[Identification of oxidative stress-related biomarkers in chronic rhinosinusitis with nasal polyps using WGCNA combined with machine learning algorithms].

Objective: To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP. Methods: Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software. Results: Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences (P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion: This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

High-Temperature Anomalous Metal States in Iron-Based Interface Superconductors.

The nature of the anomalous metal state has been a major puzzle in condensed matter physics for more than three decades. Here, we report systematic investigation and modulation of the anomalous metal states in high-temperature interface superconductor FeSe films on SrTiO_{3} substrate. Remarkably, under zero magnetic field, the anomalous metal state persists up to 20 K in pristine FeSe films, an exceptionally high temperature standing out from previous observations. In stark contrast, for the FeSe films with nanohole arrays, the characteristic temperature of the anomalous metal state is considerably reduced. We demonstrate that the observed anomalous metal states originate from the quantum tunneling of vortices adjusted by the Ohmic dissipation. Our work offers a perspective for understanding the origin and modulation of the anomalous metal states in two-dimensional bosonic systems.

[Oral submucosal fibrosis induced by active components in areca nut: a network pharmacology-based analysis and validation of the mechanism].

OBJECTIVE: To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis (OSF) and the possible mechanism. METHODS: The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software. The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia (2015), PubChem, Chemical book, and SciFinder databases. The potential active components, core targets, biological functions and signaling pathways affecting OSF were analyzed by network pharmacology. The targets of OSF were obtained by integrating Genecards and KEGG databases. The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine (TCMSP), and the target-compound, compound-TCM, target-compound-TCM network was constructed. Molecular docking was used to analyze the component-target binding. Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF. RESULTS: The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways. In the clinical samples, the expressions of PI3K protein decreased and the expressions p-PI3K, AKT1 and PAkt all increased significantly in OSF tissue, where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected. The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals. CONCLUSION: The main active ingredients including arecoline, arecaine, and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia, thus leading to the occurrence of oral submucosal fibrosis.

[Effects of gelatin methacrylate anhydride hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells in the treatment of full-thickness skin defect wounds in mice].

Objective: To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice. Methods: This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3rd and 4th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification (n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results: The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group (P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550±23, 235±9, and 856±35, respectively, which were significantly higher than 188±14, 97±6, and 370±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively, P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups (P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group (P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group (P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions: hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

[Reassessment of practice of Chinese surgeons since introduction of the watch and wait strategy after neoadjuvant therapy for rectal cancer].

Objective: To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer. Methods: A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ2 or Fisher's exact probability tests. Results: The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ2=12.83, P<0.001; χ2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion: Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.

The Clinical Significance of Subtle Distal Fallopian Tube Abnormalities: A Multicentre Prospective Observational Study.

Background: Subtle distal fallopian tube abnormalities are a group of diseases characterised by small variations in tubal anatomy. The clinical significance of these abnormalities need to be studied. Objectives: The purpose of this multicentre prospective observational study was to investigate whether subtle distal fallopian tube abnormalities are related to infertility and endometriosis. Materials and Methods: The investigation was carried out in five medical centres in China and France from February to July 2021 and included reproductive-age patients who underwent gynaecological laparoscopy. Subtle abnormalities included Hydatid of Morgagni (HM) , fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis, and accessory fallopian tube. Results: 642 patients were enrolled in the study and 257 (40.0%) were diagnosed with subtle tube abnormalities. Hydatid of Morgagni was the most common abnormality (22.7%; n=146), followed by fimbrial agglutination (19.8%; n=127), tubal diverticula (6.9%; n=44), accessory tube (2.0%; n=13), and tubal accessory ostium (1.9%; n=12). Fimbrial phimosis was the least common abnormality (0.3%; n=2). The prevalence of subtle fallopian tube abnormalities was significantly higher among infertile patients (188/375, 50.1%) than those without history of infertility (69/267, 25.8%, ᶍ2=38.332, P=0.000). 209 patients were diagnosed with endometriosis during surgery, and the prevalence of subtle abnormalities was significantly higher in the endometriosis group than in those without endometriosis (61.2%, [128/209] vs. 29.8% [129/433], ᶍ2=58.086, P=0.000). Conclusions: Higher prevalence of subtle tubal abnormalities suggests that they may contribute to infertility. They are highly related to endometriosis and indicate fimbrial abnormalities of endometriosis. What is new?: This is the largest multicentre study to investigate the subtle distal fallopian tube abnormalities in infertile women. Compared to previous studies, this study includes the main subtle distal abnormalities and the control group patients without a history of infertility.

