Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m². Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression. Through pharmacologically probing the function of epigenetic regulators in prostate cancer cells and organoids, we identified bromodomain protein BRD4 as a crucial player. Integrated ChIP-seq and RNA-seq analysis of tumors revealed, for the first time, that BRD4 directly activates hundreds of genes in the LP programs which include neurogenesis, axonogenesis, EMT and stem cells and key drivers such as POU3F2 (BRN2), ASCL1/2, NeuroD1, SOX2/9, RUNX1/2 and DLL3. Interestingly, BRD4 genome occupancy is reprogrammed by anti-AR drugs from facilitating AR function in CRPC cells to activating the LP programs and is facilitated by pioneer factor FOXA1. Significantly, we demonstrated that BRD4 inhibitor AZD5153, currently at clinical development, possesses potent activities in complete blockade of tumor growth of both de novo neuroendocrine prostate cancer (NEPC) and treatment-induced NEPC PDXs and that suppression of tumor expression of LP programs through reduction of local chromatin accessibility is the primary mechanism of action (MOA) by AZD5153. Together, our study revealed that BRD4 plays a fundamental role in direct activation of tumor LP programs and that its inhibitor AZD5153 is highly promising in effective treatment of the lethal forms of the diseases.

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective To explore the mechanism of electroacupuncture improving myocardial ischemia-reperfusion injury(MIRI),electroacupuncture PC6 Attenuates TRPV1 pathway in spinal cord C5-T6 dorsal root ganglion(DRG)on MIRI rats was observed.Methods After one week of experimental feeding,30 SD rats with normal electrocardiogram were randomly divided into sham-operated group and model group,PC6 group,non-meridian and non-acupuncture group,and PC6+capsaicin(TRPV1 receptor agonist)group,with 6 rats in each group.The MIRI model was prepared by ligation of the left anterior descending(LAD)coronary artery in the other groups.The next day after modeling,electroacupuncture of the"PC6"point in the EA group,electroacupuncture of the caudal"non-meridian non-points"in the the non-meridian non-acupuncture point group,and electroacupuncture of the"PC6"point after intraperitoneal injection of capsaicin in the PC6+capsaicin group,20 min/d for 7 days.ECG was used to record the changes of ST level and LF/HF ratio in rats.Evans blue-TTC double staining and HE staining was used to observe the myocardial infarction area and the changes of myocardial tissue morphology.ELISA was used to detect the levels of serum CK-MB and cTnI.Immunofluorescence staining was used to the phenomenon of sympathetic-sensory coupling with TH-CGRP positive labeling in the DRG of rats.qPCR was to detect the mRNA expression of TRPV1,TH,CGRP,SP,ERK and AKT in rat DRG.Results Compared with the sham-operated group,rats in the model group showed significant higher ST level and LF/HF ratio(both P<0.001),and IA/AAR ratio increased significantly(P<0.0001).Massive inflammatory cell infiltration,serum CK-MB,cTnI levels up-regulated significantly(both P<0.0001).The formation of TH-CGRP-labeled sympathetic budding phenomenon in the DRG and the TRPV1,TH,CGRP in the DRG,SP,ERK,and AKT mRNA expression levels increased significantly(both P<0.01).Compared with the model group,the ECG of the endograft group was significantly improved(both P<0.001).The IA/AAR ratio decreased significantly in PC6 group(P<0.001).The myocardial infarction area reduced significantly(P<0.0001).The levels of serum CK-MB and cTnI down-regulated significantly(both P<0.0001),and the phenomenon of sympathetic sprouting within DRG was not evident,and the DRG of the 6 corresponding mRNA expression decreased significantly(both P<0.01).Compared with the PC6 group,the effect of treatment was not obvious in the non-meridian and non-acupuncture group and PC6+capsaicin group,and the electrocardiogram,IA/AAR ratio,myocardial infarcted area,and serum CK-MB,and cTnI levels did not improve(both P<0.01),and a large number of sympathetic budding phenomena were seen in the DRG.The expression of the mRNA corresponding to the phase of 6 increased significantly(both P<0.01).Conculsion Electroacupuncture PC6 may reduce myocardial injury by inhibiting TRPV1 pathway-mediated sympatheticsprouting in dorsal root ganglia.