[Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome].

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence.

PURPOSE: For treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection (3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy. MATERIAL AND METHODS: We reviewed 1282 patients with thoracic esophageal squamous cell carcinoma (ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC. RESULTS: The lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence accounted for 84.92%, 36.07% and 22.30%, respectively (χ2=264.776, P=0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively (χ2=313.600, P=0.000). Cervical metastases were significantly associated with N stage and Preoperative cervical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases (LNM), tumor location and N stage. CONCLUSIONS: The main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. The abdominal areas might be irradiated for lower TEC patients with preoperative abdominal LNM.

[Suitability of estimated urine protein using different estimated 24 h urine creatinine equations in children with glomerular diseases].

Objective: To assess the reliability of estimated urine protein to predict 24 h urine protein excretion in children with glomerular diseases. Methods: Four hundred and forty-three children with glomerular diseases, who were admitted to pediatric department of Peking University First Hospital from January 2001 to December 2021, were enrolled in the cross-sectional study. The 24 h estimated urine creatinine which calculated by 6 previously described equations, 24 h measured urine creatinine, measured urine protein-to-creatinine ratio(UPCR), 24 h urine protein (24 hUP) and urinary sediment analysis with microscopy were collected, estimated urine protein was computed as the product of measured UPCR and estimated or measured 24 h urine creatinine. Spearman correlation analysis, Bland-Altman analysis and linear regression analysis were used to compare the correlation, agreement and accuracy between estimated urine protein and 24 hUP, and the effect of urinary protein level and erythrocyte numbers on their relationship was analyzed. Results: Of 443 children with glomerular diseases (aged (11±4) years, 221 male, 222 female), there were 216 participants with nephrotic syndrome, 78 participants with IgA nephropathy, 47 participants with Alport syndrome, 42 participants with lupus nephritis, 58 participants with purpura nephropathy, and 2 participants with isolated proteinuria. Spearman correlation analysis showed a strong correlation between estimated urine protein and 24 hUP (r=0.90, P<0.05), and the correlation improved after multiplying the measured UPCR by 24 h measured urine creatinine (r=0.94, P<0.05). Improved correlation was also observed using the estimated urine creatinine which calculated by Hellerstein formula, Ghazali-Barratt formula, Ellam formula, Walser formula, Cockcroft-Gault formula, Ix formula (r=0.93, 0.94, 0.90, 0.90, 0.94, 0.93, all P<0.05).Bland-altman analysis showed that the difference between measured UPCR and 24 hUP was (-0.30±2.22) g, consistency limit was -4.65-4.04, and the consistency improved after 24 h measured urine creatinine correction (difference was (0.27±1.31) g, consistency limit -2.30-2.84). The consistency of estimated urine protein was further improved after correction by different formulas, and the Cockcroft-Gault formula showed the best consistency between estimated urine protein and 24 hUP (difference was (0.11±1.18)g, consistency limit was -2.20-2.42). Linear regression analysis showed that measured UPCR had poor accuracy in predicting 24 hUP (R2=0.55, α=0.48, ß=0.60, P<0.05), and the accuracy improved after 24 h measured urine creatinine correction, the accuracy of estimated urine protein for predicting 24 hUP was further improved by using different formulas, and Cockcroft-Gault formula was the best (R2=0.81, α=0.18, ß=0.96, P<0.05). With the increase of urinary protein level and the decrease of urinary erythrocyte numbers, the correlation, agreement and accuracy between estimated urine protein and measured UPCR and 24 hUP were improved(all P<0.05). Except Ellam and Ix formulas, estimated urine protein using the rest four formulas outperformed measured UPCR(all P<0.05). Conclusion: The 24 h urine creatinine excretion rate (obtained by the Cockcroft-Gault equation)-weighted urine protein-to-creatinine ratio more reliably predicts 24 hUP than measured UPCR alone in children with glomerular diseases.

[C1q or IgA deposition in glomeruli of children with primary membranous nephropathy].

Objective: To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods: The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney U test and Fisher's exact probability test were used for comparison between the groups. Results: Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) vs. 7 (3, 12) years, Z=-2.52, P=0.011), a lower preceding infection rate (45% (9/20) vs. 11/13, P=0.032) and lower spontaneous remission rate (0 vs. 4/13, P=0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 vs. 5/15, P=0.031) and low albumin levels at renal biopsy ((25±6) vs. (29±7) g/L, t=2.14, P=0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all P>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) vs. 6.0 (2.5, 22.3) months, Z=-2.27, P=0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all P>0.05). Conclusion: Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.

[Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In Tube in the diagnosis of pulmonary tuberculosis].

Objective: To compare the screening value of QuantiFERON-TB Gold Plus (QFT-Plus) and QuantiFERON®-TB Gold in tube (QFT-GIT) in the auxiliary diagnosis of pulmonary tuberculosis (TB). Methods: A screening test was performed. Patients who were hospitalized in Guangzhou Chest Hospital and underwent QFT-GIT testing from October to December 2020 were prospectively included as research subjects, QFT-Plus testing was added. And the basic information, clinical manifestations, laboratory test results, imaging examinations and other data of these patients were collected. A total of 207 patients were included and divided into tuberculosis group and non-tuberculosis group according to these data. There were 124 cases in the tuberculosis group (94 confirmed patients and 30 clinically diagnosed patients), including 90 males and 34 females, aged 18-93 years, with a median age of 57 (38, 67) years. The non-tuberculosis group included 83 patients (16 patients with non-tuberculous Mycobacteria and 67 patients with other lung diseases), including 49 males and 34 females, with a median age of 60 (51, 68) years. The confirmed patients were subdivided into three grades of low, medium and high Mycobacteriam tuberculosis (MTB) bacterial load, and three grades of mild, moderate and severe pulmonary tuberculosis. The results of QFT-Plus and QFT-GIT were compared, and the levels of IFN-γ in different antigen tubes were compared. Differences between different groups were compared using Mann-Whitney U test and Kruskal-Wallis H test. Results: The QFT-Plus showed a high degree of agreement with the QFT-GIT (κ=0.786, 95%CI: 0.740-0.832), while the main discordant result was QFT-GIT negative/QFT-Plus positive, accounting for 15/17. The sensitivity of QFT-GIT was 80.7%(95%CI: 0.706-0.880), the specificity was 76.3%(95%CI: 0.649-0.850), the positive predictive value was 79.8%(95%CI: 0.697-0.873), and the negative predictive value was 77.3%(95%CI: 0.659-0.859), repectively. QFT-Plus showed a sensitivity of 84.3%(95%CI: 0.743-0.910), a specificity of 78.8% (95%CI: 0.679-0.868), and a positive predictive value of 80.5%(95%CI: 0.703-0.879), the negative predictive value being 82.9%(95%CI: 0.721-0.902), slightly improved to that of the QFT-GIT. Also, this study found that there were significant differences in IFN-γ values between different MTB load or disease severity (P<0.05). Conclusions: There is a good consistency between the QFT-Plus test and the QFT-GIT test, both of which show good application value in the auxiliary diagnosis of pulmonary tuberculosis. Moreover, because of the addition of tuberculosis-specific CD8 cell antigen, the QFT-Plus test has higher sensitivity, lower uncertainty and more application value. This study also found that the bacterial load and disease severity of patients with pulmonary tuberculosis may have a certain correlation with the measured value of IFN-γ.

The bipolar charge plasma spectrometer (BCPS) based on the 2π-field-of-view double-channel electrostatic analyzer.

In this paper, we propose a bipolar charge plasma spectrometer based on the double-channel electrostatic analyzer for simultaneously measuring thermal ions and electrons with a 2π hemispherical field-of-view. Both ions and electrons within the wide field-of-view enter the spectrometer, pass through the variable geometric factor channel, and are then separated by the double-channel electric fields. Two microchannel plates are accommodated at the exit of the analyzer for ion and electron detection. The main performance of the spectrometer has been obtained from on-ground calibration. With the electrostatic deflectors and the cylindrically symmetric structure, the spectrometer provides simultaneous measurements of thermal ion and electron velocity distributions with a shared field-of-view of 360° (azimuth angle) by 90° (elevation angle) and a broad energy range for both ions and electrons. The ion analyzer constant and the electron analyzer constant are 11.1 and 9.7, respectively. The detecting energy range of 33.3-44.4 keV for ions and 29.1-38.8 keV for electrons can be obtained by using the sweeping electrostatic analyzer voltage range of 3-4000 V. The ion and electron energy resolutions are 9.6% and 6.1%, respectively. The variable geometric factor function provides a large geometric factor adjusting range for both ion and electron measurements by two orders of magnitude, which fulfills the requirements of a large dynamic flux range for simultaneous measurements of space thermal plasma in the solar wind and magnetosphere.

