Objective To establish a sandwich enzyme-linked immunosorbent assay (ELISA) method for the quantitative detection of Chromogranin A (CHGA) in saliva, and to explore its preliminary application in the testing of saliva samples. Methods Recombinant human CHGA protein was used to immunize BALB/c mice, and monoclonal antibodies (mAbs) were prepared and screened using conventional hybridoma technology. A double-antibody sandwich ELISA detection method was constructed, and the matrix effect of saliva samples was optimized. This method was then applied to detect the concentration of CHGA in the saliva of stressed individuals. Results Twenty-one stable hybridoma cell lines secreting high affinity anti-human CHGA antibodies were obtained. A pair of detection antibodies with the best effect was selected, and the optimal coating concentration was determined to be 10 μg/mL, with the optimal dilution of detection antibodies being 1:32 000. The accuracy and reproducibility of this method were verified, with both intra-batch and inter-batch variation coefficients less than 15×, and the recovery rate between 80× and 120×. The matrix effect was further optimized to make it suitable for saliva sample detection. Saliva samples from individuals in different stress states were collected, and the CHGA levels were detected using the method established in this study, indicating its potential to reflect the intensity of stress. Conclusion A reliable saliva CHGA ELISA detection method has been successfully established, and its potential as a biomarker in stress-related research has been preliminarily explored.
Saliva/metabolism* ; Enzyme-Linked Immunosorbent Assay/methods* ; Humans ; Animals ; Mice, Inbred BALB C ; Mice ; Chromogranin A/immunology* ; Antibodies, Monoclonal/immunology* ; Female ; Male ; Reproducibility of Results ; Adult

Advances in targeted therapy and immunotherapy have significantly improved clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC), reshaping treatment paradigms. However, most patients ultimately face drug resistance, with limited options for subsequent therapies and suboptimal treatment efficacy, presenting a prominent challenge in current clinical practice. Antibody-drug conjugates (ADCs), characterized by high efficacy and favorable safety profiles, have emerged as a promising therapeutic frontier in recent years. This systematic review provides a comprehensive overview of the latest advancements in ADCs-based therapies for lung cancer, alongside discussions of the prevailing challenges in this rapidly evolving domain.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Immunoconjugates/therapeutic use* ; Lung Neoplasms/immunology* ; Antineoplastic Agents/therapeutic use* ; Immunotherapy

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Objective To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer.Methods We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer,who were randomly divided into a training dataset(60%)and a testing dataset(40%).Using univariate analysis,multiple logistic regression analysis,and LASSO regression analysis,we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer.We employed an integrated learning approach that combined GBM,XGBOOST,and MLP algorithms for optimization of the model performance through parameter adjustments.Results The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age,Gn initiation dose,number of assisted reproduction cycles,and number of embryos transferred.The variables included in the LASSO model selection included female age,FSH levels,duration and initial dose of Gn usage,number of assisted reproduction cycles,retrieved oocytes,embryos transferred,endometrial thickness on HCG day,and progesterone level on HCG day.The nomogram demonstrated an accuracy of 0.642(95%CI:0.605-0.679)in the training dataset and 0.652(95%CI:0.600-0.704)in the validation dataset.The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725(95%CI:0.680-0.770)in the training dataset and 0.718(95%CI:0.675-0.761)in the validation dataset.Conclusions The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

Immunotherapy has changed the treatment landscape of advanced non-small cell lung cancer(NSCLC),showing great potential in the treatment of untreated and relapsed or refractory(R/R)patients.However,numerous issues that need further exploration remain with the wide application of immunotherapy.They include the exploration of biomarkers for efficacy prediction,the optimization of immunotherapy modalities,immune-related adverse effects,and the management of special populations.This review summarizes the progress of the research on immunotherapy for advanced NSCLC and discusses its challenges and future directions.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics* ; Phylogeny ; Fungal Proteins ; Cell Nucleus ; Histones ; Stress, Physiological/genetics*

