ObjectiveTo investigate the dynamic expression profiles and potential regulatory mechanisms of long non-coding RNAs （lncRNAs） in male reproductive system aging. MethodsA naturally aging C57BL/6 mouse model was used and 4 mice were selected each at 3， 15， and 21 months of age. RNA was extracted from seven regions of the male reproductive tract （testis， efferent duct， initial segment of epididymis， caput epididymis， corpus epididymis， cauda epididymis， and vas deferens）， followed by RNA sequencing and bioinformatics analysis. ResultsRegion-specific dynamic expression profiles of lncRNAs were constructed in the testis， epididymis （efferent duct， initial segment， caput， corpus， and cauda）， and vas deferens of male mice. Combined with gene functional enrichment analysis， the functional associations of lncRNAs were elucidated in reproductive system aging. The differentially expressed lncRNAs in the aging testis were primarily involved in hormone biosynthesis and extracellular matrix organization， while those in the initial segment of the epididymis were closely related to cell recognition and epithelial cell migration. A comprehensive lncRNA expression atlas associated with male reproductive aging was established. ConclusionLncRNAs may participate in male reproductive aging through the regulation of the reproductive microenvironment， which provides key molecular targets and a research foundation for understanding age-related fertility decline.

ObjectiveTo investigate the effects of Guizhi Jia Longgu Mulitang on the expression difference of interleukin-10 （IL-10） and tumor necrosis factor -α （TNF-α） in related organs of insomnia rats with sensory dysfunction dominated by lung and study the mechanism of Guizhi Jia Longgu Mulitang in improving insomnia. MethodSD rats were randomly divided into the blank group， model group， western medicine group， and traditional Chinese medicine （TCM） group， with 10 rats in each group. The rats were deprived of sleep by shallow water environment method in a long platform， and the modeling lasted for 42 d. The blank group and model group were given 0.05 mL·kg^-1 normal saline by gavage， and the western medicine group and TCM group were given drugs during modeling. To be specific， the western medicine group was given 0.105 mg·kg^-1 dexzopiclone tablet by gavage， while the TCM group was given 7 600 mg·kg^-1 Guizhi Jia Longgu Mulitang by gavage， both lasting for 28 days. After successful modeling， the Morris water maze experiment was performed on the 42nd day to detect the motion and spatial memory ability of rats. The levels of IL-10 and TNF-α in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression of IL-10 and TNF-α in the lung and brain tissue of rats was detected by Western blot. The levels of IL-10 and TNF-α in the lung and brain tissue of rats were detected by immunohistochemistry. ResultCompared with the blank group， the sleep stages non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) of the model group were significantly shortened （P<0.5， P<0.01）， and the wake stage was significantly increased （P<0.01）. The total time and distance of platform exploration were significantly increased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly decreased （P<0.01）. ELISA results showed that the serum IL-10 level was significantly decreased （P<0.01）， and TNF-α level was significantly increased （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain and lung tissue of rats was significantly decreased （P<0.01）， and the protein expression of TNF-α was significantly increased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in the brain and lung tissue of rats was significantly decreased （P<0.01）， and that of TNF-α was significantly increased （P<0.01）. Compared with the model group， the NREM stage and REM stage of the western medicine group and the TCM group were significantly increased （P<0.5， P<0.01）， and the wake stage was shortened （P<0.5）. The total time and distance of platform exploration were significantly decreased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly increased （P<0.05， P<0.01）. The serum IL-10 level was significantly increased （P<0.01）， and the serum TNF-α level was significantly decreased according to the ELISA results （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.01）， and the protein expression of TNF-α was significantly decreased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.05， P<0.01）， and the expression of TNF-α was significantly decreased （P<0.05， P<0.01）. ConclusionGuizhi Jia Longgu Mulitang can improve the expression of IL-10 and TNF-α in brain and lung tissue of insomnia rats with sensory dysfunction dominated by lung， prolong sleep time， and then improve insomnia. The mechanism may be related to improving the expression level of inflammatory factors.

