[The application and effect of bispherical augment in acetabular defects reconstruction].

Objective: To evaluate the clinical effect of bispherical augment in acetabular defects reconstruction in hip revision. Methods: This is a retrospective case series study. A retrospective analysis of 119 patients (124 hips) patients who underwent hip revision surgery and reconstructed with bispherical augment for acetabular bone defects from January 2019 to December 2023 was performed. There were 57 males (58 hips) and 62 females (66 hips), aged (65.0±11.8) years (range:40 to 102 years). The body mass index was (23.9±3.5) kg/m2 (range:16.1 to 32.2 kg/m2). Acetabular bone defects were typed as follows: 2 hips in Paprosky type ⅡA, 29 hips in type ⅡB, 34 hips in type ⅡC, 31 hips in type ⅢA, and 28 hips in type ⅢB, of which 9 patients (9 hips) were combined with pelvic discontinuity. Differences in Harris hip score(HHS) and lower limb discrepancy(LLD) were compared between preoperatively and final follow-up. The height of the hip center of rotation and the horizontal distance from the center of rotation to the teardrop were measured by radiographs before and after surgery, and prothesis stability and the occurrence of postoperative complications were evaluated. Data were compared using the paired sample t test. Results: All patients successfully completed the operation. The operation time was (167.0±53.4)minutes (range:90 to 380 minutes) and the intraoperative bleeding was (345.3±124.2) ml (range:100 to 1 200 ml). The height of the hip center of rotation decreased from (39.7±13.0) mm preoperatively to (21.8±7.1) mm postoperatively and the horizontal distance from the center of rotation to the teardrop increased from preoperative (34.0±10.1)mm preoperatively to (38.5±5.9)mm preoperatively, and the differences were statistically significant (t=15.859,P<0.01;t=5.266,P<0.01). All the patients were followed up for (26.1±15.4)months (range:6 to 60 months). At the last follow-up, HHS improved from (35.2±10.0)points preoperatively to (85.5±9.5)points, and the difference was statistically significant (t=50.723,P<0.01). LLD decreased from (2.1±1.1) cm preoperatively to (0.5±0.5) cm, and the difference was statistically significant (t=13.767, P<0.01). All acetabular components were stable and free of displacement on imaging during follow-up. Three patients suffered dislocation and received closed reduction, all prosthesis were in good position during follow-up. No dislocation, loosening, fracture, recurrence of infection and vascular nerve injury occurred in other patients. Conclusion: Bispherical augment can effectively reconstruct acetabular bone defects, restore the hip center of rotation, and improve hip joint function scores at short or mid-term follow-up.

Epoxyeicosatrienoic Acids Attenuate LPS-Induced NIH/3T3 Cell Fibrosis through the A2AR and PI3K/Akt Signaling Pathways.

Inflammation plays a crucial role in progression of fibrosis. Epoxyeicosatrienoic acids (EET) have multiple protective effects in different diseases, but their ability to inhibit the development of LPS-induced fibrosis remains unknown. The potential therapeutic effects of 11,12-EET were studied in in vitro model of LPS-induced fibrosis. Mouse embryonic fibroblast cells NIH/3T3 were pre-incubated with 1 µM 11,12-EET and/or a structural analogue and selective EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid before exposing to LPS. The effect of EET was evaluated by the protein and mRNA expression of NF-κB, collagens I and III, and α-smooth muscle actin by Western blotting and quantitative reverse transcription PCR, respectively. LPS provoked inflammation and fibrosis-like changes accompanied by elevated expression of NF-κB and collagens in NIH/3T3 cells. We also studied the effects of 11,12-EET on the A2AR and PI3K/Akt signaling pathways in intact and LPS-treated NIH/3T3 cells. 11,12-EET prevented inflammation and fibrosis-like changes through up-regulation of A2AR and PI3K/Akt signaling pathways. Our findings demonstrate the potential antifibrotic effects of 11,12-EET, which can be natural antagonists of tissue fibrosis.

[The association between visceral adipose thickness and gestational diabetes mellitus in the first trimester].

Objective: To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13+6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results: A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [RR(95%CI): 1.34 (1.08-1.67)], and 61% [RR(95%CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [RR(95%CI): 1.42 (1.22-1.65)] and 70% [RR(95%CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old (P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m2, and the GDM risk increased by 57% [RR(95%CI): 1.57 (1.22-2.04)] in Q3 and 65% [RR(95%CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion: High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.

