Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To identify risk factors associated with lymphatic leakage after laparoscopic radical prostatectomy(LRP)and to develop a machine learning-based nomogram for predicting such outcomes to support clinical prevention strategies.Methods We retrospectively analyzed perioperative data from 248 patients who underwent radical prostatectomy for prostate cancer between January 2020 and January 2024.Independent risk factors were identified through univariate and multivariate logistic regression analyses.A predictive model was developed,and its diagnostic performance was assessed by the area under the receiver operating characteristic curve(AUC).Five-fold cross-validation was performed to evaluate the model's generalizability.A nomogram was subsequently constructed to facilitate individualized risk quantification.Results Among the 248 patients,89(35.9%)developed lymphatic leakage,while 159(64.1%)did not.Independent risk factors for lymphatic leakage included intraopera-tive lymph node dissection(OR=5.415,95%CI:2.167～13.532,P<0.001),intraoperative plasma transfusion(OR=2.952,95%CI:1.524～5.718,P=0.001),and postoperative fasting duration of≥2 days(OR=1.412,95%CI:1.089～1.829,P=0.009).The predictive model showed good discrimination and calibration(AUC=0.711,95%CI:0.647～0.776,P<0.001;sensitivity:0.764;specificity:0.597).Model robustness was confirmed through five-fold cross-validation(training set AUC=0.822;test set AUC=0.829).The nomogram provided a clinically useful tool for quantifying individual risk of lymphatic leakage.Conclusions Intraoperative lymph node dissection,plasma transfusion,and postoperative fasting lasting≥2 days are independent risk factors for lymphatic leakage following radical prostatectomy.The validated predictive model demonstrates favorable clinical utility.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Objective To identify risk factors associated with lymphatic leakage after laparoscopic radical prostatectomy(LRP)and to develop a machine learning-based nomogram for predicting such outcomes to support clinical prevention strategies.Methods We retrospectively analyzed perioperative data from 248 patients who underwent radical prostatectomy for prostate cancer between January 2020 and January 2024.Independent risk factors were identified through univariate and multivariate logistic regression analyses.A predictive model was developed,and its diagnostic performance was assessed by the area under the receiver operating characteristic curve(AUC).Five-fold cross-validation was performed to evaluate the model's generalizability.A nomogram was subsequently constructed to facilitate individualized risk quantification.Results Among the 248 patients,89(35.9%)developed lymphatic leakage,while 159(64.1%)did not.Independent risk factors for lymphatic leakage included intraopera-tive lymph node dissection(OR=5.415,95%CI:2.167～13.532,P<0.001),intraoperative plasma transfusion(OR=2.952,95%CI:1.524～5.718,P=0.001),and postoperative fasting duration of≥2 days(OR=1.412,95%CI:1.089～1.829,P=0.009).The predictive model showed good discrimination and calibration(AUC=0.711,95%CI:0.647～0.776,P<0.001;sensitivity:0.764;specificity:0.597).Model robustness was confirmed through five-fold cross-validation(training set AUC=0.822;test set AUC=0.829).The nomogram provided a clinically useful tool for quantifying individual risk of lymphatic leakage.Conclusions Intraoperative lymph node dissection,plasma transfusion,and postoperative fasting lasting≥2 days are independent risk factors for lymphatic leakage following radical prostatectomy.The validated predictive model demonstrates favorable clinical utility.

Objective:To explore the clinical value of plasma von Willebrand factor antigen(VWF:Ag)and VWF activity(VWF:GPIbM)based on ABO blood group in the risk assessment of deep vein thrombosis(DVT).Methods:A total of 163 patients with DVT who sought medical treatment from March 2021 to December 2022 were selected as the case group,and 135 healthy volunteers during the same period were selected as the control group.The differences of ABO blood groups,plasma VWF:Ag and VWF:GPIbM levels between the two groups were compared.Receiver operating characteristic(ROC)curves were used to evaluate the clinical value of VWF testing in predicting DVT events.Logistic regression analysis was applied to identify risk factors for DVT.Results:The levels of plasma VWF:Ag and VWF:GPIbM in the DVT group were significantly higher than those in the control group both overall and across ABO blood type subgroups(P＜0.01).Within the DVT group,the levels of plasma VWF:Ag and VWF:GPIbM in patients with non-O blood type were significantly higher than those with blood type O[VWF:Ag:219.74％±63.64％vs 162.21％±56.03％,P＜0.01;VWF:GPIbM:228.10％(185.15％,249.10％)vs 148.25％(116.48％,225.48％),P＜0.01].The area under the ROC curve(AUC)of VWF:Ag for predicting DVT events was 0.855,with a cut-off value of 142.4％,sensitivity of 82.2％and specificity of 72.6％;the AUC of VWF:GPIbM was 0.861,with a cut-off value of 141.2％,sensitivity of 84.7％,and specificity of 71.1％.Univariate analysis showed that both VWF:Ag and VWF:GPIbM were influencing factors for DVT events(P＜0.05).Multivariate logistic regression analysis indicated that VWF:Ag＞142.4％(OR=13.961,95％CI:7.654-25.464,P＜0.01)and VWF:GPIbM＞141.2％(OR=17.615,95％CI:9.155-33.892,P＜0.01)were independent risk factors for DVT events.Conclusion:Levels of VWF:Ag and VWF:GPIbM are significantly elevated in non-O blood type DVT patients.VWF:Ag＞142.4％and VWF:GPIbM＞141.2％are independent risk factors for DVT events.VWF testing based on ABO blood group aids in the precision prevention and control of DVT.

