Sophora tonkinensis: response and adaptation of physiological characteristics, functional traits, and secondary metabolites to drought stress.

The medicinal plant Sophora tonkinensis is a characteristic Chinese shrub of karst areas. The arid climate in karst areas produces high-quality S. tonkinensis; however, the mechanisms of drought tolerance are not clear, which restricts sustainable plantings of S. tonkinensis. This study involved a 20-day drought stress experiment with potted S. tonkinensis and threee soil water regimes: control (CK), mild drought (MDT), and severe drought (SDT). Plant morphology, biomass, physiological indicators, alkaloid content, and other changes under drought stress were monitored. The content of soluble sugars and proteins, and activity of antioxidant enzymes in leaves and roots were higher under drought than CK, indicating that S. tonkinensis is tolerant to osmotic stress in early drought stages. Content of matrine and oxymatrine increased gradually with increasing drought duration in the short term. The epidermis of S. tonkinensis leaves have characteristics of desert plants, including upper epidermal waxy layer, lower epidermal villi, and relatively sunken stomata, suggesting that S. tonkinensis has strong drought tolerance. In conclusion, drought stress changed the cell structure of S. tonkinensis, induced antioxidant enzyme activity and increased its resistance to drought.

[Relationship between smoking and the risk of morbidity of chronic obstructive pulmonary diseases among residents aged 30 years and above in Sichuan Province: a prospective study].

Objective: To investigate the morbidity of chronic obstructive pulmonary diseases (COPD) in residents aged 30 years and above in Sichuan Province, and analyze the effect of smoking on the risk of morbidity on COPD. Methods: From 2004 to 2008, people were randomly selected from Pengzhou, Sichuan Province. All the local people aged 30-79 years were asked to receive questionnaire survey, physical examination and pulmonary function testing, and long-term follow-up to determine the morbidity of COPD. Cox proportional hazard regression model was used to analyze the relationship between smoking and COPD. Results: In 46 540 participants, the current smoking rates were 67.31% in males and 8.67% in females, there were 3 101 new cases of COPD, with a cumulative incidence of 6.66%. Adjusted for age, gender, occupation, marriage, income level, educational level, BMI, daily total physical activity, current cooking frequency, whether there was smoke exhaust device at present and frequency of passive smoking exposure, multivariate Cox proportional hazard regression analysis showed that compared with the non-smoking population, current smoking and quitting smoking increased the risk of COPD, with HR of 1.42 (95%CI:1.29-1.57) and 1.34 (95%CI:1.16-1.53). Compared with people who never or occasionally smoke, the risk of morbidity on COPD increased with the increase of average daily smoking volume, mixed smoking at present, mixed smoking at the beginning increased the risk of COPD, with HR of 1.79 (95%CI: 1.42-2.25) and 2.12 (95%CI: 1.53-2.92), started smoking at the age of <18 years old and ≥18 years old increased the risk of COPD, with HR of 1.61 (95%CI:1.43-1.82) and 1.34 (95%CI: 1.22-1.48), inhaling into the mouth, throat and lung during smoking increased the risk of COPD, with HR of 1.30 (95%CI: 1.16-1.45), 1.63 (95%CI: 1.45-1.83) and 1.37 (95%CI: 1.21-1.55). Adjusted for multiple confounding factors and adjusted for regression dilution bias, the average daily smoking volume, the age of starting smoking and the depth of smoking inhalation had an impact on the incidence of COPD, and the gender difference was particularly prominent. Conclusions: Smoking increased the risk of morbidity on COPD, which was related to the average daily smoking volume, the type of smoking, the age of starting smoking and the depth of smoking inhalation. Tobacco control should comprehensively consider the specific characteristics of smoking, so as to prevent COPD.

The influence of culture and cognitive reserve on the clinical presentation of behavioural-variant frontotemporal dementia.

Characterisation of the clinical profile of behavioural-variant frontotemporal dementia (bvFTD) has predominantly been based on Western samples. Some small studies have suggested that the clinical profile may differ in culturally and linguistically diverse populations. Additionally, there is evidence that patients from non-English speaking backgrounds may have more cognitive reserve, allowing them to tolerate more disease pathology before clinical symptoms emerge. This study aims to characterise the clinical profiles of patients with bvFTD from culturally diverse backgrounds. BvFTD patients were classified as Australian-born (Australian) or Culturally and Linguistically Diverse-English-speaking (CALD-English) and Culturally and Linguistically Diverse-Language Other Than English (CALD-LOTE). Clinical features, cognitive test performance and cognitive reserve were compared between groups. Voxel-based morphometry was used to examine the neural correlates of cognitive reserve. 107 patients with bvFTD (53 Australian, 36 CALD-English, 18 CALD-LOTE) and 51 controls were included. Analysis of neuropsychiatric features revealed more elation in Australian patients compared to CALD-English patients, with trends for CALD-LOTE patients to report more irritability. CALD-LOTE patients also had higher cognitive reserve and showed relatively greater verbal than non-verbal cognitive impairment. Neuroimaging analyses revealed that higher cognitive reserve was associated with lower integrity in the frontal-temporal regions associated with typical disease pathology in bvFTD. Our findings support the hypothesis that cognitive reserve may delay early cognitive decline in culturally and linguistically diverse patients, although these patients may still show poor verbal performance due to cultural testing biases. Clinically, these results highlight the need to consider cultural and linguistic background to inform the assessment of dementia.

