[ANCA-negative granulomatosis with polyangiitis: a case report].

We reported a case of 73-year-old male with multiple pulmonary nodules and cavities. The patient was admitted with a chief complaint of "dry cough with shortness of breath for 3 months". Chest CT showed multiple irregular masses, nodules, and patchy lesions in both lungs, accompanied by the formation of cavities. He also had anemia and renal dysfunction. Despite given empirical anti-infective and anti-tuberculosis treatments, the pulmonary nodules progressed, and the cavities enlarged. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative twice. Bronchoscopic biopsy was performed. The mucosal pathology of the right middle lobe lesion showed little necrosis, focal granulomatous structure formation, and relevant vasculitis and remaining vessel wall structure in the necrosis lesions by elastic fiber staining. A clinical diagnosis of ANCA-negative necrotizing granulomatous polyangiitis was made and the patient was treated with glucocorticoids and cyclophosphamide. The nodules and cavities shrank, and some lesions were absorbed.

Taxonomic and ecophysiological characteristics of actinobacteria in soils of the dry steppe zone of the Selenga Highlands (Western Transbaikalia).

Arid habitats have recently attracted increasing attention in terms of biodiversity research and the discovery of new bacterial species. These habitats are among the target ecosystems suitable for isolating new strains of actinobacteria that are likely to produce new metabolites. This paper presents the results on the isolation of actinobacteria from soils of the dry steppe zone of the Selenga Highlands, the characterization of their taxonomic diversity, as well as ecological and trophic properties. The bacterial counts on ISP 4 medium ranged from 6.6 × 105 to 7.1 × 106 CFU/g. The highest bacterial counts were observed in the subsurface and middle horizons of the studied soils. 28 strains of Gram-positive bacteria represented by thin-branched mycelium, coccoid and bacilliform forms were isolated. According to the results of 16S rRNA gene analysis, the isolated strains were representatives of Streptomyces, Arthrobacter, Glycomyces, Kocuria, Microbacterium, Micromonospora, Nocardioides, Pseudarthrobacter, and Rhodococcus (Actinomycetota). One isolate that showed low 16S rRNA gene sequence similarity with previously isolated and validly described species was a new species of the genus Glycomyces. It was shown that all tested strains are mesophilic, prefer neutral or slightly alkaline conditions, have growth limits in the temperature range of 5-45 °C and pH 6-9. The optimal NaCl concentration for growth of most strains was 0-1 %. The strains under study were capable of utilizing a wide range of mono- and disaccharides and polyatomic alcohols as a carbon source. The isolated strains were capable of using both organic (proteins and amino acids) and inorganic (ammonium salts and nitrates) compounds as nitrogen sources. The examinations of extracellular enzymes showed that all isolates were capable of producing catalase and amylase; 78.6 % of the total number of isolates produced protease and lipase; 53.6 %, cellulase; and 28.6 %, urease. The data obtained expand current knowledge about the diversity of microbial communities in soils of the Selenga Highlands and also confirm the potential of searching for new actinobacteria species in these soils.

[Efficacy analysis of selective genicular artery embolization in the treatment of knee pain secondary to osteoarthritis].

