A novel HLA-DRB4 allele, HLA-DRB4*01:179.

One nucleotide substitution in codon 30 of HLA-DRB4*01:03:01:01 results in a novel allele, HLA-DRB4*01:179.

Recognition of the HLA-DRB3*03:65 allele in a Chinese individual.

We report a novel HLA-DRB3*03 allele, now named DRB3*03:65, identified by next-generation sequencing.

[Effects of reductive soil disinfestation and organic fertilizer application on microbial community stability in a facility vegetable soil]. / 强还原处理和施用有机肥对设施蔬菜地土壤微生物群落稳定性的影响.

Reductive soil disinfestation (RSD) is an effective method for remediating degraded facility vegetable soils. However, the effectiveness of RSD using green manure as a carbon source in the field has not yet been clarified. We investigated the effects of RSD and organic fertilizer application on soil microbial community composition, diversity, and stability in a degraded facility vegetable soil. There were six treatments, including no fertilization (CK), no fertilization and soil flooded and mulched with plastic film (FF), soil amended with chicken manure (OM), soil amended with chicken manure and flooded and mulched with plastic film (OMR), soil amended with Sesbania cannabina (TF), and soil amended with S. cannabina and flooded and mulched with plastic film (TR). The results showed that the OMR and TR treatments significantly decreased bacterial Chao1 index, altered bacterial and fungal community structure, and increased the relative abundances of Bacillus, Rhodococcus, Clostridium, and Penicillium. The TR treatment significantly reduced the relative abundance of Fusarium. Results of redundancy analysis and Mantel test analysis suggested that soil ammonium nitrogen and dissolved organic carbon contents were the key factors influencing bacterial community composition, and soil pH was the key factor affecting fungal community composition. Results of cohesion analysis showed that the OMR and TR treatments significantly improved bacterial community stability, and that there was no difference between OMR and TR treatments. The TR treatment enhanced fungal community stability, which was significantly higher than the OMR treatment. Therefore, the RSD with green manure as carbon source could be effective remediation practice to improve soil health.

GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

The clinical application of V-Y advanced flap pedicled with freestyle perforator flap for repairing small range defects in the anterior knee region.

Introduction: This study aims to investigate the clinical efficacy of V-Y advanced flap pedicled with freestyle perforator flap for repairing small range defects in the anterior knee region. Methods: 8 patients with skin and soft tissue defect/necrosis in the anterior knee area admitted to the Changshu No.1 People's Hospital from January 2021 to January 2022 were selected, with a defect range of 4 cm × 3 cm-9 cm × 6 cm, designed a V-Y advanced flap pedicled with freestyle perforator flap to repair the wound in the anterior knee area. Adjust the size and position of the flap according to the number and position of perforating branches found during the surgery, with a cutting area of 6 cm × 5 cm-14 cm × 10 cm and the supply area was directly pulled and sutured. Results: 4 patients were repaired by flaps pedicled with 2 perforating branches, 2 patients were repaired by flaps pedicled with 1 perforating branch and 2 patients were repaired by flaps pedicled with 3 perforating branches. 4 patients were repaired by flaps pedicled with 2 perforating branches, 2 patients were repaired by flaps pedicled with 1 perforating branch and 2 patients were repaired by flaps pedicled with 3 perforating branches. All flaps survived and following up for 6-15 months, the blood supply, appearance, and color of the flap were satisfactory, and the functions of knee joint flexion and extension were well preserved. Discussion: The V-Y advancement flap pedicled with freestyle perforator flap has the advantages of reliable blood supply, simple surgical operation, texture and thickness similar to the skin of the anterior knee area, and direct suture of the donor area. It is a perforator flap with good repair effect for small scale defects in the anterior knee area.

Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Evaluating the causal effect of atherosclerosis on the risk of intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IDD) and atherosclerosis are two common age-related conditions that can cause significant morbidity. While previous studies have suggested an association between the two conditions, the nature of this association remains unclear. Methods: We used Mendelian randomization (MR) to investigate the causal relationship between IDD and atherosclerosis. We identified genetic variants associated with IDD using summary statistics from a large genome-wide association study (GWAS). These variants were then used as instrumental variables to infer causal relationships with atherosclerosis in summary statistics from a separate GWAS. Results: Our MR analysis provided evidence for a causal relationship between IDD and atherosclerosis. We found that the genetic predisposition to atherosclerosis was associated with a higher risk of IDD (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.07-11.74, p = 0.04). The IVW estimates were consistent with the observational findings and other robust MR methods. Sensitivity analyses suggested that our findings were robust to potential sources of bias. Conclusions: Our study provides evidence for a causal link between IDD and atherosclerosis, suggesting that interventions targeting atherosclerosis could have potential benefits for reducing the risk of IDD. Further research is needed to explore the underlying mechanisms that link these two conditions and to investigate potential therapeutic interventions.

Corrigendum: Identification and validation of immune-related methylation clusters for predicting immune activity and prognosis in breast cancer.

[This corrects the article DOI: 10.3389/fimmu.2021.704557.].

Perioperative immunotherapy: the main clinical treatment for resectable non-small cell lung cancer.

Phase 3 clinical trials of perioperative immunotherapy for resectable non-small cell lung cancer (NSCLC): In recent years, immunotherapy for NSCLC is not only limited to advanced disease, but also has shown gratifying efficacy for early resectable NSCLC. With the publication of the results of several phase 3 clinical trials, perioperative immunotherapy will become one of the main treatment modalities for resectable NSCLC.

Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (ß = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (ß = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Diagnostic and Prognostic Ability of Contrast-Enhanced Unltrasound and Biomarkers in Hepatocellular Carcinoma Subtypes.

OBJECTIVE: To investigate the diagnostic and prognostic value of contrast-enhanced ultrasound (CEUS) and clinical indicators of the vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular-massive subtype in hepatocellular carcinoma (MTM-HCC). METHODS: This retrospective study included patients who underwent preoperative CEUS and hepatectomy for HCC between August 2018 and August 2021. Multivariable logistic regression was performed to select independent correlated factors of VETC-HCC and MTM-HCC to develop nomogram models. The association between model outcomes and early postoperative HCC recurrence was assessed using Kaplan-Meier curve and Cox regression analysis. RESULTS: The training cohort included 182 patients (54.3 ± 11.3 years, 168 males) and the validation cohort included 91 patients (54.8 ± 10.6 years, 81 males). Multivariate logistic regression analysis revealed that α-fetoprotein (AFP) levels (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.49-3.42, p < 0.001), intratumoral nonenhancement (OR: 2.40, 95% CI: 1.02-5.64, p = 0.044), and the perfusion pattern in the CEUS arterial phase (OR: 2.27, 95% CI: 1.05-4.91, p = 0.038) were independent predictors of VETC-HCC. Besides, the former two were also independently associated with MTM-HCC (AFP level: OR: 2.36, 95% CI: 1.36-4.09, p = 0.002; intratumoral nonenhancement: OR: 3.72, 95% CI: 1.02-13.56, p = 0.046). Nomogram models were constructed based on the aforementioned indicators. Kaplan-Meier curve analysis indicated that predicted VETC-HCC or MTM-HCC exhibited higher rates of early recurrence (log-rank p < 0.001 and p = 0.002, respectively). Cox regression analysis showed that a high risk of VETC-HCC was independently correlated with early recurrence (p = 0.011). CONCLUSION: CEUS combined with AFP levels can predict VETC-HCC/MTM-HCC and prognosis preoperatively.

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

The association between lipid biomarkers and osteoarthritis based on the National Health and Nutrition Examination Survey and Mendelian randomization study.

To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97-1.16), 0.95 (0.85-1.06), 0.94 (0.86-1.02) and 0.89 (0.80-0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA.

The Impact of Contrast-Associated Acute Kidney Injury on All-Cause Mortality in Older Patients After Coronary Angiography:A 7.5-year Follow-Up.

Older patients (≥75 years) after coronary angiography constitute an increasing proportion, but only limited data are available regarding the prognosis of geriatric contrast-associated acute kidney injury (CA-AKI). Patients (≥75 years) undergoing coronary angiography between December 2010 and September 2013 were consecutively enrolled. CA-AKI was defined as an increase in serum creatinine of 25% or .5 mg/dL from the baseline within 48-72 h of contrast exposure. All-cause mortality was assessed during median 7.5 years (interquartile range [IQR] 6.7-8.7 years) follow-up period. In total, 571 patients aged >75 years undergoing coronary angiography were enrolled in a single center study; 82 (14.4%) patients had CA-AKI. The all-cause mortality during the median 7.5 years follow-up period was 22.0% in patients with CA-AKI and 13.1% in patients without CA-AKI (P = .015). After adjusting for potential confounding factors, the multivariable analysis indicated that CA-AKI was related to an increased risk of all-cause mortality during the median 7.5-year follow-up (hazard ratio [HR]: 2.46; 95% CI: 1.29-4.7; P = .006). CA-AKI is a significant and independent predictor of long-term mortality for patients aged over 75 years who underwent coronary angiography.

Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment.

BACKGROUND: Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment. METHODS: From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC. RESULTS: In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC. CONCLUSIONS: The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.

Next-generation HLA sequencing reveals the novel HLA-A*33:244 allele.

The novel HLA-A*33:244 allele contains a c.553G>A substitution in exon 3 compared with A*33:03:01:01.

An Interpretable Radiomics Model Based on Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to develop and validate an interpretable radiomics model based on two-dimensional shear wave elastography (2D-SWE) for symptomatic post-hepatectomy liver failure (PHLF) prediction in patients undergoing liver resection for hepatocellular carcinoma (HCC). METHODS: A total of 345 consecutive patients were enrolled. A five-fold cross-validation was performed during training, and the models were evaluated in the independent test cohort. A multi-patch radiomics model was established based on the 2D-SWE images for predicting symptomatic PHLF. Clinical features were incorporated into the models to train the clinical-radiomics model. The radiomics model and the clinical-radiomics model were compared with the clinical model comprising clinical variables and other clinical predictive indices, including the model for end-stage liver disease (MELD) score and albumin-bilirubin (ALBI) score. Shapley Additive exPlanations (SHAP) was used for post hoc interpretability of the radiomics model. RESULTS: The clinical-radiomics model achieved an AUC of 0.867 (95% CI 0.787-0.947) in the five-fold cross-validation, and this score was higher than that of the clinical model (AUC: 0.809; 95% CI: 0.715-0.902) and the radiomics model (AUC: 0.746; 95% CI: 0.681-0.811). The clinical-radiomics model showed an AUC of 0.822 in the test cohort, higher than that of the clinical model (AUC: 0.684, p = 0.007), radiomics model (AUC: 0.784, p = 0.415), MELD score (AUC: 0.529, p < 0.001), and ALBI score (AUC: 0.644, p = 0.016). The SHAP analysis showed that the first-order radiomics features, including first-order maximum 64 × 64, first-order 90th percentile 64 × 64, and first-order 10th percentile 32 × 32, were the most important features for PHLF prediction. CONCLUSION: An interpretable clinical-radiomics model based on 2D-SWE and clinical variables can help in predicting symptomatic PHLF in HCC.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma.

BACKGROUND: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.

Achieving Efficient CO2 Electrolysis to CO by Local Coordination Manipulation of Nickel Single-Atom Catalysts.

Selective electroreduction of CO2 to C1 feed gas provides an attractive avenue to store intermittent renewable energy. However, most of the CO2-to-CO catalysts are designed from the perspective of structural reconstruction, and it is challenging to precisely design a meaningful confining microenvironment for active sites on the support. Herein, we report a local sulfur doping method to precisely tune the electronic structure of an isolated asymmetric nickel-nitrogen-sulfur motif (Ni1-NSC). Our Ni1-NSC catalyst presents >99% faradaic efficiency for CO2-to-CO under a high current density of -320 mA cm-2. In situ attenuated total reflection surface-enhanced infrared absorption spectroscopy and differential electrochemical mass spectrometry indicated that the asymmetric sites show a significantly weaker binding strength of *CO and a lower kinetic overpotential for CO2-to-CO. Further theoretical analysis revealed that the enhanced CO2 reduction reaction performance of Ni1-NSC was mainly due to the effectively decreased intermediate activation energy.