BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

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

OBJECTIVES: To summarize the clinical and genetic characteristics of epilepsy with intellectual disability caused by SETD1B gene variants in children. METHODS: A retrospective analysis was conducted on the clinical data of three children with SETD1B gene variants diagnosed and treated at the Department of Pediatric Neurology of Xiangya Hospital of Central South University. Relevant literature was reviewed to summarize the clinical characteristics of this condition. RESULTS: All three children presented with symptoms during infancy or early childhood, including mild intellectual disability and myoclonic seizures, with two cases exhibiting eyelid myoclonia. After treatment with three or more antiepileptic drugs, two cases achieved seizure control or partial control, while one case remained refractory. Each of the three children was found to have a heterozygous variant in the SETD1B gene (one deletion, one frameshift, and one missense variant). To date, 54 cases with SETD1B gene variants have been reported, involving a total of 56 variants, predominantly missense variants (64%, 36/56). The main clinical manifestations included varying degrees of developmental delay (96%, 52/54) and seizures (81%, 44/54). Among the 44 patients with seizures, myoclonic (20%, 9/44) and absence seizures (34%, 15/44) were common, with eyelid myoclonia reported in six cases. Approximately one-fifth of these patients had poorly controlled seizures. CONCLUSIONS The primary phenotypes associated with SETD1B gene variants are intellectual disability and seizures, and seizures exhibit distinct characteristics. Eyelid myoclonia is not uncommon.
Humans ; Intellectual Disability/complications* ; Epilepsy/complications* ; Male ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Child, Preschool ; Child ; Retrospective Studies

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

OBJECTIVES: To explore the correlation of hypertension with postoperative cognitive dysfunction and its possible mechanism. METHODS: Twelve-week-old spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were both randomized into control group and surgical group (n=8). In the latter group, the rats received carotid artery exposure surgery under sevoflurane anesthesia to establish models of postoperative learning and memory impairment. Postoperative cognitive function changes of the rats were evaluated using behavioral tests. The hippocampus of the rats were collected for determining ATP level and mitochondrial membrane potential (MMP) and for detecting expressions of UCP2 and astrocyte markers (GFAP and NOX4) using Western blotting and immunofluorescence staining. Serum levels of ROS, IL-6, IL-1β and TNF‑α were detected using ELISA. Nissl staining was used to examine hippocampal neuronal loss in the CA1 region. RESULTS: The SHRs exhibited exacerbated learning and memory deficits following the surgery as shown by significantly reduced performance in novel object recognition tests and context-related and tone-related fear conditioning experiments. Compared with WKY rats, the SHRs had significantly decreased mitochondrial UCP2 expression and MMP in the hippocampus, increased hippocampal ATP level, and markedly increased serum levels of ROS and inflammatory factors, showing also increased activation of hippocampal astrocytes and microglia and reduced number of neurons positive for Nissl staining. CONCLUSIONS Hypertension can exacerbate major postoperative learning and memory impairment in rats possibly as a result of UCP2-mediated mitochondrial dysfunction and oxidative stress damage, which further leads to astrocyte overactivation and neuronal damage.
Animals ; Rats, Inbred SHR ; Rats ; Uncoupling Protein 2 ; Rats, Inbred WKY ; Hypertension/physiopathology* ; Hippocampus/metabolism* ; Mitochondria/metabolism* ; Down-Regulation ; Male ; Memory Disorders/etiology* ; Mitochondrial Proteins/metabolism*

In recent years, with the development of organ preservation, surgical techniques, perioperative management and immunosuppression regimens, the success rate of liver transplantation and survival rate of the recipients have been significantly enhanced. Liver transplantation has become the optimal treatment for patients with end-stage liver disease. However, biliary complications still commonly occur after liver transplantation, especially biliary anastomotic stricture. Severe biliary anastomotic stricture will not only increase the cost of treatment, but also lead to graft loss and even affect the survival rate of recipients. Therefore, timely diagnosis and treatment of biliary anastomotic stricture play a significant role in improving the survival rate of liver transplant recipients. In this article, the risk factors, clinical symptoms, diagnosis and treatment of biliary anastomotic stricture after liver transplantation were reviewed, aiming to provide novel ideas for the research, diagnosis and treatment of biliary anastomotic stricture after liver transplantation, and further enhance clinical efficacy of liver transplantation and the quality of life of recipients.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).