Systemic and cerebrospinal fluid biomarkers for tuberculous meningitis identification and treatment monitoring.

IMPORTANCE: Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study's findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.

Uncovering hub genes in sepsis through bioinformatics analysis.

In-depth studies on the mechanisms of pathogenesis of sepsis and diagnostic biomarkers in the early stages may be the key to developing individualized and effective treatment strategies. This study aimed to identify sepsis-related hub genes and evaluate their diagnostic reliability. The gene expression profiles of GSE4607 and GSE131761 were obtained from the Gene Expression Omnibus. Differentially co-expressed genes between the sepsis and control groups were screened. Single-sample gene set enrichment analysis and gene set variation analysis were performed to investigate the biological functions of the hub genes. A receiver operating characteristic curve was used to evaluate diagnostic value. Datasets GSE154918 and GSE185263 were used as external validation datasets to verify the reliability of the hub genes. Four differentially co-expressed genes, FAM89A, FFAR3, G0S2, and FGF13, were extracted using a weighted gene co-expression network analysis and differential gene expression analysis methods. These 4 genes were upregulated in the sepsis group and were distinct from those in the controls. Moreover, the receiver operating characteristic curves of the 4 genes exhibited considerable diagnostic value in discriminating septic blood samples from those of the non-septic control group. The reliability and consistency of these 4 genes were externally validated. Single-sample gene set enrichment analysis and gene set variation analysis analyses indicated that the 4 hub genes were significantly correlated with the regulation of immunity and metabolism in sepsis. The identified FAM89A, FFAR3, G0S2, and FGF13 genes may help elucidate the molecular mechanisms underlying sepsis and drive the introduction of new biomarkers to advance diagnosis and treatment.

HIV/AIDS Knowledge, Depression, and HIV-Related Stigma Among Elderly Men in Rural China: A Hierarchical Regression Analysis.

This study explored the current status and influencing factors of HIV-related stigma among elderly men (≥50 years old) in rural Chengdu, China. A structured face-to-face interview survey was conducted among 286 elderly males from three towns in Chengdu using convenience sampling, 240 men (83.9%) who had heard of HIV/AIDS were included in the analysis. Hierarchical regression was used to examine the associated factors of HIV-related stigma, including demographic variables, HIV/AIDS knowledge level, receiving HIV/AIDS-related health education in the past year, depression, and anxiety, and to examine the moderating effect of educational level on HIV/AIDS knowledge and HIV-related stigma. Hierarchical regression analysis showed that men with lower HIV/AIDS knowledge scores, primary school or below educated, and depression had higher HIV-related stigma total score and social stigma dimensional scores than their counterparts. In addition, living alone was associated with higher HIV-related stigma, and elderly men with lower monthly income and those without HIV/AIDS-related health education in the past year had higher levels of social stigma. Higher HIV/AIDS knowledge score was significantly associated with lower HIV-related stigma level among those with middle school or above education level, but no such effect in those with primary school or below. In conclusion, the HIV-related stigma level among elderly men in rural Chengdu was high and positively associated with depression. HIV/AIDS education should target elderly men with low education, living alone, and low income, and interventions to promote mental health may work together to reduce HIV-related stigma in the rural elderly population.

A kidney-brain neural circuit drives progressive kidney damage and heart failure.

Chronic kidney disease (CKD) and heart failure (HF) are highly prevalent, aggravate each other, and account for substantial mortality. However, the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain limited. Here, we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ (SFO) and thereby to paraventricular nucleus (PVN) and rostral ventrolateral medulla that modulates sympathetic outflow. This kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each model. Interruption of the pathway by kidney deafferentation, selective deletion of angiotensin II type 1a receptor (AT1a) in SFO, or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and HF. Thus, kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both organs. These results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease conditions. This suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.

Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction.

