[Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study].

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

[Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses].

OBJECTIVE: To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. METHODS: High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. RESULTS: Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5- and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. CONCLUSION: TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

[Research on pediatric hereditary kidney disease: from now to the future].

Hereditary kidney disease is an important cause of chronic kidney disease in children. With the progress of genome sequencing, single-cell technology, and organoid cultures, the research on hereditary kidney disease has entered a new era. How to integrate big data resources, discover new disease-causing genes, and develop effective treatment methods will be the focus of future research. This article discusses the classification, research progress, challenges and prospects of pediatric hereditary kidney disease, so as to provide valuable insights into the research of hereditary kidney disease in children.

Association between workplace health promotion service utilisation and depressive symptoms among workers: a nationwide survey.

OBJECTIVES: Workplace-related factors are associated with the risk of depression. Despite implementation of workplace health promotion (WHP) programmes in China to promote the physical and mental well-being of workers, the relationship between WHP and depression has received limited attention. This study investigated the association between WHP service utilisation and depressive symptoms among workers. STUDY DESIGN: This was a cross-sectional survey. METHODS: A researcher-designed questionnaire was used to collect information on socio-demographic and occupational characteristics, WHP service utilisation, and mental health status. The Lasso method was used for variable selection to achieve dimension reduction, and logistic regression was used to assess the association between WHP service utilisation and depressive symptoms. RESULTS: The analysis included 11,710 workers, of whom 17.0% had depressive symptoms. Lasso regression resulted in 6 of 18 WHP services showing significant negative associations with depressive symptoms, including occupational safety training, mental health services, health check-ups, sports activities, fitness rooms, and healthy canteens. The logistic regression results showed that, after adjusting for sociodemographic and occupational factors, utilisation of these six services was associated with a decreased likelihood of depressive symptoms. The adjusted odds ratio (aOR) was 0.84 (95% confidence interval [CI]: 0.73-0.96) for occupational safety training, aOR: 0.82 (95% CI: 0.68-0.99) for mental health services, aOR: 0.80 (95% CI: 0.71-0.90) for health check-ups, aOR: 0.68 (95% CI: 0.57-0.80) for sports activities, aOR: 0.59 (95% CI: 0.47-0.74) for fitness rooms and aOR: 0.72 (95% CI: 0.59-0.87) for healthy canteens. CONCLUSIONS: Utilisation of WHP services was associated with a lower prevalence of depressive symptoms. Implementation of WHP services and the provision of a supportive workplace environment should be prioritised to benefit the mental health of workers.

Simplified integration of optimal self-management behaviors is associated with improved HbA1c in patients with type 1 diabetes.

PURPOSE: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c. METHODS: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c. RESULTS: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels. CONCLUSIONS: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03610984.

Dominant contribution of atmospheric nonlinearities to ENSO asymmetry and extreme El Niño events.

Extreme El Niño events have outsized impacts and strongly contribute to the El Niño Southern Oscillation (ENSO) warm/cold phase asymmetries. There is currently no consensus on the respective importance of oceanic and atmospheric nonlinearities for those asymmetries. Here, we use atmospheric and oceanic general circulation models that reproduce ENSO asymmetries well to quantify the atmospheric nonlinearities contribution. The linear and nonlinear components of the wind stress response to Sea Surface Temperature (SST) anomalies are isolated using ensemble atmospheric experiments, and used to force oceanic experiments. The wind stress-SST nonlinearity is dominated by the deep atmospheric convective response to SST. This wind-stress nonlinearity contributes to ~ 40% of the peak amplitude of extreme El Niño events and ~ 55% of the prolonged eastern Pacific warming they generate until the following summer. This large contribution arises because nonlinearities consistently drive equatorial westerly anomalies, while the larger linear component is made less efficient by easterly anomalies in the western Pacific during fall and winter. Overall, wind-stress nonlinearities fully account for the eastern Pacific positive ENSO skewness. Our findings underscore the pivotal role of atmospheric nonlinearities in shaping extreme El Niño events and, more generally, ENSO asymmetry.

[Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging].

