OBJECTIVE To investigate the clinical effectiveness of triptorelin combined with Biejiajian pill in the treatment of adenomyosis （AM）. METHODS Totally 186 patients with AM admitted to Nanyang First People’s Hospital from January 2022 to October 2024 were selected as subjects and randomized into control group （n＝93） and observation group （n＝93） using the random number table method. Patients in the control group received subcutaneous injections of triptorelin acetate around the umbilicus. In addition to the treatment of control group， patients in the observation group orally administered Biejiajian pill. Both groups underwent treatment for 12 weeks and were followed up for 6 months post-treatment. The clinical efficacy， recurrence and the occurrence of adverse drug reactions were compared between the two groups. Traditional Chinese medicine （TCM） symptoms， endometrial receptivity indicators （endometrial thickness， uterine volume， endometrial resistance index and vascular index）， laboratory indexes （serum luteinizing hormone， follicle stimulating hormone， estradiol， carbohydrate antigen 125， insulin-like growth factor-1， and matrix metalloproteinase 9） were compared between the two groups before and after treatment. RESULTS A total of 164 patients completed the treatment and follow-up， among whom 80 cases were in control group and 84 cases in the observation group. The overall effective rate in the observation group was significantly higher than that in the control group， while the incidence of low estrogen levels and recurrence rate were significantly lower in the observation group compared to the control group （P＜0.05）. There were no statistically significant differences in the incidence of nausea or abnormal liver and kidney function between the two groups （P＞0.05）. After treatment， the pain Visual Analogue Scale scores， Pictorial Blood Loss Assessment Chart， TCM symptoms scores， endometrial thickness， uterine volume， endometrial resistance index， and laboratory indicators in both groups were significantly lower than those before treatment within the same group （P＜0.05）. Moreover， these values were significantly lower in the observation group compared to the control group （except for follicle stimulating hormone） （P＜0.05）. The endometrial vascular index of the two groups was significantly higher than that in the same group before treatment， and the observation group was significantly higher than the control group （P＜0.05）. CONCLUSIONS Triptorelin combined with Biejiajian pill has a definite therapeutic effect on AM， which can effectively improve the degree of dysmenorrhea and menstrual flow， improve endometrial receptivity， lower the recurrence rate in patients， and demonstrate good safety.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

OBJECTIVE To observe the clinical efficacy， safety and recurrence of Kuntai capsules combined with Estradiol tablets/Estradiol dydrogesterone tablets in the treatment of diminished ovarian reserve （DOR） as well as their effects on ovarian reserve function， sex hormones， and lymphocyte subsets. METHODS A retrospective analysis was conducted on the clinical data of 165 DOR patients in Nanyang First People’s Hospital. Among them， 80 patients who received Estradiol tablets/Estradiol dydrogesterone tablets （take one tablet per day according to the medication sequence on the instruction） were included in the control group， while 85 patients who additionally took Kuntai capsules （2.0 g per dose， three times daily） were included in the observation group. The treatment duration for both groups was three months. Clinical efficacy， the incidence of adverse drug reaction （ADR）， recurrence rate， and changes in Traditional Chinese Medicine （TCM） syndrome scores， ovarian reserve function indicators [anti-Müllerian hormone （AMH）， inhibin B （INHB）， antral follicle count （AFC）， endometrial thickness， and ovarian volume]， sex hormones [follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）]， and T lymphocyte subsets （CD3 +， CD4 +， CD8 +， and CD4 +/CD8 +） were compared before and after treatment. RESULTS The cure and significant improvement rate in the observation group was significantly higher than in the control group （82.35% vs. 65.00%， P＜0.05）. Compared to baseline levels， both groups showed significant reductions in TCM syndrome scores， FSH， LH， CD3+ and CD8+ levels after treatment， while AMH， INHB， E2， CD4 +， CD4 +/CD8 +， AFC， endometrial thickness， and ovarian volume significantly increased （P＜0.05）. The degree of improvement in these indicators was significantly greater in the observation group than in the control group （P＜0.05）. There was no significant difference in the total incidence of ADR between the two groups（P＞ 0.05）. However， the recurrence rate within six months post-treatment was significantly lower in the observation group compared to the control group （5.88% vs. 21.25%， P＜0.05）. CONCLUSIONS Kuntai capsules combined with Estradiol tablets/ Estradiol dydrogesterone tablets have a significant therapeutic effect on DOR， which can improve ovarian reserve function of the patient， regulate sex hormone levels and T lymphocyte subsets， and reduce recurrence rates， with a high safety profile.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*

