Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

The traditional Chinese medicine(TCM) industry is a crucial part of China's pharmaceutical sector and plays a strategic role in ensuring public health and promoting economic and social development. In response to the practical demand for high-quality development of the TCM industry, this paper focused on the bottlenecks encountered during the digital and intelligent transformation of TCM production systems. Specifically, it explored technical strategies and methodologies for constructing the best TCM production mode. An innovative artificial intelligence(AI)-centered technical architecture for TCM production was proposed, focusing on key aspects of production management including process modeling, state evaluation, and decision optimization. Furthermore, a series of critical technologies were developed to realize the best TCM production mode. Finally, a novel AI-driven TCM production mode characterized by a closed-loop system of "measurement-modeling-decision-execution" was presented through engineering case studies. This study is expected to provide a technological pathway for developing new quality productive forces within the TCM industry.
Artificial Intelligence ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional/methods* ; Humans

OBJECTIVE: To investigate the clinical effect and adverse reactions of dapoxetine hydrochloride versus paroxetine in the treatment of primary premature ejaculation by cross-comparison. METHODS: Based on the clinic-visit time, we equally randomized 148 patients with primary premature ejaculation into groups A and B for a cross-comparison test, the former treated with paroxetine at 20 mg once nightly and the latter with dapoxetine hydrochloride at 30 mg on demand, both for 6 successive weeks, during which we observed the therapeutic effects and adverse reactions. Following 4 weeks of drug discontinuance, we administered dapoxetine hydrochloride at 30 mg on demand for group A and paroxetine at 20 mg once nightly for group B, both for another 6 successive weeks, followed by observation and comparison of the therapeutic effects and adverse reactions. RESULTS: There were no statistically significant differences in the initial characteristics of the two groups of patients (P > 0.05). Compared with the baseline, the mean intra-vaginal ejaculation latency time (IELT) was dramatically improved after treatment in both groups A (4.43 min) and B (7.12 min), increased by 3.99% and 6.72%, respectively (P<0.001). The patients treated with paroxetine showed significantly longer IELT than those taking dapoxetine hydrochloride in both groups (P<0.001). Findings of the Premature Ejaculation Profile (PEP) and spouses' conditions indicated significant improvement after treatment in the average scores of the four indicators of PEP, that is, perceived control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse and ejaculation-related interpersonal difficulty, as well as in the overall experience and partner's satisfaction and orgasm frequency. Adverse reactions to medication were found in 20.8% of the cases in group A and 9.7% in group B, but none was serious. Preference survey following drug withdrawal revealed a preference for paroxetine (61.9%) over dapoxetine (26.8%), and that only a few of the patients thought of the two drugs as comparable or both ineffective. CONCLUSION In term of overall effectiveness, paroxetine was superior to dapoxetine in the treatment of primary premature ejaculation. And the patients obviously preferred the former to the latter, which might be partly attributed to the higher price of dapoxetine.
Humans ; Benzylamines/therapeutic use* ; Male ; Premature Ejaculation/drug therapy* ; Naphthalenes/therapeutic use* ; Paroxetine/therapeutic use* ; Adult ; Treatment Outcome ; Middle Aged ; Young Adult ; Selective Serotonin Reuptake Inhibitors/therapeutic use*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Traditional Chinese medicine (TCM) has become an important treasure trove of natural resources for the development of new medicines due to their diverse compositions, significant therapeutic effects, and few side effects. The screening of active ingredients in TCM represents a crucial step in elucidating the material basis and mechanism of action of TCM. At present, efficient and precise molecular recognition techniques based on intermolecular interactions have been extensively employed for the identification of active ingredients in TCM. This paper presents a review of the fundamental principles underlying solution-phase/affinity ligand fishing, solid-phase/affinity ligand fishing, molecular imprinting and molecular docking techniques, with a particular focus on their applications in the screening of active ingredients in TCM. Furthermore, the paper compares the advantages and disadvantages of the various techniques and identifies the limitations of existing techniques. In conclusion, the paper identifies the prospective trajectory of molecular recognition techniques in the domain of TCM research. This paper not only provides theoretical references for the development of new methods of active ingredient screening but also helps to promote the modernization and internationalization of TCM.