Impact of adenomyosis on pregnancy outcomes: a retrospective consecutive cohort study.

OBJECTIVE: This retrospective study explored the potential connection between adenomyosis and pregnancy outcomes. PATIENTS AND METHODS: A study included data from a total of 1,208 pregnancies. The adenomyosis group included 334 pregnant women with adenomyosis, and women in the control group (n=874) had uncomplicated pregnancies. Data on pregnancy complications and maternal and neonatal outcomes were compared. RESULTS: The incidence of gestational hypertension, gestational diabetes, and placenta previa was higher in the adenomyosis group compared to the control group (p<0.05). Adenomyosis was linked to a higher risk of postpartum hemorrhage (1,000-1,500 ml) but a lower risk of premature rupture of membranes (PROM) (p<0.05). Diagnosis of adenomyosis correlated with increased incidence of low fetal weight (20.3% vs. 21.3%, p<0.05) and a low APGAR score at 1 min (p<0.05). CONCLUSIONS: Adenomyosis correlated with a higher incidence of gestational hypertension, placenta previa, and gestational diabetes. At the same time, adenomyosis correlated with a significantly lower incidence of PROM compared to uncomplicated pregnancy. There was a significant increase in the incidence of postpartum hemorrhage and a higher risk of low fetal weight and lower APGAR score at 1 min in pregnancies with adenomyosis.

Removal of intraglandular calculi in Wharton's duct: clinical outcome and treatment algorithm.

The aim of this study was to propose a treatment strategy for intraglandular submandibular calculi based on calculus site. Seventy-three consecutive patients with impalpable intraglandular submandibular calculi were enrolled retrospectively. The calculi were classified as either post-hilar type, central type, or superficial type. Treatment approaches included transoral duct slitting (TDS), interventional basket retrieval (IBR), intraductal laser lithotripsy (ILL), and transcervical lithotomy (TCL). Complete calculus removal with gland preservation was achieved in 64 patients (87.7%). The success rate for post-hilar, central, and superficial calculi was 86.4% (51/59), 90.9% (10/11), and 100% (3/3), respectively. The treatment approach applied in patients with treatment success was TDS in 32 cases, IBR in 20, ILL in nine, and TCL in three. During follow-up (median 17.3 months), one patient experienced gland atrophy and three had ductal stenosis; the remaining 60 patients (93.8%, 60/64) had good clinical outcomes. In the eight failure cases operated by TDS, the deeply situated calculi could not be detached despite the parenchymal incision in five cases, while the procedure was ceased due to the patient's inability to cooperate in the other three cases. In the remaining failure case, the submandibular gland was sacrificed after calculus extraction via TCL. Application of the proposed treatment algorithm might help preserve gland function in patients with intraglandular submandibular calculi.

[Pelvic coronal inclination change in adolescent flexible flatfoot surgically treated with arthroereisis].

Objective: To evaluate adolescent pelvic coronal inclination angle change after flatfoot treated with arthroereisis. Method: A case-series study. From June 2018 to September 2020, 25 children with flexible flat foot and pelvic obliquity were included in this retrospective study in Peking University Shenzhen Hospital. There were 17 males and 8 females with a mean age of (11.2±2.2) years (9-15 years). There were 5 cases of unilateral flatfoot and 20 cases of bilateral flatfoot. All of the patients were surgically treated with arthroereisis. Regular follow-up was done in 3 months, 1 and 2 years postoperatively. Weightbearing fluoroscopy of entire lower limb and foot were investigated to measure Meary's angle, calcaneal pitch angle, height difference at ankle and pelvic plane, pelvic inclination and sacrum-iliac distance (F value) on coronal plane. Results: The mean Mearys' angle at 3 month postoperatively was improved when compared with that before the operation (3.1°±1.5° vs 25.9°±4.3°, P<0.001), and it remained at the same level 2 years after the operation (compared with that at 1 year after the operation, P=0.748). The calcaneal pitch angle improved significantly at 3-month follow-up when compared with that before the operation (16.6°±2.4° vs 9.9°±1.5°, P<0.001), and there was no significant change between 1 year and 2 years after operation (P=0.542). The height difference at mortise plane were also reduced at the 3-month follow-up(P<0.001), and it remained at the same level at 1 year and 2 years after the operation (P=0.159). Pelvic height difference decreased dramatically from (12.4±1.7) mm (before operation) to (7.1±1.2) mm(3 month after the operation) (P<0.001), it decreased to (3.6±1.8) mm 1 year after the operation (compared with that at 3 months after the operation, P<0.001), and no further reduction was observed 2 years after the surgery (P=0.483). The pelvic inclination angle and sacrum-iliac distance were also improved at 3-month follow-up when compared with those before the operation (both P<0.001), and they declined further 1 year after the operation(both P<0.05), but the decreasing trend disappeared at the 2-year follow-up (both P>0.05). Conclusion: For adolescent flexible flat foot patients with pelvic obliquity, the coronal inclination and pelvic height discrepancy would partially recovered with correction of flatfoot deformity, but it could not be completely corrected in the mean follow-up period of 2 years after the operation.

