Objective:To investigate the differences between high-frequency ultrasound-guided manual detorsion combined with surgery(MD+S)and surgery alone in the treatment of testicular torsion,and to provide some new evidence for the timely diagno-sis and treatment of the disease.Methods:We retrospectively analyzed the clinical data on 134 cases of unilateral testicular torsion within 48 hours treated in our hospital by MD+S or by surgery alone from January 2015 to May 2022.We statistically analyzed the age distribution,and duration and degrees of testicular torsion,followed by comparison between the two groups.Results:In the 134 ca-ses,the median age of onset was 15(13-19)years old,the median onset-to-visit time was 15(8-25)hours,and the median de-gree of torsion was 360°(180°-1080°).Of the total number of patients,21 underwent testicular excision and the other 113 were treated with the testis preserved,with no statistically significant difference in age distribution between the two groups(P＞0.05),and a higher rate of testis resection in those with longer duration and greater angle of torsion(P＜0.05).Totally,33 of the patients were assigned to the MD+S group and 101 to the surgery alone group.According to the actual clinical conditions and excluding those with torsion time longer than 24 hours and torsion angle greater than 720 °,28 of the patients underwent ultrasound-guided MD+S(with 1 case of testis resection,3.6％),and 68 received surgery alone(with 7 cases of testis resection,10.3％).The rate of testis resection was higher in the surgery alone than that in the MD+S group,but with no statistically significant difference between the two groups(P＞0.05),which was considered to be related to the small sample size in this study.Conclusion:The popularization of testicular torsion knowledge can shorten the onset-to-visit time,and reasonable manual detorsion before emergency surgery can reduce the rate of testis resection.

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Background: Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. Objective: To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. Methods: A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. Results: LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. Conclusion BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Glycosylation is one of the most important reactions in living organisms as it results in the formation of glycoconjugates with diverse biological functions. Sugar nucleotides are structurally composed of sugar and nucleoside diphosphate or monophosphate, which are widespread within a variety of biological cells. As glycosyl donors for the transglycosyl reactions catalyzed by Leloir-type glycosyltransferases, sugar nucleotides are essential for the synthesis of glycans and glycoconjugates. However, high costs and limited availability of nucleotide sugars prevent applications of biocatalytic cascades on an industrial scale. Therefore, attentions on synthetic strategies of sugar nucleotides have been increasing to achieve their wide applications in various fields. The 9 common sugar nucleotides in mammals have been fully studied with large-scale synthesis through chemical, enzymatic (chemo-enzymatic) and cell factory strategies. In addition to common sugar nucleotides, many rare sugar nucleotides are present in plants and bacteria. Although unnatural sugar nucleotides cannot be synthesized in organisms, they have great potential in research as substrates for glycosyltransferases in carbohydrate synthesis, as enzyme inhibitors in biochemical studies, and as components of glycoconjugate biosynthesis. Therefore, increasing attention has been paid to explore the efficient synthesis of unnatural sugar nucleotides. Currently, strategies for chemical synthesis of sugar nucleotides have been greatly improved, such as the use of effective catalysts for forming pyrophosphate bonds and the development of entirely new synthesis protocols. Multiple sugar nucleotides, especially unnatural sugar nucleotides, are synthesized chemically. However, chemical synthesis requires tedious protection and deprotection steps, resulting in complex steps, high cost and low yield. In contrast, enzymatic (chemo-enzymatic) and cell factory methods have significant advantages such as high yield, easy operation and easy process scale-up in the preparation of sugar nucleotides. Hence, they are prominent strategies for sugar nucleotide preparation. Herein, the biosynthesis and application of sugar nucleotides are reviewed, mainly focusing on the 9 sugar nucleotides common in mammals. The early strategies for enzymatic synthesis of sugar nucleotides generally used de novo synthesis pathway. With the discoveries of enzymes involved in salvage pathway of sugar nucleotide synthesis and the development of one-pot multienzyme (OPME) method, the synthesis of sugar nucleotides was greatly simplified. Cell factory method employs the microbial living cells as a “processing plant” by engineering their metabolic pathways through genetic engineering technology. The cell factory method has high yield, and has been applied for efficient synthesis of several sugar nucleotides. Moreover, the strategy of gram-scale synthesis of multiple rare sugar nucleotides by cascade reactions from common sugar nucleotides using sugar nucleotides synthases cloned from different sources was illustrated. In recent years, the synthesis cost of sugar nucleotides has been further reduced through various ways, such as regeneration of nucleotides, regeneration of organic cofactors, and application of immobilized enzyme technology. Furthermore, through the continuous improvement of sugar nucleotide purification process, the use of high concentration of multi-enzyme cascade and rapid non-chromatographic purification process, the synthesis of multiple sugar nucleotides and their derivatives from monosaccharides was achieved, which gradually broke the limitations of the existing strategy. With the efficient synthesis of sugar nucleotides, their applications in various fields have been increasingly explored, including the synthesis of glycans and glycoconjugates, biochemical characterization of glycosyltransferases and bioorthogonal labeling strategies, which are of great significance to the research of biochemistry, glycobiology and the development of related pharmaceutical products.

