Lung cancer is the leading cause of cancer-related deaths worldwide, characterized by high incidence and mortality rates. The primary reasons for treatment failure in lung cancer patients are tumor invasion and drug resistance, particularly resistance to chemotherapeutic agents and epidermal growth factor receptor (EGFR) mutant targeted therapy, which considerably undermine the therapeutic outcomes for those with advanced lung cancer. Epithelial-mesenchymal transition (EMT) serves as a crucial biological process closely associated with physiological or pathological processes such as tissue embryogenesis, organogenesis, wound repair, and tumor invasion. Numerous studies have indicated that EMT, mediated through various signaling pathways, plays a pivotal role in the initiation, progression, and metastasis of lung cancer, while it is also closely associated with drug resistance in lung cancer cells. Therefore, research focusing on the molecular mechanisms and pathophysiology related to EMT can contribute to reversing drug resistance in drug treatment for lung cancer, thereby improving prognosis. This article reviews the progress in research on EMT in the invasion, metastasis, and drug resistance of lung cancer based on relevant domestic and international literature.
Humans ; Epithelial-Mesenchymal Transition/drug effects* ; Drug Resistance, Neoplasm ; Lung Neoplasms/physiopathology* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Animals ; Antineoplastic Agents/therapeutic use*

Objective Chronic atrophic gastritis(CAG)is often accompanied by intestinal flora disorder and intestinal symptoms,forming the phenomenon of"stomach disease involving intestine".This study explored the dynamic correlation between intestinal symptoms and qi-stagnation degree in patients with CAG qi-stagnation syndrome and analyzed the characteristics of gut microbiota from the perspective of"spleen-stomach system serving as the pivotal hub of qi movement"in TCM.Methods According to the syndrome element differentiation method,410 patients with CAG were divided into four groups:non-qi-stagnation group,mild qi-stagnation group,moderate qi-stagnation group and severe qi-stagnation group.Correlation analysis and 16S intestinal flora sequencing technology were used to analyze the correlation and differential flora between the degree of CAG qi-stagnation and intestinal symptoms.Results Patients with CAG qi-stagnation syndrome were often accompanied by intestinal symptoms such as frequent flatulence,poor defecation and alternating loose-constipated stools.The frequency of cases was significantly positively correlated with the degree of qi-stagnation"non-mild-moderate-severe"(P<0.05).There was a difference in the abundance of gut microbiota between the four groups of CAG qi-stagnation none,mild,moderate and severe.The relative abundance of Streptococcus,Subdoligranulum,Eubacterium_coprostanoligenes_group and Haemophilus was positively correlated with the degree of qi-stagnation.The relative abundance of Ruminococcus_torques_group and Butyricicoccus showed a negative correlation,and Haemophilus was statistically significant among the four groups(P<0.05).Conclusion This study can provide clinical evidence and micro-mechanism for the connotation of"gastrointestinal co-morbidities"and"different diseases with the same syndrome",which may open up new ideas for clinical diagnosis and treatment.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Objective Chronic atrophic gastritis(CAG)is often accompanied by intestinal flora disorder and intestinal symptoms,forming the phenomenon of"stomach disease involving intestine".This study explored the dynamic correlation between intestinal symptoms and qi-stagnation degree in patients with CAG qi-stagnation syndrome and analyzed the characteristics of gut microbiota from the perspective of"spleen-stomach system serving as the pivotal hub of qi movement"in TCM.Methods According to the syndrome element differentiation method,410 patients with CAG were divided into four groups:non-qi-stagnation group,mild qi-stagnation group,moderate qi-stagnation group and severe qi-stagnation group.Correlation analysis and 16S intestinal flora sequencing technology were used to analyze the correlation and differential flora between the degree of CAG qi-stagnation and intestinal symptoms.Results Patients with CAG qi-stagnation syndrome were often accompanied by intestinal symptoms such as frequent flatulence,poor defecation and alternating loose-constipated stools.The frequency of cases was significantly positively correlated with the degree of qi-stagnation"non-mild-moderate-severe"(P<0.05).There was a difference in the abundance of gut microbiota between the four groups of CAG qi-stagnation none,mild,moderate and severe.The relative abundance of Streptococcus,Subdoligranulum,Eubacterium_coprostanoligenes_group and Haemophilus was positively correlated with the degree of qi-stagnation.The relative abundance of Ruminococcus_torques_group and Butyricicoccus showed a negative correlation,and Haemophilus was statistically significant among the four groups(P<0.05).Conclusion This study can provide clinical evidence and micro-mechanism for the connotation of"gastrointestinal co-morbidities"and"different diseases with the same syndrome",which may open up new ideas for clinical diagnosis and treatment.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].

