Traditional antibody drug conjugates(ADC)combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells,but there are still many shortcomings in stability,targeting,efficacy,and safety.Novel ADC,such as bi-specific,site-specific,dual-payload,and pro-drug type ADC,can be optimized by simultaneously binding 2 different antigens or epitopes,selecting more stable linkers,coupling with specific amino acid sites of antibodies,carrying different drug payloads,and adopting prodrug strategies,while retaining the characteristics of traditional ADC.Significantly improving the stability,targeting,efficacy and safety of drugs can better meet the needs of clinical treatment.Novel ADC will play a more important role in cancer treatment in the future.Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.

Objective To explore the risk factors of perioperative blood transfusion in patients with recurrent nasopharyngeal carcinoma undergoing nasal endoscopic surgery,and construct a nomogram predic-tion model.Methods A retrospective analysis was conducted on the clinical data of 262 patients who un-derwent the nasal endoscopic surgery from January 2021 to May 2023.The patients were divided into two groups according to perioperative blood transfusion or not:non-transfusion group and transfusion group.Uni-variate and multivariate logistic regression were conducted to identify independentrisk factors of perioperative blood transfusion,and a nomogram prediction model was developed.The receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated.Results The incidence of blood transfusion in patients with recurrent nasopharyngeal carcinoma undergoing nasal endoscopic surgery was 46(17.6％).Multivariate logistic regression analysis revealed that preoperative hemoglobin level 70 to＜100 g/L(OR=6.178,95％CI 2.271-16.805,P＜0.001),preoperative albumin level 25 to＜35 g/L(OR=2.126,95％CI 1.021-4.424,P=0.044),and classification of surgery grade Ⅲ or Ⅳ (OR=4.725,95％CI 1.634-13.584,P=0.004)were independent risk factors for predicting perioper-ative blood transfusion in patients with recurrent nasopharyngeal carcinoma undergoing nasal endoscopic sur-gery.The AUC of the nomogram model was 0.769(95％CI 0.701-0.838),the sensitivity was 67.6％,and the specificity was 76.1％.Conclusion Preoperative hemoglobin level 70 to＜100 g/L,preoperative albumin level 25 to＜35 g/L,and classification of surgery grade Ⅲ or Ⅳ are independent risk factors of perioperative blood transfusion in patients with recurrent nasopharyngeal carcinoma undergoing nasal endo-scopic surgery.The nomogram model established based on the above risk factors has good predictive ability for perioperative blood transfusion.

Although immunotherapy has made a breakthrough in the treatment of cancer,the emergence of drug resistance has limited be-nefits in most patients,and reversing immunotherapy resistance remains a hotly debated and unresolved issue.The tumor microenviron-ment(TME)comprises a large number of T lymphocytes.During the biological processes of proliferation,activation,and the effect of tumor-infiltrating lymphocytes(TILs),TILs face severe local metabolic stress,resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements.This process of adaptive changes in the metabolic pattern is closely related to the pheno-type and function of TILs,affecting immunotherapy efficacy and mediating immunotherapy resistance.In recent years,with the study of TIL metabolism and the search for specific metabolic regulatory points,targeting the TIL metabolic pathway could restore the tumor-killing func-tion and reverse immunotherapy resistance.This review explores the relationship between the metabolic reprogramming of TILs and im-mune resistance,and provides a new strategy for reversing immune resistance.

