Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To establish and evaluate a new real-time quality control method that can identify the random errors by using the backpropagation neural network (BPNN) algorithm and taking blood glucose test as an example.Methods:A total of 219 000 blood glucose results measured by Siemens advia 2 400 analytical system from January 2019 to July 2020 and derived from Laboratory Information System of Beijing Chaoyang Hospital Laboratory Department was regarded as the unbiased data of our study. Six deviations with different sizes were introduced to generate the corresponding biased data. With each biased data, BPNN and MovSD algorithms were used and tested, and then evaluated by traceability method and clinical method.Results:For BPNN algorithm, the block size was pre-set to 10 and the false-positive rate in all biases was within 0.1%. For MovSD, however, the optimal block size and exclusive limit were 150 and 10% separately and its false-positive rate in all biases was 0.38%, which was 0.28% higher than BPNN. Especially, for the least two error factors of 0.5 and 1, all the random errors were not detected by MovSD; for the error factor larger than 1, random errors could be detected by MovSD but the MNPed was higher than that of BPNN under all deviations. The difference was up to 91.67 times. 460 000 reference data were produced by traceability procedure. The uncertainty of BPNN algorithm evaluated by these reference data was only 0.078%.Conclusion:A real-time quality control method based on BPNN algorithm was successfully established to identify random errors in analytical phase, which was more efficient than MovSD method and provided a new idea and method for the identification of random errors in clinical practice.

Objective: To analyze the relationship between tumor deposits(TD) and clinicopathological features of locally advanced gastric cancer(LAGC) patients. Methods: The clinicopathological characteristics of 300 LAGC patients undergoing radical gastrectomy in Renmin Hospital of Wuhan University from Jan 2014 to Jul 2017 were collected. The relationship between clinicopathological features and prognosis of LAGC patients and TD status in LAGC patients were analyzed retrospectively. Results: TD were positive in 65(21.7%) patients. Univariate analysis showed that the depth of invasion, lymph node metastasis, pTNM stage, tumor size, vascular invasion, preoperative tumor markers were correlated with the status of TD(all P<0.05). Multivariate Logistic regression analysis showed that lymph node metastasis, pTNM stage, vascular invasion and depth of invasion were independent risk factors for positive TD (allP<0.05). Univariate analysis on prognosis of LAGC patients showed lesion location, degree of differentiation, lymph node metastasis, pTNM stage, tumor size, positive TD, number of TD and vascular invasion are associated with prognosis of LAGC (all P<0.05). Multivariate COX regression analysis showed that the number of TD >3 was an independent risk factor for the prognosis of LAGC patients(HR=2.242, 95% CI: 1.484-3.386, P=0.000). The median survival time of TD-positive LAGC was less than TD-negative group(χ²=91.077, P<0.001). The median survival time of TD number>3 group was significantly shorter than that in TD number<3 group and TD-negative group(χ²=192.969, P<0.001). Conclusions TD are closely related to tumor stage in LAGC patients. The status of TD is an independent risk factor for the prognosis of LAGC. Multiple TDs indicate poor prognosis of LAGC patients.

Objective:To establish the quantitative method for eucalyptol in Chimonanthus salicifolius S. Y. Hu by GC. Methods:The GC method was performed on a Zebron ZB-WAX column (60 m × 0. 32 mm,0. 5 μm) with programmed temperature of 60-200℃, an FID detector was used, the detector temperature was 250℃, the inlet temperature was 220℃, and the carrier gas was nitrogen with high purity. Results:A good linearity of eucalyptol was within the range of 0. 012 6-0. 503 4 mg·ml-1(r=0. 999 8), and the average recov-ery was 100. 68%(RSD=1. 51%,n=6). Conclusion:The method is simple, accurate and quick with good reproducibility, and suitable for the quality control of Chimonanthus salicifolius S. Y. Hu.

AIM:To study the expression of Jagged 2/Notch3 signaling molecules in pulmonary vascular wall of pulmonary hypertensive rats induced by monocrotaline .METHODS: SD rats were randomly divided into normal control group (C group,n=15), solvent control group (S group,n=15) and monocrotaline model groups (M group,n=15).The model of pulmonary hypertension was established by a single subcutaneous injection of monocrotaline (50 mg/kg).The rats in S group were given a single subcutaneous injection of the same dose of solvent .After 4 weeks, the pulmonary vascular remodeling was assessed by HE staining , and the mean pulmonary artery pressure ( mPAP) and right ventricular systolic pressure (RVSP) were determined by right heart catheterization .The expression of Jagged2/Notch3 /Hes5 molecules in the pulmonary vascular wall was detected by immunohistochemical method and real -time PCR.RESULTS:Compared with S group and C group , the percentage of medial wall thickness of smaller arteries in model group increased significantly (P<0.01).The levels of mPAP and RVSP in M group were significantly higher than those in S group and C groups (P<0.01).The results of real-time PCR showed that the expression of Jagged 2, Notch3 and Hes5 was significantly increased in M group compared with S group and C group .The data from immunohistochemical detection indicated that Jagged 2 mainly expressed in the intima of small lung artery , Notch3 and Hes5 mainly expressed in the medial smooth muscle cells .Com-pared with S group and C group , the expression of Jagged 2 and Notch3 was significantly increased in the lung small arteries of M group.CONCLUSION:The activation of Jagged2/Notch3 signaling pathway might play an important role in the for-mation of pulmonary hypertension .

