To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.

OBJECTIVE: To observe the dynamic changes of microvascular injury and repair in the penumbra of traumatic brain injury (TBI) rats with effective cerebral perfusion microvascular imaging using optical coherence tomography angiography (OCTA). METHODS: Transparent closed cranial windows were placed in craniotomy rats after TBI caused by weight drop. All the rats in TBI group and control group underwent head MRI examination on the first postoperative day, and the changes of cerebral cortical microvessel density were measured by OCTA through cranial windows on d0, d2, d4, d6, and d8. On the second day after the operation, the same number of rats in the two groups were selected to complete the immunohistochemical staining of brain tissue with pimonidazole, an indicator of hypoxia. RESULTS: MRI T2W1 and immunohistochemical staining demonstrated that edema and hypoxia in the traumatic brain tissue extended deeply throughout the entire cortex. OCTA showed that the cortical surface veins of the rats in both groups were significantly dilated and tortuous after operation, and recovered to the postoperative day level on d8. The effective perfusion microvessel density of the rats in both groups gradually recovered after a temporary decrease, and the TBI group decreased from 39.38%±4.48% on d0 to 27.84%±6.01% on d2, which was significantly lower than that on d0, d6, and d8 (P < 0.05). The highest value was 61.71%±7.69% on d8, which was significantly higher than that on d0, d2, and d4 (P < 0.05). The control group decreased from 44.59%±7.78% on d0 to 36.69%±5.49% on d2, which was significantly lower than that on d0, d6, and d8 (P < 0.05). The highest value was 51.92%±5.96% on d8, which was significantly higher than that on d2, and d4 (P < 0.05). Comparing the two groups, the effective perfusion microvessel density in the TBI group was significantly lower than that in the control group on d2 (P=0.021), and significantly higher than that in the control group on d8 (P=0.030). CONCLUSION OCTA can be used as a method of imaging and measurement of effective perfusion microvessels in the injured cerebral cortex of TBI rats. After TBI, the effective perfusion microvessel density in the wound penumbra gradually recovered after decreasing, and increased significantly on d8.
Animals ; Brain Injuries, Traumatic/physiopathology* ; Rats ; Tomography, Optical Coherence/methods* ; Male ; Rats, Sprague-Dawley ; Microvessels/pathology* ; Microvascular Density ; Cerebral Cortex/blood supply* ; Cerebrovascular Circulation

OBJECTIVE: To explore the feasibility of establishing a temporary trauma team led by trauma experts in primary hospitals for disaster medical rescue. METHODS: In the coal mine flooding accident in Xiaoyi City, Shanxi Province on December 15, 2021, according to the local emergency plan and the characteristics of the accident, the trauma experts trained the medical staff from the local primary hospital on advanced trauma life support (ATLS) and damage control surgery (DCS) in the short time interval between the occurrence of the mine disaster and the admission of medical staff to the disaster scene. A temporary trauma team composed of trauma experts, ATLS team, and DCS team was formed to provide early diagnosis and treatment for survivors before and in the hospital. RESULTS: The miners were found on the 36th hour of the disaster. All 22 miners were male, and 2 died underground. Another 20 people were rescued 39－43 hours after the disaster, with a median age of 48 years (34-57 years). All the survivors suffered from hypothermia, dehydration, maceration of feet and other injuries. There were 18 cases of acute inhalation tracheobronchitis, 14 cases of electrolyte acid-base disturbance, 6 cases of trunk contusion, 1 case of psoas major hematoma, and 1 case of lower extremity hematoma. Deep vein thrombosis was in 4 cases. The ATLS team focused on injury assessment, rewarming and rehydration within 50－60 minutes before admission, and completed auxiliary examinations within 2 hours after admission to clarify the diagnosis. The DCS team evaluated 6 patients with mechanical blunt trunk injury and excluded the indication of emergency surgery. The trauma experts conducted the whole process of supervision and quality control of disaster rescue. The positive rate of capillary refill test in the all survivors at the third hour of admission was significantly lower than that immediately after being rescued (75.0% vs. 15.0%, P=0.000 3), and they were discharged 4－7 days after admission. CONCLUSION Under the leadership of trauma experts and relying on the medical staff of primary hospitals, it is feasible to establish and train a temporary trauma team with ATLS and DCS functions to participate in the medical rescue of disasters, which is in line with the current national conditions of China.
Humans ; Adult ; Middle Aged ; Male ; Rescue Work/organization & administration* ; China ; Disasters ; Patient Care Team/organization & administration* ; Wounds and Injuries/therapy* ; Advanced Trauma Life Support Care/organization & administration* ; Disaster Planning/organization & administration* ; Emergency Medical Services/organization & administration*

OBJECTIVE To predict potential quality markers(Q-markers) in Yinhua Miyanling tablets based on fingerprinting and network pharmacology methods. METHODS HPLC fingerprints of 13 batches of Yinhua Miyanling tablets were established, and the similarity analysis was carried out using the "Chromatographic Fingerprint Evaluation System for Traditional Chinese Medicine" to identify the common peaks and attribute them. The fingerprints of Yinhua Miyanling tablets were investigated using chemometrics, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis in combination with SPSS 26.0 and SIMCA 14.1 software to identify the major signature components responsible for the differences. The network pharmacology was used to screen and analyze the targets and pathways of Yinhua Miyanling tablets, construct a "drug-component-target-pathway" network diagram, and predict the Q-Marker and core targets of Yinhua Miyanling tablets. RESULTS HPLC fingerprint of Yinhua Miyanling tablets was established, and 27 common peaks including chlorogenic acid, mangostin, wild baicalin, lignocerin and quercetin were identified. Chemical pattern recognition analysis screened five components as differential markers for Yinhua Miyanling tablets. Five active ingredients, 20 core targets and 20 key pathways were screened by network pharmacology, showing that all five active ingredients could be used as potential Q-Markers. CONCLUSION The method is stable, accurate and feasible for screening five chemical components as potential Q-Markers for Yinhua Miyanling tablets. It provides a reference for the overall control of the quality of Yinhua Miyanling tablets, and also lays the foundation for further research on the mechanism of action of Yinhua Miyanling tablets.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

