Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective To investigate the protective effect of high-altitude hypoxia acclimatization against hepatic ischemia-reperfusion injury(HIRI)in rats,as well as the mechanism of action of high-altitude hypoxia acclimatization in activating autophagy.Methods A total of 56 male Sprague-Dawley rats were randomly divided into plain sham-operation group(P-S group),plain model group(P-M group),acute high-altitude hypoxia sham-operation group(AHH-S group),acute high-altitude hypoxia model group(AHH-M group),high-altitude hypoxia acclimatization sham-operation group(HHA-S group),high-altitude hypoxia acclimatization model group(HHA-M group),and high-altitude hypoxia acclimatization model group with the adenosine monophosphate-activated protein kinase(AMPK)inhibitor compound C(HHA-M-CC group),with 8 rats in each group.The rats in the acute high-altitude hypoxia groups and the high-altitude hypoxia acclimatization groups were placed in a low-pressure oxygen chamber at an altitude of 5 000 meters for 1 week and 12 weeks,respectively;the rats in the sham-operation groups were given laparotomy to expose the portal vein without vascular clamping;the rats in the HHA-M-CC group were given abdominal injection of 20 mg/kg CC at 1 hour before surgery,while those in the other groups were given injection of an equal volume of normal saline.An automatic biochemical analyzer was used to measure the levels of liver function parameters including alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil);HE staining was used to observe liver histopathological changes;transmission electron microscopy was used to observe the formation of autophagosomes in liver tissue;RT-qPCR was used to measure the mRNA expression levels of AMPK and Unc-51 like autophagy activating kinase 1(ULK1)in liver tissue;Western Blot was used to measure the protein expression levels of phosphorylated AMPK(p-AMPK),phosphorylated ULK1(p-ULK1),Beclin-1,and microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ).An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was sued for comparison between two groups.Results Compared with the AHH-M and HHA-M-CC groups,the HHA-M group had significantly reductions in the levels of ALT,AST,and TBil(all P<0.05),alleviation of liver histopathological injury,a significant reduction in Suzuki score(all P<0.05),a reduction in the degree of abnormal morphological structure of hepatocytes under transmission electron microscopy,and significant increases in the number of autophagosomes,the mRNA expression levels of AMPK and ULK1(all P<0.05),and the protein expression levels of p-AMPK,p-ULK1,Beclin-1,and LC3Ⅱ(all P<0.05).Conclusion High-altitude hypoxia acclimatization can alleviate HIRI in SD rats by activating the AMPK/ULK1 signaling pathway and enhancing autophagy in hepatocytes.

Objective To investigate the protective effect of high-altitude hypoxia acclimatization against hepatic ischemia-reperfusion injury(HIRI)in rats,as well as the mechanism of action of high-altitude hypoxia acclimatization in activating autophagy.Methods A total of 56 male Sprague-Dawley rats were randomly divided into plain sham-operation group(P-S group),plain model group(P-M group),acute high-altitude hypoxia sham-operation group(AHH-S group),acute high-altitude hypoxia model group(AHH-M group),high-altitude hypoxia acclimatization sham-operation group(HHA-S group),high-altitude hypoxia acclimatization model group(HHA-M group),and high-altitude hypoxia acclimatization model group with the adenosine monophosphate-activated protein kinase(AMPK)inhibitor compound C(HHA-M-CC group),with 8 rats in each group.The rats in the acute high-altitude hypoxia groups and the high-altitude hypoxia acclimatization groups were placed in a low-pressure oxygen chamber at an altitude of 5 000 meters for 1 week and 12 weeks,respectively;the rats in the sham-operation groups were given laparotomy to expose the portal vein without vascular clamping;the rats in the HHA-M-CC group were given abdominal injection of 20 mg/kg CC at 1 hour before surgery,while those in the other groups were given injection of an equal volume of normal saline.An automatic biochemical analyzer was used to measure the levels of liver function parameters including alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil);HE staining was used to observe liver histopathological changes;transmission electron microscopy was used to observe the formation of autophagosomes in liver tissue;RT-qPCR was used to measure the mRNA expression levels of AMPK and Unc-51 like autophagy activating kinase 1(ULK1)in liver tissue;Western Blot was used to measure the protein expression levels of phosphorylated AMPK(p-AMPK),phosphorylated ULK1(p-ULK1),Beclin-1,and microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ).An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was sued for comparison between two groups.Results Compared with the AHH-M and HHA-M-CC groups,the HHA-M group had significantly reductions in the levels of ALT,AST,and TBil(all P<0.05),alleviation of liver histopathological injury,a significant reduction in Suzuki score(all P<0.05),a reduction in the degree of abnormal morphological structure of hepatocytes under transmission electron microscopy,and significant increases in the number of autophagosomes,the mRNA expression levels of AMPK and ULK1(all P<0.05),and the protein expression levels of p-AMPK,p-ULK1,Beclin-1,and LC3Ⅱ(all P<0.05).Conclusion High-altitude hypoxia acclimatization can alleviate HIRI in SD rats by activating the AMPK/ULK1 signaling pathway and enhancing autophagy in hepatocytes.

