The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.

OBJECTIVES: Verrucous epidermal nevus (VEN), seborrheic keratosis (SK), verruca plana (VP), verruca vulgaris (VV), and nevus sebaceous (NS) are common verrucous proliferative skin diseases with similar clinical appearances, often posing diagnostic challenges. Dermoscopy and reflectance confocal microscopy (RCM) can aid in their differentiation, yet their specific features under these tools have not been systematically described. This study aims to summarize and analyze the dermoscopic and RCM features of VEN, SK, VP, VV, and NS. METHODS: A total of 121 patients with histopathologically confirmed verrucous proliferative skin diseases were enrolled. Dermoscopy and RCM imaging was used to observe and analyze the microscopic features of these conditions. RESULTS: Under dermoscopy, the 5 diseases displayed distinct characteristics: VEN typically showed gyriform structures; SK was characterized by gyriform structures, comedo-like openings, and milia-like cysts; VP and VV featured dotted vessels and frogspawn-like structures; NS presented as brownish-yellow globules. RCM revealed shared features such as hyperkeratosis and acanthosis across all 5 diseases. Specific features included gyriform structures and elongated rete ridges in VEN; pseudocysts and gyriform structures in SK; evenly distributed ring-like structures in VP; vacuolated cells and papillomatous proliferation in VV; and frogspawn-like structures in NS. CONCLUSIONS These 5 verrucous proliferative skin conditions exhibit distinguishable features under both dermoscopy and RCM. The combination of these 2 noninvasive imaging modalities holds significant clinical value for the differential diagnosis of verrucous proliferative skin diseases.
Humans ; Dermoscopy/methods* ; Diagnosis, Differential ; Microscopy, Confocal/methods* ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Keratosis, Seborrheic/pathology* ; Young Adult ; Warts/diagnosis* ; Child ; Aged ; Skin Diseases/pathology* ; Nevus, Sebaceous of Jadassohn/diagnosis* ; Skin Neoplasms/diagnosis* ; Child, Preschool

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

The neonatal Fc receptor(FcRn)prolongs the half-life of immunoglobulin G(IgG)and promotes its recycling by binding to and making it an important receptor for maintaining serum IgG homeostasis.However,the abnormal accumulation of pathogenic IgG is closely related to the occurrence of various neuroimmune diseases.FcRn antagonists can significantly reduce the level of pathogenic IgG by blocking the binding of FcRn to IgG,thereby effectively alleviating the clinical symptoms of related diseases.As an emerging targeted therapeutic drug,FcRn antagonists have shown their potential in treating IgG-mediated neuroimmune diseases.This article summarizes the mechanism of action,types and clinical research progress of FcRn antagonists with the aim of providing new ideas for the precise treatment of IgG-mediated neuroimmune diseases.Future research should focus on the long-term safety of drugs,expansion of indications and individualized treatment strategies to further enhance their clinical application value.

Objective:To analyze the latent prevalence of hepatitis B and type 2 diabetes and their correlation through an observational study.Methods:This study used a case-control design. The cases with diabetes were recruited through the diabetes management system and village doctors, while the controls without diabetes were screened from volunteers recruited by village health clinics. Capillary blood samples were collected from the study participants for the measurement of real-time blood glucose level, and venous blood samples were taken from them for the detections of HBV serological markers. Firth logistic regression model was used to fit the relationship between HBsAg positive status and diabetes status.Results:The study included 1 218 diabetes patients, 62 patients with impaired fasting glucose and 491 cases without diabetes. In the cases without diagnosis of diabetes, 11.15% had impaired fasting blood glucose and 4.43% had diabetes. Among those who reported no or unknown diagnosis of hepatitis B, 1.73% were positive for HBsAg, while 18.80% were positive for both HBV core antibody and surface antibody, indicating latent infection of hepatitis B virus. In the non-diabetes group, 0.81% reported hepatitis B history, and in the diabetes group, 2.76% reported hepatitis B history. After adjustment, the HBsAg positive rate was higher in the diabetes group ( OR=2.90, 95% CI: 1.21-6.91). Conclusions:Both diabetes and hepatitis B exhibited a high degree of latent prevalence. The HBsAg positive rate was significantly higher in those with diabetes than in those without diabetes, indicating a potential correlation. These findings highlighted the importance of strengthened screening and management of comorbidities.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

Objective:To analyze the latent prevalence of hepatitis B and type 2 diabetes and their correlation through an observational study.Methods:This study used a case-control design. The cases with diabetes were recruited through the diabetes management system and village doctors, while the controls without diabetes were screened from volunteers recruited by village health clinics. Capillary blood samples were collected from the study participants for the measurement of real-time blood glucose level, and venous blood samples were taken from them for the detections of HBV serological markers. Firth logistic regression model was used to fit the relationship between HBsAg positive status and diabetes status.Results:The study included 1 218 diabetes patients, 62 patients with impaired fasting glucose and 491 cases without diabetes. In the cases without diagnosis of diabetes, 11.15% had impaired fasting blood glucose and 4.43% had diabetes. Among those who reported no or unknown diagnosis of hepatitis B, 1.73% were positive for HBsAg, while 18.80% were positive for both HBV core antibody and surface antibody, indicating latent infection of hepatitis B virus. In the non-diabetes group, 0.81% reported hepatitis B history, and in the diabetes group, 2.76% reported hepatitis B history. After adjustment, the HBsAg positive rate was higher in the diabetes group ( OR=2.90, 95% CI: 1.21-6.91). Conclusions:Both diabetes and hepatitis B exhibited a high degree of latent prevalence. The HBsAg positive rate was significantly higher in those with diabetes than in those without diabetes, indicating a potential correlation. These findings highlighted the importance of strengthened screening and management of comorbidities.