ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

The early angiopathy of systemic sclerosis (SSc) is a key hub connecting inflammation and fibrosis. The animal models that simulate the pathological characteristics of SSc are of great significance to study the etiology, pathogenesis and treatment of SSc with vascular involvement. This review of the characteristics of different animal models of SSc with vascular involvement provides a reference for relevant researchers to select appropriate models in the process of exploring the pathogenesis of SSc with vascular involvement.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective To explore the correlation of body mass index,urinary protein and tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)during pregnancy with the severity of preeclampsia and pregnancy outcome.Methods A total of 63 patients with preeclampsia who were examined in Xingtai People's Hospital from April 2022 to April 2023 were enrolled in the study,33 patients with mild preeclampsia were included in the mild group and 30 patients with severe preeclampsia were included in the severe group.Physi-cal characteristics,urinary protein and sTWEAK levels between the groups were recorded,and the patients were followed up to explore the correlation with pregnancy outcome.Results The systolic and diastolic blood pressure of patients in the mild group were lower than those in the severe group,and the plasma albumin was higher than that in the severe group(P＜0.05).There was no statistically significant difference in pre preg-nancy weight and pre pregnancy body mass index between the mild and severe groups of patients(P＞0.05).The delivery weight and weight gain during pregnancy in the mild group were lower than those in the severe group(P＜0.05).The 24-hour urinary protein quantification in the mild group was lower than that in the se-vere group,and the sTWEAK expression level was higher than that in the severe group(P＜0.05).The pre pregnancy weight,pre pregnancy body mass index,delivery weight,and weight gain during pregnancy in the good pregnancy outcome group were all lower than those in the adverse pregnancy outcome group(P＜0.05).The 24-hour urinary protein quantification in the good pregnancy outcome group was lower than that in the adverse pregnancy outcome group,and the sTWEAK expression level was higher than that in the adverse pregnancy outcome group(P＜0.05).Receiver operating characteristic(ROC)curve analysis revealed that the area under the curve(AUC)of pre pregnancy body mass index,pre pregnancy weight,delivery weight,gestational weight gain,24-hour urinary protein quantification,and sTWEAK expression levels for predicting adverse pregnancy outcomes in patients were 0.906,0.690,0.919,0.664,0.908,and 0.793,respectively.The AUC for predicting adverse pregnancy outcomes in patients by combining pre pregnancy body mass index,de-livery weight,24-hour urinary protein quantification,and sTWEAK expression level was 0.932.Conclusion Body mass index,urinary protein and sTWEAK levels during pregnancy are closely associated with the severity of pre-eclampsia and pregnancy outcomes,and these indicators may help identify high-risk pregnant women early and take appropriate interventions to improve pregnancy outcomes.

Thyroid nodules are a common endocrine disorder with complex pathogenesis that remains incompletely understood. In recent years, studies have revealed that the gut microbiota may play a critical role in the occurrence and progression of thyroid nodules. This review systematically summarizes the current research progress on the association between gut microbiota and thyroid nodules, with a particular focus on potential mechanisms through which gut dysbiosis influences nodule formation via immune regulation, metabolic pathways, and gut barrier function. Evidence suggests that reduced gut microbial diversity, decreased abundance of specific beneficial bacteria, and an increased proportion of pro-inflammatory bacteria may contribute to a pro-inflammatory environment and metabolic disturbances associated with thyroid nodules. Furthermore, this review explores the potential of interventions such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation in modulating gut microbiota and improving thyroid nodule outcomes. Although direct clinical evidence is currently lacking, the regulation of gut microbiota has emerged as a promising direction for the diagnosis and treatment of thyroid nodules, demonstrating significant clinical potential. Future efforts should focus on advancing basic and clinical research strategies to facilitate the translational application of findings in this field.