Associations of Cardiovascular and Non-Cardiovascular Comorbidities with Dementia Risk in Patients with Diabetes: Results from a Large UK Cohort Study.

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for dementia. However, it remains unclear whether the presence of comorbidities could further increase dementia risk in diabetes patients. OBJECTIVES: To examine the associations between cardiovascular and non-cardiovascular comorbidities and dementia risk in T2D patients. DESIGN: Population-based cohort study. SETTING: The UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: 489,205 T2D patients aged over 50 years in the UK CPRD. MEASUREMENTS: Major cardiovascular and non-cardiovascular comorbidities were extracted as time-varying exposure variables. The outcome event was dementia incidence based on dementia diagnosis or dementia-specific drug prescription. RESULTS: During a median of six years follow-up, 33,773 (6.9%) incident dementia cases were observed. Time-varying Cox regressions showed T2D patients with stroke, peripheral vascular disease, atrial fibrillation, heart failure or hypertension were at higher risk of dementia compared to those without such comorbidities (HR [95% CI] = 1.64 [1.59-1.68], 1.37 [1.34-1.41], 1.26 [1.22-1.30], 1.15 [1.11-1.20] or 1.10 [1.03-1.18], respectively). Presence of chronic obstructive pulmonary disease or chronic kidney disease was also associated with increased dementia risk (HR [95% CI] = 1.05 [1.01-1.10] or 1.11 [1.07-1.14]). CONCLUSIONS: A range of cardiovascular and non-cardiovascular comorbidities were associated with further increases of dementia risk in T2D patients. Prevention and effective management of these comorbidities may play a significant role in maintaining cognitive health in T2D patients.

Clinical and urodynamic features of secondary tethered cord syndrome: How can they be found longitudinally?

PURPOSE: Secondary tethered cord syndrome (TCS) can be diagnosed with signs of progressive deterioration in urological or neuro-orthopedic systems following primary untethering surgery. Though urological deterioration is a common secondary TCS manifestation, a paucity of diagnostic criteria makes diagnoses challenging. A detailed description of urological deterioration may help diagnose secondary TCS. Thus, the clinical and urodynamic features of the current secondary TCS cases were described. MATERIALS AND METHODS: Fifty-one patients who had undergone reuntethering for secondary TCS experienced improvement or stabilization of progressive problems. Moreover, their clinical and videourodynamic changes were longitudinally described. RESULTS: Loss of postoperative spontaneous voiding was the first urological secondary TCS sign for those who could void spontaneously. Urological problems mostly occurred during elementary school (6-12 years). Major urological presentations were recalcitrant urinary tract infection or urinary incontinence. Follow-up videourodynamic studies revealed typical changes, from acontractile bladder to overactive and low-complaint bladders. While detrusor overactivity did not always occur during the progression, detrusor sphincter dyssynergia was always present in all patients with urological deterioration. All patients postoperatively showed significant urodynamic improvement regardless of preoperative bladder dysfunction. This included four cases of restoring spontaneous voiding. Nine patients experienced newly appearing nonprogressive neuro-orthopedic complications despite their urological improvement. CONCLUSIONS: Urological deterioration should prompt secondary TCS suspicion, and changes in clinical patterns and videourodynamic studies helped diagnose it. However, reuntethering can effectively address urological problems at the cost of some neuro-orthopedic functions in some patients.

Nitrogen doped titanium dioxide as an aesthetic antimicrobial filler in dental polymers.

OBJECTIVE: To develop an aesthetic resin composite using a nitrogen-doped titanium dioxide (NTiO2) filler that possesses antimicrobial properties against cariogenic bacteria. METHODS: N-TiO2 powder was manufactured by calcining commercial TiO2 with urea. Free radical release from the N-TiO2 powder under visible light irradiation was analysed using UV-Vis spectrophotometry. The N-TiO2 powder was incorporated into a dental resin and the photocatalytic activity assessed using a dye under both visible light and dark conditions. Using XTT assay to measure the cellular metabolic activity, the antibacterial properties of the N-TiO2 /resin composite discs were tested using Streptococcus mutans. RESULTS: Doping nitrogen of TiO2 resulted in a band gap shift towards the visible light spectrum, which enabled the powder to release reactive oxygen species when exposed to visible light. When incorporated into a dental resin, the N-TiO2/resin composite still demonstrated sustained release of reactive oxygen species, maintaining its photocatalytic activity and showing an antibacterial effect towards Streptococcus mutans under visible light conditions. SIGNIFICANCE: N-TiO2 filled resin composite shows great promise as a potential aesthetic resin based adhesive for orthodontic bonding.

