AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Objective:To investigate the risk factors for delirium after free flap reconstruction surgery in elderly patients with head and neck cancer.Methods:This study retrospectively collected clinical data from 309 elderly patients with head and neck cancer who underwent radical resection and free flap reconstruction surgery in the Department of Operation & Anesthesiology, College & Hospital of Stomatology, Guangxi Medical University from January 2018 to December 2022. Among them, there were 197 males (63.8%) and 112 females (36.2%), with an average age of (66.8±5.5) years old. Based on the delirium diagnostic criteria outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, patients were evaluated for postoperative delirium within one week after surgery. They were then divided into a delirium group ( n=75) and a non-delirium group ( n=234). Perioperative indicators potentially related to postoperative delirium, including age, gender, past medical history, tumor characteristics, hematological tests, perioperative sleep disturbances, surgical procedures, intraoperative fluid intake and output, anesthetic dosage, postoperative pain, etc, were collected from the relevant medical record system.Variables with P<0.05 were included in a multivariate Logistic regression model to screen for independent risk factors for delirium. Results:The incidence of delirium after free flap reconstruction surgery for head and neck cancer in elderly patients was 24.3% (75/309). Multivariate Logistic regression analysis showed that male gender ( OR=2.802, P=0.005), perioperative sleep disturbances ( OR=7.104, P<0.001), and moderate-to-severe postoperative pain ( OR=6.903, P<0.001) were risk factors for postoperative delirium. Conclusions:Male gender, perioperative sleep disturbances, and moderate-to-severe postoperative pain are independent risk factors for delirium in these patients.

Objective To explore the efficacy of bilateral facial muscle training combined with visual electromyography biofeedback on facial nerve function recovery in patients with idiopathic facial nerve palsy. Methods Patients with idiopathic facial nerve palsy admitted to Shanghai Fifth People’s Hospital, Fudan University from July 2022 to July 2024 were selected and randomly divided into a control group and an intervention group. The control group received conventional physical factor therapy, while the intervention group received bilateral facial muscle training combined with visual electromyography biofeedback therapy based on the control group’s regimen. After 20 treatment sessions, the total effective rate, the House-Brackmann (H-B) facial nerve grading system, the Sunnybrook Facial Grading System (SFGS) score, and the average value ratio of maximal amplitudes of bilateral frontalis and zygomaticus muscles were compared between the two groups. Results A total of 90 patients were included, 45 in each group. After 20 treatment sessions, the total effective rate was significantly higher in the intervention group than in the control group (84.4% vs 75.6%, P＝0.003). Compared with the control group, the intervention group demonstrated a significantly lower H-B grade (P＝0.003) and a higher SFGS score (P＝0.001). The average value ratios of maximal amplitudes of the affected versus healthy side frontalis (P＝0.013) and zygomatic (P＝0.022) muscles were higher in the intervention group than in the control group. Conclusions Bilateral facial muscle training combined with visual electromyography biofeedback is an effective approach for treating idiopathic facial nerve palsy, effectively promoting the recovery of facial nerve function, and improving facial symmetry and facial muscle function.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objective:To investigate the risk factors for delirium after free flap reconstruction surgery in elderly patients with head and neck cancer.Methods:This study retrospectively collected clinical data from 309 elderly patients with head and neck cancer who underwent radical resection and free flap reconstruction surgery in the Department of Operation & Anesthesiology, College & Hospital of Stomatology, Guangxi Medical University from January 2018 to December 2022. Among them, there were 197 males (63.8%) and 112 females (36.2%), with an average age of (66.8±5.5) years old. Based on the delirium diagnostic criteria outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, patients were evaluated for postoperative delirium within one week after surgery. They were then divided into a delirium group ( n=75) and a non-delirium group ( n=234). Perioperative indicators potentially related to postoperative delirium, including age, gender, past medical history, tumor characteristics, hematological tests, perioperative sleep disturbances, surgical procedures, intraoperative fluid intake and output, anesthetic dosage, postoperative pain, etc, were collected from the relevant medical record system.Variables with P<0.05 were included in a multivariate Logistic regression model to screen for independent risk factors for delirium. Results:The incidence of delirium after free flap reconstruction surgery for head and neck cancer in elderly patients was 24.3% (75/309). Multivariate Logistic regression analysis showed that male gender ( OR=2.802, P=0.005), perioperative sleep disturbances ( OR=7.104, P<0.001), and moderate-to-severe postoperative pain ( OR=6.903, P<0.001) were risk factors for postoperative delirium. Conclusions:Male gender, perioperative sleep disturbances, and moderate-to-severe postoperative pain are independent risk factors for delirium in these patients.