Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

ObjectiveTo explore the intervention effect and molecular mechanism of Dabufei decoction in Dunhuang formula combined with cisplatin on Lewis lung adenocarcinoma-bearing mice. MethodFifty C57BL/6J mice were used， with 10 randomly assigned to the blank group （without modeling）， and 40 subcutaneously inoculated with Lewis cells to establish a Lewis lung adenocarcinoma-bearing mouse model. These 40 mice were randomly divided into the following four groups （with 10 mice in each group）： Model group （equal volume of physiological saline）， cisplatin group （5 mg·kg^-1）， Dabufei decoction group （14.35 g·kg^-1·d^-1）， and Dabufei decoction combined with cisplatin group （Dabufei decoction 14.35 g·kg^-1·d^-1 + cisplatin 5 mg·kg^-1）. Each group was treated continuously for 14 days. The general condition of the mice was observed， body weight changes were recorded， and the tumor inhibition rate， spleen index， and thymus index were calculated. Peripheral blood white blood cell （WBC）， platelet （PLT）， and hemoglobin （HGB） were detected by routine blood tests. Flow cytometry was used to detect the expression of CD4⁺CD25⁺FoxP3⁺ regulatory T cells （Treg） and natural killer （NK） cells in the spleen. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to determine the expression of proteins and mRNA related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway in tumor tissues. ResultCompared with the blank group， the model group showed decreased body weight （P<0.05）， spleen index， and thymus index （P<0.05）， decreased percentage of NK cells in the spleen （P<0.05）， increased percentage of Treg cells （P<0.05）， and decreased counts of WBC， PLT， and HGB （P<0.05）. Compared with the model group， the Dabufei decoction group exhibited significant tumor growth inhibition， increased body weight， and reduced tumor weight （P<0.05）， increased percentage of NK cells （P<0.05）， decreased proportion of Treg cells （P<0.05）， and increased counts of WBC， PLT， and HGB （P<0.05）. In the cisplatin group， tumor growth was significantly inhibited， body weight significantly decreased （P<0.05）， and tumor weight significantly reduced （P<0.05）. The spleen index and thymus index decreased （P<0.05）， and the percentage of Treg cells significantly decreased （P<0.05）. The counts of WBC， PLT， and HGB significantly decreased （P<0.05）. In the Dabufei decoction combined with cisplatin group， tumor growth was significantly inhibited， and tumor weight significantly reduced （P<0.05）. The levels of phosphorylated PI3K， Akt， and mTOR proteins and mRNA in tumor tissues were significantly reduced in all medication groups （P<0.05）. Compared with the cisplatin group， the Dabufei decoction combined with cisplatin group showed significantly inhibited tumor growth， reduced tumor weight （P<0.05）， increased body weight （P<0.05）， increased spleen index and thymus index （P<0.05）， increased percentage of NK cells （P<0.05）， decreased percentage of Treg cells （P<0.05）， significantly increased counts of WBC， PLT， and HGB （P<0.05）， and reduced levels of phosphorylated PI3K， Akt， and mTOR and their mRNA （P<0.05）. ConclusionDabufei decoction combined with cisplatin has a synergistic effect with reduced toxicity， effectively regulating immune function， increasing the proportion of NK cells， reducing the proportion of Treg cells， improving bone marrow suppression， and downregulating the PI3K/Akt/mTOR signaling pathway to inhibit tumor growth in Lewis lung adenocarcinoma-bearing mice.