AIM To study the neoflavonoids from Dalbergia cochinchinensis Pierre ex Laness and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells.METHODS The 70%ethanol extract from D.cochinchinensis was isolated and purified by silica gel,Sephadex LH-20 and reverse-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The CCK-8 method was used to detect their activities on H9c2 cells and protective effects on hypoxia-reoxygenation injury of H9c2 cells,and their structure-activity relationship was analyzed.RESULTS Twelve compounds were isolated and identified as latifolin(1),5-O-methyllatifolin(2),mimosifoliol(3),5-O-methydalbergiphenol(4),dalbergiphenol(5),cearoin(6),2,4-dihydroxy-5-methoxy-benzophenone(7),2-hydroxy-4,5-dimethoxybenzophenone(8),melannoin(9),2,2′,5-trihydroxy-4-methoxybenzophenone(10),dalbergin(11),4-methoxydalbergione(12).The dalbergiphenols and dalbergins had little toxicity to H9c2 cells,and dalbergiphenols had strong activity against hypoxia-reoxygenation injury of H9c2 cells.CONCLUSION Compound 8 is a new natural product.Compounds 4,9 are isolated from this plant for the first time.Dalbergiphenols may be the main neoflavonoids against hypoxia-reoxygenation injury of H9c2 cells.

AIM To compare the volatile constituents from the rhizomes and fibrous roots of Atractylodes lancea (Thunb.) DC..METHODS Paraffin sections of rhizomes and fibrous roots were made,and their transverse sections were observed under an optical microscope.Volatile oil was extracted by hydrodistillation.The contents of atractylodin,β-eudesmol,hinesol and atractyline were detected by GC-MS,and the volatile constituents were analysed.Principal component analysis and differential metabolite screening were performed by multivariate statistical analysis software.RESULTS In the transverse section of rhizomes,large oil chambers were observed,while oil cells were found in the fibrous roots.The volatile oil content in the fibrous roots is 24.88％ of that in the rhizomes.A total of 55 common components,2 unique components of rhizomes and 6 unique components of fibrous roots were detected.The ratio of β-eudesmol,hinesol,atractyline and atractylodin in the rhizomes was 22.84∶1.16∶2.78∶1.00,while that in the fibrous roots was 5.59∶0.22∶0.97∶1.00.The volatile constituents in the rhizomes were significantly different from those in the fibrous root,and the groups were well discriminated from each other.Based on the OPLS-DA model,12 differential metabolites including hinesol and β-eudesmol were screened.CONCLUSION The volatile constituents of the rhizomes and fibrous roots of A.lancea are similar,but the contents are different,and the latter has a greater potential for comprehensive utilization.

AIM To compare the volatile constituents from the rhizomes and fibrous roots of Atractylodes lancea (Thunb.) DC..METHODS Paraffin sections of rhizomes and fibrous roots were made,and their transverse sections were observed under an optical microscope.Volatile oil was extracted by hydrodistillation.The contents of atractylodin,β-eudesmol,hinesol and atractyline were detected by GC-MS,and the volatile constituents were analysed.Principal component analysis and differential metabolite screening were performed by multivariate statistical analysis software.RESULTS In the transverse section of rhizomes,large oil chambers were observed,while oil cells were found in the fibrous roots.The volatile oil content in the fibrous roots is 24.88％ of that in the rhizomes.A total of 55 common components,2 unique components of rhizomes and 6 unique components of fibrous roots were detected.The ratio of β-eudesmol,hinesol,atractyline and atractylodin in the rhizomes was 22.84∶1.16∶2.78∶1.00,while that in the fibrous roots was 5.59∶0.22∶0.97∶1.00.The volatile constituents in the rhizomes were significantly different from those in the fibrous root,and the groups were well discriminated from each other.Based on the OPLS-DA model,12 differential metabolites including hinesol and β-eudesmol were screened.CONCLUSION The volatile constituents of the rhizomes and fibrous roots of A.lancea are similar,but the contents are different,and the latter has a greater potential for comprehensive utilization.