OBJECTIVE To optimize the freeze-drying process for sheep placenta slices. METHODS An orthogonal test design was used with pre-freezing time， drying time and drying temperature as indicators to screen for the optimal freeze-drying process for sheep placenta slices. The peptide content， ethanol-soluble extract content， and freeze-drying rate of sheep placenta were used as indicators，the analytic hierarchy process-criteria importance through intercriteria correlation （AHP-CRITIC） method was employed to determine the weight of each indicator and calculate the comprehensive score， which was verified using the technique for order of preference by similarity to ideal solution （TOPSIS） model. RESULTS The optimal preparation process was found to be the pre-freezing time of 2 hours， the drying time of 16 hours， and the drying temperature of 30 °C. The average values of peptide content， ethanol-soluble extract content， and freeze-drying rate for three batches of samples were 5.883 mg/mL， 27.1%， and 95.77%， respectively； the comprehensive scores of three batches were 96.42， 99.18 and 99.58， with RSD of 1.75%. CONCLUSIONS This study successfully optimized the freeze-drying process for sheep placenta slices， which can provide a reference for the quality standard setting and industrial production of this type of slice.

Objective To establish an artificial intelligence (AI)-assisted platform for detection of parasite eggs, and to evaluate its detection efficiency and accuracy, so as to provide technical supports for elimination of parasitic diseases. Methods A total of 1 003 slides of Enterobius vermicularis, horkworm, Trichuris trichiura, Clonorchis sinensis, Taenia, Ascaris lumbricoides, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski eggs were collected, and converted into digital images with an automatated scanning microscope to create a dataset. Based on the Object Detection platform on the Baidu Easy DL model, an AI-assisted platform for detection of parasite eggs was created through procedures of uploading, labeling, training, evaluation and optimization. Then, 70% of the datasets were randomly selected for model training, and the precision, recall and average accuracy were calculated to evaluate the effectiveness of platform for recognition of parasite eggs. In addition, the platform was deployed on the computer and smart phone terminals for use. Results An AI-assisted platform for detection of parasite eggs was successfully created. If the platform was deployed using the public cloud application programming interface (API), the average accuracy, precision and recall of the platform were 93.42%, 92.55% and 89.32% for recognition of parasite eggs. If the platform was deployed using the offline software development kit (SDK), the average accuracy, precision and recall of the platform were 92.97%, 94.78% and 87.63% for recognition of parasite eggs. In addition, the precision of the platform was 97.00% and 96.23% for identification of Taenia and C. sinensis eggs, respectively. Conclusions The AI-assisted platform for detection of parasite eggs has been successfully created, which is high in the accuracy for recognition of parasite eggs and convenient in use. This platform may provide a powerful technical support for parasitic disease diagnosis.

The liver is a common metastatic site of malignant tumors,and liver metastasis is also the leading cause of death due to metastatic tumors.Metastatic liver cancer has high heterogeneity,and there has been slow progress in the treatment of metastatic liver cancer for a long time.In recent years,the development of surgical techniques,systemic therapy,and the multidisciplinary team(MDT)diagnostic and therapeutic mode has led to revolutionary changes in the clinical management of metastatic liver cancer.The article reviews the recent progress in the treatment of metastatic liver cancer from the three aspects of surgical treatment,systemic therapy,and locoregional therapy.Combined therapy based on chemotherapy,targeted therapy,and immunotherapy remains the basic multimodality therapy for metastatic liver cancer.In addition,the development of locoregional therapy has brought new treatment options for patients with metastatic liver cancer.Standardized diagnosis and treatment based on high-level evidence-based evidence and related guidelines and individualized precise treatment under the guidance of MDT will be the future directions for the clinical management of metastatic liver cancer.

Effective treatment of colorectal cancer liver metastases is crucial for improving the survival rate and quality of life of patients with colorectal cancer.With the application of systemic chemotherapy,there have been increases in the conversion rate and surgical resection rate of patients with colorectal cancer liver metastases.Non-radical resection is one of the surgical strategies in tumor surgery.This article reviews the treatment of patients with initially unresectable colorectal cancer liver metastases,including extrahepatic metastasis,R1 resection of liver metastases,staged surgery for liver metastases,and debulking surgery,as well as the application of non-radical resection in the treatment of colorectal cancer liver metastases.

