Biomechanical strength of triceps tendon repairs: systematic review and meta-regression analysis of human cadaveric studies.

PURPOSE: It is unclear which triceps tendon repair constructs and techniques produce the strongest biomechanical performance while minimizing the risk of gap formation and repair failure. We aimed to determine associations of construct and technique variables with the biomechanical strength of triceps tendon repairs. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for peer-reviewed studies on biomechanical strength of triceps tendon repairs in human cadavers. 6 articles met the search criteria. Meta-regression was performed on the pooled dataset (123 specimens). Outcomes of interest included gap formation, failure mode, and ultimate failure load. Covariates were fixation type; number of implants; and number of sutures. Stratification by covariates was performed. We found no association between fixation type and ultimate failure load; however, suture anchor fixation was associated with less gap formation compared with transosseous direct repair (ß = - 1.1; 95% confidence interval [CI]:- 2.2, - 0.04). A greater number of implants was associated with smaller gap formation (ß = - 0.77; 95% CI: - 1.3, - 0.28) while a greater number of sutures was associated with higher ultimate failure load ( ß= 3; 95% CI: 21, 125). In human cadaveric models, the number of sutures used in triceps tendon repairs may be more important than the fixation type or number of implants for overall strength. If using a transosseous direct repair approach to repair triceps tendon tears, surgeons may choose to use more sutures in their repair in order to balance the risk of larger gap formation when compared to indirect repair techniques. LEVEL OF EVIDENCE: Level III.

Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant and immune responses of lactating donkeys.

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 years of BW ± SD), weight (250.06 ± 25.18 kg), days in milk (39.11 ± 7.42 d), and averaged parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 weeks for adaptation, and 8 weeks for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including dry matter intake, milking yield, estimated milk yield, solids-corrected milk, energy-corrected milk, milk fat yield, milk protein yield, milk lactose yield, milk total solids yield, and milk solid not fat yield. The digestibility of dry matter, crude protein, acid detergent fiber, and neutral detergent fiber was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of immunoglobulin A, immunoglobulin G, and immunoglobulin M, the activities of the superoxide dismutase, catalase and total antioxidant capacity in the serum. AOCP decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites L-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, LysoPC (18:0), LysoPC (18:1(9Z), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.

Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs.

Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy1. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically2,3. Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis.

Inflammation promotes aging-associated oncogenesis in the lung.

Background: Lung cancer is the leading cause of cancer death in the world. While cigarette smoking is the major preventable factor for cancers in general and lung cancer in particular, old age is also a major risk factor. Aging-related chronic, low-level inflammation, termed inflammaging, has been widely documented; however, it remains unclear how inflammaging contributes to increased lung cancer incidence. Aim: To establish connections between aging-associated changes in the lungs and cancer risk. Methods: We analyzed public databases of gene expression for normal and cancerous human lungs and used mouse models to understand which changes were dependent on inflammation, as well as to assess the impact on oncogenesis. Results: Analyses of GTEx and TCGA databases comparing gene expression profiles from normal lungs, lung adenocarcinoma, lung squamous cell carcinoma of subjects across age groups revealed upregulated pathways such as inflammatory response, TNFA signaling via NFκB, and interferon-gamma response. Similar pathways were identified comparing the gene expression profiles of young and old mouse lungs. Transgenic expression of alpha 1 antitrypsin (AAT) partially reverses increases in markers of aging-associated inflammation and immune deregulation. Using an orthotopic model of lung cancer using cells derived from EML4-ALK fusion-induced adenomas, we demonstrated an increased tumor outgrowth in lungs of old mice while NLRP3 knockout in old mice decreased tumor volumes, suggesting that inflammation contributes to increased lung cancer development in aging organisms. Conclusions: These studies reveal how expression of an anti-inflammatory mediator (AAT) can reduce some but not all aging-associated changes in mRNA and protein expression in the lungs. We further show that aging is associated with increased tumor outgrowth in the lungs, which may relate to an increased inflammatory microenvironment.

Evaluation of postoperative outcomes in palatoplasty with three soft palate cleft repairs.

The aim of this study was to compare the postoperative clinical and functional outcomes of palatoplasty with three soft palate cleft repairs and analyse the factors potentially impacting these outcomes. A retrospective analysis was conducted on a consecutive series of 337 patients who underwent primary cleft palate repair by palatoplasty modified with either Furlow Z-plasty (P-FZP, n = 77), intravelar veloplasty (P-IVV, n = 110), or combined intravelar veloplasty-Furlow Z-plasty (P-IVV-FZP, n = 150). The postoperative outcomes evaluated included wound healing (complete closure/fistula) and velopharyngeal function. Demographic and surgical data were analysed using both univariate and multivariate analysis. There was no significant difference between the groups with regard to the sex distribution, age at repair, cleft width, cleft type, or follow-up duration. However, relaxing incisions were significantly more common with P-FZP (26.0%) and P-IVV (29.1%) compared to P-IVV-FZP (10%) (P = 0.002 and <0.001, respectively). The complete wound closure rate was significantly higher with P-IVV-FZP (97.3%) compared to P-FZP (88.3%) (P = 0.012) and P-IVV (90%) (P = 0.015). The normal velopharyngeal function rate was comparable for P-IVV-FZP (86.7%) and P-FZP (83.1%), and both rates were significantly better than the rate with P-IVV (73.6%) (P = 0.039 and 0.029, respectively). The cleft type and width were identified as factors influencing postoperative outcomes. In conclusion, it may be appropriate to prioritize the palatoplasty with combined intravelar veloplasty-Furlow Z-plasty whenever feasible.

Prognostic role of the systemic immune-inflammation index and pan-immune inflammation value for outcomes of breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This review examined the literature for evidence on the prognostic ability of systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV) for predicting overall survival (OS) and disease-free survival (DFS) in breast cancer patients. MATERIALS AND METHODS: PubMed, Embase, Scopus, and Web of Science were searched with Google Scholar for gray literature. All types of studies reporting the association between SII or PIV and OS or DFS of breast cancer were eligible. RESULTS: 13 studies on SII and 4 studies on PIV were included. Meta-analysis showed that a high SII was a significant predictor of OS (HR: 1.97 95% CI: 1.54, 2.52 I2=76%) and DFS (HR: 2.07 95% CI: 1.50, 2.86 I2=79%) in breast cancer patients. These results did not change on sensitivity analysis and were more or less stable on multiple subgroup analyses. Pooled analysis showed that high PIV was also a significant predictor of poor OS (HR: 2.63 95% CI: 1.46, 4.74 I2=71%) and DFS (HR: 1.64 95% CI: 1.23, 2.17 I2=0%) in breast cancer patients. CONCLUSIONS: High SII and PIV can predict poor OS and DFS in breast cancer patients. High heterogeneity and the observational nature of data are important limitations of the review. Further studies are needed specifically on PIV to increase the strength of the evidence.

Theoretical study of the effects of alloying elements on TiO2/Ti2AlNb interface adhesion properties.

Ti2AlNb-based alloys are expected to be applied in the manufacture of parts of aeroengines to achieve the goal of increasing the thrust-to-weight ratio. However, the poor high temperature oxidation resistance of these alloys may hinder their applications. Alloying has been proven to be effective in improving oxidation resistance properties. However, the selection of alloying elements and their influence mechanisms are rarely studied. The TiO2/Ti2AlNb interface bonding interactions and the effects of alloying elements of Si, Sc, Y, Zr, Mo and Hf were investigated via first principles calculations. The separation energy and electronic structure were studied to explore the bonding interactions between the oxide scale and Ti2AlNb matrix. When Zr and Hf are used to replace Al, the bonding properties of the TiO2/Ti2AlNb interface are improved. The tensile and shear deformations of the interfacial zones are applied to study the influence of alloying elements on the TiO2 oxide spalling on Ti2AlNb. The tensile strength is increased by more than 2 GPa when Nb is substituted by the Sc, Zr and Hf elements. Therefore, Sc, Zr, and Hf are beneficial for inhibiting oxide spalling and will have great potential to improve the oxidation resistance properties.

Endochondral Repair of Jawbone Defects Using Periosteal Cell Spheroids.

