A 42-year-old male with chest tightness and dyspnea was admitted to the hospital. Chest CT indicated diffuse interstitial lung infiltration. Despite receiving anti-infective therapy, glucocorticoid therapy, and immunosuppressive agents, the patient developed refractory hypoxaemia. Endotracheal intubation and invasive mechanical ventilation failed to improve oxygenation. Therefore the patient was diagnosed with rapidly progressive interstitial lung disease (RP-ILD) accompanied by type Ⅰ respiratory failure. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated, and oxygenation improved in this patient. The patient subsequently underwent bilateral lung transplantation with veno-arterio-venous (VAV) ECMO support. ECMO machine was withdrawn on day 1, and extubation was achieved on day 9 after surgery. Histopathology revealed fibrotic nonspecific interstitial pneumonia (NSIP) with hyaline membrane formation. The patient developed ICU-acquired myasthenia and received early rehabilitation, with gradual recovery of muscle strength. During follow-up, graft lung function remained stable. This case demonstrates that ECMO can serve as a bridge to lung transplantation in RP-ILD patients.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

The interstitial cells of Cajal (ICC) generate spontaneous pacemaker activities responsible for producing slow waves in the gut smooth muscles. Prostaglandin E2 (PGE2 ) is one of the most important prostanoids in the gut, playing a crucial role in multiple physiological and pathological processes. Because information regarding the effects of PGE2 on colonic ICC is limited, we investigated the effects of PGE2 and its underlying signaling pathways in murine colonic ICC. Whole-cell patch-clamp recordings and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to evaluate the effects of PGE2 on mouse colonic ICC. PGE2 had a dual effect on pacemaker potential in the current-clamp mode. RT-PCR data suggested the expression of EP3 and EP4 receptors in colonic ICC. Low PGE2 concentrations induced membrane depolarization and generation of pacemaker activities. And this effect is mimicked by sulprostone (an EP3 agonist). The low PGE2 concentration-induced effect was inhibited by anoctamin-1 (ANO1) or a T-type Ca2+ channel blocker. Conversely, high PGE2 concentrations induced membrane hyperpolarization and blocked pacemaker potential generation. However, this inhibitory effect was blocked by an ATP-sensitive potassium (K ATP) channel blocker but not by other K+ channel blockers. Low concentrations of PGE2 activated EP3 receptors, leading to excitation of pacemaker activity through regulation of ANO1 and T-type Ca2+ channels in colonic ICC. In contrast, higher concentrations of PGE2 activated EP4 receptors and opened ATP-sensitive K+ channels, resulting in inhibition of pacemaker activity in colonic ICC.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective: To investigate the feasibility of magnetic anastomosis for uretero-ileal anastomosis using experimental rabbit models. Methods: Six experimental rabbits were used as the models.The lower part of the left ureter was cut with scissors，the daughter magnet (DM) was placed in the middle of the ureter，and the distal end of the ureter was ligated.After that，the ileum wall was opened，the parent magnet (PM) was inserted through it，the positions of the PM and DM were adjusted so that their ends were attracted to each other，and then ileum wall incision was sutured.The operation time，intraoperative blood loss，postoperative complications and magnet discharge time were recorded.Two weeks after operation，left ureterography was performed to obtain the specimens of the uretero-ileal anastomosis，and to observe the patency of the anastomosis.The formation of the anastomosis was observed with naked eyes and light microscope. Results: Uretero-ileal magnetic anastomosis was performed successfully in 6 experimental rabbits.The operation time was 28-39（32.50±3.94） min，and the intraoperative blood loss was less than 5 mL.The rabbits recovered well after operation，and no complications were observed.All animals survived to the end point of observation.The disconnection time of magnet after operation was 9-13(10.83±1.72) days.The gross specimen showed that the anastomosis was patent.The histological observation showed that the mucosa of the anastomosis was continuous and smooth，and the anastomosis was well formed. Conclusion: Magnetic anastomosis is feasible for uretero-ileal anastomosis with simple operation and good anastomosis formation.After further experimental verification，this technique is expected to be used in clinical practice.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

Objective To explore the relationship between axillary artery and axillary vein by combining computed tomography angiography computed tomography angiography(CTA)and computed tomography venography(CTV),and to provide imaging data for establishing an effective blood circulation pathway for vascular injury in clinical transaxillary surgery.Methods The image data of 30 patients who underwent left upper limb and axillary CTA and CTV at the same time were collected.After three-dimensional reconstruction of the images by GE AW4.6 workstation,the course,branch type and variation of axillary artery,the course of axillary vein,the reflux of subordinate branches and the relationship between axillary artery and axillary vein were observed.The length of the whole segment,the length of segment and the inner diameter of the starting point of each segment were measured and statistically analyzed.Results According to the number of branches from the main trunk,the axillary artery was divided into 7 types.According to the variation of the number of blood vessels,the axillary vein was divided into 5 types;The unknown vein branches converge into 32 branches,of which the first segment accounted for 37.5％,the second segment accounted for 46.9％,and the third segment accounted for 15.6％.According to the absence of arterial branches,the relationship between axillary artery and axillary vein was divided into 2 types.Conclusion There are many types of branches of axillary arteries and branches of axillary veins,and the variation types are complex.The changes of branches of axillary arteries affect the distribution of branches of axillary veins.Combined with CTA and CTV images,the relationship between axillary vessels can be reflected clearly and intuitively,which can provide imaging reference for the establishment of new ways of blood supply and reflux in clinical axillary treatment.

Objective To evaluate the feasibility of establishing canine rectovaginal fistula ani-mal model using magnetic surgery techniques.Methods Ten female Beagle dogs were randomly di-vided into study group(n=5)and control group(n=5).The study group underwent rectovaginal fistula modeling using magnetic surgery technology,while the control group was subjected to sharp puncture of the rectovaginal septum followed by indwelling rubber tube placement to establish the model.Surgical procedure duration and postoperative adverse events were recorded in both groups.Two weeks later,the magnets and rubber tubes were removed.The formation of rectovaginal fistulas in the animals of two groups was observed,and the success rates of model construction of two groups were statistically analyzed.Results Both groups successfully completed the preparation of the recto-vaginal fistula models.The operative time in both groups was less than 2 minutes.No adverse events such as magnet detachment were observed in the study group during the postoperative period.In the control group,the rubber tube dislodged on day 6 post-surgery in one dog,leading to spontaneous healing of the fistula.Two weeks after surgery,the magnets and rubber tubes were removed.Naked-eye observation showed that the rectovaginal fistula formed well in the experimental dogs of the study group,while the rectovaginal fistula formed well in 4 experimental dogs in the control group.The success rate of model construction in the study group was 100％,and was 80％in the control group.Conclusion The construction of a canine rectovaginal fistula model by magnetosurgical techniques has the advantages of simple operation and high success rate.Magnetosurgical techniques may serve as an ideal animal model for constructing and studying the histopathological changes and treatment methods of rectovaginal fistulas.