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.

Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To summarize the operation techniques and experience of arthroscopic"pie-crustiong"release for patellofemoral joint hypertension.Methods From August 2021 to April 2023,67 patients(75 knees)suffered from isolated patellofemoral compression syndrome.The lateral retinacular of knees were arthroscopic released by pie crusting technique.All knees were assessed by AKS and Kujala scores.Results The follow-up period ranged from 3 to 18 months.All patients had good wound healing without infection,joint hematosis,fluid accumulation,and limited movement.AKS score of knee joint was(44.88±5.49)points before surgery and(69.57±4.64)points 3 months after surgery.Kujala score was(47.08±6.28)points before surgery and(68.75±4.47)points 3 months after surgery.The Vas score was(2.81±0.67)points before surgery and(0.85±0.65)points 3 months after surgery.The AKS,Kujala and Vas scores of knee joint after treatment were higher than those before treatment,and the differences were statistically significant(P＜0.05).Conclusion The treatment of arthroscopic"pie-crusting"technique can improve the patellar joint matching degree,relieve pain and improve quality of life.

Objective:To explore a simple emergency management method for elderly patients with sigmoid volvulus.Methods:The clinical data of 22 elderly patients (>70 years) with sigmoid volvulus from January 2020 to March 2024 in the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. All patients were treated with a self-made simple closed-loop enema decompression kit. The abdominal circumference, white blood cell count and C-reactive protein (CRP) before treatment and 12 h after tube placement were measured. The patients were followed for 3 months, and the recurrence was recorded. The key indexes on recurrence, including age, American Society of Anesthesiologists (ASA) classification and procedure time, were compared. Pearson correlation analysis was used to examine the relationship between age, procedure time, pain level and gas/stool output within 30 min after tube placement.Results:All 22 patients successfully underwent transanal tube decompression. The procedure time ranged from 1 to 15 min. The gas and stool output within 30 min after tube placement was 600 to 2 100 ml, The rectal tube was retained for 2 to 6 d. Compared with before treatment, the abdominal circumference, white blood cell count and CRP 12 h after tube placement were significantly lower: (85.9 ± 9.6) cm vs. (94.5 ± 10.2) cm, (9.2 ± 2.1) ×10 9/L vs. (11.4 ± 2.5) ×10 9/L and (27.8 ± 22.6) mg/L vs. (46.2 ± 38.9) mg/L, and there were statistical differences ( P<0.01). Four patients underwent elective surgery, while 18 were discharged smoothly after tube removal. No death occurred within 1 month after treatment. Five patients experienced recurrence 3 months after treatment, all were successfully retreated using the same method and discharged. There were no statistical differences in recurrence rates between aged ≥80 years and aged < 80 years patients, ASA class ≥ Ⅳ and ASA class Ⅲ patients, or procedure times ≤5 min and procedure times >5 min patients ( P>0.05). The gas/stool output within 30 min after tube placement was positively correlated with pain level (moderate/severe vs. mild) before tube placement ( r = 215.50, P = 0.015), but showed no significant correlation with age or procedure time ( P>0.05). Conclusions:The self-made simple closed-loop enema decompression kit provides a straightforward, economical and minimally invasive emergency treatment method for elderly patients with sigmoid volvulus. For patients at very high surgical risk, this kit can achieve decompression and volvulus reposition, even in cases of recurrence.

Objective:To investigate the clinical value of right-sided overlap and single-flap valvuloplasty (ROSF) in Da Vinci robotic proximal gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 12 patients who underwent ROSF in Da Vinci robotic proximal gastrectomy at The Affiliated Hospital of Xuzhou Medical University from September 2023 to May 2024 were collected. There were 7 males and 5 females, aged 62(range, 35?75)years. Observation indicators: (1) surgical conditions; (2) postoperative pathological results; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and mea-surement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Results:(1) Surgical conditions. All patients successfully completed the surgery, without conversion to laparotomy. The operation time of 12 patients was (236±24)minutes. The time of single-layer fabrication and anastomosis was (105±28)minutes. The volume of intra-operative blood loss was (36±19)mL. Time to postoperative first fluid food intake was (3.5±1.1)days. The amylase levels in the abdominal drainage fluid on postoperative days 1, 2, and 3 were (321±121)U/L, (225±97)U/L, and (85±22)U/L, respectively. Time to postoperative drainage tube removal was (5.3±1.5)days. Duration of postoperative hospital stay was (7.6±1.1)days. All 12 patients had no anasto-motic related complications such as anastomotic leakage, anastomotic bleeding, anastomotic stenosis, and had no functional complications such as gastric emptying disorders or gastroesophageal reflux after surgery. (2) Postoperative pathological results. The distance of the proximal tumor margin of the 12 patients was (1.8±1.1)cm. The distance of distal margin was (5.7±2.1)cm. Number of lymph node dissected was 31.0(range, 22.0?45.0). Number of positive lymph node dissected was 3.4±2.4. Number of lymph node dissected from the pancreatic superior margin was 14.7±4.3. Results of postoperative pathological examination in the 12 patients showed 8 cases of Ⅰ stage, 3 cases of Ⅱ stage, 1 case of Ⅲ stage of the TNM staging. (3) Follow-up. All 12 patients were followed up for 6 (range, 3?24)months. During the follow-up period, all 12 patients had no local tumor recurrence or distant metastasis. All 12 patients had no complications such as anastomotic leakage, anastomotic bleeding, or anastomotic stenosis, and did not experience symptoms of gastroesophageal reflux such as heartburn or vomiting.Conclusion:The ROSF in Da Vinic robotic proximal gastrectomy is safe and feasible.