Recapitulation of the natural healing process is receiving increasing recognition as a strategy to induce robust tissue regeneration. Endochondral ossification has been recognized as an essential reparative approach in natural jawbone defect healing. However, such an approach has been overlooked in the recent development of cell-based therapeutics for jawbone repair. Therefore, this study aimed to explore a bioinspired stem cell-based strategy for jawbone repair by mimicking the mesenchymal condensation of progenitor cells during the early endochondral ossification process. For this purpose, passage 3 of jawbone periosteum-derived cells (jb-PDCs) was cultured in our previously reported nonadherent microwells (200 µm in diameter, 148 µm in depth, and 100 µm space in between) and self-assembled into spheroids with a diameter of 96.4 ± 5.8 µm after 48 h. Compared to monolayer culture, the jb-PDC spheroids showed a significant reduction of stemness marker expression evidenced by flow cytometry. Furthermore, a significant upregulation of chondrogenic transcription factor SOX9 in both gene and protein levels was observed in the jb-PDC spheroids after 48 h of chondrogenic induction. RNA sequencing and Western blotting analysis further suggested that the enhanced SOX9-mediated chondrogenic differentiation in jb-PDC spheroids was attributed to the activation of the p38 MAPK pathway. Impressively, inhibition of p38 kinase activity significantly attenuated chondrogenic differentiation jb-PDC spheroids, evidenced by a significant decline of SOX9 in both gene and protein levels. Strikingly, the jb-PDC spheroids implanted in 6- to 8-wk-old male C57BL/6 mice with critical-size jawbone defects (1.8 mm in diameter) showed an evident contribution to cartilaginous callus formation after 1 wk, evidenced by histological analysis. Furthermore, micro-computed tomography analysis showed that the jb-PDC spheroids significantly accelerated bone healing after 2 wk in the absence of exogenous growth factors. In sum, the presented findings represent the successful development of cell-based therapeutics to reengineer the endochondral bone repair process and illustrate the potential application to improve bone repair and regeneration in the craniofacial skeleton.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[Research on the protective effect of hearing protective device for workers exposed to noise in a motor manufacturing enterprise].

Objective: To understand the current situation of noise hazard in a motor manufacturing enterprise, and to explore the protective effect of workers wearing hearing protective device and its possible influencing factors. Methods: In November 2021, a total of 179 noise workers wearing hearing protective devices in a motor manufacturing company in a city were selected as research objects. Personal attenuation rating (PAR) of workers wearing hearing protective devices was measured. Baseline PAR was analyzed for different subgroups of basic demographic information, noise exposure, and the use of hearing protective devices to evaluate the effect of the intervention. Baseline PAR was compared using nonparametric tests. Results: There were 179 workers from 35 positions in 4 types of work, and the over-standard noise rate was 51.2% (42/82), among which the noise exposure intensity of motor equipment debugging workers was the highest [94.4 dB (A) ]. Compared the baseline PAR of different characteristics, it was found that the baseline PAR of male workers, workers whose daily noise exposure time were <8 h, workers who had used the hearing protective devices for 10 to 14 years, and workers who thought the hearing protective devices were comfortable were all higher, and the differences were statistically significant (P<0.05). Baseline PAR passing rate was 43.0% (77/179), and PAR of 102 workers who did not pass baseline test increased from 0 (0, 3) dB before intervention to 14 (12, 16) dB after intervention, with statistical significance (P<0.05) . Conclusion: The noise hazard in this motor manufacturing enterprise is serious, and the protective effect of workers wearing hearing protective devices is not good. Gender, daily noise exposure time, years and comfort of wearing hearing protective device are the possible influencing factors of poor protective effect.

[Untargeted metabolomics study of dexamethasone-induced congenital cleft palate in New Zealand rabbits].

