ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

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.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective:To explore the potential categories of psychological distress in spousal caregivers of stroke patients and differences in quality of life between categories, in order to provide a theoretical basis for early clinical identification and provision of individualized and targeted interventions for psychological distress in spousal caregivers of stroke patients and improvement of their quality of life.Methods:A total of 207 spouse caregivers of stroke patients hospitalized in three class 1-Grade A hospitals in Yinchuan city of Ningxia Hui Autonomous Region, who met the inclusion and exclusion criteria were selected from December 2020 to July 2021 by convenience sampling method as study subjects. The general information questionnaire, Kessler Psychological Distress Scale, and the Mos 36-Item Short from Health Survey were used for a cross-sectional survey.Results:A total of 203 spousal caregivers of stroke patients were finally investigated, 46 males and 157 females with a age of (58.65 ± 9.66) years. Psychological distress among spousal caregivers of stroke patients was categorized into 3 potential categories:no distress group (40%, 81/203), listlessness group (45%, 91/203) and helplessness and restlessness group (15%, 31/203). The psychological distress subgroup was a factor influencing the quality of life of spousal caregivers of stroke patients ( t=-10.03, P<0.05), explaining 33.0% of the variance in quality of life. Conclusions:Psychological distress in spousal caregivers of stroke patients is significantly heterogeneous. Those in the helplessness and restlessness group have the lowest quality of life and should be given focused attention and early intervention.

Objective:To discuss the diagnosis and treatment process of the patients with parasitic leiomyoma(PM)of the abdominal wall complicated with disseminated peritoneal leiomyomatosis(DPL)after laparoscopic myomectomy,and to improve the clinical understanding and management of this condition.Methods:The clinical data of one patient with PM of the abdominal wall complicated with DPL after laparoscopic myomectomy were collected.The causes,clinical features,diagnosis,differential diagnosis and treatment process were analyzed,and the relevant literatures were reviewed.Results:The patient,a 49-year-old woman,was admitted due to a self-discovered abdominal mass lasting for one year.The physical examination results showed a palpable mass,approximately 6 cm×4 cm,in the lower left abdominal wall with poor mobility,with clear borders,and without tenderness.Another palpable mass,approximately 7 cm×5 cm,was found in the lower right abdomen with fair mobility,with clear borders,and without tenderness.The gynecological ultrasonography results showed a hypoechoic area of approximately 6.6 cm × 2.7 cm in the subcutaneous tissue below the left umbilicus and another hypoechoic area of approximately 7.6 cm×3.3 cm in the abdominal cavity below the umbilicus.The superficial ultrasonography of the local area showed a hypoechoic area of approximately 5.79 cm× 2.55 cm×4.74 cm within the left lower abdominal rectus muscle,with smooth edges,located 1.97 cm from the skin at its shallowest point and 4.73 cm at its deepest point,without penetration of the rectus sheath but adjacent to the peritoneum.The patient was diagnosed as uterine leiomyoma,abdominal mass,and post-myomectomy status.The elective surgeries for uterine leiomyoma enucleation,abdominal wall leiomyoma excision,and peritoneal leiomyoma excision were performed under combined intravenous-inhalation anesthesia.The operation procedure was successful,and the patient recovered well and was discharged smoothly.Conclusion:PM and DPL lack typical clinical features and require imaging examinations for diagnosis.Surgical exploration is the main treatment modality,and while PM and DPL are generally benign,there is a potential for malignant transformation,and the patients need further postoperative follow-up.

Objective To investigate the effects of terahertz(THz)radiation on mouse testicular tissue and its potential molecular mechanisms.Methods A total of 125 male C57BL/6J mice(6～8 weeks old)were randomly divided into control group and low-,medium-and high-radiation power groups.The mice of the latter 3 groups were exposed to THz radiation at a frequency of 2.5 T,with an average power density of 38,115,or 318 mW/cm2,for 5 or 10 min.The detection time was immediately or 24 h after exposure.HE staining was used to observe pathological damage.ELISA was employed to detect the expression of inflammatory factors in testicular tissue.RNA-seq was utilized to detect the global changes of gene expression.The differentially expressed genes(DEGs)were screened and bioinformatics was used to cluster them.The screened genes were further analyzed with RT-qPCR to determine the time-dependent and dose-dependent relationships of the expression with THz exposure.Finally,sperm quality was evaluated morphologically using a microscope.Results Three doses of THz radiation exposure did not cause significant pathological damages to mouse testicular tissue.TNF-α expression was increased immediately after exposure at average power density of 115 mW/cm2(P＜0.01),and the expression of IL-1β and TNF-α were both increased when the dose reached 318 mW/cm2(P＜0.01).However,all the 3 factors returned to normal levels in 24 h after exposure.RNA-seq results showed that THz radiation exposure caused abnormal expression of 56 genes.Cluster analysis indicated that these DEGs were mainly enriched in immune and inflammatory responses,enzyme activity,sperm development and capacitation functions.Then for 5 selected key genes,Crisp1,Adam7,Ltf,Rnase9,and Bsph1,the expression of Crisp1 and Rnase9 was decreased immediately after exposure to 115 mW/cm2 THz radiation,the dose of 318 mW/cm2 resulted in obvious changes in the expression of the 5 genes(P＜0.05),and their expression returned to normal levels in 24 h after exposure.Morphological observation displayed that exposure to all the 3 doses of THz had no influence on sperm quality.Conclusion THz radiation exposure causes temporary inflammatory response in testicular tissue and abnormal expression of sperm functions-related genes.However,these changes return to normal 24 h after exposure,and additionally,do not impair sperm quality.

Objective To investigate the clinical characteristics of 16 patients with connective tissue diseases associated interstitial lung disease(CTD-ILD)complicated with lung cancer,and to improve the cognition of the disease.Methods Clinical data of 16 patients diagnosed as CTD-ILD associated with lung cancer,who were admitted to our center,were retrospectively analyzed,including general conditions,clinical characteristics,auxiliary examinations,pathological classification of lung cancer,TNM type,treatment and clinical outcome.Results Among the 16 CTD-ILD patients with lung cancer,there were 12 males and 4 females.The mean age at diagnosis of CTD-ILD was(64.7±9.2)years,and the mean age at diagnosis of lung cancer was(66.6±8.7)years.Lung occupying space on imaging(62.5%)was the most common initial symptom in lung cancer patients,followed by cough and phlegm(12.5%)and chest pain(12.5%).Of patients with lung cancer,adenocarcinoma(8 cases,50.0%)was the most common pathological type,followed by small cell lung cancer(4 cases,25.0%).The diagnosis time of CTD-ILD was earlier than that of lung cancer in 8 cases(50.0%),with a median time of 36.0(11.3,57.0)months,followed by 7 cases(43.8%)of CTD-ILD diagnosed with lung cancer at the same time.The diagnosis time of lung cancer was earlier than that of CTD-ILD in 1 case(6.3%).The most common TNM stage for lung cancer was stage Ⅳ(9 cases,56.25%).Sixteen patients were followed up from 1 to 64 months,with a median of 8.5(1.5,14.3)months.Eleven patients(68.8%)died,including 8 patients(72.7%)died of infection and 3 patients(27.3%)died of end-stage lung cancer.Conclusion For CTD-ILD patients,close follow-up and regular imaging monitoring are necessary to help early detection of lung cancer and improve prognosis.

Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer and the third leading cause of cancer-related deaths,and it is a serious threat to human health and has become a clinical problem that needs to be solved urgently.Extracellular vesicles(EV)are membrane vesicles containing multiple components and play an important role in the development and progression of HCC.This article summarizes the effect of EVs of different origins on HCC and analyzes the mechanism of action of EV on HCC,so as to provide new perspectives for the diagnosis and treatment of HCC.

Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.