Objective Watch the proprioceptive neuromuscular facilitation(PNF)in the treatment of patients with shoulder-hand syndrome,and to explore its relevant therapeutic mechanisms.Methods Sixty patients with shoulder-hand syndrome were split into two groups at random:thirty cases each for observation and control.The control group received both standard medication and training in rehabilitation.Intradermal needles were inserted at the Jianjing,Jianyu,Binao,Qing Lengyuan,Shouwuli,and Quchi points and left in place for 48 hours for the treatment group.The PNF treatment was administered for thirty minutes every day,five times a week,whereas the control group underwent four weeks of traditional drug treatment and rehabilitation training.Before and after therapy,the following measures were used:the Disability of the Arm,Shoulder and Hand(DASH),the Activity of Daily Living Scale(ADL),the Simplified Fugl-Meyer Scale(FMA),and the Visual Analog Scale(VAS).In order to measure changes in endothelin-1(ET-1),nitric oxide(NO),and bradykinin(BK),serum was collected.Result Scale score:①Within-group comparison,compared with before treatment,VAS and DASH scores were significantly lower,FMA,a significant rise in ADL scores,differences were statistically significant(P<0.01).②Comparison between groups,compared with the control group,observation group of DASH score significantly lower after treatment(P<0.05),a significant rise in FMA and ADL scores(P<0.05),VAS score has no obvious difference(P>0.05).Laboratory index test:①Intra-group comparison:compared with before treatment,BK and ET-1 expression levels increased,NO and CGRP expression levels decreased,the differences were statistically significant(P<0.01).②Comparison between groups:Following treatment,the observation group showed increases in BK and ET-1 expression degrees as well as decreased NO and CGRP expression degrees.This difference was statistically significant(P<0.01).Conclusions Intradermal needle combined with PNF can promote shoulder pain symptoms,increase upper limb mobility,also improve quality of life in patients with shoulder-hand syndrome.One of the mechanisms may be to upregulate the expression level of BK and ET-1,and downregulate the expression level of NO and CGRP,so as to improve the microcirculation function and reduce the neurogenic inflammatory response.

Objective:To explore the relationship between depressive symptoms and childhood abuse and neg-lect in college students,and the roles of attentional control and attentional bias in their relationship.Methods:Total-ly 871 students from a medical university in Guangzhou were recruited to complete the Patient Health Question-naire-9(PHQ-9),Childhood Trauma Questionnaire(CTQ),Attention Control Scale(ACS),and Attention to Posi-tive and Negative Information Scale(APNI).The summed scores of emotional abuse,physical abuse and sex abuse subscale of CTQ were computed to measure childhood abuse,while the summed scores of emotional neglect and physical neglect subscale of CTQ were computed to measure childhood neglect.Results:Childhood abuse and child-hood neglect scores were both positively associated with PHQ-9 scores(β=0.01,0.01),and negatively associated with ACS scores(β=-0.30,-0.14).Childhood abuse scores were positively associated with negative attentional bias scores(β=0.24),and negatively associated with positive attentional bias scores(β=-0.14).Childhood neg-lect scores were negatively associated with positive attentional bias scores(β=-0.22).Attentional control and at-tentional bias played mediating roles between childhood abuse,childhood neglect and depressive symptoms,and the mediating effects accounted for 53.99％and 40.28％of the total effects,respectively.Conclusion:Depressive symptoms in college students are related to both childhood abuse and neglect,and attentional control and positive,negative attentional bias mediate such associations.

Objective:To explore the relationship between depressive symptoms and childhood abuse and neg-lect in college students,and the roles of attentional control and attentional bias in their relationship.Methods:Total-ly 871 students from a medical university in Guangzhou were recruited to complete the Patient Health Question-naire-9(PHQ-9),Childhood Trauma Questionnaire(CTQ),Attention Control Scale(ACS),and Attention to Posi-tive and Negative Information Scale(APNI).The summed scores of emotional abuse,physical abuse and sex abuse subscale of CTQ were computed to measure childhood abuse,while the summed scores of emotional neglect and physical neglect subscale of CTQ were computed to measure childhood neglect.Results:Childhood abuse and child-hood neglect scores were both positively associated with PHQ-9 scores(β=0.01,0.01),and negatively associated with ACS scores(β=-0.30,-0.14).Childhood abuse scores were positively associated with negative attentional bias scores(β=0.24),and negatively associated with positive attentional bias scores(β=-0.14).Childhood neg-lect scores were negatively associated with positive attentional bias scores(β=-0.22).Attentional control and at-tentional bias played mediating roles between childhood abuse,childhood neglect and depressive symptoms,and the mediating effects accounted for 53.99％and 40.28％of the total effects,respectively.Conclusion:Depressive symptoms in college students are related to both childhood abuse and neglect,and attentional control and positive,negative attentional bias mediate such associations.