Objective: To evaluate the efficacy and safety of selective genicular artery embolization for the treatment of the knee pain secondary to osteoarthritis. Methods: From October 2020 to July 2021, 17 patients (23 knees) aged (68±7) years with moderate to severe knee pain secondary to knee osteoarthritis were prospectively included in the General Hospital of Ningxia Medical University. There were 6 males and 11 females included in this research. Patients were assessed with knee pain, stiffness, and function with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, using the Kellgren-Lawrence (K-L) grading to evaluate the severity of KOA, and using the Magnetic Resonance Knee Osteoarthritis Score (MOAKS) to evaluate the MR imaging characteristics of the affected knee. Selective genicular artery embolization (GAE) was performed in all patients. The patients were followed up for 6 months after the procedure. Patients were assessed with the VAS score and WOMAC scale at 1 d, 1 week and 1, 3 and 6 months after the procedure to evaluate the clinical outcomes, including the improvement of knee joint pain, stiffness and function, as well as the occurrence of adverse reactions. Results: Three to seven genicular artery branches were superselected and embolized in 23 knees, and 4 to 7 genicular artery branches were embolized in 7 patients with K-L grade 4. The clinical improvement was 95.6% (22/23) at 1 month, 86.9% (20/23) at 3 months, and 91.3% (21/23) at 6 months. Twenty-three knees completed the 6-month follow-up, and the VAS score, WOMAC pain score, and total WOMAC score at 1, 3, and 6 months after surgery were (2.5±1.3), (3.4±2.4), and (19.7±9.8) points, (3.0±1.8), (4.5±3.4), and (22.3±11.3) points, (2.8±1.5), (4.1±3.0), and (20.5±11.0) points, which were lower than the (6.6±0.9), (11.4±2.6) and (47.0±12.0) points at baseline (all P<0.001). During the follow-up period, 7 patients had adverse reactions: 3 cases had skin ecchymosis in the femoral artery puncture area, 4 cases had knee joint stiffness and pain within 1 day after operation, which were relieved spontaneously in 1 week, 6 patients had joint clicking during extension and flexion activities after operation, of which 3 cases subsided spontaneously within 3 months after operation. None of the patients had major procedure-related adverse events. Conclusion: GAE has a high clinical improvement rate and a low incidence of adverse reactions in the treatment of the pain secondary to knee osteoarthritis, which provides a new treatment option for patients who fail to respond to conservative treatment.

[The application value of chronic disease self-management project in promoting pulmonary rehabilitation of patients with chronic obstructive pulmonary disease].

Objective: To explore the role of chronic disease self-management program (CDSMP) in promoting pulmonary rehabilitation of patients with chronic obstructive pulmonary disease (COPD) . Methods: In June 2017 and December 2018, 380 COPD patients were selected from the health management center of Qilu Hospital of Shandong University during the same period. They were randomly divided into the experimental group and the control group. At the end of the study, 17 cases were lost to follow-up and 5 cases were withdrawn from the study. Finally, 175 and 183 patients in the experimental group and the control group completed the study. The experimental group was treated with CDSMP for 6 months, while the control group was not intervened. Lung function and blood gas analysis results, lung rehabilitation related indicators and SF-36 scores were compared between the two groups before and after intervention. The measurement data were expressed by Mean±SD, and the comparison between the two groups was performed by t test. The count data were expressed by frequency and constituent ratio (%) . Chi square test or rank sum test was used for comparison between groups. Results: After CDSMP intervention, compared with the control group, the 6MWD, weekly moderate intensity exercise time, weekly moderate intensity exercise frequency and self exercise efficacy score of the experimental group were significantly increased, and the single exercise duration was longer, the difference was statistically significant (P<0.05) . The physiological function score, general health score, physical energy score, mental health score and total score of the experimental group were higher, and the differences were statistically significant (P<0.05) . Conclusion: CDSMP may have a certain effect in promoting lung rehabilitation in COPD patients.