Obstructive uropathy from nephrolithiasis remains a leading cause of end-stage kidney disease. Mechanisms of kidney fibrosis after relief of ureteral obstruction represent opportunities for therapeutic intervention. Here, in mouse models of ureteral obstruction, we have combined methods of virus tracing and optogenetic techniques to identify an overactive central pathway in the paraventricular nucleus (PVN)-rostral ventrolateral medulla (RVLM) that determines the fibrotic fate of kidney after relief of the obstruction. The overactive pathway is driven by kidney afferent nerves that activate angiotensin II signaling in RVLM-projecting PVN neurons to drive sympathetic discharge back to the kidney. This causes the kidney to undergo fibrosis with loss of function. Blockade of sympathetic traffic or deletion of AT1a in PVN preserves the structure of the post-obstructed kidney. Human post-obstructed kidneys also demonstrate evidence of increased sympathetic nerve activity associated with a fibrotic outcome. Manipulating these neural elements is a potential treatment strategy.

Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis.

Objective: Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients. Method: We searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay. Results: A total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR = 0.88, 95% CI [0.82, 0.95], P = 0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR = 0.77, 95% CI [0.68, 0.88], P < 0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR = 0.96, 95% CI [0.86, 1.06], P = 0.41), meanwhile, a low dose (RR = 0.89, 95% CI [0.82, 0.97], P = 0.007) of dexamethasone (RR = 0.9, 95% CI [0.83, 0.98], P = 0.01) with a long treatment course (RR = 0.89, 95% CI [0.82, 0.98], P = 0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD = 3.83, 95% CI [1.11, 6.56], P = 0.006). Conclusion: Our results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients.

Objetivo: Actualmente, los glucocorticoides se utilizan ampliamente para tratar los síntomas de la enfermedad por coronavirus 2019 (COVID-19). Sin embargo, el papel terapéutico de los glucocorticoides sigue siendo muy controvertido, por ello, nos propusimos evaluar su eficacia en el tratamiento de los pacientes con COVID-19. Método: Se realizaron búsquedas en PubMed, Embase y Cochrane Library para seleccionar los estudios adecuados. El criterio de valoración principal del estudio fue la mortalidad por todas las causas. El criterio de valoración secundario del estudio fue la duración de la estancia en el hospital. Resultados: Se evaluó un total de 9 ensayos controlados aleatorizados con 7.907 pacientes. En general, el tratamiento con glucocorticoides redujo la mortalidad por todas las causas en los pacientes con COVID-19 (RR = 0,88, IC 95% [0,82; 0,95], p = 0,002). Al realizar análisis de subgrupos, se observó que los glucocorticoides se asociaban a una disminución de la mortalidad por todas las causas en los pacientes con COVID-19 grave (RR = 0,77, IC 95% [0,68; 0,88], p < 0,0001), sin embargo no se observaron diferencias evidentes en la mortalidad por todas las causas de los pacientes con COVID-19 no grave entre el grupo de glucocorticoides y el de control (RR = 0,96, IC 95% [0,86; 1,06], p = 0,41), mientras que una dosis baja (RR = 0,89, IC 95% [0,82; 0,97], p = 0,007) de dexametasona (RR = 0,9, IC 95% [0,83; 0,98], p = 0,01) con un curso de tratamiento largo (RR = 0,89, IC 95% [0,82; 0,98], p = 0,02) fue beneficiosa para la mortalidad por todas las causas en los pacientes con COVID-19. Además, encontramos que los glucocorticoides podrían estar asociados con una mayor duración de la estancia hospitalaria en los pacientes con COVID-19 no grave (DM = 3,83, IC 95% [1,11; 6,56], p = 0,006). Conclusión: Nuestros resultados mostraron que el tratamiento con glucocorticoides estaba relacionado con una reducción de la mortalidad por todas las causas en los pacientes con COVID-19 grave. Sin embargo, en los pacientes con COVID-19 no grave, el uso de glucocorticoides no disminuyó la mortalidad por todas las causas y puede prolongar la duración de la estancia hospitalaria. Además, descubrimos que una dosis baja de dexametasona con un curso de tratamiento largo podría reducir la mortalidad por todas las causas en los pacientes con COVID-19.

Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis

Objective: Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients.MethodWe searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay.ResultsA total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR=0.88, 95% CI [0.82, 0.95], P=0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR=0.77, 95% CI [0.68, 0.88], P<0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR=0.96, 95% CI [0.86, 1.06], P=0.41), meanwhile, a low dose (RR=0.89, 95% CI [0.82, 0.97], P=0.007) of dexamethasone (RR=0.9, 95% CI [0.83, 0.98], P=0.01) with a long treatment course (RR=0.89, 95% CI [0.82, 0.98], P=0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD=3.83, 95% CI [1.11, 6.56], P=0.006).ConclusionOur results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients. (AU)

Objetivo: Actualmente, los glucocorticoides se utilizan ampliamente para tratar los síntomas de la enfermedad por coronavirus 2019 (COVID-19). Sin embargo, el papel terapéutico de los glucocorticoides sigue siendo muy controvertido, por ello, nos propusimos evaluar su eficacia en el tratamiento de los pacientes con COVID-19.MétodoSe realizaron búsquedas en PubMed, Embase y Cochrane Library para seleccionar los estudios adecuados. El criterio de valoración principal del estudio fue la mortalidad por todas las causas. El criterio de valoración secundario del estudio fue la duración de la estancia en el hospital.ResultadosSe evaluó un total de 9 ensayos controlados aleatorizados con 7.907 pacientes. En general, el tratamiento con glucocorticoides redujo la mortalidad por todas las causas en los pacientes con COVID-19 (RR=0,88, IC 95% [0,82; 0,95], p=0,002). Al realizar análisis de subgrupos, se observó que los glucocorticoides se asociaban a una disminución de la mortalidad por todas las causas en los pacientes con COVID-19 grave (RR=0,77, IC 95% [0,68; 0,88], p<0,0001), sin embargo no se observaron diferencias evidentes en la mortalidad por todas las causas de los pacientes con COVID-19 no grave entre el grupo de glucocorticoides y el de control (RR=0,96, IC 95% [0,86; 1,06], p=0,41), mientras que una dosis baja (RR=0,89, IC 95% [0,82; 0,97], p=0,007) de dexametasona (RR=0,9, IC 95% [0,83; 0,98], p=0,01) con un curso de tratamiento largo (RR=0,89, IC 95% [0,82; 0,98], p=0,02) fue beneficiosa para la mortalidad por todas las causas en los pacientes con COVID-19. Además, encontramos que los glucocorticoides podrían estar asociados con una mayor duración de la estancia hospitalaria en los pacientes con COVID-19 no grave (DM=3,83, IC 95% [1,11; 6,56], p=0,006).ConclusiónNuestros resultados mostraron que el tratamiento con glucocorticoides estaba relacionado con una reducción de la mortalidad por todas las causas en los pacientes con COVID-19 grave. (AU)

[Application of CD138 Immunomagnetic Bead Sorting Combined with Fluorescence in Situ Hybridization in Multiple Myeloma].

