Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Objective To rapidly identify and assign the chemical components in Sugemule-4 decoction by using UPLC Orbitrap Exploris MS/MS,and then conduct network pharmacological analysis,and clarify the anti-insomnia effect of Sugmule-4 decoction.Methods ACQUITY UPLC BEH C18(2.1 mm×100 mm,1.7 μm)Chromatographic column,with 0.1％formic acid aqueous solution(A)-0.1％formic acid acetonitrile solution(B)as mobile phase gradient elution.Flow rate:0.5 mL·min-1,injection volume:5 μL.Under the control of the control software(Xcalibur,Thermo Fisher Scientific),the primary and secondary mass spectrometry data are collected based on the FullScan-ddMS2 function.Combined with the self-built database and online database,the chemical components in Sugemule-4 decoction are identified by accurate relative molecular weight,fragment ion information,pyrolysis pattern and comparison of control samples.The identified chemical components were analyzed by network pharmacology,and the targets of drug and insomnia were obtained from TCMSP,SwissTargetPrediction,GeneCards,OMIM,TTD,DrugBank and DisGeNET databases respectively,and the intersection target was obtained;Protein interaction analysis was performed through STRING database.Use Metascape platform to analyze GO function and KEGG pathway,and predict the mechanism of Sugmule-4 decoction in treating insomnia.To determine the anti-insomnia effect of Sugmule-4 decoction,SD rats were divided into normal control group(K),model group(M),Sugmule-4 decoction group(S)and Anshenbunao liquid group(A).After chronic unpredictable mild stress and PCPA were used for modeling,the rats were given corresponding drugs by gavage for 7 days,then the open field text was conducted to observe the general state and behavioral changes,and detection of AChE,5-HT,and GABA levels in serum and brain tissue of rats in each group using ELISA method.Results 136 components were identified from Sugemule-4 decoction,including 37 terpenoids,34 alkaloids,26 flavonoids,20 phenylpropanoids,14 phenolic acids and 5 amino acids.The results of network pharmacology analysis show that the mechanism of Sugemule-4 decoction in treating insomnia is mainly achieved by its components such as Romucosine D,Nornantenine,Nuciferine,and(R)-ar Turbone acting on targets such as ACHE,ADORA2A,and CHRM1 through signal pathways such as Neuroactive ligand-receptor interaction,synaptic signaling,and trans synaptic signaling.This is a multi component-multi target-multi signal pathway joint implementation process.The results of pharmacodynamic experiment showed that Sugmule-4 decoction and Anshenbunao liquid could revise the general state and behavioral changes of insomnia model rats,increase the content of AChE,5-HT and GABA in serum(P<0.01).Conclusion This study comprehensively reflects the chemical components of Sugmule-4 decoction,and preliminarily summarizes the mass spectrum decomposition characteristics of various chemical components.The network pharmacology and pharmacodynamics experiments show that Sugmule-4 decoction has significant anti-insomnia effect,which provides a reference basis for the quality control and mechanism study of Sugmule-4 decoction.

Objective:To explore the surgical outcomes of focal cortical dysplasia (FCD) patients with "difficult to locate" intractable epilepsy and their influencing factors.Methods:Thirty-five FCD patients with "difficult to locate" intractable epilepsy, underwent surgical treatment after intracranial electroencephalogram (iEEG) evaluation in our hospital from January 2011 to December 2018, were chosen in our study. Engel grading was used to evaluate the surgical efficacies of these patients, and they were divided into a satisfied efficacy group (Engel grading I) and an incomplete satisfied efficacy group (Engel grading II-IV). The clinical data of patients from the 2 groups were compared. Multivariate Logistic regression analysis was performed to explore the influencing factors for surgical outcomes of FCD patients with "difficult to locate" intractable epilepsy.Results:Of these 35 patients, 26 patients (74.3%) achieved satisfied efficacy, and 4 had incomplete satisfied efficacy. As compared with those in the satisfied efficacy group, patients in the incomplete satisfied efficacy group had significantly lower total resection rate of epileptogenic foci ( P<0.05). Multivariate Logistic regression analysis showed that incomplete resection of epileptogenic foci was the influencing factor for surgical outcomes of FCD patients with "difficult to locate" intractable epilepsy ( P=0.014, OR=0.050, 95%CI: 0.005-0.547). Conclusion:The FCD patients with "difficult to locate" intractable epilepsy can achieve satisfactory results by surgical resection of epileptogenic zones after iEEG monitoring; these FCD patients with "difficult to locate" intractable epilepsy with incomplete resection of epileptogenic foci often have poor surgical outcomes.