Fibroblast growth factor 18 alleviates hyperoxia-induced lung injury in mice by adjusting oxidative stress and inflammation.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in infants, but the ways to prevent and treat BPD are still very limited. We tried to find an effective method for treating BPD by studying the effect of fibroblast growth factor 18 (FGF18) on hyperoxia-induced lung injury in mice. MATERIALS AND METHODS: We placed newborn mice in high-oxygen environment (60-70%) and collected mouse lung tissue for histological examination at 3, 7, 14 and 21 days after birth. The correlation between FGF18 and BPD was studied by analyzing the expression of FGF18 in mouse lung tissue. In addition, we used exogenous FGF18 to stimulate primary mouse type II alveolar epithelial cells (AECs II), and detected changes in oxidative stress, inflammation and NF-κB signaling pathway activity of AECs II to analyze the effects of FGF18 on AECs II. RESULTS: From the 7th day after the birth of the mouse, the lung tissue of the hyperoxia-induced mice suffered significant lung injury relative to the control group. The expression of FGF18 in lung tissue induced by hyperoxia was lower than that in the control group. Cell viability of AECs II stimulated by exogenous FGF18 increased, and FGF18 also reduced oxidative stress and inflammation levels of AECs II and inhibited the AECs II injury caused by hyperoxia. NF-κB signaling pathway activity in hyperoxia-induced lung increased, while exogenous FGF18 could reduce the expression and phosphorylation of NF-κB p65 in AECs II. CONCLUSIONS: Hyperoxia-induced lung injury was accompanied by a decrease in FGF18. FGF18 can reduce oxidative stress and inflammation levels of AECs II by inhibiting the NF-κB signaling pathway, thereby reducing hyperoxia-induced cell injury.

The diagnostic value of miR-21 combined with CT in patients with liver cancer.

PURPOSE: To explore the diagnostic value of miR-21 combined with computed tomography (CT) in patients with liver cancer. METHODS: A total of 112 patients in our hospital were confirmed liver cancer by examination, and were collected as cancer group. Another 100 patients with hepatic focal nodular hyperplasia in the same period were collected as control group. The diagnostic value of miR-21 and CT on liver cancer was observed. RESULTS: The level of miR-21 in cancer group was significantly higher than that in control group, the difference was statistically significant (p < 0.05). The alpha-fetoprotein (AFP) level was tested. It was found that the AFP level in cancer group was significantly higher than that in control group (p < 0.001). The correlation between AFP and miR-21 levels in liver cancer patients was detected. It turned out that AFP and miR-21 had correlation. According to receiver operating curve (ROC) calculation results, the best cut-off value for miR-21 diagnosis was 4.142. The sensitivity, specificity and accuracy of diagnosis of miR-21 alone were 64.29%, 87.00% and 75.00%, respectively. The sensitivity, specificity and accuracy of diagnosis of CT alone were 91.07%, 62.00% and 77.36%, respectively. There were 108 cases of true positive and 80 cases of true negative after combined diagnosis in the two groups. The sensitivity, specificity and accuracy of combined diagnosis were 96.43%, 80.00% and 88.68%, respectively. Comparing the value of single diagnosis and combined diagnosis, we found that the accuracy, sensitivity and specificity of combined diagnosis were significantly higher than that of single diagnosis (p < 0.05). CONCLUSION: CT combined with miR-21 has great diagnostic value in liver cancer and may be a potential diagnostic indicator for liver cancer.

Influences of miR-708 on cerebral ischemia-reperfusion injury through targeted regulation of ADAM17.

OBJECTIVE: The purpose of this study was to explore the influences of micro ribonucleic acid (miR)-708 on cerebral ischemia-reperfusion injury by regulating a disintegrin and metalloprotease 17 (ADAM17) in a targeted manner. MATERIALS AND METHODS: The rat model of middle cerebral artery occlusion (MCAO) was established, and the differentially expressed miRNAs in the cerebral tissues of rats with ischemia-reperfusion injury were detected via sequencing. The research was performed in control group (PC12 cells received no treatment), inhibitor group (the expression of miR-708 in PC12 cells was down-regulated using miR-708 inhibitor), and interference + inhibitor group [PC12 cells were co-treated with miR-708 inhibitor and ADAM17 small interfering RNA (siRNA)]. Then, the expression of ADAM17 in cells, proliferation ability of cells, and number of apoptotic cells were detected in each group. RESULTS: A total of 225 differentially expressed miRNAs were obtained through miRNA sequencing and bioinformatics analysis, of which miR-708, miR-169, miR-26, and miR-96 were highly expressed, whereas miR-122, miR-118, and miR-177 were lowly expressed in rats in ischemia-reperfusion group. Compared with that in control group, the level of miR-708 declined significantly in inhibitor group after treatment with miR-708 inhibitor. After treatment with miR-708 inhibitor, the protein expression level of ADAM17 in inhibitor group was evidently higher than that in control group, while its protein expression level in interference + inhibitor group was significantly decreased and restored, after interference of ADAM17 siRNA with protein expression. In comparison with control group, inhibitor group had increased apoptotic cells after miR-708 inhibitor treatment (p<0.05). Besides, after interference of ADAM17 siRNA with protein expression, there were a smaller number of apoptotic cells in interference + inhibitor group (p<0.05), showing mitigated apoptosis. Moreover, the proliferation ability of cells treated with miR-708 inhibitor in inhibitor group was weaker than that in control group (p<0.05), whereas the proliferation ability of cells in interference + inhibitor group was restored to a certain degree after ADAM17 siRNA interfered with the protein expression (p<0.05). CONCLUSIONS: MiR-708 can modulate ADAM17 in a targeted manner to affect cellular proliferation and apoptosis in cerebral ischemia-reperfusion injury.

The effect of myocardial infarction-associated transcript 2 (Mirt2) and miR-101 on sepsis-induced myocardial injury in rats.

OBJECTIVE: The aim of this study was to explore the effect of myocardial infarction associated transcript 2 (Mirt2) and miR-101 on sepsis-induced myocardial injury in rats and its mechanism. MATERIALS AND METHODS: Sprague Dawley (SD) rats were divided into sham group, CLP group, CLP + adeno-associated virus (AAV)-lncRNA Mirt2 group, CLP + AAV-NC group and CLP + AAV-lncRNA Mirt2 + agomiR-101 group. Rat CLP model was constructed. PanoViewb1500 was used to detect left ventricular systolic blood pressure (LVSP), left ventricular end diastolic blood pressure (LVEDP), ejection fraction (EF) and fraction shortening (FS) values. Thereafter, Mirt2 and miR-101 expression levels were detected by real-time polymerase chain reaction (RT-PCR), myocardial pathological damage was detected by hematoxylin-eosin (HE) staining, and Interleukin-1ß (IL-1ß) expression was by immunohistochemical staining. Next, enzyme linked immunosorbent assay (ELISA) was performed to detect the levels of serum inflammatory factors, tumor necrosis factor α (TNF-α), IL-1ß, Interleukin-6 (IL-6), myeloperoxidase (MPO), cardiac troponin I (cTn I) and creatine kinase isoenzyme (CK-MB). After that, Western blot was used to detect the expression of inflammatory factors and Phosphatidylinositol-3-kinases (PI3K)/protein-serine-threonine kinase (AKT) signaling pathway. Finally, Dual-Luciferase reporter gene assay was conducted to detect the relationship between Mirt2 and miR-101. RESULTS: Compared with those in the sham group, the cardiac function of the rats in the CLP group was significantly deteriorated, the cardiac structure was disordered, and the expression of pro-inflammatory related factors was significantly increased. Compared with those in CLP group, the cardiac function of the CLP + AAV-lncRNA Mirt2 group was alleviated, the PI3K/AKT signaling pathway was activated, the cardiac structure was slightly disordered, and the expression of pro-inflammatory related factors was reduced. To some extent, miR-101 could directly inhibit the effect of Mirt2. CONCLUSIONS: Mirt2 can silence miR-101 and inhibit myocardial inflammatory response in sepsis rats through the PI3K/AKT signaling pathway, thus improving cardiac structure and function.

[Several considerations on the establishment of a new public health and preventive medicine system in national level].