OBJECTIVE: To compare the effects of direct fluorescence in situ hybridization (D-FISH) detection without sorting and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) on cytogenetic analysis of patients with multiple myeloma (MM). METHODS: FISH test results of 229 patients with initial MM were retrospectively analyzed. The patients were divided into two groups, 140 patients were tested with D-FISH and 89 patients with MACS-FISH. The combination probe was designed as P53, D13S319, RB1, 1q21, and IgH. Cytogenetic detection results were compared between the two groups. RESULTS: The total detection rate of cytogenetic abnormalities in D-FISH group was 52.9%, and that in MACS-FISH group was 79.8%. There was a significant difference in the cytogenetic abnormality rate between the two groups (P=0.020). The abnormal genes with the highest detection rate in the two groups were 1q21 and IgH, respectively, while the lowest was P53. There was no significant difference in the percentage of P53 positive cells (positive rate) between the two groups, while D13S319, RB1, 1q21, and IgH showed significant difference in positive cell rate (P=0.0002, P<0.0001, P=0.0033, P=0.0032). There was no significant correlation between the proportion of plasma cells (PC) detected by bone marrow morphology and cytogenetic abnormality rate in the D-FISH group, while there was a correlation between the proportion of PC detected by flow cytometry and cytogenetic abnormality rate (r=0.364). The PC proportion detected by bone marrow morphology and flow cytometry in the MACS-FISH group had no correlation with the cytogenetic abnormality rate and positive cell rate of the 5 genes mentioned above. Additionally, the PC proportion detected by bone marrow morphology and flow cytometry showed significant difference (P<0.0001). CONCLUSION: CD138 immunomagnetic bead sorting combined with FISH technology can significantly improve the abnormality detection rate of MM cytogenetics.

Effectiveness of corticosteroids to treat coronavirus disease 2019 symptoms: A meta-analysis.

OBJECTIVE: Currently, corticosteroids are widely used to treat coronavirus disease 2019 (COVID-19) symptoms. However, the therapeutic role of corticosteroids remains highly controversial. To that end, we aimed to assess the efficacy of corticosteroids in treating COVID-19 patients. METHOD: We searched PubMed, Embase, and Cochrane Library to select suitable studies. Our primary study endpoint was all-cause mortality. The secondary study endpoint was the length of hospital stay. RESULTS: A total of 9 randomized controlled trials (RCTs) with 7907 patients were assessed. The pooled result indicated that corticosteroids treatment could significantly reduce all-cause mortality in patients with COVID-19 (RR=0.88, 95% CI [0.82, 0.95], P=0.002). When subgroup analyses were performed, we found that corticosteroids were associated with decreased all-cause mortality in severe COVID-19 patients (RR=0.77, 95% CI [0.68, 0.88], P<0.0001), however no obvious difference was observed in all-cause mortality of non-severe COVID-19 patients between the corticosteroid and control group (RR=0.96, 95% CI [0.86, 1.06], P=0.41), meanwhile, a low dose (RR=0.89, 95% CI [0.82, 0.97], P=0.007) of dexamethasone (RR=0.9, 95% CI [0.83, 0.98], P=0.01) with a long treatment course (RR=0.89, 95% CI [0.82, 0.98], P=0.02) was beneficial for all-cause mortality in COVID-19 patients. Additionally, we found that corticosteroids might be associated with a longer length of hospital stay in non-severe COVID-19 patients (MD=3.83, 95% CI [1.11, 6.56], P=0.006). CONCLUSION: Our results showed that corticosteroid therapy was related to a reduction in all-cause mortality in severe COVID-19 patients. However, in patients with non-severe COVID-19, the use of corticosteroids did not decrease all-cause mortality and may prolong the duration of hospital stay. In addition, we revealed that a low dose of dexamethasone with a long treatment course could reduce all-cause mortality in COVID-19 patients.

Urinary Matrix Metalloproteinase 7 Activated by Oxidative Stress Predicts Kidney Prognosis in Myeloperoxidase-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Aims: Effective and applicable predictors of end-stage kidney disease (ESKD) are needed for patients with myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV) and kidney involvement. We investigated whether urinary matrix metalloproteinase-7 (uMMP7) was associated with kidney injury severity and incident ESKD in MPO-AAV. Results: A prospective two-stage study was conducted in 150 patients with newly diagnosed MPO-AAV in two independent cohorts. uMMP7 was measured on the days of initial and repeat kidney biopsies. In stage I, a higher initial uMMP7 level was associated with a lower estimated glomerular filtration rate (eGFR), higher level of proteinuria, and greater extent of kidney pathologic lesions. This elevated uMMP7 protein level is activated and potentially derived from the enhanced kidney production induced by oxidative stress. In stage II, uMMP7 at initial biopsy was independently associated with the incidence of ESKD over 6 years. The higher uMMP7 group (vs. lower) had an adjusted hazard ratio of 3.79 (95% confidence interval [CI], 1.49-6.09) for ESKD in the test cohort. Findings were similar in the validation cohort. A combination of data from the two cohorts revealed that adding uMMP7 into clinical or clinicopathologic models significantly improved risk discrimination for future ESKD. Innovation: An elevated uMMP7 level in MPO-AAV was independently associated with severe kidney injury and incident ESKD. Conclusions: uMMP7 in MPO-AAV improves identification of patients at risk of ESKD and may enable early and optimized therapy to improve outcomes. Antioxid. Redox Signal. 37, 246-256.

Efficacy and safety of dexmedetomidine in sepsis patients requiring mechanical ventilation: a systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Currently, dexmedetomidine is widely used in the treatment of sepsis patients requiring mechanical ventilation; however, its role remains controversial. The aim of this study was to assess the efficacy and safety of dexmedetomidine in sepsis patients requiring mechanical ventilation. METHODS: The PubMed, Embase and Cochrane Library electronic databases were searched to identify relevant studies; Review Manager version 5.4 was used to perform the meta-analysis. Primary outcomes included the all-cause mortality rate at the longest follow-up available and the duration of mechanical ventilation. Secondary outcomes included length of intensive care unit (ICU) stay, length of hospital stay, and adverse events (bradycardia). RESULTS: Five randomized controlled trials (RCTs), including 926 patients, were assessed. Overall, dexmedetomidine did not reduce all-cause mortality in mechanically ventilated patients with sepsis (relative risk [RR]: 0.9, 95% confidence interval [CI]: 0.77 to 1.05, p = 0.18, I2 = 37%). However, dexmedetomidine was associated with decreases in the length of hospital stay (mean difference [MD]: -2.99, 95% CI: -4.72 to -1.26, p = 0.0007, I2 = 0%), ICU length of stay (MD: -1.15, 95% CI: -2.06 to -0.24, p = 0.01, I2 = 32%) and duration of mechanical ventilation (MD: -0.72, 95% CI: -1.38 to -0.07, p = 0.03, I2 = 20%). However, dexmedetomidine increased the risk for bradycardia (22% versus 12.6%, respectively; RR: 1.73, 95% CI: 1.24 to 2.41, p = 0.001, I2  = 0%). WHAT IS NEW AND CONCLUSION: Results suggested that dexmedetomidine did not reduce all-cause mortality in mechanically ventilated patients with sepsis. However, it was associated with decreases in length of hospital stay, ICU length of stay and duration of mechanical ventilation, although it increased the risk for bradycardia.

Increase of donor derived tumor occurrence by transfer of ex vivo expanded antigen specific regulatory T cells.

OBJECTIVES: Using regulatory T cells (Tregs) as a cellular therapy to control rejection is an attractive immunosuppressive strategy in transplantation, but immunosuppression mediated by Tregs need to be investigated before application. METHODS: In our experiment, mature Dendritic Cells (DCs) were generated through inducing bone marrow cells of C57BL/6 (H-2b) mice. CD4+CD25+Tregs were sorted by magnetic activated cell sorting (MACS) from BALB/C (H-2d) mice, and Tregs were expanded ex vivo with anti-CD3/CD28 microbeads and high concentration of recombinant murine (rm) IL-2 for 14 days, after that, expanded polyclonal Tregs were collected and cocultured with mature DCs (H-2b) in the presence of lower concentration of rmIL-2 for 7 days to get antigen-specific Tregs. Subsequently, BALB/C mice were randomly divided into three groups: BALB/c mice were inoculated with 5 × 105 B16-F10 (H-2b) cells via tail vein, the other were inoculated with 1 × 107 BALB/c expanded polyclonal Tregs and 5 × 105 B16-F10, the last with 1 × 107 antigen-specific BALB/c Tregs and 5 × 105 B16-F10 cells. After 14 days, mice were sacrificed and the black tumor nodules in lungs were counted. RESULTS: Adoptive transfer of ex vivo expanded polyclonal Tregs rendered BALB/c mice (recipient) susceptible to MHC-mismatched tumor (B16-F10 cells, H-2b). If ex vivo expanded polyclonal Tregs from BALB/c were cocultured with mature DCs from C57BL/6 after expansion, suppression of tumor immunity against B16-F10 cells was further. CONCLUSION: We suggested that ex vivo expanded antigen-specific Tregs could more dampen recipient tumor immunity compare with polyclonal Tregs, and the increased risk of donor derived tumor should be considered.