Fast and slow skeletal myosin binding protein-C and aging.

Aging is associated with skeletal muscle strength decline and cardiac diastolic dysfunction. The structural arrangements of the sarcomeric proteins, such as myosin binding protein-C (MyBP-C) are shown to be pivotal in the pathogenesis of diastolic dysfunction. Yet, the role of fast (fMyBP-C) and slow (sMyBP-C) skeletal muscle MyBP-C remains to be elucidated. Herein, we aimed to characterize MyBP-C and its paralogs in the fast tibialis anterior (TA) muscle from adult and old mice. Immunoreactivity preparations showed that the relative abundance of the fMyBP-C paralog was greater in the TA of both adult and old, but no differences were noted between groups. We further found that the expression level of cardiac myosin binding protein-C (cMyBP-C), an important modulator of cardiac output, was lowered by age. Standard SDS-PAGE along with Pro-Q Diamond phosphoprotein staining did not identify age-related changes in phosphorylated MyBP-C proteins from TA and cardiac muscles; however, it revealed that MyBP-C paralogs in fast skeletal and cardiac muscle were highly phosphorylated. Mass spectrometry further identified glycogen phosphorylase, desmin, actin, troponin T, and myosin regulatory light chain 2 as phosphorylated myofilament proteins in both ages. MyBP-C protein-bound carbonyls were determined using anti-DNP immunostaining and found the carbonyl level of fMyBP-C, sMyBP-C, and cMyBP-C to be similar between old and adult animals. In summary, our data showed some differences regarding the MyBP-C paralog expression and identified an age-related reduction of cMyBP-C expression. Future studies are needed to elucidate which are the age-driven post-translational modifications in the MyBP-C paralogs.

Cryptanshinone extract of Salvia miltiorrhiza stimulates pediatric acute myeloid leukemia stem cell apoptosis and the anti-inflammatory mechanism via accelerating microRNA-211-5p to supress Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway activation.

This study was designed to explore cryptanshinone (CPT) extract of Salvia miltiorrhiza stimulating pediatric acute myeloid leukemia (AML) stem cell (LSC) apoptosis and anti-inflammatory mechanism via accelerating microRNA (miR)-211-5p to restrain Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway activation. Obtaining blood samples from pediatric acute myeloid leukemia patients and healthy volunteers and detecting miR-211-5p and JAK2 were performed. Purchase of the human AML cell line KG1a was conducted, and sorting of KG1a cells was to gain LSC. Test of miR-211-5p and JAK2, the phosphorylation of JAK2/STAT3 was implemented. Pretreatment of LSCs was with CPT. Variation of miR-211-5p and JAK2 in LSCs was via plasmid transfection to explore their actions in cell advancement with apoptosis and inflammation. Identification of the targeting of miR-211-5p with JAK2 was implemented. In results: MiR-211-5p was declined in endometrial cancer, while JAK2 was elevated; CPT was available to boost LSC apoptosis and restrain the inflammation; elevated miR-211-5p or repressive JAK2 was available to strengthen the acceleration of CPT on LSCs apoptosis and the repression of inflammation; MiR-211-5p targeted JAK2; augmented JAK2 was available to turn around the action of elevated miR-211-5p. We conclude that CPT extract of Salvia miltiorrhiza stimulated pediatric LSC apoptosis and restrained the inflammation via accelerating microRNA (miR)-211-5p to suppress JAK2/STAT3 pathway activation.

[Establishment and validation of a predictive model for neurogenic urinary tract injury in children].

