Dissection of the antitumor mechanism of tetrandrine based on metabolite profiling and network pharmacology.

RATIONALE: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated. METHODS: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology. RESULTS: A total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K-Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway. CONCLUSIONS: The metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation.

Integrative Analysis of Transcriptomic and Metabolomic Data for Identification of Pathways Related to Matrine-Induced Hepatotoxicity.

Matrine (MT) is a major bioactive compound extracted from Sophorae tonkinensis. However, the clinical application of MT is relatively restricted due to its potentially toxic effects, especially hepatotoxicity. Although MT-induced liver injury has been reported, little is known about the underlying molecular mechanisms. In this study, transcriptomics and metabolomics were applied to investigate the hepatotoxicity of MT in mice. The results indicated that liver injury occurred when the administration of MT (30 or 60 mg/kg, i.g) lasted for 2 weeks, including dramatically increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc. The metabolomic results revealed that steroid biosynthesis, purine metabolism, glutathione metabolism, and pyruvate metabolism were involved in the occurrence and development of MT-induced hepatotoxicity. Further, the transcriptomic data indicated that the downregulation of NSDHL with CYP51, FDFT1, and DHCR7, involved in steroid biosynthesis, resulted in a lower level of cholic acid. Besides, Gstps and Nat8f1 were related to the disorder of glutathione metabolism, and HMGCS1 could be treated as the marker gene of the development of MT-induced hepatotoxicity. In addition, other metabolites, such as taurine, flavin mononucleotide (FMN), and inosine monophosphate (IMP), also made a contribution to the boosting of MT-induced hepatotoxicity. In this work, our results provide clues for the mechanism investigation of MT-induced hepatotoxicity, and several biomarkers (metabolites and genes) closely related to the liver injury caused by MT are also provided. Meanwhile, new insights into the understanding of the development of MT-induced hepatotoxicity or other monomer-induced hepatotoxicity were also provided.

Talaromyces Marneffei Infection in an HIV-Negative Child with a CARD9 Mutation in China: A Case Report and Review of the Literature.

BACKGROUND: Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus causing systemic mycosis. Due to the atypical symptoms and diverse imaging findings, T. marneffei-infected patients may be misdiagnosed thus preventing timely antifungal therapy. Moreover, HIV-negative patients with T. marneffei infection may be congenitally immunocompromised because of the mutation of immune-related genes. CASE PRESENTATION: We describe a case of an HIV-negative child who developed disseminated T. marneffei infection in a nonendemic area. Chest CT showed similar imaging changes of miliary pulmonary tuberculosis, while there was no other evidence of tuberculosis infection, and empirical antituberculosis treatment was not effective. Lymphocyte subset analysis showed reduced natural killer cells, and the immunoglobulin profile showed low levels of IgM, C3 and C4. A bone marrow smear revealed T. marneffei infection, and ascites culture also proved T. marneffei infection. Despite antifungal treatment, the child died of multiple organ failure. Two gene mutations in caspase recruitment domain-containing protein 9 (CARD9) were detected, which had not been reported previously in T. marneffei-infected patients. CONCLUSIONS: HIV-negative patients with CARD9 mutations may be potential hosts of T. marneffei. Abnormalities in the immunoglobin profile and lymphocyte subset may provide clues for immunocompromised patients, and further genetic testing is advised to identify gene mutations in HIV-negative patients with T. marneffei infection.

B(C6 F5 )3 /Chiral Phosphoric Acid Catalyzed Ketimine-Ene Reaction of 2-Aryl-3H-indol-3-ones and α-Methylstyrenes.

The enantioselective ketimine-ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine-ene reactions of 2-aryl-3H-indol-3-ones with α-methylstyrenes were achieved by utilizing a B(C6 F5 )3 /chiral phosphoric acid (CPA) catalyst. These ketimine-ene reactions proceed well with low catalyst loading (B(C6 F5 )3 /CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2-allyl-indolin-3-ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C6 F5 )3 significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen-bonding interactions, especially the enhanced N-H⋅⋅⋅O hydrogen-bonding interaction, differentiates the free energy of the transition states of CPA and B(C6 F5 )3 /CPA, thereby inducing the improvement of stereoselectivity.