Objective:To investigate the effects of botulinum toxin A (BTX-A) injection on ocular surface in patients with blepharospasm and dry eye.Methods:In this prospective study, 56 patients (83 eyes) with essential blepharospasm who were treated with BTX-A in the Department of Ophthalmology of Jiaxing Hospital of Traditional Chinese Medicine from April 2020 to January 2022 were included. The patients were divided into blepharospasm with dry eye group (group A, 50 eyes) and simple blepharospasm group (group B, 33 eyes) according to whether they were accompanied by dry eye. The Oculus Keratograph was used to evaluate tear meniscus height (TMH), tear break-up time (BUT), ocular bulbar redness, and corneal fluorescein staining. The OPD-Scan III analyzer was used to measure the corneal surface regularity index. The Ocular Surface Disease Index and meibomian gland analysis were performed to diagnose dry eye before treatment. Paired t-tests and Wilcoxon signed-rank tests were conducted to analyze the data. In patients with unilateral conditions, the ocular surface data of the affected and healthy eyes were compared before treatment. The severity of blepharospasm was evaluated in both groups before treatment and 1 week after treatment. Results:Among the 56 patients, 57.1% (32/56) were diagnosed with dry eye. One week after BTX-A injection treatment, both groups demonstrated varying degrees of improvement in their conditions. In patients with unilateral blepharospasm, pre-treatment ocular surface examinations indicated that the affected eye had a lower tear BUT of (6.67 ± 3.86) seconds and a lower TMH of (0.18 ± 0.07) mm compared with the healthy eye, which showed (10.20 ± 5.95) seconds for BUT and (0.20 ± 0.05) mm for TMH ( t = -3.94, -2.44, both P < 0.05). Additionally, the ocular bulbar redness value was significantly higher in the affected eye [(1.75 ± 0.38)] than in the healthy eye [(1.65 ± 0.47), t = 2.16, P < 0.05]. After treatment, both groups exhibited significant increases in BUT and TMH compared with their pre-treatment values ( t = -6.27, -4.21, -2.56, -3.12, all P < 0.05). Furthermore, both groups showed significant decreases in ocular bulbar redness values compared with pre-treatment values ( t = 3.04, 3.32, both P < 0.05). In group A, the corneal fluorescein staining score post-treatment was significantly lower than the pre-treatment value ( Z = 2.10, P < 0.05). However, in group B, the FL score did not show a significant difference between pre-treatment and post-treatment. ( Z = 0.03, P > 0.05). There were also no significant differences in the surface regularity index between the two groups both before and after treatment ( t = 1.35, 0.65, both P > 0.05). Conclusions:Blepharospasm can affect the stability of the tear film on the ocular surface, and BTX-A injection can help relieve dry eye caused by essential blepharospasm.

Lung cancer is one of the malignant tumours with the highest morbidity and mortality rates worldwide today, posing a major threat to human health. Accurate diagnosis and standardised treatment play a crucial role in improving the survival rate of lung cancer patients. In recent years, the rapid rise of artificial intelligence (AI) has brought about significant changes in the medical field, providing a new diagnostic and treatment model for lung cancer, and making a series of breakthroughs in lung cancer diagnostic imaging, pathological diagnosis, surgical oncology, radiotherapy, and drug development and treatment. This article introduces the current status of AI application in the field of lung cancer diagnosis and treatment, and extensively discusses the current challenges and future prospects, hoping to provide references and suggestions for future clinical practice.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Lung squamous cell carcinoma (LUSC) is an important pathological subtype of NSCLC. The complex immune escape mechanism limits the effectiveness of immunotherapy. Ficolin-3 (FCN3) is a crucial immunomodulatory molecule that regulates immune escape by remodeling the tumor microenvironment. However, the role of FCN3 in LUSC remains unclear. This study employed bioinformatics methods to analyze LUSC samples from The Cancer Genome Atlas (TCGA) database. The aim of this study was to explore the potential biological functions and prognostic significance of FCN3 in LUSC. METHODS: A pan-cancer analysis characterized the expression patterns and prognostic value of FCN3 across various cancer types. Simultaneously, the expression patterns of FCN3 in LUSC samples from the TCGA database and its relationship with prognosis were analyzed. The Nomogram model and somatic mutation analysis, differential expression analysis, correlation analysis, as well as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were constructed to explore the potential mechanisms of FCN3. Additionally, immune infiltration analysis, immune escape score (TIDE), and correlation analysis of immune-related molecules were used to reveal the regulatory role of high FCN3 levels on immunity in LUSC. Furthermore, the correlation between FCN3 expression characteristics and drug sensitivity was evaluated. Finally, in vitro experiments verified the expression characteristics of FCN3 in LUSC. RESULTS: The expression level of FCN3 in LUSC tissues was significantly lower than that in normal tissues. Patients with high FCN3 expression in LUSC had a poorer prognosis compared to those with low expression. Different expression levels of FCN3 were associated with the abundance of immune cell infiltration and immune cell dysfunction. It was also linked to the expression of immune checkpoints, immune stimulatory molecules, major histocompatibility complex (MHC) class molecules, and chemotherapy drug sensitivity. CONCLUSIONS High expression of FCN3 in LUSC is associated with poor prognosis and is linked to immune cell infiltration, immune-related pathways, and immune-related molecules. FCN3 may be a potential prognostic marker and a new target for immunotherapy in LUSC.
Humans ; Lung Neoplasms/immunology* ; Immunotherapy ; Biomarkers, Tumor/metabolism* ; Prognosis ; Lectins/metabolism* ; Carcinoma, Squamous Cell/immunology* ; Ficolins ; Gene Expression Regulation, Neoplastic