Objective: To establish a predictive model for upper urinary tract damage in children with neurogenic bladder and verify its efficacy. Methods: From January 2011 to December 2021, 143 children with NB in the Children's Hospital of Chongqing Medical University and 84 children with NB in the First Affiliated Hospital of Zhengzhou University were selected as the research objects. The former is set as the training set and the latter is set as the validation set, and the general parameters of the two are compared. The independent risk factors of upper urinary tract damage in children with NB were screened out by Lasso regression, and multivariate logistic regression analysis and a nomogram prediction model was established. The models were validated internally and externally on the training set and validation set, respectively, and the area under the receiver operating curve (ROC) was used to verify the accuracy of the model. Results: A total of 227 children with NB were included in this study, including 121 males and 106 females, aged (10.2±3.8) years. There was no significant difference in other parameters except age between the training set and validation set (all P>0.05); Lasso regression and multivariate logistic regression analysis showed that detrusor leakage point pressure (DLPP) ≥ 40 cmH2O (OR=4.76, 95%CI: 2.01-11.26, 1 cmH2O=0.098 kPa), overactive bladder (OAB) (OR=3.08, 95%CI: 1.34-7.04), bladder compliance (BC)<20 ml/cm H2O (OR=3.65, 95%CI: 1.41-9.47), history of previous urinary tract infection (OR=2.73, 95%CI: 1.09-6.81), and abdominal pressure/other voiding patterns (OR=2.86, 95%CI: 1.20-6.82) were risk factors for upper urinary tract damage in children with NB (all P<0.05). The above parameters were used to establish a nomogram model of upper urinary tract damage in children with NB. The internal and external validation results show that the AUC values for the training and validation sets were 0.84 (95%CI: 0.77-0.91) and 0.86 (95%CI: 0.79-0.94), respectively. Conclusion: The prediction model of upper urinary tract damage in children with NB constructed in this study has high discrimination, accuracy and clinical applicability, which can help clinicians identify high-risk patients and make individualized treatment design for these patients.

A high-concentrate diet induces an inflammatory response and oxidative stress and depresses milk fat synthesis in the mammary gland of dairy cows.

Although high-concentrate diet feeding can temporarily increase milk production, it can cause a series of metabolic diseases, such as subacute ruminal acidosis (SARA) and milk fat depression. The main purpose of this experiment was to study the effects of a high-concentrate diet on the inflammatory response, oxidative stress, and milk fat synthesis in the mammary gland of dairy cows. Twelve Holstein cows equipped with rumen fistulas were randomly divided into 2 groups, each with 6 cows, fed a low-concentrate diet (LC) and a high-concentrate diet (HC). On d 20 and 21 of the experiment, rumen fluid was collected to measure pH, and milk samples were collected for milk component analysis and lipopolysaccharide (LPS) concentration testing. On d 21, mammary vein blood was collected to detect the LPS concentration. At the end of the 21-d experimental period, mammary gland tissue was collected, and the expression of inflammatory response-, oxidative stress-, and milk fat synthesis-related genes and proteins in the mammary gland was analyzed by real-time quantitative PCR and western blot. The pH of rumen fluid in the HC group was significantly lower than that in the LC group, and the pH of 2 time points in the HC group was lower than 5.6, indicating that a high-concentrate diet induced SARA. The LPS concentration of the peripheral blood in HC group increased significantly compared with that in the LC group. For the inflammatory response, the proinflammatory cytokines (IL-6 and IL-1α) and innate immune factors (lingual antimicrobial peptide and tracheal antimicrobial peptide) in the mammary gland of the HC group were significantly increased, and the TLR4-NF-κB signaling pathway was activated. For oxidative stress, after HC diet feeding, the content of malondialdehyde in mammary vein blood and mammary gland tissue increased, the content of glutathione in mammary vein blood decreased, the activity of superoxide dismutase and the total antioxidant capacity in mammary gland tissue and mammary vein blood decreased, and the expression of antioxidant enzymes and antioxidant transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2) in mammary gland decreased. For milk fat metabolism, HC diet feeding reduced the milk fat content in milk samples and the triacylglycerol content in the mammary gland and inhibited the expression of de novo synthase (ACACA and FASN), long-chain fatty acid converting enzymes (ACSL1 and SCD), fatty acid transporters (CD36, FATP, FABP3, and LPL), triacylglycerol synthase (AGPAT6, DGAT1, and LPIN1), lipid droplet releasing enzyme (PLIN1), and transcription factors sterol regulatory element binding protein (SREBP1) and peroxisome proliferator activated receptor gamma (PPARG). In summary, a HC diet can induce SARA with increased concentration of LPS in the peripheral vein, stimulate inflammatory reactions and oxidative stress, and inhibit milk fat synthesis in the mammary gland of dairy cows.

Antigen Presentation and Proteome Study of Exosomes Secreted by Co-Culture of Macrophages and Talaromyces marneffei.

