ObjectiveTo study the effect of Tanreqing injection （TRQ） on the pulmonary flora in the rat model of chronic obstructive pulmonary disease （COPD）. MethodWistar rats were randomized into control， model， and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ （2 g·kg^-1）. At the end of the experiment， after blood collection from the abdominal aorta of the rats， the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected， and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal， and those of the model group showed neutrophil infiltration， telangiectasia， lung hemorrhage and emphysema in individual cases， and thickening of collagen fibers in the trachea. Compared with the model group， the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group， the model group showcased increased alveolar space （P<0.01）， which was reduced in the TRQ group （P<0.05）. Compared with the control group， the model group showed increased wall thickness （P<0.01）， and the increase was attenuated in the TRQ group （P<0.01）. TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level， the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas， compared with the control group. After treatment with TRQ， the relative abundance of g_Stenotrophomonas increased， and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group， and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD， which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

This study aims to investigate the effect and mechanism of the herb pair Agrimoniae Herba-Coptidis Rhizoma in inhibiting angiogenesis in the colorectal cancer inflammatory microenvironment by using the method of network pharmacology and the zebrafish model. The method of network pharmacology was employed to obtain the active components, potential core targets, and signaling pathways regulated by the herb pair in inhibiting angiogenesis in the inflammatory microenvironment of colorectal cancer, on the basis of which the underlying mechanism was predicted. The zebrafish model of colorectal cancer was established, and the inflammatory microenvironment was modeled. The effects of different concentrations of the herb pair on the area, number, and length of intersegmental vessels(ISVs) of the zebrafish model were observed. Western blot and real-time quantitative PCR were employed to measure the protein and mRNA levels, respectively, of vascular endothelial growth factor A(VEGFA), vascular epidermal growth factor receptor 2(VEGFR2, also known as kdrl, Flk1), and vascular epidermal growth factor receptor 3(VEGFR3, also known as Flt4). A total of 18 active components and 488 potential targets of Agrimoniae Herba-Coptidis Rhizoma were predicted, and 108 common targets were shared by the herb pair and the disease. According to the results of KEGG pathway enrichment analysis, the angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway were selected for verification. The zebrafish experiment showed that compared with the blank group, the model group showed increased area, number, and length of ISVs in the inflammatory microenvironment. Compared with the model group, the herb pair decreased the area, number, and length of ISVs in a concentration-dependent manner. Compared with the blank group, the model group showed up-regulated protein and mRNA levels of VEGFA, kdrl, and Flt4 in the inflammatory microenvironment. Compared with the model group, the herb pair down-regulated the protein and mRNA levels of VEGFA, kdrl, and Flt4 in a concentration-dependent manner. The results indicated that in the colorectal cancer inflammatory microenvironment, the herb pair Agrimoniae Herba-Coptidis Rhizoma could inhibit angiogenesis via multiple components, targets, and pathways. The anti-angiogenesis effect might be related to the down-regulation of the expression levels of angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway.
Zebrafish ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Colorectal Neoplasms/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Microenvironment/drug effects* ; Angiogenesis Inhibitors/pharmacology* ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Signal Transduction/drug effects* ; Coptis chinensis ; Inflammation/drug therapy* ; Angiogenesis

OBJECTIVE: To conduct qualitative and quantitative analyses of Tripterygium hypoglaucum in Yinning Tablets, a compound preparation of traditional Chinese herbal medicine. METHODS: Thin-layer chromatography (TLC) was used for qualitative analysis of Tripterygium hypoglaucum in Yining Tablets and the analytical protocols were optimized. High-performance liquid chromatography (HPLC) was used to quantitatively analyze the content of triptolide (the main active ingredient of Tripterygium hypoglaucum) in Yinning Tablets. RESULTS: The results of TLC analysis showed that the test sample of Yinning Tablets and the positive control samples both produced clear, well separated spots without obvious interference in the blank samples. Assessment of the influences of the thin-layer plates from different manufacturers, temperature and humidity on the test results demonstrated good durability of the test. HPLC analysis of triptolide showed a good linear relationship within the concentration range of 1-100 μg/mL (regression equation: A=22.219C-19.165, r=0.9999); the contents of triptolide in 3 batches of Yinning tablets were 0.34, 0.34, and 0.28 μg per tablet, all within the range of 0.28-0.34 μg per tablet. It was finally determined that each Yinning tablet should not contain more than 0.6 μg of triptolide. CONCLUSION TLC and HPLC are simple, accurate, durable and specific for qualitative and quantitative analyses of Tripterygium hypoglaucum in Yinning Tablets.
China ; Chromatography, High Pressure Liquid/methods* ; Plant Preparations ; Tablets ; Tripterygium/chemistry*