Objective:To evaluate the efficacy of neonatal resuscitation simulation exercise for perinatal medical personnel.Methods:From August 2020 to July 2021, perinatal medical personnel receiving simulated training of neonatal resuscitation in our hospital were prospectively enrolled. The professional backgrounds of the trainees were collected and their performances on both knowledge skills and behavioral skills were scored. The knowledge skills included pre-resuscitation preparation, initial resuscitation, positive pressure ventilation, tracheal intubation, chest compression and umbilical vein catheterization. The behavioral skills included situational awareness, problem solving, resource utilization, communication and leadership. SPSS 26.0 was used for data analysis.Results:Among the 200 participants, 127(63.5%) were neonatal/pediatric doctors and nurses, 65(32.5%) were obstetricians and midwives, 8(4.0%) were anesthesiologists and the ratio of doctors to nurses was 1.74∶1. The score of knowledge skills was (19.52±2.92) at the beginning of the simulation exercise and (27.02±2.72) at the end. The scores on preparation before resuscitation, initial resuscitation and positive pressure ventilation were significantly improved ( P<0.05). The score of behavioral skills was (16.60±2.34) at the beginning and (20.58±1.77) at the end. The scores of resource utilization, communication and leadership were significantly improved ( P<0.05). Conclusions:The simulation exercise provides multidisciplinary teamwork training for perinatal medical personnel, may significantly improve neonatal resuscitation skills and is worth promoting.

Objective:To investigate the clinical, genetic, and pathological features of nemaline myopathy type 8 (NEM8) caused by KLHL40 gene variation. Methods:The clinical data, gene sequencing results, and musculoskeletal pathophysiology of two cases (a pair of twins) with NEM8 admitted to our hospital in July 2022 were collected. CNKI, VIP, Wanfang, Yiigle, PubMed, Embase, and Web of Science Database were searched with the English and Chinese terms "nemaline myopathy type 8", "nemaline body myopathy type 8", and " KLHL40" from January 2007 to February 2023. The clinical, genetic, and musculoskeletal characteristics of the NEM8 cases were summarized using the descriptive statistical analysis method. Results:(1) Case report: The mother (G2P2) of the twins (Ⅳ-2 and Ⅳ-3) was conceived by IVF-embryo transfer and delivered at 37 +1 gestational weeks. The two cases were dizygotic twins whose maternal grandmother had lip and palate cleft. The first baby (Ⅳ-1) of the woman exhibited absent left pinna, contracture at the end of both fingers, talipes equinovarus in both feet and died of respiratory failure two hours after birth. Fetal edema and fetal movement delay in the twins and varus right foot in one twin were found during pregnancy. Both cases developed intrapartum asphyxia with the clinical manifestations of generalized muscle weakness, respiratory failure, dysphagia, multiple joint contractures, and fractures. The families withdrew the treatment and the twins died after maintaining life with ventilators for 53 days after birth. Whole exome sequencing of the pedigree found c.1779G>T (p.W593C) homozygous variants of the KLHL40 gene in the twins and c.1779G>T (p.W593C) heterozygous variants of the KLHL40 gene in the parents, both were de novo. Musculoskeletal pathophysiology indicated that muscle fibers are thin and round with a fetal shape and absent rod. (2) Literature review: Among the 29 cases of NEM8, including two current cases and 27 cases retrieved from 15 papers, eight cases terminated the pregnancies, and 21 were live births; seven cases (24.1%) with positive family history; 19 cases (65.5%) were found with abnormalities during pregnancy, including abnormal fetal movements, polyhydramnios, joint contracture, and fetal edema. Of the 21 live births, 20 cases had intrapartum asphyxia, 21 had postnatal respiratory failure, 20 had generalized muscle weakness, and 19 had dysphagia. Among the 29 cases, 17 cases (58.6%) were homozygous variants of the KLHL40 gene, and 12 cases (41.4%) were compound heterozygous variants. The detection rate of c.1516A>C(p.Thr506Pro) was the highest [72.4% (21/29)], followed by c.602G>A(p.Trp201*) [17.2% (5/29)]. Out of the 15 cases who underwent musculoskeletal pathological examination, all had abnormal muscle fiber size and morphology; 10 cases had rods. Conclusions:NEM8 should be considered for those with abnormal fetal movements, polyhydramnios, joint malformation, fetal edema during the fetal period and failure to establish respiration at birth as well as postnatal generalized muscle weakness, respiratory failure, dysphagia, multiple joint contractures, and fracture. Moreover, genetic detection should be performed as soon as possible. NEM8 can be diagnosed in ones with KLHL40 gene homozygous or compound heterozygous variants and musculoskeletal pathological results of abnormal size and shape of muscle fibers, regardless of the presence of rods.

The poor prognosis of triple negative breast cancer (TNBC) results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis, which is associated with high recurrence and short overall survival. Here we developed a strategy by employing tumor-targeted self-assembled nanoparticles to coordinately regulate BACH1 (BTB domain and CNC homology 1) and mitochondrial metabolism. The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative (BD) were used to prepare nanoparticles (BH NPs) followed by the modification of chondroitin sulfate (CS) on the surface of BH NPs to achieve tumor targeting (CS/BH NPs). CS/BH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites, glycolysis and metastasis-associated proteins, which were related to the inhibition of BACH1 function. Meanwhile, decreased mitochondrial membrane potential, activated caspase 3/9 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism. In a xenograft mice model of breast cancer, CS/BH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs. In sum, the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CS/BH nanoparticles for the treatment of TNBC.