The Impact of the Restoration of Invisible Orthodontic Titanium Alloy Implant Without Bracket on Individuals Afflicted with Dental Malocclusion and Arch Deficiency Accompanied by Periodontitis and a Local Periodontal Inflammation.

Objective: To investigate the impact of the restoration of non-bracket invisible orthodontic titanium alloy implant on individuals with dental malocclusion and arch deficiency accompanied by periodontitis and local periodontal Inflammation. Method: A cohort of 120 patients presenting with dental malocclusion and defects compounded by periodontitis, were treated at our institution between January 2021 and January 2022; these patients were enrolled in a randomized controlled trial.. These patients were allocated into two groups. The control group (comprising 60 cases) underwent titanium alloy implant restoration, while the research group (also with 60 cases) received titanium alloy implant restoration following invisible orthodontic treatment without brackets. A one-year post-treatment follow-up was conducted, during which various parameters, including pain levels, aesthetic improvement, inflammatory response, dental function, oral hygiene, and the incidence of adverse events, were evaluated and compared before and after treatment between the two groups. Results: After six months of treatment, the visual analog scale (VAS) in the study group was lower than that in the control group (P < .05). After 6 months of treatment, the research team observed the changes in gingival crevicular interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Interleuckin-1 (IL-1), plaque index (PLI), and soft dirt index (DI) were all lower than those in the control group (P < .05). After 6 months of treatment, the research group had higher scores for tooth functions such as chewing, swallowing, speech expression, and occlusion than the control group, as well as higher pink and white aesthetics indexes (P < .05). The difference in the incidence rate of adverse outcomes between the research and control group was not distinct (P > .05). Conclusion: In case of dental malocclusion accompanied by periodontal disease, the utilization of titanium implants for rectifying dental arch deformities without the use of orthodontic brackets, devoid of orthodontic brackets, has demonstrated notable efficacy in alleviating patients' periodontal discomfort, their oral hygiene, and dental functionality. This modality is conducive to augmenting dental aesthetics without incurring heightened rates of unfavorable consequences, thereby enhancing treatment outcomes.

Subtle Structural Changes across the Boundary between A2AR/A2BR Dual Antagonism and A2BR Antagonism: A Novel Class of 2-Aminopyrimidine-Based Derivatives.

Aberrantly elevated adenosine in the tumor microenvironment exerts its immunosuppressive functions through adenosine receptors A2AR and A2BR. Antagonism of A2AR and A2BR has the potential to suppress tumor growth. Herein, we report a systemic assessment of the effects of an indole modification at position 4, 5, 6, or 7 on both A2AR/A2BR activity and selectivity of novel 2-aminopyrimidine compounds. Substituting indole at the 4-/5-position produced potent A2AR/A2BR dual antagonism, whereas the 6-position of indole substitution gave highly selective A2BR antagonism. Molecular dynamics simulation showed that the 5-cyano compound 7ai had a lower binding free energy than the 6-cyano compound 7aj due to water-bridged hydrogen bond interactions with E169 or F168 in A2AR. Of note, dual A2AR/A2BR antagonism by compound 7ai can profoundly promote the activation and cytotoxic function of T cells. This work provided a strategy for obtaining novel dual A2AR/A2BR or A2BR antagonists by fine-tuning structural modification.

Maximizing Polysaccharides and Phycoerythrin in Porphyridium purpureum via the Addition of Exogenous Compounds: A Response-Surface-Methodology Approach.

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L-1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L-1), phycoerythrin (102.95 mg L-1), and polysaccharide (1.42 g L-1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.

Survival after minimally invasive radical hysterectomy with protective colpotomy for early-stage cervical cancer: A systematic review and meta-analysis.

