ABSTRACT Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). Materials and Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. Results: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. Conclusions: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients’ quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success. Objective safety patientreported patient reported (US . (LMGU) Methods 202 2022 symptomfree symptom free reobstruction. reobstruction re obstruction. obstruction re-obstruction Patientreported Patient healthrelated related , (HRQoL) OHRQoL, (OHRQoL) surgery 1 Results Overall 4 included 3 97.56% 9756 97 56 (97.56% followup follow up 2 range 1541 15 15-41 Specifically 6month month 12month p 0.05 005 0 05 domains Twentyeight Twenty eight 68.3% 683 68 (68.3% 75.6% 756 75 (75.6% respectively However Moreover Conclusions progress (LMGU 20 (HRQoL (OHRQoL 97.56 975 5 (97.56 154 15-4 0.0 00 68.3 (68.3 75.6 7 (75.6 97.5 (97.5 15- 0. 68. (68. 75. (75. 97. (97. (68 (75 (97 (6 (7 (9 (

ABSTRACT CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient’s clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance. CONTEXT tsutsugamushi manifestations meningoencephalitis pneumonitis myocarditis shock However syndrome REPORT 59yearold yearold 59 year old admission liver hospitalization 17 CONCLUSION s uncertain 5

ABSTRACT Through a long-term micro-area positioning experiment (2006-2017), the precise fertilization locations of spring maize (Zea mays L.) in Jilin, China, were investigated using an embedded cement bucket pot. The effects of different fertilization placements and additional application of organic manure on maize yield, biomass, grain nutrient uptake, and soil fertility were examined. Six treatments were designed: base fertilizer + topdressing shallow application (BF1TD1); base fertilizer deep + topdressing shallow application (BF2TD1); base fertilizer + topdressing deep application (BF1TD2); base fertilizer deep + topdressing deep application (BF2TD2); base fertilizer + topdressing + organic manure shallow application (BF1TD1 + OS); and base fertilizer + topdressing shallow application + organic manure deep application (BF1TD1 + OD). After 12 years of continuous experimentation, the findings revealed that BF2TD2, BF1TD1 + OS, and BF1TD1 + OD exhibited 10.59 %, 25.17 %, and 29.34 % higher average yields than BF1TD1, respectively. Deep topdressing was more beneficial in increasing maize yield and nutrient accumulation, and additionally, increasing the use of organic fertilizer enhanced plant biomass and nutrient uptake. Over the 12 years considered, the soil organic matter in the 0-20 cm and 20-40 cm layers increased by 45.96 % and 80.61 %, respectively, and the soil pH increased from 0.38 to 0.48. In general, the deep application of organic manure was more beneficial for soil retention as it can increase soil fertility in the 0-40 cm layer. Considering the high yield and nutrient absorption and utilization of maize, technical advancement for soil fertilizer in whole-field tillage layers was crucial. longterm long term microarea micro area 20062017, 20062017 2006 2017 , (2006-2017) Zea L. L Jilin China pot uptake examined designed BFTD BF TD (BF1TD1) BF2TD1 (BF2TD1) BF1TD2 (BF1TD2) BF2TD2 (BF2TD2) (BF1TD OS OS) OD. . OD) 1 experimentation BF1TD 1059 10 59 10.5 2517 25 17 25.1 2934 29 34 29.3 respectively accumulation additionally considered 020 0 20 0-2 2040 40 20-4 4596 45 96 45.9 8061 80 61 80.6 038 38 0.3 048 48 0.48 general 040 0-4 layer wholefield whole field crucial 2006201 200 201 (2006-2017 BF2TD (BF2TD1 (BF1TD2 (BF2TD2 105 5 10. 251 2 25. 293 3 29. 02 0- 204 4 20- 459 9 45. 806 8 6 80. 03 0. 04 0.4 200620 (2006-201 (BF2TD 20062 (2006-20 (2006-2 (2006- (2006 (200 (20 (2 (

ABSTRACT Introduction: This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting. Methods: Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors. Results: Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01). Conclusion: VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting. Introduction vasoactiveinotropic vasoactive inotropic (PMV grafting Methods not VIS6h VISh h max calculated (ROC Results 25 5 group 19 nonPMV non 208 20 8 20.8% 9 pairs 0500 0 500 0.500 0.805. 0805 0.805 . 805 (0.805) 65 6 6. 787 78 7 78.7 723 72 3 72.3 specificity odds ratio1301 ratio 1 301 ratio=1.301 95 10911551 091 551 1.091~1.551 P<0.01. P001 P P<0.01 01 P<0.01) Conclusion 2 20.8 050 50 0.50 080 0.80 80 (0.805 78. 72. ratio130 30 ratio=1.30 1091155 09 55 1.091~1.55 P00 P<0.0 20. 05 0.5 08 0.8 (0.80 ratio13 ratio=1.3 109115 1.091~1.5 P0 P<0. 0. (0.8 ratio1 ratio=1. 10911 1.091~1. P<0 (0. ratio=1 1091 1.091~1 P< (0 ratio= 109 1.091~ ( 10 1.091 1.09 1.0 1.