Objective:To investigate the prevalence and prognosis of non-alcoholic fatty liver disease (NAFLD) complicated with coronary vulnerable plaque (VP).Method:Consecutive patients were included who had undergone coronary artery CT angiography (CCTA) from January 1, 2011 to January 30, 2015 at the First People′s Hospital of Neijiang. NAFLD was diagnosed according to the liver imaging findings (liver/spleen CT ratio≤1.0) and clinical data. Baseline data, diagnosis, vulnerable plaque were recorded and followed up. The end points included all-cause death rate, cardiac death rate, non-fatal myocardial infarction rate, and elective coronary revascularization rate.Result:A total of 1 069 patients were eventually recruited in this study, including 316 (29.6%) cases diagnosed as NAFLD. In patients with NAFLD, 130 (41.1%) cases had vulnerable plaque, which was significantly higher than 217 of 753 non-NAFLD patients (28.8%) ( P<0.01). The percentages of spotty calcification, low attenuation plaque, positive remodeling and napkin ring sign in NAFLD cohort were 36.5%, 14.2%, 17.6% and 6.8% respectively, while those corresponding in non-NAFLD cohort were 18.4%, 6.3%, 5.8% and 3.2% respectively. The proportion of each vulnerable feature in NAFLD cohort was significantly higher than that in the non-NAFLD cohort, with P values of 0.016, 0.028, 0.019 and 0.042, respectively. The cardiac mortality rate in NAFLD group was significantly higher than and that of non-NAFLD group (7.0% vs. 3.6%, P=0.044). Multivariate Cox analysis suggested that NAFLD was not an independent risk factor for cardiac death. NAFLD subgroup ( n=316) was divided into VP positive group (NAFLD+VP+, n=130) and VP negative group (NAFLD+VP-, n=186). The mean follow-up time was 4.6±1.3 years. All-cause mortality rate, cardiac death rate, elective coronary artery reconstruction rate, non-fatal myocardial infarction rate in NAFLD+VP+group were 20.8%, 12.3%, 25.4%, 13.8% respectively, which were significantly higher than those corresponding rates in NAFLD+VP-group (5.9%, 3.2%, 8.6%, 6.5%) ( P<0.01, 0.002,<0.01, and 0.032 respectively). Conclusion:The incidences of cardiac mortality, elective coronary revascularization, and non-fatal myocardial infarction are significantly higher in patients with NAFLD than those without. NAFLD combined with vulnerable plaque of coronary arteries predicts worse prognosis.

OBJECTIVE: To evaluate the feasibility of applying intracranial lead reconstruction in deep brain stimulation (DBS) therapy for Parkinsonism. METHODS: We retrospectively collected the clinical data from 27 patients with Parkinson's disease (PD), who received bilateral subthalamic nucleus (STN) DBS therapy between January, 2016 and December, 2017. According to the position of the selected optimal stimulating contact of the implanted leads, the patients were divided into group A with the stimulating contacts of the bilateral leads in the STN, group B with unilateral stimulating contacts in the STN, and group C with bilateral stimulating contacts outside the STN. All the patients were assessed for improvement using Hoehn-Yahr stage, the third part of United Parkinson's Disease Rating Scale (UPDRS Ⅲ), Schwab and England Activities of Daily Living (SE-ADL), and L-dopa equivalent daily dose (LEDD). The consistency between the optimal stimulating contact selected by lead reconstruction and that by standard postoperative programming procedure was also evaluated. RESULTS: The patients in all the 3 groups showed postoperative improvements in Hoehn-Yahr stage, UPDRS Ⅲ score, SE-ADL score, and LEDD in the medication-off state. But at 12 months of the follow-up, such improvements were maintained only in the patients of group A. The optimal stimulating contacts selected by lead reconstruction and standard postoperative programming procedure had a matching rate of up to 77.78% (42/54), and the coordinates of the optimal contacts selected by the two methods showed no significant difference. CONCLUSIONS Intracranial lead reconstruction facilitates the study of the association between the implant site of the leads and the clinical outcome of DBS therapy for PD and allows the precise selection of the optimal contact of the implanted leads in postoperative programming of DBS.
Activities of Daily Living ; Deep Brain Stimulation ; Humans ; Parkinson Disease ; Retrospective Studies ; Treatment Outcome

