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 explore the application of goal-directed fluid therapy based on pulse pressure variation rate(PPV)combined with low central venous pressure(LCVP)technique in liver surgery.Methods A total of 86 patients who underwent liver lobe/segment resection in our hospital from January 2022 to December 2023 were included,and randomly divided into two groups by random sequence method.Patients in the conventional group were treated with LCVP technique,while patients in the test group were given PPV goal-directed intervention on the basis of the conventional group.The surgical indicators,hemodynamic indicators,cognitive function,adverse reactions and recovery of gastrointestinal function of patients in the two groups were compared.Results There was no statistically significant difference in the operation time,Pringle maneuver time,first postoperative exhausting time or first postoperative defecation time of patients between the two groups(P>0.05).However,the intraoperative blood loss,intraoperative fluid infusion volume and hospital stay of patients in the test group were all less/shorter than those in the conventional group(P<0.05).Compared with the time point of T0,patients in the two groups showed increased heart rate(HR)but decreased mean arterial pressure(MAP)and central venous pressure(CVP)at time points of T1 and T2(P<0.05).There was no statistically significant difference in the HR or MAP of patients between the two groups at time points of T0,T1,T2 and T3(P>0.05).At time points of T1 and T2,the CVP of patients in the test group was lower than that in the conventional group(P<0.05).One day after operation,the mini-mental state examination(MMSE)score of patients in the test group was higher than that in the conventional group(P<0.05).The MMSE scores 7 days after operation of patients in the two groups were higher than those 1 day after operation(P<0.05).Patients in the test group had a lower total incidence of adverse reactions and a shorter recovery time of gastrointestinal function than those in the conventional group(P<0.05).Conclusion The goal-directed fluid therapy based on PPV combined with LCVP technique has a good application effect in liver surgery,which can reduce intraoperative blood loss and fluid infusion volume of patients,shorten hospital stay,increase hemodynamic stability,improve postoperative cognitive dysfunction,and promote the recovery of gastrointestinal function,with a relatively high treatment safety.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Objective To explore the application of goal-directed fluid therapy based on pulse pressure variation rate(PPV)combined with low central venous pressure(LCVP)technique in liver surgery.Methods A total of 86 patients who underwent liver lobe/segment resection in our hospital from January 2022 to December 2023 were included,and randomly divided into two groups by random sequence method.Patients in the conventional group were treated with LCVP technique,while patients in the test group were given PPV goal-directed intervention on the basis of the conventional group.The surgical indicators,hemodynamic indicators,cognitive function,adverse reactions and recovery of gastrointestinal function of patients in the two groups were compared.Results There was no statistically significant difference in the operation time,Pringle maneuver time,first postoperative exhausting time or first postoperative defecation time of patients between the two groups(P>0.05).However,the intraoperative blood loss,intraoperative fluid infusion volume and hospital stay of patients in the test group were all less/shorter than those in the conventional group(P<0.05).Compared with the time point of T0,patients in the two groups showed increased heart rate(HR)but decreased mean arterial pressure(MAP)and central venous pressure(CVP)at time points of T1 and T2(P<0.05).There was no statistically significant difference in the HR or MAP of patients between the two groups at time points of T0,T1,T2 and T3(P>0.05).At time points of T1 and T2,the CVP of patients in the test group was lower than that in the conventional group(P<0.05).One day after operation,the mini-mental state examination(MMSE)score of patients in the test group was higher than that in the conventional group(P<0.05).The MMSE scores 7 days after operation of patients in the two groups were higher than those 1 day after operation(P<0.05).Patients in the test group had a lower total incidence of adverse reactions and a shorter recovery time of gastrointestinal function than those in the conventional group(P<0.05).Conclusion The goal-directed fluid therapy based on PPV combined with LCVP technique has a good application effect in liver surgery,which can reduce intraoperative blood loss and fluid infusion volume of patients,shorten hospital stay,increase hemodynamic stability,improve postoperative cognitive dysfunction,and promote the recovery of gastrointestinal function,with a relatively high treatment safety.

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 assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.

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.

In today's society， depression is a kind of highly prevalent chronic mental illness. It leads to a high disability rate and a heavy economic burden. Depression is defined by fundamental symptoms of low mood and diminished pleasure. Its causes and mechanisms remain unclear， and it presents a broad spectrum of symptoms and a persistent nature that significantly impacts both physical and mental well-being. Treatment in Western medicine primarily focuses on alleviating symptoms， yet it entails numerous adverse effects and contraindications. Traditional Chinese medicine （TCM） treatment is based on resolving depression， which is often accompanied by soothing liver， and the key medicine is Bupleuri Radix. Bupleuri Radix associated prescriptions refer to a class of prescriptions using Bupleuri Radix as the sovereign medicinal or having a high dose of Bupleuri Radix， which are widely used in the field of anti-depression. Previous studies from animal experiments， clinical research， and modern pharmacological research have confirmed that Bupleuri Radix associated prescriptions have precise anti-depression efficacy in multiple ways and at multiple levels， but lack a comprehensive and systematic summarization. This paper summarized and analyzed the literature related to the clinical application and mechanism of action of Bupleuri Radix associated prescriptions in anti-depression treatment. The results showed that the anti-depression mechanism of the Bupleuri Radix associated prescriptions （such as Xiaochaihu Tang， Xiaoyao San， Sini San， Chaihu Shugan San， and Chaihu jia Longgu Muli San） was associated with the effects of regulating monoamine neurotransmitters， the brain-derived neurotrophic factor （BDNF）， intestinal flora， and the hypothalamic-pituitary-adrenal （HPA） axis， inhibiting inflammatory responses， and modulating related signaling pathways. Applying them in clinical practice can effectively alleviate patient symptoms， lower the TCM syndrome score and the severity of depression， and also reduce adverse reactions. This underscores advantages of TCM in depression treatment， which offers patients a secure， effective， and more individualized alternative treatment regimen. On this basis， the shortcomings of current studies and the future trend were analyzed. This study aimed to provide an evidence-based medicine basis for the research and development of novel antidepressant medications.