BACKGROUND:Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury;however,the specific mechanism is still not clear.Therefore,revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE:To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS:Allen's impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group.The serum of rats of each group was collected.H9c2 cells were divided into a blank control group,a sham operated rat serum group,a spinal cord injury rat serum group and a luteolin pretreatment group.The cells in blank control group were only cultured with ordinary culture medium.The cells in the sham operated rat serum group were treated with medium containing 10%serum from sham operated rat.The cells in the spinal cord injury rat serum group were treated with medium containing 10%serum from spinal cord injury rat.The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10%rat serum from spinal cord injury rat.After 24 hours of culture,the survival rate of each group of H9c2 cells was measured by CCK-8 assay.Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION:Compared with the blank control group,there was no significant change in cell survival rate in the sham operated rat serum group(P>0.05).Compared with the sham operated rat serum group,the cell survival rate(P<0.01)and the expression of LC3 protein(P<0.05)in spinal cord injury rat serum group was significantly reduced,and the expression of p62 protein was significantly increased(P<0.05).Compared with the spinal cord injury rat serum group,the survival rate of cells in the luteolin pretreatment group significantly increased(P<0.000 1);the expression of LC3 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05).The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.

Standardized reporting is a crucial factor affecting the use of patient guidelines （PGs）， particularly in the reporting and presentation of recommendations. This paper introduced the current status of PG reporting， including the research on PG content and presentation formats， and provided comprehensive recommendations for PG reporting from aspects such as overall framework， recommendations， presentation format， and readability. First， the presentation of PG recommendations should include clearly defined clinical questions， recommendations and their rationale， and guidance on how patients should implement the interventions； for specific content in the PG， such as level of evidence， level of recommendation， it is recommended to explain in text the reasons for giving different levels of recommendation， i.e.， to present the logic behind giving the level of recommendation to the patient； additional information needed in the recommendation framework should be supplemented by tracing references or authoritative textbooks and literature that support the recommendations. Subsequently， the PG text should be written based on the Reporting Checklist for Public Versions of Guidelines （RIGHT-PVG） reporting framework. Finally， to enhance readability and comprehension， it is recommended to refer to the Patient Education Materials Assessment Tool （PEMAT） for translating PG content. To enhance the readability of PGs， it is suggested to present the PG content in a persona-lized and layered manner.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To elucidate the effect of bepridil, an Na +/Ca 2+ exchanger (NCX) inhibitor, on the proliferation, migration and apoptosis of melanoma cells, and to explore their potential underlying mechanisms. Methods:Six paraffin-embedded tissue specimens were collected from 3 patients histopathologically diagnosed with melanocytic nevi and 3 patients histopathologically diagnosed with melanoma in the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January to December 2023. NCX1 expression in tissues was determined by immunohistochemical staining, and Western blot analysis was performed to verify the expression of NCX1 in primary melanocytes and melanoma cell lines A375, A875, SKMEL-28, M14, MV3, and SK-MEL-5. Cell counting kit 8 (CCK8) assay was conducted to evaluate the effect of bepridil at different concentrations on the viability of melanoma cells, and the proliferation curve was drawn to calculate the half inhibitory concentration (IC50) of bepridil. Some melanoma cells were then treated with bepridil at IC50 (bepridil groups), and cells treated with dimethyl sulfoxide-containing media served as control groups. Intracellular Ca 2+ levels were assessed in A375 and SK-MEL-28 cells using the Fluo-4 calcium assay kit, the migration and apoptosis of A375, SK-MEL-28, and A2058 cells were estimated by Transwell assay and flow cytometry respectively. The effects of bepridil treatment on gene expression and pathways in A375 cells were evaluated by transcriptome sequencing, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The content of reactive oxygen species (ROS) in melanoma cells after the bepridil treatment was detected by flow cytometry, and the expression of