It is known that intracellular pathogens interact and react with the cellular immune system through exosomes produced by macrophages. This study aimed to determine whether co-culture of macrophages and Talaromyces marneffei induces exosomes and leads to immune responses. T. marneffei was incubated to collect conidia, co-cultured with human macrophages, which then induced exosomes. In cellular experiments, after extraction and purification, the exosomes were then observed by electron microscopy and detected by flow cytometry and mass spectrometry. In animal experiments, flow cytometry and enzyme-linked immunosorbent assay were used to examine whether exosomes were antigenpresenting. The results showed that purified exosomes produced a pro-inflammatory response and stimulated production of TNF-α in non-fungal-treated macrophages. Protein mass spectrometry analysis of exosomes also indicated their potential ability to activate the internal immune response system and the pro-inflammatory response. Translation and ribosomes were the most abundant GO terms in proteins, and the most relevant KEGG pathway was the biosynthesis of secondary metabolites. Furthermore, in vivo experiments revealed that exosomes induced activation of lymphocytes and increased expression of TNF-α and IL-12 in the lung, mediastinum, and spleen area. In conclusion, exosomes can be released by co-culture of T. marneffei and macrophages, having antigen-presenting functions, promoting macrophage inflammation, and initiating adaptive immune responses. These processes are inextricably linked to the translation of secondary metabolites, ribosomes and biosynthesis.

[Safety and efficacy of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute B cell lymphoblastic leukemia].

Objective: This study aimed to evaluate the safety and efficacy of humanized CD19-targeted chimeric antigen receptor T-cell (CAR-T) in patients with relapsed/refractory acute B cell lymphoblastic leukemia (R/R B-ALL) . Methods: The clinical data of 41 patients with R/R B-ALL treated with humanized CD19-targeted CAR-T cells in the First Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to July 2021 were analyzed. Results: Cytokine release syndrome occurred in all patients, and 63.4% (26/41) were grades 1-2. Immune effector cell-associated neurotoxicity syndrome developed in three patients. On median day 15 (9-47) , the complete remission rate was 95.1% (39/41) , of which 38 patients tested negative for bone marrow minimal residual disease detected by flow cytometry. Among the 39 patients with complete remission, 17 patients did not receive further treatment, and 70.6% (12/17) remained in remission at the end of follow-up, with a progression-free survival of 11.6 months of the two patients with the earliest infusion. Another 17 patients underwent consolidation allogeneic hematopoietic stem cell transplantation (10 cases) or CD22 CAR-T cell sequential therapy (seven cases) after remission, and 76.5% (13/17) of the patients were still in remission at the end of follow-up. The remaining five patients who did not receive consolidation therapy relapsed at a median of 72 (55-115) days after CAR-T cell therapy. Conclusion: In patients with R/R B-ALL, the humanized CD19-targeted CAR-T cells had a high response and manageable toxicity.

[ELF4 promotes proliferation and inhibits apoptosis of human insulinoma cells by activating Akt signaling].

OBJECTIVE: To investigate the effect of overexpression of the oncogenic transcription factor ELF4 on proliferation and apoptosis in human insulinoma cells and explore the underlying mechanism. METHODS: A human insulinoma BON cell line with stable overexpression of ELF4 (BON-ELF4 cells) was constructed using a recombinant retrovirus vector and the expression of ELF4 protein was verified using Western blotting. MTT assay was used to assess the proliferation of BON-ELF4 cells and BON-Vector cells, and the cell apoptosis induced by treatment with epirubicin (0.1 µmol/L for 24 h) was analyzed by detecting the expressions of cleaved caspase-8, caspase-9, and PARP using Western blotting. Flow cytometry with Annexin VFITC/PI staining was performed to analyze the numbers of apoptotic BON-Vector or BON-ELF4 cells. The expressions of phosphorylated Akt and total Akt in the cells were detected using Western blotting. RESULTS: BON-ELF4 cell line with stable overexpression of ELF4 was successfully established. ELF4 overexpression significantly promoted the proliferation (P < 0.05) and obviously suppressed epirubicin- induced apoptosis in BON cells, resulting also in significantly reduced expressions of cleaved caspase-8, caspase-9 and PARP (P < 0.05). The results of flow cytometry showed a significantly lower apoptotic rate in BON-ELF4 cells than in BON-Vector cells following epirubicin treatment (6.03% vs 22.90%). The phosphorylation levels of Akt (Thr308 and Ser473) were significantly increased (P < 0.05) while the level of total Akt remained unchanged (P>0.05) in ELF4- overexpressing cells. CONCLUSION: ELF4 overexpression enhances the proliferation and suppresses apoptosis of insulinomas cells by activating Akt signaling.