BACKGROUND: With the rapid development of Internet technology and social media, a growing number of companies now not only transfer their traditional offline business interactions to online but also engage in online customer relationship management, market share expansion and brand building. Consumer interaction in the virtual brand community has become progressively more important in consumers' purchase decision. OBJECTIVES: The purpose of establishing virtual brand community is to obtain brand loyalty, but the existing research rarely discusses the impact of member interaction on brand loyalty. To address this research gap, we explore the influence mechanism between virtual brand community member interaction and brand loyalty. METHOD: To verify the research hypothesis, we distributed and collected 393 valid questionnaires on wenjuan.com, one of the largest online questionnaire service companies in China. RESULTS: Our results reveal that virtual brand community members' interaction has a positive impact on brand loyalty. In addition, community identification also has a partial mediating effect. Moreover, media richness regulates the relationship between member interaction and community identification. CONCLUSION: This article mainly investigates the virtual brand community member interaction behaviours. We also explore the influences of different dimensions of virtual brand community interaction on community identification and member brand loyalty. CONTRIBUTION: This article deepens our understanding of online platform members' participance behaviours.

Resumo Fundamento: A associação entre a duração do sono e a aterosclerose foi relatada em muitos estudos observacionais. No entanto, pouco se sabe sobre a sua importância como fator de risco para aterosclerose ou como consequência negativa da aterosclerose. Objetivo: Este estudo teve como objetivo avaliar a associação causal entre a duração do sono e o risco de aterosclerose usando estatísticas resumidas de estudos de associação genômica ampla (GWAS) disponíveis publicamente. Métodos: Empregamos um método de randomização mendeliana (RM) de duas amostras com 2 coortes do MRC-IEU (n = 460.099) e do UK Biobank (n = 361.194) para investigar a associação causal entre a duração do sono e o risco de aterosclerose. Três métodos, incluindo a técnica de variância inversa ponderada (IVW), escore de perfil ajustado robusto (RAPS) e abordagem de mediana simples e ponderada, foram usados para obter resultados confiáveis, e uma razão de chances com intervalo de confiança (IC) de 95% foi calculada. P<0,05 foi considerado diferença estatística. Além disso, foram utilizadas análises de regressão: MR-Egger regression, Radial MR, MR-PRESSO e leave-one-out para avaliar os possíveis efeitos de pleiotropia. Resultados: Não foi encontrada associação causal entre duração do sono e aterosclerose [OR (IC95%): 0,90 (0,98-1,00), p = 0,186]. As análises Leave-one-out, MR-Egger, e MR-PRESSO não conseguiram detectar pleiotropia horizontal. Conclusões: Esta análise de RM não indicou nenhuma associação causal entre a duração do sono geneticamente prevista e a aterosclerose nas populações europeias. Fundamento observacionais entanto Objetivo GWAS (GWAS publicamente Métodos (RM MRCIEU MRC IEU n 460.099 460099 460 099 361.194 361194 361 194 métodos IVW, IVW , (IVW) RAPS (RAPS confiáveis IC (IC 95 calculada P005 P 0 05 P<0,0 estatística disso regressão MREgger MR Egger regression MRPRESSO PRESSO leaveoneout leave one out Resultados OR IC95% IC95 (IC95%) 090 90 0,9 0,981,00, 098100 0,98 1,00 98 1 00 (0,98-1,00) 0,186. 0186 0,186 . 186 0,186] Leaveoneout, Leaveoneout Leave out, Leave-one-out MREgger, Egger, horizontal Conclusões europeias 460.09 46009 46 09 361.19 36119 36 19 (IVW 9 P00 P<0, IC9 (IC95% 0, 981 0,981,00 09810 098 100 1,0 (0,98-1,00 018 0,18 18 460.0 4600 4 361.1 3611 3 P0 P<0 (IC95 0,981,0 0981 10 1, (0,98-1,0 01 0,1 460. 361. P< (IC9 0,981, (0,98-1, 0,981 (0,98-1 (0,98- (0,98 (0,9 (0, (0 (

