The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

Objective To summarize the clinical characteristics of primary pigmented nodular adrenocortical disease(PPNAD)and provide a reference for its clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical characteristics,laboratory tests,imaging examinations,treatment plans,and follow-up data of 10 PPNAD patients diagnosed and treated at the First Medical Center of Chinese PLA General Hospital from January 2008 to October 2024.Databases including CNKI,Wanfang Data Knowledge Service Platform,and PubMed were searched,and the clinical characteristics of 120 PPNAD patients reported in the literature were summarized in combination with literature reviews.Results The age at diagnosis of the 10 PPNAD patients ranged from 15 to 55 years,with a median age of onset of 21.5 years.Seven patients had the protein kinase A regulatory subunit 1 alpha(PRKAR1A)gene mutations,meeting the diagnosis criteria for Carney syndrome.One patient presented with hypertension only,while the remaining 9 patients showed typical Cushing's syndrome manifestations such as thin skin and moon face,among whom 5 experienced stagnation of height growth.In 7 patients,the adrenocorticotropic hormone(ACTH)levels were<2.2 pmol/L,with the disrupted circadian rhythm of cortisol,and the cortisol levels at midnight ranged from 243.24 to 679.83 pmol/L.None of the patients showed suppression in the low-dose dexamethasone suppression test,and 8 patients had an increase in urinary free cortisol(UFC)after dexamethasone suppression.Adrenal CT showed that 9 patients presented with unilateral adrenal nodules accompanied by contralateral thickening or bilateral adrenal nodular thickening.All 10 patients underwent initial unilateral adrenalectomy,and during follow-up,4 patients experienced symptom recurrence and underwent contralateral adrenalectomy.Most of the 120 patients reported domestically and internationally showed typical Cushing's syndrome manifestations.Surgical resection of the adrenal gland was the main treatment modality.Gene mutations were predominantly in PRKAR1A,with a few in PDE11A and PRKACA.Conclusions PPNAD is more likely to occur in adolescents.Patients with typical Cushing's syndrome manifestations should undergo screening.Imaging manifestations are atypical,and a definitive diagnosis depends on pathological and genetic diagnoses.Bilateral adrenalectomy combined with long-term postoperative hormone replacement therapy is the standard treatment protocol.Patients who undergo early unilateral adrenalectomy require long-term follow-up,with contralateral adrenalectomy performed when necessary.

Objective:To investigate the clinical efficacy of acupoint pressing acupuncture combined with moxibustion at Baihui acupoint on infantile cold and nasal obstruction caused by exogenous wind and cold. Methods:This study included a total of 120 children with exogenous wind and cold-induced infantile cold and nasal obstruction who were treated at the Jinhua Maternal & Child Health Care Hospital from February 2021 to May 2022. They were divided into three groups using a random number table method, namely the acupoint pressing acupuncture group, the moxibustion group, and the combined therapy group, each containing 40 children. Based on routine treatment, children in the acupoint pressing acupuncture group received acupoint ( Yintang, Shuangyingxiang, Shuangbitong) pressing acupuncture treatment, while those in the moxibustion group underwent mild moxibustion at Baihui acupoint, and those in the combined therapy group underwent acupoint ( Yintang, Shuangyingxiang, Shuangbitong) pressing acupuncture Baihui combined with mild moxibustion at Baihui acupoint. The clinical efficacy of each group was evaluated. At 2, 24, 48, and 72 hours after treatment, differences in nasal congestion symptom scores were compared among the three groups. Sleep quality was also compared among the three groups before and after treatment. Results:The response rate in the combined therapy group was 92.5% (37/40), which was significantly higher than 75% (30/40) in the acupoint pressing acupuncture group and 65% (26/40) in the moxibustion group ( χ2 = 4.50, 9.04, both P < 0.05). At 2, 24, 48, and 72 hours after treatment, the nasal congestion symptom score in the combined therapy group was (2.05 ± 0.55) points, (1.80 ± 0.64) points, (1.33 ± 0.59) points, and (0.90 ± 0.18) points, respectively, while it was (2.43 ± 0.59) points, (2.15 ± 0.57) points, (1.73 ± 0.84) points, and (1.18 ± 0.80) points, respectively, in the acupoint pressing acupuncture group, and (2.50 ± 0.59) points, (2.13 ± 0.78) points, (1.88 ± 0.81) points, and (1.45 ± 0.81) points, respectively, in the moxibustion group. At the above-mentioned time points, the nasal congestion symptom score was statistically significant among the three groups ( F = 3.15, 9.27, 16.17, 20.22, all P < 0.05). After treatment, daytime sleep duration and nocturnal sleep duration in the combined therapy group were (3.41 ± 0.31) hours and (12.36 ± 1.17) hours, respectively, which were significantly longer than (2.95 ± 1.07) hours and (11.33 ± 1.38) hours in the acupoint pressing acupuncture group and (2.93 ± 0.98) hours and (11.21 ± 1.93) hours in the moxibustion group ( F = 6.37, 12.31, both P < 0.05). Nocturnal wake time, the number of night wakings, and sleep onset time in the combined therapy group were (18.74 ± 2.21) minutes, (1.64 ± 0.18) times, and (15.43 ± 2.03) minutes, respectively, which were significantly shorter or less than (21.13 ± 3.78) minutes, (2.15 ± 0.66) times, and (17.63 ± 5.24) minutes in the acupoint pressing acupuncture group, and (20.53 ± 2.90) minutes, (2.11 ± 0.32) times, and (17.22 ± 2.88) minutes in the moxibustion group ( F = 15.93, 15.36, 10.11, all P < 0.05). There was a significant difference in sleep quality score among the three groups ( F = 23.45, P < 0.05). Conclusion:The combination of acupoint pressing acupuncture and moxibustion at Baihui acupoint is highly effective against infantile cold and nasal obstruction caused by exogenous wind and cold. The combined therapy can alleviate the symptoms of nasal congestion in children and improve sleep quality.

BACKGROUND:Intervertebral disc degeneration is caused by damage and degeneration of the nucleus pulposus and annulus fibrosus tissues inside the intervertebral disc,resulting in structural and functional changes of the intervertebral disc.However,there is yet no effective drug treatment for intervertebral disc degeneration. OBJECTIVE:To investigate the inhibitory effect of syringin on intervertebral disc degeneration. METHODS:A total of 10 male Sprague-Dawley rats were selected,and the coccygeal intervertebral disc(Co4/Co5)of each rat was set as model group,Co5/Co6 intervertebral disc as syringin group,and Co6/Co7 intervertebral disc as control group.The control group did not receive any treatment.In the model group and syringin group,a miniature puncture needle was used to puncture the annulus fibrosus to establish an intervertebral disc degeneration model.Immediately after modeling,2.5 μL of normal saline and syringin solution(5 μmol/L)were given in the model and syringin groups,respectively.Four weeks after injection,the samples were taken.The degree of intervertebral disc degeneration in rats was observed by hematoxylin-eosin and safranine O-fast green staining.The expressions of type Ⅱ collagen,aggrecan and matrix metalloproteinases 3 and 13 in intervertebral disc tissue were analyzed by immunohistochemical staining. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the model group,the height of intervertebral disc decreased,the cartilage endplate became thinner and cracked,the fibrous ring structure was disordered and cracked,and the nucleus pulposus disappeared;in the syringin group,the height of intervertebral disc was normal or slightly lower than that in the control group,the degree of cartilage endplate degeneration was lighter than that in the model group,the fiber circle permutation was relatively regular with no cracks,and the nucleus pulposus was partially shrunk.Safranine O-fast green staining showed that in the model group,the cartilage endplate of the intervertebral disc was defective and the calcified layer of cartilage became thinner,showing obvious degeneration.The structure and morphology of intervertebral disc cartilage endplate in the syringin group recovered to some extent.Immunohistochemical staining showed that,compared with the control group,the expressions of type Ⅱ collagen and aggrecan in the intervertebral disc cartilage were decreased in the model group(P<0.000 1),while the expressions of matrix metalloproteinases 3 and 13 increased(P<0.000 1).Compared with the model group,the expressions of type Ⅱ collagen and aggrecan in the intervertebral disc cartilage tissue were increased in the syringin group(P<0.001,P<0.000 1),while the expressions of matrix metalloproteinases 3 and 13 decreased(P<0.001,P<0.000 1).These results showed that syringin could improve the structure and function of intervertebral disc by inhibiting the expression of matrix metalloproteinases 3 and 13 and increasing the expression of type Ⅱ collagen and aggrecan,thus preventing and slowing down the procession of intervertebral disc degeneration.

