OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Ovarian cancer is one of the most common gynecologic cancers in the world.Over the past few decades,there has been considerable research reporting on the mechanisms of cancer development and progression,with multiple nerve as well as neurotransmitters involved.Nerve innervation is also found in ovarian cancer.And in ovarian cancer,various nerves and neurotransmitters play different roles.They are involved in ovarian cancer cells'proliferation metastasis,apoptosis and changes in the tumor microenvironment.Further understanding of the role of these nerve endings in the development of ovarian cancer is essential for understanding the mechanisms of cancer progression.This will be important for subsequent research focusing on tumor regulation.While glucocorticoids and sympathetic nerve-released norepinephrine are able to promote ovarian cancer progression,serotonin may inhibit cancer cell growth.Also,parasympathetic and sensory nerves are capable of having either a positive or negative effect on ovarian tumors.These relevant studies offer the possibility of new therapeutic options for oncology,it may be possible to mitigate the progression of cancer with inexpensive receptor inhibitors or agonists.This will facilitate the subsequent exploration of therapeutic possibilities forovarian cancer and other cancer-related treatments.In this review,we also present some insights into the role of the nervous system in the regulation of ovarian cancer,which we hope will provide new insights into the innervation and progression of ovarian cancer.

Objective To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide(FeNO)and conventional ventilatory lung function parameters in diagnosing bronchial asthma(referred to as"asthma")in children.Methods A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group,and 85 healthy children undergoing routine health checks as the control group.The study compared the differences in serum 14-3-3β protein concentrations between the two groups,analyzed the correlation of serum 14-3-3β protein with clinical indices,and evaluated the diagnostic efficacy of combining 14-3-3β protein,FeNO,and conventional ventilatory lung function parameters for asthma in children.Results The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group(P<0.001).Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E,and a negative correlation with conventional ventilatory lung function parameters(P<0.05).Cross-validation of combined indices showed that the combination of 14-3-3β protein,FeNO,and the percentage of predicted value of forced expiratory flow at 75%of lung volume had an area under the curve of 0.948 for predicting asthma,with a sensitivity and specificity of 88.9%and 93.7%,respectively,demonstrating good diagnostic efficacy(P<0.001).The model had the best extrapolation.Conclusions The combination of serum 14-3-3β protein,FeNO,and the percentage of predicted value of forced expiratory flow at 75%of lung volume can significantly improve the diagnostic efficacy for asthma in children.

BACKGROUND: Previous studies have extensively investigated traditional predictors of cardiovascular disease (CVD) development, progression, and prognosis. However, the influence of novel indicators such as Klotho, on CVD prevalence and prognosis in the general population remains unclear. METHOD: This was an observational study that utilized cross-sectional and longitudinal methods to examine the general population in the National Health and Nutrition Examination Survey (NHANES) 2007-2016. The participants were divided into four groups according to the Klotho quartiles. Primary outcome was CVD [coronary artery disease (CAD), congestive heart failure, and stroke], secondary outcomes were all-cause mortality and cardiovascular mortality. Survey-weighted binary logistic regression analysis was used to analyze the association between Klotho and the prevalence of primary outcome, and the restricted cubic spline (RCS) curve was used to further analyze the nonlinear relationship. Subgroup analyses were conducted to investigate the association between Klotho values and CVD prevalence using survey-weighted binary logistic regression. The incidence of the secondary outcomes among four groups was assessed through Kaplan-Meier survival analysis. Additionally, the relationship between Klotho values and secondary endpoints was explored using survey-weighted Cox proportional hazards regression across various patient subpopulations. RESULTS: A total of 12,146 participants (56.8 ± 10.7 years, 48.5% male) were included in our study. The total incidence of CVD was 9.9% (n = 1201), of which 4.7% (n = 574) were CAD, 3.7% (n = 454) were congestive heart failure, and 4.1% (n = 497) were stroke. Binary logistics regression analysis showed that higher Klotho quartiles were associated with the decreased prevalence of CVD [Quartile 4 vs. Quartile 1: odds ratio (OR) (95% CI): 0.77 (0.64-0.93), P = 0.006] and congestive heart failure [Quartile 4 vs. Quartile 1: 0.75 (0.56-0.99), P = 0.048], However, no significant associations were found between Klotho levels and the outcomes of CAD or stroke. RCS curve illustrated a high Klotho value was negatively correlated with the prevalence of CVD (nonlinear P = 0.838), congestive heart failure (nonlinear P = 0.110) and stroke (nonlinear P = 0.972). No significant interactions were observed in any subgroups regarding the associations between Klotho and prevalence of CVD. After a median follow-up period of 93 months (range: from 1 to 160 months), there were 1228 cases (10.1%) of all-cause mortality in the general population, including 296 cases (2.4%) of cardiovascular mortality. The Kaplan-Meier curves indicated that lower Klotho levels were associated with a significant increase in all-cause mortality across the general population, CVD population, and non-CVD population. As Klotho levels decreased, there was also a notable rise in cardiovascular mortality in both the general population and the CVD population. In the overall population, Cox regression analyses demonstrated that higher Klotho values were associated with a decreased risk of both all-cause and cardiovascular mortality. And no significant interaction was observed in the CVD subgroup regarding the association between Klotho and mortality. CONCLUSION High Klotho level was associated with low prevalence of CVD and low risk of mortality in general population.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by non-specific,persistent inflammation in the intestines.This chronic inflammation often increases the risk of serious complications such as colorectal cancer.Dysplasia acts as a driver of cancer development and plays a connecting role in the occurrence and development of chronic intestinal inflammation and colorectal cancer.Cell proliferation/apoptosis imbalance is the driving factor for dysplasia development.The abnormal proliferation/apoptosis of intestinal mucosal epithelial cells may be affected by cyclooxygenase-2(COX-2),tumor suppressor gene p53,or both.Therefore,reasonable regulation of COX-2/p53 axis may be a key to achieving intestinal mucosal proliferation/apoptosis balance.This article discusses the effects and mechanism of COX-2 and p53 in regulating the occurrence and development of dysplasia in UC from the proliferation/apoptosis imbalance of intestinal mucosal epithelial cells,aiming to provide a reference for understanding the mechanism of dysplasia in UC and developing targeted therapeutic drugs.
Colitis, Ulcerative/metabolism* ; Humans ; Cyclooxygenase 2/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Intestinal Mucosa/metabolism* ; Apoptosis ; Cell Proliferation

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.
Humans ; Animals ; Serotonin ; Insular Cortex ; Pruritus/chemically induced* ; Cerebral Cortex/physiology* ; Neurons