Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quantitative CT(QCT)BMD examination were retrospectively enrolled and divided into training set(n=304)and test set(n=76)at a ratio of 8∶2.The mean BMD of L1-L3 vertebrae were measured based on QCT.Spongy bones of T5-T10 vertebrae were segmented as RO1,radiomics(Rad)features were extracted,and machine learning(ML),Rad and deep learning(DL)models were constructed for classification of osteoporosis(OP)and evaluating BMD,respectively.Receiver operating characteristic curves were drawn,and area under the curves(AUC)were calculated to evaluate the efficacy of each model for classification of OP.Bland-Altman analysis and Pearson correlation analysis were performed to explore the consistency and correlation of each model with QCT for measuring BMD.Results Among ML and Rad models,MLBagging OP and RadBagging-OP had the best performances for classification of OP.In test set,AUC of MLBagging-OP,RadBagging-op and DLOP for classification of OP was 0.943,0.944 and 0.947,respectively,with no significant difference(all P＞0.05).BMD obtained with all the above models had good consistency with those measured with QCT(most of the differences were within the range of(x)±1.96s),which were highly positively correlated(r=0.910-0.974,all P＜0.001).Conclusion AI models based on non-contrast chest CT had high efficacy for classification of OP,and good consistency of BMD measurements were found between AI models and QCT.

Child ; Humans ; Toxoplasmosis, Cerebral ; Hematopoietic Stem Cell Transplantation ; Thalassemia

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G^-) bacteria (62.8%), 40 Gram-positive (G⁺) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G⁺ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;
Bacteremia/epidemiology* ; Bacteria ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Sepsis

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

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.
Animals ; Apoptosis ; Boron/toxicity* ; Mice ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Trichloroacetic Acid/toxicity* ; Tumor Suppressor Protein p53/metabolism*

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （P<0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （P<0.05， P<0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （P<0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （P<0.05， P<0.01）， and the BUN increased significantly on the 14th day （P<0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （P<0.05， P<0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （P<0.05， P<0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （P<0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

Objective:To investigate whether the adverse reactions of Xuebijing injection (XBJJ) are mainly pseudoallergic reactions and explore the influencing factors of its pseudoallergic reactions. Method:Mouse model of pseudoallergic reaction was used to study the anaphylactoid reaction of XBJJ which at 0.5, 1 and 2 times of the highest clinical concentration. Next, we compared the differences in pseudoallergic reactions caused by XBJJ for different storage times after preparation. Specifically, XBJJ was prepared into different concentrations, stored for 10 minutes, 2.5 hours, 6 hours and 24 hours, and then injected into the tail vein of mice. Finally, three different injection speeds of 3 seconds, 45 seconds and 90 seconds were selected for XBJJ injection, and then the differences in the paeudoallergic reactions induced by XBJJ in mice under different injection speeds were compared. Result:XBJJ induces pseudoallergic reactions in mice when the drug concentration is higher than the clinically recommended concentration. Compared with storage for 10 minutes after preparation, the degree of pseudoallergic reaction in mice induced by the same concentration of XBJJ increased with the extension of storage time. In addition, when XBJJ was injected in 3 s (the injection rate was 0.083 mL·s^-1), it produced the strongest pseudoallergic reaction. Conclusion:The adverse reactions induced by XBJJ are mainly pseudoallergic reactions. Excessive storage time after preparation and fast injection speed of XBJJ will lead to aggravation of pseudoallergic reactions in mice. When XBJJ is used clinically, it should strictly follow the usage, dosage, concentration, and drip rate recommended in the drug instruction manual. Rational drug use is of positive significance for improving the safety of XBJJ.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Acetabulum/surgery* ; Developmental Dysplasia of the Hip ; Follow-Up Studies ; Hip Dislocation, Congenital/surgery* ; Humans ; Magnetic Resonance Imaging ; Osteotomy ; Retrospective Studies ; Treatment Outcome