[Development and validation of prognostic nomogram for malignant pleural mesothelioma].

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

[Y-box-binding protein 1 mediates sorafenib resistance via the extracellular signal regulated-protein kinase pathway in hepatoma cells].

Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.

[Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft].

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

CCDC3 Gene Regulates the Proliferation of Breast Cancer Cells.

We studied the effect of CCDC3 on the viability of human breast cancer cell line MDA-MB-231. The levels of CCDC3 mRNA and the corresponding protein in MDA-MB-231, MCF-7, T-47D, and HCC1937 cell lines were measured by reverse transcription quantitative real-time PCR and Western blotting. Since MDA-MB-231 cells had higher expression of mRNA CCDC3 and CCDC3 protein, we used this cell line for transfection with small interfering RNA by lentivirus. Cell Counting Kit-8 and clone formation assay were used to detect the effects of CCDC3 knockdown on cell viability; flow cytometry was used to detect the effects of CCDC3 knockdown on cell apoptosis and cell cycle. In MDA-MB-231 cell line, the CCDC3 protein level was significantly down-regulated after CCDC3 knockdown in comparison with the control group (p<0.05). The cell viability and the number of clones in the CCDC3 knockdown group were significantly reduced (p<0.05), while the apoptosis rate significantly increased (p<0.05). Thus, after CCDC3 knockdown, cell viability is weakened in MDA-MB-231 cells, and cell apoptosis rate is increased. Therefore, CCDC3 gene is promising as a new candidate target for BC treatment.

Anomalous quantized plateaus in two-dimensional electron gas with gate confinement.

Quantum information can be coded by the topologically protected edges of fractional quantum Hall (FQH) states. Investigation on FQH edges in the hope of searching and utilizing non-Abelian statistics has been a focused challenge for years. Manipulating the edges, e.g. to bring edges close to each other or to separate edges spatially, is a common and essential step for such studies. The FQH edge structures in a confined region are typically presupposed to be the same as that in the open region in analysis of experimental results, but whether they remain unchanged with extra confinement is obscure. In this work, we present a series of unexpected plateaus in a confined single-layer two-dimensional electron gas (2DEG), which are quantized at anomalous fractions such as 9/4, 17/11, 16/13 and the reported 3/2. We explain all the plateaus by assuming surprisingly larger filling factors in the confined region. Our findings enrich the understanding of edge states in the confined region and in the applications of gate manipulation, which is crucial for the experiments with quantum point contact and interferometer.

Fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia: systematic review and meta-analysis.

OBJECTIVE: It is debated whether fetal endoscopic tracheal occlusion (FETO) is beneficial to fetuses with congenital diaphragmatic hernia (CDH) and whether FETO has different effects in moderate and severe CDH. We conducted a systematic review and meta-analysis including the latest evidence to assess the overall effects of FETO on clinical outcomes of CDH. METHODS: We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang Database to retrieve eligible studies published before 8 September 2022. No language or study design restrictions were applied. Studies were included if CDH fetuses underwent FETO surgery and were compared with a cohort that underwent expectant management, with at least one outcome reported. The primary outcomes were mortality at 1, 6 and 12 months after birth, rates of pulmonary hypertension, use of extracorporeal membrane oxygenation (ECMO) and prematurity. Meta-analysis was conducted to obtain pooled odds ratios (ORs) and mean differences. The quality of included studies and pooled evidence was also assessed. RESULTS: A total of 1187 CDH fetuses from 20 studies were included in the quantitative synthesis. FETO significantly reduced 1-month (OR, 0.56 (95% CI, 0.34-0.93); P = 0.02, number needed to treat (NNT) = 7.67) and 6-month (OR, 0.34 (95% CI, 0.18-0.65); P = 0.0009, NNT = 5.26) CDH mortality (moderate/low quality of evidence). Subgroup analysis suggested that the effects of FETO on the rates of pulmonary hypertension and ECMO usage were significant in severe CDH (low/moderate quality of evidence) but not in moderate CDH (low/very low quality of evidence). FETO was also associated with an increased risk of preterm prelabor rupture of membranes before 37 weeks' gestation (OR, 4.94 (95% CI, 2.25-10.88); P < 0.0001, number needed to harm (NNH) = 3.13) and preterm birth before 37 weeks (OR, 5.24 (95% CI, 3.33-8.23); P < 0.00001, NNH = 2.79) (high/moderate quality of evidence). However, FETO was not associated with severe complications, such as preterm birth before 32 weeks, placental abruption or chorioamnionitis (very low/low quality of evidence). CONCLUSIONS: FETO is associated with a reduction in mortality, rate of pulmonary hypertension and ECMO usage in severe CDH, while it reduces only the risk of mortality in moderate CDH. Although FETO increases the risk of late prematurity, it does not result in extreme prematurity. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[Liver transplantation for the treatment of acute liver failure in 3 cases with NBAS gene deficiency and literature review].