[Tanshinone IIA alleviates lipopolysaccharide-induced renal tubular epithelial cell apoptosis by inhibiting RIP3/FUNDC1 signaling pathway].

OBJECTIVE: To investigate the effect of tanshinone IIA pretreatment on acute renal injury in lipopolysaccharide (LPS)-induced septic mice and explore the possible mechanism. METHODS: Thirty C57BL/6 mice were randomized for treatment with saline (control), 10 mg/kg LPS for 24 h, or 10 mg/kg tanshinone IIA 15 min before LPS treatment. After the treatments, serum creatinine and blood urea nitrogen levels of the mice were detected, renal pathologies were observed with PAS staining, and renal expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 were detected with Western blotting. In the cell experiment, cultured normal human renal tubular epithelial cells (HK-2) were treated with LPS (10 mg/mL), LPS+ siNC, LPS+ siRIP3, or LPS+tanshinone IIA (10 mg/L), and the changes in cell apoptosis were examined with TUNEL staining; Western blotting was performed to detect the expression levels of RIP3, cleaved caspase-3 and p18-FUNDC1, and qRT-PCR was used to detect the expression of RIP3 mRNA. RESULTS: LPS challenge for 24 h significantly increased serum creatinine and blood urea nitrogen levels in the mice, caused obviously damages in the proximal renal tubules, and increased renal expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 proteins. Tanshinone IIA pretreatment significantly improved LPS-induced renal injury in the mice, alleviated apoptosis of the renal cells, and inhibited the expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 proteins. In HK-2 cells, LPS stimulation significantly increased the protein expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 and induced obvious cell apoptosis. Pretreatment with tanshinone IIA strongly inhibited the expression of RIP3 and p18-FUNDC1 and reduced LPS-induced apoptosis of HK-2 cells. CONCLUSION: Tanshinone IIA can reduce LPS-induced apoptosis of renal tubular epithelial cells by inhibiting RIP3/FUNDC1 signal pathway.

[Expert consensus on early prediction and diagnosis of diabetic kidney disease].

Diabetic kidney disease (DKD) is a type of chronic kidney disease (CKD) caused by diabetes. The clinical diagnosis of DKD is usually based on the presence of increased albuminuria and/or decreased estimated glomerular filtration rate (eGFR), and exclusion of other causes of CKD. The clinical features of DKD are proteinuria, gradual decline in renal function, and severe renal failure in the later stages, which is one of the main causes of death in patients with diabetes. Any single biomarker might be insufficient to evaluate renal injury; thus, multiple methods and markers are needed. In addition, diabetic patients should be paid more attention to the kidney, and kidney damage should be evaluated with standardized assessment aimed at strengthening the early prediction and diagnosis of DKD.

[Analysis on the law of height growth spurt in adolescence of children and adolescents in Zhongshan City].

OBJECTIVE: To analyze the characteristics of the age at peak height velocity and peak height velocity of primary and middle school students in Zhongshan City, Guangdong Province, and to explore the law of the sudden increase in adolescent height in this area, and to understand the law of height growth spurt in adolescence by longitudinal tracking of the height of children and adolescents in Zhong-shan City. METHODS: Based on the physical examination database of primary and middle school students in Zhongshan City, Guangdong Province from 2005 to 2016, individuals who had been continuously tracked for more than 6 times were selected as research samples. SITAR model was used to fit the height data of the sample population, and the age at peak height velocity and peak height velocity were calcula-ted. RESULTS: A total of 49 579 subjects were included in this study, including 26 524 boys and 26 008 urban students. The median follow-up ages of boys and girls were 7.74 and 7.72 years, respectively. The boy's height spurt peak age was (12.72±0.89) years, and later than the girls at the age of (10.98±0.95) years (t=207.639, P < 0.001), the boy's height spurt peak velocity of (10.12±1.49) cm/year, higher than the girls of (8.35±1.12) cm/year (t=150.826, P < 0.001). The gender differences of height spurt peak age and height spurt peak speed in urban and rural students were consistent with the whole sample. The height surge peak age of urban male students was earlier than that of rural male students, and the height surge peak speed of urban female students was lower than that of rural female students. CONCLUSION: The peak age of the surge of girls was earlier than that of boys, but the peak rate of the surge of girls was lower than that of boys, the peak age of urban students was earlier than that of rural students, but the peak rate of urban boys was lower than that of rural boys in Guangdong Province.

