OBJECTIVE To investigate the effects of quercetin （QUE） on intervertebral disc degeneration in rats with lumbar intervertebral disc herniation （LDH） and explore its mechanism based on the forkhead box protein O3/silent information regulator 1 （FOXO3/Sirt1） pathway. METHODS A rat model of LDH was established. The successfully modeled rats were randomly divided into LDH group （gavaged with and intraperitoneally injected with an equal volume of normal saline）， QUE-L group （gavaged with 50 mg/kg QUE+intraperitoneally injected with an equal volume of normal saline）， QUE-H group （gavaged with 100 mg/kg QUE+ intraperitoneally injected with an equal volume of normal saline）， and QUE-H+EX-527 （a Sirt1 inhibitor） group （gavaged with 100 mg/kg QUE+intraperitoneally injected with 1 mg/kg EX-527）， with 12 rats in each group. Additionally， 12 healthy normal rats were selected as the control group （gavaged with and intraperitoneally injected with an equal volume of normal saline）. All rats were administered the corresponding agents once daily for consecutive 8 weeks. After the final administration， the pain threshold and serum levels of inflammatory factors in rats were measured； pathological damage of lumbar intervertebral disc tissue was observed， the apoptosis of nucleus pulposus cells in lumbar intervertebral disc tissue was assessed， and the expression levels of matrix metalloproteinase-3 （MMP-3）， phospholipase A2 （PLA2）， as well as apoptosis-related proteins and FOXO3/Sirt1 pathway- related proteins in intervertebral disc tissue were determined. RESULTS Compared with LDH group， pathological damage of intervertebral disc tissue were improved significantly in QUE-L group and QUE-H group； paw withdrawal mechanical threshold， paw withdrawal thermal latency， the serum levels of transforming growth factor-β1 and interleukin-10 （IL-10） as well as the expression levels of B-cell lymphoma-2 （Bcl-2）， FOXO3 and Sirt1 were significantly increased or prolonged （P＜0.05）. Serum levels of tumor necrosis factor-α and IL-1β， histopathological score of intervertebral disc tissue， apoptotic rate of nucleus pulposus cells， positive expressions of MMP-3 and PLA2 in intervertebral disc tissue and expression levels of Bcl-2 associated X protein were significantly decreased （P＜0.05）. Compared with the QUE-H group， the QUE-H+EX-527 group presented aggravated pathological damage of intervertebral disc tissue， and the trends of all the above indicators were significantly reversed（P＜0.05）. CONCLUSIONS QUE can ameliorate intervertebral disc degeneration in LDH rats， and its mechanism may be related to the activation of the FOXO3/Sirt1 pathway.

Objective To investigate the role and molecular mechanisms of Exo70 in the metastasis of pancreatic cancer cells. Methods Stable cell lines with Exo70 knockdown or overexpression were established using lentiviral infection. The migration ability of pancreatic cancer cells was assessed by Transwell assay. The morphology, particle size, and secretion levels of exosomes were observed using transmission electron microscopy. Changes in the expression of Exo70 and exosomal marker proteins were detected by Western blot. The localization of multivesicular bodies (MVBs) was examined by immunofluorescence. Results Exo70 knockdown inhibited the migration ability of pancreatic cancer cells and substantially reduced the total amount of exosome secretion. By contrast, Exo70 overexpression enhanced the migration ability of pancreatic cancer cells. Immunofluorescence results showed that Exo70 knockdown induced the perinuclear accumulation of CD63 and LAMP2, leading to an increase in MVB accumulation and lysosomal degradation in pancreatic cancer cells. Conclusion Exo70 promotes the normal transport of MVBs and maintains exosome secretion. Its knockdown enhances the lysosomal degradation of MVBs, resulting in impaired exosome biogenesis and secretion and thereby inhibiting the migration of pancreatic cancer cells.

ObjectiveTo analyze the epidemiological characteristics of influenza virus in severe acute respiratory tract infection (SARI) cases in Jingzhou City, so as to provide a scientific basis for the formulation of influenza prevention and control policies in Jingzhou City. MethodsSARI surveillance was carried out in two sentinel hospitals in Jingzhou City from 2018 to 2023. Respiratory tract samples were collected from cases and influenza virus nucleic acid was measured using real-time fluorescent polymerase chain reaction (RT-PCR). ResultsA total of 2 603 SARI samples were tested from 2018 to 2023, and 338 samples were positive for influenza virus nucleic acid, with a detection rate of 12.99%. The highest positive detection rate was 20.22% in 2019, followed by 14.29% in 2022, and the lowest detection rate was 7.75% in 2020. There were significant differences for the positive detection rates of influenza in each monitoring year (χ²=30.386, P<0.001). There were epidemic peaks in the five surveillance years from 2018 to 2023 except 2020. There were winter epidemic peaks during 2018‒2019 and 2021‒2022, and an obvious summer epidemic peak was also observed from 2019 to 2022. H1N1, H3N2, B-Victoria and B-Yamagata were alternately prevalent in the six surveillance years. In 2019, H1N1, H3N2 and B-Victoria were alternately prevalent with time progress, in 2021 only B-Victoria was prevalent, and in 2022 H3N2 and B-Victoria were prevalent. There was no statistically significant difference for the positive detection rates of influenza virus between different genders (χ²=0.178, P=0.673). Among the four age groups, the positive rate of influenza virus in the age group of 15‒<25 years old was the highest (40.91%), followed by the age group of 25‒<60 years old (21.31%). There were statistically significant differences for the positive rates of influenza virus among different age groups (χ²=24.496, P<0.001). ConclusionThe surveillance of SARI cases in Jingzhou City could serve as an effective supplement to the surveillance of ILI in sentinel hospitals. It is suggested to expand the surveillance scope, strengthen public education and outreach on the prevention and control of respiratory diseases, thereby providing a scientific basis for influenza prevention and control.

OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

Since the beginning of the new century, advances in understanding the intricate interactions between oncology and the immune system have accelerated the rapid development of immune checkpoint inhibitors for the treatment of non-small cell lung cancer. However, resistance to immunotherapy is inevitable. Therefore, uncovering the mechanisms of immunotherapy resistance, proposing strategies to overcome resistance, and identifying future research directions are imperative. Given the limitations of space in each article, this review will explore the complex mechanisms underlying immunotherapy resistance. These mechanisms involve almost all cell types within the body, excluding foreign cancer cells. Notably, these cells serve as recipients (either inhibitory or stimulatory, or both) and producers of signals, playing different roles in various contexts. At the molecular level, these mechanisms include genetic and epigenetic abnormalities in all cells within the microenvironment, as well as the influence of a variety of protein kinase, growth factors, and cytokines with temporal and spatial heterogeneity. At the macroscopic level, host factors such as nutritional metabolism, comorbidities, and microbiota within the organs, as well as neuro-psychological regulation, influence the efficacy of immunotherapy.

Objective To evaluate the molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches. Methods A semi-dry and semi-wet ditch with O. hupensis snails was selected in the second branch field of Jiangbei Farm, Jiangling County, Hubei Province in May 2023, and divided into 4 experimental areas, named groups A1, A2, B1 and B2. Environmental cleaning was performed in groups A1 and B2, and was not conducted in groups A2 or B2. Then, 50% wettable powder of niclosamide ethanolamine salt was sprayed with drones at an effective dose of 2 g/m² in groups A1 and A2, and 5% niclosamide ethanolamine salt granule was sprayed with drones at an effective dose of 2 g/m² in groups B1 and B2. O. hupensis snails were surveyed using the systematic sampling method 1, 3, 5, 7, 14 days after spraying, and the natural mortality and corrected mortality of O. hupensis snails were calculated. Results The occurrence of frames with living snails, mean density of living snails and natural mortality of snails were 97.50% (117/120), 6.30 snails/0.1 m² and 1.18% (9/765) in the test ditch before spraying, respectively. There were significant differences in the mortality of snails among four groups 1, 3, 5, 7 and 14 days after spraying niclosamide formulations with drones (χ² = 17.230, 51.707, 65.184, 204.050 and 34.435, all P values < 0.01). The overall mortality rates of snails were 94.51% (1 051/1 112), 79.44% (908/1 143), 96.54% (977/1 012) and 88.55% (1 021/1 153) in groups A1, A2, B1 and B2 (χ² = 207.773, P < 0.05), respectively. In addition, there was no significant difference in the overall snail mortality between groups A1 and B1 (P > 0.05), and the snail mortality in groups A1 and B1 were both statistically different from that in groups A2 and B2 (all P values < 0.05). Conclusion Both 50% wettlable powder of niclosamide ethanolamine salt and 5% niclosamide ethanolamine salt granule sprayed with drones are active against O. hupensis snails in ditches, and environmental cleaning may improve the molluscicidal effect.