Abstract Background: The association between the length of sleep and atherosclerosis has been reported in many observational studies. However, little is known about its significance as a risk factor for atherosclerosis or as a negative consequence of atherosclerosis. Objective: This study aimed to assess the causal association between sleep duration and the risk of atherosclerosis using publicly available genome-wide association studies (GWAS) summary statistics. Methods: We employed a two-sample Mendelian randomization (MR) method with 2 cohorts from MRC-IEU (n=460,099) and UK Biobank (n=361,194) to investigate the causal association between sleep duration and the risk of atherosclerosis. Three methods including the inverse-variance weighted (IVW) technique, Robust adjusted profile score (RAPS), and simple-and weighted-median approach were used to obtain reliable results, and an odds ratio with a 95% confidence interval (CI) was calculated. P<0.05 was considered as a statistical difference. In addition, MR-Egger regression, Radial MR, MR-PRESSO, and leave-one-out analyses were used to assess the possible pleiotropy effects. Results: No causal association of sleep duration with atherosclerosis was found [OR (95%CI): 0.90 (0.98-1.00), p = 0.186]. Leave-one-out, MR-Egger, and MR-PRESSO analyses failed to detect horizontal pleiotropy. Conclusions: This MR analysis indicated no causal association between genetically predicted sleep duration and atherosclerosis across European populations. Background However Objective genomewide genome wide GWAS (GWAS statistics Methods twosample two sample (MR MRCIEU MRC IEU n=460,099 n460099 n 460 099 (n=460,099 n=361,194 n361194 361 194 (n=361,194 inversevariance inverse variance IVW (IVW technique RAPS, RAPS , (RAPS) simpleand simple weightedmedian median results 95 CI (CI calculated P005 P 0 05 P<0.0 difference addition MREgger Egger regression MRPRESSO, MRPRESSO PRESSO, PRESSO leaveoneout leave one out effects Results OR 95%CI 95CI (95%CI) 090 90 0.9 0.981.00, 098100 0.98 1.00 98 1 00 (0.98-1.00) 0.186. 0186 0.186 . 186 0.186] Leaveoneout, Leaveoneout Leave out, Leave-one-out MREgger, Egger, Conclusions populations n=460,09 n46009 46 09 (n=460,09 n=361,19 n36119 36 19 (n=361,19 (RAPS 9 P00 P<0. (95%CI 0. 981 0.981.00 09810 098 100 1.0 (0.98-1.00 018 0.18 18 n=460,0 n4600 4 (n=460,0 n=361,1 n3611 3 (n=361,1 P0 P<0 0.981.0 0981 10 1. (0.98-1.0 01 0.1 n=460, n460 (n=460, n=361, n361 (n=361, P< 0.981. (0.98-1. n=460 n46 (n=460 n=361 n36 (n=361 0.981 (0.98-1 n=46 n4 (n=46 n=36 n3 (n=36 (0.98- n=4 (n=4 n=3 (n=3 (0.98 n= (n= (0.9 (n (0. (0 (

Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets. nonsmall non small NSCLC, , (NSCLC) exploration pharmacology bioinformatics validation research HIT20 HIT HIT2 0 HIT2.0 STD CTD DisGeNET proteinprotein protein PPI, (PPI) GO, (GO) KEGG, (KEGG) docking A54 cells NCIH460, NCIH460 NCIH NCI H460, H460 H NCI-H460 realtime real time PCR 6 databases cancerrelated related PI3KAKT PIKAKT PI3K AKT PI K pathway microRNAs HIF1 HIF 1 HIF- etc CASP3 CASP CTNNB1 CTNNB JUN IL6 IL MAPK3 HIF1A HIFA STAT3 STAT AKT1 TP53 TP CCND1 CCND VEGFA EGFR downregulated down regulated 6, IL-6 (NSCLC HIT2. (PPI (GO (KEGG A5 NCIH46 H46 NCI-H46 KAKT PIK TP5 IL- NCIH4 H4 NCI-H4 NCI-H