Performance and simulated moment uncertainties of an ion spectrometer with asymmetric 2π field of view for ion measurements in space.

Space plasma instruments provide 3D particle velocity distribution functions. Because of telemetry limitations, these cannot be transmitted in high time resolution and the plasma needs to be characterized by moments of the velocity distribution function. These moment uncertainties have vital effects on the reliability and accuracy of onboard plasma moments. We assess the measurement accuracy for magnetosheath and solar wind ions using an ion spectrometer with an asymmetric field of view designed for the all-sky measurement of low-energy ions in the magnetosheath and solar wind. We focus on moment uncertainties for the ideal spectrometer, not considering the background counts, which may have considerable effects on the uncertainties in real life. To obtain number density, bulk velocity, and temperature, different orders of moments are integrated assuming a Maxwellian velocity distribution. Based on the design specifications, we use simulations to estimate systematic and random errors for typical plasma conditions. We find that the spectrometer resolution is adequate for determining the density of solar wind (∼7% error) and magnetosheath ions (∼4% error). The resolution is also adequate for determining the temperature of solar wind (∼10% error) and magnetosheath ions (∼2% error). For high speed flows with a bulk velocity of 750 km/s and a temperature of 20 eV, the maximum density and temperature errors become 9% and 7%, respectively. The bulk velocity errors are less than 2% for all cases. The contributions of heavy ions to the systematic errors are less than 5% for magnetosheath ions and less than 8% for solar wind ions.

High expression level of interleukin-1β is correlated with poor prognosis and PD-1 expression in patients with lung adenocarcinoma

Purpose Cytokines are vital pro-inflammatory factors and involved in tumor immune infiltration, and immune infiltration is closely related to PD-1/PD-L1 blockades immunotherapy. This study aims to explore the associations between cytokines and prognosis and also PD-1/PD-L1 expression in early lung adenocarcinoma, which is seldom reported. Methods 324 early lung adenocarcinoma patients with prior surgical resection were included and the associations between overall survival time and clinical factors and also cytokines including IL-1β, IL-6 and TNF-α were analyzed by multivariate cox regression and Kaplan–Meier curve (log-rank test). Resected tumor samples were randomly obtained to detect the PD-1/PD-L1 expression by immunohistochemistry, and Chi square test was used for relations between cytokines and PD-1/PD-L1 expression. Results In this study group, 26.2% patients showed a high level of IL-1β and patients with high IL-1β level showed 19 months shortened mOS than those with normal IL-1 β expression (mOS: 24.00, 95%CI 11.98–36.02 vs 43.00, 95% CI 37.37–48.63, p = 0.017). Among detected samples, the positive rate of PD-1 was 25.0% (13/52), and the positive rate of PD-L1 was 37.3% (19/52). The positive rate of PD-1 was 36.1% higher in high-IL-1 β-level group as compared to normal-IL-1β-level group (50.0% vs 13.9%, p = 0.012). No significant association was found between IL-1 β and PD-L1 expression. Conclusion High expression level of IL-1β was correlated with poor prognosis and higher positive rate of PD-1 expression, which gave us insights into biomarkers of survival prediction and immunotherapy in lung adenocarcinoma. Further studies were still needed (AU)

[Isolation, identification and safety evaluation of Lactobacillus gasseri strain LGV03 isolated from the vagina of healthy women].

OBJECTIVE: To characterize the bacterial strain LGV03 isolated from the reproductive tract of healthy women and evaluate its safety. METHODS: The bacterial strains were isolated and purified using MRS agar by dilution plating and streak plate method. Gram staining was used to observe the morphology of the isolated strains and identify Gram-negative and -positive strains. The physiological and biochemical properties of the bacteria was assessed using VITEK ANC card. Strain LGV03 was identified by molecular biology and phylogenetic analysis and tested for hemolysis on blood agar plates. E-test method was performed to examine the sensitivity of strain LGV03. The concentration of lactic acid in the culture supernatant of LGV03 was measured using a biochemical analyzer. The safety of LGV03 was evaluated in mice using acute oral toxicity test. RESULTS: The isolated bacterial strain LGV03 showed good growth under anaerobic conditions at 37 ℃ on MRS medium and formed round, milky white, moist, and opaque colonies with neat margins. The strain LGV03 was positive for Gram staining, rod-shaped with a size range of (0.4-0.5) × (0.9-6.3) µm, and was identified as Lactobacillus gersonii. LGV03 was sensitive to PG, AM, MP, VA, EM and LZ. In MRS medium LGV03 could produce lactic acid, which reached its saturation concentration after 18 h with a final concentration of 1.72 mg/mL. The mice with acute oral exposure to LGV03 showed no significant changes of body weight or organ weight as compared with normal saline-treated mice. CONCLUSION: The bacterial strain LGV03 isolated from the female reproductive tract was identified as Lactobacillus gersonii with potential probiotic effects and good safety profile.