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective:To construct a temperature-sensitive hydrogel (PF-CA@AS-IV hydrogel) composed of Pluronic F-127 (PF-127)/calcium alginate (CA) loaded with astragaloside IV (AS-IV), and to explore its repair effect and potential mechanism on diabetic skin ulcers (DSU).Methods:The PF-CA@AS-IV hydrogel loaded with AS-IV and gelling at 37 ℃ was prepared. Its temperature sensitivity, rheological properties, and morphology were characterized. A rat model of DSU was established, and the rats were randomly divided into blank control group, model group, AS-IV spray group, PF-CA hydrogel group, and PF-CA@AS-IV hydrogel group ( n=5 each). After 21 days of intervention, the wound healing rate of each group was evaluated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of granulation tissue, and immunohistochemistry was applied to detect the expression level of CD34, a marker of new blood vessels. Results:Rheological analysis showed that the storage modulus (G′) of PF-CA@AS-IV hydrogel began to exceed the loss modulus (G″) at 33 ℃, and a stable three-dimensional network structure was formed at 37 ℃. Scanning electron microscopy confirmed its loose and porous microstructure. Animal experiment results indicated that compared with the blank control group, the model group had a significantly lower wound healing rate, massive infiltration of inflammatory cells, and fewer new capillaries and CD34 expression (all P<0.05). Compared with the model group, each treatment group can promote wound healing, reduce inflammatory infiltration and increase the positive expression of CD34 to varying degrees (all P<0.05), and the curative effect of PF-CA@AS-IV hydrogel group is the most significant, which is better than that of AS-IV spray group and PF-CA hydrogel group (all P<0.05). Conclusions:PF-CA@AS-IV hydrogel can effectively regulate inflammatory response and promote angiogenesis through sustained release of AS-IV, thereby accelerating DSU healing, and has good translational potential in the field of chronic wound repair.

ObjectiveTo explore the potential mechanism of Erchen Decoction （二陈汤， ECD） in improving metabolic syndrome （MS） with phlegm syndrome. MethodsForty mice were randomly divided into a blank group of 10 mice and a modeling group of 30 mice. The MS model with phlegm syndrome was induced in the modeling group by high-fat diet. Thirty successfully modeled mice were randomly divided into a model group， a ECD group， and a metformin group， with 10 mice in each group. The ECD group was given 0.4 g/（kg·d） of ECD， while the metformin group was intervened with 11.1 g/（kg·d） of metformin solution， and the blank group and the model group were given 0.02 ml/（g·d） of sterilized drinking water， all by gavage， once daily for 4 weeks. Body weight， abdominal circumfe-rence， body length， Lee's index and food intake were recorded. Blood glucose and blood lipid levels including fasting blood glucose， triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. ELISA was used to detect serum leptin levels， while HE staining was used to observe liver pathological changes. Western Blot and q-PCR were used to detect protein and mRNA expression of hypothalamic leptin receptor （LepR）， pro melanocortin （POMC）， and neuropeptide Y （NPY） in the hypothalamus. Immunofluorescence was used to detect fluorescence expression of POMC and NPY in the hypothalamic arcuate nucleus region. ResultsPathological results showed that the mice in the model group had numerous fat vacuoles in hepatocytes and significant liver fat deposition， while the ECD and metformin groups showed reduced fat vacuoles and less liver fat deposition. Compared to those in the blank group， the mice in the model group mice showed liver fat deposition， increased body weight， abdominal circumference， Lee's index and food intake； fasting blood glucose， TG， TC， LDL-C， and serum leptin levels were elevated， while HDL-C was decreased； the expression of LepR， POMC protein levels and their mRNA expression decreased， while the protein level and mRNA expression of NPY increased； the fluorescence expression of POMC in the arcuate nucleus was reduced， while NPY fluorescence expression increased （P＜0.05 or P＜0.01）. Compared to the model group， the ECD group and metformin group showed significant improvements in the above indicators （P＜0.05 or P＜0.01）. Compared to the ECD group， the metformin group showed a reduction in body weight and NPY fluorescence expression， and an increase in HDL-C levels （P＜0.05 or P＜0.01）. ConclusionECD can downregulate serum leptin levels and improve glucose and lipid metabolism in the MS of phlegm syndrome. Its mechanism of action may be to reduce liver fat deposition and thereafter affect the expression of neuropeptides related to feeding activity in the hypothalamus.