Minimally invasive surgery on treatment of early-stage cervical cancer is debatable. Traditional approaches of colpotomy are considered responsible for an inferior oncological outcome. Evidence on whether protective colpotomy could optimize minimally invasive technique and improve prognoses of women with early-stage cervical cancer remains limited. We produced a systematic review and meta-analysis to compare oncological outcomes of the patients treated by minimally invasive radical hysterectomy with protective colpotomy to those treated by open surgery according to existing literature. We explored PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2022. Inclusion criteria were: (1) randomized controlled trials or observational studies published in English, (2) studies comparing minimally invasive radical hysterectomy with protective colpotomy to abdominal radical hysterectomy in early-stage cervical cancer, and (3) studies comparing survival outcomes. Two reviewers performed the screening, data extraction, and quality assessment independently. A total of 8 retrospective cohort studies with 2020 women were included in the study, 821 of whom were in the minimally invasive surgery group, and 1199 of whom were in the open surgery group. The recurrence-free survival and overall survival in the minimally invasive surgery group were both similar to that in the open surgery group (pooled hazard ratio, 0.88 and 0.78, respectively; 95% confidence interval, 0.56-1.38 and 0.42-1.44, respectively). Minimally invasive radical hysterectomy with protective colpotomy on treatment of early-stage cervical cancer had similar recurrence-free survival and overall survival compared to abdominal radical hysterectomy. Protective colpotomy could be a guaranteed approach to modifying minimally invasive technique.

Tibial transverse transport induces mobilization of endothelial progenitor cells to accelerate angiogenesis and ulcer wound healing through the VEGFA/CXCL12 pathway.

BACKGROUND: Tibial transverse transport (TTT) can promote the healing of chronic foot ulcers, but the specific cellular and molecular mechanisms by which TTT promotes wound healing remain unclear. METHODS: New Zealand White rabbits were selected to induce foot ulcer models. The treatment included unilateral TTT surgery and bilateral TTT surgery. Observation of tissue neovascularization structure by HE staining and CD31 immunofluorescence detection. Collagen fiber formation was detected through the Masson staining. The mobilization of endothelial progenitor cell (EPCs) were analyzed by VEGFR2 immunofluorescence detection and flow cytometry detection of the number of VEGFR2/Tie-2-positive cells in peripheral blood. ELISA and qPCR assay were performed to detect VEGFA and CXCL12 levels. RESULTS: The complete healing time of ulcer surfaces in sham, unilateral and bilateral TTT groups was about 22 days, 17 days and 13 days, respectively. TTT treatment significantly increased the deposition of granulation tissue and epithelialization of wounds. It also led to an increase in collagen fiber content and the level of the microvascular marker CD31. Furthermore, TTT treatment upregulated the levels of VEGFA and CXCL12 in peripheral blood and wound tissues, as well as increased the expression of VEGFR2 in wound tissues and the proportion of VEGFR2/Tie-2 in peripheral blood. Moreover, these effects of TTT treatment in the bilateral group was more significant than that in the unilateral group. CONCLUSIONS: TTT may facilitate wound fibroblasts to release VEGFA and CXCL12, causing EPC mobilization, thus promoting angiogenesis and ulcer wound healing.

Engineering APOBEC3A deaminase for highly accurate and efficient base editing.

Cytosine base editors (CBEs) are effective tools for introducing C-to-T base conversions, but their clinical applications are limited by off-target and bystander effects. Through structure-guided engineering of human APOBEC3A (A3A) deaminase, we developed highly accurate A3A-CBE (haA3A-CBE) variants that efficiently generate C-to-T conversion with a narrow editing window and near-background level of DNA and RNA off-target activity, irrespective of methylation status and sequence context. The engineered deaminase domains are compatible with PAM-relaxed SpCas9-NG variant, enabling accurate correction of pathogenic mutations in homopolymeric cytosine sites through flexible positioning of the single-guide RNAs. Dual adeno-associated virus delivery of one haA3A-CBE variant to a mouse model of tyrosinemia induced up to 58.1% editing in liver tissues with minimal bystander editing, which was further reduced through single dose of lipid nanoparticle-based messenger RNA delivery of haA3A-CBEs. These results highlight the tremendous promise of haA3A-CBEs for precise genome editing to treat human diseases.

A predictive model for intraabdominal infection after radical gastrectomy in elderly patients.

