Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.
MicroRNAs/physiology* ; PPAR gamma/metabolism* ; Femur Head Necrosis/metabolism* ; Humans ; Signal Transduction/physiology* ; Lipid Metabolism/physiology* ; Animals ; Cell Differentiation ; Mesenchymal Stem Cells/cytology* ; Glucocorticoids/adverse effects*

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Mice ; Animals ; Diabetes Mellitus, Type 2/genetics* ; Streptozocin/pharmacology* ; Diet, High-Fat/adverse effects* ; Proteomics ; Inflammation ; TOR Serine-Threonine Kinases ; Autophagy ; Mammals

To establish a method for determining the contents of six alkaloids (jatrorrhizine hydrochloride, columbamine hydrochloride, epiberberine hydrochloride, coptisine hydrochloride, palmatine hydrochloride, berberine hydrochloride) in six types of Coptidis Rhizoma pieces (crude pieces, ginger juice stir-fried pieces, vinegar stir-fried pieces, wine steamed pieces, wine stir-fried pieces, evodiae juice stir-fried pieces) by RP-HPLC, and explore the relationship with the curative effect of traditional Chinese medicine (TCM) and pharmacodynamics results. The chromatographic column was Welch XtimateTM C₁₈ (4.6 mm×250 mm, 5 μm), with 0.1% triethylamine solution (adjust pH at 10 with ammonium bicarbonate and ammonia) as mobile phase A and acetonitrile as mobile phase B for gradient elution (0-15 min, 10%-25%B; 15-25 min, 25%-30%B; 25-40 min, 30%-45%B) at a rate of 1.0 mL•min⁻¹. The column temperature was set at 30 ℃, and the wavelength was set at 270 nm. The six alkaloids showed a good linear relationship within the range of 0.85-16.96 mg•L⁻¹ (r=0.999 7), 1.25-24.96 mg•L⁻¹ (r=0.999 9), 2.05-40.96 mg•L⁻¹ (r=0.999 9), 3.65-72.96 mg•L⁻¹ (r=0.999 9), 2.88-57.60 mg•L⁻¹ (r=0.999 8), and 13.25-264.96 mg•L⁻¹ (r=0.999 6) respectively. The average recoveries (n=9) of the six alkaloids were 102.4% (RSD 1.2%), 101.8% (RSD 1.3%), 100.3% (RSD 1.8%), 100.7%(RSD 1.8%), 101.2% (RSD 1.5%) and 97.90% (RSD 2.0%) respectively, and their average contents were 3.55, 4.49, 9.12, 19.17, 15.69, 62.56 mg•g⁻¹, respectively. This determination method was accurate and repeatable, which could be used for the content determination in six types of Coptidis Rhizoma pieces. Data analysis on contents determination and preliminary pharmacodynamics results was conducted by using principal component analysis (PCA) and hierarchical clustering analysis (HCA). The analysis results showed that three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces) had significant differences with crude pieces, and the wine steamed Coptidis Rhizoma pieces showed most difference with crude pieces especially, mainly related to triglyceride (TG) and fasting blood glucose levels (FBG) in serum. In addition, columbamine hydrochloride was most affected among the six alkaloids. Those three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces), had more advantages for "anti-diabetes" in TCM clinical application, especially in the treatment of diabetic hyperlipidemia.

OBJECTIVETo investigate the efficacy of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (nCPAP) in preterm infants aged 26-31(+6) weeks with respiratory distress syndrome after ventilator weaning.

METHODSA total of 161 preterm infants were randomly divided into two groups after ventilator weaning: HHHFNC treatment (n=79) and nCPAP treatment (n=82). The two groups were subdivided into 26-28(+6) weeks and 29-31+6 weeks groups according to the gestational age. The treatment failure rate, reintubation rate within 7 days after extubation, incidence of complications, and mortality during hospitalization were compared between the two groups.

RESULTSThe treatment failure rate and reintubation rate showed no significant differences between the HHHFNC and nCPAP groups. The preterm infants aged 26-28(+6) weeks in the HHHFNC group had a significantly higher treatment failure rate than those in the nCPAP group (P<0.05), while the reintubation rate showed no significant difference. As for the preterm infants aged 29-31(+6) weeks, the treatment failure rate and reintubation rate showed no significant differences between the two groups. The incidence of complications and mortality showed no significant differences between the HHHFNC and nCPAP groups.

CONCLUSIONSIn preterm infants aged 29-31(+6) weeks, HHHFNC has a similar efficacy as nCPAP after ventilator weaning, while in those aged less than 29 weeks, HHHFNC should be used with great caution if selected as the first-line noninvasive respiratory support.