Based on the new mission of public health set in the Healthy China strategy and the insufficient response to COVID-19, this article pointed out the problems of the current public health and preventive medicine system from the macro-system level, meso-organization level, and micro-individual level, including insufficient strategic planning, resource input, institutional coordination, talent training and team building. It was creatively proposed that a disease prevention and control bureau should be set up outside the health commission to implement the vertical management at four levels, from national level to province-level, including autonomous region, municipality directly under the central government, city-level and district/county-level. The disease prevention and control bureau should consist of a strategic research institute, a center for disease prevention and control (CDC), a human resources training base, and a scientific research institute, which could perform their own duties and rely on each other. Enhancing the functions of strategic planning, overall coordination, and evidence-based decision-making in the original system, emphasizing the foresight and continuity of scientific research, and allowing the CDC to focus more on health management and emergency response could better facilitate in protecting the public health, improving the health and quality of life of the entire population, and guaranteeing the social stability and development.

Effects of lamivudine on cell proliferation of liver cancer and expressions of HBsAg, HBeAg, and MMP-9 in patients.

OBJECTIVE: To explore the effects of lamivudine on cell proliferation of liver cancer and expressions of HBsAg, HBeAg, and MMP-9 in hepatoma cells. MATERIALS AND METHODS: In the intervention group, HepG2.2.15 cells were cultured with lamivudine at 100, 200, and 300 µmol/L for 24 hours, 48 hours, and 72 hours. In the control group, HepG2.2.15 cells were cultured without lamivudine. MTT assay was used to assess the proliferative activity of cells after the intervention by lamivudine for 24 hours, 48 hours, and 72 hours. ELISA was used to measure the expression levels of HBsAg, HBeAg, and MMP-9 after the intervention by lamivudine for 48 hours and 72 hours. RESULTS: There was no significant difference between the intervention group and the control group in the proliferation activity of cells (p>0.05). After 48 hours and 72 hours of intervention by lamivudine, the expressions of MMP-9, HBsAg, and HBeAg in the control group were statistically lower than those in the intervention groups with lamivudine at 100 µmol/L, 200 µmol/L, and 300 µmol/L (p<0.05). The expressions of MMP-9, HBsAg, and HBeAg in HepG2.2.15 gradually decreased with the increase of intervention concentration and intervention time of lamivudine (p<0.05). CONCLUSIONS: Lamivudine cannot directly inhibit the proliferation of liver cancer cells, but it can reduce the expressions of MMP-9, HBsAg, and HBeAg in hepatoma cells, inhibit the replication of HBV disease in hepatoma cells, and suppress tumor growth.

[Crouzon syndrome with secretory otitis media: a case report and literature review].

Summary Clinical data from a case of Crouzon syndrome with secretory otitis media in our department was collected and the related literatures were reviewed. Whole exome sequecing and Sanger sequencing were performed to analyze genetic cause. The 6-year old patient with Crouzon syndrome had snoring and mouth breathing during sleep for 2 years, and was found hearing loss for 2 weeks. The results of endoscopy showed adenoid hypertrophy and secretory otitis media of both ears. And CT scan proved chronic rhinosinusitis. Myringotomy and adenoidectomy were done under general anesthesia. The follow-up at 6 months showed normal sleep and hearing level. A heterozygous fibroblast growth factor receptor 2 missense mutation（c.1061C>G, p.S354C） in exon 8 was identified in this patient.

High quality nursing of children with pneumonia complicated with heart failure.

Children with severe pneumonia often have heart failure. This study explored the clinical effect of high quality nursing intervention on children with pneumonia complicated with heart failure. In the study, 96 children with pneumonia complicated with heart failure were selected and randomly divided into a conventional nursing group (n=48) and a high quality nursing group (n=48). Based on the conventional nursing, the children in one group were given high quality nursing, and comprehensive nursing was carried out in aspects such as respiratory tract, medication, psychology and diet. Then, the heart rate, respiratory rate, heart failure correction time, hospitalization time, cost and nursing satisfaction were compared between the two groups. The results showed that the heart rate of the high quality nursing group was 145.37±8.72 times/min and the respiratory rate was 45.65±6.08 times/min, which were significantly lower than those of the conventional nursing group (P less than 0.05). The correction time of heart failure was about 32 h in the high quality nursing group, and the length and cost of hospitalization were significantly lower than those in the conventional nursing group (P less than 0.05). The nursing satisfaction of the patients' family members in the high quality nursing group was also higher (P less than 0.05). This study shows that high quality nursing can promote the recovery of children with pneumonia complicated with heart failure, and is worth popularizing widely in clinics.

