Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) originator and biosimilars in the treatment of Crohn′s disease (CD).Methods:From January 2020 to January 2023, the clinical data of 73 patients who were diagnosed as CD and received ADA treatment at the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University were retrospectively analyzed. Among them, 30 patients received ADA originator treatment (National Medicine Approval Number SJ20181019; originator group), 23 patients received biosimilar A treatment (Medicine Medicine Approval Number S20190038; biosimilar A group), and 20 patients received biosimilar B (Medicine Medicine Approval Number S20190043; biosimilar B group). At 12 and 48 weeks after treatment, the clinical data of clinical remission (Crohn′s disease activity index(CDAI) score <150), clinical response (CDAI score decreased ≥ 70 from baseline), endoscopic remission (simple endoscopic score for Crohn′s disease (SES-CD) ≤ 2 or Rutgeerts score ≤ 1), endoscopic response (SES-CD decreased > 50% from baseline), and adverse drug reaction (ADR) were collected. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:After 12 weeks of ADA treatment, the overall clinical remission rate was 69.9% (51/73), which of the biosimilar A group was 69.6% (16/23), the biosimilar B group was 75.0% (15/20), and the originator group was 66.7% (20/30). The overall clinical response rate was 83.6% (61/73), which of the biosimilar A group was 82.6% (19/23), the biosimilar B group was 80.0% (16/20), and the originator group was 86.7% (26/30). The overall endoscopic remission rate was 42.5% (31/73), which of the biosimilar A group was 52.2% (12/23), the biosimilar B group was 45.0% (9/20), and the originator group was 33.3% (10/30). The overall endoscopic response rate was 63.0% (46/73), which of the biosimilar A group was 73.9% (17/23), the biosimilar B group was 70.0% (14/20), and the originator group was 50.0% (15/30). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). After 48 weeks of treatment, the overall clinical remission rate was 54.2% (32/59), which of the biosimilar A group was 8/18, the biosimilar B group was 9/15, and the originator group was 57.7% (15/26). The overall clinical response rate was 71.2% (42/59), which of the biosimilar A group was 10/18, the biosimilar B group was 12/15, and the originator group was 76.9% (20/26). The overall endoscopic remission rate was 25.4% (15/59), which of the biosimilar A group was 5/18, the biosimilar B group was 3/15, and the originator group was 26.9% (7/26). The overall endoscopic response rate was 40.7% (24/59), which of the biosimilar A group was 7/18, the biosimilar B group was 5/15, and the originator group was 46.2% (12/26). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). The overall incidence of ADR was 32.9% (24/73), which of the biosimilar A group was 30.4% (7/23), the biosimilar B group was 30.0% (6/20), and the originator group was 36.7% (11/30); and there was no statistically significant difference among the 3 groups ( P=0.847). Conclusion:ADA biosimilars A and B demonstrate comparable efficacy and safety to the originator medication in the treatment of CD.

With the widespread application of deep learning technology in radiotherapy, increasing attention has been directed toward enhancing the precision and personalization of intelligent radiotherapy for osteosarcoma. This review summarizes the recent advances in the application of deep learning to osteosarcoma image preprocessing, automatic target volume delineation, dose prediction and treatment plan optimization, early efficacy assessment, and follow-up monitoring. Bottlenecks such as data sharing, model generalization, and interpretability are analyzed. This review aims to provide a comprehensive reference for technological iteration and clinical implementation in this field, as well as a scientific basis for the determination of future research directions and the development of standardized guidelines.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

The theory of "origin essence-origin qi-origin spirit" is rooted in the theory of "essence-qi-spirit", which explains that origin essence, origin qi, origin spirit as the important material foundation, energy power and regulation center in the process of growth and development of the organism, are mutual and complementary to each other, and operate orderly under the guidance of the ministerial fire. Tumor is essentially an abnormal disorder of the growth and development process of the organism, and its occurrence and development are directly related to the mutation of origin essence and the alienation of ministerial fire, and closely related to the attenuation of origin qi, the departure of ministerial fire, and the inefficiency of origin spirit, and the delusional movement of ministerial fire. Based on the theory of "origin essence-origin qi-origin spirit", the tumor can be treated in the clinic by regulating the ministerial fire suppressing origin essence to inhibit the tumor development, strengthening the spleen and benefiting the qi to slow down the attenuation of origin qi, and nourishing the heart and cultivating the mind to stabilize the power of origin spirit in order to further improve the understanding of TCM on the etiology of tumors, and at the same time, to provide a new direction and ideas for the clinical treatment of tumors.

Objective To evaluate the diagnostic value of positive serum specific antibodies to Mycoplasma pneumoniae(MP)in children with Mycoplasma pneumoniae pneumonia(MPP).Methods PubMed,Cochrane Library,Embase,Sinomed,CNKI,Wanfang and VIP databases were searched for studies on the detection of MPP based on antibodies from the establishment of the database to March 31,2023.After literature screening and data extraction,STATA 16.0 software was used for Meta-analysis.Results A total of 9 literatures and 2 148 clinical samples were included.The combined sensitivities[M(95%CI)]of particle agglutination assay(PA)and enzyme-linked immunosorbent assay(ELISA)were 50%(31～69)and 88%(85～90),and the combined specificities[M(95%CI)]were 88%(76～95)and 88%(62～97).The combined diagnostic odds ratio(DOR)[M(95%CI)]were 5.61(3.30～9.53)and 43.82(12.78～150.19),and the summary receiver operating characteristic curve(SROC)area under the curve(AUC)were 0.80 and 0.88,respectively.Conclusion Serum MP specific antibody detection can be used for diagnosis and screening of children MPP,but needs to be combined with clinical symptoms improve the accuracy of the diagnosis.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective The pathophysiological process of acute high-altitude hypoxia-induced lung injury affects protein expression levels,which are mainly evaluated by Western blot.No systematic study has investigated changes in internal control proteins as calibration loading amounts.Methods Lung injury at an altitude of 6000 m was induced in a low-pressure,low-oxygen chamber for 8,24,and 72 h using C57BL/6J mice.Establishment of the model was confirmed by hematoxylin and eosin staining.Expression levels of various internal control proteins,including vinculin,α-tubulin,eukaryotic translation initiation factor 5(EIF5),β-actin,and glyceraldehyde 3-phosphate dehydrogenase(GAPDH)were detected by Western blot,and total protein expression was detected by Coomassie blue staining.Furthermore,the lung injury model in vitro was establised by using,Bronchial epithelial cell(BZAS-2B)andhunman umbilical vein endothelial cells(HUVECS)confirmed by TUNEL staining.Expression levels of internal control proteins were detected by Western blot,and total protein expression was detected by Coomassie Blue staining.Results Acute 8,24,and 72 h hypoxic models were successfully established in lung tissue,demonstrating consistent total protein expression and stable levels of the internal reference proteins vinculin,α-tubulin,EIF5,andβ-actin.GAPDH expression was elevated in the HH8 h,HH24 h,and HH72 h groups compared with the normoxia(Nor)group,but only the increase at HH72 h groups was significant.Similarly,8,24,and 48 h hypoxic models were successfully established in BEAS-2B cells and HUVECs,with consistent total protein expression.In BEAS-2B cells,expression levels of the internal reference proteins β-actin and GAPDH were consistent with the normoxic control(NC)group,while vinculin,α-tubulin,and EIF5 expression levels were significantly reduced under hypoxic conditions for up to 24 h.In HUVECs,vinculin and α-tubulin expression levels were also consistent with the NC group,while EIF5,β-actin,and GAPDH expression levels were significantly reduced at 8 h and increased at 48 h.Conclusions Acute hypoxia induces lung tissue injury,and protein expression levels of the internal reference proteins vinculin,α-tubulin,EIF5,and β-actin are stable,making them suitable internal references for Western blot.Additionally,Western blot detected differential expression levels of the internal reference proteins vinculin,α-tubulin,EIF5,β-actin,and GAPDH in BEAS-2B cells and HUVECs,as the most important in vitro lung tissue models of hypoxia-induced injury.

Objective To evaluate the diagnostic value of positive serum specific antibodies to Mycoplasma pneumoniae(MP)in children with Mycoplasma pneumoniae pneumonia(MPP).Methods PubMed,Cochrane Library,Embase,Sinomed,CNKI,Wanfang and VIP databases were searched for studies on the detection of MPP based on antibodies from the establishment of the database to March 31,2023.After literature screening and data extraction,STATA 16.0 software was used for Meta-analysis.Results A total of 9 literatures and 2 148 clinical samples were included.The combined sensitivities[M(95%CI)]of particle agglutination assay(PA)and enzyme-linked immunosorbent assay(ELISA)were 50%(31～69)and 88%(85～90),and the combined specificities[M(95%CI)]were 88%(76～95)and 88%(62～97).The combined diagnostic odds ratio(DOR)[M(95%CI)]were 5.61(3.30～9.53)and 43.82(12.78～150.19),and the summary receiver operating characteristic curve(SROC)area under the curve(AUC)were 0.80 and 0.88,respectively.Conclusion Serum MP specific antibody detection can be used for diagnosis and screening of children MPP,but needs to be combined with clinical symptoms improve the accuracy of the diagnosis.