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*

Objective:To observe the effect of stellate ganglion block(SGB)on serum inflammatory factors and the expression of α7nAChR protein in rats with acute peritonitis,so as to further explore the mechanism of SGB on the inflammatory response of acute peritonitis in rats.Methods:40 SPF grade male rats were randomly divided into 4 groups:blank group(Control),acute peritonitis group(AP),acute peritonitis+stellate ganglion block group(AP+SGB),acute peritonitis+stellate ganglion block+α7nAChR inhibitor methyllycaconitine group(AP+SGB+MLA),with 10 rats in each group.Inject 2％acetic acid at a dose of 1 ml/100 g into the peritoneal cavity of rats to establish an acute peritonitis model in the AP group,AP+SGB group,and AP+SGB+MLA group.Blood samples were collected from the tail vein of the rats,and the concentrations of IL-18 and TNF-α in serum were detected by ELISA.Western Blot method was used to detect the level of α7nAChR protein in the peritoneal tissues,and RT-qPCR method was used to detect the expression of α7nAChR mRNA in the peritoneal tissues.Results:Compared with Control group,the levels of IL-18 and TNF-α were increased in the other three groups(P＜0.05).Compared with AP group,serum levels of IL-18 and TNF-α in AP+SGB group were decreased(P＜0.05).Compared with AP+SGB group,serum levels of IL-18 and TNF-α were increased in AP+SGB+MLA group(P＜0.05).The expression of α7nAChR mRNA protein were higher in the three groups than group Control,(P＜0.05).Compared with AP group,α7nAChR protein and α7nAChR mRNA expression levels were higher in AP+SGB group and AP+SGB+MLA group(P＜0.05).Compared with AP+SGB group,α7nAChR protein and α7nAChR mRNA expression levels in AP+SGB+MLA group were lower(P＜0.05).Conclusion:Stellate ganglion block treatment can reduce the production of inflammatory factors and inhibit the inflammatory response of acute peritonitis in rats,and its anti-inflammatory mechanism may be related to the cholinergic anti-inflammatory pathway(CAP)mediated by α7nAChR.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Confirmed cases of Lyme disease(LD)in Ji'an City,Jiangxi Province and the clinical manifestations and region-al distribution were assessed to provide a basis for timely diagnosis and treatment.In total,133 serum samples were collected from patients with suspected LD in Ji'an Central People's Hospital from December 2021 to August 2022.Serum antibodies a-gainst Borrelia burgdorferi were detected with a two-step testing process.In addition,a specific gene of B.burgdorferi in samples was identified by nested PCR.Sequencing analysis was conducted to confirm the positive samples.Overall,25(18.80％)serum samples were positive for B.burgdorferi nucleic acid and antibodies,which included 20(15.04％)positive for antibodies and 6(4.51％)positive for nucleic acids.The sequences of the 5S-23S rRNA gene spacer of 6 samples were con-sistent with the corresponding sequences of Borrelia yangtzensis and one of the six samples was also positive for antibodies.The 25 positive samples were collected from 9 counties in Ji'an City,with the majority in Jizhou District(44％).All positive patients may experience symptoms related to LD,including joint disorders,neurological disorders,infectious fever,der-matitis,and/or chest pain.The most common symptom was joint disorders(72％).Six cases positive for B.yangtzensis nucleic acids were mainly collected in the Jizhou District,of which four had joint lesions and two had infectious fever.This study confirms the existence of LD in Jiangxi Province,which may be the first confirmation of human infection with B.yan-gtzensis in southern China.Hence,doctors in this region should consider the possibility of LD for cases presenting with related symptoms.Although LD may occur in this region,further investigations and monitoring are warranted.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

Objective To compare the anesthetic effects of remazolam and dexmedetomidine assisted sedation in the operation of finger replantation under ultrasound guided brachial plexus block.Methods 60 patients undergoing severed finger replantation were randomly divided into remazolam group(group R)and a dexmedetomidine group(group D)by random number table method,with 30 cases in each group.Both groups received a single brachial plexus block under ultrasound guidance.Group R was injected with remazolam 0.1 mg/kg,followed by 1 mg/(kg·h)pump until 10 min before the end of the operation.In group D,a load dose of 0.5 μg/kg of dexmedetomidine was injected,followed by continuous infusion at a rate of 0.5 μg/(kg·h)until 10 min before the end of surgery.The MAP,HR and SpO2 values of the two groups were compared when the patients entered the room(T0),the wound was cleaned and disinfected(T1);the tourniquet was upper(T2);the operation began(T3);the tourniquet was relaxed(T4);and the operation ended(T5).MOAA/S scores and BIS values were compared between the two groups at different time.The time from the beginning of medication to the absence of consciousness and the time of consciousness recovery after drug withdrawal were compared between the two groups.Blood lactic acid(Lac)before applying tourniquet and 15 min after relaxing tourniquet were compared between the two groups.The occurrence of intraoperative adverse reactions was recorded in the two groups.Results The MAP of patients in group R had little fluctuation at each time during the operation,and the MAP of patients in group D was significantly increased at T1,T2,T3 and T0 moments and at the same time as that in group R(P<0.05);HR in group R was stable at all times,and HR in group D significantly slowed down at T1,T2 and at the same time with group R(P<0.05).Patients in both groups achieved ideal sedation during the operation(MOAA/S score≤3 points),and the MOAA/S score of patients in group R at T5 minutes after drug withdrawal was higher than that at other moments of the same group and group D(P<0.05);the BIS value of group R was higher than that of group D(P<0.05).The loss time and recovery time of consciousness in group R were shorter than those in group D(P<0.05).The incidence of intraoperative hypertension and bradycardia in group D was significantly higher than that in group R,and the incidence of respiratory depression in group R was higher than that in group D(P<0.05).There was no significant change in lactate value between the two groups(P>0.05).Conclusion Remazolam and dexmedetomidine can satisfy sedation in brachial plexus nerve block for replantation of severed finger under ultrasound guidanc.Compared with dexmedetomidine,remazolam has better sedation control,stable hemodynamics,low incidence of circulatory adverse events.

Objective:To access the clinical value and related risk factors of aortic arch calcification (AoAC) in patients with renal secondary hyperparathyroidism (SHPT) on CT during parathyroid SPECT/CT imaging.Methods:From January 2014 to May 2021, 136 renal SHPT patients (70 males, 66 females, age (50.1±11.4) years) who underwent parathyroid 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT in Affiliated Jiangyin Hospital of Nantong University were retrospectively enrolled. AoAC score was estimated with CT(1-5), and patients were divided into none-light AoAC group (AoAC score<3) and moderate-severe AoAC group (AoAC score≥3). Independent-sample t test or Mann-Whitney U test was used to compare differences of various indicators between two groups. Univariate binary logistic regression was used to analyze the influencing factors of AoAC. Results:Of 136 renal SHPT patients, 111(81.62%) were AoAC detected by CT. There were 84 patients in none-light AoAC group and 52 patients in moderate-severe AoAC group. The age ((46.7±9.8) vs (55.7±11.6) years; t=-4.84, P<0.001), pulse pressure (52(41, 64) vs 60(51, 70) mmHg (1 mmHg=0.133 kPa); z=-3.27, P=0.001), serum corrected calcium (2.41(2.28, 2.53) vs (2.49±0.22) mmol/L; z=-2.50, P=0.013), serum phosphorus ((1.95±0.39) vs (2.14±0.48) mmol/L; t=-2.54, P=0.012), calcium phosphorus product ((4.68±1.07) vs (5.29±1.10) mmol 2/L 2;t=-3.21, P=0.013) and parathyroid hormone (PTH) level (106.30(90.15, 127.45) vs 109.90(87.93, 157.63) pmol/L; z=-2.09, P=0.036) between non-light AoAC group and moderate-severe AoAC group were significantly different. Logistic regression analysis showed that serum phosphorus (odds ratio ( OR)=7.261, 95% CI: 2.416-21.819, P<0.001), calcium and phosphorus product ( OR=1.598, 95% CI: 1.073-2.380, P=0.021) and PTH level ( OR=1.018, 95% CI: 1.007-1.029, P=0.001) were independent risk factors of AoAC. Conclusions:Hybrid SPECT/CT can be used for an effective method of evaluating AoAC in patients with renal SHPT. High serum phosphorus, high calcium phosphorus product and high PTH level may be independent risk factors of AoAC.

Based on the UHPLC-Q-Exactive-MS metabonomics technology, the effect of Hippocampus kuda Bleeker on the life span of Drosophila melanogaster was studied, and the change rule of endogenous metabolites in the aging process of Drosophila melanogaster after the intervention of Hippocampus kuda Bleeker japonicus was explored to clarify the anti-aging mechanism of Hippocampus. The natural aging model of Drosophila melanogaster was used. Different doses of raw Hippocampus and fried Hippocampus were given to observe the effects on the life span, climbing ability, sexual activity, and antioxidant enzyme activity of Drosophila melanogaster. Based on UHPLC-Q-Exactive-MS metabolomics technology, the metabolic profile of the aging Drosophila melanogaster was analyzed using metabonomics technology to explore the mechanism of Hippocampus kuda Bleeker delaying the aging of Drosophila melanogaster. The results showed that raw Hippocampus and crispy Hippocampus (1, 4 mg·mL^-1) could significantly prolong the average life span, median life span and maximum life span of male fruit flies, and significantly improve the climbing ability and sexual vitality of fruit flies. Catalase (CAT) and aldehyde content were increased, while malonaldehyde (MDA) content was decreased. Through metabonomics technology, it was identified that the Hippocampus can significantly recall 16 metabolites and participate in the biosynthesis of phenylalanine, tyrosine and tryptophan, starch and sucrose metabolism, tyrosine metabolism, cysteine and methionine metabolism, and histidine metabolism. The anti-aging mechanism is related to amino acid metabolism and sugar metabolism, which provides a substantial scientific basis for the development and utilization of Hippocampus and clarifying its role in senile diseases. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: SXULL2021028).