Objective:To investigate the change of chemical exchange saturation transfer (CEST) imaging in the bilateral substantia nigra (SN) and red nucleus (RN) of Parkinson disease (PD), and to explore the value of CEST-MRI for the clinical application of PD.Methods:This was a cross-sectional study. A total of 45 PD patients (PD group) and 21 sex-, age-, and cognitive-function matched normal control subjects (NC group) were retrospectively enrolled from December 2012 to July 2015 in Beijing Hospital. All subjects underwent brain CEST-MRI and routine MRI. Based on the MATLAB software package, the 4-pool Lorentz fitting model was applied to analyze the signal change of CEST imaging, which could acquire the mean amplitudes of the 4-pool parameters including Amide, nuclear overhauser enhancement (NOE), direct water saturation (DS) and magnetization transfer (MT) in the bilateral SN and RN. Independent samples t test and Mann-Whitney U test were used to compare CEST parameters between the PD group and the NC group and controlled by Bonferroni correction. The combined model was constructed based on parameters with inter-group differences after correction. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the diagnostic efficiency of the CEST parameters and the combined model. Results:Compared with the NC group, the left SN Amide value, left RN Amide value, and right SN NOE value were reduced in the PD group, and the difference was statistically significant ( t=-3.59, corrected P=0.026; t=-3.77, corrected P=0.016; Z=-3.27, corrected P=0.017). The left SN Amide value, the left RN Amide value, the right SN NOE value, and the combined model all had good diagnostic efficacy in the differentiation of the PD group from the HC group (AUCs of 0.78, 0.79, 0.75, and 0.81, respectively). The combined model had the highest AUC value (0.81) and specificity (97.78%), the Amide value of left SN had the highest sensitivity (93.33%). Conclusions:Quantitative analysis of CEST-MRI based on the 4-pool Lorentz fitting model shows significant differences in the CEST quantitative indicators of the SN and RN between the PD group and the NC group, demonstrating good potential for clinical application in the diagnosis of PD.

Objective:To explore the difference of clinical characteristics between senile Parkinson's disease(PD)with depression and unipolar depression.Methods:From March 2019 to March 2020, 53 patients with Parkinson's disease depression and 57 patients with unipolar depression who were admitted to the neurology department of Beijing Hospital were continuously collected.The gender, age and education level of the patients were recorded.The course of disease and other general data of the patients with Parkinson's disease were also recorded.Depression and anxiety of the patients were evaluated by Beck Depression Inventory(BDI)and Generalized Anxiety Disorder Scale(GAD-7). Quality of life of patients with Parkinson's disease was evaluated by 8-item Parkinson's disease questionnaire(PDQ-8). Differences in the assessment results and quality of life scores between the two groups were analyzed.Results:The incidence of depression comorbid with anxiety in elderly PD patients was 52.8%(28/53), lower than that in elderly unipolar depression patients comorbid with anxiety [84.2%(48/57)]( χ2=12.664, P<0.001). The scores of activity inhibition [(1.8±0.8)points]and hyposexuality [(0.4±1.0)points]in elderly PD patients with comorbid depression were higher than that in patients with unipolar depression [(1.1±0.8)points, (0.0±0.0)points]( t=4.399, 2.942, P<0.001, =0.005). Moreover, the incidence of activity inhibition(98.1%)and hyposexuality(15.1%)in PD patients with comorbid depression was higher than that in patients with unipolar depression(78.9%, 0.0%)( χ2=9.680, 9.279, both P=0.002). The scores of self-blame [(1.0±0.8)points]and pain [(1.0±0.8)points]in elderly patients with unipolar depression were higher than those in PD patients with comorbid depression [(0.5±0.7)points, (0.9±0.7)points]( t=-3.902, -2.486, P<0.001, =0.014). Moreover, the incidence of self-blame(66.7%), irritability(78.9%)and image distortion(56.1%)in elderly patients with unipolar depression was higher than that in PD patients(35.8%, 56.6%, 35.8%)( χ2=10.447, 6.320, 4.547, P=0.001, 0.012, 0.033). The scores of PDQ-8 in PD patients with comorbid depression and anxiety [14.8(10.8, 19.0)points]( Z=-3.544, P<0.001)were higher than those in PD patients with depression only [7.0(4.8, 11.0)points]. Conclusions:The focus of depression in elderly PD patients is different from that in elderly unipolar depression patients.Elderly patients with unipolar depression are more likely to be comorbid with anxiety.Depression reduces the quality of life in PD patients, and the comorbidity of anxiety further reduces the overall quality of life in PD patients with depression.

