Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.

Objective To explore the efficacy of ransapical-transcatheter aortic valve replacement(TA-TAVR)in patients with severe aortic regurgitation(AR)with different ejection fraction.Methods The clinical data of patients with severe AR undergoing TA-TAVR from November 2017 to January 2023 were retrospective reviewed,severe AR patients with left ventricular ejection fraction(LVEF)≥50％were included in the ejection fraction preserved group and patients with severe AR with LVEF＜50％were included in the reduced ejection fraction group.Clinical data of the patients in group 2 were analyzed.Results A total of 60 patients were included,including 24 in ejection fraction preserved group and 36 in reduced ejection fraction group.All group had significantly improved aortic regurgitation volume 1 day after surgery compared with preoperative volume.The left ventricular remodeling(LVR)indexes[left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPW),LVEF]improved significantly at 1 day after surgery,and remained relatively stable thereafter.The improvement in LVR in reduced ejection fraction group patients was only 3 months after surgery.Two groups of patients had a decrease in amino-terminal probrain natriuretic peptide(NT-proBNP)levels three months after surgery compared to before.Patients in ejection fraction preserved group remained stable thereafter,while patients in reduced ejection fraction group had an increase one year after surgery compared to before.The one-year heart failure rehospitalization rate in reduced ejection fraction group was higher than that in ejection fraction preserved group,and the mean scores of EQ-5D-3L and EQ-VAS were lower than those of patients in ejection fraction preserved group.Comparison of the incidence of atrial fibrillation,third degree atrioventricular block,and permanent pacemaker implantation rate,stroke incidence,leaflet thrombosis incidence,paravalvular leakage incidence,and survival rate,the usage of some drugs at 1 year in both group,there was no statistically significant difference(all P＞0.05).Conclusions TA-TAVR can effectively relieve aortic regurgitation in severe AR patients with different ejection fraction and promote left ventricular reverse remodeling.Intervention in patients with severe AR with preserved ejection fraction should be performed as early as possible.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Objective To study the cyclic peptides from sponge Reniochalina sp. under the guidance of mass spectrometry. Methods Mass spectrometry-guided procedural separation methods were used to track and isolate the cyclic peptides from the sponge genus Reniochalina. The structures of compounds were elucidated by the determination of physicochemical parameters and comparison of spectroscopic data. The preliminary cytotoxic activity of compounds was assessed by the Cell Counting Kit-8 (CCK-8) method. Results Three cyclic peptides were isolated from the sponge Reniochalina sp. and identified as stylopeptide 1 (1), hymenamide D (2) and axinastatin 2 (3). Compound 1 exhibited cytotoxicity against six human cancer cell lines with IC₅₀ values ranging from 6.09 to 17.26 μmol/L. Conclusion Compound 1 - 3 were isolated from Reniochalina sp. for the first time, and compound 1 was a cytotoxic cyclic heptapeptide.

OBJECTIVE To provide ideas for pharmaceutical care of Mycobacterium abscess infection. METHODS The diagnosis and treatment plan ，about a patient with M. abscess infection after resection of intervertebral neurilemmoma participated by clinical pharmacists ，was analyzed . According to the results of bacterial culture and drug sensitivity test of wound secretion ，the clinical pharmacist timely dealed with the adverse drug reactions during the treatment . For the tinnitus caused by the patient taking amikacin（0.4 g，intravenous drip ，q12 h），it was suggested to stop amikacin and replace it with linezolid ；however，the patient suffered from knee pain after taking linezolid . The clinical pharmacist once again suggested stopping linezolid ，continuing to use amikacin，and adjusting the dose to 0.8 g，intravenous drip ，q24 h；at the same time ，the patients were given medication guidance and ordered to have regular follow -up after discharge . RESULTS The physicians adopted the suggestions of clinical pharmacists ， and the patient did not suffer from tinnitus ，knee pain and other discomfort ，and the liver and kidney functions were normal . CONCLUSIONS Clinical pharmacists timely assist clinicians to adjust the medication plan ，which improves the effectiveness and safety of patients ’medication.

The teaching effect of "process management and evaluation" was assessed in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture-moxibustion speciality. A total of 120 postgraduates of non-acupuncture-moxibustion speciality participating in resident standardization training were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). In the control group, the conventional training mode was used. In the observation group, the "process management and evaluation" was adopted, in which, the syllabus was refined, various teaching modes were cooperated and the summary was conducted once a week. The training results were evaluated at the end of 1-month shift test and questionnaire was issued in all of the postgraduates of the two groups. In the observation group, the score for theory and the score of each of the items for technical ability, named differentiation and treatment, technical manipulation and physician-patient communication, as well as the total score were all higher than the control group successively (
Acupuncture ; Acupuncture Therapy ; Hospitals ; Humans ; Moxibustion ; Reference Standards

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

OBJECTIVE: To explore the genetic etiology of three pedigrees with a gestational history of fetal renal anomalies. METHODS: Peripheral venous blood or skin samples were derived from the probands of the three pedigrees. Copy number variation sequencing (CNV-seq) was applied to detect alterations of genome CNVs. RESULTS: The patient from pedigree 1 and the fetuses from pedigrees 2 and 3 all carried a heterozygous 17q12 deletion, with the size ranging from 1.4 Mb to 1.48 Mb encompassing the HNF1B gene. CONCLUSION The diagnosis of 17q12 microdeletion may be difficult during fetal period for its variable phenotypes. Alterations of chromosomal copy numbers need to be excluded in such patients.
Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; DNA Copy Number Variations ; Fetus ; Genetic Testing ; Hepatocyte Nuclear Factor 1-beta ; genetics ; Humans ; Pedigree ; Phenotype