OBJECTIVE To evaluate the efficacy and safety of guideline-directed medical therapy （GDMT） combined with vericiguat in treating heart failure with reduced ejection fraction （HFrEF）. METHODS A retrospective study was conducted on 346 patients with HFrEF who received standardized diagnosis and treatment at the First People’s Hospital of Changzhou from January 2023 to May 2024. They were divided into standard treatment group （n＝215） and vericiguat group （n＝131）. Patients in the standard treatment group received GDMT， while patients in the vericiguat group received GDMT combined with vericiguat. Propensity score matching （PSM） was used to balance confounding factors between two groups， and the effectiveness （including outcome and prognostic indicators） and safety （occurrence of adverse events） of both groups were evaluated. Kaplan-Meier survival curves for primary and secondary outcome events were drawn， and the influential factors of primary outcome events were screened through univariate and multivariate Cox regression analysis. RESULTS After PSM， there were 100 patients in the standard treatment group and 100 patients in the vericiguat group， and there was no statistically significant differences in baseline data between two groups （P＞0.05）. During a 1-year follow-up， there were statistically significant differences in the cumulative incidence of major outcome events between the standard treatment group and the vericiguat group， cumulative incidence of hospitalization events due to heart failure， changes in N-terminal pro-B-type natriuretic peptide levels before and after treatment between the standard treatment group and the vericiguat group （P＜0.05）. There was no statistically significant difference in the incidence of adverse events between the two groups （P＞0.05）. Multivariate Cox regression analysis results showed that left ventricular ejection fraction ≤35% was a risk factor for the occurrence of major outcome events within 1 year [hazard ratio （HR）＝ 2.090， 95% confidence interval （CI）： 1.175-3.718， P＝0.012]， while the use of vericiguat was a protective factor for the occurrence of major outcome events within 1 year （HR＝0.505， 95%CI： 0.284-0.899， P＝0.020）. CONCLUSIONS Compared with GDMT， GDMT combined with vericiguat can improve the clinical symptoms and prognosis of HFrEF patients， and has good safety.

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

In the quality control of Chinese medicine， the detection of active components and toxic and harmful components are two important links. Although conventional methods such as high performance liquid chromatography and liquid chromatography-mass spectrometry can accurately quantify the above substances， they have shortcomings such as complicated operation， high costs， inability of detection at any time， difficult detection of insoluble and macromolecular substances. Enzyme-linked immunosorbent assay （ELISA） can adsorb antigens or antibodies on the surface of solid carriers and realize qualitative or quantitative analysis of targets by using the specific reactions of antigens and antibodies. This method is praised for the simple operation， high sensitivity， strong specificity， simple requirements for experimental equipment， a wide application range， and low costs. In recent years， ELISA has been widely used in the quality control of Chinese medicine， especially in the content determination of mycotoxins represented by aflatoxin and the qualitative and quantitative analysis of active components. ELISA plays an increasingly important role with its unique advantages， providing new methods and ideas for the rapid quality examination of large quantities of Chinese medicines. This paper reviews the research progress in ELISA for the quality control of Chinese medicine in recent years and prospects its technical development and application prospects， aiming to provide reference and research ideas for further using this method to ensure the quality， safety， and controllability of Chinese medicine.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions. In this study, the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material, which provided a sufficient basis for determining the formulation and process of solid dispersions. The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4. If the ratio is greater than 1∶ 4, the glass transformation temperature of the material will increase significantly, and the solubilization effect of the solid dispersion will show a downward trend. The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150 ℃, the viscosity of the material is less than 10 000 Pa·s, and the melt can be extruded smoothly, and the best extrusion temperature of 160-180 ℃ can be obtained by combining the dissolution results. Finally, the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra. Therefore, rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level, which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.