Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria：① Age is 18 to 80 years old；② The laboratory test indicators are in line with the diagnosis of primary aldosteronism；③ The auxiliary examination proved that only one side was involved；④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows：① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery；② Postoperative loss to follow-up；③ No surgical specimens were received or the surgical specimens were incomplete，making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited，and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin（HE）staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was（49.86 ± 9.80）years，the body mass index was（25.49 ± 3.40）kg/m2，the preoperative aldosterone level was 352（2012，556）pg/ml，and the direct renin concentration was 1.63（0.50，4.56）μIU/ml. The aldosterone/renin ratio was 224.9（57.1，641.6）（aldosterone concentration unit was pg/ml，renin concentration unit was μIU/ml），the minimum blood potassium concentration was 2.87（2.50，3.40）mmol/L，and the systolic blood pressure was（144.5 ± 19.5）mmHg. Among the 114 patients，105 had adrenal nodules detected by preoperative CT，of whom 2（1.75%）had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules，2 cases had no nodules，and 22 cases（19.30%）had multiple nodules detected（17 cases had 2 nodules and 5 cases had 3 nodules）. Among them，12 cases（10.53%）presented as grossly visible multinodular lesions，while 10 cases（8.77%）appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules，13 had multiple CYP11B2-positive nodules，while the remaining had only one positive nodule. Among the 22 patients with multiple nodules，preoperative CT showed single nodules in 19 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（9.09%）. Among the 12 patients with grossly visible multinodular lesions，preoperative CT showed single nodules in 9 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（16.67%）.Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common，and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective To analyze the role and mechanism of Xiaoqinglong decoction in alleviating the pathological process of pulmonary arterial hypertension(PAH),and to observe the effect of Xiaoqinglong decoction on endothelial-mesenchymal transition(EMT)in human pulmonary arterial endothelial cell(HPAEC)and the involvement of the Toll-like receptor/nuclear factor-κB/hypoxia-inducible factor-1α(TLR/NF-κB/HIF-1α)pathway in this mechanism.Methods Thirty-six male Sprague Dawley(SD)rats and HPAEC were randomly divided into control group,model group,Xiaoqinglong decoction plus Earthworm group,Bosentan tablet group,dimethyl sulfoxide(DMSO)group,and monophosphoryl lipid A(MPL)group.PAH rat models and HPAEC models were established by hypoxic exposure.The Xiaoqinglong decoction plus Earthworm group received intragastric administration Xiaoqinglong decoction plus Earthworm(5 g·kg-1·d-1)or cultured with 10%corresponding drug serum,the Bosentan group received Bosentan(100 mg·kg-1·d-1)by gavage or cultured with 10%corresponding drug serum,the MPL group received 1 μg MPL,and the DMSO group received an equivalent volume of the DMSO and corn oil mixed solvent as a negative control for the MPL group.The hemodynamic parameters,including mean pulmonary arterial pressure(mPAP),right ventricular systolic pressure(RVSP),and the maximum rate of right ventricular pressure(+dp/dt max),were measured via right heart catheterization.After euthanasia,lung and heart tissues were collected to assess the right ventricular hypertrophy index(RVHI);hematoxylin-eosin(HE)staining was used to observe the degree of right ventricular cardiomyocyte hypertrophy and to calculate the average intima-media thickness(IMT)in small pulmonary arteries;Western blotting was used to detect the protein expression levels of proliferating cell nuclear antigen(PCNA),CD68,TLR4,NF-κB,HIF-1α,vascular endothelial cadherin,and vimentin;cell counting kit-8(CCK-8),Transwell,and scratch assays were used to observe cell proliferation and migration;Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of interleukins(IL-8,IL-6),tumor necrosis factor-α(TNF-α),endothelin-1(ET-1),and nitric oxide(NO).Results Compared with the model group,the Xiaoqinglong decoction plus Earthworm group showed significant reductions in mPAP,RVSP,RVHI,and IMT in PAH rats[mPAP(mmHg,1 mmHg≈0.133 kPa):22.17±1.94 vs.42.00±4.90,RVSP(mmHg):34.67±3.20 vs.52.83±3.76,RVHI:0.402±0.057 vs.0.822±0.101,IMT:(37.85±2.49)%vs.