Objective:To investigate the incidence of various non-motor symptoms (NMS) in early stage of Parkinson′s disease (PD) patients and the differences between the body-first and brain-first subtypes.Methods:A total of 121 patients with PD (Hoehn-Yahr stage 1-2) were recruited from PD Clinic, Department of Neurology, Beijing Hospital from January 2012 to January 2015. The general information and clinical features of the patients were collected. The minimal diagnostic criteria of parasomnias described in the International Classification of Sleep Disorders-Revised were used to diagnose rapid eye movement sleep behavior disorder (RBD).According to the sequence of RBD and motor symptoms, the patients were divided into 2 groups: body-first subtype and brain-first subtype. NMS was evaluated by the Non-Motor Symptom Questionnaire (NMSQuest). The clinical features and the incidence of various NMS were compared between the 2 groups. The Unified Parkinson′s Disease Rating Scale (UPDRS) was used to evaluate the severity of the disease, and its third part (UPDRS-Ⅲ) was used to evaluate the motor function of the patients. Hamilton Rating Scale for Depression (HAMD) and Hamilton Rating Scale for Anxiety (HAMA) were used to evaluate the depression and anxiety status of the patients. The sleep status of patients was assessed by Parkinson′s Disease Sleep Scale (PDSS). The quality of life of the patients was assessed by 39-item Parkinson′s Disease Questionnaire (PDQ-39).Results:Of all the patients, 49.59% (60/121) had the body-first subtype and 50.41% (61/121) had the brain-first subtype of PD. There was no significant difference in UPDRS-Ⅲ score between the 2 groups. The average number of NMS in all PD patients was 10.97±4.88. Body-first subtype patients had higher NMS incidence than brain-first subtype in difficulty in swallowing [46.7% (28/60) vs 23.0% (14/61), χ 2=7.507, P=0.006], nausea and vomiting [16.7% (10/60) vs 3.3% (2/61), χ 2=6.069, P=0.014], constipation [85.0% (51/60) vs 55.7% (34/61), χ 2=12.393, P<0.001], fecal incontinence [8.3% (5/60) vs 0 (0/61), χ 2=5.302, P=0.021], difficulty in remembering recent events [58.3% (35/60) vs 32.8% (20/61), χ 2=7.962, P=0.005], loss of interest [43.3% (26/60) vs 24.6% (15/61), χ 2=4.743, P=0.029], inattention [45.0% (27/60) vs 19.7% (12/61), χ 2=8.884, P=0.003], depression [55.0% (33/60) vs 34.4% (21/61), χ 2=5.181, P=0.023], intense vivid dreams [73.3% (44/60) vs 39.3% (24/61), χ 2=14.196, P<0.001] and restless legs [53.3% (32/60) vs 27.9% (17/61), χ 2=8.140, P=0.004]. The differences were significant. Body-first subtype and NMSQuest ( r=-0.489, P<0.001), UPDRS ( r=-0.189, P=0.038), HAMD ( r=-0.231, P=0.011), HAMA ( r=-0.298, P=0.001) and PDQ-39 scores ( r=-0.276, P=0.002) were negatively correlated. Body-first subtype and PDSS score was positively correlated. NMSQuest (Δ R2=0.265, P<0.001) was the main determinant of PDQ-39 score. Conclusions:PD patients are accompanied by various NMS, which is a major factor affecting the quality of life. Compared with brain-first subtype, body-first subtype might have more NMS burden and higher incidence rate in most NMS in early PD patients.

