This paper comprehensively discusses on the potential neurobiological mechanisms of acupuncture in the treatment of tobacco dependence， focusing on three important aspects， including acupuncture's regulation of tobacco dependence behavior， effects of acupuncture on withdrawal syndrome， and the role of acupuncture in preventing relapse. It is found that acupuncture can inhibit drug-seeking behavior by regulating the reward pathway and related neurons， such as dopamine， thus modulating tobacco dependence behavior. It also alleviates withdrawal symptoms by improving the oral environment of smokers and reducing negative emotions after quitting. Furthermore， acupuncture can prevent relapse by decreasing brain network activity related to smoking cravings and improving cognitive brain functions like addiction memory. Currently， research on the specific neurobiological mechanism of acupuncture in treating tobacco dependence and the involved neural circuits is limited. Future research directions are proposed， including the evaluation of clinical effects， exploration of specific therapeutic mechanisms， investigation of brain pathology， and strengthening the exploration of brain functions. Additionally， combining modern technologies to clarify the neural circuits involved in acupuncture intervention will provide a basis for acupuncture treatment of tobacco addiction.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

Objective: To investigate protective effects of nicotinamide mononucleotide (NMN) on ethanol-induced DNA damage in L02 cells, so as to provide the evidence for adjuvant therapy of NMN on alcoholic liver diseases. Methods: L02 cells were pretreated with different concentrations of NMN (0, 1, 2, 4 and 8 mmol/L) for 6 h, and then were exposed to 0.4% ethanol for 12 h. The treated cells were divided into the control group, 0.4% ethanol group and different concentrations of NMN groups. Cell viability was analyzed using trypan blue staining for determining the concentration of NMN as a protective agent. The effects of NMN on ethanol-induced DNA damage in L02 cells were evaluated using immunofluorescence detection and reactive oxygen species (ROS) assay. L02 cells were exposed to 0.4% ethanol for 12 h, cultured in a medium containing a protective concentration of NMN, and divided into PBS group and NMN group. Cell viability was detected at 0, 2, 4, 8, 16 and 32 h, and the effects of NMN on repairing ethanol-induced DNA damage were evaluated by alkaline comet assay. Results: The cell viability was lower in 0.4% ethanol group than than in the control group, and was higher in different concentrations of NMN groups than in 0.4% ethanol group (all P<0.05), with no significant difference in the cells viability between 4 mmol/L and higher concentrations of NMN groups and the control group (all P>0.05). Therefore, 4 mmol/L NMN was selected as a protective agent. The cell tail moments, relative immunofluorescence intensities of γH2AX and relative levels of ROS were higher in 0.4% ethanol group than in the control group, and lower in 4 mmol/L and higher concentrations of NMN groups than in 0.4% ethanol group (all P<0.05). The cell viability was increased and the cell tail moment was shortened with the increase of 4 mmol/L NMN intervention time; and the cell viability in 4 h and more of NMN groups were higher, and the cell tail moment were lower than that in PBS group (all P<0.05). Conclusions NMN attenuates DNA damage in a dose-dependent manner and promotes the repair of DNA damage in a time-dependent manner. NMN has a protective effect on ethanol-induced DNA damage in hepatocytes.

Objective To analyze the colorectal cancer screening of community residents in Pudong New Area in Shanghai and provide reference for the promotion and strategy optimization of colorectal cancer screening programs. Methods Residents aged 50-74 years in the colorectal cancer screening project of Pudong New Area in Shanghai from 2013 to 2023 were recruited in this analysis. The situation of primary screening and colonoscopy in the community was described, and results of different age groups in primary screening and colonoscopy surveys were evaluated. Chi-square test was used to determine differences between groups. Results From 2013 to 2023, 907 030 residents were screened in Pudong New Area, of which 183 724 residents were positive, and the positive rate was 20.3%. The positive rate was the lowest in the 50-54 age group and the highest in the 70-74 age group. The positive rate was higher in men than in women. The overall colonoscopy rate was 27.1%, with the highest rates in the 50-54 age group in men and the 55-59 age group in women, respectively. The participation rate of colonoscopy increased with the increase of the year. A total of 19 094 cases of intestinal lesions were found by colonoscopy. Among these lesions, 1 147 cases were colorectal cancer, accounting for 6.0%, and the population detection rate was 126.5/100 000. In addition, 4 751 cases of precancerous lesions were found, accounting for 24.9%, and the detection rate was 523.8/100 000. Conclusion Colorectal cancer screening improves the detection rate of precancerous lesions and early cancer and is of great significance for reducing the incidence and mortality of colon cancer. Measures should be taken to optimize the screening strategy based on age differences and increase the participation rate of primary screening and colonoscopy to achieve the best effect of local colorectal cancer prevention and treatment.

ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury， and to observe the effect of myocardial microvascular density （MVD）， phosphatidylinositol 3-kinase （PI3K）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor-1 alpha （HIF-1α）， and vascular endothelial growth factor （VEGF） signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected， with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride （ISO，80 mg·kg^-1·d^-1， 2 d） to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling， the rats were randomly divided into the model group， high， medium， and low dose groups of Gualou Xiebai Banxiatang， and the metoprolol group. The high， medium， and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42， 5.21， 2.61 g·kg^-1·d^-1， respectively， while the metoprolol group was given metoprolol at 2.6 mg·kg^-1·d^-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention， relevant tests were conducted， and serum was collected to measure heart function-related indicators. Hematoxylin-eosin （HE） and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry （IHC） was used to detect the positive expression of platelet endothelial cell adhesion molecule （CD31）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of N-terminal pro-brain natriuretic peptide （NT-proBNP） and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group， the model group showed significantly increased serum levels of LDH， CK， CK-MB， NT-proBNP， and VEGF （P<0.01）， significantly increased collagen volume fraction （CVF） （P<0.01）， significantly decreased MVD （P<0.01）， and elevated protein expression levels of PI3K， mTOR， HIF-1α， and VEGF （P<0.05， P<0.01）. Compared with the model group， the metoprolol group had significantly lower serum levels of LDH， CK， CK-MB， and NT-proBNP （P<0.01）， significantly higher VEGF levels （P<0.01）， significantly decreased CVF （P<0.01）， significantly increased MVD （P<0.01）， and significantly increased protein expression levels of PI3K， mTOR， and VEGF （P<0.01）， with no statistically significant change in HIF-1α protein expression. Compared with the model group， the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH， CK， CK-MB， and NT-proBNP （P<0.05， P<0.01）， increased VEGF levels （P<0.05， P<0.01）， significantly reduced CVF （P<0.01）， increased MVD （P<0.05， P<0.01）， and significantly increased protein levels of PI3K， mTOR， HIF-1α， and VEGF （P<0.01）. In the low dose group of Gualou Xiebai Banxiatang， compared with the model group， serum levels of LDH and NT-proBNP were decreased （P<0.05）， VEGF was increased （P<0.05）. Moreover， CVF was decreased （P<0.05）， and the protein expression levels of PI3K， mTOR， HIF-1α， and VEGF were significantly increased （P<0.01）. ConclusionGualou Xiebai Banxiatang can improve cardiac function， reduce myocardial pathological damage， enhance endothelial cell function， promote myocardial microvascular formation， and upregulate the expression of PI3K， mTOR， HIF-1α， and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.