Objective: To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation. Methods: A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups. Results: The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants (P < 0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants (P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion: LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.

[Research progress on pyroptosis in liver diseases].

Pyroptosis is a newly discovered kind of cell death modality that, due to its association with innate immunity, plays a crucial role in cytolysis and inflammatory cytokine release during host defense against infection. In recent years, studies have shown that pyroptosis plays an important role in the occurrence and development of liver diseases. This article introduces and elaborates on the most recent research progress on pyroptosis in liver diseases based on the morphological features, molecular and pathophysiological mechanisms.

Spectral modulation of high-order harmonics in relativistic laser-solid interaction.

Spectral modulation of high-order harmonics generated in relativistic laser-solid interaction is investigated. Numerical simulations show that the modulation depends on surface plasma density profile, resulting in spectral envelope modulation and regular and irregular harmonic splitting. The mathematical and physical connections between the spectral modulation of high-order harmonics and the temporal modification of attosecond pulse train are explained. Based on these understandings, we propose a possible method to produce isolated attosecond pulses by tailoring surface the plasma profile.

[Tea polyphenols ameliorates acute lung injury in septic mice by inhibiting NLRP3 inflammasomes].

OBJECTIVE: To investigate the mechanism of tea polyphenols (TP) for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice. METHODS: Sixty C57BL/6 mice were randomly assigned into sham-operated, cecal ligation and puncture (CLP) and CLP +TP treatment groups, and survival of the mice was recorded after modeling in each group. The lung wet/dry weight ratio and myeloperoxidase (MPO) activity were determined, and lung injury of the mice was evaluated using HE staining and acute lung injury score. The expressions of IL-1ß, TNF-α, IL-6, NLRP3, caspase-1 p10, ASC, MPO, and caspase-8 in the lung tissue were detected using ELISA, Western blotting, or immunohistochemical staining. MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress. Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4. RESULTS: The postoperative mortality rate at 72 h, lung wet/dry weight ratio, MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group (P < 0.05). Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors (P < 0.05) and lowered MDA and H2O2 levels in the lung tissue of the septic mice (P < 0.05). Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group. CONCLUSION: TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

[Analysis methods and case analysis of effect modification (3): effect modification in individual patient data Meta-analysis].

This paper briefly introduces the unique advantages, overall analysis ideas and existing analysis methods of individual patient data Meta-analysis in terms of effect modification. In addition to Meta-regression and subgroup analysis, this paper also introduces the analysis methods based on part of individual patient data integrated with aggregated data and summarizes the current reporting of the above mentioned methods. In addition, the application and results interpretation of the above mentioned methods in individual patient data Meta-analysis are presented in this paper by taking "Effects of sodium-glucose cotransporter 2 inhibitors on SBP in patients with type 2 diabetes" as an example and by introducing their advantages and limitations.

Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.

Implementation of sonopartogram: multicenter feasibility study.

OBJECTIVES: Well-established clinical practice to assess progress in labor involves routine abdominal palpation and vaginal examination (VE). However, VE is subjective, poorly reproducible and painful for women. In this study, our aim is to evaluate the feasibility of systematically integrating transabdominal and transperineal ultrasound assessment of fetal position, psAOP, HPD and SCD to monitor labor progress in women undergoing induction of labor (IOL). We also aim at determining if ultrasound can reduce women's pain during examinations. METHODS: Women were recruited as they presented for IOL in three maternity units. Ultrasound assessments were performed in 100 women between 37+0 and 41+6 weeks' gestation. A baseline combined transabdominal and transperineal scan was performed, including the assessment of fetal biometry, umbilical artery and middle cerebral artery Dopplers, amniotic fluid index (AFI), fetal spine and occiput positions, psAOP, HPD, SCD, and cervical length. Intrapartum scans were performed instead of VEs according to protocol. Participants were asked to indicate their level of pain by verbally giving a pain score from 0 - 10 (with 0 representing no pain) during assessment. The repeated measures data were analyzed by mixed effect models to identify the significant factors that affected the relationship between psAOP, HPD, SCD and mode of delivery. RESULTS: 223 intrapartum ultrasound scans with a median of 2 scans per participant (interquartile range (IQR) = 1 - 3), and 151 VEs were performed with a median of 1 per participant (IQR = 0 - 2). There were no adverse fetal or maternal outcomes. After excluding those with epidural anesthesia during examination, median pain score for intrapartum scan was 0 (IQR = 0 - 1) and 3 for VE (IQR = 0 - 6). Cesarean delivery and epidural anesthesia were significantly associated with slower rate of change in psAOP, HPD and SCD. Maternal height, parity and neonatal birth weight did not affect ultrasound measurements of labor progress. CONCLUSIONS: Comprehensive transabdominal and transperineal ultrasound assessment can be successfully used to assess progress in labor and can reduce the level of pain experienced during examination. Ultrasound assessment may be able to replace some transabdominal and VE examinations during labor. This article is protected by copyright. All rights reserved.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

[Clinical effect of anterolateral thigh flow-through chimeric perforator free flap transplantation in the treatment of upper limb complex tissue defects with main artery injury].

Objective: To investigate the clinical effect of anterolateral thigh flow-through chimeric perforator free flap transplantation in the treatment of upper limb complex tissue defects with main artery injury. Methods: The study was a retrospective observational study. From May 2019 to January 2022, 11 patients with upper limb complex tissue defects combined with main artery injury who met the inclusion criteria were admitted to the Department of Hand, Foot and Ankle Surgery of General Hospital of Ningxia Medical University, including 7 males and 4 females, aged from 18 to 56 years. After debridement, the area of skin and soft tissue defects was from 20 cm×6 cm to 32 cm×10 cm, and the exposed area of dead cavity or deep tissue was from 7 cm×4 cm to 10 cm×7 cm. Three patients had radial artery defects with a length of 4 to 7 cm; two patients had ulnar artery defects with a length of 5 to 8 cm; 4 patients had defects in both ulnar and radial arteries with a length of 3 to 7 cm; and in two patients, the ulnar, radial and brachial arteries were all defective with a length of 4 to 8 cm. The anterolateral thigh flow-through chimeric perforator flap was designed and cut. The skin flap area was from 22 cm×7 cm to 32 cm×11 cm, the chimeric muscle flap area was from 7 cm×4 cm to 10 cm×7 cm, and the length of the flow-through vessel in the "T" shaped vessel pedicle was from 4 to 8 cm. When transplanting the skin flap, the proximal end of the vascular pedicle was anastomosed with the proximal end of the recipient site, and the distal end of the vascular pedicle was anastomosed with the more normal blood vessel at the distal end of the forearm; the invalid cavity was filled with the muscle flap. The donor site wounds of tissue flap were closed directly or treated with skin grafting. After operation, the blood supply and survival of the flap, the survival of the distal limb, and the survival of the skin graft at the flap donor site were observed. Computed tomography angiography (CTA) was performed to observe the patency of the proximal and distal anastomotic arteries from 2 to 4 weeks after surgery. During follow-up, the texture of the flap, the survival of the grafted skin and the healing of the donor area were observed. Results: One patient (complete forearm disconnection) developed distal limb blood disorder on 5 days after surgery. CTA examination suggested embolization of the distal anastomosis of the flow-through artery. more muscle and skin and soft tissue necrosis of the distal limb showed in emergency exploration. So, amputation was performed ultimately. No vascular crisis occurred in the skin flaps of the remaining 10 patients, and all skin flaps, distal limbs and the skin grafts in flap donor sites survived well. Two to 4 weeks after surgery, the proximal and distal ends of the anastomosed arteries were good in the patency. Follow-up for 11-37 months, the flap texture was good, and all donor site wounds healed well. Conclusions: The use of anterolateral thigh flow-through chimeric perforator flap to repair upper limb complex tissue defects accompanied by main artery injury can improve the success rate of limb salvage, which can be promoted in clinical practice.

In ovo injection of AZD6244 suppresses feather follicle development by the inhibition of ERK and Wnt/ß-catenin pathways in goose embryos (Anser cygnoides).

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value.2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and ß-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while ß-catenin protein was highly expressed in the middle stage of embryo development.3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/ß-catenin pathway protein expression.4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/ß-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, ß-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of ß-catenin and p-ERK were consistent with Western blot results.5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/ß-catenin pathways.

[Analysis methods and case analysis of effect modification (2): effect modification in network Meta-analysis].

This paper briefly introduces the characteristics, research significance, and global reporting status of effect modification in network Meta-analysis, demonstrates the heterogeneity caused by effect modification in network Meta-analysis, and emphasizes the importance of exploring effect modification in network Meta-analysis. This paper also summarizes the normalized description and analysis strategies of effect modification in network Meta-analysis. Finally, by the case of "comparison of efficacy of three new hypoglycemic drugs in reducing body weight in type 2 diabetes patients", this paper demonstrates the realization of subgroup analysis and network Meta-regression in exploring effect modification, summarizes the advantages and disadvantages of the two methods, to provide references for future researchers.

[Comparing the impact of left bundle branch area pacing and traditional left ventricular pacing on right heart function following dual-chamber pacemaker implantation].

Objective: To compare the effects of left bundle branch area pacing (LBBaP) versus traditional right ventricular pacing (RVP) on left ventricular function in patients after dual-chamber pacemaker implantation. Methods: A retrospective cohort study was conducted on patients who underwent dual-chamber pacemaker implantation from March 2017 to April 2021 in Beijing Anzhen Hospital. The patients were divided into the LBBaP group and RVP group based on the placement of the ventricular lead. Follow-up was conducted until March 2022, comparing baseline and follow-up echocardiographic parameters, pacing parameters, and the incidence and timing of complications between the two groups. The complications included ventricular electrode perforation, dislocation, pericardial effusion, tricuspid valve perforation, etc. Results: A total of 163 patients aged (68.3±13.5) years were included, including 82 (50.3%) men, with 80 patients in the LBBaP group and 83 in the RVP group. Baseline left ventricular end-diastolic diameter ((50.49±4.95) mm vs. (47.43±8.15) mm, P=0.01) and left atrium (LA) ((33.14±5.94) mm vs. (30.18±3.92) mm, P=0.001) in the LBBaP group were significantly higher than those in the RVP group. Follow-up LA diameter ((37.10±6.70) mm vs. (40.10±8.90) mm, P=0.016) showed a statistically significant difference in the LBBaP group compared to the RVP group. There was no statistically significant difference between the two groups in baseline QRS duration(P=0.490). Postoperative QRS duration in the LBBaP group was significantly lower ((110.69±24.01) ms vs. (139.65±29.85) ms, P<0.010). Intraoperative threshold in the LBBaP group was significantly higher ((0.83±0.32) V/0.48 ms vs. (0.71±0.23) V/0.48 ms, P=0.004), while impedance was lower ((754.53±205.59) Ω vs. (905.41±302.75) Ω, P<0.01). Comparing with the RVP group, postoperative ventricular pacing ratio (VP) ((87.39±20.92) % vs. (79.49±25.76) %, P=0.034), threshold ((0.90±0.38) V/0.48 ms vs. (0.69±0.27) V/0.48 ms, P<0.01) in the LBBaP group were higher, and impedance ((507.45±77.37) Ω vs. (620.52±197.29) Ω, P<0.01) in the LBBaP group was lower. Postoperative follow-up period was 5 to 51 months, with a median follow-up time of 17 months. No statistically significant difference in overall complications between the LBBaP and RVP groups was found (13.8% (11/80) vs. 7.2% (6/83), P>0.05). The median time to occurrence of complications after surgery was significantly earlier in the LBBaP group (29.74 (95%CI 27.21-32.26) months vs. 46.17 (95%CI 42.48-49.86) months, P=0.030). Conclusion: LBBaP demonstrates more stable pacing parameters, substantial improvement in clinical left ventricular function, with a relatively higher threshold compared to traditional RVP, and complications occurs relatively early.