Sichuan Academy of Traditional Chinese Medicine

Mild cognitive impairment (MCI) is an intermediate condition between normal aging and dementia. Drug intervention is an important way to prevent MCI from developing into dementia. GuiLingJi (GLJ) is a traditional Chinese medicine formulae and it has the effect of enhancing memory. In view of the absence of special effective drugs for MCI, GLJ warrants investigation as a potential therapeutic agent. This study uses a rat model of MCI, induced by D-galactose injections and a semi-high-fat diet, to explore the therapeutic efficacy of GLJ in MCI and elucidate the potential underlying pharmacological mechanisms by behavioral experiments and biochemical indexes, combined with serum and hippocampal metabolomics. GLJ treatment mitigated D-galactose combined with semi-high-fat diet induced impairments, including abnormal blood lipids, oxidative stress, inflammation, cholinergic dysfunction, apoptosis, and reduced brain-derived neurotrophic factors, along with hippocampal damage. LC-MS metabolomics indicated that these effects involved unsaturated fatty acid and amino acid metabolism. By normalizing linoleic acid and α-linolenic acid levels and activating GPR120, GLJ inhibited the NF-κB/TNF-α pathway. These findings demonstrate that GLJ alleviates MCI symptoms, at least in part, by modulating fatty acid metabolism and suppressing neuroinflammation via the GPR120/NF-κB pathway. This study supports GLJ as a promising proprietary TCM formulation for MCI treatment.

Objective This study investigates the effects of quadriceps isometric contraction training (QICT) on the symptoms, postural control, and movement ability of elderly women with knee osteoarthritis (KOA). Methods Forty-two older women with KOA were randomly divided into an experimental group (n = 21) and a control group (n = 21). All participants received the same health education for 16 weeks. The experimental group underwent QICT five times per week (contraction and relaxation for 5 s each, 30 repetitions per set, 10 sets, with a 30-s rest between sets). Assessments of KOA symptoms, postural control, and movement ability were performed at baseline and after the 16-week intervention. Results 1) At the 16th week compared to baseline: The experimental group showed a 27.1% reduction in pain, a 13.8% reduction in stiffness, and a 15.7% reduction in functional impairment scores. The body sway index on a firm surface with eyes closed decreased by 14.3%. The knee extension peak torque at 180°/s increased by 31.6%, and the angle difference in the knee flexion proprioception test (30°) decreased by 24.5%. The 6MWT distance increased by 11.9%, and the time for the TUG decreased by 12.9% (P < 0.05). 2) At the 16th week, group comparisons showed that the experimental group had significantly lower pain scores, body sway index on a firm surface with eyes closed, and angle difference in the knee flexion proprioception test (30°) (P < 0.05), and significantly higher knee extension peak torque at 180°/s and 6MWT distance compared to the control group (P < 0.05). Conclusion Quadriceps isometric contraction training can significantly improve pain, stiffness, functional impairment, static balance ability, knee extension strength, and 6-min walk distance in older women with KOA, as well as enhance knee flexion proprioception. These results indicate that 16-week QICT is a safe and economical non-pharmacological intervention that can effectively improve the clinical symptoms and functional status of older women with KOA, providing a feasible treatment option for community and outpatient rehabilitation. Notably, the 31.6% increase in knee extensor peak torque (180°/s) exceeds the MCID (20%) for older adults with KOA, reflecting significant clinical benefits.

The increasing adoption of Bayesian methods in clinical trials necessitates robust sensitivity analyses to validate their assumptions, particularly the prior distribution. However, the design, implementation, and interpretation of these analyses are not well characterized. The purpose of this study is to examine the design, conduct and interpret characteristics of sensitivity analyses in Bayesian clinical trials. We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify Bayesian clinical trials published from database inception through December 2024. Two reviewers independently performed study selection and full-text screening. Data regarding sensitivity analyses were extracted in duplicate using standardized, pilot-tested data collection forms. Multivariable logistic regression was employed to examine the association between five variables with more likely reporting sensitivity analyses for prior information. Among the 171 included trials, 103 had an accessible study protocol or statistical analysis plan (SAP), of which 36 (35.0%) trials with available protocols or SAPs failed to pre-specify any sensitivity analyses. Sensitivity analyses were reported in 91 (53.2%) trials, with four reporting at least one sensitivity analysis that contradicted the primary analyses. 38 (22.2%) interpreted the results of sensitivity analysis in the discussion section. Post-hoc sensitivity analyses were explicitly described in 16 trials, only five provided a rationale for these analyses. 24 (23.3%) reported sensitivity analyses not pre-specified in the protocol, 47 (45.6%) omitted pre-specified sensitivity analyses from their results, none of these provided a justification. Of the 122 trials that reported using prior distributions, 33 (27.0%) conducted sensitivity analyses on the priors. Among the 58 trials that used informative priors, 22 (37.9%) performed sensitivity analyses; correspondingly, 11 out of 64 trials (17.2%) with non-informative priors did so. Multivariable analysis indicated that both the use of informative priors and the availability of a protocol or SAP were significantly associated with an increased likelihood of conducting sensitivity analyses for priors. This study reveals gaps in the design, conduct, and reporting of sensitivity analyses for Bayesian trials, especially concerning priors. There is a pressing need to improve and standardize the use of sensitivity analyses in Bayesian clinical trials.

<title>Abstract</title> Background Psoriasis is a chronic inflammatory skin disease in which neuroimmune interactions are increasingly recognized but remain insufficiently defined. Objective To elucidate neuroimmune mechanisms implicated in psoriasis pathogenesis and identify candidate biomarkers and therapeutic targets. Methods Publicly available psoriasis transcriptomic datasets from the Gene Expression Omnibus (GEO) were analyzed. Neuroimmune-related differentially expressed genes (NRDEGs) were screened, followed by functional enrichment analyses. Supervised diagnostic models (logistic regression, support vector machine, least absolute shrinkage and selection operator [LASSO], and random forest) were constructed. Immune cell infiltration was estimated and correlated with NRDEG expression. Protein–protein interaction networks were built, and key genes were queried against drug/active-ingredient resources. Results Sixty-eight NRDEGs were identified in psoriatic tissue. These genes were significantly enriched in immune and inflammatory pathways, including NF-κB and IL-17 signaling. Diagnostic models based on NRDEGs achieved high predictive performance across algorithms. Five key genes—ENO2, SELL, GREM2, IL1B, and LCN2—were differentially expressed between patients and controls and showed strong associations with inferred immune cell infiltration in lesions. Network analyses prioritized hub genes and mapped them to potential drug active ingredients, suggesting avenues for pharmacologic modulation of neuroimmune pathways. Conclusions Integrated bioinformatics highlights a prominent neuroimmune signature in psoriasis, nominating NRDEGs—particularly ENO2, SELL, GREM2, IL1B, and LCN2—as candidate biomarkers for diagnosis and potential therapeutic intervention. Further experimental and clinical studies are warranted to define causal roles, clarify dynamics during disease progression, and evaluate responses to targeted therapies.

Rationale:Acute ST-segment elevation myocardial infarction (STEMI) typically results from abrupt coronary occlusion, most often caused by rupture of an atherosclerotic plaque. Membranous nephropathy (MN) typically presents with nephrotic syndrome, characterized by proteinuria. STEMI as the initial manifestation of MN is exceptionally rare. This case underscores the importance of considering systemic hypercoagulable states when evaluating atypical myocardial infarction in young adults.Patient concerns:A 35-year-old man with no prior history of renal impairment, cardiovascular disease, or risk factors such as hypertension or diabetes, presented with acute chest pain and was diagnosed with STEMI. Subsequent evaluation revealed MN with nephrotic-range proteinuria. 110 days after discharge, he experienced a recurrent STEMI.Diagnoses:The 12-lead electrocardiogram demonstrated ST-segment elevation in leads II, III, and augmented vector foot, consistent with inferior-wall myocardial infarction. Emergency coronary angiography showed acute occlusion of the RCA. In the setting of nephrotic-range proteinuria and hypoalbuminemia, the infarct mechanism was most consistent with coronary thrombosis secondary to a nephrotic syndrome-associated hypercoagulable state.Interventions:During coronary angiography, aspiration thrombectomy was performed, and systemic anticoagulation and guideline-directed secondary prevention were initiated.Outcomes:Coronary flow was restored to thrombolysis in myocardial infarction grade 3, and the patient became hemodynamically stable. He was transferred to the nephrology service for targeted management of MN. One hundred ten days later, he represented with ST-segment elevation. Coronary angiography demonstrated thrombolysis in myocardial infarction grade 3 flow with only mild mid-to-distal RCA stenosis, raising suspicion of a transient coronary embolic event.Lessons:Although rare, STEMI may be the initial manifestation of MN. In young patients with myocardial infarction who exhibit clinical features of nephrotic syndrome, a hypercoagulable state should be considered. Early recognition, timely initiation of antithrombotic therapy, and multidisciplinary follow-up are essential to reduce the risk of recurrence.

Skin organoids are 3D multicellular systems formed through self-organisation invitro, driving research toward functional-related phenotypic replication from structural mimicry to functionally relevant phenotypic replication. However, this field still faces challenges in improving vascularisation, neurogenesis, and immune integration. This review provides a comprehensive overview of the latest advancements in this field. First, it organises the construction of epidermis-dermis-basement membrane units, vascular/neural/immune modules and accessory organs such as hair follicles, sweat glands, and sebaceous glands into 'component-source-function readout' to highlight key points and clinically relevant endpoints (barrier function, hair growth, sweat gland secretion, and sensation). Subsequently, it outlines the key culture and assembly elements (extracellular matrix composition and mechanics, air-liquid interface, perfusion/organ-on-a-chip and bioprinting) that influence the maturation trajectory of tissues. Then, it compares the differences in plasticity, maturity and accessibility between pluripotent stem cells, adult/primary cells and patient-derived cells. At the application level, it concludes that skin organoids have been used to model inflammation, genetic disorders, infections, and tumours, enabling simultaneous efficacy and safety readouts in drug discovery and toxicology assessment. Translation challenges include vascularisation and perfusion, neurogenesis and sensory function, immune integration, batch consistency and GMP quality, scalability and cost. We propose a staged validation pathway integrating engineering, biology and regulatory considerations, and envision optimisations combining multi-omics, chemoproteomics and artificial intelligence to accelerate the transition from research-grade prototypes to clinical applications.