(62.06±4.52)%,all P<0.05],and a significant increase in+dP/dT max(mmHg/s:2 730.83±137.89 vs.1 718.33±148.36,P<0.05).Western blotting and ELISA results showed that compared with the model group,the Xiaoqinglong decoction plus Earthworm group had significantly lower protein expression of PCNA and CD68 in lung tissue,and levels of inflammatory factors(IL-6,IL-8,TNF-α)in rat serum[lung tissue:PCNA protein expression(PCNA/GAPDH)was 1.56±0.08 vs.2.20±0.26,CD68 protein expression(CD68/GAPDH):1.46±0.09 vs.2.60±0.23;serum:IL-8(ng/L)was 39.67±6.28 vs.149.17±7.49,IL-6(ng/L):81.00±6.63 vs.211.00±25.31,TNF-α(ng/L):213.17±24.86 vs.799.50±43.51,all P<0.05].In vitro experiments,compared with the model group,Xiaoqinglong decoction plus Earthworm inhibited abnormal proliferation(A value:2.052±0.087 vs.2.242±0.057,P<0.05)and migration[number of migrating cells(per field):101.33±12.01 vs.226.67±17.56,P<0.05]of HPAEC,and reversed the EMT process,manifested as upregulation of vascular endothelial cadherin protein expression levels(vascular endothelial cadherin/GAPDH:0.39±0.06 vs.0.12±0.03,P<0.05)and downregulation of vimentin protein expression(vimentin/GAPDH:4.96±0.33 vs.7.89±0.44,P<0.05).Western blotting results indicated that compared with the model group,the protein expression levels of TLR4,the ratio of phosphorylated p65 to total p65,and HIF-1α in both lung tissue and HPAEC were significantly reduced in the Xiaoqinglong decoction plus Earthworm group[lung tissue:TLR4 protein expression(TLR4/GAPDH)was 3.13±0.20 vs.4.38±0.30,p-p65/p65 ratio:7.11±0.81 vs.12.73±1.80,HIF-1α protein expression(HIF-1α/GAPDH):2.37±0.32 vs.4.45±0.34;HPAEC:TLR4 protein expression(TLR4/GAPDH)was 1.42±0.03 vs.2.43±0.05,p-p65/p65 ratio:6.01±1.84 vs.11.28±1.06,HIF-1α protein expression(HIF-1α/GAPDH)was 3.24±0.17 vs.5.50±0.44,all P<0.05],accompanied by upregulated vascular endothelial cadherin protein expression(vascular endothelial cadherin/GAPDH:0.66±0.03 vs.0.49±0.03,P<0.05)and downregulated vimentin protein expression(vimentin/GAPDH:1.81±0.12 vs.2.47±0.10,P<0.05),indicating that Xiaoqinglong decoction plus Earthworm inhibits the EMT process in endothelial cells by suppressing the activation of the TLR/NF-κB/HIF-1α pathway.Experiments with a TLR agonist further confirmed that activation of the TLR pathway reverses the protective effects of Xiaoqinglong decoction plus Earthworm,as shown by the MPL group compared to the DMSO group having significantly increased protein expression of the p-p65/p65 ratio and HIF-1α[p-p65/p65 ratio:2.17±0.35 vs.1.08±0.14,HIF-1α/GAPDH:3.96±0.25 vs.1.03±0.10,both P<0.05],further decreased vascular endothelial cadherin protein expression(vascular endothelial cadherin/GAPDH:0.66±0.04 vs.0.99±0.02,P<0.05),further increased vimentin protein expression(vimentin/GAPDH:1.53±0.12 vs.0.93±0.07,P<0.05),along with enhanced cell migration capacity[number of migrating cells(per field):176.67±17.50 vs.107.00±11.14;cell migration rate in scratch assay:(34.32±2.82)%vs.(22.71±2.49)%,both P<0.05]and increased proliferation activity(48 hours A value:2.156±0.044 vs.1.810±0.088,P<0.05).Conclusions Xiaoqinglong decoction combined with Pheretima not only significantly reduces pulmonary artery pressure,improves cardiac function and mitigates pulmonary vascular fibrosis in PAH rats,but also alleviates pulmonary vascular remodeling by inhibiting inflammatory responses and EMT.It can further decrease the content of ET-1,increase the level of NO,and ameliorate vascular stenosis.This result further indicates that exterior-relieving medicines exert a significant dilating and supporting effect on the narrowed meridians and collaterals.

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.