A case report of a teenager with severe hand, foot, and mouth disease with brainstem encephalitis caused by enterovirus 71.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is an acute viral infection occurring mostly in infants and children. Enterovirus 71 (EV71) infection mostly occurs in children < 5 years of age. Severe cases, however, are usually encountered in children under the age of 3 years, and exceedingly rare in teenagers > 14 years and adults. CASE PRESENTATION: We report a rare case of HFMD in a 16-year-old male teenager residing in Chonqing, China. The clinical presentation was typical of HFMD and included vesicular lesions and oral mucosal ulcers, macular and vesicular lesions on palms and soles. He developed severe neurological complications that were suggestive of brainstem encephalitis. EV71 RNA was detected in the patient's faecal samples by reverse transcription-polymerase chain reaction. Specific IgM antibody to EV71 was detected in both serum and cerebrospinal fluid by ELISA. Gamma immunoglobulin therapy at 25 g/day was administered for 2 days, along with methylprednisolone, mannitol, ganglioside, and creatine phosphate sodium. The patient showed neurological improvement and recovered completely in 1 month. CONCLUSIONS: This case indicates that EV71 infection may cause HFMD in teenagers with potentially severe neurological involvement. Clinicians should be aware of the possibility of HFMD occurring in adults and teenagers as prompt treatment could be life-saving in these patients.

[Effect of augmented renal clearance on plasma concentration of vancomycin and treatment outcome in children with methicillin-resistant Staphylococcus aureus infection].

OBJECTIVE: To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin. METHODS: A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome. RESULTS: The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P<0.05). Compared with the normal renal function group, the ARC group had a significantly lower initial trough concentration of vancomycin and a significantly lower proportion of children who achieved the effective trough concentration of vancomycin (10-20 mg/L) (P<0.05). There were no significant differences in bacteriological outcome and clinical outcome between the two groups (P>0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05). CONCLUSIONS: ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.

Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of mesenchymal stromal cells (MSCs) for the prophylaxis of chronic graft-versus-host disease (cGVHD) in patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Six studies involving 365 patients were included. The pooled results showed that MSCs significantly reduced the incidence of cGVHD (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.46 to 0.86, P = 0.004). Favorable prophylactic effects of MSCs on cGVHD were observed with umbilical cord-derived, high-dose, and late-infusion MSCs, while bone marrow-derived, low-dose, and coinfused MSCs did not confer beneficial prophylactic effects. In addition, MSC infusion did not increase the risk of primary disease relapse and infection (RR 1.02, 95% CI 0.70 to 1.50, P = 0.913; RR 0.89, 95% CI 0.44 to 1.81, P = 0.752; respectively). Moreover, there was an apparent trend toward increased overall survival (OS) in the MSC group compared with that in the control group (RR 1.13, 95% CI 0.98 to 1.29, P = 0.084). In conclusion, this meta-analysis demonstrated that MSC infusion is an effective and safe prophylactic strategy for cGVHD in patients with hematological malignancies undergoing allo-HSCT.

[Association between vasoactive-inotropic score and prognosis in children with septic shock].

OBJECTIVE: To investigate the association between vasoactive-inotropic score (VIS) and prognosis in children with septic shock. METHODS: A total of 117 children with decompensated septic shock who received the treatment with vasoactive agents were enrolled. According to their prognosis, they were divided into death group with 41 children and survival group with 76 children. With the maximum VIS within the first 24 hours (24hVIS max) as the cut-off value (29.5), the children were divided into low VIS group with 78 children and high VIS group with 39 children. The 24hVIS max and the mean VIS within the first 24 hours (24hVIS mean) were calculated for all children. A receiver operating characteristic (ROC) curve analysis was performed for the association between VIS and the prognosis of septic shock. RESULTS: Compared with the survival group, the death group had significantly higher 24hVIS max, 24hVIS mean, PRISM III score, and level of lactate before the use of vasoactive agents and after 24 hours of use (P<0.05). 24hVIS max, 24hVIS mean, PRISM III score, level of lactate before the use of vasoactive agents and after 24 hours of use, and 24-hour pH had a certain value in predicting the prognosis of septic shock, but 24hVIS max had the largest area under the ROC curve. Compared with the low VIS group, the high VIS group had significantly higher number of deaths, PRISM III score, and level of lactate before treatment and after 24 hours of treatment (P<0.05). CONCLUSIONS: VIS is associated with the mortality of children with septic shock, and the severity and mortality of patients increase with the increase in VIS.

