Effects of direct-fed microbial supplementation on performance and immune parameters of lactating dairy cows.

We evaluated the effects of supplementing bacterial direct-fed microbial (DFM) on performance, apparent total-tract digestibility, rumen fermentation, and immune parameters of lactating dairy cows. One hundred fourteen multiparous Holstein cows (41 ± 7 DIM) were used in a randomized complete block design with an experiment comprising 14 d of a covariate (pre-experimental sample and data collection) and 91 d of an experimental period. Cows were blocked based on energy-corrected milk (ECM) yield during the covariate period and the following treatments were randomly assigned within each block: (1) control (CON), corn silage-based total mixed ration without DFM; (2) PRO-A, basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 109 cfu/d; and 3) PRO-B, basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and Bacillus licheniformis at 11.8 × 109 cfu/d. Milk yield, dry matter intake (DMI), and body weight were measured daily, while milk samples for component analysis were taken on 2 consecutive days of each week of data collection. Feces, urine, rumen, and blood samples were taken during the covariate period, wk 4, 7, 10, and 13 for estimation of digestibility, N-partitioning, rumen fermentation, plasma nutrient status and immune parameters. Treatments had no effect on DMI and milk yield. Fat-corrected milk (3.5% FCM) and milk fat yield were improved with PRO-B, while milk fat percent and feed efficiency (ECM/DMI) tended to increase with PRO-B compared with PRO-A and CON. Crude fat digestibility was greater with PRO-B compared with CON. Feeding CON and PRO-A resulted in higher total volatile fatty acid concentration relative to PRO-B. Percentage of neutrophils tended to be reduced with PRO-A compared with CON and PRO-B. The mean fluorescence intensity (MFI) of anti-CD44 antibody on granulocytes tended to be higher in PRO-B compared with CON. The MFI of anti-CD62L antibody on CD8+ T cells was lower in PRO-A than PRO-B, with PRO-A also showing a tendency to be lower than CON. This study indicates the potential of DFM to improve fat digestibility with consequential improvement in fat corrected milk yield, feed efficiency and milk fat yield by lactating dairy cows. The study findings also indicate that dietary supplementation with DFM may augment immune parameters or activation of immune cells, including granulocytes and T cells; however, the overall effects on immune parameters are inconclusive.

[Clinical characteristics of patients referred to cardio-oncology clinic].

To explore characteristics of outpatients in a single cardio-oncology clinic, patients visiting cardio-oncology clinic of Fuwai Hospital CAMS&PUMC (Beijing, China) from January 2020 to December 2021 were analyzed retrospectively. In total, 330 patients were included, the median age (Q1, Q3) was 58(46, 66) years, and there were 192 females (58.2%). The purposes for visit included an evaluation and treatment of cardiovascular adverse reactions (n=247, 74.8%), pre-antitumor therapy assessment (n=51, 15.5%), and management of primary or metastatic cardiac tumors (n=32, 9.7%). For patients with cardiovascular adverse reactions, the most common tumor type was breast cancer (n=88, 29.5%), followed by gastrointestinal cancer (n=70, 23.5%), and hematological cancers (n=62, 20.8%). Among them, 236 cases (95.5%) had received antitumor drugs in the past; 38 cases (15.4%) had a history of chest radiotherapy; some cases were complicated with hypertension (n=69, 23.2%) and/or hyperlipidemia (n=69, 23.2%); 42 cases (14.1%) had a history of coronary heart disease; and 16 cases (5.4%) were complicated with atrial fibrillation or flutter. Among 32 patients with cardiac tumors, 11 cases (34.4%) had primary malignant tumors; 6 cases (18.8%) had benign tumors; 2 cases (6.3%) had metastatic tumors; and 13 (40.6%) had unknown pathological types. This study explores the epidemiology of cardio-oncology in China and provides clinical insights for the future development of cardio-oncology. In the future, it is still necessary to study the benefits of cardio-oncology clinics and develop standardized indicators to evaluate their benefits.

[Association between serum potassium levels and all-cause mortality in patients with acute heart failure].