Preparation and process optimization of microbial organic copper as a feed additive / Preparação e otimização do processo de cobre orgânico microbiano como aditivo alimentar

As an essential trace element for animals, copper significantly contributes to the growth and health of animals. Compared to inorganic trace elements, organic trace elements are better supplements; notably, they are acquired through microbial transformation. Therefore, we screened for copper-enriched microorganisms from high copper content soil to obtain organic copper. Sodium diethyldithio carbamate trihydrate was applied as a chromogenic agent for determining micro amounts of intracellular copper through spectrophotometry. In total, 50 fungi were isolated after the successful application of the screening platform for copper-rich microbes. Following morphological and molecular biology analyses, the N-2 strain, identified as Aspergillus niger sp. demonstrated showed better copper enrichment potential than others. Notably, the strain tolerance to copper was nearly thrice that of Saccharomyces cerevisiae, up to 1600mg/L. The content of the organic bound copper was 22.84mg Cu/g dry cell. Using the Central Composite Design (CCD) response surface method, we optimized the fermentation condition (inoculation amount, 13%; temperature, 28(C; pH, 5.0). Compared to the original strain results under the single factor fermentation condition, we reported an increase by 24.18% under the optimized conditions. Collectively, these findings provide a reference for uncovering new and low-cost organic copper additives.(AU)

Como elemento traço essencial para os animais, o cobre contribui significativamente para o crescimento e saúde dos animais. Comparado aos oligoelementos inorgânicos, os oligoelementos orgânicos são melhores suplementos; notavelmente, eles são adquiridos através de transformação microbiana. Portanto, nós selecionamos microorganismos enriquecidos com cobre de solos com alto teor de cobre para obter cobre orgânico. O carbamato de sódio diethyldithio trihidratado foi aplicado como agente cromogênico para a determinação de micro quantidades de cobre intracelular através da espectrofotometria. No total, 50 fungos foram isolados após a aplicação bem sucedida da plataforma de triagem para micróbios ricos em cobre. Após análises morfológicas e de biologia molecular, a cepa N-2, identificada como Aspergillus niger sp. demonstrou um melhor potencial de enriquecimento de cobre do que outras. Notavelmente, a tolerância da estirpe ao cobre foi quase três vezes maior que a da Saccharomyces cerevisiae, até 1600mg/L. O conteúdo de cobre ligado orgânico era de 22,84mg Cu/g de célula seca. Usando o método de superfície de resposta Central Composite Design (CCD), nós otimizamos a condição de fermentação (quantidade de inoculação, 13%; temperatura, 28C; pH, 5,0). Em comparação com os resultados da deformação original sob a condição de fermentação de fator único, relatamos um aumento de 24,18% sob as condições otimizadas. Coletivamente, estas descobertas fornecem uma referência para descobrir novos aditivos de cobre orgânico de baixo custo.(AU)

Does active surveillance avoid overtreatment in prostate cancer? Lessons learned from salvage radical prostatectomies.

OBJECTIVE: Determine whether our institution´s active surveillance (AS) protocol is a suitable strategy to minimise prostate cancer overtreatment. MATERIAL AND METHODS: Retrospective analysis of 516 patients on AS after prostate cancer diagnosis. Population divided into "per-protocol" vs "induced" AS depending on fulfilment of protocol´s inclusion criteria. Radical prostatectomies after AS were selected and stratified based on: reclassification, progression or patient anxiety. Clinicopathological features and biochemical relapse-free survival were studied. Primary endpoint was overtreatment ratio based on the presence of insignificant prostate cancer and adverse pathological features in the surgical specimen. Kaplan-Meier curves were used to estimate the biochemical relapse-free survival and compared with log-rank test. RESULTS: 304 patients fulfilled inclusion criteria; 100 proceeded to radical prostatectomy (31% "induced", 69% "per-protocol" AS). Surgery indications were reclassification, progression and anxiety in 66%, 18% and 16% of patients respectively. Rate of positive lymph nodes was higher in the progression group (11%) compared to reclassification and anxiety (5% and 0% respectively, P = .002). Positive surgical margins were more frequently reported in the progression cohort compared to reclassification (28% vs 20%). Median follow-up from diagnosis until last radical prostatectomy was 48.3 months (32.4-70). 3 year biochemical relapse-free survival in the salvage radical prostatectomy was 85.4% (95 CI 78.3-93.2). Insignificant cancer was noticed in 7% of patients (Epstein´s vs 24% Wolters´ criteria). Rate of patients with adverse pathological features was 36%. CONCLUSIONS: The majority of patients who underwent salvage surgery after AS were not overtreated. Radical prostatectomy should be considered a safe rescue treatment.