The impact of early hyperglycaemia on children with traumatic brain injury.

OBJECTIVE: Hyperglycaemia is common amongst children with traumatic brain injury (TBI). We aim to investigate the association between early hyperglycaemia and poor clinical outcomes in children with moderate to severe TBI. METHODS: We performed a retrospective study in a tertiary paediatric hospital between May 2012 and October 2014 of all patients with TBI who were aged <16 years with a Glasgow Coma Scale (GCS) of ≤13. The primary outcome was death. Secondary outcomes were 14 ventilation-free, 14 paediatric intensive care unit (PICU)-free and 28 hospital-free days. We defined hyperglycaemia as glucose >11.1 mmol/L (200 mg/dL). RESULTS: There were 109 patients with a median age of 54 months [inter-quartile range (IQR): 17-82]. Median glucose on arrival was 6.1 mmol/L (IQR: 5.2-9.8). Median GCS in our cohort was 8 (IQR: 6-12). Multivariate logistic regression demonstrated that initial hyperglycaemia [odds ratio (OR): 15.23; 95% confidence interval (CI): 3.74-62.00; P < 0.001], and GCS <8 (OR: 13.02; 95% CI: 2.31-73.33; P = 0.004) were risk factors for mortality. Multivariate linear regression showed that initial hyperglycaemia was a risk factor for reduced ventilation-free, PICU-free and hospital-free days. CONCLUSIONS: Early hyperglycaemia predicts for in-hospital mortality, reduced ventilation-free, PICU-free and hospital-free days in children with moderate to severe TBI.

Dental caries status of students from migrant primary schools in Shanghai Pudong New Area.

BACKGROUND: In China, there is a large migrant population. A significant proportion of children of the migrant population in China are not able to attend public schools due to the lack of local household registration (HuKou). They turn to privately-operated migrant schools, which are usually under-funded, have bad environmental facilities and are inadequately staffed compared to public schools. This study aims to describe the dental caries status of students from migrant primary schools in Shanghai Pudong New Area and factors that influence their caries status. METHODS: Children (7-12 years old) from migrant primary schools in Shanghai Pudong New Area were randomly selected through a multi-stage cluster sampling method. Following the recommendation of the World Health Organization, caries experiences were recorded using the dmft index. A questionnaire to survey the children's socio-demographic characteristics and oral health-related behaviours was completed by the children's parents or guardians. RESULTS: A total of 1385 children in migrant primary schools were invited, of which 1323 joined the survey (95.5 %). Among all the surveyed subjects, the prevalence rate of dental caries was 74.7 % (65.7 % for primary teeth and 28.1 % for permanent teeth). The mean (SD) dmft scores were 3.17 (3.12), 2.74 (3.02) for the primary teeth and 0.44 (0.84) for the permanent teeth, and 99.5 % of the carious teeth received no treatment. CONCLUSIONS: Students from migrant primary schools in Shanghai Pudong New Area had bad conditions of dental caries and most of the carious teeth were left untreated. The caries experience was associated with tooth brushing habits, snacking habits, dental visit and gender.

[Pathogens and risk factors for ventilator-associated pneumonia in children with congenial heart disease after surgery].