[The relationship between gut microbiota and diet and nutrition related diseases].

The human gastro-intestinal tract is not only the habitat of gut microbiota, but also the main place that the body gets available nutrients. Therefore, the gut microbiota of human can be inseparable associated with the human nutrition. The common technologies used among gut microbiota research included metageonomic, metatranscriptomics, metaproteomics, and metabolomics. The research of gut microbiota based on above omics methods confirmed that diets were the main factors influencing the composition and expression of gut microbiota. The proportion, quantity, stable state, and metabolic changes of gut microbiota were closely related to obesity, diabetes mellitus, cardiovascular disease, and other nutritional-related diseases. Reasonable dietary intervention can adjust the disorders of gut microbiota, which can achieve prevention and treatment of obesity, diabetes, cardiovascular diseases, and other nutritional-related diseases. Although the single omics methods can be used to study the problems of some aspects of gut microbiota, the combination of multi-omics is needed to achieve the above objectives.

[Sleep problems and the association with the levels of 6-sulfatoxymelatonin in children with autism spectrum disorder].

Objective: To identify the prevalence of sleep problems in children with autism spectrum disorder (ASD) and to explore the association with the main melatonin metabolite, 6-sulfatoxymelatonin (6-SM). Method: This was a prospective case-control study. Children with ASD were recruited from Child Development and Behavioral Research Center (CDBRC) of the Harbin Medical University and Harbin Special Education School from October 2015 to April 2017 (ASD group) . Healthy controls were selected from five kindergartens and one primary school in Harbin by the stratified cluster random sampling (control group) . The Children's Sleep Habits Questionnaire (CSHQ) was used to investigate the sleep problems of the two groups. The patients were matched in a 1∶1 ratio for the age and sex, and the urine samples of case-control pairs were collected in the morning. The level of 6-SM was measured by the enzyme linked immunosorbent assay (ELISA). The student's t test was used for comparison between the ASD group and control group, and the Pearson correlation analysis was used to determine the correlation difference. Result: A total of 212 ASD children (mean (±SD) age was (6.0±2.7) years, and 181 patients (85.4%) were male), and a total of 334 healthy children(mean (±SD) age was (5.9±2.6) years, and 272 patients (81.4%) were male) were recruited. Among them, 101 matched case-control pairs completed the collection of urine samples. According to the statistical analysis, the scores of total CSHQ, bedtime resistance, sleep onset delay, sleep duration, night waking, parasomnia, sleep disordered breathing and daytime sleepiness in children with ASD were significantly higher than those in the control group (48.2±6.2 vs. 46.6±5.4, 11.4±2.5 vs. 10.7±2.8, 1.7±0.8 vs. 1.5±0.7, 4.1±1.4 vs. 3.7±1.1, 4.2±1.5 vs. 3.8±1.1, 8.5±1.5 vs. 8.3±1.4, 3.7±1.0 vs. 3.4±0.8, 11.7±2.5 vs. 12.4±2.7, t=3.16, 3.00, 3.23, 2.76, 3.19, 1.99, 3.45,-2.72, P=0.002, 0.003, 0.001, 0.006, 0.002, 0.048, 0.001, 0.007), the level of 6-SM was significantly lower in children with ASD than that of healthy controls ((1.24±0.50) vs. (1.68±0.63)µg/h, t=-5.50, P<0.01), and the total CSHQ score was negatively correlated with the level of 6-SM (r=-0.50, P<0.01). Conclusion: The children with ASD were at high risk for sleep problems, and the melatonin metabolite of ASD group was abnormal compared with that of the control group. Moreover, there was a negative correlation between the severity of sleep problems and the level of 6-SM in ASD children. The results of our study indicate that the abnormal melatonin metabolism may be one of the causes of sleep problems in children with ASD.