¿La vigilancia activa evita el sobretratamiento en el cáncer de próstata? Lecciones aprendidas de prostatectomías radicales de rescate / Does active surveillance avoid overtreatment in prostate cancer? Lessons learned from salvage radical prostatectomies

Objetivo: Determinar si el protocolo de vigilancia activa (VA) de nuestra institución es una estrategia adecuada para minimizar el sobretratamiento del cáncer de próstata.Material y métodosAnálisis retrospectivo de 516 pacientes en VA tras el diagnóstico de cáncer de próstata. La población se dividió en «VA por protocolo» vs. «VA inducida», dependiendo del cumplimiento de los criterios de inclusión del protocolo. Las prostatectomías radicales después de la VA fueron seleccionadas y estratificadas en base a reclasificación, progresión o ansiedad del paciente. Se estudiaron las características clinicopatológicas y la supervivencia libre de recidiva bioquímica. La variable principal del estudio fue el porcentaje de sobretratamiento con relación a la presencia de un cáncer de próstata insignificante y de características patológicas adversas en la pieza quirúrgica. Se utilizaron las curvas de Kaplan-Meier para estimar la supervivencia libre de recidiva bioquímica y se compararon con la prueba log-rank.ResultadosUn total de 304 pacientes cumplieron los criterios de inclusión; 100 procedieron a una prostatectomía radical (31% «VA inducida», 69% «VA por protocolo»). Las indicaciones para la cirugía fueron la reclasificación, la progresión y la ansiedad de los pacientes (66, 18 y 16%, respectivamente). (AU)

Objective: Determine whether our institution's active surveillance (AS) protocol is a suitable strategy to minimise prostate cancer overtreatment.Material and methodsRetrospective analysis of 516 patients on AS after prostate cancer diagnosis. Population divided into «per-protocol» vs «induced» AS depending on fulfilment of protocol's inclusion criteria. Radical prostatectomies after AS were selected and stratified based on reclassification, progression or patient anxiety. Clinicopathological features and biochemical relapse-free survival were studied. Primary endpoint was overtreatment ratio based on the presence of insignificant prostate cancer and adverse pathological features in the surgical specimen. Kaplan-Meier curves were used to estimate the biochemical relapse-free survival and compared with log-rank test.Results304 patients fulfilled inclusion criteria; 100 proceeded to radical prostatectomy (31% «induced», 69% «per-protocol» AS). Surgery indications were reclassification, progression and anxiety in 66%, 18% and 16% of patients, respectively. Rate of positive lymph nodes was higher in the progression group (11%) compared to reclassification and anxiety (5% and 0%, respectively; P=.002). Positive surgical margins were more frequently reported in the progression cohort compared to reclassification (28% vs 20%). Median follow-up from diagnosis until last radical prostatectomy was 48.3months (32.4-70). Three year biochemical relapse-free survival in the salvage radical prostatectomy was 85.4% (95%CI: 78.3-93.2). Insignificant cancer was noticed in 7% of patients (Epstein's vs 24% Wolters’ criteria). Rate of patients with adverse pathological features was 36%. (AU)

[A comparative study of the effects of different treatment strategies on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer].

Objective: To compare the effects of 3 treatment strategies (emergent surgery, self-expanding metallic stents, self-expanding metallic stents plus neoadjuvant chemotherapy) on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer. Methods: A retrospective cohort study was conducted. Clinical data of patients with complete obstructive left hemicolon cancer admitted to General Surgery Department of Beijing Chaoyang Hospital between January 2017 and October 2019 were retrospectively collected. Patient inclusion criteria: (1) complete obstructive left hemicolon cancer was confirmed through clinical manifestation and abdominal computed tomography; (2) adenocarcinoma was confirmed by postoperative pathology; (3) emergent radical resection of primary tumor was performed with temporary stoma, or radical resection of primary tumor and primary anastomosis was performed without stoma, 7 to 14 days after completion of insertion of self-expanding metallic stents. Patients who did not receive stoma reversion after emergent operation were excluded. According to different therapies, patients were divided into three groups: emergent surgery (ES) group, self-expanding metallic stents (SEMS) group and self-expanding metallic stents plus neoadjuvant chemotherapy (SEMS+NAC) group. Wexner score for incotinence (higher score indicates the worse anal function), Vaizey score (>10 indicates fecal incontinence) and low anterior resection syndrome (LARS) scale (higher score indicates the worse anal function) were applied to evaluate anal function of patients among groups at postoperative 1-, 6- and 12-month. EORTC QLQ-C30 questionnaire was used to assess the quality of life. Risk factors of decreased anal function were identified by logistic regression analysis. Results: A total of 72 patients were enrolled, including 27 (37.5%) patients in ES group, 23 (31.9%) in SEMS group and 22 (30.6%) in SEME+NAC group. The baseline characteristics including age, gender, tumor location, comorbidities, total blood loss, operation time and postoperative complications, were comparable among groups, except that the proportion of laparoscopic surgery was significantly lower in ES group (4/27, 14.9%) than that in SEMS (15/23, 65.2%) and SEMS+NAC group (16/22, 72.7%) with significant difference (P<0.001). The follow-up ended up to October 2020, and the overall follow-up rate was 79.2% (57/72). No significant differences existed in the Wexner score of patients among groups at postoperative 1-, 6- and 12-month (all P>0.05). The Vaizey scores at postoperative 1-month in ES, SEMS and SEMS+NAC group were 7 (0-17), 3 (0-7) and 4 (0-8) respectively with significant difference (H=18.415, P=0.001), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). Vaizey scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The LARS scores at postoperative 1-month in ES, SEMS and SEMS+NAC groups were 20 (0-37), 15 (0-24) and 16 (0-28) respectively with significant difference (H=3.660, P=0.036), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC groups (P>0.05). LARS scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The QLQ-C30 score revealed that the social function of patients in SEMS group and SEMS+NAC group was significantly better than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). The logistic regression analysis revealed that only ES was an independent risk factor of decreased anal function (OR=2.264, 95% CI: 1.098-4.667, P=0.027). Conclusion: Compared to ES, SEMS may improve quality of life and short-term anal function of patients with complete obstructive left hemicolon cancer.