An etiological analysis of a diarrhea outbreak attributed to C.perfringens was conducted.Anal swab and envi-ronmental smear samples were collected and subjected to fluorescence PCR detection of C.perfringens plc and cpe,as well as isolation and culture of C.perfringens before and after enrichment culture.The isolated colonies underwent fully automated bi-ochemical identification and time-of-flight mass spectrometry analysis.Whole genome sequencing of isolates identified as C.perfringens was performed to analyze the strain carrying virulence and resistance genes,and the genetic aggregation based on single nucleotide polymorphisms in the core genome for all isolates.The positivity rates for plc and cpe genes without bacterial enhancement were 46.15％(6/13)and 53.85％(7/13),respectively.The positivity rates for plc and cpe genes after 24 h anae-robic bacterial enhancement in BHI were 38.46％(5/13)and 53.85％(7/13).All ten isolated CP belonged to the F biotype,with virulence gene characteristics of plc+/cpb-/etx-/iA-/cpe+/cpb2+/netB-.The phylogenomic tree indicated that all ten case-patient isolates except P1 isolate(lineage 1)were closely related and clustered together in a single clade(lineage 2).Lineage 1 belonged to ST589 and carried the macrolide re-sistance gene erm(Q),whereas lineage 2 belonged to ST149 and carried the tetracycline resistance gene tetB(P).The outbreak was caused by type F C.perfringens,and most ca-ses were infected with a group of highly clonogenic cpe+col-onies.Whole genome sequencing technology can be applied to etiology analysis of C.perfringens outbreak events,and the enrichment culture and molecular screening methods for C.per-fringens based on anal swab samples should be further developed and applied.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.
Animals ; Aspergillus nidulans ; Polyketides/chemistry* ; Anthozoa/microbiology* ; Anti-Infective Agents/pharmacology* ; Alkaloids

Objective:To investigate the expression of soluble CD40 ligand (sCD40L) in serum of children with Kawasaki disease at acute stage and its diagnostic value in coronary artery disease (CAL).Methods:This study adopts case-control study method. Select 127 children with Kawasaki disease admitted to Xuzhou Children's Hospital affiliated to Xuzhou Medical University from August 2021 to August 2022. They are divided into CAL group and non-CAL group according to the degree of coronary artery involvement. Select 30 healthy children who have physical examination in this hospital at the same time as the healthy control group, and select another 30 children with acute upper respiratory tract infection and fever admitted to this hospital at the same time as the fever control group.Compare the sex, age and laboratory indicators of children with Kawasaki disease with or without CAL, and compare the difference between the serum sCD40L level of children with Kawasaki disease with or without CAL and the fever control group and the healthy control group, the serum sCD40L level of children with different degrees of coronary artery dilation, and analyze the correlation between the serum sCD40L and various laboratory indicators of children with Kawasaki disease and the influencing factors of children with Kawasaki disease complicated with CAL, To evaluate the screening effect of serum sCD40L for Kawasaki disease complicated with CAL. The measurement data with normal distribution is expressed by xˉ± s, the comparison between the two groups adopts independent sample t-test, the comparison between multiple groups adopts one-way ANOVA, and the comparison between two groups adopts LSD method and Bonferroni correction; The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison between the two groups is conducted by Mann-Whitney U test. Pearson method and Spearman mothod were used for correlation analysis. Logistic regression model was used to analyze the influencing factors of children with Kawasaki disease complicated with CAL. The diagnostic value of serum sCD40L level in Kawasaki disease complicated with CAL was analyzed by drawing the ROC curve. Results:All 127 children with Kawasaki disease were divided into CAL group (45 cases) and non-CAL group (82 cases) according to the presence or absence of CAL. The serum level of sCD40L in CAL group was higher than that in non-CAL group, healthy control group and fever control group ((7.03±0.91) μg/L vs (4.66±1.23), (1.73±0.96), (2.21±1.08) μg/L), the difference was statistically significant (all P<0.001). The serum level of sCD40L in children with coronary artery dilation in CAL group was lower than that in children with small CAA, medium CAA and large CAA ((6.04±0.22) μg/L vs (6.95±0.69), (8.02±0.57), (8.23±0.26) μg/L), the difference was statistically significant (all P<0.001). Serum sCD40L level and platelet count (PLT), C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF-α) in children with Kawasaki disease All were positively correlated ( r=0.31, P<0.001, r=0.32, P<0.001, r=0.26, P=0.003, r=0.58, P<0.001, r=0.27, P=0.002, r=0.39, P<0.001). Serum sCD40L, IL-6 and NT-proBNP were the risk factors of complicated CAL in children with Kawasaki disease (odds ratio 1.21, 1.06 and 1.01, 95% confidence interval 1.03-1.43, 1.01-1.12, 1.00-1.01, P values were 0.022, 0.011 and 0.039, respectively). The area under the curve of serum sCD40L in diagnosing Kawasaki disease complicated with CAL was 0.928 (95% confidence interval: 0.885-0.971), and the optimal critical value was 5.60 μg/L, the sensitivity was 97.8% and the specificity was 79.3%. Conclusions:The level of serum sCD40L increased in children with Kawasaki disease in acute phase, especially in children with CAL. The level of serum sCD40L increased with the severity of CAL, which is a risk factor for Kawasaki disease complicated with CAL, and has certain diagnostic value for Kawasaki disease complicated with CAL.