Objective: To investigate the relationship between different serum potassium levels at admission and discharge and all-cause mortality in patients with acute heart failure (HF). Methods: A total of 2 621 patients with acute HF who were hospitalized in the Heart Failure Center of Fuwai Hospital from October 2008 to October 2017 were analyzed. Patients were divided into three groups according to the different serum potassium levels at admission: hypokalemia with serum potassium<3.5 mmol/L (n=329), normokalemia with 3.5-5.5 mmol/L (n=2 270), and hyperkalemia with serum potassium>5.5 mmol/L (n=22). Clinical data such as patient history, comorbidities, clinical examination and drug use were collected, and systematic outpatient review or telephone follow-up was performed after patients were discharged from the hospital until January 2020. The primary outcome was all-cause death at 90 days, 2 years, and 5 years of follow-up. We compared the clinical characteristics of patients with different serum potassium levels at admission and discharge, and used a multivariate Cox proportional hazards regression model to analyze the association between serum potassium levels at admission and discharge and all-cause mortality. Results: The age of all patients was (58.0±15.3) years old, and 1 877 patients (71.6%) were male. There were 329 (12.6%) and 22 (0.8%) patients with hypokalemia and hyperkalemia at admission, and 38 (1.4%) and 18 (0.7%) at discharge, respectively. The serum potassium levels of all patients were (4.01±0.50) and (4.25±0.44) mmol/L at admission and discharge, respectively. The follow-up time[M(Q1,Q3)] of this study was 2.63(1.00,4.42)years, and a total of 1 076 all-cause deaths were recorded at the last follow-up. Compared with patients with normokalemia at discharge, discharged patients with hypokalemia and hyperkalemia were followed up for 90 days (90.3% vs 76.3% vs 38.9%), 2 years (73.8% vs 60.5% vs 33.3%) and 5 years (63.4% vs 44.7% vs 22.2%), respectively, and the difference of which in cumulative survival rates were statistically significant (all P values<0.001). The multivariate-adjusted Cox regression analysis showed that hypokalemia (HR=0.979, 95%CI: 0.812-1.179, P=0.820) and hyperkalemia (HR=1.368, 95%CI: 0.805-2.325, P=0.247) at admission were not associated with all-cause mortality risk, however, hypokalemia (HR=1.668, 95%CI: 1.081-2.574, P=0.021) and hyperkalemia (HR=3.787, 95%CI: 2.264-6.336, P<0.001) at discharge were associated with increased all-cause mortality risk. Conclusions: Both hypokalemia and hyperkalemia at discharge in hospitalized patients with acute HF were associated with increased short-and long-term all-cause mortality, and serum potassium levels should be closely monitored.

Efficacy and moderators of cognitive therapy versus behavioural activation for adults with depression: study protocol of a systematic review and meta-analysis of individual participant data.

BACKGROUND: Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data. AIMS: This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602). METHOD: Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes. CONCLUSIONS: To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.

A New Second-Generation Mindfulness-Based Intervention Focusing on Well-Being: A Randomized Control Trial of Mindfulness-Based Positive Psychology.

Second-generation mindfulness-based interventions (SG-MBIs) align well with positive psychology philosophy and practices, but trials of SG-MBIs have largely focused on ill-being. This study developed a mindfulness-based positive psychology (MBPP) intervention integrating positive psychology with an SG-MBI to enhance well-being. A randomized control trial was performed to compare MBPP with a waitlist condition among 138 Chinese participants. The results showed that MBPP significantly reduced negative emotions for subjective well-being and significantly improved environmental mastery for psychological well-being. Improvements in self-compassion and negative attitudes but not avoidance, mediated changes in well-being. Changes in positive emotions, positive relations, and awareness were associated with the amount of meditation practice. These findings showed that MBPP is promising for improving well-being and that the positive psychology components play important roles. Broadly, the study illustrated that positive psychology and SG-MBIs can be effectively integrated, and it supported the further application of SG-MBIs from the positive psychology perspective. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-022-00525-2.

Antifungal activity of puroindoline protein from soft wheat against grain molds and its potential as a biocontrol agent.

Mold growth reduces the quality of stored grains, besides producing toxins that pose a potential threat to human health. Therefore, prevention of grain mold growth during storage is important to ensure a safe and high-quality product, preferably using an eco-friendly antifungal agent. The puroindoline (PIN) protein was extracted by Triton X-114 and identified by QE mass spectrometry. Aspergillus flavus has attracted much attention because of its toxic secondary metabolites, and PIN protein showed a significant inhibition on A. flavus growth. Scanning electron microscopy revealed altered spore morphology of A. flavus following PIN protein treatment, and propidium iodide staining showed incomplete spore cell membranes. The disruption and deformation of A. flavus spores suggest that the cell walls and cell membranes were compromised. Decreased mitochondrial membrane potential and increased levels of intracellular reactive oxygen specieswere detected using JC-1 and 2,7-dichlorodihydrofluorescein diacetate staining, respectively. PIN protein could effectively inhibit the growth and aflatoxins B1 production of A. flavus in stored grains, such as wheat and rice. PIN proteins can inhibit the growth of many common grain storage molds, including Penicillium, Aspergillus spp. (A. flavus, A. glaucus, A. kawachii, A. ochraceus and A. niger), Alternaria and Fusarium graminearum, in a dose-dependent manner. PIN protein has a significant inhibitory effect on the growth of grain molds, with a stronger inhibitory effect noted in wheat and rice. Our study provides a novel and simple theoretical basis for the selection and storage of mold resistance in grains and food during storage.

[Construction of a nomogram prediction model for pathological complete response (pCR) of ipsilateral supraclavicular lymph node after neoadjuvant chemotherapy for breast cancer with first diagnosis of ipsilateral supraclavicular lymph node metastasis].

Objective: To develop a predictive model for pathologic complete response (pCR) of ipsilateral supraclavicular lymph nodes (ISLN) after neoadjuvant chemotherapy for breast cancer and guide the local treatment. Methods: Two hundred and eleven consecutive breast cancer patients with first diagnosis of ipsilateral supraclavicular lymph node metastasis who underwent ipsilateral supraclavicular lymph node dissection and treated in the Breast Department of Henan Cancer Hospital from September 2012 to May 2019 were included. One hundred and forty two cases were divided into the training set while other 69 cases into the validation set. The factors affecting ipsilateral supraclavicular lymph node pCR (ispCR)of breast cancer after neoadjuvant chemotherapy were analyzed by univariate and multivariate logistic regression analyses, and a nomogram prediction model of ispCR was established. Internal and external validation evaluation of the nomogram prediction model were conducted by receiver operating characteristic (ROC) curve analysis and plotting calibration curves. Results: Univariate logistic regression analysis showed that Ki-67 index, number of axillary lymph node metastases, breast pCR, axillary pCR, and ISLN size after neoadjuvant chemotherapy were associated with ispCR of breast cancerafter neoadjuvant chemotherapy (P<0.05). Multivariate logistic regression analysis showed that the number of axillary lymph node metastases (OR=5.035, 95%CI: 1.722-14.721, P=0.003), breast pCR (OR=4.662, 95%CI: 1.456-14.922, P=0.010) and ISLN size after neoadjuvant chemotherapy (OR=4.231, 95%CI: 1.194-14.985, P=0.025) were independent predictors of ispCR of breast cancer after neoadjuvant chemotherapy. A nomogram prediction model of ispCR of breast cancer after neoadjuvant chemotherapy was constructed using five factors: number of axillary lymph node metastases, Ki-67 index, breast pCR, axillary pCR and size of ISLN after neoadjuvant chemotherapy. The areas under the ROC curve for the nomogram prediction model in the training and validation sets were 0.855 and 0.838, respectively, and the difference was not statistically significant (P=0.755). The 3-year disease-free survival rates of patients in the ispCR and non-ispCR groups after neoadjuvant chemotherapy were 64.3% and 54.8%, respectively, with statistically significant differences (P=0.024), the 3-year overall survival rates were 83.8% and 70.2%, respectively, without statistically significant difference (P=0.087). Conclusions: Disease free survival is significantly improved in breast cancer patients with ispCR after neoadjuvant chemotherapy. The constructed nomogram prediction model of ispCR of breast cancer patients after neoadjuvant chemotherapy is well fitted. Application of this prediction model can assist the development of local management strategies for the ipsilateral supraclavicular region after neoadjuvant chemotherapy and predict the long-term prognosis of breast cancer patients.

[The role of first-aid network construction in the early treatment of patients with critically severe hydrofluoric acid burns].

Objective: To explore the role of first-aid network construction in the early treatment of patients with critically severe hydrofluoric acid burns. Methods: Twenty-seven fluorine chemical enterprises distributed in Zhejiang province, Jiangxi Province, Fujian Province, and Inner Mongolia Autonomous Region and 22 hospitals with burn/plastic department or professional burn treatment group in Zhejiang province, including Zhejiang Quhua Hospital, and 5 hospitals outside Zhejiang province were involved in the first-aid network construction as member units. As the main unit, Zhejiang Quhua Hospital was responsible for the daily maintenance and technical guidance of the first-aid network. Zhejiang Quhua Hospital was assigned as the designated emergency hospital for 20 fluorine chemical enterprises, a near emergency hospital to the other 7 fluorine chemical enterprises was assigned as the designated hospital for them. Medical records of 56 patients (all males) with critically severe hydrofluoric acid burns who admitted to 5 first-aid network hospitals from January 2006 to June 2021, meeting the inclusion criteria, were involved in the retrospective cohort study. Based on whether the enterprise belonging to the first-aid network construction or not, the patients were divided into first-aid network group (27 cases, aged (41±9) years) and non first-aid network group (29 cases, aged (42±10) years). After the patients in the first-aid network group were injured, the enterprises and hospitals linked up immediately. The hospital where the patient was treated mobilize the treatment force, equipment, materials, and drugs in advance by the first-aid network, thereby realizing seamless joint between pre-hospital first-aid and in-hospital treatment. The hospital started the first-aid process and temporarily mobilized the rescue forces, equipment, materials, and drug after patients in non first-aid network group arrived at the department of emergency of the hospital. The time from injury to medical service, the first detection time of serum calcium, the time staying in department of emergency, the duration of hypocalcemia and hypomagnesemia, and the treatment outcome of patients in the two groups were recorded. Data were statistically analyzed with chi-square test, Fisher's exact probability test, independent-sample t test, and Wilcoxon rank-sum test. Results: The time from injury to medical service, the first detection time of serum calcium, and the time staying in department of emergency of patients in first-aid network group were 40.0 (30.0, 55.0), 23.0 (17.5, 37.5), and 42.0 (37.0, 53.0) min, which were significantly shorter than 180.0 (120.0, 240.0), 31.0 (22.5, 47.5), 61.0 (52.0, 65.5) min in non first-aid network group (Z=-6.17, -1.98, -4.15, P<0.05 or P<0.01). The duration of hypocalcemia and hypo- magnesemia of patients in first-aid network group were 1.2 (1.1, 1.6) and 1.9 (1.7, 2.1) h, which were significantly shorter than 4.6 (3.1, 6.2) and 3.2 (2.5, 4.6) h in non first-aid network group (Z=-5.80, -4.81, P<0.01). Three patients (11.1%) in first-aid network group died, among whom 2 patients died at 40 min after injury and 1 patient died 9.0 h after injury. Four patients (13.8%) died in non first-aid network group at 3.0, 3.0, 4.5, and 7.0 h after injury, respectively. The mortality rates of patients in the two groups were similar (P>0.05). Conclusions: Critically severe hydrofluoric acid burn is an extremely urgent situation encountered in clinical practice. The construction of a first-aid network creates condition for on-site treatment of patients and improves the first-aid efficiency, thereby gaining time to save lives.

[Clinical characteristics of hypertrophic cardiomyopathy and restricted cardiomyopathy patients complicating with intracardiac thrombosis].

Objective: To investigate the clinical characteristics of patients with hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) complicating with intracardiac thrombosis. Methods: This is a retrospective observational study. Consecutive patients diagnosed with HCM or RCM and complicated with intracardiac thrombosis (including left and right atrium or ventricular thrombosis), who were admitted to the Heart Failure Care Unit of Fuwai Hospital, Chinese Academy of Medical Sciences, from September 2008 to September 2018, were enrolled in this study. Patients with myocardial infarction were excluded. The general clinical data of the enrolled patients, including demographic data, major complications, laboratory indicators, echocardiographic indicators, drug application and distribution of intracardiac thrombosis, were collected from electronic medical record system and analyzed. Results: A total of 98 patients were enrolled in this study, including 52 patients (53.1%) with HCM and 46 patients (46.9%) with RCM. The most common comorbidity was atrial fibrillation/flutter: 40 patients (76.9%) in HCM group and 36 patients (78.3%) in RCM group. Majority of patients received oral anticoagulants treatment: 43 patients (82.7%) in HCM group and 35 patients (76.1%) in RCM group. Intracardiac thrombosis was mainly located in the left atrium in both HCM group (39 cases (75.0%)) and RCM group (32 cases (69.6%)). Thrombosis was found in ≥ 2 chambers in 7 patients (7.1%). Rate of left atrial thrombosis was the highest (81.6% (62/76)) in HCM and RCM patients complicating with atrial fibrillation/flutter. Intra-aneurysmal thrombosis occurred in 4 out of 5 patients complicated with apical left ventricular aneurysm. The rate of left ventricular thrombosis in patients with left ventricular ejection fraction≥50% was 7.4% (4/54), which was significantly lower than that in patients with left ventricular ejection fraction<50% (34.5%(10/29)) (P<0.01). Conclusion: There are certain distribution characteristics of HCM and RCM patients with intracardiac thrombosis, and the left atrium is the most common site of thrombosis, more attention should be paid in HCM and RCM patients on the diagnosis and treatment of intracardiac thrombosis.

Development of a Self-reported Olfactory Dysfunction Questionnaire (SODQ) to screen olfactory disorders in China.

BACKGROUND: The diagnosis of olfactory dysfunction is challenging given the negligence during routine physical examination, inconvenience of diagnosis in clinical practice, and the inattention to cross-cultural adaptability. The study aimed to develop and validate a simple and effective self-reported olfactory dysfunction questionnaire (SODQ) for the initial screening of clinical olfactory disorders in China. METHODS: A total of 121 subjects participated in the study; of these, 96 subjects completed the T&T olfactometer test and 12-item questionnaire, and 25 participants were retested using the SODQ after one week. The T&T olfactometer test examined the olfactory function and the questionnaire measured the ability to perceive common odors in daily life. We evaluated the factor structure, reliability, validity, and discriminative ability of the SODQ. RESULTS: The final version of the SODQ consisted of 10 items with one factor. Test-retest and internal consistency were excellent. Convergent validity of the questionnaire with the T&T olfactory test was high. Furthermore, the discrimination ability was high for the questionnaire with an area under the curve of 0.95 and a cut-off point of 22. CONCLUSIONS: The SODQ is a brief, valid, and repeatable tool that has the potential to effectively screen for clinical olfactory disorders from a subjective perspective.

Development and validation of novel diagnostic nomogram for tuberculous pleurisy based on TB-IGRA results.

OBJECTIVE: To establish the diagnostic nomogram for tuberculous pleurisy (TP) based on TB-interferon-gamma release assays (TB-IGRA), as well as clinical and peripheral blood characteristics.MATERIAL AND METHODS: Patients who underwent TB-IGRA tests during hospitalisation and were finally diagnosed, were retrospectively and continuously enrolled. TP was divided into confirmed TP (cTP) and presumptive TP (pTP), and corresponding diagnostic nomograms were established.RESULTS: A total of 1283 patients were enrolled (median age 49 years, range 14-96; males: 63.1%). The area under the curve (AUC) of TB-IGRA was 0.81 (95%CI 0.77-0.84) for cTP (n = 272) and 0.74 (95%CI 0.71-0.78) for pTP (n = 644). The false-positive and negative rates of TB-IGRA among non-TP and cTP were respectively 32.4% and 16.8%. Based on LASSO analysis, we then selected respectively 12 and 10 predictors from clinical and peripheral blood characteristics to establish cTP and pTP nomograms (TB-IGRA was selected). The cTP and pTP nomograms had an AUC of 0.93 (95%CI 0.90-0.95) and 0.92 (95%CI 0.90-0.94) in the training group, and 0.91 (95%CI 0.87-0.96) and 0.93 (95%CI 0.89-0.96) in the validation group, respectively, which were superior to TB-IGRA test alone.CONCLUSION: Novel predictive nomograms with less invasiveness were provided based on TB-IGRA test to assist differential diagnosis of TP and non-TP patients.

[The metabolism of blood glucose and lipid in breast cancer patients after the first chemotherapy].

