ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

BACKGROUND:The analgesic effect of stagnant moving needle on myofascial pain syndrome is remarkable,but the analgesic mechanism is still unclear.OBJECTIVE:To investigate the analgesic mechanism of stagnant moving needle acupuncture in the treatment of myofascial pain syndrome.METHODS:Fifty-four SD rats were randomly divided into a blank group(n=16)and a modeling group(n=38).The models of leftmyofascial pain syndrome in the modeling group were prepared by using the method of"striking combined with centrifugal movement".Twelve weeks after modeling,six mice were randomly selected to verify the success of the modeling.The rest of the 32 rats were randomly divided into the model group and the stagnant moving needle group,with 16 rats in each group.The stagnant needle moving group was treated by stagnant moving needle into the local excitation point nodule of the left medial vastus muscle fascia in rats,twice a week,for 4 weeks.The mechanical foot contraction reflex threshold of the leftfoot were measured weekly in the pre/post modeling and post-intervention groups of rats.At 4 weeks after treatment,hematoxylin-eosin staining was used to observe the morphological changes in the muscle tissue of the leftmedial femoral muscle of rats,ELISA was used to detect the levels of substance P and β-endorphin in the serum and the gray matter around the midbrain aqueduct.Immunohistochemistry was used to detect positive expression of microglia markers(Iba-1)and c-fos in the gray matter around the midbrain aqueduct.Western blot assay was used to detect the expression level of brain-derived neurotrophic factor protein in the periaqueductal gray.RESULTS AND CONCLUSION:Compared with the blank group,the mechanical pain threshold of the rats in the model group and the stagnant moving needle group decreased after modeling(P<0.05).After 4 weeks of treatment,the mechanical pain threshold of the rats in the stagnant moving needle group was higher than that in the model group(P<0.05).Hematoxylin-eosin staining results showed that in the model group,the muscle fibers of the leftlower limb medial femoral muscle of rats were disorganized,unequal in thickness,myocytes were enlarged,with inward movement of the nucleus,rounded contracture nodules and tension bands;whereas in the stagnant moving needle group,the muscle fibers were arranged in a neat way,the myocytes were angular,and the contracture nodules were occasionally seen.Compared with the blank group,the expression of substance P in the serum of the model group was significantly higher(P<0.05),while the levels of β-endorphin in serum and substance P and β-endorphin in brain were decreased(P<0.01).Compared with the model group,the level of serum substance P in the stagnant moving needle group was decreased(P<0.05),and the levels of serum β-endorphin and brain substance P and β-endorphin were increased(P<0.05).Compared with the blank group,the positive expression of c-fos and Iba-1 and the protein of brain-derived neurotrophic factor in the model group were increased(P<0.05).Compared with the model group,the positive expression of c-fos in the stagnant moving needle group was increased(P<0.05),and the positive expression of Iba-1 and the protein of brain-derived neurotrophic factor were decreased(P<0.05).These findings suggest that stagnant moving needle may indirectly promote the release of β-endorphin by microglia polarized to the M2 phenotype and increase the excitability of c-fos neurons by inhibiting the activity of microglia in the gray matter around the periaqueductal gray and downregulating the expression of brain-derived neurotrophic factor protein,thereby reducing the degree of central sensitization and effectively relieving myofascial pain syndrome.

Objective To investigate the utility of combining breast mass growth orientation quantification with the S-Detect technique for predicting axillary lymph node(ALN)metastasis in breast cancer.Methods Data was collected from 163 breast cancer patients admitted to our hospital between March 2023 and October 2024,who were categorized into metastatic(n=62)and non-metastatic(n=101)groups based on ALN pathology results.All patients underwent routine preoperative ultrasound and S-Detect examination.Univariate and multivariate regression analyses were performed to assess the correlation between each observational index and ALN metastasis.Significant indexes were identified through screening,leading to the establishment of a logistic regression prediction model.The predictive value of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Results The univariate analysis revealed statistically significant differences(P<0.05)in the maximum diameter of the mass,border characteristics,margin features,calcification patterns,orientation angle,and blood flow between the two groups.Multifactorial analysis demonstrated that calcification,border characteristics,orientation angle,margin features,and maximum diameter independently influenced the prediction of axillary lymph node(ALN)status in breast cancer patients(P<0.05).Consequently,a logistic regression prediction model was constructed as follows:Y=-7.995+2.299×maximal diameter+1.171×border+2.137×margin+1.397×calcication+0.034×orientation angle.The area under curve(AUC)for this combined prediction model was 0.869 which significantly outperformed each independent influencing factor alone(P<0.05),indicating good agreement between this joint prediction model and pathological results(Kappa=0.701,P<0.05).Conclusions Quantification of the orientation angle of a breast mass aids in predicting axillary lymph node(ALN)metastasis and enhances the interpretation and application of non-parallel orientations.The combination of quantifying growth orientation based on breast mass with artificial intelligence S-Detect technique demonstrates promising predictive value for ALN metastasis in breast cancer,providing a reference basis for personalized treatment.