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.

Ultrasound Fusion-Guided Core Needle Biopsy for Deep Head and Neck Space Lesions: Technical Feasibility, Histopathologic Yield, and Safety.

BACKGROUND AND PURPOSE: Ultrasound is generally considered to have a minor role in guiding biopsies for deep head and neck space lesions. However, the ultrasound fusion technique may have the potential to change this opinion. This study evaluated the feasibility, histopathologic yield, and safety of ultrasound fusion-guided core needle biopsies for deep head and neck space lesions. MATERIALS AND METHODS: From March 2021 to April 2022, patients with primary deep head and neck space lesions were prospectively included in this study. Ultrasound fusion was performed with contemporaneous CT, MR imaging, or PET/CT studies, and ultrasound fusion-guided core needle biopsy was performed by using a Micro-Convex probe via 4 different needle approaches. Feasibility, histopathologic results, and biopsy-related complications were observed. Descriptive statistics were applied. RESULTS: Ultrasound-guided biopsy was feasible in all 16 patients (11 women and 5 men; mean age 46 [SD, 16] years; range, 16-76 years). The lesions were located in the parapharyngeal space, infratemporal fossa, and skull base, with a median diameter of 3.8 cm (range, 2.2-6.5 cm). An adequate and definite histopathologic yield was obtained in 15/16 (93.8%) patients; among them, 4/15 lesions (26.7%) were malignant, and 11/15 (73.6%) were benign. No major complications occurred. Minor complications were noted in 2 of the 16 (12.5%) patients (self-limiting inflammation in 1 and bleeding in 1). CONCLUSIONS: This study demonstrates that ultrasound fusion-guided biopsy of deep head and neck space lesions is feasible and safe, with a high histopathologic yield.

[Radiographic diagnosis of distal fibula avulsion fractures: Comparison of ankle X-ray and three-dimensional reconstruction of CT].

OBJECTIVE: To investigate the difference in sensitivity between X-ray and three-dimensional reconstruction of computed tomography (3D-CT) for the diagnosis of distal fibular avulsion fracture, and the radiographic presentation of the ossicle. METHODS: From January to October 2018, 92 patients with distal fibular avulsion fracture were visited for surgical treatment in Department of Sports Medicine, Peking University Third Hospital, and 60 cases were finally enrolled according to the inclusion and exclusion criteria. Intraoperative detection was regarded as the gold standard, and the diagnostic sensitivity of preoperative ankle X-ray and 3D-CT for the distal fibular avulsion fractures was statistically determined. The ossicle maximum diameter as well as the degree of its displacement were also measured. On 3D-CT, the distance from the ossicle center point to the anterior fibular tuberosity (a), the distance to the fibular tip (b), and the a/b value was used to present the ossicle displacement. RESULTS: Among the 60 patients, 36 and the 52 patients were correctly detected by X-ray and 3D-CT, respectively, and the sensitivities was 60.0% and 86.7%, respectively (P=0.004). The mean diameter of the ossicle on X-ray and 3D-CT was (9.2±3.9) mm and (10.5±3.2) mm, respectively. The mean distance from the ossicle center to the anterior fibular tuberosity (a) was (17.5±3.6) mm and the mean distance to the fibular tip (b) was (17.4±4.8) mm, with mean a/b values of 1.1±0.7. The intraclass correlation coefficients (ICC) for each measurement ranged from 0.891-0.998 with a high degree of consistency. CONCLUSION: Compared with X-ray, 3D-CT has higher sensitivity in diagnosing distal fibular avulsion fractures, can help clinicians evaluate ossicle's location and choose surgical methods, and is recommended to be performed in patients with suspected distal fibula avulsion fractures in clinical practice.