[Clinical features of patients with metastatic pheochromocytoma/paraganglioma].

Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.

[Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis].

Objective: To investigate the causality between intestinal flora and hypertrophic scars (HS) of human. Methods: This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora (n=18 473) and HS (n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results: A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions: There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

The environmental and socioeconomic effects of tuberculosis patients in the southwest of China: a population-based study.

OBJECTIVE: The objective of this study was to assess the incidence of tuberculosis (TB) and find the risk factors of TB patients with a high burden of TB in socioeconomic level, the high level of TB incidence and the great changes of economic and social factors, explore the possible factors, construct scientific and robust prediction model, and analyse whether the task of stopping TB can be accomplished by the expected global deadline. STUDY DESIGN: This was an ecological study. METHODS: Descriptive analysis, spatial and space-time scan, correlation analysis, and regression analysis were carried out, based on cases of TB in Sichuan Province and ecological data from 2006 to 2017, to explore the characters of TB and ecological factors, using the transfer function-noise model to forecast the trend of TB until 2035. RESULTS: Factors affecting the incidence of TB, increasing per capita green area, reporting status of TB among Tibetans and Yi minorities, comprehensive treatment management, total cost of TB per capita for urban residents, proportion of males with high school education, 20 to 20 h of 24-h accumulated precipitation, reducing HIV at the same time as AIDS deaths, the increase in the proportion of males in junior high school education, and the increase in the number of registered TB cases can reduce the incidence of TB. CONCLUSIONS: There was concentration mainly on enhanced control of the environment and society measures, helpful in guiding government planning to control TB. Reinforcement is required to reduce the TB of population aged 15-24 and aged 25-64 in socioeconomic level by 2035.

Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

Occupancy of orbitals and the quadrupole collectivity in 45Sc nucleus.

In the present work, the Doppler Shift Attenuation method (DSAM) was used to analyze the observed lineshapes of transitions from excited states in 45Sc, populated in the reaction 36Ar + 12C at a beam energy of 145 MeV. The interpretation and comparison of the experimental results have been performed with large-scale shell model calculations, involving different interactions like: GX1A, GX1J, FPD6, KB3 and ZBM2. KB3 and FPD6 (present work) interactions in the negative parity states, and in positive parity states ZBM2 are most pre-eminent in reproducing the results, due to the large configuration space describing strong collective effects. Furthermore, the present work also looks at the details of the shell model helping in improving the understanding for the occupancy of orbitals. The present investigation suggests the observation of stronger collectivity for positive parity states over negative parity states with predicted enhanced collectivity of states in 45Sc nucleus.

Probing

The isomer depletion of ^{93m}Mo was recently reported [Chiara et al., Nature (London) 554, 216 (2018)NATUAS0028-083610.1038/nature25483] as the first direct observation of nuclear excitation by electron capture (NEEC). However, the measured excitation probability of 1.0(3)% is far beyond the theoretical expectation. In order to understand the inconsistency between theory and experiment, we produce the ^{93m}Mo nuclei using the ^{12}C(^{86}Kr,5n) reaction at a beam energy of 559 MeV and transport the reaction residues to a detection station far away from the target area employing a secondary beam line. The isomer depletion is expected to occur during the slowdown process of the ions in the stopping material. In such a low γ-ray background environment, the signature of isomer depletion is not observed, and an upper limit of 2×10^{-5} is estimated for the excitation probability. This is consistent with the theoretical expectation. Our findings shed doubt on the previously reported NEEC phenomenon and highlight the necessity and feasibility of further experimental investigations for reexamining the isomer depletion under low γ-ray background.

[Nonalcoholic fatty liver disease and liver transplantation].

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is now the second largest indication for liver transplantation in Western countries, but viral hepatitis B and end-stage alcohol-related liver disease are still the main indications in China. With the improvement of people's living standards, the prevalence of metabolic syndrome, and the number of NAFLD patients has also gradually increased. At the same time, with the hepatitis B vaccination popularization and the nucleos(t)ide analogues and other drugs uses, it is predicted that NAFLD-related end-stage liver disease may become one of the main indications for liver transplantation in our country in the future. This article reviews the research progress of NAFLD and liver transplantation.

