Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective:To investigate the short-term efficacy of lenvatinib combined with transcatheter arterial chemoembolization (TACE) and xindilimumab in the treatment of hepatocellular carcinoma.Methods:A prospective, randomized, controlled study was conducted to divide 140 patients with hepatocellular carcinoma admitted to the First Hospital of Putian City from January 2020 to December 2023. The patients were divided into two groups by random number table method, with 70 cases in each group. The control group was treated with lenvatinib after TACE, and the observation group was treated with lenvatinib + xindilimumab after TACE. The patients were followed up for 6 months, and the number of TACE treatment in the two groups was recorded. The clinical efficacy, serum nuclear factor-κB (NF-κB), hypoxia-inducible factor-1α (HIF-1α), alpha-fetoprotein (AFP) levels, tumor blood supply diameter and drug side effects during treatment were compared between the two groups at 4 weeks and 6 months after TACE treatment.Results:There was no statistical significant difference in the number of TACE treatments between the two groups ( P>0.05). At 4 weeks of treatment, compared with the control group, the objective response rate (ORR) and disease control rate (DCR) of the observation group were significantly increased: 74.29% (52/70) vs. 57.14% (40/70), 92.87% (65/70) vs. 81.43% (57/70) ( P<0.05). After 6 months of treatment, compared with the control group, the observation group showed a significant increase in DCR: 85.71% (60/70) vs. 95.71% (67/70) ( P<0.05). Compared with the control group, the levels of serum NF-κ B, HIF-1α and AFP in the observation group were significantly reduced after 4 weeks and 6 months of treatment: (165.34 ± 40.11) ng/L vs. (187.61 ± 40.62) ng/L, (151.67 ± 36.25) ng/L vs. (165.01 ± 37.12) ng/L; (123.69 ± 20.36) μg/L vs. (148.32 ± 20.38) μg/L, (108.84 ± 20.28) μg/L vs. (121.67 ± 19.29) μg/L; (2 117.02 ± 903.36) μg/L vs. (2 469.79 ± 916.27) μg/L, (1 010.32 ± 422.34) μg/L vs. (1 159. 36 ± 412.01) μg/L ( P<0.05). Compared with the control group, the observation group showed a significant reduction in tumor blood supply diameter after 4 weeks and 6 months of treatment: 3.00 (2.00, 4.00) mm vs. 3.00 (3.00, 4.00) mm, 2.00 (1.00, 3.00) mm vs. 3.00 (2.00, 3.00) mm ( P<0.05) There was no statistically significant difference in the incidence of drug toxicity and side effects between the two treatment groups ( P>0.05). Conclusions:The concurrent administration of lenvatinib and xindilimab has been demonstrated to enhance the short-term therapeutic efficacy of TACE in patients with hepatocellular carcinoma. This combination therapy was associated with a significant reduction in serum levels of NF-κB, HIF-1α, and AFP. Additionally, it led to a notable decrease in the diameter of the tumor-feeding arteries. Preliminary safety analysis indicates that this regimen is well-tolerated, with an acceptable safety profile.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective : To investigate the relationship between lower limb alignment and knee functional gait after total knee arthroplasty (TKA) for varus knee deformity. Methods: A total of 94 patients with knee osteoarthritis and varus deformity underwent mechanically aligned TKA. The knee society score ( KSS) , hip⁃knee⁃ankle angle (HKA) , medial proximal tibial angle ( mMPTA) , and gait parameters ( step length , gait speed , cadence , thigh jerk acceleration , and thigh swing work) were assessed preoperatively and one month postoperatively. The correlation between KSS scores and changes in lower limb alignment was also analyzed. Results: The KSS clinical score of the operated knee significantly improved from 39. 19 ± 9. 55 preoperatively to 73. 01 ± 6. 90 postoperatively (P <0. 001) . The KSS functional score increased from 41. 12 ± 10. 66 to 56. 33 ± 7. 41(P < 0. 001) . Postoperative gait analysis revealed significant improvements in step length , gait speed , cadence , and thigh swing work ( P <0. 001) , while thigh jerk acceleration showed no significant change (P = 0. 525) . The HKA angle of the affected limb increased from 170. 61 ± 4. 39 preoperatively to 177. 30 ± 3. 49 postoperatively ( P < 0. 001) . Similarly , the mMPTA angle increased from 83. 95 ± 3. 32 to 89. 15 ± 1. 94 (P < 0. 001) . Correlation analysis indicated that The KSS clinical score was positively correlated with HKA ( P < 0. 001) and mMPTA ( P < 0. 05 ) of the lower limb force line. The KSS functional score was positively correlated with HKA (P < 0. 05) but not with mMPTA (P > 0. 05) . Conclusion In patients with severe knee osteoarthritis due to varus deformity , TKA significantly alleviates pain and improves both clinical and functional KSS scores within one month postoperatively. Restoring lower limb mechanical alignment is positively associated with joint functional recovery and enhances gait performance.

Objective:To investigate the short-term efficacy of lenvatinib combined with transcatheter arterial chemoembolization (TACE) and xindilimumab in the treatment of hepatocellular carcinoma.Methods:A prospective, randomized, controlled study was conducted to divide 140 patients with hepatocellular carcinoma admitted to the First Hospital of Putian City from January 2020 to December 2023. The patients were divided into two groups by random number table method, with 70 cases in each group. The control group was treated with lenvatinib after TACE, and the observation group was treated with lenvatinib + xindilimumab after TACE. The patients were followed up for 6 months, and the number of TACE treatment in the two groups was recorded. The clinical efficacy, serum nuclear factor-κB (NF-κB), hypoxia-inducible factor-1α (HIF-1α), alpha-fetoprotein (AFP) levels, tumor blood supply diameter and drug side effects during treatment were compared between the two groups at 4 weeks and 6 months after TACE treatment.Results:There was no statistical significant difference in the number of TACE treatments between the two groups ( P>0.05). At 4 weeks of treatment, compared with the control group, the objective response rate (ORR) and disease control rate (DCR) of the observation group were significantly increased: 74.29% (52/70) vs. 57.14% (40/70), 92.87% (65/70) vs. 81.43% (57/70) ( P<0.05). After 6 months of treatment, compared with the control group, the observation group showed a significant increase in DCR: 85.71% (60/70) vs. 95.71% (67/70) ( P<0.05). Compared with the control group, the levels of serum NF-κ B, HIF-1α and AFP in the observation group were significantly reduced after 4 weeks and 6 months of treatment: (165.34 ± 40.11) ng/L vs. (187.61 ± 40.62) ng/L, (151.67 ± 36.25) ng/L vs. (165.01 ± 37.12) ng/L; (123.69 ± 20.36) μg/L vs. (148.32 ± 20.38) μg/L, (108.84 ± 20.28) μg/L vs. (121.67 ± 19.29) μg/L; (2 117.02 ± 903.36) μg/L vs. (2 469.79 ± 916.27) μg/L, (1 010.32 ± 422.34) μg/L vs. (1 159. 36 ± 412.01) μg/L ( P<0.05). Compared with the control group, the observation group showed a significant reduction in tumor blood supply diameter after 4 weeks and 6 months of treatment: 3.00 (2.00, 4.00) mm vs. 3.00 (3.00, 4.00) mm, 2.00 (1.00, 3.00) mm vs. 3.00 (2.00, 3.00) mm ( P<0.05) There was no statistically significant difference in the incidence of drug toxicity and side effects between the two treatment groups ( P>0.05). Conclusions:The concurrent administration of lenvatinib and xindilimab has been demonstrated to enhance the short-term therapeutic efficacy of TACE in patients with hepatocellular carcinoma. This combination therapy was associated with a significant reduction in serum levels of NF-κB, HIF-1α, and AFP. Additionally, it led to a notable decrease in the diameter of the tumor-feeding arteries. Preliminary safety analysis indicates that this regimen is well-tolerated, with an acceptable safety profile.