Economic Impact of Progression from Mild Cognitive Impairment to Alzheimer Disease in the United States.

BACKGROUND: Limited evidence exists on the economic burden of individuals who progress from mild cognitive impairment (MCI) to Alzheimer disease and related dementia disorders (ADRD). OBJECTIVES: To assess the all-cause health care resource utilization and costs for individuals who develop ADRD following an MCI diagnosis compared to those with stable MCI. DESIGN: This was a retrospective cohort study from January 01, 2014, to December 31, 2019. SETTING: The Merative MarketScan Commercial and Medicare Databases were used. PARTICIPANTS: Individuals were included if they: (1) were aged 50 years or older; (2) had ≥1 claim with an MCI diagnosis based on the International Classification of Diseases, Ninth Revision (ICD-9) code of 331.83 or the Tenth Revision (ICD-10) code of G31.84; and had continuous enrollment. Individuals were excluded if they had a diagnosis of Parkinson's disease or ADRD or prescription of ADRD medication. MEASUREMENTS: Outcomes included all-cause utilization and costs per patient per year in the first 12 months following MCI diagnosis, in total and by care setting: inpatient admissions, emergency department (ED) visits, outpatient visits, and pharmacy claims. RESULTS: Out of the total of 5185 included individuals, 1962 (37.8%) progressed to ADRD (MCI-to-ADRD subgroup) and 3223 (62.2%) did not (Stable MCI subgroup). Adjusted all-cause utilization was higher for all care settings in the MCI-to-ADRD subgroup compared with the Stable MCI subgroup. Adjusted all-cause mean total costs ($34 599 vs $24 541; mean ratio [MR], 1.41 [95% CI, 1.31-1.51]; P<.001), inpatient costs ($47 463 vs $38 004; MR, 1.25 [95% CI, 1.08-1.44]; P=.002), ED costs ($4875 vs $3863; MR, 1.26 [95% CI, 1.11-1.43]; P<.001), and outpatient costs ($16 652 vs $13 015; MR, 1.28 [95% CI, 1.20-1.37]; P<.001) were all significantly higher for the MCI-to-ADRD subgroup compared with the Stable MCI subgroup. CONCLUSIONS: Individuals who progressed from MCI to ADRD had significantly higher health care costs than individuals with stable MCI. Early identification of MCI and delaying its progression is important to improve patient and economic outcomes.

Water uptake patterns and rooting depths of Tamarix ramosissima in the coppice dunes of the Gurbantünggüt Desert, China: a stable isotope analysis.

Tamarix ramosissima has an important role in stabilizing sand dunes in desert ecosystems. Understanding the water use strategies of T. ramosissima is essential to understand its adaptations on coppice dunes. We utilized the stable isotopes δ2H and δ18O in soil water, groundwater, and xylem water to identify monthly differences in water sources. Additionally. we explored rooting depth using 2H2O as an artificial tracer. In May, T. ramosissima derived 75% of its water from shallow and middle soil layers. In July, it absorbed 90% water from middle and deep soil layers. In August and September, it acquired approximately 80% of its water from deep soil layers. The labelling using 2H as an artificial tracer indicated that the root system of T. ramosissima could reach depths >500 cm in the coppice dunes. 2H absorption was observed at depths of 100, 200, 300 and 400 cm. Soil water is the dominant water source for T. ramosissima in the coppice dunes because groundwater is at depths >30 m. The flexible water-use strategies of T. ramosissima enable it to effectively utilize different available water sources to adapt to the arid environment. These findings improve our understanding of water uptake patterns and drought adaptation strategies of T. ramosissima in the coppice dunes of desert ecosystems.

[A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia].

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

[Fetoscopy for intrauterine diagnosis and treatment of amniotic band syndrome: a clinical analysis of 7 cases and literature review].

Objective: To summarize the clinical value of fetoscopy in the prenatal diagnosis and treatment of amniotic band syndrome (ABS). Methods: A retrospective analysis was conducted on the clinical data of seven ABS fetuses who underwent prenatal fetoscopic intervention at the Third Affiliated Hospital of Zhengzhou University from December 2020 to August 2023. Literatures related to fetoscopic treatment of ABS were searched in databases including China National Knowledge Infrastructure, Wanfang Data, and PubMed. Clinical data were extracted and the characteristics and intervention effects of fetoscopic surgery in the treatment of ABS were summarized. Results: (1) Preoperative evaluation: the gestational age at diagnosis for the seven ABS fetuses was (19.8±4.4) weeks, and the gestational age at fetoscopic intervention was (22.2±2.8) weeks. The indications for fetoscopic intervention included umbilical cord involvement (3 cases), limb amniotic band with circular constriction (2 cases), and unclear visualization of digits (3 cases). (2) Pregnancy outcomes: among the seven ABS fetuses, four cases underwent selective termination of pregnancy due to severe intrauterine limb amputation, and three cases underwent fetoscopic lysis of amniotic bands. Among the latter three cases, one case experienced intrauterine fetal death (IUFD) two weeks after the procedure, and two cases had good postoperative outcomes. (3) Literature review: a total of 40 cases, including 37 cases from 17 articles and three cases from our institution, were included in the analysis. The indications for fetoscopic surgery included limb amniotic band with circular constriction and involvement of the umbilical cord. The success rate of the surgery was 82% (33/40), and 78% (29/37) of the affected limbs retained good functionality. Premature rupture of membranes was the most common complication, with an incidence rate of 48% (16/33). The average interval from the surgery to membrane rupture was (6.1±5.1) weeks, and the average interval from the surgery to delivery was (10.5±4.1) weeks, with an average gestational age at delivery of (33.7±3.6) weeks. The pregnant women were divided into single Trocar group (27 cases) and double Trocar group (13 cases) based on the surgical approach. The success rates in single Trocar group and double Trocar group were 78% (21/27) and 12/13, respectively, and the difference was not statistically significant (χ2=0.474, P=0.491). The gestational age of delivery in the single Trocar group and double Trocar group was (32.7±3.4) and (35.4±3.2) weeks, respectively, and the difference was statistically significant (t=-2.185, P<0.05). There were no statistically significant differences in the success rate of the surgery, incidence of premature rupture of membranes, interval between surgery and membrane rupture, interval between surgery and delivery, and preterm delivery rate between the two groups (all P>0.05). Conclusions: Fetoscopy could be used for prenatal assessment and intrauterine treatment of ABS. Fetoscopic lysis of amniotic bands may be an effective method for treating ABS, which helps preserve limb function and prevent intrauterine limb amputation and IUFD.

[Genetic drivers for inflammatory protein markers in colorectal cancer: a Mendelian randomization approach to clinical prognosis study].

OBJECTIVE: To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization (MR) approach. METHODS: We obtained data pertaining to colorectal cancer from Genome-Wide Association Study (GWAS) datasets and used 91 inflammatory protein markers as the exposure variables. A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk. The robustness of the results was evaluated through heterogeneity, pleiotropy, and sensitivity analyses using 5 MR models: Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Simple Mode, and Weighted Mode. We examined the mRNA expressions of PD-L1, AXIN1, and ß-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December, 2021 and December 2023, and analyzed their correlation with the clinical characteristics of the patients. RESULTS: Using the IVW model, MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1 (OR=0.866, 95% CI: 0.754-0.994, P=0.040), ß-NGF (OR=0.914, 95% CI: 0.843-0.990, P=0.028; OR=0.884, 95% CI: 0.784-0.998, P=0.047 using Weighted Median model), and PD-L1 (OR=0.903, 95% CI: 0.824- 0.989, P=0.028). No significant heterogeneity or pleiotropy was observed, indicating good stability of the results. Sensitivity analysis confirmed the reliability of the findings. The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging, particularly in stage Ⅳ patients (P=0.007). AXIN1 and ß -NGF expression levels were significantly correlated with the degree of tumor differentiation, and their expressions were higher in poorly differentiated samples (P<0.001). CONCLUSION: Lowered expressions of inflammatory protein markers AXIN1, ß-NGF, and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation. These markers may thus serve as potential targets for colorectal cancer treatment and prevention.

[Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study].

Objective: To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer. Methods: The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results: Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026-0.828, P=0.030). Conclusion: Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

[Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells].

Objective: To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) . Methods: In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 µmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 µmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 µmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 µmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 µmol/L PQ), and inhibitor group (200 µmol/L PQ+20 µmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted. Results: The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance (P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group (P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group (P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group (P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group (P<0.05/3) . Conclusion: CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.

[Evaluation of disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings].

Objective: To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings. Methods: The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated. Results: In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot (P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion: Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.

[Interpretation of T-cell and NK-cell lymphoid proliferations and lymphomas in the 5th edition of the WHO classification of haematolymphoid tumours].

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.

Comparative transcriptomic analyses reveal key genes underlying melanin distribution during embryonic development in geese (Anser anser).

1. Melanin distribution typically exhibits a gradient dilution along the dorsal-ventral axis of the body, including in domestic geese. However, the specific genes and molecular mechanisms responsible for this melanin distribution pattern remain incompletely understood.2. The transcriptomic comparisons were conducted at three embryonic stages, specifically on embryonic d 15 (E15), 22 (E22), and 29 (E29), between the pigmented dorsal skin and the depigmented distal foot.3. Differentially expressed genes (DEGs) associated with melanin synthesis were identified, particularly TYR, TYRP1, and EDNRB2, which exhibited significantly higher expression levels in the dorsal skin at E15 and E22. However, expression levels significantly decreased in later stages (E29).4. The ASIP gene showed remarkably high-expression levels in the distal feet compared to the dorsal skin post-E22 stage (log2FC: 5.31/6.88 at E22/E29). Gene Ontology (GO) enrichment analysis detected eight terms associated with melanin synthesis and melanosome formation (p < 0.05), including melanosome membrane (GO: 0033162) and melanin biosynthetic process (GO: 0042438). Additionally, KEGG pathway analysis showed significant enrichment of the melanogenesis pathway (hsa004916) at d 22 (E22).

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

[Esthetic analysis of upper lip morphology variation after the cross-arch fixed restoration of maxillary implant-supported prostheses via radiographic methods].

Objective: To measure and analyze upper lip morphology variation before and after the cross-arch fixed restoration of the maxillary implant-supported prostheses using cone- beam CT (CBCT) to provide an esthetic objective reference for maxillary edentulous patients. Methods: There were 32 maxillary edentulous patients selected in the Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University from January 2010 to December 2023. The CBCT data of patients with maxillary full-arch implant-supported fixed prostheses were retrospectively collected before implantation (T0), at the time of radio-guide insertion (T1), and after final repair (T2). The length and thickness of the upper lip were measured and analyzed at each time point, and the correlation between the upper lip contour data and facial esthetic parameters was analyzed. Results: After the final prosthodontic treatment, the length of the upper lip was significantly increased from (21.72±2.84) mm to (24.98±2.93) mm (t=-8.13, P<0.001) compared with that before implant treatment. The widths of the middle and vermilion of the upper lip (Sm-Hm/Ls-UP), were reduced from (13.24±1.41), (12.81±1.67) mm to (11.36±1.67), (10.21±1.69) mm, with significant differences (t=7.79, P<0001; t=9.37, P<0.001). The lower face height (Sn-Gn) was increased from (54.52±4.95) mm to (58.70±4.42) mm, with significant differences (t=-11.05, P<0.001). However, the nasolabial angle reduced significantly from 95.35°± 7.70°to 90.53°±7.28°(t=7.68, P<0.001). The width of the middle of the upper lip with a radiation guide was (10.94±1.24) mm, and it increased significantly compared with that after the final prosthesis treatment (t=-0.76, P<0.05). The proportion of straight upper lip profiles accounted for 59% (19/32), and the proportion of concave upper lip profiles accounted for 41% (13/32) after the final prosthesis treatment. In addition, the results of correlation analysis showed that the nasolabial angle variation was weak and negatively correlated with residual bone height (r=-0.37, P=0.490). Conclusions: After the treatment of the maxillary full-arch implant-supported fixed prosthesis, the length of the upper lip increases, and the thickness of the upper lip becomes significantly thin. The maxillary full-arch implant-supported fixed prostheses support upper lips to improve the patients' side appearances.

Mechanism studies for relativistic attosecond electron bunches from laser-illuminated nanotargets.

To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.