ObjectiveTo identify the active components in Maimendong decoction (MMDD) against pulmonary fibrosis (PF) and validate their molecular effects in vitro, while focusing on the role of methylophiopogonanone B in regulating fibrosis.MethodsData on MMDD components and targets were gathered from databases including BATMAN-TCM and PubMed, whereas the PF gene data were sourced from GeneCards, OMIM, and TTD. Shared targets were determined using the STRING database, and molecular docking was used to analyze the essential molecules associated with fibrosis. To simulate PF conditions, human embryonic lung fibroblasts (HPF) and A549 cells were exposed to transforming growth factor-β1 (TGF-β1). Various assays were used to determine the effects of MMDD and methylophiopogonanone B on signaling pathways, apoptosis, and epithelial–mesenchymal transition.ResultsWe identified 11 active components from MMDD extracts that targeted 511 shared proteins associated with PF, revealing 10 key targets in network analysis. Gene ontology analysis indicated that processes and pathways such as apoptosis regulation and PI3K/Akt signaling were involved. In vitro experiments revealed that MMDD downregulated the expression of α-smooth muscle actin (α-SMA), collagen type I (COL-I), and collagen type III and regulated Bcl-2/Bax signaling pathways to promote apoptosis. The flow cytometry apoptosis assay revealed that MMDD promoted the TGF-β1-induced apoptosis of myofibroblasts. The primary active ingredient in MMDD, methylophiopogonanone B, reduced α-SMA, COL-I, and PI3K/Akt/mTOR-related protein levels in TGF-β1-treated HPF cells, decreased Bcl-2 and cleaved caspase 3, and increased Bax. Moreover, methylophiopogonanone B increased E-cadherin levels and reduced α-SMA, fibronectin, N-cadherin, vimentin, and snail in TGF-β1-treated A549 cells.ConclusionMethylophiopogonanone B demonstrated the potential to treat PF by inducing myofibroblast apoptosis and inhibiting EMT. However, despite encouraging initial results, further clinical research is warranted to verify the safety and efficacy of methylophiopogonanone B in the management of PF

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Objective:To compare the efficacy of different minimally invasive surgical approaches for the treatment of lumbar disc herniation (LDH).Methods:This study was a network meta-analysis (NMA). Databases the China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, China Biology Medicine disc (CBM), PubMed, Embase, Cochrane Library, and Web of Science from database inception to December 22, 2024 were searched. Randomized controlled trials (RCTs) on minimally invasive surgery (MIS) for LDH were retrieved using a combination of subject headings and free-text terms. Literature was screened according to predefined inclusion and exclusion criteria. The NMA was conducted within a Bayesian framework. Direct and indirect comparisons among the MIS approaches were presented using league tabulations. Cumulative ranking probability plots were generated using the ggplot2 package in R software. Treatment efficacy outcomes were ranked based on the surface under the cumulative ranking curve (SUCRA) value, ranging from 0 to 100%; a SUCRA value closer to 100% indicates a more favorable intervention.Results:A total of 15 RCTs were finally included. The interventions assessed were percutaneous endoscopic interlaminar discectomy (PEID), percutaneous endoscopic transforaminal discectomy (PETD), microendoscopic discectomy (MED), unilateral biportal endoscopy (UBE), transforaminal discectomy (TD), and microscopic discectomy (MD). Length of hospital stay (reported in 13 studies, n=1 414): ranked from the shortest to the longest were PETD, PEID, TD, MD, UBE, MED (SUCRA: 82.03%, 78.37%, 72.06%, 43.86%, 11.51%, 12.16%). Oswestry Disability Index (ODI) at 3 months postoperatively (reported in 10 studies, n=1 004): ranked from the lowest to the highest ODI were MD, UBE, PEID, TD, MED, PETD (SUCRA: 88.33%, 50.56%, 50.36%, 47.59%, 32.13%, 31.03%). ODI at 1 year postoperatively (reported in 10 studies, n=960): ranked from the lowest to the highest were PEID, MD, TD, MED, PETD, UBE (SUCRA: 74.03%, 66.56%, 43.22%, 42.63%, 40.75%, 32.80%). Surgical complications (reported in 12 studies, n=1 412): ranked from the lowest to the highest complication rate were MD, TD, UBE, PETD, PEID, MED (SUCRA: 81.60%, 76.55%, 72.86%, 24.43%, 23.41%, 20.97%). Conclusions:The efficacy of different MIS approaches for LDH varies. PETD is associated with the shortest postoperative hospital stay, MD is associated with the lowest ODI at 3 months and the lowest complication rate, PEID is associated with the lowest ODI at 1 year postoperatively.