High expression level of interleukin-1ß is correlated with poor prognosis and PD-1 expression in patients with lung adenocarcinoma.

PURPOSE: Cytokines are vital pro-inflammatory factors and involved in tumor immune infiltration, and immune infiltration is closely related to PD-1/PD-L1 blockades immunotherapy. This study aims to explore the associations between cytokines and prognosis and also PD-1/PD-L1 expression in early lung adenocarcinoma, which is seldom reported. METHODS: 324 early lung adenocarcinoma patients with prior surgical resection were included and the associations between overall survival time and clinical factors and also cytokines including IL-1ß, IL-6 and TNF-α were analyzed by multivariate cox regression and Kaplan-Meier curve (log-rank test). Resected tumor samples were randomly obtained to detect the PD-1/PD-L1 expression by immunohistochemistry, and Chi square test was used for relations between cytokines and PD-1/PD-L1 expression. RESULTS: In this study group, 26.2% patients showed a high level of IL-1ß and patients with high IL-1ß level showed 19 months shortened mOS than those with normal IL-1 ß expression (mOS: 24.00, 95%CI 11.98-36.02 vs 43.00, 95% CI 37.37-48.63, p = 0.017). Among detected samples, the positive rate of PD-1 was 25.0% (13/52), and the positive rate of PD-L1 was 37.3% (19/52). The positive rate of PD-1 was 36.1% higher in high-IL-1 ß-level group as compared to normal-IL-1ß-level group (50.0% vs 13.9%, p = 0.012). No significant association was found between IL-1 ß and PD-L1 expression. CONCLUSION: High expression level of IL-1ß was correlated with poor prognosis and higher positive rate of PD-1 expression, which gave us insights into biomarkers of survival prediction and immunotherapy in lung adenocarcinoma. Further studies were still needed.

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co-infected and HIV mono-infected patients: a retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups. METHODS: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association. RESULTS: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). CONCLUSIONS: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism.

[The value of left ventricular longitudinal strain in the diagnosis and differential diagnosis of myocardial amyloidosis].

Objective: To investigate the characteristics of left ventricular longitudinal strain (LS) in myocardial amyloidosis (CA), hypertrophic cardiomyopathy (HCM) and Fabry disease (FD), as well as the correlation between left ventricular LS and these diseases. Methods: A total of 14 CA patients, 28 HCM patients and 5 FD patients who visited the Department of Cardiology of the First Affiliated Hospital of Suzhou University from June 2017 to November 2019 were retrospectively included. EchoPAC software was used to analyze left ventricular LS, and univariate logistic regression analysis was used to analyze the correlation between echocardiographic LS indexes and various myocardial hypertrophy diseases. The receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of echocardiograph LS indexes in the diagnosis of various myocardial hypertrophy diseases. Results: There were significant differences in LS of left ventricular basal segment, inferior wall, posterior wall, lateral wall and posterior septum among the three groups (P<0.05). The absolute value of LS in the left ventricular basal segment decreased in the CA group; the absolute value of LS in left ventricular posterior wall and lateral wall decreased significantly in the FD group (P<0.05); the absolute values of LS in left ventricular basal segment, inferior wall, posterior septum, lateral wall and posterior wall increased significantly in the HCM group (P<0.05). The absolute value of LS < 7.9% in the left ventricular basal segment, or > 13.2% in the inferior wall and > 9.2% in the basal segment, or < 8.3% in the lateral wall and < 7.9% in the posterior wall were the indicators of high sensitivity and specificity in the diagnosis of CA, HCM and FD, respectively. Conclusions: Left ventricular LS was an important index to differentiate myocardial hypertrophy. Combined with their respective clinical characteristics, it could provide certain reference value for clinical practice.