Objective: To investigate the metabolic disorders in placental tissues of dexamethasone induced cleft palate mode. Methods: Twelve pregnant rabbits were randomly divided into dexamethasone group (experimental group, 8) and saline control group (4), and a certain amount of dexamethasone and saline were administered intramuscularly to the experimental and control groups respectively from embryonic days (ED) 13 to 16, and placental tissue samples were collected on day 21 of gestation. The corresponding profiles of the embryonic placental tissue samples were obtained by liquid chromatography-triple tandem quadrupole(LC-MS), and the metabolites of the embryonic placental tissues were characterized by principal component analysis among the dexamethasone-treated group with cleft palate (D-CP group), the dexamethasone-treated group without cleft palate (D-NCP group) and the control group. Results: There were significant metabolic differences among the D-CP group, D-NCP group and control group, with a total of 133 differential metabolites (VIP>1, P<0.05) involving in important metabolic pathways including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism, and galactose metabolism. The four metabolites, vitamin B6, galactose, lysine and urea, differed among the three groups (P<0.05). There were significant differences in vitamin B6 (0.960±0.249, 0.856±0.368, 1.319±0.322), galactose (0.888±0.171, 1.033±0.182, 1.127±0.127), lysine (1.551±0.924, 1.789±1.435, 0.541±0.424) and urea (0.743±0.142, 1.137±0.301, 1.171±0.457, respectively) levels among control group, D-NCP group and D-CP group (F=5.90, P=0.008; F=5.59, P=0.009; F=4.26, P=0.025; F=5.29, P=0.012). Conclusions: The results indicated that dexamethasone induced cleft palate may be highly correlated with metabolic disorders including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism and galactose metabolism.

[Meta-analysis comparing long-term outcomes of intersphincteric resection versus abdominoperineal resection for low rectal cancer].

Objective: To compare the long-term outcomes of intersphincteric (trans-internal and external) sphincter resection (ISR) and abdominoperineal proctocolectomy (APR) for low-grade rectal cancer. Methods: We used a meta-analytic approach to compare these procedures . Published reports comparing ISR and APR for low rectal cancer in Pubmed, Medline, EMBASE and Cochrane, China Knowledge Network (CNKI), China Biomedical Literature Database, and Vipers databases between January 2005 and January 2023 were searched and those meeting the eligibility criteria were selected for extraction of data for analysis. Inclusion criteria were as follows: (1) all reports comparing ISR and APR for low rectal cancer before January 2023; and (2) prospective randomized controlled studies or well-designed cohort studies. Exclusion criteria were as follows: (1) full text not available; (2) duplicate publications, missing primary outcome indicators, and unknown data; and (3) invalid statistical analysis. Results: Sixteen studies with 2498 patients were included in this study. Compared with the APR group, patients in the ISR group were relatively younger (weighted mean difference [WMD]=-1.82, 95%CI=-2.94 to -0.70, P=0.01), had tumors farther from the anal verge (WMD=0.43, 95%CI=0.18 to 0.67, P<0.01), and lower pathological T-stage (T3-4 stage: OR=0.54, 95%CI=0.36 to 0.81, P<0.01). In contrast, there were no statistically significant differences between the two groups in gender (P=0.78), body mass index (P=0.77), or pathological N stage (P=0.09). Compared with the APR group, patients in the ISR group had a lower rate of postoperative complications (OR=0.77, 95%CI=0.60 to 0.99, P=0.04), shorter hospital stay (WMD=-4.30, 95%CI=-7.07 to -1.53, P<0.01), higher 5-year overall survival (HR=0.54, 95%CI=0.33 to 0.88, P=0.01), and higher 5-year disease-free survival (HR=0.65, 95%CI=0.47 to 0.90, P<0.01). Five-year locoregional failure (HR=0.66, 95%CI=0.40 to 1.10, P=0.11) and time to surgery (WMD=-9.71, 95%CI=-41.89 to 22.47, P=0.55) did not differ significantly between the two groups. Conclusion: ISR is a safe and effective alternative to APR for early-stage low-grade rectal cancer.

[Comparison of intraoperative neurophysiological monitoring between patients with arthrogryposis multiplex congenita and adolescent idiopathic scoliosis].

Objective: To compare the intraoperative neurophysiological monitoring (IONM) results between patients with arthrogryposis multiplex congenita (AMC) and adolescent idiopathic scoliosis (AIS) and to analyze the influence of congenital spinal deformity on IONM in AMC patients, thus to evaluate the efficiency of IONM in AMC patients. Methods: A cross-sectional study. The clinical data of 19 AMC patients underwent correction surgery from July 2013 to January 2022 in Nanjing Drum Tower Hospital were retrospectively reviewed. There were 13 males and 6 females with a mean age of (15.2±5.6) years, and the average Cobb angle of main curve was 60.8°±27.7°. And 57 female AIS patients of similar age and curve type with the AMC patients during the same period were selected as the control group, with an average age of (14.6±4.4) years and a mean Cobb angle of 55.2°±14.2°. The latency and amplitude of samatosensory evoked potentials (SSEPs) and transcranial electric motor evoked potentials (TCeMEPs) were compared between the two groups. The difference in IONM data between AMC patients with and without congenital spinal deformity was also evaluated. Results: The success rates of SSEPs and TCeMEPs were 100% and 14/19 for AMC patients, 100% and 100% for AIS patients. The SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency, TCeMEPs-amplitude showed no significant difference between AMC patients and AIS patients (P>0.05 for all). The side-difference of TCeMEPs-amplitude showed an increasing trend in AMC patients when compared with that in AIS patients, but there was no statistical difference between the two groups [(147.0±185.6) µV vs (68.1±311.4) µV, P=0.198]. The SSEPs-amplitude value was (1.4±1.1) µV on concave side in AMC patients with congenital spinal deformity, and it was (2.6±1.2) µV on concave side in AMC patients without congenital spinal deformity (P=0.041). The SSEPs-amplitude value was (1.4±0.8) µV on convex side in AMC patients with congenital spinal deformity, and it was (2.6±1.3) µV on convex side in AMC patients without congenital spinal deformity (P=0.028). Conclusions: The values of SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency and TCeMEPs-amplitude are similar in AMC and AIS patients. The SSEPs-amplitude of AMC patients with congenital spinal deformity is lower than that of AMC patients without congenital spinal deformity.

A Variant in the IRF6 Promoter Associated with the Risk for Orofacial Clefting.

The single-nucleotide polymorphism (SNP) rs2235371 (IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.

Exosomes Derived from Endothelial Cells Inhibit Neointimal Hyperplasia Induced by Carotid Artery Injury in Rats via ROS-NLRP3 Inflammasome Pathway.

This study attempted to investigate whether exosomes derived from rat endothelial cells (EC-Exo) attenuate intimal hyperplasia after balloon injury using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence staining, Evans blue staining, and Western blotting. The results indicated that EC-Exo inhibited intimal hyperplasia in the carotid artery after balloon injury, promoted re-endothelialization, and reduced vascular inflammation and ROS-NLRP3-mediated cell pyroptosis. Thus, EC-Exo can inhibit neointimal hyperplasia after carotid artery injury in rats presumably by inhibiting the ROS-NLRP3 inflammasome and phenotypic transformation of vascular smooth muscle cells.

[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

[Effect of methylene blue labeling on therapeutic effect and prognosis of gastric cancer patients in D2 radical gastrectomy under laparoscope].

Objective: To investigate the effect of methylene blue tracing on the effect of surgical resection and the prognosis of gastric cancer patients in D2 radical surgery under laparoscope. Methods: In this retrospective cohort study, 160 patients with advanced gastric cancer who underwent surgical treatment in Xinxiang Central Hospital, the 4th Clinical College of Xinxiang Medical College from January 2016 to January 2019 were selected for retrospective analysis. Among them, 84 patients underwent laparoscopic D2 radical gastrectomy for gastric cancer combined with methylene blue labeling operation (labeling group), and the other 76 patients underwent only laparoscopic D2 radical gastrectomy for gastric cancer (control group). The difference of intraoperative and postoperative recovery, lymph node dissection, and postoperative 3-year cumulative survival rate between the two groups were analyzed. Results: The age of patients in the labeled group and the control group were (64.9±7.8) and (66.0±8.3) years old, respectively (P=0.389); And the male patients accounted for 61.9% (52 cases) and 55.3% (42 cases), respectively (P=0.394); The operation time in the labeled group was (218.5±19.6) min, which was shorter than that in the control group (230.1±17.4) min (P<0.001). There was no significant difference between the labeled group and the control group in the amount of bleeding during operation, the time of anal exhaust after operation, the time of eating after operation, the time of hospitalization after operation, and the average diameter of lymph nodes (P>0.05). The total number of dissected lymph nodes, D1 lymph nodes and D2 lymph nodes in the labeled group were significantly higher than those in the control group (all P values<0.05). The operative complication rate in the labeled group was 11.9% (10 cases), which was lower than that in the control group (25.0%, 19 cases) (P=0.032); There was no statistical significance in 3-year cumulative survival rates of patients between the labeled group (61.9%) and the control group (52.6%) (χ2=3.46,P=0.065). Conclusion: The use of methylene blue tracing in laparoscopic D2 radical surgery for gastric cancer is beneficial to reduce the operation time, improve the lymph node clearance rate, and reduce surgical complications.