Gastric cancer (GC) is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths, with a relatively high incidence among the elderly population. Surgical resection is the mainstay treatment for GC and is currently the only cure. However, the incidence of postoperative intraabdominal infections remains high and seriously affects the prognosis. This study aimed to explore the risk factors for intraabdominal infections after radical gastrectomy in elderly patients and to establish and validate a risk prediction model. We collected the clinical data of 322 GC patients, who underwent radical gastrectomy at the General Surgery Department of China Medical University Dandong Central Hospital from January 2016 to January 2023. The patients were divided into an infected group (n = 27) and a noninfected group (n = 295) according to whether intraabdominal infections occurred postoperatively. A nomogram risk prediction model for the occurrence of postoperative intraabdominal infections was developed. All patients were randomized into a training set (n = 225) and a validation set (n = 97) in a 7:3 ratio, and the model was internally validated. Of the 322 patients, 27 (8.3%) experienced postoperative intraabdominal infections. Single-factor analysis revealed associations of intraabdominal infection with body mass index, glucose, hemoglobin, albumin, and other factors. The multifactorial analysis confirmed that body mass index, glucose, hemoglobin, albumin, surgical duration, and bleeding volume were independent risk factors for intraabdominal infections. The nomogram constructed based on these factors demonstrated excellent performance in both the training and validation sets. A nomogram model was developed and validated to predict the risk of intraabdominal infection after radical gastrectomy. The model has a good predictive performance, which could help clinicians prevent the occurrence of intraabdominal infections after radical gastrectomy in elderly patients.

Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China.

Introduction: The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. Methods: This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Results: Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Conclusions: Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling.

OBJECTIVE: Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD). METHODS: An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways. RESULTS: AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 µmol/L and 1 µg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells. CONCLUSION: AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity. Please cite this article as: Han LL, Zhang X, Zhang H, Li T, Zhao YC, Tian MH, Sun FL, Feng B. Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling. J Integr Med. 2024; 22(1): 83-92.

The role of differentially expressed genes and immune cell infiltration in the progression of nonalcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC): a new exploration based on bioinformatics analysis.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver disease characterized. The condition ranges from isolated excessive hepatocyte triglyceride accumulation and steatosis (nonalcoholic fatty liver (NAFL), to hepatic triglyceride accumulation plus inflammation and hepatocyte injury (nonalcoholic steatohepatitis (NASH)) and finally to hepatic fibrosis and cirrhosis and/or hepatocellular carcinoma (HCC). However, the mechanism driving this process is not yet clear. Obtain sample microarray from the GEO database. Extract 6 healthy liver samples, 74 nonalcoholic hepatitis samples, 8 liver cirrhosis samples, and 53 liver cancer samples from the GSE164760 dataset. We used the GEO2R tool for differentially expressed genes (DEGs) analysis of disease progression (nonalcoholic hepatitis healthy group, cirrhosis nonalcoholic hepatitis group, and liver cancer cirrhosis group) and necroptosis gene set. Gene set variation analysis (GSVA) is used to evaluate the association between biological pathways and gene features. The STRING database and Cytoscape software were used to establish and visualize protein-protein interaction (PPI) networks and identify the key functional modules of DEGs, drawn factor-target genes regulatory network. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs were also performed. Additionally, immune infiltration patterns were analyzed using the cibersort, and the correlation between immune cell-type abundance and DEGs expression was investigated. We further screened and obtained a total of 152 intersecting DEGs from three groups. 23 key genes were obtained through the MCODE plugin. Transcription factors regulating common differentially expressed genes were obtained in the hTFtarget database, and a TF target network diagram was drawn. There are 118 nodes, 251 edges, and 4 clusters in the PPI network. The key genes of the four modules include METAP2, RPL14, SERBP1, EEF2; HR4A1; CANX; ARID1A, UBE2K. METAP2, RPL14, SERBP1 and EEF2 was identified as the key hub genes. CREB1 was identified as the hub TF interacting with those gens by taking the intersection of potential TFs. The types of key gene changes were genetic mutations. It can be seen that the incidence of key gene mutations is 1.7% in EEF2, 0.8% in METAP2, and 0.3% in RPL14, respectively. Finally, We found that the most significant expression differences of the immune infiltrating cells among the three groups, were Tregs and M2, M0 type macrophages. We identified four hub genes METAP2, RPL14, SERBP1 and EEF2 being the most closely with the process from NASH to cirrhosis to HCC. It is beneficial to examine and understand the interaction between hub DEGs and potential regulatory molecules in the process. This knowledge may provide a novel theoretical foundation for the development of diagnostic biomarkers and gene-related therapy targets in the process.