A patient was admitted to hospital due to umbilical pain.Gram-staining presented short,positive coc-cobacillus in the purulent secretions from the umbilical cord of the patient.Meanwhile,matrix-assisted laser desorp-tion/ionization time-of-flight mass spectrometry(MALDI-TOF MS),16S rRNA detection,and in vitro antimicro-bial susceptibility testing were performed on the isolated strains.Corynebacterium tuberculostearicum was identified by Gram-staining,MALDI-TOF MS and 16S rRNA.Antimicrobial susceptibility testing results showed that the strain was sensitive to penicillin,ceftriaxone,cefepime,meropenem,vancomycin,daptomycin,linezolid,compound sulfamethoxazole,ampicillin,gentamicin and tetracycline.Smear of microorganisms is helpful for the identification of Corynebacterium tuberculostearicum morphology,and MALDI-TOF MS is necessary for rapid identification of strains.Antimicrobial susceptibility testing can also assist the empirical treatment for infection due to this strain.

Objective:To investigate the dynamic changes of diaphragm and limb skeletal muscle in patients with sepsis by bedside ultrasound and their correlation with the ratio of blood urea/creatinine ratio (UCR) in 7 days after intensive care unit (ICU) admission.Methods:A prospective observational study was conducted. A total of 55 patients with sepsis admitted to ICU of General Hospital of Ningxia Medical University from June 2022 to February 2023 were selected as the research objects. General information, laboratory indicators [urea, serum creatinine (SCr), and UCR] on days 1, 4, and 7 of ICU admission, and prognostic indicators were observed. Bedside ultrasound was used to assess the dynamic changes of diaphragm morphology [including diaphragmatic excursion (DE), end-inspiratory diaphragm thickness (DTei), and end-expiratory diaphragm thickness (DTee)] on days 1, 4, and 7 of ICU admission, as well as limb skeletal muscle (quadriceps femoris) morphology [including rectus femoris-muscle layer thickness (RF-MLT), vastus intermedius-muscle layer thickness (VI-MLT), and rectus femoris-cross sectional area (RF-CSA)]. Diaphragm thickening fraction (DTF) and RF-CSA atrophy rate were calculated, and the incidence of diaphragm and limb skeletal muscle dysfunction was recorded. The correlation between ultrasound morphological parameters of diaphragm and quadriceps and UCR at each time points in 7 days after ICU admission was analyzed by Pearson correlation.Results:A total of 55 patients with sepsis were included, of which 29 were in septic shock. As the duration of ICU admission increased, the incidence of diaphragm dysfunction in patients with sepsis increased first and then decreased (63.6%, 69.6%, and 58.6% on days 1, 4, and 7 of ICU admission, respectively), while the incidence of limb skeletal muscle dysfunction showed an increasing trend (54.3% and 62.1% on days 4 and 7 of ICU admission, respectively), with a probability of simultaneous occurrence on days 4 and 7 of ICU admission were 32.6% and 34.5%, respectively. The UCR on day 7 of ICU admission was significantly higher than that on day 1 [121.77 (95.46, 164.55) vs. 97.00 (70.26, 130.50)], and RF-CSA atrophy rate on day 7 was significantly higher than that on day 4 [%: -39.7 (-52.4, -22.1) vs. -26.5 (-40.2, -16.4)]. RF-CSA was significantly lower on day 7 compared to day 1 [cm 2: 1.3 (1.0, 2.5) vs. 2.1 (1.7, 2.9)], with all differences being statistically significant (all P < 0.05). Pearson correlation analysis showed that RF-CSA on day 7 of ICU admission was negatively associated with the UCR on the same day ( r = -0.407, P = 0.029). Conclusions:Diaphragmatic dysfunction in patients with sepsis occurred early and can be improved. Limb skeletal muscle dysfunction occurred relatively later and progresses progressively. The RF-CSA on day 7 of ICU admission may be a reliable measure of limb skeletal muscle dysfunction in patients with sepsis, can be an indicator of early identification and diagnosis of ICU-acquired weakness (ICU-AW). Continuous loss of muscle mass occurring in septic patients is mainly associated with persistent organismal catabolism, and undergoes significant changes around a week in ICU.

