GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Objective:To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury.Methods:Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ2 test or t-test was used for statistical analysis. Results:Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference ( χ2 ?=?9.975 0, P ?=?0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference ( χ2 ?= 0.593 5, P ?=?0.441 1). Conclusion:Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

As one of the imaging features of cerebral small vessel disease, white matter hyperintensity (WMH) of presumed vascular origin is quite common in the elderly. The burden of WMH is thought to progress slowly over time and is significantly associated with cognitive decline. However, the pathogenesis of WMH remains unclear and there is no effective treatment available. Recent studies have reported that some WMH lesions can regress during follow-up, along with progression and regression occurring alternately, suggesting that longitudinal changes in WMH are not unidirectional. This article presents a systematic review of current neuroimaging studies on WMH regression to enhance the understanding of dynamic changes in WMH and to provide new theoretical evidence for WMH intervention.

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients’ factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men’s Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: “low libido”, “erectile dysfunction”, “ejaculatory dysfunction”, “premature ejaculation”, “retrograde ejaculation”, “delayed ejaculation”, “anejaculation”, and “orgasmic dysfunction” between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socioeconomic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient’s individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.
Animals ; Mice ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Histone Methyltransferases/metabolism* ; Histones/genetics* ; Morphogenesis ; Neuronal Plasticity ; Neurons/metabolism*

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Objective:To investigate the distribution and molecular characteristics of Yersinia isolated from diarrhea patients in Jiangsu Province. Methods:From 2017 to 2021, the stool samples of diarrhea patients were collected in Tongshan District of Xuzhou City and Dongtai City of Yancheng City, Jiangsu Province, where the national active monitoring sites of Yersinia enterocolitica, then Yersinia was isolated; meanwhile, suspected Yersinia strains were collected from sentinel hospitals in the province. The DNA of isolated strains was extracted for whole genome resequencing, and the data were uploaded to the EnteroBase database for Yersinia species identification; the original data were cleaned and processed for 16S ribosomal RNA (16S rRNA) gene polymorphism analysis. Five virulence genes (ail, ystA, ystB, yadA, virF) were scanned through the National Center for Biotechnology Information (NCBI) and Pathogen Virulence Factor Database (VFDB), and K-mer Tree was constructed and genomic characteristics were analyzed. Results:From 2017 to 2021, a total of 2 058 stool samples from diarrhea patients were collected, and 57 strains of Yersinia were isolated and identified; meanwhile, two Yersinia strains were collected from the sentinel hospital. Compared with EnteroBase database, 51 strains were identified as Yersinia enterocolitica, 4 strains as Yersinia proxima, 1 strain each as Yersinia aleksiciae, Yersinia massiliensis, Yersinia intermedia and Yersinia canariae. The 16S rRNA gene polymorphism analysis showed that all strains were clustered into 3 groups, which could distinguish Yersinia enterocolitica from other Yersinia. Among the 51 strains of Yersinia enterocolitica, 49 strains were virulence genotype Ⅲ(ail-, ystA-, ystB+, yadA-, virF-), two strains were virulence genotype Ⅱ(ail+, ystA+, ystB-, yadA-, virF-); and 8 other Yersinia strains were virulence genotype Ⅳ (ail-, ystA-, ystB-, yadA-, virF-). K-mer analysis could distinguish Yersinia enterocolitica from other Yersinia, JS-XZ-2020001 strain was far away from other Yersinia enterocolitica isolates, and serotype O8 strains were more concentrated. Conclusions:The clinical isolates of Yersinia enterocolitica from diarrhea patients are mainly Yersinia and other Yersinia co-exist in a small amount in Jiangsu Province, two new Yersinia species ( Yersinia proxima and Yersinia canariae) are discovered. The virulence genotype of Yersinia enterocolitica is mainly type Ⅲ. The 16S rRNA gene polymorphism analysis and K-mer analysis can effectively distinguish Yersinia enterocolitica from other Yersinia.

Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.

The increasing prevalence of chronic kidney disease (CKD) is a major global public health concern. Despite the complicated pathogenesis of CKD, renal fibrosis represents the most common pathological condition, comprised of progressive accumulation of extracellular matrix in the diseased kidney. Over the last several decades, tremendous progress in understanding the mechanism of renal fibrosis has been achieved, and corresponding potential therapeutic strategies targeting fibrosis-related signaling pathways are emerging. Importantly, extracellular vesicles (EVs) contribute significantly to renal inflammation and fibrosis by mediating cellular communication. Increasing evidence suggests the potential of EV-based therapy in renal inflammation and fibrosis, which may represent a future direction for CKD therapy.