Objective:To summarize and analyze the clinical features of McCune-Albright syndrome (MAS) in 26 children, to improve the understanding of MAS diagnosis and treatment, and to achieve early clinical diagnosis of MAS.Methods:The clinical data of 26 children with MAS treated in Department of Pediatrics, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from August 2011 to June 2021 were retrospectively analyzed.Their clinical characteristics were summarized and studied. t-test, Mann- Whitney U test, χ 2 test or Fisher′ s exact probability method was used for comparison between groups. Results:(1) Among the 26 MAS patients enrolled, there were 22 females and 4 males.The average onset age of female and male patients was (5.87±2.94) years old and (7.48±3.36) years old, respectively.(2) In female patients, there were 7 cases with the typical triad and 15 cases with the atypical triad.(3) Female patients had the first symptom of vaginal bleeding (8/22) and breast development (14/22). Among the 4 male children, 1 case had " fracture" and 3 cases " lagged behind their peers in height" at the first visit.(4) Compared with the breast development group, the vaginal bleeding group had an earlier onset age[(4.06±1.88) years old vs.(7.82±1.82) years old] ( t=5.023, P<0.001), earlier bone maturation[(1.26±0.07) vs.(1.09±0.13)] ( t=2.933, P<0.05), a greatly lowered predicted adult height[(-2.16±0.98) SDS vs.(-0.96±1.09) SDS]( t=1.352, P<0.05), a lower blood phosphorus level[(1.41±0.14) nmol/L vs.(1.67±0.24) nmol/L] ( t=1.941, P<0.05), and a significantly elevated alkaline phosphatase level[339(313, 656) U/L vs.243(205, 452) U/L] ( U=1.000, P<0.05). All patients (8 cases) in the vaginal bleeding group had fibrous dysplasia of bone.(5) Ten patients progressed to central precocious puberty (CPP). They showed an older average age of onset[(7.27±2.69)years old vs.(4.69±2.68)years old] ( U=44.000, P<0.05), significantly earlier bone maturation at diagnosis[(1.23±0.11) vs.(1.01±0.13)] ( t=1.834, P<0.05), and a lower predicted adult height[(152.00±4.62) cm vs.(162.10±6.91) cm] ( t=3.805, P<0.05), compared with those who did not progress to CPP.(6) Eleven children developed polyostotic fibrous dysplasia of bone, and most common type (8 cases) was polyostotic fibrous dysplasia of bone, primarily at lower limb bones and skulls.(7) Of the 26 children, 20 cases had scattered Café au lait pigments on the skin.The Café au lait pigmented skin lesions in 35% (7/20) cases crossed the midline. Conclusions:With complicated clinical manifestations, MAS is more common and occurs earlier in girls than boys.It is difficult to clinically diagnose MAS in boys due to the insidious onset and atypical symptoms.Female MAS patients with vaginal bleeding as the first symptom usually have an early age of onset, advanced bone age and lower predicted adult height, so they should be monitored and evaluated clinically.Vaginal bleeding is significantly associated with polyostotic fiber dysplasia of bone in MAS patients.Therefore, it is recommended that patients with vaginal bleeding should undergo a routine bone single-photon emission computed tomography scan.This helps understand the situation of occult fiber dysplasia of bone.Patients with later diagnosis and advanced bone age should be aware of the possibility of progression to CPP.

