[Objective] To compare the efficacy and safety of deglycerolized red blood cells (DRBC) and suspended red blood cells (SRBC) based on the propensity score matching (PSM) method, so as to provide evidence for the rational use of DRBC resources in clinical practice. [Methods] A total of 89 patients who received DRBC transfusion and 2 916 patients who received SRBC transfusion in our hospital from January 2023 to September 2024 were included. A 1∶1 nearest neighbor PSM was used to balance covariates such as gender, age, and body mass index (BMI). The changes of hemoglobin (Hb), red blood cell (RBC) count, hematocrit (HCT), and inflammatory markers such as white blood cell (WBC) count, neutrophil (NE) count, C-reactive protein (CRP), and Interleukin-6(IL-6) in the last 72 hours after transfusion were analyzed by SPSS 26.0 and R software to evaluate clinical efficacy and transfusion safety. [Results] The baseline of the two groups was balanced after PSM (P>0.05). There was no significant difference in the total effective rate between the DRBC group (80.9%) and the SRBC group (86.5%) (P>0.05). In the SRBC group, WBC (×10 /L) increased from 9.634±6.742 to 10.147±6.835, CRP (mg/dL) increased from 5.468±4.647 to 6.174±6.114, and IL-6(pg/mL) decreased from 213.733±587.191 to 157.255±552.626. In the DRBC group, WBC (×10 /L) decreased from 11.123±7.880 to 11.011±8.549, CRP (mg/dL) decreased from 5.729±4.761 to 5.326±4.466, and IL-6(pg/mL) decreased from 238.806±639.060 to 152.255±266.558. Compared with the before treatment, the differences between the SRBC group and DRBC group were not statistically significant (P>0.05). Among all patients included in the statistics, the overall incidence of transfusion adverse reactions was 0.205% (6/2 916) in the SRBC group, and no adverse reactions occurred in the DRBC group. The incidence in the SRBC group was higher than that in the DRBC group. [Conclusion] Based on PSM analysis, there was no significant difference in the efficacy and safety of DRBC transfusion compared with SRBC transfusion, which can provide evidence-based support for routine application.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

The impact of prenatal exposure to a mixture of heavy metals on birth weight in newborns has been a topic of ongoing interest. In this study, 258 mothers and infants from the New Hampshire Birth Cohort Study (NHBCS) were selected as the study subjects, and the concentrations of seven heavy metals in the placenta, including Aluminum (Al), Cobalt (Co), Chromium (Cr), Nickel (Ni), Plumbum (Pb), Selenium (Se) and Arsenic (As) were collected. And the birth weight of newborns, the relevant covariates of mothers and newborns were collected. Three analytical methods, Weighted Quantile Sum (WQS) regression, Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) were employed. After adjusting for maternal gestational age, pre-pregnancy BMI, smoking status, education level, parity, gestational age and newborn gender, the combined three methods showed that the total effect of mixed exposure of seven heavy metals on birth weight was negative. Specifically, the WQS analysis revealed that Se had the greatest impact on birth weight, followed by Al. The QGC results showed that the heavy metal associated with the reduction of birth weight was mainly Se and Al in female and male infants, respectively. The BKMR analysis demonstrated a negative combined effect of the seven heavy metals on birth weight in both male and female infants, with Se having the highest posterior inclusion probabilities (PIPs) for female infants (0.45), and Al having the highest PIPs for male infants (0.64) after stratification by gender. In summary, mixed exposure to heavy metals during pregnancy was associated with a decrease in newborn birth weight. Furthermore, there are gender effects with Se and Al associated with decreased birth weight in female and male infants, respectively. These findings provide a theoretical basis for the development of public health policies aimed at preventing adverse pregnancy outcomes and improving the health of newborns.

Objective To investigate the classification effect of deep neural networks in irregular time series data,and to predict the recurrence risk of 362 patients with diffuse large B-cell lymphoma(DLBCL)in a hospital in Shanxi from 2014 to 2020.Methods A total of 362 diagnosed DLBCL patients who achieved complete remission after initial chemotherapy were collected retrospectively,and the recurrence risk was predicted within the next two years.First,LASSO regression was used to screen the variables.Then a deep neural network model of irregular time series data based on GRU-ODE-Bayes was constructed and compared with some traditional models and other deep neural network models.Results Among all the models under study,the traditional models do not perform as well as the deep neural network models in classification.The GRU-ODE-Bayes model was the best,with AUC of 0.85,sensitivity of 0.84,specificity of 0.71,and G-means of 0.77.Conclusion Compared with other models,the GRU-ODE-Bayes model can predict the recurrence of DLBCL patients more accurately.It could benefit the individualized treatment for patients and decision-making for physicians.

