Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

To evaluate the effect of bronchoalveolar lavage (BAL) on the clinical prognosis of children with macrolide drug-resistant Mycoplasma pneumoniae pneumonia (MRMPP) in a retrospective cohort study based on propensity score matching (PSM).A retrospective cohort study based on propensity score matching retrospectively collected the clinical data of hospitalized patients diagnosed with mycoplasma macrolide drug-resistant pneumonia (MRMPP) in Respiratory Department of Hunan Children′s Hospital from January 2020 to August 2023. According to whether bronchoalveolar lavage (BAL) was performed during hospitalization, the children were divided into BAL group and non-BAL group, and the baseline information of the two groups was matched by propensity scores, and the clinical prognosis was compared. A total of 302 children were screened, and 150 cases were successfully matched, including 59 cases in the BAL group and 91 cases in the non-BAL group. The results showed that the differences between the non-BAL group and the BAL group before PSM( P<0.05) were significantly different in age [(4.60±2.97)years vs (5.41±3.02) years, t=-2.273, P=0.024], shortness of breath (9.4% vs 22.5%, χ 2=9.864, P=0.002), and radiographic manifestations [lung interstitial changes (29.8% vs 15.3%, χ 2=8.009, P=0.005), lung consolidation (17.3% vs 55.9%, χ 2=48.457, P<0.001), spotted flaky infiltrates (52.4% vs 27.9%, χ 2=17.056, P<0.001)], bacterial infection (3.2% vs 9.2%, χ 2=4.845, P=0.028), duration of azithromycin or doxycycline use [4(2, 5) days vs 5(3, 6) days, Z=-2.374, P=0.018], White Blood Cell Count at admission [7.94 (6.25, 10.34)×10 9/L vs 7.21 (5.65, 9.01)×10 9/L, Z=-2.445, P=0.014], D Dimer [0.58 (0.44, 0.83) μg/ml vs 0.80 (0.52, 1.12) μg/ml, Z=-3.154, P=0.002], but there was no significant difference between the two groups in the above indexes after PSM ( P>0.05). The duration of hospitalization, cough relief, disappearance of rales and fever in the BAL group was shortened in the BAL group compared with that in the non-BAL group [5 (4, 7) days vs 7 (5, 8) days, Z=-2.373, P=0.018], and the difference was statistically significant ( P<0.05). Linear regression analysis of PSM cohort study showed that BAL was negatively correlated with fever time (β=-4.369, 95% CI:-8.600--0.138, P<0.05). In conclusion, BAL can shorten the fever time of MRMPP, and early BAL in addition to conventional treatment has a positive effect on the prognosis of children.

Objective:To explore the application effect of hydration therapy in patients with intermittent claudication (IC) of peripheral arterial disease, and to provide reference for clinical application.Methods:A randomized controlled trial method was used to select 86 patients with IC of peripheral arterial disease who attended the Department of Vascular Surgery of Shanxi Bethune Hospital from June to September 2023 as the study subjects by convenience sampling method, and they were divided into the control group and the intervention group by using the method of randomized numerical table, each group had 43 cases. In the control group, routine care was provided, and in the intervention group, hydration therapy was implemented on the basis of the control group. Ankle-brachial index, transcutaneous partial pressure of oxygen, and claudication distance were assessed in both groups 1d before and 6 months after the intervention.Results:Forty-two patients in each group completed the study, 21 males and 21 females, aged (61.33 ± 8.93) years in the intervention group; 24 males and 18 females, aged (61.33 ± 9.01) years in the control group. Compared with the ankle-brachial index, transcutaneous oxygen partial pressure and limp distance of the 2 groups 1 d before intervention, the differences were not statistically significant (all P>0.05), and 6 months after the intervention, the transcutaneous oxygen partial pressure of the patients in the intervention group was (37.69 ± 8.86) mmHg (1 mmHg=0.133 kPa), and that of the control group was (29.69 ± 7.79) mmHg, and the differences between the 2 groups were statistically significant ( t=4.40, P<0.05). The differences in patients′ transcutaneous partial pressure of oxygen and limp distance before and after intervention in the intervention group were -7.00 (-13.00, -1.75) mmHg and -50.00 (-100.00, 0.00) m, respectively, and in the control group were 0.01 (-1.00, 1.00) mmHg and 0.01 (-1.25, 20.00) m, respectively, and the differences between the 2 groups were statistically were statistically significant ( Z=5.59, 4.33, both P<0.05). Conclusions:Hydration therapy improves transcutaneous oxygen partial pressure values and claudication distance in patients with peripheral arterial disease IC, and improves microcirculation of the affected limbs in patients.

To evaluate the effect of bronchoalveolar lavage (BAL) on the clinical prognosis of children with macrolide drug-resistant Mycoplasma pneumoniae pneumonia (MRMPP) in a retrospective cohort study based on propensity score matching (PSM).A retrospective cohort study based on propensity score matching retrospectively collected the clinical data of hospitalized patients diagnosed with mycoplasma macrolide drug-resistant pneumonia (MRMPP) in Respiratory Department of Hunan Children′s Hospital from January 2020 to August 2023. According to whether bronchoalveolar lavage (BAL) was performed during hospitalization, the children were divided into BAL group and non-BAL group, and the baseline information of the two groups was matched by propensity scores, and the clinical prognosis was compared. A total of 302 children were screened, and 150 cases were successfully matched, including 59 cases in the BAL group and 91 cases in the non-BAL group. The results showed that the differences between the non-BAL group and the BAL group before PSM( P<0.05) were significantly different in age [(4.60±2.97)years vs (5.41±3.02) years, t=-2.273, P=0.024], shortness of breath (9.4% vs 22.5%, χ 2=9.864, P=0.002), and radiographic manifestations [lung interstitial changes (29.8% vs 15.3%, χ 2=8.009, P=0.005), lung consolidation (17.3% vs 55.9%, χ 2=48.457, P<0.001), spotted flaky infiltrates (52.4% vs 27.9%, χ 2=17.056, P<0.001)], bacterial infection (3.2% vs 9.2%, χ 2=4.845, P=0.028), duration of azithromycin or doxycycline use [4(2, 5) days vs 5(3, 6) days, Z=-2.374, P=0.018], White Blood Cell Count at admission [7.94 (6.25, 10.34)×10 9/L vs 7.21 (5.65, 9.01)×10 9/L, Z=-2.445, P=0.014], D Dimer [0.58 (0.44, 0.83) μg/ml vs 0.80 (0.52, 1.12) μg/ml, Z=-3.154, P=0.002], but there was no significant difference between the two groups in the above indexes after PSM ( P>0.05). The duration of hospitalization, cough relief, disappearance of rales and fever in the BAL group was shortened in the BAL group compared with that in the non-BAL group [5 (4, 7) days vs 7 (5, 8) days, Z=-2.373, P=0.018], and the difference was statistically significant ( P<0.05). Linear regression analysis of PSM cohort study showed that BAL was negatively correlated with fever time (β=-4.369, 95% CI:-8.600--0.138, P<0.05). In conclusion, BAL can shorten the fever time of MRMPP, and early BAL in addition to conventional treatment has a positive effect on the prognosis of children.

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.

Calcium-activated chloride channels(CaCCs)are a class of channel proteins that trans-port chloride ions activated by intracellular calcium,which play a crucial role in regulating membrane potential,intracellular calcium balance,and cell excitability,particularly in neurons and muscle cells.In the Anoctamin(Ano)family,Ano1 is the most classic CaCC.Targeted modulators of Ano1 have poten-tial therapeutic effects against such diseases as cancer,cystic fibrosis,hypertension,diarrhea,and asthma.Since the discovery of Ano1 in 2008,several methods for screening CaCC-specific modulators have emerged including high-throughput primary screening of fluorescent proteins,electrophysiological patch clamp technique and virtual screening,and identification of small molecule modulators with diverse pharmacological effects.This paper summarizes the principles,advantages and disadvantages of the mainstream screening methods,and reviews the chemical structures and potential applications of Ano1-specific modulators discovered to date.

This work aims to explore the effect of glycolysis on the replication of porcine reproductive and respiratory syndrome virus (PRRSV) in porcine alveolar macrophages (PAMs). The changes of glucose metabolism, PRRSV protein levels, PRRSV titers, and the relative expression levels of genes and proteins in PAMs were analyzed by ELISA, qPCR, virus titration, and Western blotting after PRRSV infection. The effect of hypoxia-inducible factor-1α (HIF-1α) on PRRSV replication was subsequently assessed by specific siRNAs targeting to HIF-1α. The results showed that PRRSV infection enhanced glycolysis, elevated the levels of glucose uptake and lactate in the supernatant (P<0.05 and 0.01, respectively), reduced ATP production (P<0.05), and up-regulated the expression of hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), and pyruvate kinase isozyme type M2 (PKM2) in PAMs (P<0.05 and 0.01, respectively). Glycolysis inhibitors down-regulated the expression of PRRSV proteins and reduced virus titers (P<0.01). The knockdown of HIF-1α by siRNAs inhibited glycolysis and lowered PRRSV titers (P<0.05). In addition, the interferon pathways inhibited by PRRSV infection were reversed by the inhibition of glycolysis. These findings may facilitate further investigation of the role of glycolysis in PRRSV replication.
Porcine respiratory and reproductive syndrome virus/physiology* ; Glycolysis ; Swine ; Animals ; Virus Replication ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Macrophages, Alveolar/metabolism* ; Porcine Reproductive and Respiratory Syndrome/virology* ; Cells, Cultured ; RNA, Small Interfering/genetics*

