In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

OBJECTIVES: To assess the changes in body composition and nutritional risks faced by children with different stages of acute leukemia (AL). METHODS: Bioelectrical impedance analysis combined with anthropometric measurements was used to detect body composition. This prospective study was conducted from August 2023 to July 2024 at Shandong Provincial Hospital, examining the body composition and physical balance of children with various stages of AL and healthy children. RESULTS: The non-fat components of children with AL and healthy children both showed a linear increase with age. In the younger age group, there were no significant differences in body composition between children with AL and healthy children. However, in the older age group, the body composition of children undergoing chemotherapy for AL was significantly lower than that of healthy children (P<0.05), and muscle mass recovered first after the completion of AL chemotherapy. The proportion of children with increased trunk fat in AL children who completed chemotherapy was significantly lower than that in healthy children (P<0.05), while the incidence rate of severe left-right imbalance in body composition was significantly higher (P<0.05). Muscle distribution in children with AL primarily showed insufficient limb and overall muscle mass, whereas healthy children mainly exhibited insufficient upper limb muscle mass. CONCLUSIONS The body composition of children with AL varies at different treatment stages, indicating that nutritional status is affected by both the disease itself and the treatment. Early screening can provide a basis for reasonable nutritional intervention.
Humans ; Child ; Male ; Female ; Child, Preschool ; Body Composition ; Prospective Studies ; Adolescent ; Leukemia/metabolism* ; Infant ; Nutritional Status ; Acute Disease ; Electric Impedance

OBJECTIVE: To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS: According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS: The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.
Humans ; Male ; Tadalafil ; Erectile Dysfunction/etiology* ; Moxibustion ; Middle Aged ; Prospective Studies ; Adult ; Carbolines/administration & dosage* ; Diabetes Complications/therapy* ; Aged ; Treatment Outcome ; Combined Modality Therapy

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

The incidence rate of kidney diseases in China has always remained high.At present,the clinical treat-ment mainly focuses on symptomatic treatment to delay the progression of the disease,and there is a lack of eco-nomical and effective treatment methods.MicroRNA plays an important regulatory role in the occurrence and devel-opment of diseases.This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin(ADR)-induced renal tubular epithelial cell(TCMK-1)injury,with a focus on its potential as a therapeutic target for ADR nephropathy.First,cell viability was assessed using the CCK-8 kit,and a mouse renal tubular epithelial cell model induced by ADR was established.Subsequently,alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR.Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins.Monodansylcadaverin(MDC)staining was performed and the autophagy of cells was detected by flow cytometry.The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased(P＜0.0001).Western blotting results showed that the levels of p62(P＜0.001)and pyroptosis-related proteins(P＜0.001)were increased,while the protein levels of autophagy-related proteins were decreased(P＜0.05).The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autoph-agosomes between the ADR group and the autophagosome inhibitor group(3-MA group)(P＞0.05),indicating that after ADR induction,cell autophagy was inhibited and pyroptosis was enhanced.When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor,the relative expression level of the target gene ATG16L1 was restored(P＜0.001).Western blotting showed that the protein level of p62(P＜0.01)and pyropto-sis-related proteins(P＜0.01)were decreased,and the protein level of autophagy-related proteins was restored(P＜0.001).Flow cytometry results further indicated that cell autophagy was restored(P＜0.0001).In conclusion,ADR targets A TG1 6L1 through miR-142a-3p to reduce the autophagy level of TCMK-1,and simultaneously activates GSDMD-mediated pyroptosis.