Objective:To explore the effects of tyrosine kinase inhibitors (TKI) on SARS-CoV-2 infection, the related symptoms, and recovery in patients with chronic myeloid leukemia (CML) during the SARS-CoV-2 epidemic.Methods:A retrospective case series study was conducted. The information including general data and SARS-CoV-2 infection of 319 CML patients treated in the First Affiliated Hospital of Soochow University from January 2021 to December 2021 and 547 co-residents during the SARS-CoV-2 epidemic was collected by telephone follow-up from December 2022 to January 2023. The differences in clinical characteristics, infection rate, symptom severity, and recovery time of the SARS-CoV-2 between CML patients and their co-residents, between patients whether getting vaccine for SARS-CoV-2, between patients whether receiving TKI and among CML patients receiving different types of TKI were compared. The multivariate logistic regression analysis was used to analyze the factors influencing the infection rate, symptom severity, and recovery time of SARS-CoV-2.Results:The median age [ M ( Q1, Q3)] of CML patients was 46 years (36 years, 57 years) and all 319 CML patients included 188 (59.0%) males and 131 (41.0%) females; the median age of co-residents of CML patients was 41 years (22 years, 55 years), and all 547 co-residents included 266 (48.6%) males and 281 (51.4%) females. There were statistically significant differences in age, gender, vaccination against SARS-CoV-2 or not, infection rate [83.7% (267/319) vs. 90.5% (495/547)], distribution of symptomatic patients at different severity levels (mild, moderate, severe, and fatal), and recovery time [7 d (5 d, 14 d) vs. 6 d (2 d, 8 d)] between CML patients and co-residents (all P < 0.05). There were statistically significant differences in age, gender, SARS-CoV-2 infection rate, distribution of symptomatic patients at different severity levels and recovery time between CML patients (143 cases) and their co-residents (517 cases) who received the SARS-CoV-2 vaccine (all P < 0.05); there were no statistically significant differences in age, gender, infection rate, distribution of symptomatic patients at different severity levels and recovery time between vaccinated and unvaccinated CML patients with SARS-CoV-2 vaccine (all P > 0.05). There were 297 (93.1%) CML patients who took TKI and 22 patients who did not take TKI. There were no statistically significant differences in age and gender distribution between patients taking TKI and those not taking TKI (all P > 0.05). The infection rate of SARS-CoV-2 in patients taking TKI was lower than that of patients not taking TKI [82.5% (245/297) vs. 100.0% (22/22)], and the difference was statistically significant ( P = 0.032); however, there were no significant differences in distribution of symptomatic patients at different severity levels and recovery time between patients taking TKI and those not taking TKI (all P > 0.05). The results of multivariate logistic regression analysis showed that TKI therapy was an independent protective factor for SARS-CoV-2 infection in CML patients (taking TKI vs. not taking TKI: OR = 1.970, 95% CI: 1.093-3.554, P = 0.024), and was an independent risk factor for severe symptoms of SARS-CoV-2 infection (assigning mild, moderate, severe and fatal levels the value of 0, 1, 2, 3; OR = 0.042, 95% CI: 0.004-0.421, P = 0.007) and recovery time exceeding 7 d (> 7 d vs. ≤ 7 d, OR = 0.649, 95% CI: 0.426-0.988, P = 0.044). The third TKI therapy was given in 1 patient, and there were no statistically significant differences in SARS-CoV-2 infection rate, the symptoms at different severity levels and recovery time > 7 d between CML patients receiving first generation TKI (63 cases) and those receiving second generation TKI (77 cases) who were vaccinated against SARS-CoV-2 (all P > 0.05). Conclusions:TKI can reduce the infection rate of SARS-CoV-2 in CML patients, but will aggravate the severity of symptoms and prolong the recovery time. TKI types may have no impact on whether infected with SARS-CoV-2, the severity level of symptoms after infection and recovery time.