Association of Urinary Matrix Metalloproteinase 7 Levels With Incident Renal Flare in Lupus Nephritis.

OBJECTIVE: Flares of lupus nephritis (LN) are frequent and associated with impaired renal prognosis. One major management obstacle in LN flare is the lack of effective methods to identify at-risk patients earlier in their disease course. This study was undertaken to test the utility of measurement of urinary matrix metalloproteinase 7 (MMP-7) for the dynamic surveillance of renal disease activity and prediction of renal flares in LN. METHODS: A prospective, 2-stage cohort study was performed in patients with LN. Urinary MMP-7 levels at the time of biopsy were evaluated in 154 patients with newly diagnosed LN in 2 independent cohorts. Urinary MMP-7 levels were assessed for correlation with renal histologic activity. Furthermore, after a minimum period of 12 months of renal disease remission, urinary MMP-7 levels were monitored bimonthly for 2 years in 65 patients with LN. The association between urinary MMP-7 levels and development of LN flare was analyzed. RESULTS: Urinary MMP-7 levels were elevated in patients with LN. A higher urinary MMP-7 level in LN was associated with greater renal histologic activity. As a marker for identifying LN patients with more severe renal histologic activity (i.e., a histologic activity index of ≥7), the level of urinary MMP-7 outperformed other clinical markers and improved their predictive performance, thus linking urinary MMP-7 levels to renal disease activity. Furthermore, among patients who had follow-up measurements of urinary MMP-7 after achievement of long-term remission of renal disease activity, an elevated urinary MMP-7 level during follow-up was independently associated with an increased risk of LN flare. This elevation in the urinary MMP-7 level hinted at the risk of an LN flare at an earlier time point prior to indications using conventional laboratory measures. Thus, use of the urinary MMP-7 level in conjunction with other clinical measures improved the prognostic value for prediction of an LN flare. CONCLUSION: Urinary MMP-7 levels in LN are correlated with renal histologic activity. An elevated urinary MMP-7 level detected after achievement of long-term renal disease remission is associated with a higher risk of incident renal flare in patients with LN.

Prevalence of HIV-1 Drug-Resistance Genotypes Among Unique Recombinant Forms from Yunnan Province, China in 2016-2017.

To investigate the prevalence and characteristics of drug-resistance genotypes among unique recombinant forms (URFs) in HIV-1 infected people under long-term antiretroviral treatment failure from Yunnan Province. The plasma samples were collected from antiretroviral therapy (ART)-failure experienced individuals from 2016 to 2017 in Yunnan Province, China. The genotyping drug resistance of HIV-1 pol gene fragments was implemented using in-house assay. According to the analysis of RIP and MEGA 7.0, the HIV-1 strains related to URFs were screened for recombinant identification and drug resistance analysis. A total of 130 pol sequences of HIV-1 URF strains were obtained from 1,121 samples. The proportion of HIV-1 URF strains was 11.6% among the ART-failure individuals from 2016 to 2017 in Yunnan. The overall drug-resistance rate of HIV-1 URF strains was 56.9%. Meanwhile, the percentage of protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) resistance was 3.8% (5/130), 36.2% (47/130), and 53.8% (70/130), respectively. Mutations such as M184V/I (35.4%) in NRTIs and K103N/R/S/T (25.4%), V179D/E/T/Y (18.9%), G190A/E/R/S (13.8%), and Y181C (9.2%) in NNRTIs were common among the HIV-1 URF strains relative to other mutations. Factors such as male, sexual transmission pathway, and source of the year 2017 were significantly correlated with the development of HIV-1 URF drug resistance. The emergence of the multiple recombinant forms identified in Yunnan indicates active transmission networks of HIV-1 of different HIV-1 subtype/circulating recombinant forms cross-infection in this region. Therefore, it is necessary to further monitor the molecular epidemiology and drug resistance of HIV-1 in Yunnan.

