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.

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).

Sodium and water retention are key and controllable risk factors that contribute to the increased risk of morbidity and mortality in patients with heart failure,and long-term continuous and effective volume management is an important strategy to help patients achieve an individualized state of optimal volume balance.The gradual application of digital health technology in the field of cardiovascular disease has provided new possibilities for volume management in patients with heart failure,while the relevant domestic studies and reports remain fewer.This article reviews the application of digital health technology in the assessment of volume status,management of volume status,volume hsk waming,health education and follow-up in patients with heart failure,and analyzes the existing problems and countermeasures,to provide a reference for digital volume management in out-of-hospital heart failure patients.

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR₁, Rg₁, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
Ginsenosides ; Saponins ; Chemometrics ; Panax notoginseng ; Cardiovascular Diseases ; Chromatography, Liquid ; Tandem Mass Spectrometry

To solve the problems in the course teaching of Pharmacokinetics and change the current situation of the course, a pharmacokinetic solution program based on Excel has been developed. The program, based on Excel, is the most widely used data processing software. The data processing and drawing functions of Excel are used and encapsulated as a program by Excel-VBA. The program is specially used in pharmacokinetic teaching, which includes 25 solution templates arranged according to the 5th edition of Biopharmaceutics and Pharmacokinetics, a textbook published by the People's Medical Publishing House Co., LTD. Each solution template includes six functional areas: operation setting area, data input area, data relationship display area, return parameter output area, pharmacokinetic parameter output area and chart area. In this course, the teaching content is reorganized. Starting from a case, the concept and knowledge of pharmacokinetics are taught by explaining how to apply the program to solve case problems. After years of practice, the teaching effect has been significantly improved.

Objective:To improve the clinical differential diagnosis ability of rheumatoid arthritis (RA) complicated with gout and septic arthritis (SA).Methods:The clinical characteristics, diagnosis, and treatment of one RA patient with hyperuricemia and recurrent swelling and pain in right shoulder were reported and discussed.Results:A patient, with a history of RA for 10 years, hyperuricemia for 8 years, recurrent swelling and pain in right shoulder for 1 year. RA, gout, and SA were diagnosed before, and the response was poor after symptomatic treatment. In recent 1 month, the symptom was aggravated with the formation of fistula on the right shoulder. The laboratory tests for tuberculosis T cell interferon release test (IGRA) and tuberculin (PPD) test were negative, and the CD4 + cell count decreased. The comprehensive analysis of the imaging with right shoulder showed MSU deposition on right shoulder, with bone erosion, bone destruction, bone marrow edema, joint effusion, and multiple sites of connective tissue involvement (synovial bursa, tendon sheath, tendon, and muscle) GeneXpert MTB/RIF (GeneXpert), metagenomic next-generation sequencing (mNGS) of puncture fluid and joint fluid culture prompted Mycobacterium tuberculosis complex group. He was finally diagnosed with RA, gout, and osteoarticular tuberculosis (OAT). Symptoms were relieved after symptomatic treatment. Conclusion:RA patients with hyperuricemia have recurrent single arthritis. In addition to considering for gout, the presence of OAT should also be considered. The immune functional status of the patient and drug used may interfere with the interpretation of immune function tests. It is necessary to integrate the clinical characteristics of patients, a variety of imaging examinations, and etiological detection to confirm the diagnosis and avoid misdiagnosis.

Catheter-associated urinary tract infection (CAUTI) is one of the common nosocomial infections in burn patients. It not only extends the length of hospital stay of patients, increases the economic burden on family and society, but also seriously affects the prognosis and quality of life of patients, increases the risk of death of patients. In this paper, the epidemiological characteristics, influencing factors, and prevention measures of CAUTI in burn patients are reviewed to draw high attention of clinical medical staff and to provide some reference for clinical practice.

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

To observe and evaluate the clinical efficacy of transcutaneous auricular vagus nerve stimulation instrument for sleep disorder at high altitude plateau. Methods The patients with high altitude sleep disorder in the group were randomly divided into control group （n=30）and observation group （n=27）. The observation group received percutaneous vagal stimulation，and the control group received pseudo stimulation intervention for two weeks，five times a week. Before and after treatment，the two groups were measured with Pittsburgh Sleep Quality Index （PSQI） and Beck Depression Inventory （BDI），Generalized Anxiety Disorder （GAD-7） were evaluated. Results There was no significant difference in PSQI，BDI-21 and GAD-7 scores between the two groups before treatment （P> 0.05）；After two weeks of treatment，the total scores of PSQI and BDI-21 in the observation group were lower than those in the control group （P< 0.01），and the improvement of PSQI and BDI-21 scores in the observation group was higher than that in the control group，but there was no significant difference in GAD-7 scores between the two groups before and after treatment（P> 0.05）. Conclusion Transcutaneous auricular vagus nerve stimulation can effectively improve the sleep quality of patients with high altitude sleep disorders and reduce the level of depression. However，the intervention cycle of this trial is short and there is a lack of polysomnography indicators. It is still necessary to carry out long-term，large sample and multi-index trials to provide basis for clinical promotion.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.