Role of Bcl-2 and Bax in parotid gland atrophy.

OBJECTIVE: To investigate the expression and correlation of B-cell lymphoma-2 (Bcl-2) and Bax in the parotid gland after leading duct ligation in rat. MATERIALS AND METHODS: Atrophy of the right parotid was induced by ligating the right Stensen's duct of rats. Immunohistochemical labeling was performed to study the changes in number and distribution of Bcl-2 and Bax in each step of glandular atrophy, and every group at 1, 3, 5, 7, 14, 21, 30, 60, 90, 150, 180 days after ligation. RESULTS: Bcl-2 and Bax showed a low level of expression in normal glandular tissues. At different time points after the ligation of the main duct, Bcl-2 was highly expressed in the duct cells, and the absorbance value reached a peak value at 21-day (3.02+0.10). The 1 D expression of Bax was found in some of the cells in the 3 D, and the expression of Bax reached the peak (1.99+0.10), and the expression of Bcl-2 and Bax were decreased in some cells. Bcl-2/Bax ratio increased at 1 day-21 day, and then decreased and stabilized. CONCLUSIONS: The expression of Bax and Bcl-2 after ligation of the parotid gland is closely related to the process of the parotid gland atrophy.

Integrated Drug Expression Analysis for leukemia: an integrated in silico and in vivo approach to drug discovery.

Screening for drug compounds that exhibit therapeutic properties in the treatment of various diseases remains a challenge even after considerable advancements in biomedical research. Here, we introduce an integrated platform that exploits gene expression compendia generated from drug-treated cell lines and primary tumor tissue to identify therapeutic candidates that can be used in the treatment of acute myeloid leukemia (AML). Our framework combines these data with patient survival information to identify potential candidates that presumably have a significant impact on AML patient survival. We use a drug regulatory score (DRS) to measure the similarity between drug-induced cell line and patient tumor gene expression profiles, and show that these computed scores are highly correlated with in vitro metrics of pharmacological activity. Furthermore, we conducted several in vivo validation experiments of our potential candidate drugs in AML mouse models to demonstrate the accuracy of our in silico predictions.

Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.

AIMS/HYPOTHESIS: Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS). METHODS: A total of 100 obese women aged 33-51 years with BMI ≥ 28 kg/m² and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n = 50) or identical placebo (n = 50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes. RESULTS: At 12 weeks, a total of 92 participants completed this trail. Compared with the placebo group (n = 47), histidine supplementation significantly decreased HOMA-IR (-1.09 [95% CI -1.49, -0.68]), BMI (-0.86 kg/m² [95% CI -1.55, -0.17]), waist circumference (-2.86 cm [95% CI -3.86, -1.86]), fat mass (-2.71 kg [95% CI -3.69, -1.73]), serum NEFA (-173.26 µmol/l [95% CI -208.57, -137.94]), serum inflammatory cytokines (TNF-α, -3.96 pg/ml [95% CI -5.29, -2.62]; IL-6, -2.15 pg/ml [95% CI -2.52, -1.78]), oxidative stress (superoxide dismutase, 17.84 U/ml [95% CI 15.03, 20.65]; glutathione peroxidase, 13.71 nmol/ml [95% CI 9.65, 17.78]) and increased serum histidine and adiponectin by 18.23 µmol/l [95% CI 11.74, 24.71] and 2.02 ng/ml [95% CI 0.60, 3.44] in histidine supplementation group (n = 45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB. CONCLUSIONS/INTERPRETATION: Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes.