Background: Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus that significantly impairs patients’ quality of life. Traditional Chinese medicine (TCM), as a major component of complementary and alternative medicine, has accumulated numerous effective formulas for the clinical management of DPN. However, systematic approaches for optimizing TCM formulas remain limited. Objective: To establish a pathway-oriented approach for TCM formula optimization and to evaluate the efficacy and mechanisms of the optimized formula in DPN. Methods: We developed 2 formula optimization algorithms that defined pathway-oriented herbal correlation (HC) and herbal contribution (HO) to screen and construct a new herbal formula, Qihongtongbi (QHTB), for treating Qi deficiency and blood stasis syndrome complicated with DPN. An animal experiment was subsequently conducted to evaluate the therapeutic effectiveness of QHTB. A total of 32 specific-pathogen-free male ob/ob mice (18–20 g) were randomly divided into 4 groups: model, Mudan Granules (MDG), QHTB low- and high-dose groups (n = 8). Ten male C57BL/6J mice (18–20 g) served as the control group. Metabolomics analysis was further employed to elucidate the biological mechanisms underlying the effects of QHTB. Results: Based on our previous study on TCM medication patterns for treating DPN, 22 candidate herbs were selected for formula optimization. The top 5 candidate herbs (total HC = 25.24 × 10 ) exhibited HC values comparable to those of MDG (total HC = 26.1 × 10 ). These herbs were Carthamus tinctorius L. (HC = 5.40 × 10 ), Astragalus mongholicus Bunge (HC = 5.23 × 10 ), Salvia miltiorrhiza Bunge (HC = 5.15 × 10 ), Commiphora myrrha (T. Nees) Engl. (HC = 5.02 × 10 ), and Glycyrrhiza glabra L. (HC = 4.44 × 10 ). HO analysis showed that the cumulative HO of these 5 herbs exceeded 50%. In vivo experiments demonstrated that, compared with the model group, QHTB significantly lowered blood glucose (P < 0.05), enhanced nerve conduction velocity (P < 0.01), improved nociceptive hypersensitivity (P < 0.01), and ameliorated sciatic nerve morphology, with efficacy comparable to MDG. Serum and fecal metabolomics further revealed that QHTB exerted multipathway regulatory effects, among which nicotinate and nicotinamide metabolism represented a key mechanism. Conclusion: In summary, this study provides a methodological reference for the systematic optimization of TCM formulas.

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Aim To apply coronary angiography derived index of microcirculatory resistance(caIMR)to evaluate the effect of coronary microcirculation perfusion on myocardial remodeling after interventional therapy in patients with acute anterior ST segment elevation myocardial infarction(STEMI).Methods This was a cross-sectional study.The analysis was performed among the patients who were hospitalized for acute anterior STEMI in the First Department of the Second Affiliated Hospital of Dalian Medical University from January 2021 to July 2022 and received percutaneous coro-nary intervention(PCI)with regtelar follow-up visits.The patients were divided into low caIMR(L-caIMR)group,me-dium caIMR(M-caIMR)group and high caIMR(H-caIMR)group according to the results of caIMR.The results of ech-ocardiography at perioperative period,1 month,3 months,6 months and 1 year were analyzed and compared,including left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),interventricular septum thickness(IVST),mitral orifice flow velocity E/A,mitral annular septum e'and mitral annular wall e',etc.The difference of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and other inflammatory factors in peripheral blood of the three groups were also compared.Results A total of 75 patients diagnosed with acute anterior STEMI were recrui-ted,including 55 males.The L-caIMR group,M-caIMR group,and H-caIMR group had 26,26 and 23 cases,respec-tively.Compared with the L-caIMR group,the LAD and IVST in the M-caIMR group and the H-caIMR group exhibited an increasing tendency one month after PCI,and the increase in the H-caIMR group was more significant than that in the M-caIMR group(P＜0.05).The ejection fraction in the H-caIMR group was notably lower than that in the L-caIMR group and the M-caIMR group at 1 and 3 months after PCI(P＜0.05).Compared with the L-caIMR group,the mitral flow velocity E/A at 6 months after PCI,and the e'at the septal side and the lateral wall of the mitral annulus at 1,3,and 6 months after PCI were significantly reduced in the M-caIMR and H-caIMR groups(P＜0.05).Compared with the L-caIMR group,the levels of IL-1β,IL-6,and TNF-α showed an increasing trend in the M-caIMR group and the H-caIMR group,and the increase was greater in the H-caIMR group than that in the M-caIMR group(P＜0.05).Multivariate anal-ysis revealed that caIMR was a factor influencing the levels of IL-1 β and IL-6(P＜0.05).Conclusion CMD may be involved in the process of myocardial remodeling in patients with acute anterior STEMI after PCI,in which inflammation plays a role.

