Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

BACKGROUND: Premature menopause, defined as natural menopause before age 40, is associated with diminished ovarian reserve. Despite growing concerns regarding environmental pollutants, no large-scale population-based studies have systematically examined the association between urinary polycyclic aromatic hydrocarbon metabolites (UPAHMs) and premature menopause. METHODS: This cross-sectional study analyzed 2001-2020 NHANES data, including urinary levels of six PAH metabolites: 1-naphthol (1-NAP), 2-naphthol (2-NAP), 3-fluorene (3-FLU), 2-fluorene (2-FLU), 1-phenanthrene (1-PHE), and 1-pyrene (1-PYR). Premature menopause was self-reported as natural menopause occurring before age 40. Multivariable logistic regression assessed UPAHMs' association with premature menopause, with restricted cubic splines (RCS) evaluating nonlinear trends. Subgroup analyses examined demographic interactions. RESULTS: Among 2,565 participants, 662 reported premature menopause. Multivariable logistic regression showed significant associations between elevated urinary levels of 1-NAP (OR: 1.01, 95% CI: 1.00-1.02, P = 0.02), 2-NAP (OR: 1.01, 95% CI: 1.00-1.02, P = 0.02), and 3-FLU (OR: 1.03, 95% CI: 1.01-1.05, P = 0.01) and increased risk of premature menopause. RCS analysis revealed significant nonlinear relationships for 2-NAP, 3-FLU, 2-FLU, 1-PHE, and 1-PYR with premature menopause risk. White participants showed greater susceptibility to UPAHMs. CONCLUSION Elevated UPAHMs, particularly 1-NAP, 2-NAP, and 3-FLU, were linked to higher premature menopause risk, with nonlinear trends observed. White individuals demonstrated greater vulnerability, emphasizing the need for targeted interventions to reduce PAH exposure.
Humans ; Female ; Cross-Sectional Studies ; United States/epidemiology* ; Polycyclic Aromatic Hydrocarbons/urine* ; Adult ; Middle Aged ; Environmental Pollutants/urine* ; Nutrition Surveys ; Menopause, Premature/urine* ; Young Adult ; Environmental Exposure

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.