Objective: To analyze the metabolism of blood glucose and lipid in breast cancer patients after the first chemotherapy. Methods: Breast cancer patients who received chemotherapy for the first time from December 2016 to January 2020 were collected in our hospital, and their blood glucose and lipid levels were monitored. Patients were grouped according to different treatment plans. Non-parametric rank sum test was used for statistical analysis on SPSS software. Results: There were 1 356 female breast cancer patients were enrolled, blood glucose and lipid levels were compared before and after chemotherapy. Our results showed that baseline medium blood glucose was 5.2 mmol/L, lower than 5.3 mmol/L after chemotherapy (P<0.05). The baseline triglyceride (TG) was 1.2 mmol/L, lower than 1.6 mmol/L after chemotherapy (P<0.05). The baseline small dense low-density lipoprotein (sdLDL) was 0.7 mmol/L, lower than 0.8 mmol/L after chemotherapy (P<0.05). The baseline high density lipoprotein (HDL) was 1.3 mmol/L, higher than 1.2 mmol/L after chemotherapy (P<0.05). Patients' menstrual status and body mass index were related with blood glucose, TG, LDL and sdLDL (all P< 0.05). Conclusions: Abnormal metabolism of blood glucose and lipid are observed in breast cancer patients after the first chemotherapy. More awareness of cardiovascular disease in breast cancer patients might ensure their overall clinical benefits.

Engineering CRISPR interference system to enhance the production of pyrroloquinoline quinone in Klebsiella pneumonia.

Pyrroloquinoline quinone (PQQ) is a cofactor of glucose dehydrogenase (GDH) and thus participates in glucose utilization. In Klebsiella pneumoniae, glucose utilization involves PQQ-dependent direct oxidation pathway (DOP) and phosphoenolpyruvate-dependent transport system (PTS). It is challenging to overproduce PQQ, as its biosynthesis remains unclear. Here, we report that PQQ production can be enhanced by stimulating the metabolic demand for it. First, we developed CRISPR interference (CRISPRi) system to block PTS and thereby intensify DOP. In shake-flask cultivation, the strain with CRISPRi system (simultaneously inhibiting four PTS-related genes) produced 225·65 nmol l-1 PQQ, which was 2·14 times that of wild type. In parallel, an exogenous soluble glucose dehydrogenase (sGDH) was overexpressed in K. pneumoniae. In the shake-flask cultivation, this sGDH-overexpressing strain accumulated 140·05 nmol l-1 PQQ, which was 1·33 times that of wild type. To combine the above two strategies, we engineered a strain harbouring both CRISPRi vector and sGDH-overexpressing vector. In the shake-flask cultivation, this two-plasmid strain generated 287·01 nmol l-1 PQQ, which was 2·72 times that of wild type. In bioreactor cultivation, this two-plasmid strain produced 2206·1 nmol l-1 PQQ in 57 h, which was 7·69 times that in shake-flask cultivation. These results indicate that PQQ production can be enhanced by intensifying DOP, as the apo-enzyme GDH is intrinsically coupled with cofactor PQQ. This study provides a strategy for the production of cofactors whose biosynthesis mechanisms remain ambiguous. SIGNIFICANCE AND IMPACT OF THE STUDY: Pyrroloquinoline quinone (PQQ) is an economically important chemical, which typically serves as a cofactor of glucose dehydrogenase (GDH) and thus participates in glucose metabolism. Klebsiella pneumoniae can naturally synthesize PQQ, but current yield constrains its commercialization. In this study, the PQQ level was improved by stimulating metabolic demand for PQQ, instead of overexpressing PQQ synthetic genes, as the synthetic mechanism remains ambiguous.

The effect of four Immeasurables meditations on depressive symptoms: A systematic review and meta-analysis.

The Four Immeasurables Meditations (FIM) intervention have been shown as a promising intervention for reducing depressive symptoms. The current study is a systematic review of FIM intervention effects on depressive symptoms. Among 192 empirical research articles on FIM published before May 2019, 40 independent trials from 35 records measured depressive symptoms. The meta-analysis included 21 randomized controlled trials (RCT; n = 1468) and 16 uncontrolled trials (n = 376). The results supported overall effectiveness of FIM on depressive symptoms (d = 0.38 for RCT and d = 0.87 for uncontrolled trials). Moderator analysis indicated the effects differed across protocols, and effects were smaller in RCT using active control groups. No significant differences were observed for participant type, measures, intervention length, or intervention components. Individual studies found no direct association between meditation practice time and effects, and mindfulness and self-compassion were widely supported as mechanisms of change. Current evidence supports FIM as an effective intervention for reducing depressive symptoms, but additional studies with more rigorous designs using active control groups are needed. Further investigation should be encouraged regarding specific protocols and participants, the contribution of meditation practice, and other mechanisms such as positive emotions.