Objective:To implement evidence-based practice for eye management in ICU patients undergoing prone position ventilation and evaluate the effectiveness of applying the best evidence for eye management in this setting.Methods:Through literature retrieval, screening, and evaluation, the best evidence for eye management in ICU patients undergoing prone position ventilation was summarized and compiled into evidence review indicators. From March to June 2024, convenience sampling was used to select 29 ICU prone position ventilation patients and 30 ICU nurses at Shanghai Changzheng Hospital for baseline review to identify obstacles in clinical practice of evidence and develop action strategies based on these obstacles. From July to October 2024, 29 ICU prone position ventilation patients and 29 ICU nurses were selected for evidence-based practice to compare the implementation rates of review indicators before and after evidence-based practice, ICU nurses' knowledge, attitude and practice regarding eye management for prone position ventilation patients, as well as the intraocular pressure during prone position ventilation and the incidence of eye complications within the first week of ICU admission.Results:After evidence-based practice, the implementation rates of all 16 review indicators by ICU nurses were higher than those before evidence-based practice, and the differences were statistically significant ( P<0.05). The total score, knowledge dimension score, and practice dimension score on the Knowledge, Attitude and Practice Questionnaire on Eye Management during Prone Position Ventilation for ICU nurses were higher than those before evidence-based practice, with statistically significant differences ( P<0.05). After evidence-based practice, the intraocular pressure of ICU patients in prone position ventilation for 8 hours and at the end improved, and the differences were statistically significant ( P<0.05). The overall incidence of eye complications within one week of ICU admission decreased from 27.6% to 6.9%, with a statistically significant difference ( P<0.05) . Conclusions:Implementing evidence-based practices for eye management in ICU patients undergoing prone position ventilation can effectively increase nurses' implementation rates of review indicators, enhance their knowledge, attitude, and practice regarding eye management, and reduce the incidence of eye complications in patients.

Maidong products are categorized into "Hang Maidong" and "Chuan Maidong". Since the Ming and Qing Dynasties, "Hang Maidong" has been regarded as having superior quality, but currently, it remains in name only in the market. This article reviewed historical materia medica and local chronicles from the Ming and Qing Dynasties and analyzed the historical evolution of Maidong production areas. The history of Maidong production in Zhejiang can be traced back to the Song Dynasty, and cultivation had already developed by at least the Ming Dynasty. During the Ming and Qing Dynasties, it was consistently used as a tribute. Ming Dynasty chronicles record "Chuan Maidong", which had already been cultivated on a large scale by the Qing Dynasty. "Hang Maidong" and "Chuan Maidong" share the same origin, with the former identifiable by the "gourd waist" shape of its tuberous root. Based on this, it can be inferred that the "Maimendong" herb illustrated in the Origins of Materia Medica(Ben Cao Yuan Shi) and the Maidong stored in the Qing Palace Imperial Pharmacy were both "Hang Maidong". The protection and development of the authentic "Hang Maidong" medicinal herb are urgently needed.
China ; Drugs, Chinese Herbal/history* ; History, 17th Century ; History, Ancient ; Medicine, Chinese Traditional/history* ; History, Medieval ; History, 16th Century ; History, 18th Century ; History, 15th Century ; Plants, Medicinal/chemistry* ; History, 19th Century ; History, 20th Century ; Humans ; Materia Medica/history* ; History, 21st Century

Small animal multimodal biomedical imaging refers to the integration of multiple imaging techniques within the same system or device to acquire comprehensive physiological and pathological information of small animals, such as mice and rats. With the continuous advancement of biomedical research, this cutting-edge technology has attracted extensive attention. Multimodal imaging techniques, based on diverse imaging principles, overcome the limitations of single-modal imaging through information fusion, significantly enhancing the overall system's sensitivity, temporal/spatial resolution, and quantitative accuracy. In the future, the integration of new materials and artificial intelligence will further boost its sensitivity and resolution. Through interdisciplinary innovation, this technology is expected to become the core technology of personalized medicine and expand its applications to drug development, environmental monitoring, and other fields, thus reshaping the landscape of biomedical research and clinical practice. This review summarized the progress on the application and investigation of multimodal biomedical imaging techniques, and discussed its development in the future.
Animals ; Multimodal Imaging/trends* ; Rats ; Mice ; Artificial Intelligence ; Diagnostic Imaging/methods* ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

Episodic memory, our ability to recall past experiences, is supported by structures in the medial temporal lobe (MTL) particularly the hippocampus, and its interactions with fronto-parietal brain regions. Understanding how these brain regions coordinate to encode, consolidate, and retrieve episodic memories remains a fundamental question in cognitive neuroscience. Non-invasive brain stimulation (NIBS) methods, especially transcranial magnetic stimulation (TMS), have advanced episodic memory research beyond traditional lesion studies and neuroimaging by enabling causal investigations through targeted magnetic stimulation to specific brain regions. This review begins by delineating the evolving understanding of episodic memory from both psychological and neurobiological perspectives and discusses the brain networks supporting episodic memory processes. Then, we review studies that employed TMS to modulate episodic memory, with the aim of identifying potential cortical regions that could be used as stimulation sites to modulate episodic memory networks. We conclude with the implications and prospects of using NIBS to understand episodic memory mechanisms.
Humans ; Memory, Episodic ; Transcranial Magnetic Stimulation/methods* ; Brain/physiology* ; Nerve Net/physiology* ; Mental Recall/physiology* ; Neural Pathways/physiology*