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.

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.

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.

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.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective To investigate the feasibility and safety of using catheter fenestration technology in transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)supplied by the right inferior phrenic artery(RIPA).Methods From March 2023 to May 2023,five HCC patients,whose HCC lesions were supplied by RIP A,received TACE by using catheter fenestration technology to accomplish the superselective catheterization of RIPA after the conventional microcatheter catheterization of RIPA failed.Results Superselective catheterization of RIPA and TACE were successfully accomplished in all the 5 patients,with a surgical success rate of 100％.The time spent for superselective catheterization of RIPA was(3.2±2.39)minutes.After TACE,the levels of the tumor indicators were decreased when compared with the pre-TACE values,while the liver function indexes showed no obvious damage.Based on the mRECIST criteria,PR was obtained in 3 patients and CR was obtained in 2 patients.None of the five patients developed serious adverse reactions.Conclusion In treating patients with HCC supplied by RIPA,the use of catheter fenestration technology can safely and effectively improve the success rate of superselective catheterization of RIPA during TACE.

Objective To explore the effect of methylene blue combined with ropivacaine for sa-phenous nerve block on the postoperative analgesia in patients undergoing total knee arthroplasty.Methods Sixty patients were selected for elective TKA,24 males and 36 females,aged 60-75 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using randomized nu-merical table method:methylene blue combined with ropivacaine group(group MR)and ropivacaine group(group R),30 patients in each group.Ultrasound-guided saphenous nerve block was performed with 0.10％methylene blue+0.25％ropivacaine composite 20 ml in group MR,and ultrasound-guided saphenous nerve block was performed with 0.25％ropivacaine 20 ml in group R before the combined spinal-epidural anesthe-sia.The VAS pain scores at rest and during activity at 6,12,24,48,and 72 hours postoperatively,the maximum range of motion mobility(ROM)of the knee joint of the affected limb,the quadriceps unarmed manual muscle test(MMT)scores at 24,48,and 72 hours postoperatively,the effective number of analge-sic pump presses,and the time of the first additional time of the remedial analgesic were recorded.The com-plications related to nerve block,such as bleeding,infection,local anesthetic poisoning,nerve injury,and peripheral tissue injury were recorded.Results Compared with group R,the VAS pain score at rest was significantly lower in group MR at 12,24,48,and 72 hours postoperatively(P＜0.05).Compared with group R,the VAS pain scores during activity were significantly lower in the group MR at 48 and 72 hours postoperatively(P＜0.05).Compared with group R,ROM of the knee joint of the affected limb was signif-icantly greater in group MR at 24,48,and 72 hours postoperatively(P＜0.05).The effective number of analgesic pump presses and the rate of remedial analgesia were significantly lower in the group MR compared with group R(P＜0.05).There were no complications related to nerve block during hospital stay in both groups.Conclusion Ultrasound-guided methylene blue combined with ropivacaine for saphenous nerve block can enhance the postoperative analgesic effect,prolong the duration of analgesia,reduce the use of postoperative analgesics,and facilitate the functional exercise of the knee joint in the early postoperative pe-riod.