Objective To investigate the effect of AU-rich element RNA-binding factor 1(AUF1)on the proliferation,apoptosis,and migration abilities of hepatocellular carcinoma(HCC)cells and possible mechanisms,and to clarify the role and molecular mechanism of AUF1 in the progression of HCC.Methods The UALCAN and TCGA-HCC databases were used to analyze the expression of AUF1 in pan-cancer and investigate the association of the expression level of AUF1 with the clinicopathological features and prognosis of HCC patients.CCK-8 assay,cell apoptosis assay,and Transwell chamber assay were used to investigate the function of AUF1 at the cellular level,and RNA-seq assay was used to investigate transcriptome changes in HCC cells after AUF1 knockdown.The t-test was used for comparison of continuous data between two groups;the Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival rates.Results There were abnormal mRNA and protein expression levels of AUF1 in various tumor tissues compared with normal tissue(P<0.05).The mRNA expression level of AUF1 was positively correlated with the degree of HCC malignancy and the poor prognosis of early-stage HCC(P<0.05).Compared with the control group,the overexpression of exogenous AUF1 in HCC cells promoted the proliferation of HCC cells and inhibited the apoptosis and migration of HCC cells,while AUF1 knockdown inhibited HCC cell proliferation and promoted the apoptosis and migration of HCC cells.The RNA-seq analysis showed that AUF1 knockdown mainly affected the Wnt/β-catenin pathway and downregulated the protein expression level of β-catenin.Conclusion The abnormal expression of AUF1 is associated with the prognosis of early-stage HCC,and AUF1 may exert an oncogenic effect by activating the Wnt signaling pathway.

Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44％ (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.

[Objective] To investigate the clinical manifestations and explore the experience of diagnosis and treatment of spontaneous perirenal urine extravasation after urinary tract obstruction so as to improve the understanding of the disease. [Methods] The clinical data of 23 patients with spontaneous perirenal urine extravasation after obstruction treated at our hospital during 2018 and 2020 were retrospectively analyzed, including the primary diseases, clinical manifestations, imaging examination, treatment and prognosis. The key points of diagnosis and treatment were summarized. [Results] Of the 23 patients, there were 15 males and 8 females, with an average age of 43.4 years. These cases were diagnosed by imaging tests such as ultrasound, computed tomography urography (CTU) and CT. Ureteroscopic lithotripsy was performed in 3 patients with ureteral calculi, retrograde ureteral catheterization in 4 patients and percutaneous nephrostomy in 13 patients. Afterwards, a second phase surgery was performed based on the patients' condition. Of the 3 patients with tumor metastasis who underwent retrograde ureteral catheterization, 2 operation were successful, and 1 operation failed and then converted to nephrostomy and drainage under B-ultrasound localization. [Conclusion] CTU should be performed as soon as possible to make a definite diagnosis. Treatment can be achieved with ureteral retrograde catheterization or percutaneous nephrostomy to achieve local decompression, followed by secondary surgery to treat the primary cause of obstruction.

Sanggenon C is a kind of flavonoid compound mainly extracted from the traditional Chinese medicine Morus alba. The pharmacological effects and mechanisms of sanggenon C are systematically reviewed and summarized， and it is found that this component can improve pulmonary fibrosis by regulating transforming growth factor-β1 and nuclear factor-κB； it can exert anti- tumor effects by inhibiting the proliferation of tumor cells and inducing the apoptosis of tumor cells； it can exert cardioprotective， neuroprotective and hepatoprotective effects by regulating multiple signaling pathways， such as calcineurin/nuclear factor of activated T cells 2， peroxisome proliferators-activated receptor α， and Ras homolog gene family member A/Rho-associated coiled- coil containing protein kinase， enhancing autophagy， reducing inflammatory response and reducing the level of oxidative stress； it can treat osteoporosis by inhibiting osteoclast uptake and promoting osteoblast formation； it has certain inhibitory effect on many enzymes； it can exert anti-inflammatory effects by regulating nuclear factor-κB signaling pathway； it can exert antioxidant effects by scavenging free radicals. However， researches on the pharmacological effects of sanggenon C mostly focus on the cellular and animal field， and the specific mechanism of action is not yet clear. In the future， basic research and clinical trials are still needed to explore and verify.