Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

BACKGROUND: Electroacupuncture (EA) may affect the severity of hot flashes (HFs) associated with natural menopause and provide additional benefits for postmenopausal women. However, the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood. OBJECTIVE: We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized sham-controlled trial involved 72 women with HFs. The participants were divided equally into the intervention and control groups. The intervention group was treated with EA, while the control group was treated with sham acupuncture. The main acupoints used were Hegu (LI4), Guanyuan (RN4), Sanyinjiao (SP6), Taixi (KI3), Fuliu (KI7) and Shenshu (BL23). All participants received 18 treatment sessions, distributed across a 6-week period. The treatment was administered on three occasions per week, adhering to a fixed weekday schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) with a minimum interval of one day between sessions. Each patient received a 12-week follow-up. MAIN OUTCOME MEASURES: The HF score was the primary outcome. Participants documented the frequency and severity of HFs in a 7-day symptom diary, which provided data for calculating the HF score. Secondary outcomes were the Menopause Rating Scale (MRS), Menopause-Specific Quality of Life Questionnaire (MENQOL), Pittsburgh Sleep Quality Index (PSQI) and Traditional Chinese Medicine Syndrome Score Scale (TCMSSS), as well as estradiol (E₂), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. RESULTS: Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up (P < 0.001). Immediately after completion of the 6-week treatment cycle and at 12 weeks post-intervention, the HF scores were similar in both groups. At week 6, the intervention group showed significantly greater improvements in MRS, MENQOL (vasomotor, psychosocial, and physical), PSQI and TCMSSS scores (P < 0.05). The improvements in the MENQOL (vasomotor, and psychosocial) and PSQI total scores persisted through the follow-up (P < 0.05). However, the results showed no significant inter- or intragroup differences in sexual scores on the MENQOL (P > 0.05). EA did not significantly decrease E₂, LH or FSH levels compared to placebo. The incidence of adverse events was similar in both groups. CONCLUSION: EA does not significantly improve HFs in early postmenopausal patients. However, it enhances the quality of sleep and decreases menopausal symptoms across vasomotor, psychosocial and physical domains. TRIAL REGISTRATION Chinese Clinical Trial Registry (http://www.chictr.org.cn); Trial ID: ChiCTR2300072002. Please cite this article as: Wang HX, Yu XT, Hu J, Chen JJ, Mei YT, Chen YF. Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial. J Integr Med. 2025; 23(5):519-527.
Humans ; Female ; Electroacupuncture ; Hot Flashes/therapy* ; Middle Aged ; Acupuncture Points ; Quality of Life ; Menopause ; Treatment Outcome ; Adult

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

AIM To screen the material basis for Rhei Radix et Rhizoma on improving human umbilical vein endothelial cell(HUVECs)injury before and after carbonization.METHODS The HPLC fingerprints were established,after which difference analysis was performed by orthogonal partial least squares discriminant analysis.The LPS-induced HUVECs injury model was established,then NO,MDA levels and SOD activity were detected.Gray correlation analysis and partial least squares regression were adopted in the investigation of spectrum-effect relationship,and active constituents were screened.RESULTS There were 22 and 20 common peaks in the fingerprints for 17 batches of raw products and carbonized products,respectively,along with the similarities of more than 0.8.Twelve main difference components were observable,among which gallic acid,5-hydroxymethylfurfural,catechin,aloe rhodopsin-8-O-β-D-glucoside,rhubarbic acid-8-O-β-D-glucoside and sennosides A were identified.The carbonized products demonstrated stronger effect on improving HUVECs injury than the raw product.The correlations of common peaks were more than 0.5 in the fingerprints for raw products and carbonized products,and peaks 3,5,11,12,15,19,23 exhibited significant effects on their efficacy(VIP values＞1).CONCLUSION This accurate,reliable and reproducible method can provide a basis for clarifying the material basis for hemostatic efficacy of Rhei Radix et Rhizoma and its carbonized product.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses