This study aimed to investigate the effects of the peptide secreted protein isthmin-1 (ISM1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. ISM1 expression in NSCLC was detected by immunohistochemistry (IHC). ISM1 was overexpressed in lung cancer cell lines by transient transfection of ISM1 plasmids, or establishing ISM1 overexpression stable cell lines, or by treating cells with recombined ISM1 (rISM1). CCK-8 was used to examine cell growth. The intracellular signal transduction pathways regulated by rISM1 were analyzed by transcriptome sequencing, and verified by qRT-PCR and Western blot. The levels of intracellular ROS and apoptosis were further detected using the kit. The results showed that the expression of ISM1 was decreased in human NSCLC tissue samples compared to normal lung tissue samples. Overexpression of ISM1 or rISM1 treatment significantly suppressed the growth of lung cancer cells. RNA sequencing revealed that rISM1 mainly regulated the FoxO signaling pathway. rISM1 treatment decreased the expression of FoxO3 and FoxO1, increased reactive oxygen species (ROS) production, and induced cell apoptosis. These results suggest that ISM1 can inhibit the growth of NSCLC by regulating the FoxO signaling pathway. These findings provide new strategies for cancer therapy.

Objective To assess the echogenicity of the ultrasound-guided catheter and its associated delivery system. Methods The study consisted of in vitro characterization experiments and animal studies. In the in vitro phase, the acoustic and mechanical properties of the ultrasound-guided catheter were compared with those of the traditional MPA2 catheter, including parameters such as echo intensity, recognizability, and angle dependence. In the animal experiments, a ventricular septal defect (VSD) model was established in miniature pigs to compare the procedural performance of the ultrasound-guided delivery system versus the conventional system. Evaluation indicators included the time required for the system to cross the VSD, the detection rate of the system within the right ventricle, and the occurrence of intraoperative complications. Results The ultrasound-guided catheter demonstrated a significantly higher mean echo intensity than the MPA2 catheter [(237.3±1.8) dB vs. (190.9±13.1) dB, P<0.001] and a markedly improved recognizability rate (82.3%±5.6% vs. 26.7%±3.2%, P<0.001), along with better angle independence and image quality. In animal experiments, the ultrasound-guided delivery system significantly reduced the time required to cross the VSD [(18.5±5.7) min vs. (30.3±4.5) min, P<0.001] and substantially increased the detection rate within the right ventricle (100.0% vs. 30.0%). No severe complications occurred in any experimental animal. Conclusion The ultrasound-guided catheter and its corresponding delivery system exhibite superior ultrasound visibility and operational performance in both in vitro and animal experiments, indicating strong potential for clinical application.

ObjectiveTo explore the potential mechanism of acupuncture with the method of soothing the liver and regulating the mind in improving depressive disorder. MethodsEighteen C57BL/6J mice were randomly divided into blank group， model group， and acupuncture group， with 6 mice in each group. The model group and the acupuncture group were subjected to depression induction by intraperitoneal injection of lipopolysaccharide （LPS）， while the blank group received an equal volume of normal saline once daily for seven consecutive days. Concurrently， the acupuncture group received "soothing the liver and regulating the mind" acupuncture intervention starting from the first day of modeling， once daily for 14 days； whereas the blank group and the model group were only restrained without acupuncture. The sucrose preference test was used to assess sucrose preference rate， the open-field test to measure center stay time and total travel distance， and the forced swim test to evaluate immobility time. Hematoxylin-eosin （HE） staining was performed to observe hippocampal morphological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in hippocampal tissue. Western blot analysis was conducted to examine the protein expression levels of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the hippocampus. ResultsCompared to the blank group， the model group showed a significant reduction in sucrose preference rate， center stay time， and total travel distance， along with a significant increase in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， as well as TLR4 and NF-κB protein expression （P＜0.01）， and the histological examination revealed blurred hippocampal neuronal boundaries， loose arrangement， and some neurons exhibiting nuclear pyknosis and deep staining. Compared to the model group， the acupuncture group demonstrated a significant increase in sucrose preference rate， center stay time， and total travel distance， along with a significant reduction in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， and TLR4 and NF-κB protein expression （P＜0.01）， and the histological analysis showed that hippocampal neurons in the acupuncture group were more tightly arranged， with reduced nuclear pyknosis and deep staining. ConclusionAcupuncture with the "soothing the liver and regulating the mind" method can significantly improve depression-like behavior， potentially by inhibiting the hippocampal TLR4/NF-κB signaling pathway and alleviating inflammatory responses.

Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.

Secondary osteoporosis is common in patients with early breast cancer, manifesting as low back pain, bone and joint symptoms, and osteoporotic fractures. Bisphosphonate and denosumab can reduce the incidence of fractures by minimizing bone loss, though they differ in efficacy, treatment course, and side effects. Patients should consider the pros and cons when selecting a drug. Recent studies also focus on decreasing the incidence of bone metastases. This article reviews recent advancements in the use of these two drugs for managing bone health in early breast cancer.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

Objective To analyze the burden of disease of malignant tumors in Kunshan City from 2006 to 2021. Methods The global burden of disease research methodology was applied. The indicators of cancer incidence, mortality, and disability-adjusted life years (DALYs) in Kunshan were calculated using the data from the Tumor Registry System and Death Registry System in Kunshan. The changes in cancer were compared. Results In 2021, the number of incidences and deaths and the DALYs of cancer were 4724 cases, 1618 cases, and 20887.90 person-years, respectively. The incidence, mortality, and DALYs rates were 427.42/100000, 146.39/100000, and 18.90‰. Compared with those in 2006, the incidence rate increased by 53.40%, and the mortality and DALYs rates decreased by 24.23% and 25.73%, respectively. The DALYs rate of cancer was higher for males than for females at 22.12‰ and 15.91‰ in 2021, respectively. The DALYs rate increased with age, and it started to increase sharply after 45 years of age. The top 10 cancers in 2021 in terms of DALYs were lung cancer, stomach cancer, colorectal cancer, liver cancer, pancreatic cancer, breast cancer, leukemia, esophageal cancer, brain and nervous system cancer, and gallbladder and biliary tract cancer, accounting for 83.83% of all cancers. The proportion of years lived with disability (YLD) in DALYs increased continuously (27% in 2021), with females increasing faster than males. Conclusion The disease burden of cancer in Kunshan City remains high, and the incidence of cancer must be reduced by developing comprehensive measures and continuously strengthening the capacity of early screening and treatment of cancer.

The liver is one of the essential hubs for maintaining the homeostasis of the organism.Liver aging not only heightens its susceptibility to acute injuries and chronic liver diseases, but also triggers a " chain reaction" of multi-organ aging and dysfunction.With the continuous deepening of the aging population in China, how to prevent, monitor, and evaluate the occurrence, development, and prognosis of liver aging has become an important issue in the field of geriatrics research.Thus, the identification and widespread application of liver aging biomarkers is the key to solving this problem.Therefore, this article reviews the research progress of liver aging-related biomarkers, aiming to provide a basis for the precise prevention and targeted intervention of liver diseases related to aging.