Can neoadjuvant chemoradiotherapy before lateral pelvic lymph node dissection improve local control and prognosis in rectal cancer patients with clinically suspected lateral lymph node metastasis? A multicenter lateral node study in China.

AIMS: Selective lateral pelvic lymph node (LPN) dissection (LPND) following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer is widely recognized. This study aimed to determine the effects of nCRT before LPND on local control and prognosis of rectal cancer patients. MATERIALS AND METHODS: Data were retrieved from a prospective database for rectal cancer patients with clinical LPN metastasis receiving total mesorectal excision and LPND at three institutions between January 2012 and December 2019. Selection bias was minimized using propensity score matching (PSM) and short-term and clinical outcomes were compared. RESULTS: Patients (n = 213) were enrolled and grouped as either nCRT (n = 97) or non-nCRT (n = 116). PSM was used to identify 83 matched pairs. In the matched cohort, nCRT patients had a longer operation duration (310.6 vs. 265.0 min, P = 0.001), lower pathological LPN metastasis rate (32.5% vs. 48.2%, P = 0.040), and fewer harvested lymph nodes (22 vs. 25, P = 0.018) compared to the non-nCRT group. However, after PSM, the two groups had similar estimated overall 3-year survival (79.5% vs. 80.7%, P = 0.922), 3-year disease-free survival (66.1% vs. 65.5, P = 0.820), and 3-year local recurrence-free survival (88.6% vs. 89.7%, P = 0.927). Distant metastasis was the predominant recurrence pattern in the overall (45/58, 77.6%) and matched (33/44, 75.0%) cohorts. CONCLUSIONS: LPND without nCRT is effective and sufficient in preventing local recurrence in patients with LPN metastases. Future prospective randomized controlled studies are warranted to confirm these findings. Since systemic metastasis is the predominant recurrence pattern in patients with LPN metastasis post-LPND, improved perioperative systemic chemotherapy is needed to prevent micrometastasis.

Feasibility, Indications, and Prognostic Significance of Selective Lateral Pelvic Lymph Node Dissection After Preoperative Chemoradiotherapy in Middle/Low Rectal Cancer: Results of a Multicenter Lateral Node Study in China.