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5’end or 3’end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5’ end or 3’ end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications. Introduction aging (TL trait disease (TERC operation elderly Methods leukocytes (BIS analyses 5end 5 3end 3 detected 10 surgery Results r 078 0 78 0.78 0.001, 0001 0.001 , 001 0.001) 084 84 0.84 0.004, 0004 0.004 004 0.004) 083 83 0.83 085 85 0.85 0.029. 0029 0.029 . 029 0.029) 0.58, 058 58 (0.58 021 21 0.21 019 19 0.19 0.12 012 12 variables However Conclusions complications 1 07 7 0.7 000 0.00 00 08 8 0.8 002 0.02 02 0.58 05 (0.5 2 0.2 01 0.1 0. 0.0 0.5 (0. (0 (

RESUMEN Se informa de un lipoblastoma perineal en una niña de 5 años localizado en el labio mayor derecho. La lesión aumentó gradualmente en 6 meses. En la ecografía y la resonancia magnética (RM), se observó un tumor heterogéneo sólido limitado con componente graso. Tras su extirpación quirúrgica, el estudio anatomopatológico confirmó un lipoblastoma. El lipoblastoma es un tumor mesenquimatoso benigno poco frecuente de la lactancia y la primera infancia. Los síntomas varían en función de la localización; pueden observarse signos de compresión de los órganos adyacentes. Este tipo de tumores inusuales de los tejidos blandos son más frecuentes en menores de 3 años. Los lipoblastomas se localizan predominantemente en las extremidades, pero también pueden encontrarse en la cabeza y el cuello, el tronco, el mediastino, el riñón, el mesenterio, el retroperitoneo y el perineo. Se debe sospechar su presencia en función de los hallazgos de la ecografía y la RM.

Abstract Objectives: The degree of endolymphatic hydrops in Meniere’s disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere’s disease. Methods: This study included 54 patients (62 ears) with Meniere’s disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and puretone audiometry. Endolymphatic hydrops were assessed according to Gurkov’s criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed. Results: Pure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both p<0.05). There was no significant correlation between vestibular endolymphatic hydrops and pure-tonal audiometry or staging (all p > 0.05). The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p<0.05). The degree of cochlear hydrops was correlated with the audiometry, low-frequency hearing thresholds, mid-frequency hearing thresholds and staging (p<0.01). Conclusion: The types and sites of endolymphatic hydrops based on a 3D-real inversion recovery sequence can be used to indicate the degree of hearing loss in patients with Meniere's disease. Level of evidence: Level III. Objectives Menieres Meniere s However inconsistent Methods 5 62 (6 ears threedimensional three dimensional Gurkovs Gurkov 2011. 2011 . (2011) pure analysed Results both p<0.05. p005 p<0.05 0 05 p<0.05) puretonal tonal all 0.05. 005 0.05 0.05) midfrequency mid frequency (p<0.05) lowfrequency low p<0.01. p001 p<0.01 01 (p<0.01) Conclusion 3Dreal Dreal 3D D evidence III 6 ( 201 (2011 p00 p<0.0 00 0.0 (p<0.05 (p<0.01 20 (201 p0 p<0. 0. (p<0.0 2 (20 p<0 (p<0. (2 p< (p<0 (p< (p

Resumen Antecedentes: La enfermedad de injerto contra huésped (EICH) es una complicación importante después del trasplante alogénico de células madre hematopoyéticas. Objetivos: Para dilucidar el papel de TLR4, el principal receptor de LPS bacteriano, en el desarrollo de GVHD, construimos un modelo de GVHD en ratones knockout para TLR4 (TLR4-/-) y monitoreamos el quimerismo celular. Métodos: En este estudio, usamos PCR para identificar si se establecieron ratones knockout para TLR4 (TLR4-/-). Antes del trasplante, pretratamos a los ratones con irradiación para obtener la dosis de irradiación adecuada. Se aplicó citometría de flujo para medir el estado de quimerismo, las distribuciones de APC y células T en ratones receptores TLR4+/+ y TLR4-/-. Resultados: El estado general de los receptores de TLR4-/- fue mejor que el de los receptores de TLR4+/+, y los ratones receptores de TLR4-/- mostraron manifestaciones de GVHD menos graves que los ratones receptores de TLR4+/+. La mayoría de las APC y las células T en el bazo del ratón huésped se derivaron de las células del donante, y las células T CD4+, incluidas las células T de memoria, se encontraban en su mayoría en los ratones huéspedes. Conclusión: En general, nuestros datos muestran que la eliminación de TLR4 atenuó el desarrollo de GVHD, lo que sugiere que TLR4 podría usarse como un nuevo objetivo y paradigma terapéutico en las terapias de GVHD.

Abstract Background: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Objective: To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4-/-) mice and monitored the cell chimerism. Methods: In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4-/-) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4+/+ and TLR4-/- recipient mice. Results: The general condition of TLR4-/- recipients was better than that of TLR4+/+ recipients, and the TLR4-/- recipient mice showed less severe GVHD manifestations than the TLR4+/+ recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4+ T-cells, including memory T-cells, were in the majority in host mice. Conclusion: In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using “Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence”. MicroRNA29a3p MicroRNAap MicroRNA 29a 3p p cancers unclear microRNA29a3p microRNAap microRNA 4 201 collected years probe factors recurrentmetastasis, recurrentmetastasis recurrent metastasis, metastasis studied Ki Ki6 Ecadherin E cadherin noncancer non red vessels, vessels , vessels) followup follow size Tstage, Tstage T stage, stage T-stage differentiation p< (p 0.05. 005 0.05 . 0 05 0.05) Ecadherin. cadherin. Moreover miRNA29a3p+Ki67+Ecadherin miRNA29a3pKi67Ecadherin miRNAapKiEcadherin miRNA 3p+Ki67+E indexes invasion Oxford EvidenceBased Evidence Based Evidence. Evidence” 20 00 0.0 miRNA29a3p pKi 3pKi67E pKiE 2 0. miRNAap

Abstract Background Significant association between bullous pemphigoid (BP) and stroke has been reported. This study aimed to evaluate the level of anti-BP180 antibody in stroke patients to explore the relationship between BP and stroke in their pathogenesis. Methods We collected serum samples from stroke patients and matched controls between February 2019 and June 2020. The anti-BP180 antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Results A total of 1183 stroke patients including 970 with cerebral infarction (CI), 192 with intracerebral hemorrhage (ICH), 21 with CI and ICH, and 855 controls were enrolled in this study. Anti-BP180 autoantibody values were significantly higher in stroke patients than in controls (p < 0.001). Anti-BP180 autoantibody-positive rates were 12.51% (148) in stroke patients and 4.68% (40) in controls (p < 0.001, OR = 2.65). In anti-BP180 autoantibody-positive subjects, the values were significantly higher in stroke patients than in controls (p < 0.001). However, only 10 (6.76%) stroke patients and 3 (7.5%) controls had high values (> 100 RU/mL) (p = 0.87). Stratified analysis showed that anti-BP180 antibody positive rates were independent of age, sex, and stroke subtypes in the stroke group. Positive rates in patients with both CI and ICH were nearly two times higher than those in patients with either CI or ICH alone (p = 0.11, OR = 1.94). Study limitations This study had a limited sample size and lacked quantitative criteria for stroke severity. Conclusions Anti-BP180 antibody values and positive rates were higher in stroke patients than in controls, suggesting that stroke patients may have higher of developing BP. (BP reported antiBP180 antiBP anti BP180 anti-BP18 pathogenesis 201 2020 enzymelinked enzyme linked ELISA. ELISA . (ELISA) 118 97 CI, , (CI) 19 (ICH) 2 85 AntiBP180 AntiBP Anti Anti-BP18 p 0.001. 0001 0.001 0 001 0.001) autoantibodypositive 1251 12 51 12.51 148 (148 468 4 68 4.68 40 (40 2.65. 265 2.65 65 2.65) subjects However 1 6.76% 676 6 76 (6.76% 7.5% 75 7 5 (7.5% > ( RU/mL RUmL RU mL 0.87. 087 0.87 87 0.87) age sex group 011 11 0.11 1.94. 194 1.94 94 1.94) severity antiBP18 BP18 anti-BP1 20 202 (ELISA 9 (CI (ICH 8 AntiBP18 Anti-BP1 000 0.00 00 125 12.5 14 (14 46 4.6 (4 26 2.6 6.76 67 (6.76 7.5 (7.5 08 0.8 01 0.1 1.9 antiBP1 BP1 anti-BP AntiBP1 Anti-BP 0.0 12. (1 4. 2. 6.7 (6.7 7. (7. 0. 1. 6. (6. (7 (6