OBJECTIVE: To explore the feasibility and efficacy of laparoscopic transcystic drainage and common bile duct exploration in the treatment of patients with difficult biliary stones. METHODS: Between April 2020 and December 2021, eighteen patients with difficult biliary stones received laparoscopic transcystic drainage (C-tube technique) and common bile duct exploration. The clinical characteristics and outcomes were retrospectively collected. The safety and effectiveness of laparoscopic transcystic drainage and common bile duct exploration were analyzed. RESULTS: Among the eighteen patients with difficult biliary stones, thirteen patients received traditional laparoscopic transcystic drainage, and the remaining five received modified laparoscopic transcystic drainage. The mean surgical duration were (161±59) min (82-279 min), no bile duct stenosis or residual stone was observed in the patients receiving postoperative cholangiography via C-tube. The maximum volume of C-tube drainage was (500±163) mL/d (180-820 mL/d). Excluding three patients with early dislodgement of C-tube, among the fifteen patients with C-tube maintained, the median time of C-tube removal was 8 d (5-12 d). The duration of hospital stay was (12±3) d (7-21 d) for the 18 patients. Five C-tube related adverse events were observed, all of which occurred in the patients with traditional laparoscopic transcystic drainage, including two abnormal position of the C-tube, and three early dislocation of the C-tube. All the 5 adverse events caused no complications. Only one grade one complication occurred, which was in a patient with modified laparoscopic transcystic drainage. The patient demonstrated transient fever after C-tube removal, but there was no bile in the drainage tube and the subsequent CT examination confirmed no bile leakage. The fever spontaneously relieved with conservative observation, and the patient recovered uneventfully with discharge the next day. All the 18 patients were followed up for 1-20 months (median: 9 months). Normal liver function and no recurrence of stone were detected with ultrasonography or magnetic resonance cholangiopancreatography (MRCP). CONCLUSION Laparoscopic transcystic drainage combined with common bile duct exploration is safe and feasible in the treatment of patients with difficult biliary stones. The short-term effect is good. Modified laparoscopic transcystic drainage approach may reduce the incidence of C-tube dislocation and bile leak.
Humans ; Retrospective Studies ; Biliary Tract Surgical Procedures/adverse effects* ; Gallstones/etiology* ; Drainage/methods* ; Laparoscopy/adverse effects* ; Common Bile Duct/surgery*

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system X_c^-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.
Breast Neoplasms/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Female ; Ferroptosis ; Glutathione/metabolism* ; Humans ; Iron/metabolism*

Objective:To summarize the diagnosis and treatment process of abdominal involvement in 229 children with IgA vasculitis and to provide reference for clinic treatment.Methods:A total of 229 pediatric patients, diagnosed as IgA vasculitis with abdominal involvement admitted to the Department of Pediatric Nephrology of Shengjing Hospital, China Medical University from January 1st 2018 to December 31st 2019, were retrospectively analyzed in the study and were divided into three groups according to Numerical Rating Scale to compare indexes in different degrees of abdominal pain.Results:The duration of hospitalization was related with degree of abdominal pain, as the more severe the abdominal pain was, the longer the hospitalization time was( P<0.001). The incidence of bloody stool were also proportionate to the degree of abdominal pain( P<0.001). With the aggravation of abdominal pain, the proportion of intestinal wall edema increased, as the highest proportion was severe group( P<0.001). The proportion of renal involvement in severe group was significantly higher than that in non-severe group( P<0.001). Twenty cases of intestinal wall edema with decreasing of albumin were treated by intravenous hormone therapy after albumin infusion as the results of no intestinal complications occurred.Compared with the mild and moderate groups, the white blood cells of the severe group were higher( P<0.001)and the albumin was lower( P<0.05). It was no significant difference in hemoglobin, serum amylase and serum lipase among three groups.The mean value of CRP had no difference among three groups and was higher than that of normal.Interleukin(IL)-6 in severe group was higher than that in other two groups( P<0.05), but there was no significant difference in IL-2, IL-4, IL-10, IL-17 and tumor necrosis factor.In terms of treatment, 40 cases were treated with immunoglobulin and four cases with hemoperfusion.The average duration of intravenous glucocorticoid application was related to the degree of abdominal pain among three groups.The longest duration was severe group(16.00±6.91)d and the shortest one was mild group(6.71±3.75)d. Conclusion:Pediatric patients diagnosed as IgA vasculitis with severe abdominal pain whose part of inflammatory indexes increased and albumin decreased obviously should complete imaging examinations to evaluate the extent of intestinal wall edema.If diagnosed as hypoalbuminemia and intestinal wall edema distinctly, hormone therapy should be given after albumin infusion to prevent severe complications such as intestinal perforation.For pediatric patients of IgA vasculitis with severe abdominal symptoms, on the basis of hormone therapy, immunoglobulin and hemoperfusion could be used to quickly remove abnormal immune substances to slow down the disease.

BACKGROUND: Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells. METHODS: We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry. RESULTS: The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. CONCLUSION Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.