One patient was admitted to a hospital due to"sepsis,chronic kidney disease,type 2 diabetes,shock,and cerebral infarction".Patient's blood specimen was taken for clinical examination.Aerobic and anaerobic culture results of catheter blood and venous blood were both positive.The pathogen was identified as Staphylococcus pas-teuri by VITEK MS,and the patient was diagnosed as catheter-related bloodstream infection caused by Staphylo-coccus pasteuri.Clinical empirical use of piperacillin for anti-infection treatment was ineffective,and vancomycin was eventually used for treatment based on in vitro antimicrobial susceptibility testing.Patient's condition improved after removing the venous catheter.There are currently no reported cases of Staphylococcus pasteuri in China.Ear-ly identification of pathogen and adjustment of treatment plans based on antimicrobial susceptibility testing results are crucial for effective treatment of this case.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Corydalis Rhizoma is a commonly used traditional Chinese medicine(TCM) for regulating Qi and relieving pain in clinical practice, with remarkable efficacy. However, its pharmacodynamic substances are not yet fully understood and require further research. In this study, 24 compounds were isolated and identified from the aqueous extracts of vinegar-processed Corydalis Rhizoma using techniques such as macroporous adsorption resin column chromatography, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Their structures were determined based on their physicochemical properties and spectroscopic methods, including UV, IR, HR-MS, 1D NMR, and 2D NMR. Among these, compounds 1 and 2 are two rare natural α-carbonamide alkaloids, named yanhuoxamide A(compound 1) and yanhuoxamide B(compound 2), respectively. Compounds 3-24 are known compounds, identified as xanthoplanine(3), stigmast-4-ene-3,6-dione(4), norchelerythrine(5), ethyl ferulate(6), 6-hydroxymethyl-3-pyridinol(7), 6-(\[1,3\]dioxolo\[4,5-g\]isoquinoline-5-carbonyl)-2,3-dimethoxy-benzoic acid methyl ester(8), 1H-indole-3-carbaldehyde(9), 4-hydroxy-3-methoxy ethyl cinnamate(10), berberal(11), oblongine trifluoroacetate(12), thalbaicalidine(13), cyclopiamide(14), nicotinamide(15), dehydrocorypalline trifluoroacetate(16), 6-acetonyldihydrochelerythrine(17), 6-acetonyldihydrosanguinarine(18), norsanguinarine(19), oxysanguinarine(20), bulbocapnine(21), corydine(22),(-)-(13aS)-stylopine(23), and(-)-(9S,13S)-pallidine(24). Among these, compounds 3-15 were isolated from the genus Corydalis for the first time, and compounds 16-24 were isolated from Corydalis Rhizoma for the first time. Additionally, the inhibitory activity of compounds 1 and 2 on acetylcholinesterase(AChE) was evaluated.
Corydalis/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Molecular Structure ; Amides/chemistry* ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid ; Alkaloids/chemistry*