ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

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 epidemic characteristics and factors influencing mortality in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients in heilongjiang region. Methods The clinical data of 712 HIV-infected patients attending our hospital from January 2019 to December 2023 were analyzed retrospectively. The HCV infections were detected by ELISA, and epidemic characteristics of HIV/HCV co-infected patients were analyzed . Co-infected patients (n=116) were classified into survival group (n=90) and death group (n=26) according to the follow-up results, and risk factors for the mortality of HIV/HCV co-infected patients were identified. Results The prevalence of HIV/HCV co-infection was 16.29%, and the prevalence was the highest in 30-50 age group, accounting for 25.47%. There was no significant difference in co-infection rates by gender and marital status (P>0.05). The co-infection rate was the highest among farmers (26.85%) by occupation and among intravenous drug users (61.90%) by route of infection. No statistical difference was found in gender, marital status, and occupational status between survival group and death group (P>0.05), whereas statistical difference was found in age at diagnosis of HIV infection, route of infection, antiretroviral treatment, percentage of CD4+T lymphocytes, and interval between diagnosis and initiation of treatment between two groups (P<0.05). Multivariate Logistic regression analysis denoted that age at diagnosis of HIV infection (OR=1.827, 95% CI: 1.263-2.722), route of infection (OR=1.796, 95% CI: 1.248-2.503), antiretroviral treatment (OR=1.724, 95% CI: 1.202-2.367), percentage of CD4+T lymphocytes (OR=2.536, 95% CI: 1.776-3.739), and the time interval between diagnosis and initiation of treatment (OR=1.953, 95% CI: 1.431-2.952) were all associated with the risk of mortality in co-infected patients (P<0.05). Conclusion The overall prevalence of HIV/HCV co-infection is 16.29% in heilongjiang region . In order to reduce the mortality rate of superinfection , we should focus on patients who are ≥ 40 years old, intravenous drug use , no antiviral therapy , low CD4+ T lymphocyte levels for the first time , and have a long interval between diagnosis and initiation of treatment.

Objective:To investigate the effects of Xiaomudan Granules on PERK/eIF2α/ATF4 pathway and lipid metabolism in NAFLD mice.Methods:Totally 60 mice were divided into a normal group of 10 mice and a high-fat diet group of 50 mice. The high-fat diet group was given a high-fat diet to establish a NAFLD mouse model. The high-fat feed group was divided into model group, metformin group, and Xiaomudan Granules low-, medium-, and high-dosage groups according to the random number table method. Xiaomudan Granules low-, medium-, and high-dosage groups were orally administered with concentrated Xiaomudan Granules at dosages of 11.7, 23.4, and 46.8 g/kg, respectively. The metformin group was orally administered with metformin solution at a dose of 0.2 g/kg, while the normal group and model group were orally administered with distilled water of equal volume once a day for 8 consecutive weeks. The liver oil red O staining of mice was observed in each group. The protein expressions of p-PERK, p-eIF2α, ATF4, C/EBP homologous protein (CHOP), CCAAT enhancer binding protein alpha (C/EBPα), C/EBPβ, and steroid regulatory element binding protein 2 (SREBP2) were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of ATF4, CHOP, C/EBPα, C/EBPβ, and SREBP2.Results:The liver tissue structure and steatosis of mice were improved in Xiaomudan Granules groups. Compared with the model group, the expressions of p-PERK/PERK, ATF4, C/EBPα, C/EBPβ, and SREBP2 proteins decreased in Xiaomudan Granules groups and the metformin group ( P<0.01 or P<0.05). The expressions of p-eIF2α/eIF2α and CHOP proteins decreased in the Xiaomudan Granules medium- and high-dosage groups and the metformin group ( P<0.01); compared with the model group, the levels of ATF4, CHOP, C/EBPα, and C/EBPβ mRNA in Xiaomudan Granules groups and the metformin group decreased ( P<0.01), while the levels of SREBP2 mRNA in the Xiaomudan Granules medium- and high-dosage groups and the metformin group decreased ( P<0.01). Conclusion:Xiaomudan Granules may improve liver lipid metabolism and reduce liver fat deposition in NAFLD mice by regulating the PERK/eIF2α/ATF4 pathway.

Objective To observe the clinical efficacy of Lingnan fire needle therapy combined with conventional western medicine in the treatment of mild to moderate uterine prolapse.Methods A total of 96 patients diagnosed with mild to moderate uterine prolapse in the outpatient and inpatient departments of Dongguan Humen Traditional Chinese Medicine Hospital from January 2023 to January 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 48 cases in each group.Both groups received health education,and the control group received conventional western medicine treatment.The observation group received Lingnan fire needle therapy in addition to the control group's treatment.The treatment course consisted of 12 sessions,with one course completed.After treatment,the clinical efficacy of the two groups was evaluated.Changes in TCM syndrome scores,pelvic floor muscle strength,and ultrasound imaging characteristics were observed before and after treatment.The serum levels of osteopontin(OPN),connective tissue growth factor(CTGF),and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1(MMP-9/TIMP-1)were compared before and after treatment.The safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 97.92%(47/48),while it was 77.08%(37/48)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the TCM syndrome scores and total scores in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the pelvic floor muscle strength and ultrasound imaging characteristics in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these aspects compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the serum levels of OPN,CTGF,and MMP-9/TIMP-1 in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Lingnan fire needle therapy combined with conventional western medicine can significantly improve symptoms and pelvic floor muscle strength in patients with mild to moderate uterine prolapse,with notable efficacy and high safety.The mechanism may be related to the regulation of OPN,CTGF,and MMP-9/TIMP-1 levels.