AIM: To investigate the relationship between objective ocular torsion and near stereopsis in patients with primary superior oblique overaction(PSOOA).METHODS: Retrospective study. A total of 59 strabismus patients with PSOOA who underwent strabismus surgery at Renmin Hospital of Wuhan University between January 2019 and November 2023 were collected. Based on the collected fundus photographs and the position of the fovea relative to the horizontal line through the optic disc, the eyes were categorized as incyclotorsion, excyclotorsion, or no cyclotorsion. Additionally, the fovea-disc angle(FDA)and the relationship between objective ocular torsion status, FDA, and near stereopsis function in the patients were further measured and analyzed.RESULTS: Totally 59 patients(92 eyes)showed superior oblique overaction. There were no cases of excyclotorsion, 32 cases with no cyclotorsion, and 27 cases with incyclotorsion. The total binocular FDA was significantly smaller in the no-cyclotorsion group compared with the incyclotorsion group(2.83°±2.89° vs 16.12°±5.74°, P<0.001). The preservation rates of near stereopsis were 66% and 15% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P<0.001), and the preservation rates of fine near stereopsis were 38% and 11% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P=0.02). Among all patients, near stereopsis was correlated with total binocular FDA(r=-0.526, P<0.001), with the strongest correlation observed with the FDA of the incyclotorsion(r=-0.546, P<0.001). In the incyclotorsion group, there was no correlation between near stereopsis and total binocular FDA(r=-0.366, P=0.060), with a negative correlation between near stereopsis and the FDA of both the incyclotorsion and the overaction(r=-0.424, P=0.028; r=-0.485, P=0.010). In the no-cyclotorsion group, near stereopsis was not correlated with total binocular FDA, incyclotorsion FDA, or overaction FDA.CONCLUSION:PSOOA patients with incyclotorsion have a lower preservation rate of near stereopsis than those without cyclotorsion. Near stereopsis function of patients with PSOOA is negatively correlated with total binocular FDA, especially the greater the FDA of the incyclotorsion and overaction, the worse the near-stereoscopic function.

ObjectiveTo compare the differences in intestinal absorption of nanophase（NP） formed by single decoction and combined decoction of Ginseng Radix et Rhizoma（GRR） and Zingiberis Rhizoma Recens（ZRR） in rats， and to investigate the effects of new NP formed by the combined decoction on the absorption of main components in GRR and ZRR. MethodDifferential centrifugation and dialysis techniques were used to enrich NP in the single and combined decoctions of GRR and ZRR， respectively. The microstructure， particle size， Zeta potential and concentration of the NP were analyzed by transmission electron microscope， particle size analyzer and nanoparticle tracking analyzer. Based on everted gut sac model， the index components in the intestinal absorption solution of NP from the single and combined decoctions were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）. The per unit area actual value of cumulative intestinal absorption（Q_actual）， absorption rate constant（K_a） and apparent permeability coefficient（P_app） were used as the evaluating indexes to investigate the absorption characteristics of the aforementioned NP in the duodenum， jejunum， ileum and colon. ResultIrregularly spherical NP was present in the single and combined decoctions， and the contents of components in NP of the combined decoction were mostly lower than those in the single decoction. In these NP， ten components could be absorbed into the intestinal sac， with the main absorption site being the small intestine， and the P_app was greater than 1×10^-5 cm·min^-1. Compared with NP in the single decoction， the Q_actual and K_a of ginsenoside Rb₁， ginsenoside Rf， 4-gingerol and 6-shogaol were significantly increased in NP of the combined decoction， while ginsenoside Re and 6-gingerol were significantly decreased（P<0.01）. Except for ginsenoside Re and ginsenoside Rd， the P_app of the remaining constituents was significantly increased in NP of the combined decoction（P<0.01）. In addition， the maximum intestinal segment site of Q_actual was shifted forward for ginsenoside Rb₁， ginsenoside Rd and ginsenoside Ro， while shifted backward for ginsenoside Rg₁， ginsenoside Re and 8-gingerol. The maximal intestinal segment sites of K_a and P_app of ginsenoside Rb₁， ginsenoside Rg₁， ginsenoside Rd and ginsenoside Ro shifted forward， while ginsenoside Re and 4-gingerol were shifted backward. ConclusionThe combined decoction of GRR and ZRR is helpful to promote the absorption of the effective components of the two， and changes the absorption behavior of the effective components in some intestinal segments. This study provides a reference for the subsequent research on the compatibility mechanism of the two medicines.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.