OBJECTIVE: To explore the mechanism of acupuncture on improving ovarian hypofunction in aged rats from two perspectives: the overall regulation of the hypothalamic-pituitary-ovarian (HPO) axis and the local ovarian follicle stimulating hormone (FSH)/cyclic adenosine monophosphate (cAMP) signaling pathway. METHODS: Six 3-month-old female SPF-grade Sprague-Dawley (SD) rats were selected as the blank group. Another twelve 9-month-old female SD rats were randomly divided into a model group and an acupuncture group, with six rats in each. The acupuncture group received acupuncture at "Baihui" (GV20), "Guanyuan" (CV4), and bilateral "Ciliao" (BL32) for 20 min per session, once every other day, for a total of 10 sessions. Vaginal smear tests were performed daily to observe the estrous cycle of the rats. Ovarian morphology was observed using HE staining, and follicles at various stages were counted. ELISA was used to detect levels of serum FSH, luteinizing hormone (LH), estradiol (E₂), anti-müllerian hormone (AMH), hypothalamic gonadotropin-releasing hormone (GnRH), pituitary FSH and LH, and ovarian cAMP. Immunohistochemistry and Western blot were used to detect the protein expression of ovarian cAMP protein kinase catalytic subunit, FSH receptor (FSHR), and P450. Real-time quantitative PCR was used to measure mRNA expression levels of FSHR and P450 in ovarian tissue. RESULTS: Compared with the blank group, the model group showed an increased rate of estrous cycle disorder (P<0.01), reduced granulosa cell layers with blurred boundaries and disordered arrangement, decreased numbers of developing follicles at all stages, and increased numbers of atretic follicles (P<0.01); the serum levels of FSH and LH were increased (P<0.01), while E₂ and AMH levels were decreased (P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were elevated (P<0.01), and ovarian cAMP level was decreased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were reduced (P<0.01), and ovarian FSHR and P450 mRNA expression was decreased (P<0.01). Compared with the model group, the acupuncture group showed a reduced rate of estrous cycle disorder (P<0.01), clear granulosa cell margins, increased numbers of primordial and secondary follicles, and decreased numbers of atretic follicles (P<0.01); the serum FSH and LH levels were decreased (P<0.01, P<0.05), while E₂ and AMH levels were increased (P<0.05, P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were decreased (P<0.01, P<0.05), and ovarian cAMP level was increased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were elevated (P<0.01), and ovarian FSHR and P450 mRNA expression was increased (P<0.01). CONCLUSION Acupuncture could delay ovarian hypofunction in aged rats, possibly through regulating the HPO axis and the FSH/cAMP signaling pathway.
Animals ; Female ; Rats ; Rats, Sprague-Dawley ; Follicle Stimulating Hormone/genetics* ; Acupuncture Therapy ; Ovary/metabolism* ; Signal Transduction ; Humans ; Cyclic AMP/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Aging/metabolism* ; Hypothalamus/metabolism* ; Pituitary Gland/metabolism* ; Gonadotropin-Releasing Hormone/metabolism*