OBJECTIVE: To investigate the distribution and drug sensitivity of pathogens and risk factors for ventilator-associated pneumonia (VAP) in children with congenial heart disease (CAD) after surgery. METHODS: According to the occurrence of VAP, 312 children with CAD who received mechanical ventilation after surgery for 48 hours or longer between January 2012 and December 2014 were classified into VAP (n=53) and non-VAP groups (n=259). Sputum samples were collected and cultured for pathogens in children with VAP. The drug sensitivity of pathogens was analyzed. The risk factors for postoperative VAP were identified by multiple logistic regression analysis. RESULTS: The sputum cultures were positive in 51 out of 53 children with VAP, and a total of 63 positive strains were cultured, including 49 strains of Gram-negative bacteria (78%), 9 strains of Gram-positive bacteria (14%) and 5 strains of funqi (8%). The drug sensitivity test showed that Gram-negative bacteria were resistant to amoxicillin, piperacillin, cefotaxime and ceftazidime, with a resistance rate of above 74%, and demonstrated a sensitivity to amikacin, polymyxin and meropenem (resistance rate of 19%-32%). Single factor analysis showed albumin levels, preoperative use of antibiotics, duration of mechanical ventilation, times of tracheal intubation, duration of anesthesia agent use, duration of acrdiopulmonary bypass, duration of aortic occlusion and use of histamin2-receptor blockade were significantly different between the VAP and non-VAP groups (P<0.05). The multiple logistic regression showed albumin levels (<35 g/L), duration of mechanical ventilation (≥ 7 d), times of tracheal intubation (≥ 3), duration of acrdiopulmonary bypass (≥ 100 minutes) and duation of aortic occlusion (≥ 60 minutes) were independent risk factors for VAP in children with CAD after surgery. CONCLUSIONS: Gram-nagative bacteria are main pathogens for VAP in children with CAD after surgery. The antibiotics should be used based on the distribution of pathogens and drug sensitivity test results of pathogens. The effective measures for prevention of VAP should be taken according to the related risk factors for VAP to reduce the morbidity of VAP in children with CAD after surgery.

A review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology of Abri Herba (Ji-Gu-Cao).

Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.

Chemical profiling of Zhi-Ke-Bao pills and its potential mechanism against cough by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and network pharmacology.

Zhi-Ke-Bao pills (ZKB), a traditional Chinese medicine preparation composed of 13 herbs, is generally used to treat cough caused by external wind cold, phlegm, etc in clinical applications, and it plays a core role in relieving cough caused by COVID-19 and influenza in China. Till now, the understanding of its chemical constituents was dramatically limited due to its chemical complexity, restricting its clinical application or development. In this work, a developed ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) method, a targeted and non-targeted strategy and network pharmacology were used to comprehensively characterize the chemical compositions in ZKB and predict its mechanism against cough. A total of 164 compounds (148 targeted compounds and 16 non-targeted ones) were identified or tentatively characterized in ZKB, including 65 flavonoids, 25 alkaloids, 19 organic acids, 41 saponins, 9 coumarins, 2 phenylpropanoids, 2 anthraquinones, and 1 other types. Among them, 37 compounds were unambiguously identified by comparison to reference standards. Meanwhile, the fragmentation behaviors of five main chemical structure types were also summarized. 309 targets and two core signaling pathways of ZKB against cough were predicted by network pharmacology, including MAPK and PI3K-Akt signaling pathways. It was the first time to characterize the chemical compounds of ZKB and reveal its potential mechanism against cough, providing the material basis for further quality control or pharmacodynamic evaluation of ZKB.