Inhibition of microRNA-543 alleviates sepsis-induced acute kidney injury via targeting Bcl-2.

OBJECTIVE: Sepsis has a high morbidity and mortality and is prone to cause acute kidney injury (AKI). Here, we aimed to demonstrate the function and molecular mechanism of microRNA-543 (miR-543) in septic AKI. MATERIALS AND METHODS: MiR-543 inhibitor or NC was transfected into LPS-treated HK-2 cells to observe lipopolysaccharide (LPS)-induced inflammation and apoptosis. The detection of inflammation and apoptosis of HK-2 cells relies on Western blot, quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: MiR-543 expression was increased in LPS-treated HK-2 cells. By transfecting miR-543 inhibitor into HK-2 cells, miR-543 expression was dramatically reduced. The downregulation of miR-543 remarkably inhibited the inflammation and apoptosis, which was manifested by the reduction of inflammatory cytokines (TNF-α, IL-6, IL-1ß), the reversal of apoptosis-related proteins expression (Bcl-1, Bax), the increase of cell viability and the decrease of the proportion of apoptotic cells. The result of Luciferase activity assay demonstrated that miR-543 directly targets Bcl-2. CONCLUSIONS: MiR-543 expression was increased in LPS-treated HK-2 cells, and silencing miR-543 could inhibit LPS-induced inflammation and apoptosis in HK-2 cells via targeting Bcl-2.

[Study on clinical symptoms and influencing factors of influenza-associated severe acute respiratory illness in children younger than 5 years old in Suzhou of China, 2011-2017].

Objective: To study the influencing factors of influenza-associated severe acute respiratory illness (SARI) in children younger than 5 years of old in Suzhou, and to provide evidence to support the improvement of prevention and control strategies for influenza in children. Methods: We conducted a prospective influenza surveillance for hospitalized SARI and outpatient influenza-like illness (ILI) at Children's Hospital of Soochow University from April 2011 to March 2017. We compared the clinical and other characteristics of influenza-positive patients with SARI to those with ILI to find the differences and to identify influencing factors of influenza-associated SARI, using χ2 test and unconditional logistic regression. Results: We found 786 cases of influenza-associated ILI and 413 cases of influenza-associated SARI during the study period. Cough, runny nose, shortness of breath, asthma or wheezing were more common in influenza-associated SARI than in influenza-associated ILI (P<0.01). Univariate and multivariate logistic regression showed that the influencing factors which significantly associated with increased risk of influenza-associated SARI were as follows: younger age (<6 months OR=3.6, 6-23 months aOR=2.5), respiratory infection history within 3 months (aOR=4.5), chronic lung disease history (OR=3.4), fever above 39.0 ℃ (39.0-39.9 ℃ aOR=2.4, ≥40.0 ℃ aOR=6.0), and the presence of A/H1N1 (aOR=2.3), A/H3N2 (aOR=1.9). Conclusion: Children younger than 2 years old, with a history of chronic lung disease, a history of respiratory infection within 3 months, or with a fever peak above 39.0 ℃ should seek medical advice as soon as possible or receive annual influenza vaccination to reduce the incidence of influenza-associated serious outcomes.

Inhibition of microRNA-495 inhibits hypoxia-induced apoptosis in H9c2 cells via targeting NFIB.

OBJECTIVE: Acute myocardial infarction (AMI) is a serious cardiovascular disease that threatens human life. MicroRNA is considered to be an important participant in the pathophysiology of AMI. This article focused on the role of microRNA-495 (miR-495) in regulating apoptosis after myocardial infarction (MI) and its underlying mechanisms. MATERIALS AND METHODS: H9c2 cells were cultured in an incubator containing 1% O2 to establish a cell model of MI. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was utilized to detect miR-495 expression in H9c2 cells. The effects of miR-495 and NFIB on hypoxia-treated H9c2 cells were observed by Western blot, lactate dehydrogenase (LDH) detection, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, flow cytometry, and terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) staining. Luciferase reporter gene experiment was used to prove the regulatory relationship between miR-495 and NFIB. RESULTS: Hypoxia induced injury to H9c2 cells, which was manifested by decreased cell viability, increased LDH release, increased pro-apoptotic proteins (Bax, Cleaved Caspase-3) expression, decreased anti-apoptotic protein (Bcl-2) expression, and increased in the rate of apoptosis and TUNEL positive cells. MiR-495 expression was remarkably increased in H9c2 cells treated with hypoxia. Inhibiting miR-495 expression markedly alleviated the hypoxia-induced injury in H9c2 cells, while silencing NFIB aggravated the hypoxia-induced damage. In addition, NFIB was confirmed to be the target of miR-495. CONCLUSIONS: MiR-495 expression was increased in hypoxia-treated H9c2 cells. Silencing miR-495 could significantly inhibit hypoxia-induced apoptosis of H9c2 cells by targeting NFIB.

[The study on the detection method for mercury in blood with direct mercury analyzer].

Objective: To establish a method for determining mercury in blood with direct mercury analyzer. Methods: After the whole blood sample was extracted by solvent and removed by nitric acid, it was then measured by direct mercury analyzer. Results: After optimizing the conditions of the instrument, the linear range was 0.3-60.0 µg/L and the curve correlation coefficient was higher than 0.999. The lower limit of quantitations was 0.3 µg/L and the minimum quantitative concentration was 3.0 µg/L. The recovery and relative standard deviations (RSD) was 95.2%-97.6% and 1.4%-3.3%. Conclusion: The method is stable, reliable, easy to operate and has high sensitive. It can be used to determine mercury in blood.

[Complexity of Detecting CRISPR/Cas9-Mediated Homologous Recombination in Zebrafish].

Homology-directed (HD) genome modification offers an opportunity to precisely modify the genome. Despite reported successful cases, for many loci, precise genome editing remains challenging and inefficient in vivo. Here we report an effort to precisely knock-in a GFP reporter into gad locus mediated by CRISPR/Cas9 system in the zebrafish Danio rerio. PCR artifact was detected in testing for homologous recombination (HR), but was mitigated by optimizing PCR condition and decreasing the injected targeting plasmid concentration. Under this optimized condition, time course analysis revealed a decline of the HR-positive embryos at embryogenesis progressed. GFP signals also diminished at later developmental stages. The GFP signals were consistent with PCR detection, both of which suggested the loss of targeted insertion events at later stages. Such loss of insertion might be one underlying reason for the inability to obtain germ-line transgenic lines with GFP knocked into the gad locus. Our results suggest that the low HR efficiency associated with CRISPR-mediated knock-in is in part due to loss of insertion after targeted integration into the gad locus.

Circ-ABCB10 promotes proliferation and invasion of esophageal squamous cell carcinoma cells by modulating microRNA-670-3p.

OBJECTIVE: Circ-ABCB10 is a non-coding RNA newly discovered in recent years. It has been observed to serve as an oncogene in a variety of tumors, but its biological function in esophageal squamous cell carcinoma (ESCC) is still unknown. The purpose of this study was to investigate the circ-ABCB10 expression in ESCC and its possible molecular mechanism. PATIENTS AND METHODS: Circ-ABCB10 expression in ESCC tissue samples and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The impacts of circ-ABCB10 on the biological functions of ESCC cells were examined by cell counting kit-8 (CCK-8) and transwell assays. Moreover, bioinformatics analysis was used to determine the binding sites between miRNAs and circ-ABCB10, and the binding relationship was verified by qRT-PCR and Luciferase assay. RESULTS: QRT-PCR analysis revealed that circ-ABCB10 expression in both ESCC tissues and cell lines was higher than that in the normal control group. Patients in high TNM stage exhibited a higher expression of circ-ABCB10 than those in low stage, and this high expression predicted a poor prognosis of ESCC patients. Inhibiting circ-ABCB10 expression remarkably inhibited the growth and metastasis of ESCC cells. In addition, it was demonstrated that circ-ABCB10 could bind to microRNA-670-3p and inhibit its expression. Downregulation of microRNA-670-3p partially reversed the inhibitory impact of low-expressing circ-ABCB10 on cell growth and migration rate. CONCLUSIONS: Circ-ABCB10 accelerates the metastasis and proliferation of ESCC cells by binding to microRNA-670-3p. This circ-ABCB10 / microRNA-670-3p axis may become a potential therapeutic target for ESCC therapy.