[Re-understanding of the biological behavior of anaplastic thyroid carcinoma].

Anaplastic thyroid carcinoma (ATC) is one of the most malignant tumors. However, in recent years, the prognosis of the disease has also changed quietly, and there have been reports of successful clinical treatment and significantly prolonged survival time. Based on the successful treatment of a 79-year-old patient and more than three years of follow-up, as well as the clinical analysis of 45 ATC patients, the author deeply believes that it is necessary to re-examine the understanding of ATC and urgently adjust the clinical strategies. If ATC can be diagnosed early and treated by comprehensive treatment based on radical surgery, the prognosis of a considerable number of patients can be greatly improved, the overall survival time will be greatly prolonged, and a considerable number of patients may achieve clinical cure. In addition, genetic testing and targeted therapy bring a new hope for the survival of some patients.

Stability of nasal symmetry following primary cleft lip and nasal repair: five years of follow-up.

Despite advances in cleft lip treatment, various levels of residual deformity remain after primary repair of cleft lip and palate. The aim of the current study was to compare the stability of short- and long-term postoperative nasal symmetry. This retrospective study included 100 consecutive non-syndromic patients with unilateral complete cleft lip who underwent primary cleft lip repair with follow-up of 5 years. Measurements taken from basal and frontal standard photograph views, obtained preoperatively (T1) and immediately (T2), 1 year (T3), and 5 years postoperative (T4), were analysed. Paired and independent t-tests were applied to assess the significance of differences and relationships, while the inter-class correlation coefficient was used to assess reliability; P < 0.05 was considered significant. The male to female ratio was 1:1; mean age at the time of surgery was 0.43 ± 0.25 years. All patients showed significant improvements following unilateral complete cleft lip repair. All variables measured at T3 revealed a significant relapse when compared to T2, except alar base position, which showed a constant mean across all postoperative follow-ups. Late relapse (T3-T4) was not significant for alar collapse, alar base position, or columellar angle (all P > 0.05). On the other hand, columellar height (P = 0.003), and nostril height (P = 0.038) and width (P = 0.007) showed significant improvements during the late relapse period. In conclusion, the majority of the relapse and changes following the nasal cleft repair occurred within the first postoperative year. However, nasal asymmetries tended to remain stable or reduced during the first 5 postoperative years.

Can surgeons rely on growth-related changes to achieve lip height and width symmetry in unilateral complete cleft lip repair?

Surgeons face difficulties achieving simultaneous lip height and width symmetry while repairing unilateral complete cleft lip, so one is often sacrificed at the expense of the other. The aim of this study was to evaluate the effect of growth on lip height and width symmetry, to guide the surgeon to the best decision. The study patients (N = 105) were divided into two groups based on the treatment method: 42 were treated with the modified rotational advancement technique (MRA group) and 63 with the Millard rotation-advancement technique (RA group). Furthermore, based on lip height and width symmetry at 6 months postoperative, the patients were divided into three groups: 38 with symmetrical lip height and width (SL), 41 with horizontal lip width more symmetrical than lip height (RAW), and 26 with vertical lip height more symmetrical than lip width (RAH). Measurements were taken preoperatively (T0), 6 months (T1) and 5 years (T2) postoperatively. The MRA group had significantly more symmetrical lip height than the RA group at T1 (P = 0.003) and T2 (P = 0.002); however no statistically significant difference in lip width symmetry was observed between the two groups. In relation to the effects of growth, only lip width symmetry in the RAH group improved significantly between T1 and T2 (P = 0.023). In conclusion the improvement in lip width symmetry following 5 years of postoperative growth did not achieve the same symmetry as when lip width symmetry was achieved intraoperatively. Thus, the MRA technique could be used to obtain intraoperative symmetry of lip height and width.