The comparative analysis of Lonicerae Japonicae Flos and Lonicerae Flos: A systematical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) were once used as the same herb in China, but they were distinguished by Chinese Pharmacopoeia in 2005 in terms of their medicinal history, plant morphology, medicinal properties and chemical constituents. However, their functions, flavor, and meridian tropism are the same according to the Chinese pharmacopoeia 2020 edition, making researchers and customers confused. AIM OF THE REVIEW: This review aimed to provide a comparative analysis of LJF and LF in order to provide a rational application in future research. MATERIALS AND METHODS: The information was gathered from China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations (all chosen articles were reviewed attentively from 1980.1 to 2023.8). RESULTS: Till now, 507 chemical compounds have been isolated and identified in LJF, while 223 ones (79 overlapped compounds) are found in LF, including organic acids and derivatives, flavonoids, triterpenoids, iridoids, and essential oil components, etc. In addition, the pharmacological activities of LJF and LF, especially for their anti-influenza efficacy and mechanism, and their difference in terms of pharmacokinetic parameters, toxicology, and clinical applications were also summarized. CONCLUSION: The current work offers comparative information between LJF and LF in terms of botany, traditional uses, phytochemistry, ethnopharmacology, pharmacokinetics, toxicology, and pharmacology, especially their anti-influenza activities. Despite the same clinical applications and similar chemical components in LJF and LF, differentiated components were still existed, resulting in differentiated pharmacological activities and pharmacokinetics parameters. Moreover, the research about anti-influenza mechanism and functional substances of LJF and LF is dramatically limited, restricting their clinical applications. In addition, few studies have investigated the metabolism feature of LF in vivo, which is one of the important bases for revealing the pharmacological mechanism of LF. At the same time, the toxicity of LJF and LF is not fully studied, and the toxic compounds of LJF and LF need to be screened out in order to standardize the drug use and improve their rational applications.

The phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity of Forsythiae Fructus: An updated systematic review.

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Protection against hyperoxia-induced lung fibrosis by KGF-induced MSCs mobilization in neonatal rats.

MSCs have been shown to improve functional and pathological outcome in lung fibrosis. However, low in vivo cell engraftment of the transplanted cells limits their overall effectiveness. KGF (also known as FGF-7) is a critical mediator of pulmonary epithelial repair through stimulation of epithelial cell proliferation. However, the role of KGF in MSCs and its therapeutic effects have not been identified. In this study, we investigated the effect of KGF on MSCs and its preventive role in hyperoxia-induced fibrosis in neonatal rats. Neonatal rats exposed to normoxia or hyperoxia were randomly assigned to receive intraperitoneal injections of normal saline (PL), MSCs, or KGF pretreated MSCs on the fourth day of exposure. Our results showed that as compared to PL, while MSCs attenuated lung fibrosis, KGF pretreated MSCs exhibited enhanced preventive effect against lung fibrosis. This effect was partly attributed to enhanced mobilization of MSCs to the fibrotic lungs. In addition, the SHH signaling pathway, which is associated with the differentiation of stem cells was activated by KGF. Our data suggest that MSCs, especially KGF preconditioned MSCs, can attenuate lung fibrosis and KGF may regulate the MSCs behavior by activating SHH pathway.

[The expression of α-smooth muscle actin during the lung injury induced by hyperoxia].

OBJECTIVE: To explore the expression of α-smooth muscle actin (α-SMA) during the lung injury induced by hyperoxia in infantile rats. METHODS: Sixty-four male Sprague-Dawley (SD) rats about 3 weeks were randomly assigned into normal control group which exposured to room air [fraction of inspired oxygen (FiO(2)) was 0.21] and hyperoxia exposure group (95%O(2)) according to random digits table. Eight rats in each group were randomly sacrificed at day 1, 7, 14 and 21.Pulmonary tissue remodeling was observed by hematoxylin-eosin (HE) staining. Immunohistochemistry method was performed to evaluate the expression of α-SMA in pulmonary tissue, further Western blotting was also made to determine the expression of α-SMA. RESULTS: The early histopathologic changes after HE were inflammation and edema in pulmonary tissue, while the later changes were interstitial hyperplasia and fibroblast proliferation. The expression of α-SMA was very slight in bronchial epithelium, alveolar epithelium and alveolar interstitium in normal control group, but increased with the time of hyperoxia exposure prolonged and peaked at 21st day. Western blotting detected that the expression of α-SMA after hyperoxia exposure for 1 day and 7 days in hyperoxia exposure group presented no difference compared with normal control group (1.02±0.12 vs. 1.00±0.13, 1.05±0.14 vs. 0.99±0.12, both P>0.05), but the expression of α-SMA after hyperoxia exposure for 14 days and 21 days was increased compared with normal control group (1.27±0.21 vs. 1.05±0.15, 2.26±0.28 vs. 1.05±0.14, P<0.05 and P<0.01). CONCLUSIONS: Pulmonary fibrosis remodeling was caused by hyperoxia exposure. The expression of α-SMA in pulmonary tissue in hyperoxia exposure groups obviously increased, and could play an important role in pulmonary fibrosis remodeling.