[Hospitalization rates for influenza-associated severe acute respiratory illness in children younger than five years old in Suzhou of China, 2016-2018].

We analyzed the influenza surveillance data of Children's Hospital of Suzhou University from 2016 to 2018 and estimated the hospitalization burden of children under 5 years old due to influenza infection in Suzhou. The results showed that the influenza virus positive rate of 1 451 severe acute respiratory infection (SARI) cases in Children's Hospital of Suzhou University was 13.6% (95%CI: 11.8%-15.3%; 197 cases), among which the influenza pandemic intensity in 2017-2018 was relatively high, and A/H1N1 was the main pandemic virus. It was estimated that the hospitalization rate of influenza-related SARI in children under 5 years old in Suzhou was 6.9‰ (95%CI: 6.6‰-7.2‰), among which the hospitalization rate of children aged<6 months was higher, up to 11.4‰ (95%CI: 9.9‰-12.8‰).

Downregulation of lncRNA MEG3 attenuates high glucose-induced cardiomyocytes injury by inhibiting mitochondria-mediated apoptosis pathway.

OBJECTIVE: The aim of the present work was to investigate the effects and mechanisms of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) in cardiomyocytes injury and apoptosis induced by high glucose (HG) in vitro. MATERIALS AND METHODS: HG-induced rats' cardiomyocytes with si-MEG3 transfection were constructed. Cell viability and lactate dehydrogenase (LDH) level were examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and LDH assay kits, respectively. Cardiomyocytes apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. The expressions of Bcl-2, Bax, cleaved caspase-9 and cleaved caspase-3 proteins were determined by Western blot. The expression of lncRNA MEG3 was measured by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). RESULTS: Our results indicated that the expression of MEG3 was significantly upregulated in HG-treated cardiomyocytes. The downregulation of MEG3 could attenuate cardiomyocytes injury and apoptosis by decreasing the Bax/Bcl-2 ratio, cleaved caspase-9 and cleaved caspase-3 expression. CONCLUSIONS: The downregulation of MEG3 could attenuate cardiomyocytes injury and apoptosis induced by HG. The molecular mechanism was associated with the inhibition of the mitochondria-mediated apoptosis pathway.

New Isotope

A new short-lived neutron-deficient isotope ^{220}Np was synthesized in the fusion-evaporation reaction ^{185}Re(^{40}Ar,5n)^{220}Np at the gas-filled recoil separator SHANS. Based on the measurement of the correlated α-decay chains, the decay properties of ^{220}Np with E_{α}=10040(18) keV and T_{1/2}=25_{-7}^{+14} µs were determined, which are in good agreement with theoretical predictions. From the new experimental results coupled with the recently reported α-decay data of ^{219,223}Np, the α-decay systematics for Np isotopes around N=126 was established, which allows us for the first time to test the robustness of the N=126 shell closure in Z=93 Np isotopes. The results also indicate that, in the region of nuclei with Z≥83, the proton drip line has been reached for all odd-Z isotopes up to Np.

[Interactions between transforming growth factor beta and signal transducer and activator of transcription 3 in the development of liver fibrosis].

Liver fibrosis is a common pathological response in chronic liver injury. In the pathological process of hepatic injury, signaling pathways associated with hepatic fibrosis, which mediates the repair, proliferation and fibrosis of the liver secrete different cytokines. In these pathways, transforming growth factor beta (TGFß) and signal transducer and activator of transcription 3 (STAT3) play key roles in the proliferation and activation of hepatic stellate cells (HSCs) and promote epithelial mesenchymal transition. In addition, it is also involved in the process of proliferation and transformation of collagen and extracellular matrix molecules into myofibroblasts. TGFß and STAT3 molecular-related signaling pathways mediate the loss of epithelial phenotype and gene expression in mature epithelial cells, transforming them into mesenchymal cells, and producing anti-apoptosis to hepatocytes and promoting the proliferation of HSCs. However, the mechanisms by which STAT3 and TGFß molecules are involved in the development and progression of liver fibrosis are not sound distinct. In this review, we attempt to know the mechanisms and interactions of TGFß and STAT3 molecules that mediate potential liver fibrosis, and promote their role in promoting HSCs production and epithelial mesenchymal transition.