Objective:To summarize the clinical phenotype and genetic characteristics of deficiency in ELF4 gene X-linked (DEX).Methods:A case series study was conducted to retrospectively analyze the clinical data and genetic testing results of 2 cases of DEX treated at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and the First Hospital of Jilin University from January 2023 to April 2024. And literature up to April 2024 was searched from the PubMed database, as well as CNKI and Wanfang databases, using keywords such as "ELF4 deficiency" "deficiency in ELF4, X-linked""ELF4 gene". The main clinical manifestations and genotypes of DEX were summarized.Results:Both patients were male, with onset ages of 3 months and 3 years, respectively. Both patients presented with recurrent oral ulcers and abdominal pain. And the laboratory examination showed a significant increase in inflammatory markers. Intestinal examinations showed multiple intestinal ulcers, and both patients developed intestinal fistulas. Whole exome sequencing found ELF4 c.799C>T, p Arg267Trp and ELF4 c. 248-7G>A, both maternal variants. Based on clinical and genetic results, DEX were diagnosed. In terms of treatment, both patients underwent surgical treatment during the acute phase of the disease and received anti-tumor necrosis factor α therapy, but recurrent gastrointestinal symptoms were still observed in Patient 1, while the clinical effect in Patient 2 was still acceptable. However, the inflammatory markers in both patients were not normal even after treatment. Literature review found 18 patients including 2 patients in this study, reported in 5 English articles and no Chinese reports. Thirteen patients had disease onset age before 5. The main clinical manifestations were fever (12/17), oral ulcers (14/18), abdominal pain (8/18), diarrhea (6/18), perianal ulcers (5/17), ileum ulcers (6/16), colon ulcers (7/16), skin involvement (7/17) and recurrent infections (7/18); laboratory examinations found increased erythrocyte sedimentation rate (13/15) as well as C-reactive protein (9/9), and anemia (13/15); in terms of immunological function, there is a decrease in natural killer cells (9/15) as well as a decrease in class switching memory B cells (8/9). The main types of gene variantions were missense variantions (6/18), nonsense variantions (4/18) or frameshift variantions (3/18).Conclusions:DEX should be considered when an early-onset male patient manifested with recurrent fever, oral ulcers or mucosal ulcers, with elevated inflammatory markers, with or without recurrent infection. It is recommended to perform lymphocyte subsets analysis, gastrointestinal endoscopy and genetic testing to support the diagnosis.

Objective To evaluate the characteristics of dose distribution of neuronal networks in vitro on microelectrode arrays(MEAs)under 2.6 GHz radiofrequency(RF)exposure.Methods The MEAs were coupled with a real-time RF exposure setup,and electromagnetic simulation software was used to calculate the RF dose absorbed in cultured neuronal networks.A fiber-optic temperature probe was used for experimental validation and monitoring of the cell temperature during RF exposure.The MEAs were used to record the electrical activity of neurons.Results For an input power of 1 W,a specific absorption rate(SAR)level of(15.51±2.48)W/kg was calculated,and the variability of the SAR distribution was 16%.In our experimental system,the temperature elevation of neurons was up to 0.15℃for an SAR of 4 W/kg RF exposure.Conclusion The exposure device can provide high SAR efficiency and uniformity in the 2.6 GHz band,which is suitable for studying the real-time effects of RF fields on the electrical activity of neuronal networks in the 5G network band.

BACKGROUND:Red light irradiation and silver ion dressing are mostly used to treat chronic difficult healing wounds clinically,but the optimal irradiation time of red light irradiation and silver ion dressing for chronic non-healing wounds,and the combination of different silver ion dressings have not been determined. OBJECTIVE:To investigate the optimal irradiation time and dressing combination of red light and silver ion dressing in the therapy of chronic non-healing wounds. METHODS:The chronic non-healing wound model was made by applying Staphylococcus aureus on the whole skin defect and subcutaneous hydrocortisone injection in SD rats.72 rat models were randomly divided into 4 groups with 18 rats in each group by random number table method.The rats were treated on the basis of standard dressing change and the following therapy:A1B1 group(red irradiation 20 minutes + lipid hydrocolloidal silver sulfate dressing),A1B2 group(red light irradiation 20 minutes + calcium alginate fiber dressing),A2B1 group(red light irradiation 30 minutes + lipid hydrocolloidal silver sulfate dressing),and A2B2 group(red light irradiation 30 minutes + calcium alginate fiber dressing);change dressing,irradiate once,and change dressing every 24 hours.After 14 days of continuous treatment,wound healing rate,bacterial colony number,inflammatory response,histomorphology and angiogenesis were detected in each group. RESULTS AND CONCLUSION:(1)With the extension of treatment time,the wound healing rate of rats in the four groups was increased,and the wound healing rate of rats in the A2B2 group at 3,7,and 14 days after treatment was higher than that in the other three groups(P<0.05).(2)The wound bacterial culture results on day 7 after treatment demonstrated that the number of bacterial colonies in the A2B2 group was lower than that in the other three groups(P<0.05).Western blot assay exhibited that with the extension of treatment time,the protein expressions of tumor necrosis factor α and interleukin-6 in wound tissue of rats in the four groups were decreased,while the protein expressions of interleukin-10 were increased.The protein expressions of tumor necrosis factor α and interleukin-6 in the A2B2 group were lower than those in the other three groups(P<0.05).The protein expression of interleukin-10 in the A2B2 group was higher than that of the other three groups(P<0.05).(3)The wound hematoxylin-eosin staining on day 14 after treatment demonstrated that a large number of collagen fibers in the A2B2 group were parallel distributed and the most closely connected,which was significantly better than the other three groups.(4)The results of immunofluorescence staining indicated that the fluorescence intensity expression of CD31 in the A2B2 group was higher than that in the A1B1,A1B2 and A2B1 groups(P<0.05).q-PCR detection at 3,7,and 14 days after treatment exhibited that the mRNA expressions of vascular endothelial growth factor a and vascular endothelial growth factor receptor 2 in the A2B2 group were higher than those in the other three groups(P<0.05).Western blot assay at 3,7 and 14 days after treatment revealed that the protein expressions of vascular endothelial growth factor a and vascular endothelial growth factor receptor 2 in the A2B2 group were higher than those in the other three groups(P<0.05).(5)These findings confirm that 30 minutes of red light irradiation combined with silver alginate fiber dressing has better results in treatment of chronic non-healing wounds.

Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.