Objective:To investigate the grey matter alterations of Parkinson′s disease (PD) patients with and without sleep disorders, and to explore the relationship between different sleep-related problems and clinical variables as well as grey matter volume (GMV) in PD.Methods:Forty-six PD patients and 38 healthy controls (HCs) were recruited from January 2018 to December 2021 in the Department of Neurology, Beijing Hospital. PD patients were divided into PD with sleep disorders (PD-S, n=26) and PD without sleep disorders (PD-nS, n=20) subgroups (cutoff points of 82 for Parkinson′s Disease Sleep Scale or less than 5 for each item was considered as an indicator of substantial sleep disorder). The Mini-Mental State Examination (MMSE), the third part of the Unified Parkinson′s Disease Rating Scale (UPDRS-Ⅲ), Hamilton Rating Scale for Anxiety (HAMA), Hamilton Rating Scale for Depression (HAMD), Non-Motor Symptoms Questionnaire (NMSQ), and Parkinson′s Disease Questionnaire-39 (PDQ-39) were used to evaluate cognitive function, motor symptoms, anxious and depressive symptoms, non-motor symptoms, and the quality of life of the patients. Optimized voxel-based morphometry was applied to the magnetic resonance imaging brain images in all participants,and multiple linear regression analysis was used to test the correlation between GMV and sleep quality in patients with PD. Results:Compared with the HCs, PD-nS patients showed decreased GMV in bilateral limbic lobe, parahippocampal gyrus, amygdala, cingulate gyrus, hippocampus, right cerebellum, bilateral frontotemporal lobe, bilateral occipital lobe and the left parietal lobe. PD-S group exhibited reduced GMV in bilateral limbic lobe, parahippocampal gyrus, amygdala, right cerebellum, bilateral frontotemporal lobe and bilateral parietal-occipital lobe, compared to the HCs. Compared with PD-nS, PD-S patients revealed higher depressive (HAMD score: 12.19±5.59 vs 6.95±3.19, t=-4.01, P<0.001), anxious (HAMA score: 12.04±5.32 vs 7.25±4.68, t=-3.18, P=0.003), and non-motor symptoms scores (NMSQ score: 12.92±5.18 vs 9.90±4.10, t=-2.14, P=0.038), poorer quality of life (PDQ-39 score: 35.31±22.01 vs 22.40±9.00, t=-2.71, P=0.010), and reduced GMV in the left insula, frontal, and parietal lobe ( P<0.001, uncorrected, cluster>100). There was a marked relationship between sleep quality and the reduced GMV of the right medial temporal gyrus (β=0.006, 95% CI 0.002-0.010, P=0.003), left middle frontal gyrus (β=0.006, 95% CI 0.002-0.010, P=0.002), the right cerebellum (β=0.014, 95% CI 0.005-0.023, P=0.003), and the right medial occipital gyrus (β=0.017, 95% CI 0.011-0.024, P<0.001). Significant grey matter changes were associated with nocturnal restlessness, mainly within the left limbic lobe, bilateral occipital lobe, the right cerebellum, and parietal lobe (β=0.008, 95% CI 0.006-0.010, P<0.001). Furthermore, nocturia in PD was related to certain grey matter atrophy, including bilateral limbic lobe, the right inferior parietal gyrus, and bilateral frontal lobe (β=0.010, 95% CI 0.008-0.013, P<0.001). The symptom of daytime dozing was correlated with GMV reduction in the right occipital lobe, the left temporal lobe (β=0.014, 95% CI 0.010-0.019, P<0.001). There were also several compensatory brain regions, including bilateral frontal lobe, the left limbic lobe and cingulate ( P<0.001, uncorrected, cluster>60). Conclusions:Sleep disturbance is common in PD, which is related to the anxious and depressive symptoms, non-motor symptoms, and the quality of life. PD patients with different sleep disorders show grey matter alterations in severeal brain regions, which are associated with sleep quality, nocturnal restlessness, psychosis, and daytime dozing.