BACKGROUND: Lateral pelvic lymph node dissection after preoperative chemoradiotherapy can decrease local recurrence to lateral compartments, thereby providing survival benefits. OBJECTIVE: The safety of lateral pelvic lymph node dissection after preoperative chemoradiotherapy was investigated, and the surgical indications and survival benefits of lateral pelvic lymph node dissection were established on the basis of preoperative characteristics. DESIGN: A multicenter retrospective study. SETTINGS: Three hospitals in China. PATIENTS: Four hundred nine patients with clinical evidence of lateral pelvic lymph node metastasis. INTERVENTIONS: Patients who received lateral pelvic lymph node dissection were divided into 2 groups depending on whether they received chemoradiotherapy (n = 139) or not (n = 270). MAIN OUTCOME MEASURES: The safety, indications, and survival benefits of lateral pelvic lymph node dissection after preoperative chemoradiotherapy were investigated. RESULTS: The surgery times were significantly prolonged by preoperative chemoradiotherapy (291.3 vs 265.5 min; p = 0.021). Multivariate analysis demonstrated that poor/mucinous/signet-ring adenocarcinoma (OR = 4.42, 95% CI, 2.24-11.27; p = 0.031) and postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm (OR = 15.2, 95% CI, 5.89-53.01; p < 0.001) were independent predictive factors for lateral pelvic lymph node metastasis. Multivariate prognostic analysis showed that swollen lateral pelvic lymph nodes beyond the obturator or internal iliac as well as the involvement of 3 or more lateral pelvic lymph nodes were independent adverse prognostic factors. LIMITATIONS: The retrospective nature of the study and the small sample size were the limitations of this study. CONCLUSIONS: Preoperative chemoradiotherapy combined with lateral pelvic lymph node dissection is a practicable procedure with acceptable morbidity. Postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm and poor/signet/mucinous adenocarcinoma could be used for predicting lateral pelvic lymph node metastasis after chemoradiotherapy. However, lateral pelvic lymph node dissection should be carefully considered in patients with swollen lateral pelvic lymph nodes beyond the obturator or internal iliac region or involvement of multiple lateral pelvic lymph nodes. See Video Abstract at http://links.lww.com/DCR/C133 . VIABILIDAD, INDICACIONES E IMPORTANCIA PRONSTICA DE LA DISECCIN SELECTIVA DE GANGLIOS LINFTICOS PLVICOS LATERALES DESPUS DE QUIMIORRADIOTERAPIA PREOPERATORIA EN CNCER DE RECTO MEDIO/INFERIOR RESULTADOS DE UN ESTUDIO MULTICNTRICO DE GANGLIOS LATERALES EN CHINA: ANTECEDENTES:La disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria puede disminuir la recurrencia local en los compartimentos laterales, lo que brinda beneficios de supervivencia.OBJETIVO:Se investigó la seguridad de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria, y se establecieron las indicaciones quirúrgicas y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales en función de las características preoperatorias.DISEÑO:Estudio retrospectivo multicéntrico.ESCENARIO:Tres hospitales en China.PACIENTES:Cuatrocientos nueve pacientes con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales.INTERVENCIONES:Los pacientes que recibieron disección de ganglios linfáticos pélvicos laterales se dividieron en dos grupos dependiendo de si recibieron quimiorradioterapia (n = 139) o no (n = 270).PRINCIPALES MEDIDAS DE RESULTADO:Se investigaron la seguridad, las indicaciones y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria.RESULTADOS:Los tiempos de cirugía se prolongaron significativamente con la quimiorradioterapia preoperatoria (291,3 vs 265,5 min, p = 0,021). El análisis multivariable demostró que el adenocarcinoma mal diferenciado/mucinoso/en anillo de sello (odds ratio = 4,42, intervalo de confianza del 95%, 2,24-11,27; p = 0,031) y el diámetro del eje corto de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia ≥7 mm (odds ratio = 15,2, intervalo de confianza del 95%, 5,89-53,01; p < 0,001) fueron factores predictivos independientes de metástasis en los ganglios linfáticos pélvicos laterales. El análisis pronóstico multivariable mostró que la inflamación de los ganglios linfáticos pélvicos laterales más allá del obturador o la ilíaca interna, así como la afectación de tres o más ganglios linfáticos pélvicos laterales, eran factores pronósticos adversos independientes.LIMITACIONES:La naturaleza retrospectiva del estudio y el pequeño tamaño de la muestra.CONCLUSIONES:La quimiorradioterapia preoperatoria combinada con la disección de los ganglios linfáticos pélvicos laterales es un procedimiento practicable con una morbilidad aceptable. Posterior a la quimiorradioterapia, el diámetro del eje corto de los ganglios linfáticos pélvicos laterales ≥7 mm y el adenocarcinoma pobre/en sello/mucinoso podrían usarse para predecir la metástasis en los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia. Sin embargo, la disección de los ganglios linfáticos pélvicos laterales debe considerarse cuidadosamente en pacientes con ganglios linfáticos pélvicos laterales inflamados más allá del obturador o de la región ilíaca interna o compromiso de múltiples ganglios linfáticos pélvicos laterales. Consulte Video Resumen en http://links.lww.com/DCR/C133 . (Traducción-Dr. Felipe Bellolio ).

Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

FOXC1 Promotes Osteoblastic Differentiation of Bone Marrow Mesenchymal Stem Cells via the Dnmt3b/CXCL12 Axis.

Bone defects have remained a clinical problem in current orthopedics. Bone marrow mesenchymal stem cells (BM-MSCs) with multi-directional differentiation ability have become a research hotspot for repairing bone defects. In vitro and in vivo models were constructed, respectively. Alkaline phosphatase (ALP) staining and alizarin red staining were performed to detect osteogenic differentiation ability. Western blotting (WB) was used to detect the expression of osteogenic differentiation-related proteins. Serum inflammatory cytokine levels were detected by ELISA. Fracture recovery was evaluated by HE staining. The binding relationship between FOXC1 and Dnmt3b was verified by dual-luciferase reporter assay. The relationship between Dnmt3b and CXCL12 was explored by MSP and ChIP assays. FOXC1 overexpression promoted calcium nodule formation, upregulated osteogenic differentiation-related protein expression, promoted osteogenic differentiation, and decreased inflammatory factor levels in BM-MSCs, and promoted callus formation, upregulated osteogenic differentiation-related protein expression, and downregulated CXCL12 expression in the mouse model. Furthermore, FOXC1 targeted Dnmt3b, with Dnmt3b knockdown decreasing calcium nodule formation and downregulating osteogenic differentiation-related protein expression. Additionally, inhibiting Dnmt3b expression upregulated CXCL12 protein expression and inhibited CXCL12 methylation. Dnmt3b could be binded to CXCL12. CXCL12 overexpression attenuated the effects of FOXC1 overexpression and inhibited BM-MSCs osteogenic differentiation. This study confirmed that the FOXC1-mediated regulation of the Dnmt3b/CXCL12 axis had positive effects on the osteogenic differentiation of BM-MSCs.

Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.

Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44-56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology.

Revolutionizing sphincter preservation in ultra-low rectal cancer: exploring the potential of transanal endoscopic intersphincteric resection (taE-ISR): a propensity score-matched cohort study.

BACKGROUND: With the optimization of neoadjuvant treatment regimens, the indications for intersphincteric resection (ISR) have expanded. However, limitations such as unclear surgical field, impaired anal function, and failure of anal preservation still exist. Transanal total mesorectal excision can complement the drawbacks of ISR. Therefore, this study combined these two techniques and proposed transanal endoscopic intersphincteric resection (taE-ISR), aiming to explore the value of this novel technique in anal preservation for ultra-low rectal cancer. MATERIAL AND METHODS: Four high-volume centres were involved. After 1:1 propensity score-matching, patients with ultra-low rectal cancer underwent taE-ISR ( n =90) or ISR ( n =90) were included. Baseline characteristics, perioperative outcomes, pathological results, and follow-up were compared between the two groups. A nomogram model was established to assess the potential risks of anal preservation. RESULTS: The incidence of adjacent organ injury (0.0% vs. 5.6%, P =0.059), positive distal resection margin (1.1% vs. 8.9%, P =0.034), and incomplete specimen (2.2% vs. 13.3%, P =0.012) were lower in taE-ISR group. Moreover, the anal preservation rate was significantly higher in taE-ISR group (97.8% vs. 82.2%, P =0.001). Patients in the taE-ISR group showed a better disease-free survival ( P =0.044) and lower cumulative recurrence ( P =0.022) compared to the ISR group. Surgery procedure, tumour distance, and adjacent organ injury were factors influencing anal preservation in patients with ultra-low rectal cancer. CONCLUSION: taE-ISR technique was safe, feasible, and improved surgical quality, anal preservation rate and survival outcomes in ultra-low rectal cancer patients. It held significant clinical value and showed promising application prospects for anal preservation.

Carvedilol Plus NUC for Patients With HBV-Compensated Cirrhosis Under Virological Suppression: A Randomized Open-Label Trial.

INTRODUCTION: Portal hypertension progression can be relieved after controlling the etiology of liver cirrhosis. Whether beta-blockers could additionally enhance the effects during treatment, particularly for small esophageal varices (EV), was unclear. This study aims to assess the efficacy of add-on carvedilol to delay EV progression during anti-hepatitis B virus (HBV) treatment in HBV-related cirrhosis. METHODS: This randomized controlled trial enrolled patients with virologically suppressed HBV-compensated cirrhosis and small/medium EV. The participants were randomly assigned to receive nucleos(t)ide analog (NUC) or carvedilol 12.5 mg plus NUC (1:1 allocation ratio). The primary end point was the progression rate of EV at 2 years of follow-up. RESULTS: A total of 238 patients (small EV, 77.3%) were randomized into 119 NUC and 119 carvedilol plus NUC (carvedilol [CARV] combination group). Among them, 205 patients (86.1%) completed paired endoscopies. EV progression rate was 15.5% (16/103) in the NUC group and 12.7% (13/102) in the CARV combination group (relative risk = 0.79, 95% confidence interval 0.36-1.75, P = 0.567). Subgroup analysis on medium EV showed the CARV combination group had a more favorable effect in promoting EV regression (43.5% vs 13.1%, P = 0.022) than NUC alone, but not in small cases ( P = 0.534). The incidence of liver-related events (decompensation, hepatocellular carcinoma, or death/liver transplantation) within 2 years was similar between the 2 groups (11.2% vs 10.4%, P = 0.881). DISCUSSION: The overall results did not show statistically significant differences between the added carvedilol strategy and NUC monotherapy in preventing EV progression in patients with virologically suppressed HBV-compensated cirrhosis. However, the carvedilol-added approach might offer improved outcomes specifically for patients with medium EV (NCT03736265).

Nickel molybdate/cobalt iron carbonate hydroxide heterojunction with oxygen vacancy enables interfacial synergism to trigger oxygen evolution reaction.

The development of electrocatalysts with excellent performance toward oxygen evolution reaction (OER) for the production of hydrogen is of great significance to alleviate energy crisis and environmental pollution. Herein, the heterostructure (NMO/FCHC-0.4) was fabricated by the coupling growth of NiMoO4 (NMO) and cobalt iron carbonate hydroxide (FCHC) on nickel foam as an electrocatalyst for OER. The interfacial synergy on NMO/FCHC-0.4 heterojunction can promote the interfacial electron redistribution, affect the center position of d band, optimize the adsorption of intermediate, and improve the conductivity. Beyond, oxygen defect sites are conducive to the adsorption of intermediates, and increase the number of active sites. Real-time OER kinetic simulation revealed that the interfacial synergism and molybdate could reduce the adsorption of hydroxide, promote the deprotonation step of M-OH, and facilitate the formation of M-OOH (M represents the metal active site). As a result, NMO/FCHC-0.4 displays excellent OER electrocatalytic performance with an overpotential of 250/280 mV at the current density 100/200 mA cm-2 and robust stability at 100 mA cm-2 for 100 h. This work provides deep insights into the roles of interfacial electronic modulation and oxygen vacancy to design high-efficiency electrocatalysts for OER.

eALT-F: A New Non-Invasive Staging Method to Identify Medium to High-Risk Patients with HCC from Ultra-High HBV Viral Load Population - China, 2010-2023.

Background: The objective of this study was to examine the clinical characteristics of individuals with ultra-high hepatitis B virus (HBV) viral load and develop a novel staging method for chronic hepatitis B (CHB) that can more effectively identify patients with medium to high hepatocellular carcinoma (HCC) risk. Methods: A total of 2,118 patients with HBV DNA >1×107 IU/mL who visited Peking University People's Hospital between January 2010 and March 2023 were enrolled retrospectively. Clinical data from the first visit were obtained and analyzed. The traditional phases and new 'eALT-F' stages were compared to evaluate the risk of HCC. Results: In the overall patients, more than one-third of the patients were under 30 years old. Additionally, a small proportion of older people (>60 years) also had ultra-high HBV viral load (4.3%). 9.1% and 6.7% of individuals with ultra-high HBV viral load showed FIB-4>3.25 and aMAP≥50, respectively. In the traditional stages of CHB, which are based on HBeAg and alanine aminotransferase (ALT) [the upper limit of normal (ULN) ALT level at 40 IU/L for both men and women], regardless of phase, a certain proportion of patients were at risk of developing HCC (4.1%, 6.4%, 25.0%, and 20.3%). However, in the new 'eALT-F' stages, which are based on HBeAg, ALT (the ULN of ALT level at 30 IU/L for men and 19 IU/L for women), and/or FIB-4 levels (>1.45), aMAP≥50 was only observed in chronic hepatitis patients with positive or negative HBeAg (6.4% and 22.1%, respectively). Conclusions: The 'eALT-F' staging method, based on HBeAg, ALT (males: the ULN of ALT was 30 IU/L, females: 19 IU/L) and/or FIB-4 levels, was more effective in identifying medium to high-risk patients with HCC from patients with ultra-high HBV viral load than the traditional staging methods.