ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective To investigate the diagnostic value of magnetic resonance imaging(MRI)-based intratumoral and peritumoral radiomics of prostate cancer(PCa)for bone metastases.Methods A total of 211 patients diagnosed with PCa by biopsy pathology at Gansu Provincial People's Hospital from January 2018 to January 2023 were retrospectively analyzed.These patients were randomly divided into a training set(n=147)and a validation set(n=64)in a 7:3 ratio.Regions of interest(ROIs)were delineated from the patients'T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),and apparent diffusion coefficient imaging(ADC)sequences to extract radiomic features.Z-score(normalization)and the LASSO algorithm were used for feature dimensionality reduction,selection,and construction.A predictive model was then built using a logistic regression(LR)machine learning classifier.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to assess the model's performance.Calibration curves and decision curves(DCA)were plotted to evaluate the model's fit and clinical net benefit.Results Radiomic features were extracted from the tumor and peritumoral regions in each patient's T2WI,DWI,and ADC images,with a total of 312 features from each region.The LASSO regression model ultimately identified 10 intratumoral radiomic features closely related to bone metastasis,including 2 T2 sequence features,7 DWI features,and 1 ADC sequence feature;and 9 peritumoral radiomic features,including 4 T2 sequence features,3 DWI features,and 2 ADC sequence features.The predictive model based on intratumoral radiomic features achieved an AUC of 0.845(95%CI 0.747-0.943),while the predictive model based on peritumoral radiomic features had an AUC of 0.818(95%CI 0.716-0.919).A combined nomogram model incorporating intratumoral features,peritumoral radiomic features,and clinical features(including Gleason score,total prostate specific antigen,and body mass index)yielded an AUC of 0.936(95%CI 0.902-0.970).Calibration curves indicated that the combined model had good fit,and DCA demonstrated that the combined model provided better clinical net benefit.Conclusions Peritumoral radiomics has excellent predictive value for bone metastasis in newly diagnosed PCa.Combining with intratumoral radiomics features and clinical features,it significantly enhances the predictive capability of the model.

AIM: To analyze the clinical characteristics of acute acquired concomitant esotropia(AACE)in patients among different age groups.METHODS: Retrospective analysis of clinical data. A total of 112 non-Swan type AACE patients who underwent surgery at Peking University People's Hospital from January 2015 to December 2022 were retrospectively analyzed. Clinical data were collected and the characteristics were compared, including gender, age, diopter, duration of disease, daily time spent on near work, angles of deviation before and after surgery, stereopsis, etc. According to age, patients were divided into three groups: <18 years old group(22 cases), 18-45 years old group(67 cases), and >45 years old group(23 cases). The clinical characteristics of patients were compared in each group.RESULTS: A total of 112 patients were included in the study, comprising 56 males and 56 females, with a median age of 29.50(19.25, 41.75)years old. Among them, 97 patients had myopia(86.6%). There were 93 patients(83.0%)who spent more than 8 h on near work. The age group <18 years old had the shortest duration before surgery, with a median time of 1.00(0.50, 1.00)a, the minimum negative diopter, with a median diopter of -0.75(-3.19, -0.56)D in the right eye and the diopter of -1.25(-2.81, -0.75)D in the left eye, and the maximum preoperative near angle of deviation, with a median angle of 30.00(18.50, 80.00)PD, and the maximum preoperative distant angle of deviation, with a median angle of 35.00(23.75, 80.00)PD. All these differences were statistically significant compared with other two groups(both P<0.05). For the age group from 18 to 45 years old, the median near angle of deviation was 20.00(14.00, 30.00)PD, and the median distant angle of deviation was 25.00(20.00, 35.00)PD, both of which were higher than those in the age group >45 years old(both P<0.05). For the age group >45 years old, the median near angle of deviation after surgery was -4.50(-7.50, 0)PD, and the median distant angle of deviation after surgery was 4.50(0, 9.50)PD, which were smaller than those in other two groups(all P<0.05). The age group >45 years old had the hiughest surgical success rate(100%). The preoperative stereopsis was better in age group >45 years old than the group <18 years old(P<0.05). The postoperative stereopsis of the age group of 18 to 45 years old and the age group >45 years old was better than age group <18 years old(both P<0.05).CONCLUSION: Surgical patients with AACE are mainly in the age group from 18 to 45 years old. The characteristic of angle of deviation is that distant angle of deviation is greater than near angle of deviation. The patients <18 years old have larger preoperative angles of deviation than adults, while their stereoacuity is worse than adults in the early postoperative period. It is recommended that augmented-dose surgery should be performed in AACE patients who are in the age group of 18 to 45 years old(5-10 PD). A conservative surgery should be designed for hyperopia young children without established binocular vision.

Objective Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of hospitalization and death in patients with chronic obstructive pulmonary disease (COPD). Exploring the prognostic factors of AECOPD patients will assist in optimizing treatment strategies and standardizing disease management. Methods This study retrospectively collected the clinical data of 664 patients with AECOPD admitted to the Respiratory Department of Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2013 to September 2019. The 3-year survival rate and treatment of the patients were investigated. According to whether the patients died,they were divided into a non-survivors group and a survivors group,and clinical data such as basic information,comorbidities,and auxiliary examination results were compared between the two groups. Incorporating clinical experience of researchers and previous research evidence,a secondary screening of variables was conducted to ultimately determine the covariates to be included in the multifactorial Cox proportional hazards regression model,and the factors affecting the 3-year survival rate of the patients were analyzed. Results A total of 664 cases were included in this study,including 362 males and 302 females,with an average age of (77.25±6.89) years old. The 3-year all-cause mortality rate of older hospitalized patients with AECOPD was 20.48％(136 patients). Older age (HR:1.071,95％CI:1.040-1.102,P<0.001);smoking history (HR:1.788,95％CI:1.173-2.723,P=0.007);Charlson comorbidity index (HR:1.209,95％CI:1.029-1.421,P=0.022);lower arterial partial pressure of oxygen (HR:1.014,95％CI:1.006-1.022,P<0.001);higher brain natriuretic peptide(HR:1.001,95％CI:1.000-1.001,P=0.025);cor pulmonale(HR:1.896,95％CI:1.235-2.908,P=0.004);respiratory failure (HR:2.437,95％CI:1.378-4.311,P=0.003);TCM syndrome differentiation elements,including kidney (HR:1.639,95％CI:1.055-2.546,P=0.028) and fluid retention (HR:2.512,95％CI:1.653-3.816,P<0.001),were independent risk factors for 3-year all-cause death of older hospitalized patients with AECOPD. Long-term regular use of bronchiectasis (HR:0.474,95％CI:0.324-0.695,P<0.001) was an independent protective factor for 3-year all-cause death. Conclusion The 3-year survival rate of elderly hospitalized patients with AECOPD is relatively low,with the TCM syndrome elements manifested as lung-kidney qi deficiency,yang deficiency with water retention,and blood stasis obstruction. Patients with moderate to severe impairment of lung function due to COPD have an increased risk of death within 3 years. Therefore,for such patients,nourishing lung-kidney qi,resolving phlegm and water retention,activating blood circulation to remove blood stasis and dredging collaterals,combined with regular use of bronchodilators,may help improve their 3-year survival rate.

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity