Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.

Objective : To develop and to validate a combined model integrating18F-FDG PET/CT radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia. Methods : A retrospective study was conducted on a cohort of 232 patients diagnosed with lymphoma or lymphoid inflammatory hyperplasia. Comparative analyses of clinical and traditional imaging indicators were performed to identify inter-group differences. The clinical features were delineated and extracted using medical software including 3D-Slicer and Lifex. Selection of the features was performed to construct a PET/CT-based radiomics Logistic model, with a combined model integrating PET/CT with clinical features then used to evaluate the discriminative efficacy of these models. Results: Analysis of inter-group differences indicated that age, CTmean, and metabolic tumor volume(MTV)were effective for differentiating between lymphoma and lymphoid inflammatory hyperplasia(P<0.05). The PET/CT-based radiomics Logistic model differentiated between lymphoma and lymphoid inflammatory hyperplasia, with an area under curve(AUC) of 0.924(95%CI: 0.884-0.960) and 0.863(95%CI: 0.774-0.939) in the training and testing cohorts, respectively. The integrated Logistic model that combined PET/CT-based radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia achieved an AUC of 0.933(95%CI: 0.889-0.969) in the training cohort and 0.884(95%CI: 0.792-0.964) in the testing cohort. Decision curve analysis(DCA) demonstrated that the integrated model provided the greatest clinical net benefit. Conclusion The hybrid model integrating18F-FDG PET/CT radiomics with clinical features shows robust diagnostic efficacy to distinguish between lymphoma and lymphoid inflammatory hyperplasia.

N?ive CD4+T cells play a key role in the initiation and maintenance of immune response.In the effect of cytokines and costimulatory molecules,they differentiate into Th1,Th2,Treg and Th17.Increasing evidences indicated that Th17 and Treg cells produce a significant effect on immune stability,autoimmune disease and cancer.Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is the most common type of prostatitis,accounting for 90%～95%,which is closely correlated with the progression of be-nign prostatic hyperplasia and prostate cancer.Benign and malignant diseases of the prostate share much similarity in immune microen-vironment.Thus,this review summarizs the latest research progress on the mechanism of Th17/Treg cells in prostatic disease.

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Neurons/metabolism* ; Brain/metabolism*

Objective:To evaluate the performance of rural practitioners of endoscopic cleaning and disinfection participating in the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers and to analyze the influencing factors.Methods:The questionnaires for skill assessment were designed based on the skill scheme and clinical practice of the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China, and the App Early diagnosis, Early treatment was used as the examination platform. The practitioners in 539 county hospitals from 25 provinces participating in the program in 2019 were assessed for techniques and skills for endoscopic cleaning and disinfection and the excellence rate was calculated. Multivariate logistic regression model was used to analyze the influencing factors for the examination. Results:A total of 1 671 endoscopic cleaning and disinfection practitioners participated in the assessment with the score of 73.41±16.60. The passing rate was 85.82%, and the excellence rate was 44.94%. Among all questions, the correct rate of "opportunistic screening flow chart" was the highest (98.21%), and that of "the evaluation index for mass screening" was the lowest (57.89%). The multivariate logistic regression analysis showed that the excellence rate was high in practitioners who had a bachelor degree or above ( OR=1.627,95% CI:1.319-2.007, P<0.001), the career for 5 to <15 years (5 to <10 years: OR=1.329,95% CI:1.045-1.689, P=0.020; 10 to <15 years: OR=1.384,95% CI:1.026-1.867, P=0.033), working in eastern and central regions (eastern regions: OR=3.476,95% CI:2.368-5.103, P<0.001;central regions: OR=4.028,95% CI:2.679-6.057, P<0.001) and with full understanding of the screening scheme ( OR=1.547,95% CI:1.246-1.921, P<0.001) . Conclusion:Practitioners on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China have mastered the basic screening scheme and skills for endoscopic cleaning and disinfection. The education background, duration of the career, area and understanding of screening scheme are influencing factors for the excellence rate of endoscopic cleaning and disinfection.

Objective:To analyse the current status of parturients' readiness for discharge, family functioning and psychological consistency, and to explore the relationship readiness for discharge, family functioning and psychological consistency.Methods:This was a cross-sectional study. Using the convenient sampling method, a total of 429 parturient women admitted to Obstetrics Department in two ClassⅢ Grade A hospitals in Yinchuan City from March to July 2022 were selected as the research objects. General Information Questionnaire, Family Assessment Device (FAD) , Readiness for Hospital Discharge Study-New Mother Form (RHDS-NMF) and Sense of Coherence-13 (SOC-13) were used to investigate the patients. A total of 429 questionnaires were sent out in this study, and 418 questionnaires were effectively collected, with an effective recovery rate of 97.44% (418/429) .Results:The total score of RHDS-NMF in 418 parturient women was (131.18±24.96) , the total score of FAD was (127.76±15.57) , and the total score of SOC-13 was (54.59±7.22) . The discharge readiness of parturient women was negatively correlated with family function ( r=-0.332, P<0.01) , while discharge readiness was positively correlated with psychological consistency ( r=0.253, P<0.01) . The mediation effect analysis results showed that psychological consistency played a partial mediating role between family function and discharge readiness in parturient women, with a mediation effect value of -1.105 ( P<0.05) , accounting for 27.1% of the total effect. Conclusions:Psychological consistency plays a partial mediating role between family function and discharge readiness in parturient women. Medical staff should pay attention to the evaluation and intervention of parturients' psychological consistency, enhance their level of psychological consistency and improve readiness for discharge.

The blood samples of 294 Chinese Han patients with type 1 diabetes mellitus(T1DM) and 199 controls were collected and their genomic DNAs were extracted. The single nucleotide polymorphisms rs17534481, rs12095738, rs2988276, and rs6668182 of CD247 gene were detected. The results showed that rs17534481 polymorphism of CD247 gene was associated with T1DM in Chinese Han population, and T allele was a protective factor for type 1 diabetes mellitus( OR=0.667, P=0.037). There was no significant difference in genotype frequency and allele frequency of rs12095738, rs2988276, and rs6668182 between type 1 diabetes group and control group( P>0.05).