Objective To explore the impact of non-pharmaceutical interventions(NPIs)on the prevalence of respiratory pathogens in adults,and to understand the scientific value and long-term effect of NPIs.Methods A retrospective study was conducted to collect the clinical data and laboratory examination data of adult patients with respiratory tract infection in West China Hospital,Sichuan University from 2017 to 2023,and the patho-gen,population,season and other aspects were analyzed in different periods.The analysis period included 2017 to 2019(before the implementation of NPIs),2020 to 2022(during the implementation of NPIs),and January to December 2023(after the implementation of NPIs).Results A total of 33 068 adult patients with respira-tory tract infection were included.The overall prevalence of 8 adult respiratory pathogens from 2017 to 2019(26.95％)was higher than that from 2020 to 2022(8.70％),and the difference was statistically significant(P＜0.05).There were significant differences in the prevalence of pathogens among different genders,ages and seasons in the first,middle and last three periods of NPIs implementation(P＜0.05).Before the imple-mentation of NPIs,the seasonal peak of respiratory prevalence appeared from January to March each year.With the implementation of NPIs,the seasonal peak of respiratory prevalence appeared from January to March 2020(10.09％),October to December 2021(9.32％),July to September 2022(15.23％),respectively.After the implementation of NPIs,the seasonal peak of respiratory prevalence appeared from October to December 2023(21.20％).Among the 8 pathogens,the change of prevalence of influenza A virus H1N1(2009)was the most obvious,and the prevalence was 17.42％,0.00％and 6.99％before,during and after the implementation of NPIs,respectively.Conclusion Due to the influence of NPIs and other factors,the epidemic characteristics of respiratory pathogens have changed from 2017 to 2023.Attention to the emerging characteristics of patho-gen prevalence is important for the prevention,diagnosis and control of respiratory infectious diseases during public health emergencies.

Objective To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer.Methods We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer,who were randomly divided into a training dataset(60%)and a testing dataset(40%).Using univariate analysis,multiple logistic regression analysis,and LASSO regression analysis,we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer.We employed an integrated learning approach that combined GBM,XGBOOST,and MLP algorithms for optimization of the model performance through parameter adjustments.Results The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age,Gn initiation dose,number of assisted reproduction cycles,and number of embryos transferred.The variables included in the LASSO model selection included female age,FSH levels,duration and initial dose of Gn usage,number of assisted reproduction cycles,retrieved oocytes,embryos transferred,endometrial thickness on HCG day,and progesterone level on HCG day.The nomogram demonstrated an accuracy of 0.642(95%CI:0.605-0.679)in the training dataset and 0.652(95%CI:0.600-0.704)in the validation dataset.The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725(95%CI:0.680-0.770)in the training dataset and 0.718(95%CI:0.675-0.761)in the validation dataset.Conclusions The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

Objective To explore the efficacy and safety of subretinal injection of conbercept in treating refractory neovascular age-related macular degeneration(nAMD).Methods In this prospective clinical study,17 eyes of 17 pa-tients diagnosed with refractory nAMD at the Department of Fundus Disease,the Affiliated Eye Hospital of Nanchang Uni-versity from March 2022 to September 2023 were enrolled.The 10 g·L-1 conbercept was injected into the subretinal area of the macular area using a 41G ultra-fine microneedle.If retinal exudation was found in the macular area by optical coherence tomography during the follow-up,the intravitreal injection of 10 g·L-1 conbercept was performed.The best corrected vis-ual acuity(BCVA),central macular retinal thickness(CMT),number of injections and complications were recorded before and 1,3,6,and 12 months after the operation.Results Compared with the preoperative values,the BCVA of patients significantly improved(all P＜0.001)1,3,6 and 12 months postoperatively.There was no significant change in BCVA at each time point after operation(all P＞0.05).Compared with pre-operation,CMT of patients significantly decreased at 1,3,6 and 12 months after operation(all P＜0.001).From 1 month to 12 months after the operation,the CMT of patients gradually decreased(all P＜0.001).Pearson correlation analysis showed that there were positive correlations between pre-operative BCVA and preoperative CMT,preoperative BCVA and 12-month postoperative BCVA(r=0.643,P=0.005;r=0.634,P=0.006).During the treatment,the number of anti-vascular endothelial growth factor injections in 17 eyes was(1.35±0.61)times,with 1 time in 12 eyes,2 times in 4 eyes,and 3 times in 1 eye.Correlation analysis showed that the number of injections was positively correlated with preoperative CMT(r=0.664,P=0.004).No intraoperative or postop-erative complications related to the operation occurred in 17 eyes.Conclusion Subretinal injection of conbercept,which can reduce CMT and improve visual prognosis,is a safe and effective treatment method for refractory nAMD.