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars. 919 91 9 >91.9 nonsyndromic non syndromic genes PAX genotypephenotype genotype phenotype 2 China (China 201 2021 wholeexome whole exome WES (WES SWISSMODEL SWISS MODEL threedimensional three dimensional proteins reference NM_001372076.1 NM0013720761 NM 001372076 1 c1010CA cCA c 1010C A C p.T337K pT337K pTK p T337K T K (p.T337K c330331insGT cinsGT 330 331insGT insGT p.D113Afs*9 pD113Afs9 pDAfs D113Afs D Afs (p.D113Afs*9 then molars >91. 20 202 NM_001372076. NM001372076 00137207 CA pT TK 33 p.D113Afs* pD pD113Afs DAfs (p.D113Afs* >91 NM_001372076 NM00137207 0013720 3 p.D113Afs (p.D113Afs >9 NM_00137207 NM0013720 001372 > NM_0013720 NM001372 00137 NM_001372 NM00137 0013 NM_00137 NM0013 001 NM_0013 NM001 00 NM_001 NM00 0 NM_00 NM0 NM_0 NM_

Abstract Objective: This study aimed to perform a meta-analysis to investigate the diagnostic safety and accuracy of Ultrasound-Guided Core Needle Biopsy (US-CNB) Axillary Lymph Nodes (ALNs) region in patients with Breast Cancer (BC). Methods: The authors searched the electronic databases PubMed, Scopus, Embase, and Web of Science for clinical trials about US-CNB for the detection of ALNs in breast cancer patients. The authors extracted and pooled raw data from the included studies and performed statistical analyses using Meta-DiSc 1.4 and Review Manager 5.3 software. A random effects model was used to calculate the data. At the same time, data from the Ultrasound-guided Fine-Needle Aspiration (US-FNA) were introduced for comparison with the US-CNB. In addition, the subgroup was performed to explore the causes of heterogeneity. (PROSPERO ID: CRD42022369491). Results: In total, 18 articles with 2521 patients were assessed as meeting the study criteria. The overall sensitivity was 0.90 (95% CI [Confidence Interval], 0.87‒0.91; p = 0.00), the overall specificity was 0.99 (95% CI 0.98‒ 1.00; p = 0.62), the overall area under the curve (AUC) was 0.98. Next, in the comparison of US-CNB and US-FNA, US-CNB is better than US-FNA in the diagnosis of ALNs metastases. The sensitivity was 0.88 (95% CI 0.84‒ 0.91; p = 0.12) vs. 0.73 (95% CI 0.69‒0.76; p = 0.91), the specificity was 1.00 (95% CI 0.99‒1.00; p = 1.00) vs. 0.99 (95% CI 0.67‒0.74; p = 0.92), and the AUC was 0.99 vs. 0.98. Subgroup analysis showed that heterogeneity may be related to preoperative Neoadjuvant Chemotherapy (NAC) treatment, region, size of tumor diameter, and the number of punctures. Conclusion: US-CNB has a satisfactory diagnostic performance with good specificity and sensitivity in the preoperative diagnosis of ALNs in BC patients. Objective metaanalysis meta UltrasoundGuided Ultrasound Guided USCNB US CNB (US-CNB (ALNs BC. . (BC) Methods PubMed Scopus Embase MetaDiSc Meta DiSc 14 1 4 1. 53 5 3 5. software time Ultrasoundguided guided FineNeedle Fine USFNA FNA (US-FNA USCNB. CNB. addition PROSPERO ID CRD42022369491. CRD42022369491 CRD CRD42022369491) Results total 252 criteria 090 0 90 0.9 95% 95 (95 Confidence Interval, Interval , Interval] 0.87‒0.91 087091 87 91 0.00, 000 0.00 00 0.00) 099 99 098 98 0.98 100 0.62, 062 0.62 62 0.62) (AUC Next USFNA, FNA, metastases 088 88 0.8 084 84 0.84 0.91 091 0.12 012 12 vs 073 73 0.7 0.69‒0.76 069076 69 76 0.91, 0.91) 1.0 0.99‒1.00 099100 0.67‒0.74 067074 67 74 0.92, 092 0.92 92 0.92) NAC (NAC treatment diameter punctures Conclusion (BC CRD4202236949 25 09 9 0. (9 0.87‒0.9 08709 8 0.0 10 06 0.6 6 08 0.1 01 07 7 0.69‒0.7 06907 0.99‒1.0 09910 0.67‒0.7 06707 CRD420223694 2 ( 0.87‒0. 0870 0.69‒0. 0690 0.99‒1. 0991 0.67‒0. 0670 CRD42022369 0.87‒0 087 0.69‒0 069 0.99‒1 0.67‒0 067 CRD4202236 0.87‒ 0.69‒ 0.99‒ 0.67‒ CRD420223 0.87 0.69 0.67 CRD42022 CRD4202 CRD420 CRD42 CRD4