ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

OBJECTIVE: To explore clinical efficacy of autologous platelet-rich plasma(PRP) in treating Rockwood type Ⅲ acromioclavicular dislocation. METHODS: From January 2019 to July 2021, 32 patients with Rockwood type Ⅲ acromioclavicular dislocation were treated with minimally invasive adjustable titanium plate internal fixation, and were divided into PRP group and control group according to whether PRP treatment was performed, with 16 patients in each group. In PRP group, there were 10 males and 6 females, aged from 28 to 47 years old with an average of (36.75±7.14) years old;the time from injury to surgery ranged from 1 to 31 h with an average of (26.13±3.98) h;5 patients on the left side and 11 patients on the right side;PRP was injected once during operation and the 4th and 8th weeks after operation respectively. In control group, there were 8 males and 8 females, aged from 30 to 52 years old with an average of (38.50±5.48) years old; the time from injury to surgery ranged from 1 to 29 h with an average of (25.48±3.11) h;7 patients on the left side and 9 patients on the right side; minimally invasive surgical treatment was performed. Visual analogue scale(VAS) was used to evaluate pain and Constant-Murley score for shoulder joint function was used to evaluate the recovery of shoulder joint movement function before operation and 1, 3, 6, and 12 months after operation respectively. RESULTS: All patients were followed up for 12 to 28 months with an average of (18.3±5.2) months. All incisions patients healed well without adverse events such as infection. Postoperative VAS of PRP group at 1, 3, and 6 months were (5.5±1.2), (3.7±1.6), and (2.4±1.2), respectively, while were lower than those of control group (6.6±1.4), (4.9±1.1), and (3.7±1.3), respectively;and had statistical differences between two groups (P<0.05). There was no statistically significant difference in VAS between two groups before operation and 12 months after operation (P>0.05). Postoperative Constant-Murley scores of PRP group at 1, 3, and 6 months were (64.09±11.61), (73.19±12.89), and (82.61±14.81) points, respectively, which were higher than those of control group were (52.32±17.42), (61.65±14.43), and (72.52±11.04) respectively;and the differences were statistically significant (P<0.05). There was no statistically significant difference in Constant-Murley scores at 12 months after operation between two groups (P>0.05). In PRP group, there was no statistically significant difference at 6 months and 12 months after operation (P>0.05), while there were statistically significant differences at the other time points (1 month after operation compared with before operation, 3 months after operation compared with 6 months after operation, and 3 months after operation compared with 1 month after operation) (P<0.05). In control group, there was no statistically significant difference when comparing 1 month and 3 months after operation (P>0.05), while at the other time points (1 month after operation with before operation, 3 months after operation with 6 months after operation, and 6 months after operation with 12 months after operation), the differences were all statistically significant (P<0.05). CONCLUSION Adjustable titanium plate fixation combined with postoperative injection of PRP for the treatment of Rockwood type III acromioclavicular joint dislocation has effect of promoting the recovery of shoulder joint function and reducing pain.
Humans ; Male ; Female ; Adult ; Middle Aged ; Platelet-Rich Plasma ; Acromioclavicular Joint/surgery* ; Bone Plates ; Titanium ; Joint Dislocations/therapy* ; Fracture Fixation, Internal/methods*

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

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

Adenoid cystic carcinoma is a malignant tumor of the head and neck, this article reports a case of a large adenoid cystic carcinoma of the skull base, with the lesion involving the sphenoid sinus, sphenoid bone wings, pterygopalatine fossa, nfratemporal fossa, hard palate, and other structures. The treatment plan consisted of surgical excision, primary reconstrction of the surgical defect,and postoperative radiotherapy, resulting in a favorable prognosis for the patient.
Humans ; Carcinoma, Adenoid Cystic/surgery* ; Maxillary Sinus/surgery* ; Maxillary Sinus Neoplasms/surgery* ; Palate, Hard/surgery* ; Skull Base Neoplasms/surgery* ; Surgical Flaps

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*