Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To compare the cost-effectiveness between sodium valproate and levetiracetam in the treatment of childhood epilepsy and provide an economic basis for clinical medication choices. Methods A cost-effectiveness analysis was conducted using a decision tree model to compare the effectiveness and drug costs of sodium valproate and levetiracetam in treating childhood epilepsy. Single-factor sensitivity analysis and probabilistic sensitivity analysis were used to assess the impact of parameter variations on the study results. Results The treatment cost of levetiracetam was significantly higher than that of sodium valproate. The incremental cost-effectiveness ratio （ICER） of levetiracetam compared to sodium valproate was ¥8 628.43. Sensitivity analysis results were consistent with the base-case analysis. The probabilistic sensitivity analysis showed that, over a 6-month treatment period, levetiracetam became a more cost-effective option when the willingness-to-pay （WTP） threshold was ¥9,000 or higher. One-way sensitivity analysis revealed that the price of levetiracetam was the most influential factor affecting the ICER. Conclusion When the WTP per effective pediatric epilepsy case is ¥9,000 or higher, levetiracetam demonstrates a cost-effectiveness advantage.

Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

Objective:To evaluate the efficacy of multimodal prehabilitation in patients with refractory functional constipation undergoing Jinling procedure(modified Duhamel surgery).Methods:In this prospective randomized controlled trial,80 patients with refractory functional constipation scheduled for Jinling procedure at the Department of General Surgery,the General Hospital of Eastern Theater Command between January 2020 and December 2021 were enrolled.Participants were randomly assigned to either the observation group(n=40,multimodal prehabilitation)or control group(n=40,routine nursing care).Outcome measures included:time to first flatus,time to first ambulation,defecation volume on postoperative day 5,length of hospitalization,nutritional markers(hemoglobin,albumin,total protein at postoperative day 7),anxiety/depression scores(Hospital Anxiety and Depression Scale,HADS),and total complication rates.Results:Compared to controls,the first ventilation time(48.02±6.15)h,first ambulation time(49.92±5.58)h,defecation volume on the fifth day(234.50±51.03)mL,hospital stay(13.15±2.64)d,anxiety score(43.68±3.45)points,depression score(43.81±1.58)points,and the total incidence of postoperative complications(15%)were significantly lower in the observation group(all p values<0.05).By contrast,the serum levels of hemoglobin(115.60±11.60)g/l,albumin(41.19±5.79)g/L and total protein(61.64±4.94)g/L on day 7 post-operatively were significantly higher in the observation group than those in the control group(P<0.05).Conclusions:Multimodal prehabilitation enhances postoperative intestinal recovery,reduces complications,improves nutritional status,and shortens hospital stays in refractory functional constipation patients undergoing Jinling procedure,supporting its clinical adoption.

Objective To investigate the predictive value of serum vasoactive intestinal peptide(VIP)and 5-hydroxytryptamine(5-HT)levels on the outcome of spinal cord electrical stimulation(SCS)in patients with postherpetic neuralgia(PHN).Methods A total of 96 PHN patients who received SCS treatment in Ziy-ang Central Hospital from January 2022 to December 2023 were selected.According to the disease outcomes of all PHN patients after 6 months of treatment,a good group(n=71)and a poor group(n=25)were set up.The clinical data of the two groups were collected and the serum VIP and 5-HT levels were detected in all pa-tients before treatment.The predictive value of serum VIP and 5-HT on disease outcome after SCS treatment in PHN patients was evaluated by receiver operating characteristic(ROC)curve,and the influencing factors of disease outcome after SCS treatment in PHN patients was explored by multivariate Logistic steppe gression a-nalysis.Results The levels of serum VIP and 5-HT in poor group were higher than those in good group(P＜0.05).The area under the curve(AUC)of serum VIP and 5-HT for predicting the disease outcome of PHN patients after SCS treatment were 0.829(95％CI:0.779-0.874)and 0.743(95％CI:0.693-0.793),respec-tively,and the AUC of combined prediction was 0.941(0.891-0.986).There were no significant differences in age,gender,body moss index,education,location of onset,hypertension and drinking history between the two groups(P＞0.05).The time of initial hospital admission in the poor group was longer than that in the good group,skin rash area in the poor group was larger than that in the good group,and diabetes mellitus and smoking history in the poor group were higher than those in the good group(P＜0.05).The time of admis-sion for initial treatment＞3 d(OR=2.188,95％CI:1.383-3.461),skin rash area＞10 cm2(OR=2.018,95％CI:1.283-3.173),diabetes mellitus(OR=2.264,95％CI:1.379-3.717),serum VIP level ≥41.78 ng/L(OR=3.022,95％CI:1.685-5.420),serum 5-HT level ≥99.27 ng/mL(OR=3.579,95％CI:1.885-6.793)were the influencing factors of disease outcome after SCS treatment in PHN patients(P＜0.05).Con-clusion The elevated levels of serum VIP and 5-HT before treatment are associated with poor outcomes after SCS in patients with PHN,and could be used as potential markers to predict the outcomes of SCS in patients with PHN.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Allergic diseases,also known as hypersensitivity diseases,are a systemic disorder affecting nearly 40%of the global population.Although they vary in affected sites and clinical manifestations,they share many common features.For example,allergic diseases are the same type Ⅰ hypersensitivity reaction;the disease mechanism is based on the inability of the positive deficiency to resist the evil,and the allergens induce the onset of the disease;the course of the disease is similar to the patient's physique;the onset of the disease is closely related to the taiyin meridian of the hand and the foot;and the disease locations in traditional Chinese medicine can be categorized as the"orifices",so that the different diseases can be treated with the same treatment.Chinese medicine believes that spleen deficiency is the initiating factor of immune dysfunction,and lung deficiency is the key to the occurrence of allergic diseases,and regulating the lung and spleen is the key point of treatment for allergic diseases.The method of"cultivating the earth and generating gold"is good at adjusting the spleen and stomach and restoring the function of the lungs,which is the key to"same treatment for different diseases"of allergic diseases.Therefore,the purpose of this article is to explore the commonalities of allergic diseases and the role of the method of"cultivating the earth and generating gold"in the treatment of allergic diseases under the perspective of"same treatment for different diseases".

Objective To establish an expert consensus on home exercise for prevention and rehabilitation of breast cancer related lymphedema.Methods Evidence-based nursing method was used to systematically retrieve and evaluate relevant studies in databases and guideline networks,with a search period from the establishment of the databases to October 2023.Evidence was synthesized to form the expert consensus draft after literature screening,quality evaluation,evidence extraction and evidence integration.Then the final draft was formed through expert discussion meeting and 2 rounds of expert letter consultation.Results The consensus includes 5 dimensions with a total of 22 items,involving evaluation of home exercise,management of home exercise,principles of home exercise,program of home exercise and significance of home exercise.Conclusion This"consensus"was constructed in a scientific and rigorous way,and can provide guidance for promoting the home exercise for prevention and rehabilitation of breast cancer related lymphedema,and ensure the safe and effective implementation of home exercise rehabilitation.