The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

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*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To analyze the short-term efficacy and safety of tislelizumab combined with neoadjuvant chemotherapy in the treatment of resectable esophageal squamous cell carcinoma (ESCC) .Methods:The clinical data of 56 patients with ESCC who received neoadjuvant therapy combined with surgical resection in the Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University from April 2021 to October 2023 were collected. According to the different preoperative neoadjuvant therapy methods, the patients were divided into neoadjuvant chemotherapy combined with immunotherapy group (chemoimmunization group, n=24) and neoadjuvant chemotherapy group (chemotherapy group, n=32). The postoperative tumor regression grade, objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR) rate, major pathological remssion (MPR) rate, R0 resection rate, perioperative indicators, and security were compared between the two groups. Results:In chemoimmunization group, the tumor regression grade was better than that in chemotherapy group, with a statistically significant difference ( Z=9.39, P=0.025). The ORR and the DCR were 75.00% (18/24) and 91.67% (22/24) in chemoimmunization group, and 46.88% (15/32) and 65.62% (21/32) in chemotherapy group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=5.21, P=0.022). The R0 resection rate was 87.50% (21/24) in chemoimmunization group, which was higher than that of the chemotherapy group [59.38% (19/32) ], with a statistically significant difference ( χ2=5.31, P=0.021). The pCR rate and MPR rate were 29.17% (7/24) and 54.17% (13/24) in chemoimmunization group, and 6.25% (2/32) and 28.12% (9/32) in chemotherapy group, there was no statistically significant difference in pCR rate ( χ2=3.78, P=0.052), but there was a statistically significant difference in MPR rate ( χ2=3.89, P=0.048). The interval between the end of neoadjuvant treatment and the start of surgery was (42.71±8.29) days in chemoimmunization group, and (42.25±8.03) days in chemotherapy group. The intraoperative blood loss of patients was (215.54±57.85) ml in chemoimmunization group, and (229.65±57.74) ml in chemotherapy group. The operation time of patients was (293.52±37.50) minutes in chemoimmunization group, and (295.31±37.66) minutes in chemotherapy group. The postoperative hospitalization time of patients was (17.90±3.49) days in chemoimmunization group, and (18.42±3.82) days in chemotherapy group, all with no statistically significant differences ( t=0.21, P=0.835; t=0.90, P=0.370; t=0.18, P=0.861; t=0.52, P=0.603). In terms of postoperative complications, there was no statistically significant difference in the total incidence of postoperative complications between the two groups [62.50% (15/24) vs. 84.38% (27/32), χ2=0.59, P=0.440]. The main adverse drug reactions in the two groups included decreased white blood cell count, nausea and vomiting, liver dysfunction, pruritus, hypothyroidism, etc. Most of them were grade 1-2, 3 cases were grade 3, and no grade 4 adverse reactions occurred. The total incidence of adverse reactions was 62.50% (15/24) in chemoimmunization group, and 65.62% (21/32) in chemotherapy group, with no statistically significant difference ( χ2=0.06, P=0.809) . Conclusion:For the preoperative neoadjuvant therapy of resectable ESCC, the combination of tislelizumab and chemotherapy has better short-term efficacy and better safety than the single chemotherapy scheme, which can improve the surgical efficacy.

Chlamydia psittaci is a zoonotic respiratory infection.To provide a reference basis for psittaciosis-specific pre-vention and control,we conducted a retrospective analysis reviewing the clinical and epidemiological characteristics of three pa-tients.All patients had a history of avian or bird contact,and their clinical symptoms were primarily high fever and pneumonia.Chlamydia psittaci nucleic acid testing was conducted on the patients'close contacts,surrounding occupational populations,and their living environments.No positive findings were observed among the cases'close contacts and surrounding occupational populations,whereas environmental positivity was detected in the feces of the patients'neighbors(25.0％,3/12)and in the ef-fluent(22.2％,2/9)of a wild bird activity area.Positive samples were subjected to ompA gene sequencing,which revealed that the strains in three patients were genetically sequence-identical to that found in pigeon feces.This study enhances under-standing of the epidemic caused by Chlamydia psittaci,elucidates its transmission mechanisms,and provides critical insights for subsequent investigations and management of the disease.

Aim To disclose the subcellular localiza-tion,expression pattern,cellular physiological function and possible molecular mechanism of C12ORF56,a novel gene located at q14.2 of chromosome 12,in the pathogenesis of lung cancer.Methods ONCOMINE database was applied to investigate the mRNA level dif-fering of C12ORF56 between normal and lung cancer tissues.Analysis based on LinkedOmics,Metascape,String and GSEA database or tools provided indication of potential cellular physiological functions of C12ORF56 in the developing of lung cancer.C12ORF56 was knocked down via siRNA and the pro-liferation of NCI-H1073 cells were observed by EdU and CCK-8 assay.RT-qPCR was used to detect the ex-pression level of C12ORF56 of lung cancer cells on dif-ferent cycle phases.The core sequence regions of pro-moter affecting the transcription of C12ORF56 gene were analyzed by Jaspar online-tools and verified by dual-luciferase assay.Results C12ORF56 was highly expressed in lung cancer cells,especially in squamous cell lung cancer.C12ORF56 correlated with cell cy-cle,cancer immune,DNA replication.Knockdown of C12ORF56 reduced NCI-H1703 cell proliferation.Conclusion The up-regulation of C12ORF56 is in-volved in the development of lung cancer by enhancing lung cancer cell proliferation.

Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.