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

A 52-year-old female patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), asthma and allergic rhinitis and was treated with mepolizumab (100 mg, once every 4 weeks). Three days after the second administration, the patient developed dark yellow urine, and abnormal liver function indicators were found on day 6 after administration. Laboratory tests showed total bilirubin (TBIL) of 22 μmol/L, direct bilirubin (DBIL) of 14.9 μmol/L, alanine aminotransferase (ALT) of 461 U/L, aspartate aminotransferase (AST) of 129 U/L, and alkaline phosphatase (ALP) of 296 U/L. After a comprehensive assessment, it was considered that mepolizumab may caused liver injury in the patient. Magnesium isoglycyrrhizinate, glutathione, and ursodeoxycholic acid were used for liver protection. Five days later, the urine color became lighter and liver function indicators improved (TBIL 17.4 μmol/L, DBIL 9.8 μmol/L, ALT 214 U/L, AST 85 U/L, ALP 226 U/L). After about 2 weeks of continued liver protection treatment, liver function returned to normal. Mepolizumab treatment was suspended and during the follow-up for about half a year, the patient did not experience liver function abnormalities or other discomforts again.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective:To observe the effects of low expressed Angiotensin-converting enzyme 2 ( Ace2) gene on senescence related signals of alveolar type Ⅱ epithelial cells in silicotic mice. Methods:In March 2022, 20 8-12W SPF male wild-type C57BL/6 mice and 20 Ace2 gene knockdown mice (Ace2 +/-, C57BL/6 background) were randomly divided into wild-type control group, Ace2 low expression group, wild-type silicosis group, Ace2 low expression silicosis group, with 10 mice in each group. In vitro MLE-12 cells were divided into control group, MLN-4760 (ACE2 inhibitor) group, SiO 2 group and SiO 2+MLN-4760 group. The expression of ACE2, collagen I (Col I), fibronectin 1 (Fn1), α-smooth muscle actin (α-SMA), phosphorylation-ataxia telangiectasia-mutated serine/threonine kinase (p-ATM), phosphorylation-ATM Rad3-related kinase (p-ATR), p-p53, p21 and p16 in mice and MLE-12 cells were detected by Western blotting. The expression and location of β-galactosidase were detected by immunofluorescence, β-galactosidase (SA-β-Gal) staining were used to detect the senescence of MLE-12 cells. Results:HE and VG staining results showed that typical silicon nodules with collagen deposition were formed in the lung of wild-type silicotic mice and Ace2 low expression silicotic mice. Immunofluorescence staining results showed that β-galactosidase was mainly located in alveolar type Ⅱ epithelial cells. Western blot results showed that, compared with wild-type silicosis group, the expression of Col I, α-SMA, p-ATM, p-ATR, p-p53, p21 and p16 in Ace2 low expression silicosis group were significantly up-regulated by 540.71%、26.58%、336.84%、139.58%、152.78%、120.10% and 994.63% ( P<0.05). In MLE-12 cells, results of western blot showed that compared with SiO 2 group, the expression levels of p-ATM, p-ATR, p-p53, p21 and p16 in SiO 2+MLN-4760 group were significantly up-regulated by 168.71%、750.78%、149.51%、554.26% and 254.07% ( P<0.05). Immunofluorescence staining results showed that compared with SiO 2 group, β-galactosidase positive cells were strongly up-regulated in SiO 2+MLN-4760 group, and SA-β-Gal staining results showed that compared with SiO 2 group, the number of senescent cells in SiO 2+MLN-4760 group increased by 63.18% ( P<0.05) . Conclusion:Low expression of Ace2 gene activated senescence related signals of alveolar type Ⅱ epithelial cells and promoted the progression of silicotic fibrosis in mice.

Objective To observe the value of 2D SECara-Net and 3D U2-Net models constructed based on 2D maximal intensity projection(MIP)and 3D time-of-flight MR angiography(3D TOF-MRA)images,respectively,also of their combination for MRA detecting unruptured saccular intracranial aneurysms(USIA).Methods Totally 973 patients with single USIA and 300 subjects who underwent healthy physical examination were retrospectively collected and divided into training set(n=923,containing 723 cases of USIA and 200 healthy subjects)and test set(n=350,containing 250 cases of USIA and 100 healthy subjects)at the ratio of 7:3.Pre-processed 3D TOF-MRA and the obtained 2D-MIP images in training set were imported into 3D U2-Net and 2D SECara-Net models for training and adjusting parameters,respectively.The efficiency of 2 models and their combination for detecting USIA were evaluated.Results The sensitivity,specificity and accuracy of 2D SECara-Net model for detecting USIA in test set was 78.80％(197/250),95.00％(95/100)and 83.43％(292/350),of 3D U2-Net model was 82.80％(207/250),86.00％(86/100)and 83.71％(293/350),respectively.The specificity of 2D SECara-Net model was higher than that of 3D U2-Net model(P=0.030),while no significant difference of sensitivity nor accuracy was found between 2 models(both P＞0.05).The specificity of the combination of the 2 models was 99.00％(99/100),higher than that of 3D U2-Net model(P＜0.05),and the sensitivity and accuracy of the combination was 91.20％(228/250)and 93.43％(327/350),respectivelty,both higher than those of 2 single models(all P＜0.05).Conclusion 2D SECara-Net and 3D U2-Net models had similar,sensitivity and accuracy for MRA detecting USIA.Combination of them could improve the detecting efficacy.