Objective To investigate the protective effects of secretomes released by three-dimensional cultured mesenchymal stem cells(MSCs)on neurons subjected to seawater immersion(SW)and stretch injury(SI),and to provide new insights into neuronal repair following SW combined with traumatic brain injury(TBI).Methods MSCs were cultured using the hanging drop method,and the conditioned medium(CM)containing MSCs secretomes was collected.A cellular model combining SW with SI was established using mouse hippocampal neuronal cells(HT22 cells).HT22 cells were randomly assigned to five groups:control,SI,SI+SW,SI+CM,and SI+SW+CM groups.Cell viability was assessed using the CCK-8 assay,apoptosis rate was measured by flow cytometry,cell migration ability was evaluated by scratch assay,and the expression levels of apoptosis-related proteins Bcl-2 and Bcl-2-associated protein(Bax),and ferroptosis-related proteins long-chain acyl-CoA synthetase 4(ACSL4)and cyclooxygenase-2(COX-2)were detected by Western blotting.Results Immersion in 15%seawater for 12 h significantly decreased HT22 cell viability(P<0.05).The CCK-8 assay indicated that cell viability in both the SI and SI+SW groups was significantly lower than that in control group after 12 h of treatment(P<0.05).Treatment with CM containing MSCs secretomes significantly increased cell viability in SI+CM group compared to SI group(P<0.0001),and in SI+SW+CM group compared to SI+SW group(P<0.001).Flow cytometry results revealed that the apoptosis rate in SI and SI+SW groups was significantly higher than that in control group(P<0.05 or P<0.001),while in SI+CM group was lower than that in SI group(P<0.05),and in SI+SW+CM group was lower than that in SI+SW group(P<0.05).Western blotting showed that compared to control group,SI and SI+SW groups exhibited reduced Bcl-2 expression level(P<0.01 or P<0.0001)and increased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.0001).Compared to SI group,the SI+CM group displayed increased Bcl-2 expression level(P<0.05)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.05).Compared to SI+SW group,SI+SW+CM group exhibited increased Bcl-2 expression level(P<0.01)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.001).Scratch assay results demonstrated that at both 12 h and 24 h,the cell migration rate in SI and SI+SW groups was significantly lower than that in control group(P<0.01 or P<0.0001),while the migration rate in SI+CM group was significantly higher than that in SI group(P<0.0001 or P<0.01),and the migration rate in SI+SW+CM group was significantly higher than that in SI+SW group(P<0.0001).Conclusion Secretomes derived from MSCs cultured using the hanging drop method can alleviate neuronal damage caused by SW and TBI,potentially offering a therapeutic approach for SW combined with TBI.

Objective To investigate the impact of silymarin(SM)on the malignant growth of glioma cells and the regulatory mechanism on the miR-124-3p/WEE1 axis.Methods Glioma U87 cells were grouped into control,SM low,medium,and high concentration groups,and SM high concentration + miR-124-3p inhibitor group(SM high + miR-124-3p inhibitor group).CCK-8 was used to measure the proli-feration rate of cells;Transwell? assay was applied to assay the migration and invasion of cells;cell cycle progression was detected by flow cytometry;Western blotting was applied to measure the expression of cyclin D1 and apoptosis-related proteins;the levels of miR-124-3p and WEE1 mRNA were determined by qRT-PCR;and a luciferase activity test was applied to verify the targeting relationship between miR-124-3p and WEE1;in addition,the establishment,administration,and analysis of a NOD/SCID mouse model of intracranial trans-planted tumor were conducted.Results Compared with the control group,the cell proliferation,the numbers of migrating and invading cells,the expression of cyclin D1,and the level of WEE1 mRNA in the various SM treatment groups decreased,the number of cells in G0/G1 phase,the expression of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3 and miR-124-3p increased(P＜0.05);furthermore,transfection of miR-124-3p inhibitor reversed the inhibitory effect of SM on the malignant behavior of glioma cells.In vivo experiments with mice showed that the weights and volumes of tumors in the SM treatment group were lower than those in the model group(P＜0.05),and there was no discernible change in the weight of the mice(P＞0.05).Conclusion SM can inhibit the malignant growth of glioma cells by upregulating miR-124-3p and downregulating WEE1.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Humans ; Otosclerosis/surgery* ; Stapes ; Stapes Surgery/adverse effects* ; Arteries

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.
Artificial Intelligence ; Medicine, Chinese Traditional ; Reproducibility of Results ; Quality Control ; Intelligence ; Pharmaceutical Preparations