[Cross-reaction of seasonal influenza vaccine immune serum against Eurasian Avian-like H1N1 swine influenza virus].

Objective: To evaluate the cross-reaction of seasonal influenza vaccine immune serum against Eurasian avian-like H1N1 swine influenza virus. Methods: Nine human infected Eurasian avian-like H1N1 swine influenza virus strains were obtained from national influenza surveillance network laboratories in Jiangsu, Hebei, Shandong, Yunnan, Hunan, Fujian and Tianjin provinces, and their genetic characteristics of hemagglutinin were analyzed by deep sequencing. 30 volunteers were recruited respectively from children (2-5 years old), adults (24-57 years old) and elderly (60-84 years old) who received 2019-2020 seasonal influenza vaccine in Anning city, Yunnan Province in October 2019, and serum samples were collected before and 1 month after vaccination. The hemagglutination inhibition test was used to evaluate the cross-reaction of serum before and after immunization against 4 strains of human infection with Eurasian avian-like H1N1 swine influenza virus isolated since 2015. Results: The homology of hemagglutinin genes of 9 Eurasian avian-like H1N1 swine influenza viruses was similar, but the difference of hemagglutinin heavy chain and light chain amino acid genes with A (H1N1) pdm09 (vaccine strain) were 90-101 and 24-30 amino acids respectively. The antibody titer of vaccine strain antiserum to vaccine strain was 2 560; the antibody titers of the vaccine strain antiserum to Eurasian avian-like H1N1 swine influenza virus and the Eurasian avian-like H1N1 swine influenza virus antiserum to vaccine strain were same as 640. The proportion of children, adults and elderly vaccinated with seasonal influenza vaccine with antibody titer ≥40 against vaccine strain was 90.0%, 70.0% and 73.3%, respectively; while the proportion merely were 46.7%, 36.7% and 33.3%-43.3% to 4 strains of Eurasian avian-like H1N1 swine influenza virus, respectively. Conclusion: Seasonal influenza vaccination does not provide effective cross-protection against Eurasian avian-like H1N1 swine influenza virus.

[Effect of piRNA NU13 in regulating biological behaviors of human Wilms tumor cells in vitro].

OBJECTIVE: To investigate the role of the differential piRNA NU13 derived from piwil2-induced cancer stem-like cells (piwil2-iCSCs) in regulating biological behaviors of Wilms tumor cells (G401). OBJECTIVE: The expressions of piRNA NU13 and NOP56 were detected in Wilms tumor cell line G401 using RT-qPCR. G401 cells were transfected with piRNA NU13 mimics and inhibitor for its over-expression and inhibition, and the transfection efficiency was verified with RT-qPCR. The changes in proliferation of G401 cells after transfection were detected using CCK8 assay, and cell apoptosis was analyzed using flow cytometry. Wound healing assay and Transwell assay were performed to examine the changes in migration and invasion abilities of the transfected cells. The binding of NOP56 and piRNA NU13 was detected using dual luciferase experiment. The protein expressions of MMP2, MMP9, BAX, Bcl2, and NOP56 in the cells were detected with Western blotting. OBJECTIVE: RTqPCR showed that the expression of piRNA NU13 decreased significantly in human Wilms tumor G401 cells as compared with that in renal tubular epithelial cell line HK2 (P < 0.05), and NOP56 was highly expressed in G401 cells and Wilms tumor tissues (P < 0.05). Over-expression of piRNA NU13 significantly suppressed the proliferation, migration and invasion of G401 cells, promoted cell apoptosis (P < 0.05), inhibited the expression of MMP2, MMP9 and Bcl2, and enhanced the expression of BAX (P < 0.05). The results of dual luciferase experiment showed that piRNA NU13 did not bind to NOP56 directly but regulated the expression of NOP56 in an indirect manner. OBJECTIVE: piRNA NU13 is down-regulated and NOP56 is highly expressed in Wilms tumor. piNU13 may regulate the expression of NOP56 indirectly to inhibit the proliferation, migration and invasion and promote apoptosis of Wilms tumor cells in vitro.

[Impact of inflammatory reaction levels and culprit plaque characteristics on preprocedural thrombolysis in myocardial infarction flow grade in patients with ST-segment elevation myocardial infarction].

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm2 vs. 1.4(1.1-1.9)mm2, all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.

Sodium butyrate relieves lung ischemia-reperfusion injury by inhibiting NF-κB and JAK2/STAT3 signaling pathways.

OBJECTIVE: Ischemia-reperfusion (IR) is the main cause of acute lung injury (ALI) in clinical lung transplantation, extracorporeal circulation, lung sleeve resection, trauma and cardiopulmonary resuscitation. The inflammatory response and oxidative stress following IR are factors that cause and aggravate its secondary damage. The purpose of this study was to investigate the efficacy and mechanism of sodium butyrate (NaB) on lung ischemia-reperfusion injury (LIRI). MATERIALS AND METHODS: We used male C57BL/6 mice to construct the LIRI model and administered the mice with NaB. By examining the expression of inflammatory factors and oxidative stress-related molecules in mouse lung tissue, we investigated the effects of NaB on inflammation and oxidative stress in lung tissue after IR. In addition, the changes in the activity of the NF-κB and JAK2/STAT3 signaling pathways were also examined to determine the mechanism of NaB. RESULTS: The expression levels of the inflammatory factors (IL-1ß, IL-6 and TNF-α) in lung tissue of mice after IR were significantly increased, while NaB reduced the expression of inflammatory factors. In addition, the oxidative stress level of mouse lung tissue after IR increased significantly, showing the decrease of antioxidant molecules SOD1/2, catalase (CAT), and Peroxiredoxin 1 (Prdx1), while the intake of NaB increased the antioxidant level of mouse lung tissue. The activities of NF-κB and JAK2/STAT3 signaling pathways were significantly increased in lung tissue after IR, whereas NaB inhibited the activity of NF-κB and JAK2/STAT3 signaling pathways. CONCLUSIONS: NaB relieves LIRI by inhibiting NF-κB and JAK2/STAT3 signaling pathways to reduce inflammation and oxidative stress levels in lung tissue of mice after IR.

Clash of the calculators: External validation of prostate cancer risk calculators in men undergoing mpMRI and transperineal biopsy.

Objective: To compare the accuracy of the European Randomized Study of Screening for Prostate Cancer (ERSPC) RC, MRI-ERSPC-RC, and Prostate Biopsy Collaborative Group (PBCG) RC in patients undergoing transperineal prostate biopsy. Patients and methods: We identified 392 patients who underwent mpMRI before transperineal prostate biopsy across multiple public and private institutions between January 2017 and August 2019. The estimated probabilities of detecting PCa and significant PCa were calculated using the MRI-ERSPC-RC, ERSPC-RC, and PBCG-RC. Receiver operating characteristic (ROC) curves for each calculator were generated and the area underneath the curve (AUC) was compared. Calibration and clinical utility were assessed with calibration plots and decision curve analysis, respectively. Results: PCa was detected in 285 patients (72.7%) with significant PCa found in 200 patients (51.1%). ROC curve analysis found the MRI-ERSPC-RC outperformed the ERSPC-RC and PBCG-RC. For the prediction of PCa, the AUC was 0.756, 0.696, and 0.675 for the MRI-ERSPC-RC, ERSPC-RC, and PBCG-RC, respectively. The AUC for the prediction of significant PCa was 0.803, 0.745, and 0.746 for the MRI-ERSPC-RC, ERSPC-RC, and PBCG-RC, respectively. Conclusions: Our study validated the ERSPC-RC, MRI-ERSPC-RC, and PBCG-RC in a cohort undergoing transperineal prostate biopsy with the MRI-ERSPC-RC performing the best. These RCs may enable improved shared decision making and help to guide patient selection for biopsy.