Effects of steam explosion pretreatment and Lactobacillus buchneri inoculation on fungal community of unensiled and ensiled total mixed ration containing wheat straw during air exposure.

AIM: To compare the effects of steam explosion and Lactobacillus buchneri inoculation on fungal community in ensiled total mixed ration (TMR) during aerobic exposure. METHODS AND RESULTS: The TMRs were prepared using wheat straw with or without steam explosion, sweet potato residue, lucerne hay, maize meal and soybean meal, and ensiled with or without L. buchneri inoculation. Fungal communities were detected by high-throughput sequencing. All ensiled TMRs were well ensiled and steam explosion has a major effect on improving aerobic stability. The fungal species, such as Xeromyces bisporus and Cryptococcus victoriae, that dominated in the TMR decreased after ensiling, with a concomitant increase in Candida humilis, Pichia kudriavzevii, Aspergillus flavus and Phanerochaete chrysosporium. Most mould species decreased, with C. humilis and P. kudriavzevii dominating during aerobic exposure. CONCLUSION: Steam explosion could improve the aerobic stability in ensiled TMR by inhibition of C. humilis. SIGNIFICANCE AND IMPACT OF THE STUDY: High-throughput sequencing used in this study provides insight into the fungal community in ensiled TMR during aerobic exposure, which could contribute towards elucidating the mechanism by which aerobic deterioration develops.

[Effects of tranexamic acid on the blood conservation and the long-term prognosis in pediatric patients undergoing repair for tetralogy of fallot].

Objective: To evaluate the perioperative tranexamic acid (TXA) on blood conservation in pediatric patients undergoing complete repair for tetralogy of fallot (TOF) and its impact on short-term or long-term adverse event and mortality. Methods: The study was a retrospective cohort study. From January 2009 to December 2010, 386 consecutive patients aged from 31 days to 8 years old, ASA physical status Ⅱ or Ⅲ, receiving primary complete repair for TOF in Fuwai Hospital were enrolled in the study. They were divided into two groups: the control group (n=161) and the TXA group (n=225), according to whether TXA was used during the operation. Patients and their families were followed up by telephone in the 8th-year after surgery. The amount of perioperative blood loss, allogeneic transfusion, short-term or long-term adverse event and mortality were recorded and analyzed. Results: The patients in the TXA group were associated with significant decreased 12 h and total postoperative blood loss compared with the control group [(7.8±0.3) ml/kg vs (8.8±0.3) ml/kg, t=2.412, P<0.05; and (14.0±0.6) ml/kg vs (17.0±0.7) ml/kg, t=3.141, P<0.05]. There were no significant differences in both the volume and incidence of red blood cell, plasma, and platelet transfusion, postoperatively (P>0.05). There were no significant differences in the incidence of reoperation for bleeding and prolonged mechanical ventilation, ICU stay, postoperative hospital length of stay, the short-term and long-term incidence of seizure, stroke, renal failure, deep venous thrombosis, pulmonary embolism and death between the two groups(P>0.05). Conclusion: TXA can decrease postoperative blood loss, but has little impact on the allogeneic blood transfusion, as well as the short-term or long-term adverse event and mortality in pediatric patients undergoing complete repair for TOF.

[The value of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in evaluating the stability of atherosclerotic plaques].

Objective: Positron emission tomography-computed tomography (PET-CT) has been used to quantify inflammatory response in the body. The aim of the present study was to explore the possibility of using this method to evaluate the stability of atherosclerotic plaques and the efficacy of atorvastatin in stabilizing atherosclerotic plaques. Methods: Twenty New Zealand male white rabbits were included and divided into the atorvastatin intervention group and the control group, with 10 rabbits in each group. Rabbits in both groups were fed with a high fat diet for 20 weeks, and treated with thoracoabdominal aortic balloon-pulling to establish atherosclerosis model at the end of the 2nd week. Rabbits in atorvastatin intervention group was given atorvastatin intragastrically once a day. At the 8th week, thoracoabdominal aortic ultrasound was used to detect plaques in all rabbits. Blood was drawn at the 3rd and the 20th week, respectively, to measure blood lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). At the end of experiment, survival animals were scanned by (18)F-FDG PET-CT, and the average and maximum standard uptake values (SUVmean, SUVmax) of aortic segments were measured. Thereafter, the animals were sacrificed and aortic specimens of rabbits were taken and examined by immunohistochemistry. The pathological indexes were measured and compared. Results: At the end of experiment, the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), hs-CRP [ (4.58±0.51) ng/ml vs.(5.87±0.66) ng/ml, P<0.01], MMP-9[ (43.93±2.16) ng/ml vs. (50.77±2.32) ng/ml, P<0.01], SUVmean (0.59±0.15 vs. 0.68±0.20, P<0.05) , SUVmax (0.68±0.20 vs. 0.81±0.27, P<0.05) , plaque area [ (0.36±0.24) mm(2) vs. (0.50±0.34) mm(2), P<0.05) ] and density of macrophage[ (4.34±1.54) % vs. (5.65±1.89) %, P<0.01] in the atorvastatin intervention group were significantly lower than those in the control group. In contrast, fiber cap thickness of the plaque[ (4.12±0.66) µm vs. (2.96±0.37) µm, P<0.01] in the atorvastatin intervention group was higher than that of the control group, and the difference was statistically significant. The arterial plaque areas were positively correlated with SUVmean (r=0.27, P<0.05) and SUVmax (r=0.43, P<0.01) . Fiber cap thickness was negatively correlated with SUVmean (r=-0.38, P<0.05) and SUVmax (r=-0.47, P<0.01) . The density of macrophage were positively correlated with SUVmean (r=0.52, P<0.01) and SUVmax (r=0.51, P<0.01) . Conclusion: (18)F-FDG PET/CT can be used to evaluate the efficacy of atorvastatin by the stability of atherosclerotic plaques.

MicroRNA-486-5p inhibits ovarian granulosa cell proliferation and participates in the development of PCOS via targeting MST4.

OBJECTIVE: To explore whether microRNA-486-5p affected the proliferation of ovarian granulosa cells by targeting MST4 (silk/threonine protein kinase 4), thereby promoting the development of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The level of microRNA-486-5p in PCOS tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After microRNA-486-5p up-regulation in KNG cells, the mRNA and protein level of related genes was examined using qRT-PCR and western blot assay, respectively. Meanwhile, cell proliferation and cell cycle were analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. After insulin treatment of KNG cells, expressions of microRNA-486-5p and MST4, cell proliferation as well as cell cycle, were detected by qRT-PCR, CCK-8 and flow cytometry, respectively. Furthermore, cell proliferation and cycle situation were examined after simultaneous up-regulation of MST4 and microRNA-486-5p in vitro. RESULTS: MicroRNA-486-5p expression in PCOS tissues was significantly lower than that of normal tissues. In KNG cells, up-regulation of microRNA-486-5p significantly inhibited cell proliferation and cell cycle. The levels of cycle-associated proteins including CDK2 and CCNB1 decreased significantly. The results of dual-luciferase reporter gene assay showed that microRNA-486-5p could bind to MST4. After up-regulating microRNA-486-5p, both the mRNA and protein levels of MST4 decreased remarkably. MST4 expression was found significantly elevated in PCOS tissues as well. After overexpression of MST4, cell proliferation was enhanced, cell cycle was promoted, and expressions of cycle-related proteins increased. After treatment with different concentrations of insulin in KNG cells, the expression level of microRNA-486-5p decreased in a concentration-dependent manner. However, opposite results were observed in MST4 level. Meanwhile, the proliferation ability and cell cycle of insulin-treated cells were significantly enhanced. In addition, the inhibitory effect of microRNA-486-5p on cell proliferation and cell cycle could be partially reversed by simultaneous up-regulation of MST4 and microRNA-486-5p. CONCLUSIONS: MicroRNA-486-5p can bind to MST4 in a targeted manner and inhibit the proliferation of ovarian granulosa cells, thereby inhibiting the development of PCOS.