Objective:To investigate the genetic safety of allogeneic bone marrow mesenchymal stem cells (BMSCs) transplantation in traumatic brain injury (TBI).Methods:(1) In vivo experiment: BMSCs from male SD rats were isolated and cultured. Moderate TBI models were prepared by implanting and fixing micro-drug injection cannula into the left ventricle of 12 female SD rats, and 3 d after that, striking the right cerebral cortex of the rats with pneumatic precision percussion device was performed. Four h, and 3, 6, 9, and 12 d after modeling, TBI rats were given a single/multiple BMSCs infusion (2.5×10 5/time, total volume 10 μL) by cannula; 48 and 72 h, and 10 and 14 d after modeling, brain tissues of TBI rats (3 at each time point) were prepared into paraffin specimens. Immunofluorescent staining was used to detect the microglia activation, and RNAscope ? technology was used to detect the co-localization of astrocytes, neurons, microglia and transplanted BMSCs to observe whether the allogeneic BMSCs were integrated with the host brain cells after transplantation into TBI host. (2) In vitro experiment: the frozen and revived microglial cell line BV2 was transfected with green fluorescent protein (GFP)-positive lentiviral particles, and then, BMSCs prelabeled with pHrodo RED probe and BV2 cells pretreated with lipopolysaccharide were co-cultured in a certain ratio (BV2:BMSCs=1:1, 1:2, 2:1); after 36 and 72 h of co-culture, the phagocytosis between the 2 kinds of cells was observed under confocal fluorescence inverted microscope to observe the specific action forms of microglia on BMSCs. Results:(1) In vivo experiment: 48 and 72 h, and 10 and 14 d after modeling, no colocalization of transplanted BMSCs with astrocytes or neurons was found in paraffin sections of brain tissue in TBI rats; however, 10 and 14 d after modeling, microglia in TBI rats were obviously activated and migrated to the left lateral ventricle and choroid plexus, and co-localization of microglia with transplanted BMSCs was observed. (2) In vitro experiment: phagocytosis occurred after co-culture of BV2 cells at different proportions with BMSCs for 36 and 72 h. Conclusion:After transplantation, allogeneic BMSCs do not integrate with astrocytes or neurons of the TBI host, but they could be phagocytosed by microglia, indicating that allogeneic BMSCs transplantation for TBI is genetically safe.

Objective:To develop a model of stellate ganglion block (SGB) in mice and investigate the effect of SGB on cerebral cortical blood flow.Methods:Thirty clean-grade healthy male C57BL/6 mice, aged 8-9 weeks, weighing 23-27 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), left SGB group (group L), left normal saline group (group SL), right SGB group (group R) and right normal saline group (group SR). Group C received no intervention.SGB was performed with 0.25% ropivacaine 0.08 ml via percutaneous posterior approach in L and R groups, while the equal volume of normal saline 0.08 ml was given instead at the location of left and right stellate ganglion in SL and SR groups, respectively.The cerebral cortical blood flow was determined using laser speckle contrast imaging system before SGB (T 0) and at 10, 30, 60, 90 and 120 min after SGB (T 1-5). Results:Mice developed ptosis on the block side, indicating that the model of SGB was successfully developed in L and R groups.There was no significant difference in cerebral cortical blood flow at each time point among C, SL and SR groups ( P>0.05), and cerebral cortical blood flow on the block side decreased at T 1, began to increase at T 2, peaked at T 3, and decreased at T 5 which was still higher than that at T 0 in group L and group R ( P<0.01). Compared with C and SL groups, the left cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group L ( P<0.01). Compared with C and SR groups, the right cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group R ( P<0.01). There were no significant differences in cerebral cortical blood flow at each time point between group C and group SL and between group C and group RL ( P>0.05). Conclusions:The mouse model of SGB via percutaneous posterior approach is successfully developed.Unilateral SGB can affect cerebral cortical blood flow on the block side, which shows a transitory decrease followed by a sustained significant increase.

Objective To analyze the characteristics of the muscle strength around the knee joint of chondromalacia patellae patients, and to explore the difference with normal people.Methods In March, 2021, 70 knee-onset chondromalacia patellae patients (experimental group) and 35 normal people (control group) were measured isokinetic muscle strength of flexion and extension of knee in angular velocities of 60°/s and 180°/s.Results At 60°/s and 180°/s, the peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles on the affected side in the experimental group were lower than that of the control group (U > 1097.0, P<0.001). The peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles at 60°/s and extensor muscles at 180°/s were lower on the affected side than on the healthy side in the experimental group (|Z| > 2.121, P<0.05). The peak torque ratios at 60°/s and 180°/s were more in the affected knees than in the healthy knees of experimental group and in the control group (U > 1810.0, |Z| >3.691, P<0.01).Conclusion The explosive force and endurance of the knee flexor and extensor has weakened in patients with chondromalacia patellae, and there is imbalance in knee joint muscle strength.