Objective To investigate the relationship between serum levels of hepatocyte growth factor(HGF)and lipoxygenase-4(LXA4)in patients with acute exacerbation of bronchiectasis and the severity of the disease,and their evaluation value for the prognosis.Methods A total of 138 patients diagnosed with and treated for acute exacerbation of bronchiectasis between January 2019 and January 2021 in the hospital were selected as acute exacerbation group.Based on the bronchiectasis severity index(BSI score),patients were di-vided into mild group(40 cases),moderate group(46 cases),and severe group(52 cases).Additionally,pa-tients were categorized into a good prognosis group(85 cases)and a poor prognosis group(53 cases)based on their clinical outcomes.70 stable bronchiectasis patients treated concurrently were selected as the stable stage group.Furthermore,70 healthy individuals who underwent physical examinations during the same period was included as the control group.Serum HGF and LXA4 levels were measured by enzyme-linked immunosorbent assay.Logistic regression model was used to explore the factors affecting the prognosis of patients with acute exacerbation of bronchiectasis.The predictive effect of serum HGF and LXA4 levels on the prognosis of pa-tients with acute exacerbation of bronchiectasis was analyzed by receiver operating characteristic(ROC)curve.Results Compared with the stable stage group and the control group,the acute exacerbation group had higher serum HGF levels and lower LXA4 levels(all P＜0.05).The more severe the condition was in the a-cute exacerbation group,the higher the serum HGF level and the lower the LXA4 level.Compared with the good prognosis group,the poor prognosis group had lower levels of hemoglobin,albumin,and serum LXA4,while the number of acute exacerbations,proportion of severe BSI scores,and serum HGF levels were higher(all P＜0.05).In the acute exacerbation group,the more severe the disease,the higher the serum HGF level and the lower the LxA4 level.The number of acute exacerbations(OR=1.185,P＜0.001),BSI score(OR=1.280,P＜0.001),and serum HGF(OR=1.189,P＜0.001)were risk factors for poor prognosis in patients,while serum LXA4(OR=0.827,P＜0.001)was a protective factor.The area under the curve of the combined detection of serum HGF and LXA4 for evaluating poor prognosis in patients was 0.912(95％CI:0.862-0.955),which was larger than that of the single detection(Z=4.254,3.819,all P＜0.001).Conclusion The serum HGF level increases and LXA4 level decreases in patients with acute exacerbation of bronchiectasis,which are related to the severity of the disease.Combined detection has high predictive value for poor progno-sis in patients.

Objective To explore the clinical value of micro ribonucleic acid(miR)-27a and miR-1299 in predicting the long-term prognosis of patients with esophageal cancer.Methods A total of 89 patients with esophageal cancer in the hospital were enrolled between June 2020 and June 2022,and all underwent Minimally invasive thoracic and laparoscopic resection of esophageal cancer.The expression levels of miR-27a and miR-1299 were detected by real-time fluorescence quantitative polymerase chain reaction(PCR)before surgery,and level of serum ferritin(SF)was detected by enzyme linked immunosorbent assay.The relationship between miR-27a,miR-1299,SF and clinicopathology in patients with esophageal cancer was analyzed.All were followed up till February 2023 after surgery,and survival of patients was record.The relationship between miR-27a,miR-1299,SF and prognosis was analyzed.The risk factors of long-term prognosis in patients with esophageal cancer were analyzed by multivariate Cox regression model.The relationship between miR-27a,miR-1299 and serum SF was analyzed by Pearson.Results There were significant differences in miR-27a,miR-1299 and serum SF among patients with different tumor staging,lymph node metastasis and differentiation degree(P＜0.05).The results of survival analysis showed that overall survival rates in high-expression miR-27a and SF groups were lower than those in low-expression miR-27a and SF groups(P＜0.05),while which was higher in high-expression miR-1299 group than low-expression miR-1299 group(P＜0.05).Cox regression analysis showed that miR-27a ≥2.54,miR-1299＜4.18 and serum SF ≥223.78 μg/L(P＜0.05)were independent risk factors of postoperative long-term prognosis of patients with esophageal cancer.Pearson correlation analysis showed that level of serum SF was positively correlated with relative expression level of miR-27a(P＜0.05,r=0.612),while negatively correlated with relative expression level of miR-1299(P＜0.05,r=-0.517).Conclusion The miR-27a,miR-1299 and serum SF are related to tumor staging,lymph node metastasis and differentiation degree in patients with esophageal cancer,which can be applied to evaluate postoperative long-term prognosis.

Objective:To investigate the risk factors for the relapse of autoimmune pancreatitis (AIP) after steroid therapy.Methods:Clinical data of 72 AIP patients treated with steroids in Nanjing Drum Tower Hospital from January 2012 to December 2023 were collected retrospectively. AIP patients were divided into relapse group ( n=25) and non-relapse group ( n=47) based on the presence or absence of their relapse after steroid therapy. Patients' age of onset, gender, history of diabetes mellitus, first clinical manifestations, serum IgG4 and CA19-9 level, imaging features and other organ involvements were recorded. Oral prednisone was used at an initial dose of 0.6 mg·kg -1·d -1, gradually reduced to 5-10 mg/d and then maintained at a low dose. The follow-up period started from steroid initiation to the last follow-up or relapse. The presence of maintenance steroid treatment, time interval between onset and steroid initiation, the presence of significant IgG4 decrease and the presence of persistently enlarged pancreas after therapy were recorded. The cumulative relapse rate curve after steroid therapy was drawn by Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazard regression model. The receiver operator characteristic curves (ROC) were plotted and the area under the curve (AUC) was calculated. The Log-Rank test was used to analyze the differences on the relapse between different groups. The subgroup forest plot was drawn to assess the effect of risk factors on the relapse of AIP in different subgroups. Results:The 72 patients with AIP had a median follow-up of 42 (12-127) months. 34.7% (25/72) of patients relapsed after steroid therapy during the follow-up period. The percentages of patients whose first clinical manifestation was abdominal distension or acute pancreatitis, whose interval between onset and steroid initiation was more than 1 year and whose pancreases were persistently enlarged after steroid therapy in the relapse group were higher than those in the non-relapse group, and the differences were all statistically significant (all P value <0.05). The 1-, 3- and 5-year cumulative relapse rate after steroid therapy was 20.8%, 34.1% and 37.8%, respectively. Univariate analysis found that the first clinical manifestations of abdominal distension or acute pancreatitis, interval between onset and steroid initiation more than 1 year, and persistently enlarged pancreas after steroid therapy were all significantly associated with relapse (all P value <0.05). Multivariate analysis found that interval between onset and steroid initiation more than 1 year and persistently enlarged pancreas after steroid therapy were independent risk factors for relapse of AIP [hazard ratio ( HR)=3.606 and 6.515, 95% confidence interval (95% CI) 1.362-9.854 and 2.088-20.326]. Kaplan-Meier survival curves showed that the relapse rate after steroid therapy was higher in AIP patients whose interval between onset and steroid initiation was more than 1 year than in those whose interval was less than 1 year (55.6% versus 27.8%), and the relapse rate in AIP patients with persistently enlarged pancreas after steroid therapy was higher than that in those without it (77.8% versus 28.6%), and the differences were both statistically significant (both P<0.05). Subgroup forest plot showed that persistently enlarged pancreas after steroid therapy was an independent risk factor for relapse of AIP regardless of the presence of a diabetes mellitus history, the first manifestation of abdominal pain, the diffuse or focal type in pancreatic imaging, and the presence of dilated pancreatic duct or not (all P value <0.05). Conclusions:Time interval between onset and steroid initiation more than 1 year and persistently enlarged pancreas after steroid therapy were independent risk factors for the relapse of AIP after steroid therapy.