Objectives:To explore the dynamic changes of right ventricular global longitudinal strain (RVGLS) on echocardiography during the process of right ventricular fibrosis with right ventricular pressure overload.Methods:Animal models with RV pressure overload (n=5) were established by main pulmonary artery (PA) banding in piglets.The ratio of RV pressure to left ventricular (LV) pressure was greater than 60％ as assessed by the pressure measuring needle during the operation.Pre-and post-operative echocardiography were performed.Histopathological examination of RV tissues was performed at the end of the experiment.Results:During the establishment of the animal models,2 piglets died due to hemorrhagic shock,while 3 piglets survived and were included in the analysis.Systolic RV pressure,systolic PA pressure and mean PA pressure(measured at the proximal end of the constriction) were significantly increased immediately after PA banding,mean RV pressure and mean PA pressure were significantly inreased at 14 weeks postopseratively (all P<0.05).Tricuspid annulus plane systolic excursion and peak early diastolic velocity of tricuspid annulus (TV e') decreased immediately after operation (all P<0.05).They returned to the pre-operative level in the following three weeks.The absolute values of RVGLS were reduced after PA banding (all P>0.05).The RVGLS of the inner membrane layer began to recover after 3 weeks,and the RVGLS of the middle and outer membrane layers began to recover after 7 weeks.However,the time to peak RVGLS was significantly prolonged and could not be restored even untill the end of the experiment (14 weeks after surgery)(all P<0.05).At the end of the experiment,pathological examination revealed fibrous tissue hyperplasia in both the myocardial interstitium and endocardium.Conclusions:The measurement of intracardiac pressure and pathological results confirmed the success of the establishment of the animal model of increased right ventricular afterload.Both stress and strain cannot truly represent the intrinsic characteristics of the myocardium under pressure overload.The prolonged time to peak of longitudinal strain might indirectly reflect the progression of myocardial injury more persistently during the process of increased right ventricular afterload and myocardial injury.

Objectives:To explore the dynamic changes of right ventricular global longitudinal strain (RVGLS) on echocardiography during the process of right ventricular fibrosis with right ventricular pressure overload.Methods:Animal models with RV pressure overload (n=5) were established by main pulmonary artery (PA) banding in piglets.The ratio of RV pressure to left ventricular (LV) pressure was greater than 60％ as assessed by the pressure measuring needle during the operation.Pre-and post-operative echocardiography were performed.Histopathological examination of RV tissues was performed at the end of the experiment.Results:During the establishment of the animal models,2 piglets died due to hemorrhagic shock,while 3 piglets survived and were included in the analysis.Systolic RV pressure,systolic PA pressure and mean PA pressure(measured at the proximal end of the constriction) were significantly increased immediately after PA banding,mean RV pressure and mean PA pressure were significantly inreased at 14 weeks postopseratively (all P<0.05).Tricuspid annulus plane systolic excursion and peak early diastolic velocity of tricuspid annulus (TV e') decreased immediately after operation (all P<0.05).They returned to the pre-operative level in the following three weeks.The absolute values of RVGLS were reduced after PA banding (all P>0.05).The RVGLS of the inner membrane layer began to recover after 3 weeks,and the RVGLS of the middle and outer membrane layers began to recover after 7 weeks.However,the time to peak RVGLS was significantly prolonged and could not be restored even untill the end of the experiment (14 weeks after surgery)(all P<0.05).At the end of the experiment,pathological examination revealed fibrous tissue hyperplasia in both the myocardial interstitium and endocardium.Conclusions:The measurement of intracardiac pressure and pathological results confirmed the success of the establishment of the animal model of increased right ventricular afterload.Both stress and strain cannot truly represent the intrinsic characteristics of the myocardium under pressure overload.The prolonged time to peak of longitudinal strain might indirectly reflect the progression of myocardial injury more persistently during the process of increased right ventricular afterload and myocardial injury.