Objective:To investigate the clinical features and associated chronic pain in corticobasal syndrome (CBS).Methods:Clinical data of 8 patients diagnosed as probable CBS or possible CBS admitted to Beijing Hospital during January 2010 to June 2020 were retrospectively analyzed. The clinical information included sex, age, course of disease, chief complaint, neurological examination, blood biochemistry, tumor marker, infection and other laboratory tests; the neuropsychological evaluation included Mini-Mental State Examination (MMSE) scale and Hamilton Depression Scale (HAMD); the imaging studies included cranial magnetic resonance imaging (MRI) and/or 18F-Fluorodeoxyglucose positron emission tomography ( 18F-FDG PET). Results:The main clinical manifestations were asymmetrical movement disorders, including rigidity, tremor, myoclonus and abnormalities in posture and gait. Patients showed poor response to levodopa treatment. Among 8 patients, 7 had apraxia, 5 patients had alien hand, and 5 patients had various degrees of cognitive dysfunction. The cranial MRI demonstrated mild cerebral atrophy which was slightly more severe in the contralateral side of the initially affected limb in 7 of the 8 patients. The 18F-FDG PET scan revealed asymmetric decreased metabolism in the frontal, parietal, temporal, and occipital lobe, as well as in basal ganglia, which was more severe in the contralateral side of the initially affected limb in 5 of the 8 patients. Six of the 8 patients were associated with pain, including dystonic pain in 3 patients, neuropathic pain in 1 patient, musculoskeletal pain in 1 patient, and unexplained pain in 1 patient. Pain was the onset symptom in 1 patient and pain was relieved by taking levodopa in another patient. Conclusions:CBS is characterized by asymmetric dyskinesia and cognitive impairment, and often associated with apraxia, cortical sensory deficits, and alien limb. The MRI and PET are helpful for CBS diagnosis. Pain may be one of the common non-motor symptoms in CBS.

Objective:To investigate the accurrence and related factors of depression in patients with parkinson's disease (PD).Methods:One hundred PD patients with Parkinson′s disease (PD) were enrolled in Department of Neurology in Beijing Hospital from March to June 2019. The depressive mood, sleep status and health-related quality of life of PD patients were evaluated by Beck Depression Scale (BDI), Parkinson′s Disease Sleep Scale 2 (PDSS-2), and 8 items of Parkinson′s Disease Questionnaire (PDQ-8). Spearman correlation analysis and multivariate regression analysis were used to analyze the related factors of PD depression. Nonparametric test was used to analyze the differences between different sleep disorder domains in PD patients with depression.Results:The total score of BDI in 100 PD patients ranged from 0 to 44, with an average of 9.9±8.6 points; the total score of PDSS-2 ranged from 0 to 43, with an average of 12.0±9.2; the total scores of PDQ-8 ranged from 0 to 24, with an average of 6.4±6.0 points. The detection rate of depression in 100 PD patients was 42.0% (42/100), and the total BDI score of 22 patients with mild depression ranged from 10 to 15 with an average of 13.0±1.9; the total BDI score of 14 patients with moderate depression ranged from 16 to 25, with an average of 19.1±3.0; the total BDI score of 6 patients with major depression ranged from 28 to 44 points, with an average of 33.3±6.4. The depression in PD patients was positively correlated with PDQ-8 score ( t=8.908, P<0.01) and PDSS-2 score ( t=2.286, P=0.02); and 85.7% (36/42) of PD patients with depression had sleep disturbance. The score of sleep disturbance domain of PD patients with depression (9.8±3.9) was higher than that of nocturnal motor symptom domain (4.8±4.5) and nocturnal PD non-motor symptom domain (4.1±3.3) ( P<0.01). The scores of emotional health, relationship with loved ones, attention, communication ability dimensions of PDQ-8 were positively correlated with PD depression ( P<0.05). Conclusion:Depression is a common non-motor symptom of PD patients; and PD patients with depression suffer from reduced quality of life and are more prone to sleep disorders.

Enteral nutrition plays an irreplaceable role in the nutritional treatment of critically ill patients. In order to help clinical medical staff to manage the common complications during the implementations of enteral nutrition for critically ill patients, the consensus writing team carried out literature retrieval, literature quality evaluation, evidence synthesis. Several topics such as diarrhea, aspiration, high gastric residual volume, abdominal distension, etc. were assessed by evidence-based methodology and Delphi method. After two rounds of expert investigations, Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition) developed, and provided guidance for clinical medical staff.