Objective:To explore the clinical value of plasma von Willebrand factor antigen(VWF:Ag)and VWF activity(VWF:GPIbM)based on ABO blood group in the risk assessment of deep vein thrombosis(DVT).Methods:A total of 163 patients with DVT who sought medical treatment from March 2021 to December 2022 were selected as the case group,and 135 healthy volunteers during the same period were selected as the control group.The differences of ABO blood groups,plasma VWF:Ag and VWF:GPIbM levels between the two groups were compared.Receiver operating characteristic(ROC)curves were used to evaluate the clinical value of VWF testing in predicting DVT events.Logistic regression analysis was applied to identify risk factors for DVT.Results:The levels of plasma VWF:Ag and VWF:GPIbM in the DVT group were significantly higher than those in the control group both overall and across ABO blood type subgroups(P＜0.01).Within the DVT group,the levels of plasma VWF:Ag and VWF:GPIbM in patients with non-O blood type were significantly higher than those with blood type O[VWF:Ag:219.74％±63.64％vs 162.21％±56.03％,P＜0.01;VWF:GPIbM:228.10％(185.15％,249.10％)vs 148.25％(116.48％,225.48％),P＜0.01].The area under the ROC curve(AUC)of VWF:Ag for predicting DVT events was 0.855,with a cut-off value of 142.4％,sensitivity of 82.2％and specificity of 72.6％;the AUC of VWF:GPIbM was 0.861,with a cut-off value of 141.2％,sensitivity of 84.7％,and specificity of 71.1％.Univariate analysis showed that both VWF:Ag and VWF:GPIbM were influencing factors for DVT events(P＜0.05).Multivariate logistic regression analysis indicated that VWF:Ag＞142.4％(OR=13.961,95％CI:7.654-25.464,P＜0.01)and VWF:GPIbM＞141.2％(OR=17.615,95％CI:9.155-33.892,P＜0.01)were independent risk factors for DVT events.Conclusion:Levels of VWF:Ag and VWF:GPIbM are significantly elevated in non-O blood type DVT patients.VWF:Ag＞142.4％and VWF:GPIbM＞141.2％are independent risk factors for DVT events.VWF testing based on ABO blood group aids in the precision prevention and control of DVT.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective:To compare the clinical outcomes between all-inside and conventional transtibial tunnel reconstructions for posterior cruciate ligament (PCL) injuries.Methods:A retrospective study was conducted to analyze the clinical data of the 108 patients who had been treated for PCL injuries at Department of Arthrosis Surgery, Xuzhou Renci Hospital, from March 2021 to March 2023. There were 48 females and 60 males, with an age of (30.3±10.8) years and an injury-to-surgery interval of (25.7±6.4) days. Of them, 49 left and 59 right knees were affected. By the difference in the tunnel reconstruction, the patients were divided into 2 groups: an all-inside group ( n=52) in which the PCL was reconstructed using the all-inside techniques and a conventional group in which the PCL was reconstructed using the conventional techniques. The following were observed and compared: operation time and postoperative hospital stay; visual analogue scale (VAS) pain scores, The International Knee Documentation Committee (IKDC) subjective scores and Lysholm knee function scores at preoperation, postoperative 3 months and the last follow-up; posterior drawer test, posterior sag sign, reverse Lachman test and the diameter and morphology of the PCL shown by the knee joint MRI at the last follow-up. Results:The baseline characteristics were comparable between the 2 groups ( P>0.05). All patients were followed up for (12.3±1.2) months. The all-inside group incurred significantly longer operation time [(128.3±7.6) min] than the conventional group [(103.5±6.9) min] ( P<0.05), but no significant difference was observed in postoperative hospital stay between the 2 groups ( P> 0.05). There was no significant difference in VAS pain score, IKDC subjective score, or Lysholm score between the 2 groups at preoperation, postoperative 3 months or the last follow-up ( P>0.05). In both groups, the VAS pain scores, IKDC subjective scores and Lysholm scores at postoperative 3 months and the last follow-up were significantly improved compared with those at preoperation ( P<0.05). At the last follow-up, the posterior drawer test, posterior sag sign, reverse Lachman test were negative in both groups, and the knee joint MRI showed good diameter and morphology of the PCL reconstructed. Conclusions:Both conventional and all-inside reconstructions yield satisfactory clinical outcomes for PCL injuries, demonstrating comparable functional recovery and complication incidence. However, the all-inside technique requires longer operation time than the conventional approach.