OBJECTIVE To investigate the improvement effects and mechanism of Achyranthes bidentata total saponins （ABS） extract on vascular endothelial dysfunction in spontaneously hypertensive rat （SHR） based on cytochrome P450 4A （CYP4A）/20-hydroxyeicosatetetraenoic acid （20-HETE）/G protein-coupled receptor 75 （GPR75） axis. METHODS Ten Wistar- Kyoto rats were taken as the normal control group. Forty SHR were first stratified by systolic blood pressure and then， within each stratum， randomly assigned using a random-number table to the model group （MOD group）， captopril positive control group （CAP group， 10 mg/kg）， ABS low- and high-dose extract groups （ABS-L group， ABS-H group， 60 and 120 mg/kg）， with 10 rats in each group. Animals in each group were given the corresponding drug or equal volume of pure water by gavage， once a day， for 28 consecutive days. After the last administration， systolic blood pressure of rats was measured. The levels of vasoactive substances， inflammatory factors and oxidative stress indicators in serum were measured. The pathological changes of rat thoracic aorta were observed. The level of reactive oxygen species （ROS） in aortic tissue was analyzed. The expressions of endothelial nitric oxide synthase （eNOS）， CYP4A， GPR75， nuclear factor-κB p65 （NF-κB p65）， phosphorylated NF-κB p65， p22phox， and reduced nicotinamide adenine dinucleotide phosphate oxidase 4（NOX4） in thoracic aorta tissue were detected. RESULTS After 28 d of treatment， compared with MOD group， the systolic blood pressure of rats in the ABS-L and ABS-H groups decreased significantly. The levels of 20-HETE， angiotensin Ⅱ， interleukin-1β， interleukin-6， tumor necrosis factor-α， intercellular cell adhesion molecule-1 and malondialdehyde in serum were significantly reduced （P＜0.05 or P＜0.01）， while the levels of nitric oxide， superoxide dismutase， glutathione peroxidase and catalase were significantly increased （P＜0.05 or P＜0.01）. Intimal damage of thoracic aorta was reduced， and endothelial cell morphology was improved. The expressions of ROS， CYP4A， GPR75， p22phox， NOX4 and the phosphorylation level of NF-κB p65 protein in thoracic aorta were down-regulated or reduced （P＜0.05 or P＜0.01）， while the expression of eNOS was up-regulated （P＜0.05 or P＜0.01）. CONCLUSIONS ABS extract may alleviate the inflammatory response and oxidative stress in SHR effectively by down-regulating the expression of CYP4A， reducing the production of 20-HETE， inhibiting the activation of GPR75， and subsequently suppressing the activation of downstream NF-κB and NOX4， thereby improving hypertension-related vascular endothelial dysfunction.

OBJECTIVE To study the mechanism of action of Rehmannia glutinosa-medicated serum （RG） in regulating lipopolysaccharide （LPS）-induced polarization of BV2 microglia to interfere with neuroinflammation. METHODS An in vitro neuroinflammation model of BV2 cells induced by LPS was established. Cells were divided into control group， LPS group， 10%RG group， 20%RG group， BAY 11-7082 [nuclear factor kappa B （NF-κB） inhibitor] group， and 20%RG+BAY 11-7082 group. Except for the control group， cells in all other groups were pretreated with corresponding drugs for 12 h and then stimulated with LPS for 24 h. The morphology of cells in each group was observed， and the fluorescence intensity of ionized calcium binding adaptor molecule 1 （Iba-1）， inducible nitric oxide synthase （iNOS）， CD206， the mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， iNOS， IL-4， IL-10， transforming growth factor-β （TGF-β）， arginase-1 （Arg-1）， and the Toll-like receptor 4 （TLR4）/NF-κB/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） signaling pathway-related protein expression were detected. RESULTS Compared with the control group， the LPS group showed significant changes in cell morphology， exhibiting a typical M1 activated morphology. The fluorescence intensity of Iba-1 and iNOS， the relative expression levels of TNF-α， IL-6， IL-1β， iNOS mRNA， the relative expression levels of TLR4， NLRP3， caspase-1 p20， IL-1β p17 protein， and the phosphorylation levels of NF-κB p65 and inhibitor of nuclear factor kappa B α were significantly increased （P＜0.05）. The fluorescence intensity of CD206 and the relative expression levels of IL-4， IL-10， TGF-β， and Arg-1 mRNA were significantly reduced （P＜0.05）. Compared with the LPS group， the changes in the above indicators in the cells of the 10%RG group， 20%RG group， BAY 11-7082 group， and 20%RG+BAY 11-7082 group were significantly reversed （P＜0.05）， and there was no statistically significant difference in the comparison of the last three groups （P＞0.05）. CONCLUSIONS RG can effectively inhibit the overall activation of microglia and correct their M1/M2 polarization imbalance， and its mechanism may be closely related to the inhibition of excessive activation of the TLR4/NF-κB/NLRP3 signaling pathway.

ObjectiveTo establish a mouse model of hypoxic pulmonary hypertension (HPH) through intermittent hypoxia induction, and to develop a comprehensive and reliable evaluation system for the HPH model, thereby providing experimental evidence for mechanistic studies and translational applications related to this disease. MethodsTwenty-four male specific pathogen-free (SPF) BALB/c mice were randomly divided into a control group and a model group, with 12 mice per group. Mice in the model group were placed in a hypobaric oxygen chamber control system to establish the HPH model, whereas mice in the control group received no intervention. After 28 days of modeling, a comprehensive evaluation of the pathophysiological characteristics of both groups was performed using a general condition scoring scale, echocardiography, hemodynamic measurements, blood gas analysis, hematological tests, organ coefficient determination, histopathological examination, and enzyme-linked immunosorbent assay (ELISA). In addition, correlation analyses were conducted among echocardiographic parameters, the contents of endothelin‑1 (ET‑1) and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) in lung tissue, and other measured indices. ResultsWith prolonged modeling duration time, body weight, water intake, and activity level of mice in the model group were significantly decreased compared with the control group (P<0.05). Echocardiography showed that, compared with the control group, the model group exhibited increased right ventricular dimensions (P<0.01), right ventricular anterior wall thickening (P<0.01), and widened main pulmonary artery diameter (P<0.01), whereas the peak systolic velocity across the pulmonary valve, tricuspid annular plane systolic excursion, and peak systolic velocity of the tricuspid annulus were significantly decreased (P<0.001); tricuspid regurgitation was observed in some model animals. Hemodynamic results revealed that right ventricular systolic pressure was elevated in the model group compared with the control group (P<0.001). Blood gas analysis showed that pH, partial pressure of oxygen, oxygen saturation, actual bicarbonate, and total carbon dioxide were all decreased in the model group compared with the control group (P<0.01). Hematological indices demonstrated that lymphocyte counts (P<0.05) and reticulocyte counts (P<0.001) were decreased in the model group compared with the control group. Compared with the control group, the organ coefficients of heart and lung in the model group were significantly increased (P<0.05 and P<0.001). Pathological examination revealed that the right ventricular hypertrophy index was significantly increased in the model group (P<0.001), with varying degrees of damage to the right ventricle, pulmonary artery, and pulmonary vessels; both the pulmonary artery wall thickness percentage and the pulmonary wall area percentage were significantly elevated (P<0.001). ELISA results showed that the levels of ET‑1 and NT‑proBNP in lung tissues were significantly increased in the model group compared with the control group (P<0.05 and P<0.001, respectively). Correlation analysis indicated that some echocardiographic parameters were highly correlated with multiple indices in the development of HPH (P<0.05). ConclusionEchocardiography can accurately assess a series of hemodynamic changes in HPH, including right ventricular structural, functional impairment, and pulmonary hypertension. Laboratory tests not only help verify whether the model has been successfully established, but also provide deeper insights into the pathogenesis of HPH, evaluate the effects of interventions, and offer scientific evidence for clinical outcomes. Pathological examination can further confirm the alterations in pulmonary vascular remodeling and increased right heart load. This multimodal analysis provides a reliable animal model and evaluation paradigm for both basic and translational research on HPH, and is of great significance for exploring disease mechanisms and developing precision therapeutic strategies.