OBJECTIVE To explore the effect and mechanism of Buyang huanwu decoction （BYHWD） on mitochondrial dynamics in rats with cerebral ischemia-reperfusion injury （CIRI）. METHODS CIRI rats were randomly divided into CIRI group， low-dose BYHWD （L-BYHWD， intragastric administration of 3.15 mg/kg BYHWD） group， high-dose BYHWD （H-BYHWD， intragastric administration of 12.60 mg/kg BYHWD） group， positive control （intraperitoneal administration of 150 mg/kg Extract of Ginkgo biloba leaves injection） group， H-BYHWD+solvent control （intragastric administration of 12.60 mg/kg BYHWD+ intraperitoneal injection of 20 mg/kg DMSO） group and H-BYHWD+Compound C （intragastric administration of 12.60 mg/kg BYHWD+intraperitoneal injection of 20 mg/kg Compound C） group， with 15 rats in each group. Additionally， 15 rats were assigned to the sham operation group. All rats received the corresponding medications or saline solution via intragastric administration or intraperitoneal injection once daily for 4 consecutive weeks. After the last administration， the cerebral infarct volume of rats was measured； the ultrastructure of mitochondria in endothelial cells in the ischemic penumbra （IP） region was observed； the mitochondrial membrane potential was evaluated； the fluorescence colocalization area ratio of optic atrophy 1 （OPA1） to cluster of differentiation 31 （CD31） in the IP region was detected； the expressions of mitofusin 2 （MFN2）， OPA1， mitochondrial fission 1 protein （Fis1）， and proteins related to the AMP-activated protein kinase （AMPK）/dynamin-related protein 1 （Drp1） pathway in the IP region were determined. RESULTS Compared with the sham operation group， mitochondria in endothelial cells of the IP region in brain tissue of rats in the CIRI group were swollen， mostly spherical， with fractured cristae and severe vacuolation； the percentage of cerebral infarct volume， Fis1 expression level and phosphorylation level of Drp1 were increased significantly （P＜0.05）， while mitochondrial membrane potential in the IP region， fluorescence colocalization area ratio of OPA1 to CD31， the expressions levels of MFN2 and OPA1， and phosphorylation level of AMPK were significantly decreased （P＜0.05）. These indicators were improved in the L-BYHWD group， H-BYHWD group， and positive control group， M025） compared with the CIRI group （P＜0.05）. Compared with the H-BYHWD group and H-BYHWD+solvent control group， the above indicators of rats in the H-BYHWD+Compound C group showed significant reversal（P＜0.05）. There was no statistically significant difference in the above indicators between the H-BYHWD+solvent control group and the H-BYHWD group （P＞0.05）. CONCLUSIONS BYHWD may improve CIRI by activating the AMPK/Drp1 pathway and ameliorating mitochondrial dynamic disorders.

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

The armadillo repeat containing 5 (ARMC5) gene is part of a family of protein-coding genes that are rich in armadillo repeat sequences, are ubiquitously present in eukaryotes, and mediate interactions between proteins, playing roles in various cellular processes. Current research has demonstrated that reduced expression or absence of the ARMC5 gene in various tumor tissues can lead to uncontrolled cell proliferation, thereby inducing a range of diseases. The ARMC5 gene was initially extensively studied in the context of bilateral macronodular adrenocortical disease (BMAD), with harmful pathogenic variants in ARMC5 identified in approximately 50% of BMAD patients. With advancing research, scientists have discovered that ARMC5 pathogenic variants may also have potential effects on other diseases and could be associated with increased susceptibility to certain cancers. This review aims to present the latest research progress on how the ARMC5 gene plays its role in tumors. It outlines the basic structure of ARMC5 and the regions where it functions, as well as the diseases currently proven to be associated with ARMC5. Moreover, some evidence suggests its relation to embryonic development and the regulation of immune system activity. In conclusion, the ARMC5 gene is a crucial focal point in genetic and medical research. Understanding its function and regulation is of great importance for the development of new therapeutic strategies related to diseases associated with its pathogenic variants.
Humans ; Neoplasms/genetics* ; Armadillo Domain Proteins/genetics* ; Animals ; Genetic Predisposition to Disease ; Cytoskeletal Proteins/genetics* ; Tumor Suppressor Proteins/genetics*

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*