determining the differential diagnosis. Umbilical metastasis is usually indicates a poor prognosis. However, the present case suggests that long-term survival is possible.

The Extraordinary Case of a Woman with a 30-Year-Long Diffuse Leishmaniasis Cured with One Single Ampoule of Intranasal Pentavalent Antimoniate.

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.

[Chronic abdominal pain and fever in an Ivoirian woman: Mycobacterium avium-intracellulare duodenitis in an AIDS patient in Abidjan, Cote d'Ivoire]. / Douleurs abdominales chroniques et fièvre chez une ivoirienne.

Duodenal infection by Mycobacterium avium-intracellulare is a common opportunistic disease in HIV-infected patients. Individuals with CD4 counts <50 cells/mm3 are at highest risk. The main symptoms are diarrhea, abdominal pain, weight loss, and fever. Endoscopic examination shows various abnormalities including disseminated nodules that may be yellowish, whitish, or pinkish in color. Other mucosal lesions may be found such as erosion, erythema, or friable edematous aspect. Since these findings are non-specific, it is important to obtain biopsy specimens for histological and microbiological examination. The most common histologic features are atrophic mucosa resembling Whipple's disease with strongly positive PAS staining. The presence of BARR in macrophages is typical of MAI. Diagnosis is based on identification of the bacteria using either conventional culture techniques or polymerase chain reaction (PCR). Differential diagnosis includes other gastrointestinal infections associated with AIDS, i.e., microsporidiosis, cryptosporidiosis, giardiosis, anguillulosis, CMV, and isoporosis. The course of the disease is usually unfavorable even with antibiotic treatment. The purpose of this report is to describe a case of duodenitis due to atypical mycobacterial infection in a 30-year-old woman who was seropositive for human immunodeficiency virus. She was hospitalized due to fever with deterioration of her general condition (more than 10% of body weight loss) and chronic abdominal pain with inflammation. Diagnosis of MAI was confirmed by biopsy and Ziehl-Neelsen coloration. The patient was treated with rifampicine, isoniazide, ethambutol, and pyrazinamide in association with stavudine, lamuvidine and efavirenz. Despite improvement of general condition, fever persisted and the patient died after 40 days of treatment.

Tibetan Medical Formula Shi-Wei-Gan-Ning-Pill Protects Against Carbon Tetrachloride-Induced Liver Fibrosis - An NMR-Based Metabolic Profiling.

Liver fibrosis is a severe health problem, threatening the life quality and causing death, raising great concerns worldwide. Shi-Wei-Gan-Ning-Pill (SWGNP) is a traditional Tibetan recipe used to treat hepatic injuries; however, its hepatoprotective mechanism has not yet fully clarified. In this study, histological staining, biochemical assays, and elements determination were applied to evaluate the anti-fibrotic efficacy of SWGNP on a carbon tetrachloride (CCl4) induced hepato-fibrosis rat model. NMR-based metabolomics combined with orthogonal partial least squares-discriminant analysis (OPLS-DA), canonical regression analysis, and correlation networks analysis was used to characterize the potential biomarkers as well as metabolic pathways associated with the hepatoprotective activity of SWGNP. The results showed that SWGNP could significantly attenuate the pathological changes and decrease the levels of fibrosis markers (ColIV, HA, LN, and PCIII), and regulate the disordered elements distribution. Multivariate analysis and correlation network analysis revealed that SWGNP could protect rats against CCl4-induced liver fibrosis through anti-oxidation, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. In conclusion, this integrated metabolomics approach provided new insights into the mechanism of the hepatoprotective effect of SWGNP in liver fibrosis disease.