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.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective:To analyze the trend of lipid changes in patients and individuals undergoing physical examination at Zhongshan Hospital of Fudan University from 2014 to 2024, providing evidence for the formulation of cardiovascular disease prevention and control strategies.Methods:A total of 2 657 835 individuals (general population) who underwent lipid testing during medical visits or physical examinations at Zhongshan Hospital of Fudan University from January 1, 2014, to December 31, 2024, were selected. Among them, 6 234 individuals who were tested consecutively for 11 years were considered as the fixed population. Lipid levels were analyzed across different genders and age groups. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were analyzed. The trends in lipid changes and the abnormal rates of TC (≥5.18 mmol/L) and LDL-C (≥3.40 mmol/L) in both the general and fixed populations were statistically analyzed.Results:The median age of the general population was 53 (41, 63) years, with 1 498 533 males (56.4%); 1 149 662 individuals (43.3%) were from the physical examination group. The median age of the fixed population was 52 (39, 62) years, with 3 262 males (52.3%); 2 955 individuals (47.4%) were from the physical examination group. Over an 11-year period, the logarithmically transformed TG (lnTG) in the general population slightly increased from 1.35 mmol/L to 1.36 mmol/L (Sen slope=0.007 mmol·L -1·year -1; S=27, P=0.043). Although there were fluctuations in TC, LDL-C, and HDL-C, the trends were not statistically significant ( P>0.05). However, in the subset of the population undergoing regular health check-ups, TC showed a steady increase over time ( S=27, P=0.043). Within a fixed population over the same 11-year period, there were no statistically significant changes in lipid profiles ( P>0.05). Nevertheless, in the fixed subset undergoing regular health check-ups, both TC and lnTG exhibited an upward trend (TC: S=27, P=0.043; lnTG: S=31, P=0.020), while in the fixed subset seeking medical attention, TC and LDL-C demonstrated a downward trend (TC: S=-31, P=0.020; LDL-C: S=-27, P=0.043). Trends in lipid profiles varied among different genders and age groups. Specifically, both men and women aged 20-<40 years old showed an increase in TC, abnormal TC rates, and abnormal LDL-C rates ( P<0.05). Conversely, in the fixed population, women over 60 years old exhibited a decrease in TC, abnormal TC rates, and abnormal LDL-C rates ( P<0.05). Conclusion:During the period from 2014 to 2024, there were slight fluctuations in the average lipid levels of both the general and fixed populations. Notably, TC, abnormal TC rates, and abnormal LDL-C rates increased among men and women aged 20-<40 years old, while these parameters decreased among women over 60 years old in the fixed population.

Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.

Objective:To explore the clinical value of combination of contrast-enhanced ultrasound(CEUS)and magnetic reso-nance imaging(MRI)in the diagnosis of parotid gland tumors.Methods:167 patients with parotid gland tumors were diagnosed by CEUS and MRI respectively and in combination.With postoperative pathological diagnosis result as the gold standard,the diagnos-tic value of CEUS combined with MRI(CEUS+MRI)was analyzed.Results:171 tumors were confirmed by postoperative pathology in 167 patients,including 143 benign tumors(83.63％)and 28 malignant tumors(16.37％).The benign tumors were mainly pleo-morphic adenoma(65 tumors,45.45％),Warthin tumor(40 tumors,27.97％)and basal cell adenoma(13 tumors,9.09％).Among the malignant tumors,mucoepidermoid carcinoma(7 tumors,25.00％),adenoid cystic carcinoma(6 tumors,21.43％)and acinic cell carcinoma(3 tumors,10.71％)were the most common.CEUS showed 39 cases of malignant parotid gland tumors and 132 cases of benign parotid gland tumors.The sensitivity,specificity and accuracy rate of CEUS were 57.14％,83.92％and 79.53％respectively.The MRI ADC values were manifested as pleomorphic adenoma＞malignant tumor＞Warthin tumor(P＜0.05).MRI showed 53 cases of malignant parotid gland tumors and 118 cases of benign parotid gland tumors,and the sensitivity,specifici-ty and accuracy rate of MRI diagnosis were 67.86％,76.22％and 74.85％respectively.CEUS+MRI revealed 33 cases of malig-nant parotid gland tumors and 138 cases of benign parotid gland tumors,the sensitivity,specificity and accuracy rate of CEUS+MRI diagnosis were 78.57％,92.31％and 90.06％respectively.The specificity and accuracy rate of CEUS+MRI were significantly higher than those of single examination(x2=4.806,13.951,7.348,13.664,allP＜0.05).Conclusion:Both CEUS and MRI have certain clinical value in the diagnosis of parotid gland tumors,and the specificity and accuracy rate of CEUS+MRI are significantly higher than those of single examination.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Male ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans

To investigate the effects of phosphorus fertilizer on the morphological traits, active ingredients and rhizosphere soil microbial community of Polygala tenuifolia. The phosphorus fertilizer was calculated in terms of P_2O_5. Five treatments were set up: 0(CK), 17(P1), 34(P2), 51(P3), and 68(P4) kg per Mu(1 Mu≈667 m~2). A randomized block design was adopted. Samples of P. tenuifolia and its rhizosphere soil were collected under different superphosphate fertilizer treatments. Illumina high-throughput sequencing was used to analyze the rhizosphere soil microbial community, 9 morphological traits were measured and the content of 11 active ingredients were determined. The results showed that the whole plant weight, shoot fresh weight, root weight, and root peel thickness were the highest under P1 treatment, increasing by 34.41%, 38.80%, 39.21%, and 3.17% respectively compared to CK. Under P2 treatment, the plant height, stem diameter, root thickness, and core thickness were significantly higher than CK. Phosphorus fertilizer had a significant impact on the content of tenuifolin, sibiricose A5, sibiricose A6, arillanin A, 3,6'-disinapoyl sucrose, and polygalaxanthone Ⅲ. Correlation analysis results showed that the relative abundance of Arthrobacter, Bacillus, norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, MND1 and other bacteria, as well as the relative abundance of Neocosmospora, Paraphoma and other fungi were positively correlated with root diameter, wood core diameter, the whole plant weight, root weight, shoot fresh weight of P. tenuifolia. Bacillus, Neocosmospora, Subulicystidium were significantly positively correlated with oligosaccharides such as 3,6'-disinapoyl sucrose, sibiricose A5、sibiricose A6、glomeratose A、arillanin A and tenuifoliside C. Arthrobacter, Humicola, Aspergillus, Paraphoma were positively correlated with tenuifolin and norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, Fusarium were positively correlated with polygalaxanthone Ⅲ. Evidently, appropriate phosphorus application is conducive to the growth and quality improvement of P. tenuifolia, and can increase the abundance of beneficial microorganisms in the soil.
Rhizosphere ; Phosphorus/pharmacology* ; Soil Microbiology ; Polygala/anatomy & histology* ; Fertilizers/analysis* ; Bacteria/metabolism* ; Soil/chemistry* ; Microbiota/drug effects* ; Plant Roots/metabolism*

This study predicts the potential mechanism of Hippocampus in the treatment of knee osteoarthritis(KOA) through network pharmacology, with preliminary verification using molecular docking and animal experiments. The database was used to screen the active chemical components of Hippocampus and the targets of KOA, and Gene Ontology(GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and molecular docking were performed on the relevant core targets to preliminarily explore the potential targets and mechanisms of Hippocampus in the treatment of KOA. A rat KOA model was constructed by intra-articular injection of sodium iodoacetate, and the rats were intervened with different doses of Hippocampus decoction and celecoxib. The expression of relevant targets was detected through hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), RT-qPCR, and Western blot to further validate the network pharmacology results. A total of 23 drug-like components of the Hippocampus were screened, and 128 common targets with KOA were identified, involving interleukin-17(IL-17) signaling pathway, transcription factor(FoxO) signaling pathway, tumor necrosis factor(TNF) signaling pathway. Molecular docking results showed that the screened core chemical components exhibited good affinity with key targets. HE staining demonstrated that Hippocampus improved the morphology of the cartilage layer. ELISA confirmed that Hippocampus significantly reduced the levels of IL-6 and TNF-α in the serum of KOA rats. Western blot and RT-qPCR analysis showed that Hippocampus significantly reduced the expression of IL-6, TNF-α, matrix metalloproteinase(MMP) 13, IL-17A, nuclear factor κB activator 1(ACT1), tumor necrosis factor receptor-associated factor 6(TRAF6) and nuclear factor κB(NF-κB) in cartilage tissue. The results suggest that Hippocampus can alleviate the degree of joint damage in the KOA rat model induced by sodium iodoacetate. The mechanism of action is related to the inhibition of the IL-17 signaling pathway, reduction of inflammation, and inhibition of extracellular matrix(ECM) degradation.
Animals ; Molecular Docking Simulation ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Male ; Osteoarthritis, Knee/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Humans ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Hippocampus/chemistry*