Genotypic drug resistance of HIV-infected MSM who failedin antiviral therapy in Yunnan Province / 预防医学

Objective@#To learn the genotypic drug resistance of men who have sex with men ( MSM ) with HIV who failed in antiviral therapy in Yunnan Province, in order to provide basis for improving the effect of antiviral therapy.@*Methods@#The patients who were infected with HIV-1, homosexual transmitted and failed in antiviral therapy in Yunnan Province from 2014 to 2019 were recruited. Their plasma samples were tested by reverse transcription nested polymerase chain reaction ( RT-nPCR ) , the fragments were spliced using ContigExpress, and the resistance to 8 protease inhibitors ( PIs ) , 7 nucleoside reverse transcriptase inhibitors ( NRTIs ) and 5 non-nucleoside reverse transcriptase inhibitors ( NNRTIs ) were obtained from the HIV drug resistance data website of Stanford University.@*Results@#A total of 205 HIV/AIDS cases were included, 169 positive plasma samples were amplified, 112 cases were drug resistant, and the rate of drug resistance was 66.27%. The patients who were aged 30-49 years ( 76.09% ) , had genotype of CRF01_AE ( 76.34% ) or treated by AZT+3TC+NVP ( 77.08% ) had higher resistance rate. The resistance rates of NNRTIs, NRTIs and PIs were 62.72%, 49.70% and 2.96%, respectively; the resistance rates of NVP and EFV in NNRTIs were 62.72% and 61.54%. The main mutation site associated with NNRTIs was K103, accounting for 21.89% ( 37 cases ) ; the main mutation site associated with NRTIs was M184, accounting for 39.64% ( 67 cases ) ; the main mutation sites associated with PIs were M46L/K, accounting for 2.96% ( 5 cases ) , resulting in high resistance to NFV.@*Conclusions@#The drug resistance rate of HIV-infected MSM with failure of antiviral therapy in Yunnan Province is relatively high, with CRF01_AE as the main gene subtype of drug resistance. The drug resistance rate of NNRTIs is relatively high, especially NVP and EFV.

High-sensitivity C-reactive protein as a predictive factor of acute kidney injury following aneurysmal subarachnoid hemorrhage: a prospective observational study.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a well-recognized biomarker of neurologic complications and clinical outcome of stroke patients. However, whether hs-CRP can predict the occurrence of acute kidney injury (AKI) in aneurysmal subarachnoid hemorrhage (aSAH) patients is still unclear. The objective of this study was to assess the feasibility of using serum hs-CRP level to predict the occurrence of AKI in aSAH patients. METHODS: One hundred sixty-four aSAH patients were enrolled into a prospective observational study. AKI was diagnosed using the modified Kidney Disease Improving Global Outcomes (KDIGO) standard. The relationship between serum hs-CRP level at admission and occurrence of AKI was analyzed. RESULTS: AKI occurred in 17 patients (10.4%) in this cohort. Patients with AKI had significantly higher hs-CRP levels than those without. The mortality of the AKI group tends to be higher than that of the non-AKI group, but the difference was not statistically significant (4/17 (23.5%) vs. 13/147 (8.8%), P = 0.081). After adjusting for possible confounding factors including World Federation of Neurosurgical Societies grade, diabetes, and serum creatinine, multivariate analysis revealed that serum hs-CRP level and antibiotic therapy were both significant factors independently associated with AKI following aSAH (serum hs-CRP: OR = 1.2, 95% confidence interval (CI) = 1.1-1.3, P = 0.003; antibiotic therapy: OR = 5.8, 95%CI = 1.6-20.7, P = 0.007). Receiver operating characteristic curve analysis showed that hs-CRP had a sensitivity of 76.5% and a specificity of 64.6% for predicting the development of AKI on the basis of the best thresholds. The post hoc log-rank test revealed that patients having serum hs-CRP level > 6.6 mg/L had a significantly higher AKI rate than patients having serum hs-CRP level ≤ 6.6 mg/L (P = 0.001). CONCLUSIONS: Serum hs-CRP level might be helpful as a predictor for the development of AKI in aSAH patients. Delayed cerebral ischemia occurrence rate and mortality of patients with AKI tend to be higher than those of patients without in this cohort; however, they were not significantly different.

Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China.

BACKGROUND: Understanding the prevalence and evolution of HIV-1 drug resistance (DR) and associated mutation patterns is critical to implementing free antiretroviral therapy in Yunnan, the first antiretroviral treatment location in China. Here We provide a basis for understanding the occurrence and development of HIV-1 resistance in Yunnan and a theoretical foundational for strategy to delay HIV-1 drug resistance and achieve successful individualized treatment. METHODS: Plasma samples from different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to September 2016, and those from drug-resistant individuals were genotyped using in-house assays, 88 patients were selected for the study who had been on treatment for ≥6 months (and for whom drug resistance was then measured), and each patient had at least 3 genotype resistance tests and who were enrolled to analyze mutation and evolution of HIV resistance. RESULTS: 264 Pol sequences of 88 patients were obtained. Drug resistance levels to eight drugs increased to varying degrees with prolonged treatment. Resistance to efavirenz (EFV) and etravirine (ETR) showed the highest change, comparisons of resistant changes to second and first and to third and second agents showed altered level of drug resistance were 25 and 20 cases, 28 and 18 cases, respectively. The smallest change was Lopinavir/Ritonavir (LPV/r) present 2 and 3 cases; Resistance to lamivudine (3TC) and lopinavir/ritonavir (LPV/r) was high among patients detected thrice, whereas other drugs were distributed in all resistance levels. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs). CONCLUSIONS: We found dynamic genotypic changes in HIV-1 drug-resistance in Yunnan, with prolonged treatment, and drug resistance was inevitable. However, resistance to different drugs occurred at varying times, and mutation site emergence was the main cause. These findings enhance our understanding of evolution and regulation, and are valuable for developing HIV-1 DR prevention strategies in Yunnan.

SPAG6 regulates cell apoptosis through the TRAIL signal pathway in myelodysplastic syndromes.

Myelodysplastic syndromes (MDSs) are a group of malignant clone hematopoietic stem-cell diseases, and the evolution and progression of MDS depend on the abnormal apoptosis of bone marrow cells. Our previous studies have indicated that sperm-associated antigen 6 (SPAG6), located in the uniparental disomy regions of myeloid cells, is overexpressed in patients with MDS as compared to controls, and SPAG6 can inhibit apoptosis of SKM-1. However, the concrete mechanism is still unclear. In the present study, it was found that the TNF-related apoptosis-inducing ligand (TRAIL)signal pathway was activated when the expression of SPAG6 was inhibited by SPAG6-shRNA lentivirus in SKM-1 cells. Additionally, the results of flow cytometry, Cell Counting Kit-8 assay and western blot analysis implied that the TRAIL signal pathway could be inhibited by a high expression of SPAG6. However, SPAG6 cannot influence the expression of TRAIL death receptors, except for FADD. Additionally the interaction between FADD and TRAIL death receptors also increased in SKM-1 cells infected with SPAG6-shRNA lentivirus. Thus, our study demonstrates that SPAG6 may regulate apoptosis in SKM-1 through the TRAIL signal pathway, indicating that SPAG6 could be a potential therapeutic target.