Endoscopic transforaminal lumbar interbody fusion (TLIF) offers substantial advantages in the management of degenerative spinal diseases, including accelerated postoperative recovery. However, its technical complexity and steep learning curve pose risks for nerve root injury. Optimizing nerve root protection in full-endoscopic facet-sparing TLIF (FE fs-TLIF) and full-endoscopic facet-resecting TLIF (FE fr-TLIF) is essential for enhancing surgical safety. This study aimed to improve the nerve root protection in FE fs-TLIF and FE fr-TLIF by optimizing cage glider selection and insertion techniques based on the specific cage shape—banana-shaped or bullet-shaped. The goal was to ensure safe cage positioning and mitigate nerve root injury during discectomy, endplate preparation, and cage insertion. These strategies were validated through cadaveric simulations and clinical implementation. In FE fr-TLIF utilizing bullet-shaped (straight) cages, one-tip and two-tip cage gliders effectively protected the traversing nerve root by facilitating medial cage entry, thereby minimizing irritation of the exiting nerve root. Conversely, in FE fr-TLIF with banana-shaped cages, the lateral tilt of the cage holder during implantation required the use of a two-tip cage glider to protect the traversing and exiting nerve roots, thereby mitigating the potential risk of nerve irritation. In FE fs-TLIF, a one-tip cage glider is preferred for safeguarding the exiting nerve root, while the traversing root is inherently protected by the medial wall of the facet joint. The use of a two-tip cage glider in FE fs-TLIF can cause injury to the nerve root during glider insertion. In addition to the selection of cage gliders, improper cage insertion steps can also contribute to postoperative neurapraxia. The appropriate selection of cage gliders with corresponding insertion techniques is critical for nerve root protection in endoscopic TLIF. Tailoring these choices to the specific approach (FE fs-TLIF or FE fr-TLIF) and cage type (banana or bullet) enhances surgical safety and clinical outcomes.

Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

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.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Suhuang Zhike Capsules are widely used in clinical practice for the treatment of respiratory diseases and have been included in Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance and National Essential Medicines List. However, problems remain, such as unclear definitions of treatment courses and unidentified contraindications for certain populations. Therefore, this consensus was developed collaboratively by clinical experts in traditional Chinese medicine(TCM) related to pulmonary diseases, respiratory, and critical care medicine, as well as methodology and pharmacy experts, adhering strictly to the consensus development procedures established by the China Association of Chinese Medicine for clinical application of Chinese patent medicines, with the aim to guide the correct clinical use of Suhuang Zhike Capsules for the treatment of cough variant asthma, post-infectious cough, and other respiratory diseases. This consensus employed questionnaire surveys and expert interviews to identify clinical concerns based on the PICOS principle and conduct evidence evaluation and GRADE grading. Utilizing nominal group techniques and GRADE networking methods, it resulted in 17 recommendations and consensus suggestions. The consensus further clarifies the indications, TCM syndromes, usage, and clinical safety of Suhuang Zhike Capsules in the treatment of cough variant asthma and post-infectious cough, aiming to promote standardized medication use and facilitate the rational clinical application of Suhuang Zhike Capsules.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Consensus ; Capsules ; Respiratory Tract Diseases/drug therapy* ; Medicine, Chinese Traditional