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

Objective:To analyze the intervention effect of rehabilitation platform-based online psycho-education on patients with bipolar disorder (BD) in remission stage.Methods:In this randomized controlled study, 91 patients with BD in remission stage who attended the community health center in Xicheng District, Beijing from July to August 2021 were randomly divided into a test group (46 cases) and a control group (45 cases) according to a 1∶1 ratio using the random number table. Baseline data were collected from both groups, and the control group received conventional medication and community telephone follow-up, while the test group was given online mental health education in the form of a WeChat subscription number on this basis, including BD mental health education course push (twice a week) and disease self-management (daily recording of mood, sleep, medication, exercise and gratitude diary), and the intervention period was 6 months in both groups. During the intervention, one patient in the test group was admitted to hospital due to exacerbation of mental illness and the trial was terminated. A total of 90 cases were included in the study. The scores of Medication Adherence Rating Scale (MARS), Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS) and Perceived Devaluation-Discrimination Scale (PDD) were assessed at baseline, after 3 months and 6 months of intervention in both groups, respectively. And the differences in baseline data between the two groups were compared using two independent samples t test and χ2 test, and the repeated-measures ANOVA was used to compare the differences in MARS, HAMD, YMRS, and PDD scores between the two groups before and after the intervention, and to analyze the intervention effects of network mental health education based on the rehabilitation platform on patients in remission stage of BD. Results:After 6 months of intervention, MARS scores in the test group was significantly higher than that in the control group [(8.47±1.75) vs (7.47±1.85)], and was significantly higher than that at baseline (7.36±2.13) and after 3 months of intervention (8.04±1.68) (all P<0.05). YMRS and PDD scores in the test group were significantly lower than those at baseline after 3 and 6 months of intervention [YMRS, 2.0(1.0,4.0),2.0(0,3.0) vs 3.0(1.0,5.5); PDD, (31.18±4.65), (30.13±4.76) vs (32.51±4.51)] (all P<0.05); the differences in YMRS and PDD scores in the control group were not statistically significant (all P>0.05). There was no statistically significant difference in HAMD scores between the two groups before and after the intervention (all P>0.05). Conclusion:Combining mental health education based on rehabilitation platform with conventional medication and community management can significantly improve the medication compliance of patients with BD in remission stage, and improve their manic symptoms and reduce the stigma of the disease.

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

With the population aging， the morbidity and mortality of cancer patients continue to rise. At present， the treatment methods for tumors include surgery， chemotherapy， radiotherapy， targeted therapy， and immunotherapy. However， most chemotherapeutic drugs can cause severe side effects and drug resistance. Therefore， as an alternative therapy， traditional Chinese medicine （TCM） treatment can effectively relieve the clinical symptoms of tumor patients， improve the quality of life， inhibit or stabilize the development of tumors， and prolong the survival period of patients. Due to the good safety of Chinese medicine， its potential anti-cancer activity has attracted increasing attention. Ganoderma lucidum， a treasure of Chinese medicinal material， is a medicinal fungus with a history of more than 2 000 years in China. So far， many studies have proposed the anti-cancer properties of G. lucidum. G. lucidum has extensive pharmacological activities， such as anti-tumor， anti-atherosclerosis， and anti-aging. It can also regulate immunity， protect the liver and the heart， and reduce blood glucose and lipid. The chemical composition of G. lucidum is complex. At present， it is proved to contain polysaccharides， triterpenoids， alkaloids， nucleosides， amino acids， and various trace elements. The anti-tumor mechanisms of polysaccharides and triterpenoids in G. lucidum are mainly achieved by apoptosis induction， immune regulation， anti-angiogenesis， and induction of cell cycle arrest. Currently， it has been widely used in the adjuvant treatment of complex tumors such as lung cancer， liver cancer， cervical cancer， prostate cancer， breast cancer， and colon cancer. The present study reviewed the bioactivities and mechanisms of triterpenoids and polysaccharides in G. lucidum in recent years and highlighted the anti-tumor effects and mechanisms to provide references for the further development and utilization of G. lucidum.

OBJECTIVES: To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model. METHODS: The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry. RESULTS: Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group. CONCLUSIONS This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.
Rats ; Animals ; Hydrocortisone/pharmacology* ; Amygdala/metabolism* ; Adrenocorticotropic Hormone/pharmacology* ; Apoptosis ; Body Weight

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.
Asians ; Drugs, Chinese Herbal ; Female ; Humans ; Medicine, Chinese Traditional ; Medicine, East Asian Traditional ; Nonprescription Drugs ; Pregnancy ; Tension-Type Headache