Objective Watch the proprioceptive neuromuscular facilitation(PNF)in the treatment of patients with shoulder-hand syndrome,and to explore its relevant therapeutic mechanisms.Methods Sixty patients with shoulder-hand syndrome were split into two groups at random:thirty cases each for observation and control.The control group received both standard medication and training in rehabilitation.Intradermal needles were inserted at the Jianjing,Jianyu,Binao,Qing Lengyuan,Shouwuli,and Quchi points and left in place for 48 hours for the treatment group.The PNF treatment was administered for thirty minutes every day,five times a week,whereas the control group underwent four weeks of traditional drug treatment and rehabilitation training.Before and after therapy,the following measures were used:the Disability of the Arm,Shoulder and Hand(DASH),the Activity of Daily Living Scale(ADL),the Simplified Fugl-Meyer Scale(FMA),and the Visual Analog Scale(VAS).In order to measure changes in endothelin-1(ET-1),nitric oxide(NO),and bradykinin(BK),serum was collected.Result Scale score:①Within-group comparison,compared with before treatment,VAS and DASH scores were significantly lower,FMA,a significant rise in ADL scores,differences were statistically significant(P<0.01).②Comparison between groups,compared with the control group,observation group of DASH score significantly lower after treatment(P<0.05),a significant rise in FMA and ADL scores(P<0.05),VAS score has no obvious difference(P>0.05).Laboratory index test:①Intra-group comparison:compared with before treatment,BK and ET-1 expression levels increased,NO and CGRP expression levels decreased,the differences were statistically significant(P<0.01).②Comparison between groups:Following treatment,the observation group showed increases in BK and ET-1 expression degrees as well as decreased NO and CGRP expression degrees.This difference was statistically significant(P<0.01).Conclusions Intradermal needle combined with PNF can promote shoulder pain symptoms,increase upper limb mobility,also improve quality of life in patients with shoulder-hand syndrome.One of the mechanisms may be to upregulate the expression level of BK and ET-1,and downregulate the expression level of NO and CGRP,so as to improve the microcirculation function and reduce the neurogenic inflammatory response.

The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.

This study aimed to assess the efficacy and safety of gilteritinib combined with chemotherapy in treating newly diagnosed FLT3-mutated acute myeloid leukemia (AML). We retrospectively collected clinical data from 16 patients newly diagnosed with FLT3-mutated AML at Jiangsu Province Hospital. Patients received induction therapy with the classic "3 + 7" regimen or the VA regimen, and all patients were immediately supplied with gilteritinib after detecting FLT3-ITD/TKD mutations. Of the 16 patients, 12 were male and 4 were female, with a median age of 52.5 years (range: 15-76 years). Additionally, 15 patients had FLT3-ITD mutations and 1 had FLT3-TKD mutation. The complete remission (CR/CRi) rate was 93.8% (15/16) after the first cycle of gilteritinib-based induction therapy, with 13 patients achieving MRD negativity detected with flow cytometry. All patients achieved a CR MRD- during the consolidation phase. FLT3 mutation clearance was achieved among all 14 patients who underwent next-generation sequencing (NGS) analysis. The 12-month overall survival and relapse-free survival rates were both 73.9%, respectively, with a median followup of 18 months. Nine (56.2%) patients experienced infectious fever during the induction therapy. Three patients had grade 3 QTc prolongation during consolidation and maintenance therapy. Treatment-related adverse events were generally tolerable.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective:To explore the genetic background for a patient with refractory myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with co-morbid neutrophilia patient.Methods:A MDS/MPN patient who was admitted to the First Affiliated Hospital of Nanjing Medical University in May 2021 was selected as the study subject. RNA sequencing was carried out to identify fusion genes in his peripheral blood mononuclear cells. Fusion gene sequence was searched through transcriptome-wide analysis with a STAR-fusion procedure. The novel fusion genes were verified by quantitative real-time PCR and Sanger sequencing.Results:The patient, a 67-year-old male, had progressive thrombocytopenia. Based on the morphological and molecular examinations, he was diagnosed as MDS/MPN with co-morbid neutropenia, and was treated with demethylating agents and Bcl-2 inhibitors. Seventeen months after the diagnosis, he had progressed to AML. A novel fusion gene NCOR1: : GLYR1 was identified by RNA-sequencing in his peripheral blood sample, which was verified by quantitative real-time PCR and Sanger sequencing. The patient had attained morphological remission after a DCAG regimen (a combinatory chemotherapy of decitabine, cytarabine, aclarubicin and granulocyte colony-stimulating factors) plus Chidamide treatment. A significant decrease in the NCOR1: : GLYR1 expression was revealed by quantitative real-time PCR at post-chemotherapy evaluation. Conclusion:NCOR1: : GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

Patients with low-prognosis undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment are mainly manifested as poor ovarian response to exogenous gonadotropin stimulation and a lower clinical pregnancy rate than normal responders of the same age. In the past, Bologna criteria was used to define and diagnose those patients. In 2016, the Patient Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) group proposed a new subdivision standard for low prognosis population in order to improve the homogeneity of them, which conceptually moved from poor response to poor prognosis and provided a classification basis for clinical treatment guidance and clinical counselling for POSEIDON patients. There are various controlled ovarian hyperstimulation protocols applied to POSEIDON groups, which have different effects on clinical application among different subgroups. This article will describe and summarize the progress of different ovulation induction regimens and adjuvant treatment strategies for patients with low-prognoses based on the POSEIDON criteria.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).