Objective:To understand the current status of existential distress in patients with advanced lung cancer and analyze its influencing factors, so as to provide a reference for developing targeted intervention programs.Methods:A total of 320 patients with advanced lung cancer were selected using convenience sampling from two Class Ⅲ Grade A hospitals in Weifang between February 2022 and August 2023. The data were collected using a General Information Questionnaire, the Chinese Version of the Existential Distress Scale (EDS), the Social Support Revalued Scale (SSRS), the Chinese Version of the Strategies Used by People to Promote Health (SUPPH), and Patient Health Questionnaire-9 (PHQ-9). Spearman correlation analysis was conducted to analyze the relationships between EDS, SSRS, SUPPH, and PHQ-9 scores, and multiple linear regression analysis was used to identify the influencing factors of existential distress in patients with advanced lung cancer. A total of 320 questionnaires were distributed, with 318 valid responses, yielding a valid response rate of 99.38% (318/320) .Results:The total EDS score for the 318 patients was 3.00 (2.00, 4.00). EDS scores were positively correlated with PHQ-9 scores and negatively correlated with SSRS and SUPPH scores ( P<0.01). Multiple linear regression analysis showed that marital status, social support, self-management efficacy, and depression were influencing factors of existential distress in patients with advanced lung cancer ( P<0.05) . Conclusions:Patients with advanced lung cancer experience mild existential distress. Medical staff should assess existential distress levels, paying close attention to patients who are divorced or widowed, have low levels of social support and self-management efficacy, or are experiencing depression. Early interventions should be developed to alleviate negative emotions and help patients rebuild their sense of meaning, thereby improving psychological well-being and reducing survival distress.

Objective To explore the mechanism of Yanggan Anhun Decoction in the treatment of insomnia with liver failing in storing soul type based on network pharmacological methods;To perform animal model validation.Methods The drug components and targets of Yanggan Anhun Decoction were retrieved from TCMSP and BATMAN-TCM databases,and the targets of insomnia with liver failure store soul type were retrieved from GeneCards,NCBI and DisGeNET databases.By constructing a protein-protein interaction(PPI)network and analyzing GO and KEGG pathway enrichment,the signaling pathway of Yanggan Anxin Decoction in treating insomnia with liver failing in storing soul type was determined,and molecular docking was performed between the main active components and core targets.24 SD rats were randomly divided into normal group,model group,TCM group and Western medicine group,with 6 rats in each group.The insomnia model rats with liver failing in storing soul type were constructed by compound multi factor stimulation method,and were given drugs for 14 days.The cognitive memory ability of rats were detected by Morris water maze test;Nissl staining was used to observe the morphology and number of Nissl bodies in the hypothalamus of rats;serum IL-6 and TNF-α contents were detected by ELISA;IL-6 and TNF-α in hypothalamus and Bcl-2,Bax protein expression levels of rats were detected by immunohistochemistry.The relative expressions of p38 MAPK,p-p38 MAPK,Bcl-2,Bax proteins in the hypothalamus of rats were detected by Western blot.Results A total of 301 active components,321 potential targets and 92 key targets were obtained.Key active components such as quercetin,kaempferol,luteolin,wogonin,sebiferic acid and β-sitosterol,as well as core targets such as MAPK,IL6 and TNF were obtained after screening.The key targets mainly focused on various signaling pathways such as TNF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,dopaminergic synapse,and neuroactive ligand-receptor interaction,etc.Kaempferol,quercetin,digitonin and other flavonoids had good binding activity and stability with MAPK,TNF,IL6 and showed good affinity.The results of animal experiments showed that,compared with the normal group,the cognitive memory ability of the model group decreased(P<0.05),Nissl bodies were stained shallowly,the density was lower,the cell body was shrunk and deformed,the cell nucleus was broken and dissolved,and the serum and hypothalamic IL-6,TNF-α increased(P<0.05),the expressions of p-p38 MAPK/p38 MAPK and Bax in hypothalamus increased(P<0.05),while the expressions of Bcl-2 and Bcl-2/Bax decreased(P<0.05);compared with the model group,the cognitive memory ability of the TCM group and the Western medicine group were improved,the number of Nissl bodies significantly increased,the nucleus was clear,the cell body shrinkage and deformation were improved(P<0.05),the levels of IL-6 and TNF-α in serum and hypothalamus decreased(P<0.05),while the expressions of p-p38 MAPK/p38 MAPK and Bax decreased,and the expression of Bcl-2 and Bcl-2/Bax increased(P<0.05).Conclusion Yanggan Anhun Decoction may play its effects in treating insomnia with liver failing in storing soul type by regulating MAPK,TNF,IL6,Bcl-2,Bax and other core targets,and interfering with p38MAPK signaling pathway.

Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
Mice ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Mice, Nude ; Epithelial-Mesenchymal Transition ; Thyroid Neoplasms/pathology* ; Extracellular Vesicles/pathology* ; Mesenchymal Stem Cells ; Transcription Factors, TFIII/metabolism* ; Neoplastic Stem Cells/pathology*