Psychological impact of the COVID-19 epidemic among healthcare workers in paediatric intensive care units in China.

To perform a mental health evaluation and an early psychological intervention for healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) epidemic, an online survey was conducted among 3055 HCWs in the paediatric intensive care units (PICUs) of 62 hospitals in China on March 26, 2020, by the Neurology and Sedation Professional Group, Emergency Department, Paediatrics Branch, Chinese Medical Association. The questionnaire was divided into three parts, including general information, the Impact of Event Scale-Revised (IES-R), and the Depression Anxiety Stress Scale-21 (DASS-21). The results show that a total of 970 HCWs (45.99%) were considered to meet the clinical cut-off scores for posttraumatic stress (PTS), and the proportions of participants with mild to extremely severe symptoms of depression, anxiety and stress were 39.69%, 36.46% and 17.12%, respectively. There was no significant difference in the psychological impact among HCWs of different genders. Married HCWs were 1.48 times more likely to have PTS than unmarried HCWs (95% Cl: 1.20-1.82, p <0.001). Compared with junior professional title participants, the PTS-positive rate of HCWs with intermediate professional titles was 1.91 times higher (90% Cl: 1.35-2.70, p<0.01). Those who had been in contact with confirmed COVID-19 cases were 1.40 times (95% Cl: 1.02-1.92, p <0.05) more likely to have PTS than those who did not have contact with COVID-19 cases or did not know the relevant conditions. For depression, the proportion of HCWs with intermediate professional titles was significantly higher, at 1.65 times (90% Cl: 1.17-2.33, p <0.01) that of those with junior professional titles. The depression of HCWs at work during the epidemic was 1.56 times that of HCWs on vacation (95% Cl: 1.03-2.37, p <0.05), and their anxiety was 1.70 times greater (95% Cl: 1.10-2.63, p <0.05). Participants who had been in contact with confirmed COVID-19 cases had more pronounced anxiety, 1.40 times that of those who did not have contact with COVID-19 cases or did not know the relevant conditions (95% Cl: 1.02-1.92, p <0.05). There was no significant correlation between the variables and the positive results of stress symptoms. In total, 45.99%, 39.69%, 36.46% and 17.12% of PICU HCWs were affected by PTS, depression, anxiety and stress, respectively, to varying degree. Married status, intermediate professional titles and exposure history were independent risk factors for PTS. Intermediate professional titles and going to work during the epidemic were independent risk factors for depression, and going to work and exposure history during the epidemic were independent risk factors for anxiety. In the face of public health emergencies, HCWs not only specialize in paediatric intensive care but also, as a high-risk group, must actively take preventive measures and use mitigation strategies.

[Sperm DNA damage and unexplained recurrent spontaneous abortion].

OBJECTIVE: To explore the relationship of sperm DNA damage with unexplained recurrent spontaneous abortion (URSA). METHODS: Sperm DNA fragmentation was evaluated by sperm chromatin dispersion (SCD), and the results were expressed in terms of DNA fragmentation index (DFI). DFIs were measured in the male partners of 56 women with URSA (the experiment group) and of 31 without URSA (the control group). RESULTS: The DFI was shown to be (11.0% - 56.9%) in the experiment group, 21 (37.5%) of the subjects over 30%, as compared with (10.0% -36.8%) in the control group, only 8 (25.8%) of the subjects over 30%, significantly higher in the former than in the latter (29.4% vs 25.5%, P < 0.05). CONCLUSION: There is a relationship between sperm DNA damage and URSA.