Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

AIM: To screen the predictors of disease progression risk in patients with diabetic macular edema(DME), establish a joint prediction model and analyze its predictive efficiency.METHODS:A retrospective selection was made of 240 patients with DME who were treated in our hospital from July 2021 to October 2024 as the research subjects. The patients were divided into a low-risk group(n=102)and a high-risk group(n=138)based on the central macular thickness(CMT)and whether the fovea was accumulated. The basic information of the patients and relevant examination data such as glycolipid metabolism indicators and liver and kidney function indicators were collected. The indicators with differences in the univariate analysis(P<0.05)were included in the multivariate analysis to screen out the independent influencing factors of disease progression in DME patients and construct a predictive model. The fitting effect of the prediction model was evaluated by the area under the receiver operating characteristic curve, and the prediction model was verified by sensitivity, specificity and Youden index.RESULTS: The general data of the two groups of patients are comparable, and there was no statistically significant difference in blood pressure between the two groups of patients(both P>0.05). Univariate analysis showed that the glycated hemoglobin(HbA1c), fasting blood glucose(FBG), advanced glycation end products(AGEs), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), serum creatinine(Scr), uric acid(UA), and cystatin C(Cys-C)at 3 and 6 mo in the high-risk group at baseline, 3 and 6 mo were higher than those in the low-risk group(all P<0.01). The baseline, 3 and 6 mo estimated glomerular filtration rate(eGFR), total bilirubin(TBIL), and 3 and 6 mo high-density lipoprotein cholesterol(HDL-C)in the high-risk group were all lower than those in the low-risk group(P<0.05). Regression analysis showed that baseline HbA1c, 3 mo FBG, 3 mo AGEs, baseline LDL-C, 3 mo TG, 3 mo eGFR, baseline TBIL, and 6 mo TBIL were risk factors for disease progression in DME patients. The area under curve(AUC)of the combined prediction model was 0.909(95%CI: 0.872-0.945), with a sensitivity of 79.00% and a specificity of 94.10%.CONCLUSION: HbA1c, FBG, AGEs, LDL-C, TG, eGFR and TBIL are risk factors for the risk of disease progression in patients with DME. The combined prediction model can provide a reference for predicting the risk of disease progression in patients with DME.

A 43-year-old male patient presented with recurrent edema in different anatomical sites for over 10 years, with facial edema worsening 1 day prior to admission. He had been repeatedly admitted to dermatology, general surgery, and emergency departments of external hospitals due to " acute abdomen" and " laryngeal edema, " resistant to antihistamines and glucocorticoid therapy. Physical examination revealed non-pitting swelling of the right upper eyelid, bilateral cheeks, and lips asymmetrically. On the night of admission, he developed acute laryngeal edema with dyspnea, which was promptly treated, leading to clinical stabilization. Laboratory screening during the attack revealed decreased serum complement C4 levels, along with reduced functional activity and concentration of C1 esterase inhibitor, confirming a diagnosis of type 1 hereditary angioedema. The patient received lanadelumab for prophylaxis and achieved satisfactory clinical outcomes. He remains under long-term follow-up.

Objective To explore the incidence rate and independent risk factors of synchronous multiple early gastric cancer (SMEGC) in patients with early gastric cancer, and to provide evidence for early screening and intervention of high-risk population. Methods A retrospective analysis was performed on 308 patients with early gastric cancer who received treatment in the hospital from March 2019 to March 2024. The incidence rate of SMEGC was counted, and the risk factors were analyzed by univariate and multivariate Logistic regression analyses. Results Among the 308 patients with early gastric cancer in this study, 23 cases were SMEGC and 285 were single early gastric cancer, which were included in the SMEGC group and the single group respectively. The incidence rate of SMEGC was 7.47% (23/308). Compared with the single group, the proportions of male, smoking history, tumor diameter≤2 mm, chronic atrophic gastritis and intestinal metaplasia degree were higher in the SMEGC group (2=4.331、8.608、4.618、6.490、4.897，P=0.037、0.003、0.032、0.001、0.027). Logistic regression analysis suggested that chronic atrophic gastritis (OR=3.133, 95%CI: 1.240-7.918) and moderate-to-severe intestinal metaplasia (OR=3.171, 95%CI: 1.252-8.029) were independent risk factors for SMEGC (P<0.05). Conclusion Some patients with early gastric cancer are SMEGC. Chronic atrophic gastritis and moderate-to-severe intestinal metaplasia are independent risk factors affecting the occurrence of SMEGC. It is recommended to regularly screen high-risk patients and optimize management strategies to reduce the risk of SMEGC.

OBJECTIVE: To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS). METHODS: The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The symptom duration of CTS was 12-120 months (mean, 48.7 months) and the thenar muscle atrophy duration was 6-48 months (mean, 13.4 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before operation and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up. RESULTS: All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There was no complications such as wound infection, scar pain of wrist, or tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation ( P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation ( P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied. CONCLUSION The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.
Humans ; Tendon Transfer/methods* ; Male ; Middle Aged ; Carpal Tunnel Syndrome/physiopathology* ; Female ; Decompression, Surgical/methods* ; Aged ; Adult ; Thumb/physiopathology* ; Endoscopy/methods* ; Retrospective Studies ; Median Nerve/surgery* ; Treatment Outcome ; Plastic Surgery Procedures/methods*

OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.