Objective To compare the differences in clinical characteristics between persistent atrial fibrillation(PsAF)combined with heart failure with preserved ejection fraction(HFpEF)and heart failure with reduced ejection fraction(HFrEF),and to clarify the influencing factors and predictive efficacy of PsAF combined with heart failure(HF).Methods A total of 117 inpatients with PsAF admitted to Laiyang Hospital of Traditional Chinese Medicine from February 2023 to February 2025 were selected and divided into PsAF+HFpEF group(n=42),PsAF+HFrEF group(n=34),and PsAF group(n=41)according to the type of HF.The baseline data,serum uric acid(UA)levels and echocardiographic parameters[left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),left atrium diameter(LAD),right ventricular diameter(RVD),left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),stroke volume(SV)and pulmonary artery systolic pressure(PASP)]of three groups of patients were compared.Multivariate Logistic regression analysis was used to identify the independent influencing factors of PsAF combined with HF,and the receiver operating characteristic(ROC)curve was drawn to evaluate the predictive efficacy.Results The proportions of New York Heart Association(NYHA)cardiac function grade Ⅲ-Ⅳ and hyperuricemia,and heart rate,N-terminal pro-brain natriuretic peptide(NT-proBNP),UA in patients of PsAF+HFpEF group and PsAF+HFrEF group were significantly higher than those in PsAF group(P＜0.05).The serum creatinine level of patients in PsAF+HFrEF group was significantly higher than that in PsAF+HFpEF group and PsAF group(P＜0.05).The levels of LVESD,LVEDD,LAD,RVD,PASP,LVEDV and LVESV in PsAF+HFrEF group were significantly higher than those in PsAF group(P＜0.05).The LVESD,LVEDD,LAD,LVEDV and LVESV of patients in PsAF+HFpEF group were significantly lower than those in PsAF+HFrEF group(P＜0.05),LAD and PASP were significantly higher than those in PsAF group(P＜0.05).There was a statistically significant difference in LVEF among three groups of patients(P＜0.05),in sequence:PsAF group＞PsAF+HFpEF group＞PsAF+HFrEF group.Multivariate Logistic regression analysis showed that NT-proBNP,UA,and NYHA cardiac function grade Ⅲ-Ⅳ were all independent risk factors for PsAF complicated with HF,and LVEF was an independent protective factor(P＜0.05).The area under the curve for combined prediction of PsAF combined with HF by NT-proBNP+UA+LVEF was 0.967.Conclusion NT-proBNP,UA and LVEF are all independent predictors of PsAF complicated with HF.The combination of three has highly efficient predictive value and provides an efficient tool for clinical risk stratification.

Practice shows that the Outline of the"Healthy China 2030"Plan is an effective means and way to cope with the growing medical needs of the people and realize the health of all people in China,and the benign interaction and synergistic development of the reform of the health insurance payment method reform and the development of public hospitals is precisely one of the policy focuses for the high-quality promotion of the construction of Healthy China.Based on the synergy theory and SFIC model,it explains the basic logic of the synergistic development of public hospital development and health insurance payment method reform,and sort out the optimization path of the synergistic development of the two:clarify the construction goal,and reach the starting conditions of effective synergistic development;give full play to the catalytic leadership led by the Party building,and build the foundation of synergistic reform;improve the system design,and build a policy system that fits the actual situation;create a good cooperative and interactive relationship to optimize the process of policy synergy.

Radiotherapy remains one of the primary therapeutic modalities for various cancers. However, individual heterogeneity exists in treatment outcomes and adverse reactions. In recent years, the interaction between the gut microbiota and radiotherapy has garnered increasing attention. The gut microbiota plays a crucial role in modulating host immune responses, maintaining intestinal barrier integrity, and participating in metabolic processes, thereby influencing both the efficacy and tolerance of radiotherapy. Modulating gut microbiota composition through probiotics, antibiotics, or dietary interventions may reduce the toxic side effects induced by radiotherapy, thereby enhancing therapeutic outcomes. Despite numerous challenges in mechanistic studies and clinical application, current research has shed light on cancer therapies. This review emphasizes the significant role of gut microbiota in radiotherapy, impacting treatment outcomes and patients’ tolerance and quality of life. Future research should further explore the links between microbiota regulation and optimization of radiotherapy outcomes, with the prospect of translating these strategies into clinical practice to provide more personalized treatment options for patients.

Objective:To evaluate the alveolar ridge preservation effect of immediate implantation at extraction site with the im-proved CBCT measuring method.Methods:Eighty patients with extraction site were divided into test group A,B,C and control group.The patients were treated by means of immediate implant placement combined with large flap surgery,guided bone regener-ation(GBR)using mass Bio-Oss bone particles in the group A(the thickness of facial bone wall＜1 mm);The patients were trea-ted by means of immediate implant placement combined without flap surgery and bone graft in the group B(the thickness of facial bone wall ≥1 mm and＜2 mm)and C(the thickness of facial bone wall ≥2 mm),the CGF was implanted in the jumping space only when the thickness of jumping space was＞2 mm.In the control group,the alveolar sockets healed naturally without any in-tervention or treatment.CBCT was taken before surgery,immediately after surgery,and 6 months after surgery to evaluate the height and width of alveolar bone,the thickness of facial bone wall and jumping space.Results:The reduction of alveolar ridge height in group A,B,C and control group was(0.41±0.13,0.94±0.18,0.59±0.12,1.31±0.19)mm,The reduction of alveolar ridge width in group A,B,C and control group was(0.93±0.10,1.48±0.21,1.12±0.17,1.66±0.16)mum.The re-sults of four groups were statistically different(F=177.0,P＜0.001;F=125.3,P＜0.001).The alveolar ridge thickness of facial bone wall in group A,B,C and con-trol group was(0.98±0.25,2.39±0.28)mm,(1.43±0.52,2.10±0.33)mm,(2.17±0.41,2.79±0.27)mm before surgery and six months after immediate implantation.The results of each group were statistically different between before surgery and six months after immediate implantation(t=16.45,P＜0.001;t=7.357,P＜0.001;t=5.488,P＜0.001).Patients in three test groups had the thickness of jumping space＞2 mm and ≤2 mm,and the reduction of alveolar ridge width was(0.78±0.18,0.88±0.17)mm.The results were statistically different(t=17.18,P=0.018).Conclusion:The alveolar ridge preservation was obtained by means of immediate implant placement combined with large flap surgery,guided bone regeneration(GBR)using mass Bio-Oss bone particles at extraction site with the thickness of facial bone wall＜1 mm;The alveolar ridge preservation was obtained without flap surgery and GBR at extraction site with the thickness of facial bone wall≥1 mm.The preservation of soft and hard tissue was better in the axial palatal side of immediate implantation with the thickness of jumping space＞2 mm than that with the thickness of jumping space≤2 mm.