endoplasmic reticulum stress- and mitochondrial apoptotic pathway-related molecules was determined by Western blot analysis. Comparisons between two groups were performed by t test. Results:Immunohistochemical assay showed that the expression of NCX1 was significantly higher in the melanoma tissues (0.320 ± 0.020) than in the melanocytic nevus tissues (0.235 ± 0.008, t = 4.04, P = 0.016) ; Western blot analysis showed that the NCX1 protein bands were darker in color in the melanoma cell lines than in the primary melanocytes. CCK8 assay showed a gradual decrease in melanoma cell viability with increasing concentrations of bepridil. In the A375 and SK-MEL-28 cells, the fluorescence intensity of calcium was higher in the bepridil groups after the treatment with bepridil at IC50 (25 μmol/L) (64.82 ± 2.98, 75.84 ± 2.07, respectively) than in the corresponding control groups (37.10 ± 2.33, 66.54 ± 1.47, respectively, both P < 0.05) ; in the A375, SK-MEL-28, and A2058 cells, the migration ability was lower in the bepridil groups (103.00 ± 9.07, 67.33 ± 7.22, 61.33 ± 1.76, respectively) than in the corresponding control groups (400.00 ± 25.17, 276.70 ± 14.63, 116.00 ± 10.69, respectively, all P < 0.05), while their apoptosis rates were higher in the bepridil groups (5.72% ± 0.06%, 13.58% ± 0.86%, 25.76% ± 1.95%, respectively) than in the corresponding control groups (3.99% ± 0.50%, 6.47% ± 0.88%, 8.01% ± 0.36%, respectively, all P < 0.05). Transcriptome sequencing revealed 119 up-regulated genes and 164 down-regulated genes in bepridil-treated A375 cells compared with control cells, and the differentially expressed genes were mainly associated with metabolic pathways, endoplasmic reticulum stress, and tumor-related pathways. The ROS levels were higher in bepridil-treated A375, SK-MEL-28, and A2058 cells (1 907 ± 33, 7 607 ± 535, 3 380 ± 300, respectively) than in the corresponding control groups (1 646 ± 16, 4 386 ± 163, 2 110 ± 66, respectively, all P < 0.05). Western blot analysis showed that the expression of C/EBP homologous protein and activating transcription factor 4 was higher in bepridil-treated A375 and SK-MEL-28 cells than in the corresponding control groups, but was lower in the A375 and SK-MEL-28 cells treated with bepridil and BAPTA (a calcium chelator) than in the corresponding cells treated with bepridil alone. Conclusion:The NCX inhibitor bepridil could increase intracellular Ca 2+ levels, suppress the proliferation and migration, and promote the apoptosis of melanoma cells, which may be closely related to biological processes such as endoplasmic reticulum stress.

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 establish a new animal model of filum terminale traction tethered cord syndrome to explore its pathogenesis.Methods Sixteen New Zealand white rabbits were randomly divided into the traction group and the sham group,with 8 rabbits in each group.The traction group used silk thread to establish a model of filum terminale traction tethered cord syndrome,while the sham group only cut the filum terminale without traction.After 8 weeks,the behavioral Talov score,lumbosacral MRI examination,somatosensory evoked potential detection,urodynamic index test and pathological analysis were completed.Results At the 8th week after surgery,the hindlimb injury was obvious in the traction group,and the Talov scores at the 4th and 8th weeks after operation were lower than those in the sham group(P<0.001).The lumbosacral MRI results at 8 weeks after surgery showed that the distal filum terminale was pulled by silk thread,with bladder abnormal enlargement in sagital MRI in the traction group,while axial MRI showed the spinal cord within the spinal canal was subjected to mechanical forces in the downward and dorsal directions;the sagittal and axial MRI of the sham group showed that the spinal cord was located in the middle of the spinal canal and the bladder size was normal.At the 8th week after surgery,the amplitude in the traction group was significantly lower than that in the sham group(P<0.001),and the amplitude decreased by more than 50% .The overall latency period in the traction group was slightly longer than that in the sham group(P<0.05).The results of urodynamic examination showed that the maximum bladder capacity in the traction group was significantly higher than that in the sham group(Z=-3.361,P<0.001),the bladder pressure was significantly lower than that in the sham group(Z=-3.361,P<0.001),and the bladder compliance was significantly higher than that in the sham group(P<0.001).Pathological staining showed that the traction of the filum terminale on the spinal cord led to nerve tissue damage and degeneration of bladder epithelial cells.Conclusion This study successfully established a model of filum terminale traction tethered cord syndrome of New Zealand white rabbits,which can provide reference for exploring the pathogenesis of tethered cord and understanding the pathological process of spinal cord injury.