Objective To understand the distribution and drug resistance of pathogens isolated from blood culture samples Chang’an Hospital from 2012 to 2014 to provide basis for rational use of antibacterial drugs.Methods The clinical date of distribution,changes and drug resistance of main pathogens in blood culture samples during 2012 and 2014 in chang anhospi-tal were retrospectively analyzed.Results 512 pathogenic bacterial strains were isolated from 4 792 blood culture samples in 2012~2014.Among them,gram-negative bacteria accounted for 62.50% (320/512),Escherichia coli ,Klebsiella pneumoni-ae and Pseudomonas aeruginosa accounted for 25.20% (129/512),14.26% (73/512)and 8.20% (42/512)respectively;Gram-positive bacteria accounted for 29.30% (150/512),Staphylococcus aureus and Coagulase-negative Staphylococcus ac-counted for 11.52% (59/512)and 10.16% (52/512)respectively.The rate of fungi was 7.62% (39/512).Susceptibility re-sults showed that Escherichia coli and Klebsiella pneumoniae had highly sensitive to carbapenems,but had a varying degrees of resistance to other antibacterial drugs.The rate of drug resistant of Gram-positive cocci to Penicillin,Erythromycin and Clindamycin had been a high level,but no strains being resistant to van comycin and linezolid had been detected.Conclusion The pathogens causing bloodstream infection widely distribute,and have highly drug-resistant.It is necessary to under-stand the distribution of pathogens isolated from blood culture as well as the changes of drug resistance in a timely manner so as to guide the reasonable clinical medication.

Objective To investigate the prevalence of multidrug resistant genes in Klebsiella pncumoniae.MethodsTwenty strains of multidrug resistant Klebsiella pneumoniae were isolated from burn patients.Susceptibility of these strains to 14 antibiotics was detected by KB method.PCR was used to detect oqxA,smrKpn,qacE,tehA,mdfA and qacEΔl-sul1 genes.ResultsThe antibiotic sensitivity rates of 20 multidrug resistant Klebsiella pneumoniae isolates to antibiotics tested were ＜ 30％ except that to imipenam.The positive rates of efflux pump genes mdfA,qacEΔl-sull and oqxA were 65％,100％ and 100％,respectively; while those ofsmrKpn,qacE and tehA were 0％,0％ and 15％.ConclusionoqxA gene has been detected in multidrug resistant Klebsiella pneumoniae from burn patients with high positive rate.

Objective To explore the difference of cognitive function and psychosocial function between remitted bipolar disorder(BPD) and remitted schizophrenia.Methods 8 neuropsychological tests (17 items)which evaluate attention,verbal learning and memory,visual memery and executive function were given to 30 remitted BPD,32 remitted schizophrenia and 34 normal controls.The differences of cognitive functions between the three groups were compared using multivariate analysis of variance (MANOVA).Psychosocial functions of remitted BPD and remitted schizophrenia were both evaluated by Global Assessment Function (GAF),and the difference of Psychosocial functions between the two groups was also tested by MANOVA.Results1.Remitted schizophrenia showed dysfunction in neuropsychological tests except Stroop C and digit span subtest-forward compared with controis.but Remitted BPD only showed dysfunction in 9 neuropsychological items compared with controls.There was no significantly differences on WCST,digit span subtest-backward,and TMT-B between remitted BPD and remitted schizophrenia,the degree of impairment of the two groups was same.But scores from logical memory sub-test and Stroop CW of remitted schizophrenia were significantly lower than that of remitted BPD( ( 8.13 ± 3.35),( 12.11 ±3.72),(6.00 ±3.09),(9.78 ±3.60);(48.61±15.73),(69.33 ±21.04),P＜0.05).There was significant difference on scores of GAF between remitted BPD and remitted schizophrenia.Conclusion There are some overlap in cognitive impairment in remitted BPD and remitted schizophrenia,but in remitted schizophrenia the cognitive profile is characterized by generalized and severer pattern of deficits.The psychosocial function of remitted BPD is better than that of remitted schizophrenia.