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Objective:To establish and validate a predictive model for non-curative resection of rectal neuroendocrine tumors (R-NETs) ≤20 mm.Methods:Data from patients with R-NETs treated at the First Affiliated Hospital of Soochow University and the Suzhou Ninth People's Hospital from January 2013 to December 2023 were retrospectively analyzed. Clinical data, endoscopic findings, and pathological characteristics were analyzed. Univariate analysis was performed using independent sample t-tests and Chi-square tests. Variables were screened using the forward stepwise binary logistic regression to establish a risk prediction model for non-curative resection of R-NETs ≤20 mm, with subsequent construction of a nomogram. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. The consistency between predicted and observed probabilities was assessed using calibration curves, and the clinical net benefit of the model was evaluated using decision curve analysis. Results:A total of 213 patients were included, with age of 50.53±11.42 years, and 102 (47.9%) were male. The distance of the lesion from the dentate line was 7.11±2.79 cm, and the tumor long diameter was 8.24±3.75 mm. Compared to curative resection cases, non-curative resection cases were more likely to exhibit tumor surface depression, higher tumor G-stage, higher Ki-67 index and higher chromograninA (CgA) positivity rate ( P<0.05). Through forward variable selection in binary logistic regression, a model was established with Ki-67 index ( P=0.014, OR=1.214, 95% CI: 1.039-1.417), surface depression ( P=0.027, OR=2.348, 95% CI: 1.100-5.013), and CgA positivity ( P<0.001, OR=5.399, 95% CI: 2.764-10.544) as parameters, with a corresponding nomogram. The area under the ROC curve of the model was 0.766 (95% CI: 0.696-0.837), and clinical decision curve analysis confirmed its good clinical net benefit. The calibration curve showed good consistency between predicted and observed probabilities. Conclusion:This study establishes a risk prediction model for non-curative resection of R-NETs ≤20 mm based on surface depression, Ki-67 index, and CgA positivity. The model demonstrates strong predictive performance and offers valuable guidance for clinical endoscopists.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objective:To establish and validate a predictive model for non-curative resection of rectal neuroendocrine tumors (R-NETs) ≤20 mm.Methods:Data from patients with R-NETs treated at the First Affiliated Hospital of Soochow University and the Suzhou Ninth People's Hospital from January 2013 to December 2023 were retrospectively analyzed. Clinical data, endoscopic findings, and pathological characteristics were analyzed. Univariate analysis was performed using independent sample t-tests and Chi-square tests. Variables were screened using the forward stepwise binary logistic regression to establish a risk prediction model for non-curative resection of R-NETs ≤20 mm, with subsequent construction of a nomogram. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. The consistency between predicted and observed probabilities was assessed using calibration curves, and the clinical net benefit of the model was evaluated using decision curve analysis. Results:A total of 213 patients were included, with age of 50.53±11.42 years, and 102 (47.9%) were male. The distance of the lesion from the dentate line was 7.11±2.79 cm, and the tumor long diameter was 8.24±3.75 mm. Compared to curative resection cases, non-curative resection cases were more likely to exhibit tumor surface depression, higher tumor G-stage, higher Ki-67 index and higher chromograninA (CgA) positivity rate ( P<0.05). Through forward variable selection in binary logistic regression, a model was established with Ki-67 index ( P=0.014, OR=1.214, 95% CI: 1.039-1.417), surface depression ( P=0.027, OR=2.348, 95% CI: 1.100-5.013), and CgA positivity ( P<0.001, OR=5.399, 95% CI: 2.764-10.544) as parameters, with a corresponding nomogram. The area under the ROC curve of the model was 0.766 (95% CI: 0.696-0.837), and clinical decision curve analysis confirmed its good clinical net benefit. The calibration curve showed good consistency between predicted and observed probabilities. Conclusion:This study establishes a risk prediction model for non-curative resection of R-NETs ≤20 mm based on surface depression, Ki-67 index, and CgA positivity. The model demonstrates strong predictive performance and offers valuable guidance for clinical endoscopists.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.