Objective:To investigate the clinical manifestations, serological and cerebrospinal fluid test results for syphilis, imaging features, and prognoses of cerebral syphilitic gumma.Methods:The clinical data of 1 patient with cerebral syphilitic gumma admitted to Department of Neurology, Second Affiliated Hospital of Soochow University in March 2023 were retrospectively analyzed. Papers about cerebral syphilitic gumma were searched from journals in Journal Citation Reports Q1 from 2000 to 2019, journals from 2020 to 2024 in PubMed, WOS, Embase, and Scopus databases, and journals from 2000 to 2024 in Wanfang Database, CNKI, and VIP database; the clinical data of 54 patients with cerebral syphilitic gumma reported in above databases and 1 patient in our hospital were collected for pooled analysis.Results:The main clinical manifestations of 55 cerebral syphilitic gumma patients included headache (32, 58.2%), lateral limb/facial weakness (25, 45.5%), nausea and vomiting (14, 25.5%), dizziness (11, 20.0%), sensory disturbances (10, 18.2%), blurred vision (7, 12.7%), seizure (5, 9.1%)), hearing loss (5, 9.1%), tinnitus (5, 9.1%), memory loss (3, 5.5%), aphasia (3, 5.5%), dysarthria (2, 3.6%), drop attack (2, 3.6%), weakness in opening eyes (2, 3.6%), unresponsiveness (1, 1.8%), Argyll-Robertson pupil (1, 1.8%), tabes dorsalis gait (1, 1.8%), and fever (1, 1.8%). In 51 patients who reported complete serologic test results, 45 patients (88.2%) were positive for non-specific antibodies to syphilis, and all patients were positive for specific antibodies to syphilis. In 34 patients underwent cerebrospinal fluid examination, 25 (73.5%) were positive for non-specific antibodies to syphilis, and 32 (94.1%) were positive for specific antibodies to syphilis. Isolated intracranial lesion (43, 78.2%) was mostly common in imaging test, and the frequently involved cranial sites were, orderly, the frontal lobe (14, 25.5%), parietal lobe (14, 25.5%), temporal lobe (5, 9.1%), frontotemporal lobe (3, 5.5%), frontoparietal lobe (2, 3.6%), parieto-occipital lobe (2, 3.6%), nucleus pulposus (1, 1.8%), clivus (1/55, 1.8%), and cerebral peduncle of the midbrain (1, 1.8%). Thirty patients (54.5%) were misdiagnosed as having other intracranial space-occupied diseases, orderly, glioma (11, 36.7%), metastatic tumors (5, 16.7%), meningiomas (4, 13.3%), other unexplained intracranial space-occupying (4, 13.3%), brain abscess (3, 10.0%), cavernous hemangioma (1, 3.3%), intracranial lymphoma (1, 3.3%), auditory nerve and pituitary tumors (1, 3.3%). Of the 42 patients who reported prognosis after anti-syphilitic treatments, 41 had varying degrees of improvement, and one died of brain herniation.Conclusion:Because of atypical clinical manifestations and lack of clear diagnostic criteria, cerebral syphilitic gumma is often misdiagnosed as intracranial tumors; cerebral syphilitic gumma should be considered in patients with positive non-specific antibodies to syphilis/specific antibodies to syphilis in serum and cerebrospinal fluid having neurological symptoms and intracranial space-occupied foci; timely diagnosed and treated patients can prognosed well.

Transcatheter mitral valve edge-to-edge repair (TEER) has become an important treatment opinion for patients with severe mitral regurgitation (MR) at high risk for surgery. The devices and procedural techniques of TEER are complex and require excellent team cooperation. However, there is still a lack of standardized clinical pathways in China. Based on the latest evidence, the expert group wrote this clinical pathway to guide and optimize TEER therapy in clinical practice. It demonstrates the following key issues of clinical concern: (1) TEER team building; (2) preoperative clinical evaluation of TEER patients; (3) imaging assessment before TEER procedure; (4) standardized procedures for TEER; (5) TEER for complex MR; (6) the standard process of perioperative comprehensive management; and (7) full life-cycle rehabilitation and follow-up. This clinical pathway might be helpful to facilitate the standardized development of TEER therapy and application, and promote the improvement of management and life quality for patients with MR.

Based on the research results of aspiration in patients with dysphagia after ischemic stroke at home and abroad, this paper reviews the definition, detection methods, and risk factors of aspiration and emphasizes the incidence rate and severity of this disease. The authors conclude that preventing aspiration can decrease the incidence rate of aspiration pneumonia, change the clinical outcome of patients, and thereby save medical resources.