Intrahepatic cholangiocarcinoma(ICC)typically has an insidious onset,and most patients have already progressed to advanced stages by the time of initial diagnosis,missing the opportunity for radical surgery.Surgical treatment is the main approach for ICC,but the high early recurrence rate after surgery and poor prognosis remain significant challenges.In recent years,there have been continuous breakthroughs in chemotherapy,immunotherapy,targeted therapy,and combination therapies for ICC,ushering in a new era for systemic treatment.With the improvement of treatment effects,conversion therapy,and neoadjuvant therapy have emerged as prominent topics of interest.However,with the deepening of clinical diagnosis and treatment practices,complex and unresolved issues have gradually emerged,triggering extensive discussions among scholars at home and abroad.Currently,there is no clear,standardized diagnostic and therapeutic process for conversion therapy and neoadjuvant therapy in the guidelines of the National Comprehensive Cancer Network or the Chinese Society of Clinical Oncology.This article aims to comprehensively review the latest progress in neoadjuvant and conversion therapy for ICC and deeply explore the controversial focuses therein,with the expectation of providing useful references for clinical practice and promoting the further development of this field.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To investigate the effect of different degrees of neuromuscular blockade on postoperative pain of patients receiving laparoscopic radical gastrectomy.Methods:A prospective randomized-controlled study was conducted. A total of 128 patients undergoing laparoscopic radical gastrectomy with American Society Anesthesiologists grade Ⅰ or Ⅱ in Shanxi Province Cancer Hospital from May 2023 to October 2024 were selected, and all patients were randomly divided into deep neuromuscular blockade group (group D, 64 cases) and moderate neuromuscular blockade group (group M, 64 cases) according to the random number table method. The patients in both groups were treated with general intravenous anesthesia combined with transversus abdominis plane block under the monitoring of a train-of-four (TOF) stimulus of the adductor pollicis muscle. The intraoperative pneumoperitoneum pressure was maintained at 12 mmHg (1 mmHg=0.133 kPa). Patient controlled analgesia (PCA) was connected with intravenous analgesia pump after operation. The surgical field exposure scores, the length of operation, anesthetic drug dosage, time of tracheal tube removal (the time from administration of muscle relaxant antagonists until spontaneous breathing returns to normal and the removal time of tracheal tube), time for neuromuscular blockade to recover to a train-of-four stimulus ratio (TOFr) ≥ 0.9, duration of stay in the post-anesthesia care unit (PACU), occurrence of PACU hypoxemia (blood oxygen saturation < 90%) in the PACU, postoperative visual analogue pain score (VAS), occurrence of shoulder pain, total number of presses and effective presses of the analgesic pump were recorded in both groups.Results:There were no statistically significant differences in the baseline data of the 2 groups (all P > 0.05). The surgical field exposure score in group D was higher than that in group M [(4.7±0.5) points vs. (4.0±0.7) points], the total dosage of rocuronium in group D was more than that in the group M [(192±15) mg vs. (141±21) mg], and the differences were statistically significant ( t values were -2.70 and -3.21 respectively, both P < 0.05). There were no significant differences in the time to extubation, the time for neuromuscular blockade recover to TOFr ≥0.9 and the length of stay in PACU, the incidence of hypoxemia in the PACU and the VAS scores at rest and during activity at 1 h and 6 h after surgery between the 2 groups (all P > 0.05). The VAS scores at rest and during activity at 24 h, 48 h and during activity at 72 h after operation in group D were lower than those in group M, and the differences were statistically significant (all P < 0.05). The incidence of shoulder pain after surgery in group D was lower than that in group M [20.0% (9/58) vs. 35.5% (20/58)], and the difference was statistically significant ( χ2 = 5.56, P < 0.05). The total number of postoperative analgesic pump presses and the number of effective presses in group D were less than those in group M, and the differences were statistically significant (both P < 0.05). Conclusions:Laparoscopic radical gastrectomy under deep neuromuscular blockade may alleviate postoperative pain of patients.