This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

BACKGROUND: Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients. However, the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI) with BP control among hypertension patients is seldom reported, which needs to provide more evidence by prospective intervention studies. We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program. METHODS: Between January 2013 and December 2014, a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China. Workplaces were randomly divided into intervention (n = 40) and control (n = 20) groups. Basic information on employees at each workplace was collected by trained professionals, including sociodemographic characteristics, medical history, family history, lifestyle behaviors, medication status and physical measurements. After baseline, the intervention group received a 2-year intervention to achieve BP control, which included: (1) a workplace wellness program for all employees; (2) a guidelines-oriented hypertension management protocol. HLI including nonsmoking, nondrinking, adequate physical activity, weight within reference range and balanced diet, were coded on a 5-point scale (range: 0-5, with higher score indicating a healthier lifestyle). Antihypertensive medication use was defined as taking drug within the last 2 weeks. Changes in HLI, antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention. RESULTS: Overall, 4655 employees were included (age: 46.3 ± 7.6 years, men: 3547 (82.3%)). After 24 months of the intervention, there was a significant improvement in lifestyle [smoking (OR = 0.65, 95% CI: 0.43-0.99; P = 0.045), drinking (OR = 0.52, 95% CI: 0.40-0.68; P < 0.001), regular exercise (OR = 3.10, 95% CI: 2.53-3.78; P < 0.001), excessive intake of fatty food (OR = 0.17, 95% CI: 0.06-0.52; P = 0.002), restrictive use of salt (OR = 0.26, 95% CI: 0.12-0.56; P = 0.001)]. Compare to employees with a deteriorating lifestyle after the intervention, those with an improved lifestyle had a higher BP control. In the intervention group, compared with employees not using antihypertensive medication, those who consistent used (OR = 2.34; 95% CI: 1.16-4.72; P = 0.017) or changed from not using to using antihypertensive medication (OR = 2.24; 95% CI: 1.08-4.62; P = 0.030) had higher BP control. Compared with those having lower HLI, participants with a same (OR = 1.38; 95% CI: 0.99-1.93; P = 0.056) or high (OR = 1.79; 95% CI: 1.27~2.53; P < 0.001) HLI had higher BP control. Those who used antihypertensive medication and had a high HLI had the highest BP control (OR = 1.88; 95% CI: 1.32-2.67, P < 0.001). Subgroup analysis also showed the consistent effect as the above. CONCLUSION These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Surgical intervention for malignant bone tumors frequently results in bone defects located at the metaphysis of the long bones in the lower extremities.The morphological heterogeneity of the metaphysis poses significant challenges for conventional treatment methods to adequately conform to the defect area.The utilization of three-dimensional(3D)-printed titanium bone repair scaffolds has emerged as an effective reconstructive approach for metaphyseal bone defects,as these scaffolds offer precise shape conformity and provide adequate mechanical support.However,the current commonly used scaffolds do not adequately replicate the biomechanical environment of bone defects,resulting in suboptimal bone ingrowth within the scaffolds and subsequent prosthesis loosening and failure post-operation.Bone is a highly force-responsive organ,and its fate is regulated by biomechanical signals.Consequently,designing scaffolds with consideration of biomechanical principles to ensure mechanical compatibility between the scaffolds and the bone defect sites is a critical factor influencing the success of bone defects reconstruction.This review primarily introduces the biomechanical factors influencing bone defect repair and the advancements in designing 3D-printed titanium bone repair scaffolds biomechanically matched with bones,offering theoretical guidance for scaffold design and preparation.