Catheters ; Continuous Positive Airway Pressure ; adverse effects ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Noninvasive Ventilation ; adverse effects ; methods ; Ventilator Weaning

Objective: To investigate the distribution of pathogens and drug resistance in bile and the association between the pregnane X receptor (PXR) gene polymorphisms, traditional Chinese medicine (TCM) syndromes and the risk of cholesterol gallstone disease (CGD). Methods: A total of 392 samples were enrolled in this study from January 2014 to February 2015, among which 192 patients were with CGD, and 200 samples were healthy. Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing. The patients were divided into hepatochlic hygropyrexia, stagnation of liver-qi, and the accumulation of damp. The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis. Results: A total of 192 cases were detected in 230 of bile culture pathogens, including Gram-negative bacteria 133 (57.83%), Gram-positive bacteria 76 (33.04%), and fungi 21 (9.13%). The top five pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Candida albicans, and Enterococcus feces, of which 110 cases was of single infection, 48 cases of mixed infection of two strains, eight cases of mixed infection of three bacteria. Among 59 Escherichia coli, the yield extended-spectrum beta-lactamases had 40 (67.80%). The hepatochlic hygropyrexia was the most TCM syndrome, followed by stagnation of liver-qi, and the accumulation of damp was least. Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes (P < 0.05). In hepatochlic hygropyrexia patients the Gram-negative bacteria was most. There was significant differences between CGD group and control group in rs6785049 (P < 0.001). Comparison with wild-type portable GG, GA genotype increased the risk of the occurrence of gallstones (OR = 0.40, 95%CI: 0.16-0.79); likewise, carrying the GA+AA genotype also increased the risk (OR = 0.38, 95%CI: 0.19-0.81). There was no significant differences in rs2276707, rs3814055 site polymorphic loci alleles in CGD group and control group. Conclusions: In the treatment of cholelithiasis, bile samples should be collected for bacterial culture and sensitivity test, and drugs should be strictly chosen based on the results. The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny, and gallstones can be early detected and prevented by detecting genotypes. rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.

OBJECTIVETo explore natural herbs to maintain the bactericidal activity of hydrogen peroxide (H).

METHODSEighteen extracts of Chinese herbs were prepared complying with the standard protocol. Each of the solutions was then mixed with 1% H2O2. The mixtures were handled with two approaches: autoclaved daily for one, two or three times; stored at room temperature from one through five years. Then the bactericidal activity were evaluated by assaying the minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) against Gram positive (Staphylococcus aureus, ATCC25923) and Gram negative (Escherichia coli, ATCC12421) bacteria.

RESULTSWhile mixed with 1% H2O2, 10 out of 18 kinds of assessed Chinese herbs displayed MBC values at 1:12800 or higher after three times of autoclaving, and 8 of them preserved such level of MBC value after stored at room temperature for three years. Some Chinese herbs, i.e. R. Scutellariae, R. Coptidis, R. Bupleuri, H. Epimedii, C. Phelledendri and F. Chrysanthemi, can significantly maintain the bactericidal activity of diluted H2O2.

CONCLUSIONSCertain Chinese herbs can effectively stabilize the bactericidal activity of H2O2 undergoing autoclave or long-term storage. This paper reported a brandnew pharmaceutical function of Chinese herbs and provided experimental data for the potential enhancement of H2O2 usage while its stability level is promoted.

Anti-Bacterial Agents ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Escherichia coli ; drug effects ; Hydrogen Peroxide ; pharmacology ; Microbial Sensitivity Tests ; Staphylococcus aureus ; drug effects ; Sterilization ; Time Factors

Objective To investigate the nutritional status of iodine among residents in Chongqing, and to facilitate scientific prevention and control of iodine deficiency disorders. Methods Select 9 towns in each of the 40 districts (counties) in Chongqing, and collect 40 resident edible salt samples in each of the selected town to detect salt iodine by direct titrimetry. Select 5 towns on the site of the east, west, south, north and middle of every district (county), select 20 children aged 8 to 10 in each of the selected town to collect urine samples and detect urinary iodine by As-Ce catalytic spectrophotometric assay. Results The median of iodine of 14 217 salt specimens by household was 292 mg/kg with a coverage rate of qualified iodized salt of 98.90%( 14 061/14 217). The consumption rate of qualified iodized salt was 95.59%( 13 590/14 217). The median of urinary iodine for 4050 children aged 8 to 10 was 247.20μg/L, of which < 50 μg/L accounted for 4.60%(186/4050), 50-99μg/L accounted for 7.28% (295/4050), 100 - 199 μg/L accounted for 26.44% (1071/4050), 200 - 299 μg/L accounted for 25.58% (1036/4050), 300 μg/L or more, accounted for 36.10% (1462/4050). However, no significant difference was observed between different age groups(x2 = 3.77, P > 0.05). At district (county) level, the median of urinary iodine in 10(25.00%) districts (counties) was 100 - 200 μg/L, that in other 23(57.50%) districts (counties) was 200 - 300 μg/L, and that in other 7(17.50%) districts/counties was greater than 300 μg/L, and statistical significance was observed between different districts/counties (x2 = 441.95, P < 0.01). Conclusions Current iodine nutrition among residents in Chongqing is adequate. While there is excess, need to reduce the amount of salt iodization.