Objective To explore the related factors affecting postoperative pneumonia in patients with cavernous cerebrovascular malformation (CCM).MethodsClinical data of 151 CCM patients admitted to our hospital from January 2010 to January 2017 were retrospectively collected. Patients were divided into postoperative pneumonia group (n=11) and postoperative non-pneumonia group (n=140) according to the occurrence of postoperative pneumonia. Univariate Logistic regression analysis, multivariate Logistic regression analysis and receiver operating characteristic (ROC) curve were used to screen the relevant factors influencing the occurrence of postoperative pneumonia in CCM patients and evaluate the predictive value of relevant factors in postoperative pneumonia.ResultsAs compared with patients from postoperative non-pneumonia group, patients from postoperative pneumonia group had significantly increased modified Rankin scale (mRS) scores and significantly higher percentage of CCM combined with hemorrhage, and significantly decreased Glasgow coma scale (GCS) scores (P<0.05). Multivariate Logistic regression analysis showed that preoperative GCS scores (OR=4.75, 95％CI: 1.14-19.80,P=0.032) and mRS scores (OR=15.61, 95％CI: 3.22-75.58,P=0.001) were independent factors influencing the occurrence of postoperative pneumonia. ROC curve showed that the sensitivity and specificity of mRS scores≥4 to predict postoperative pneumonia were 45.5％ and 95.7％, respectively, and the sensitivity and specificity of GCS scores≤13 to predict postoperative pneumonia were 54.5％ and 85.7％, respectively.ConclusionFor CCM patients with preoperative GCS scores≤13 or mRS scores≥4, more attention should be paid to perioperative lung management and occurrence of postoperative pneumonia should be vigilant.

Objective The aim of our study was to establish an endoscopic endonasal transsphenoidal surgical training model, and to examine its application value. Methods The endoscopic endonasal transsphenoidal surgical training models were made.After assessments,the models was used for endoscopic operation training for 8 neurosurgeons with no experiences of endoscopic operation. Results The available operating space of this model is similar to the actual operating space in endoscopic endonasal transsphenoidal surgery. The egg fixed on the model has many layers of structure, such as eggshell, shell membrane, egg white and egg yolk, which constituted a good practice object. All students indicated that they could benefit from the training using this model. The skill in grinding the eggshell [(1.07 ± 0.221)cm2/min vs.(1.45±0.27)cm2/min, P<0.001]was significantly improved and the chance for shell membrane rupture (8 vs. 2, P=0.007) was significantly reduced in the last-time practice compared with the first-time practice (P<0.001). Conclusion The endoscopic endonasal transsphenoidal surgical training model is helpful for neurosurgeons to practice the basic operation of endoscopic surgery and to improve their surgical skills,and can be used repeatedly.It can be used in basic operation training before the training using cadaver cranium.

Objective To investigate the distance change of bilateral internal carotid artery in acromegalic patients. Methods Twenty patients with acromegaly were included in this study from August 2016 to March 2018 in Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University. There were 7 males and 13 females with an average age of 40.2±12.6 years (range from 21 to 62 years old). Forty sex and age matched patients with non-functional pituitary adenoma were selected as controls. The 3D printing software was used for reconstructing the internal carotid artery. Distances of the bilateral internal carotid arteries were measured on the reconstructed images. Results The maximum distance between bilateral siphon carotid ectasias (25.1±3.9 mm vs. 23.2±2.9 mm, P=0.041) and distance between bilateral lacerum segments (26.2 ±3.1 mm vs. 23.8 ±4.1 mm, P=0.022) were significantly longer in patients with acromegaly than in those without. Although the distance between bilateral cavernous segments (20.7 ±4.3 mm vs. 22.4 ±3.1 mm, P=0.076) tended to be shorter, the difference was not statistically significant. The distance between bilateral ophthalmic segments was not significantly different between the two groups (15.7±5.1 mm vs. 16.0±2.5 mm, P=0.783). Conclusion The distance of bilateral internal carotid artery of acromegalic patients is different from that of patients with non-functional pituitary adenomas. Patients with acromegaly have significantly longer distance between bilateral siphon carotid ectasias and distance between bilateral lacerum segments compared with the patients with non- functional pituitary adenomas.

Objective To explore whether receptor interacting protein (RIP)1/RIP3 pathways participate in glutamate induced cell death in HT-22 neuronal cells and investigate the potential neuroprotection ofnecrostatin-1 in glutamate induced cell death in HT-22.Methods (1) In vitro cultured mouse hippocampal neuronal HT-22 cells were divided into control group,zVAD group,necrostatin-1 (Nec-1) group,glutamate group,glutamate+zVAD group,glutamate+zVAD+Nec-1 group and glutamate+Nec-1 group;they were treated with zVAD,Nec-1 and glutamate at the final concentrations of 20 μmol/L,30 μmol/L and 3 mmol/L for 24 h.Cell viability was detected using a luminescence-based commercial kit Cell Titer-Glo (CTG).Necrotic cell death was measured by propidium iodide (PI) and HE stainings.(2) HT-22 cells were divided into control group Ⅰ,glutamate group Ⅰ and glutamate+Nec-1 group Ⅰ;MitoSox Red was used to detect mitochondrial reactive oxygen species (ROS) level.(3) HT-22 cells were divided into control group Ⅱ,glutamate group Ⅱ and glutamate+tertiary butyl-hydroxyanisole (BHA) group;the final concentration of BHA was 100 μmol/L;necrotic cell death was measured by PI and HE stainings after 24 h of treatment.(4) HT-22 cells were divided into RIP3 siRNA and control group Ⅲ,and then,they were transfected with RIP3 siRNA or negative siRNA,respectively;the RIP3 protein expression was determined by Westem blotting after 72 h of treatment.(5) HT-22 cells were divided into negative siRNA+Control,RIP3 siRNA,negative siRNA+glutamate and RIP3 siRNA+glutamate groups;the cells were transfected with RIP3 siRNA or Negative siNRA,respectively;48 h later,the glutamate groups were treated with 3 mmol/L glutamate;PI positive cells and cell viability were measured by PI and HE stainings and CTG at 24 h after glutamate treatment.Results (1) As compared with control group,percentage of PI positive cells was greatly increased and cell viability was decreased in glutamate group and glutamate+zVAD group,with statistically significant differences (P＜0.05);as compared with those in the glutamate group,percentage of percentage of PI positive cells was was significantly decreased and cell viability was statistically increased in glutamate+Nec-1 group (P＜0.05).(2) ROS level in HT-22 cells of the glutamate group was significantly increased than that in the control group Ⅰ (P＜0.05);however,ROS level in HT-22 cells of glutamate+Nec-1 group Ⅰ was significantly decreased than that in glutamate group Ⅰ (P＜0.05).(3)Percentage of PI positive cells in the glutamate group Ⅱ was significantly higher than that in the control group Ⅱ (P＜0.05),and that in the glutamate+BHA group was statistically lower than that in the glutamate group Ⅱ (P＜0.05).(4) The RIP3 protein expression in the RIP3 siRNA group was obviously down-regulated as compared with that in the control group Ⅲ.(5) As compared with those in the negative siRNA group,percentage of PI positive cells was statistically increased and cell viabilities were statistically decreased in glutamate group (P＜0.05);however,percentage of PI positive cells was significantly decreased and cell viability was significantly increased in RIP3 siNRA+glutamate group as compared with those in the glutamate group (P＜0.05).Conclusion RIP1/RIP3 pathway and ROS might mediate glutamate induced cell death in HT-22 cells.