Objective:To investigate the liver-protective effect of Peipi Shugan Decoction (PSD) in rats with liver fibrosis through network pharmacology and experimental animal models.Methods:TCMSP was used to retrieve the active components of Peipi Shugan Decoction, GeneCards database was used to obtain the liver fibrosis related targets, and Venny 2.1 was used to obtain the intersection targets. A protein-protein interaction (PPI) network was constructed using the STRING 12.0 database, and Go function and KEGG pathway enrichment analysis were performed through David database. A total of 60 male Sprague-Dawley (SD) rats were divided into two groups: a blank control group ( n=10) and a model establishment group ( n=50) with random number table method. Liver fibrosis models were induced in the model group by intraperitoneal injection of a 40% CCl?- olive oil solution. After successful modeling, the rats were randomly assigned to the following groups ( n=10 per group): model group, colchicine group, and Peipi Shugan Decoction low-, medium-, and high-dosage groups. The colchicine group received colchicine suspension at 0.2 ml/kg via intragastric administration. Peipi Shugan Decoction low-, medium-, and high-dosage groups were administered the decoction at dosages of 2.81, 5.63, and 11.25 g/kg, respectively. The blank control and model groups received an equal volume of normal saline. All treatments were administered once daily for 8 consecutive weeks. HE staining and Masson staining were used to observe the morphological changes of liver tissue and the deposition of collagen fibers. he levels of GPT, GOT and ALP were detected by automatic biochemical analyzer. The expressions of JAK2/STAT1 signaling pathway related proteins, α - smooth muscle actin (α-SMA) and Collagen Ⅰ in rat liver were detected by Western blot. The expression of α-SMA protein in liver tissue was detected by immunohistochemistry. The number and ratio of CD4 + T cells and CD8 + T cells in liver tissue were analyzed by flow cytometry. The levels of IL-6, IL-1β and TNF-α in serum were detected by ELISA. Results:A total of 94 active components were screened out from Peipi Shugan Decoction; the prediction analysis results revealed that this compound formula shared 122 common targets with liver fibrosis diseases; The top five core targets with degree values in the PPI network are AKT1, TNF, IL-6, TP53, and IL-1β. GO enrichment analysis further indicated that Peipi Shugan Decoction mainly achieved anti-liver fibrosis effects by regulating JAK2/STAT1 signaling pathway and other mechanisms. Compared with the model group, the colchicine group and Peipi Shugan Decoction low-, medium-, and high-dosage groups exhibited decreased serum levels of GPT, GOT, ALP, IL-6, TNF-α, and IL-1β ( P<0.05), as well as reduced expression of α-SMA in liver tissue ( P<0.05). Peipi Shugan Decoction medium- and high-dosage groups showed increased protein expression of p-STAT1/STAT1 in liver tissue ( P<0.05), while Peipi Shugan Decoction high-dosage group demonstrated decreased α-SMA protein expression ( P<0.05). Additionally, Peipi Shugan Decoction medium- and high-dosage groups exhibited reduced expressions of CD4 + and CD8 + ( P<0.05). Conclusions:Peipi Shugan Decoction has the characteristics of multi-component, multi-target and multi-pathway in the treatment of liver fibrosis. Its mechanism is mainly related to activating the JAK2/STAT1 signaling pathway, inhibiting cellular inflammatory responses and hindering the activation of hepatic stellate cells (HSC).

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Surgical intervention for malignant bone tumors frequently results in bone defects located at the metaphysis of the long bones in the lower extremities.The morphological heterogeneity of the metaphysis poses significant challenges for conventional treatment methods to adequately conform to the defect area.The utilization of three-dimensional(3D)-printed titanium bone repair scaffolds has emerged as an effective reconstructive approach for metaphyseal bone defects,as these scaffolds offer precise shape conformity and provide adequate mechanical support.However,the current commonly used scaffolds do not adequately replicate the biomechanical environment of bone defects,resulting in suboptimal bone ingrowth within the scaffolds and subsequent prosthesis loosening and failure post-operation.Bone is a highly force-responsive organ,and its fate is regulated by biomechanical signals.Consequently,designing scaffolds with consideration of biomechanical principles to ensure mechanical compatibility between the scaffolds and the bone defect sites is a critical factor influencing the success of bone defects reconstruction.This review primarily introduces the biomechanical factors influencing bone defect repair and the advancements in designing 3D-printed titanium bone repair scaffolds biomechanically matched with bones,offering theoretical guidance for scaffold design and preparation.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). Materials and Methods: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates.In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. Results: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0–40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%–86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%–19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%–11.4%), 26.8% (95% CI: 2.7%– 44.9%), and 51.2% (95% CI: 0%–79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). Conclusion Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.