Objective To find out the distribution pattern of environmental fluoride in the coal-burning endemic fluorosis areas to provide scientific evidence for establishing prevention and remedial measures in Chongqing. Methods According to historical data in Chongqing In 2008, 4 endemic villages(Lingyun and Lizi Villages of Wushan County, and Taiping and Daqing Villages of Pengshui County) and 2 non-endemic villages (ShuangLou and XianLong Villages of Yongchuan County) were investigated. Dental fluorosis of children in 8 to 12 year old and residents over 16 years of age for clinical skeletal fluorosis were examined in four endemic villages. Five households from each of 6 villages were taken, where 500 g of coal, mixed clay with coal, mixed coal of soil, coal cinder, soil were sampled; 15 people were taken in each village, each household gathering 500 g of corn, rice, potatoes, vegetables, grain and vegetable, 100 g of dried pepper and 250 ml of drinking water were sampled from 15 families of each village. Household drinking water samples were collected 1, each 250 ml. For those having tea-drinking habit, each household was collected 50 g of tea and 600 ml of drinking tea, the amount of fluoride were determined. Indoor and outdoor air was collected and measured in 5 households in each village. Results The detected rate of dental fluorosis of children in endemic areas was 74.65% (736/986). The detected rate of skeletal fluorosis of adult was 7.20%(736/986). The average fluoride content of coal, mixed clay with coal, mixed coal of soil, cinder coal, soil in the endemic villages was (310.56±209.46), (360.51±224.96), (293.62±65.15), (186.59±133.66), (497.54±294.70)mg/kg. The average fluoride content in non-endemic villages was (48.68±10.62), (275.66±62.69), (152.20±34.43), (209.14±188.66),269.98±58.21)mg/kg. The fluoride content level of endemic villages was significantly higher than that of non-endemic villages(t=7.67,31.54,5.82, 5.82, all P<0.05). The average fluoride content of drinking water, corn, pepper, flee, potato and vegetable in the endemic villages was (0.30±0.14)mg/L, (1.83±2.67), (23.50±91.80), (0.77±0.25), (0.44±0.11), (0.48±0.18)mg/kg, The average fluoride content in non-endemic village was (0.18±0.06)mg/L, (2.21±0.46), (2.82±2.51), (1.31±0.21), (0.64±0.41), (1.10±0.77)mg/kg. The fluoride content in drinking water and pepper in the endemic villages was significantly higher than that of the non-endemic villages(t=7.79, 2.33, all P<0.05). The fluoride content of rice, potato and vegetable in the non-endemic villages was significantly higher than that of the endemic villages(t=39.29,4.69,4.01, all P<0.05). There was no significant difference of fluoride content of tea and drinking tea between endemic villages[(99.41±55.83)mg/kg, (1.59±0.91)mg/L] and non-endemic villages[(79.95±43.78)mg/kg, (1.80±1.16)mg/L, t=1.01, 0.27, all P>0.05]. The amount of drinking tea in the endemic village[(1.45±0.68)L/d] was higher than that in non-endemic village[(1.00±0.47)L/d, t=4.27, P<0.05]. The average fluoride content of indoor air in the endemic village[(12.77±8.08)μg/m3] was higher than that in non-endemic village [(1.16±1.08)μg/m3, t=9.49, P<0.01]. There was no significant difference of fluoride content of outdoor air between endemic village and non-endemic village[(1.10±1.57), (0.39±0.31)μg/m3, t=2.01, P>0.05)]. Conclusions The fluoride source of coal-burning endemic fluorosis areas are coal and mixed coal of soil in Chongqing. Fluoride enters into human bodies mainly via respiratory, not from food. Although fluoride is rich in pepper, people don't eat it, so reducing the fluoride content in indoor air is the principle measure. Drinking tea may be was one factor of endemic fluorosis, which needs to be further studied.